The Laryngoscope
Lippincott Williams & Wilkins
© 2007 The American Laryngological,
Rhinological and Otological Society, Inc.
Abnormal Sensorimotor Integrative
Function of the Larynx in Congenital
Laryngomalacia: A New Theory of Etiology
Dana Mara Thompson, MD, MS
Objectives/Hypothesis: Laryngomalacia is an
enigmatic disease in which laryngeal tone is weak, result-
ing in dynamic prolapse of tissue into the larynx. Senso-
rimotor integrative function of the brainstem and periph-
eral reflexes are responsible for laryngeal tone and
airway patency. The goal of this study was to elucidate
the etiology of decreased laryngeal tone through evaluat-
ing the sensorimotor integrative function of the larynx.
The secondary goal was to evaluate factors and medical
comorbidities that contribute to the wide spectrum of
symptoms and outcomes.
Study Design: Prospective and retrospective collec-
tion of evaluative data on infants with congenital laryn-
gomalacia at two tertiary care pediatric referral centers.
Methods: Two hundred one infants with laryngo-
malacia were divided into three groups on the basis of
disease severity (mild, moderate, severe). Patients were
followed prospectively every 8 to 12 weeks until symptom
resolution or loss to follow-up. Sensorimotor integrative
function of the larynx was evaluated in 134 infants by
laryngopharyngeal sensory testing (LPST) of the laryn-
geal adductor reflex (LAR) by delivering a duration- (50
ms) and intensity- (2.5–10 mm Hg) controlled air pulse to
the aryepiglottic fold to induce the LAR. Medical records
were retrospectively reviewed for medical comorbidities.
Results: The initial LPST was higher (P ⬍ .001) in
infants with moderate (6.8 mm Hg) and severe disease
(7.4 mm Hg) compared with those with mild disease (4.1
mm Hg). At 1, 3, and 6 months, infants with moderate
and severe disease continued to have a higher LPST
compared with those with mild disease. At 9 months, the
From the Department of Pediatric Otolaryngology–Head and Neck
Surgery, Cincinnati Children’s Hospital Medical Center, University of
Cincinnati College of Medicine, Cincinnati, Ohio, U.S.A.; and the Depart-
ment of Otorhinolaryngology, Head and Neck Surgery, Mayo Clinic and
Mayo Eugenio Litta Children’s Hospital, Rochester, Minnesota, U.S.A.
Editor’s Note: This Manuscript was accepted for publication Febru-
ary 12, 2007.
Send correspondence to Dr. Dana M Thompson, Department of Pe-
diatric Otolaryngology, Cincinnati Children’s Hospital, 3333 Burnet Ave,
Cincinnati, OH 45229-3039. E-mail: Dana.thompson@cchmc.org
DOI: 10.1097/MLG.0b013e31804a5750
Laryngoscope 117: June 2007 Supplement
LPST decreased in all subjects (3.1–3.5 mm Hg, P ⫽ .14),
which also correlated with symptom resolution. Neuro-
logic, genetic, and cardiac diseases were more common in
infants with severe disease (P ⬍ .001). Gastroesophageal
reflux disease (GERD) and feeding problems more com-
mon in those with moderate and severe disease (P ⬍ .001).
Apgar scores were lower in those with severe disease (P ⬍
.001). Most symptoms resolved within 12 months of pre-
sentation. Those with GERD benefited from treatment.
Supraglottoplasty resulted in few complications. Multiple
comorbidities (⬎3) influenced the need for tracheotomy.
Conclusions: Laryngeal tone and sensorimotor inte-
grative function of the larynx is altered. The degree of
alteration correlated with disease severity, indicating that
factors that alter the peripheral and central reflexes of the
LAR have a role in the etiology of signs and symptoms of
laryngomalacia. GERD, neurologic disease, and low Apgar
scores influenced disease severity and clinical course, ex-
plaining the spectrum of disease symptoms and outcomes.
Sensorimotor integrative function improved as symptoms
resolved.
Key Words: Laryngomalacia, stridor, sensory test-
ing, laryngeal adductor reflex, gastroesophageal reflux dis-
ease, laryngopharyngeal reflux, supraglottoplasty.
Laryngoscope, 117(Suppl. 114):1–33, 2007
INTRODUCTION
Laryngomalacia is a condition where laryngeal tone is
weak and results in dynamic prolapse of supraglottic tissue
into the airway, causing inspiratory stridor and airway ob-
struction. The diagnosis is suggested by inspiratory stridor
that worsens with agitation, crying, feeding, or supine posi-
tioning and is confirmed by flexible laryngoscopy. Findings
may include prolapse of the arytenoid cartilages or the
supra-arytenoid mucosa, shortened aryepiglottic folds, and
an “omega”-shaped or a retroflexed epiglottis.1– 4
Laryngomalacia: Spectrum of Disease
Presentation and Clinical Course
Laryngomalacia is the most common laryngeal
anomaly and affects up to 45% to 75% of all infants with
Thompson: Laryngomalacia, a New Theory of Etiology
1
congenital stridor.5–10 The typical presentation is inspira-
tory stridor that begins within the first 10 days of life and
increases over the initial few months, with a symptom
peak at 6 to 8 months. Although most cases are a benign,
self-limiting process that resolves between 12 to 24
months of age,6 there are varying degrees of disease se-
verity. Most patients are rarely seen by the otolaryngolo-
gist and are cared for by their primary care physician
where expectant management or treatment by reposition-
ing the infant is usually effective. Others present with
additional symptoms of regurgitation, feeding difficulty
with or without weight loss, inconsequential cyanosis, and
gastroesophageal reflux disease (GERD). It has been im-
plied that infants in this clinical spectrum have associated
GERD,11–17 but the role of antireflux therapy has not been
established. Although GERD is a well-established co-
morbidity of laryngomalacia,11,12 the association and
impact of GERD on the symptoms of laryngomalacia are
under-explored. No studies evaluate the benefit of re-
flux treatment.
Up to 22% of cases are severe and have major
complications of upper airway obstruction that may be
life threatening. These complications include airway
obstruction with cyanosis, life-threatening apnea, feed-
ing difficulty with failure to thrive, developmental de-
lay, pectus excavatum, cor pulmonale, cardiac failure,
asphyxiation, and death.10,14,18 –20 Those with severe dis-
ease usually require surgical intervention.1,4,14,18,21–29
Options include bypassing the affected larynx by a tra-
cheotomy or endoscopic microsurgical techniques of
trimming the redundant tissues of the larynx, also
known as “supraglottoplasty.” With increasing experi-
ence and success with supraglottoplasty over 20 years,
this has become the procedure of choice. Retrospective
studies that evaluate supraglottoplasty treatment
report symptom reversal and success in 70% to 100%
of cases.1,14,28,29 The complication rate is less than
8%.30 Because of the high associated morbidity, trache-
otomy is usually reserved for supraglottoplasty fail-
ures or patients with complex medical diseases and
comorbidities.4,14,28
Laryngomalacia affects the full spectrum of infants
and includes those with neurologic disease, cardiopulmo-
nary disease, congenital anomalies, syndromes, and other
medical comorbidities.3,4,12,14,30 –38 No studies to date es-
tablish whether medical comorbidities correlate with dis-
ease severity irrespective of the symptoms at presenta-
tion. Studies that evaluate the influence of medical
comorbidities are restricted to surgical series and suggest
that comorbidities have a negative impact on supraglotto-
plasty outcomes.4,14,26,28,30
Otolaryngologists who manage infants with laryngo-
malacia understand the disease severity spectrum and
appreciate that not all laryngomalacia is a benign, self-
limited process. Some infants require feeding and reflux
management intervention, and others may require surgi-
cal intervention. Why some infants have mild symptoms
and others develop life-threatening complications is
poorly understood.
Laryngoscope 117: June 2007 Supplement
2
Etiologic Theories of Laryngomalacia
Although the condition was first described in 1843,
the etiology remains elusive.39 Several theories have been
proposed without consensus or compelling supporting ev-
idence. The anatomic theory proposes that the etiology is
abnormal anatomic placement of flaccid laryngeal tissue
causing stridor and airway obstruction.1,2,7,40 – 42 The car-
tilaginous theory, also termed “chondromalacia,” proposes
that the laryngeal cartilage is abnormal, immature, and
pliable, leading to airway obstruction and stridor.21,43,44
The neurologic theory includes several proposed mecha-
nisms. Neuromuscular hypotonia is the most commonly
cited neurologic etiologic cause.31 Others have proposed
compromised airway patency from an abnormal neural
pathway originating in the nucleus ambiguus45 or dis-
rupted cortical function.41 In addition, GERD11 has been
implicated as a causative factor because of a high associ-
ation between the two. Some support multiple etiologic
theories of laryngomalacia.1,24,42,46
Despite these multiple etiologic theories, the litera-
ture best supports a neurologic mechanism. Neurologic
abnormalities have been reported in up to 20% of infants
with laryngomalacia.14,23,29,31,47– 49 Central nervous sys-
tem (CNS) sedation of infants results in classic signs and
symptoms of laryngomalacia with collapse of laryngeal
tissue.50 CNS insults such as seizures, strokes, or hypoxic
brain injury can lead to acquired laryngomalacia in adults
and children. The insult occurs at the brainstem nuclei for
breathing and airway patency.51–54 This parallel suggests
a cause and effect relation between abnormal integration
of sensorimotor function at the brainstem and acquired
laryngomalacia. Many cases of acquired laryngomalacia
resolve with improvement or reversal of the underlying
neurologic condition.52 Using acquired laryngomalacia as
an example provides a basis for a cogent argument that
congenital laryngomalacia could be a consequence of al-
tered or underdeveloped sensorimotor brainstem reflexes,
akin to a CNS insult. In a similar manner to acquired
laryngomalacia, it is possible that the symptoms of con-
genital laryngomalacia resolve as the brainstem nuclei
and their sensorimotor reflexes mature in a process, sim-
ilar to symptom resolution after improvement or reversal
of the underlying CNS condition.
Sensorimotor Integrative Function of Larynx
Although a neurologic theory is the most popular and
best supported, it is unclear whether the alteration is
neuromuscular or whether the problem is located in the
peripheral nervous system,46 CNS,45,50 or both. The sup-
port of a peripheral vagal nervous system alteration as an
etiology of airway obstruction was first demonstrated in
the study of Thomson and Turner46 at the turn of the 20th
century. In a model used to study congenital stridor, vagal
denervation of larynges showed symptomatic passive me-
dial prolapse of supraglottic structures and laryngeal ob-
struction. This study suggests that there are conceptual
parallels to the effects of vagal denervation and laryngeal
tone in the etiology of laryngeal obstruction and congeni-
tal laryngomalacia.
Sensorimotor integration of peripheral sensory affer-
ent reflexes, brainstem function, and the motor efferent
Thompson: Laryngomalacia, a New Theory of Etiology
Fig. 1. (A) Neurologic pathway of intact laryngeal adductor reflex. (B) Neurologic pathway of altered laryngeal adductor reflex (LAR). SLN ⫽
superior laryngeal nerve.
response are responsible for laryngeal function and tone.
This is a vagal nerve-mediated reflex known as the laryn-
geal adductor reflex (LAR). The LAR is activated by sen-
sory stimulation of the mechanoreceptors and chemore-
ceptors of the superior laryngeal nerve (SLN) located in
the region of the aryepiglottic fold.55,56 As seen in Figure 1,
stimulation of these receptors sends sensory afferent
information by the SLN to brainstem nuclei that regulate
respiration and swallowing. Information is then inte-
grated between the nucleus tractus solitarius and nucleus
ambiguus. From here, an involuntary efferent response by
way of the vagus nerve results in a motor response of
adduction of the vocal folds and a swallow.55,57–59 This
efferent vagal response is also responsible for laryngeal
tone. Dysfunction anywhere along the afferent, brain-
stem, or efferent pathway of the LAR can result in altered
laryngeal function and tone. In laryngomalacia, it is plau-
sible that the laryngeal sensorimotor integrative function
between the brainstem and the peripheral afferent and
efferent reflexes of the LAR is altered and may have a role
in the etiology and causation of the signs and symptoms of
the disease, namely weak laryngeal tone, apnea, and swal-
lowing problems (Fig. 1).
Sensorimotor integrative function of the larynx and
the LAR can be tested by laryngopharyngeal sensory test-
ing (LPST). This is done by applying a duration- (50 ms)
and intensity- (2.5–10 mm Hg) controlled air pulse to the
aryepiglottic fold and observing a response of glottic closure
and swallow.60 – 67 Normative LPST data for an adult are
between 2 to 4 mm Hg, with an average of 2.3 mm Hg.68,69
Normative data are not available for infants and children;
however, infants without neurologic disease or develop-
mental delay who were evaluated for airway obstruction
have an average LPST of 4.3 mm Hg.67 An elevated LPST
of greater than 5 mm Hg indicates that there is an abnor-
mality or pathology somewhere along the pathway of the
LAR. An elevated LPST of greater than 6 mm Hg in
children or adults suggest that CNS and brainstem pa-
thology may be involved.62,63,65,69,70
Comparison of LPST data is available in infants and
toddlers with reflux disease and infants with apnea.65,66,71
GERD and laryngopharyngeal reflux (LPR) have been
Laryngoscope 117: June 2007 Supplement
implicated in causing dysfunction of the sensory afferent
limb of the LAR. An LPST of 6.3 mm Hg in infants and
toddlers and 5.8 mm Hg in adults is seen in patients with
GERD and LPR. The acid alters laryngeal sensation,
thereby changing the air pulse intensity required to acti-
vate the sensory afferent reflex.61,65,66,71–73 The clinical
result of altered laryngeal sensation in infants and tod-
dlers is coughing, choking, and discoordinate swallow-
ing.71 These are common symptoms in patients with la-
ryngomalacia and GERD. LPST decreases (3.5 mm Hg in
infants/toddlers, 3.8 mm Hg in adults) after antireflux
treatment. This finding shows that acid reflux treatment
improves laryngeal sensation. The clinical outcome is im-
proved swallow function.71,72 The resultant sensory abnor-
malities may explain why infants with laryngomalacia
and GERD develop coughing, choking, and swallowing
problems.
Infant apnea occurs because of underdeveloped cen-
tral mechanisms that control breathing. An elevated
LPST (6.3 mm Hg) is also seen in premature infants with
apnea,67 some of whom have GERD, suggesting a combi-
nation of a peripheral afferent sensory and central brain-
stem abnormality that may contribute to airway tone.
OBJECTIVES/HYPOTHESIS
Experimental Evaluation of Laryngomalacia
Disease Etiology
Circumstantial clinical and experimental evidence sug-
gest that alteration anywhere along the pathway of the LAR
results in weak laryngeal tone and compromised function. It
is possible that alteration of the sensorimotor integrative
function of the larynx causes the signs, symptoms, and clin-
ical examination findings of laryngomalacia. This may ex-
plain why some infants with a “laryngomalacia”-appearing
larynx have symptoms and others do not. The degree of
alteration may result in a broader spectrum of symptoms
and may explain why there is variation in disease symp-
tom presentation. The primary goal of this study was to
elucidate the etiology of decreased laryngeal tone seen in
laryngomalacia by evaluating the sensorimotor integra-
tive function of the larynx assessed by LPST.
Thompson: Laryngomalacia, a New Theory of Etiology
3
Evaluation of Disease Spectrum Presentation
and Clinical Course
The reason for the broad spectrum of symptoms and
disease presentation is poorly understood. Through eval-
uation of demographic characteristics, symptom severity,
the presence of medical comorbidities, and correlation of
LPST threshold data, the secondary goal of this study was
to determine why this spectrum exists. The influences of
the medical and surgical interventions that reflect the
practice of the author and colleagues are also evaluated.
PATIENTS AND METHODS
Between June 1998 and June 2003, evaluative data were
collected in a combination of prospective and retrospective fash-
ions from 223 patients with congenital laryngomalacia evaluated
by the author and colleagues at two tertiary care pediatric refer-
ral centers. Institutional review board approval was obtained at
both institutions. Infants were excluded if follow-up was less than
3 months, as were those infants diagnosed with laryngomalacia
after 3 years of age, and those with conditions that mimic laryn-
gomalacia, such as a type I laryngeal cleft. Demographic data and
presenting clinical symptoms were documented at the time of the
initial interview and before group assignment. Before confirming
the diagnosis of laryngomalacia by flexible laryngoscopy, infants
were divided into three clinical groups. Group assignment was
determined by disease severity at the time of the first presenta-
tion to a physician (primary care physician n ⫽ 173; otolaryngol-
ogist n ⫽ 28) for any symptom related to laryngomalacia. Group
1 infants, with mild disease, included those who presented with
inconsequential inspiratory stridor with or without coughing
symptoms during feeding. Group 2 infants, with moderate dis-
ease, included infants with inspiratory stridor and the addition of
any of the following symptoms: difficult to feed with or without
weight loss but no failure to thrive, coughing, and choking during
feeding with air gasping events, frequent regurgitation, inconse-
quential cyanosis, inconsequential brief apneic episodes, and in-
consequential intermittent dyspnea with retractions that did not
require medical intervention. Group 3 infants, with severe dis-
ease, included infants with inspiratory stridor and life-
threatening complications that include any of the following: fail-
ure to thrive, cyanosis requiring medical intervention, dyspnea
with retractions requiring medical intervention, pectus excava-
tum, life-threatening apneic episodes, hypoxia, pulmonary hyper-
tension, or cor pulmonale.
After group assignment, the diagnosis was confirmed by
flexible laryngoscopy, and the laryngeal findings were recorded.
No sedation was given. With pulse oximetry monitoring, the
infant was positioned in the upright or semi-reclined position in
the lap of a caregiver with gentle restraint. Two percent viscous
lidocaine was applied to the outer surface of the scope before
insertion in the nose. Flexible laryngoscopy was performed with
either a 2.5 mm diameter flexible laryngoscope or a 4.0 mm
diameter scope with a channel for an air pulse delivery.
To determine whether there was an alteration in the sen-
sorimotor function of the larynx, 134 patients, a subgroup of the
laryngomalacia patient cohort, had LPST of the LAR with use of
the 4.0 mm diameter flexible laryngoscope (FNL 10 AP Laryngo-
scope, Pentax Precision Instruments Corp., Orangeburg, NY)
that was equipped with an accessory channel and interfaced to a
calibrated air pressure device for delivery of an air pulse (AP-
4000 Air Pulse Sensory Stimulator, Pentax, Golden, CO). A
duration- (50 ms) and intensity- (2.5–10 mm Hg) controlled air
pulse was delivered to the aryepiglottic fold to induce the
LAR.60,61,65,67,68 The tip of the laryngoscope was advanced to
within 2 to 3 mm of the aryepiglottic fold. Starting at an intensity
Laryngoscope 117: June 2007 Supplement
4
of 2.5 mm Hg, the intensity of the air pulse was increased in 0.5
mm Hg increments to a maximum of 10.0 mm Hg. A positive LAR
response was determined by observing vocal cord closure and a
swallow response. The intensity level in mm Hg required to
induce the LAR was recorded.
The infants were followed prospectively every 8 to 12 weeks
until symptom resolution or loss to follow-up. At each follow-up
visit, parents were queried whether presenting symptoms were
the same, worse, or better or whether there were any new or
additional symptom developments. Changes, improvement, and
resolution of symptoms were documented at each visit. Infants
who had LPST testing were retested at follow-up intervals to
determine whether there was any change in the threshold to
induce the LAR.
The treatment and management strategies reflected the
clinical practice of the author and colleagues. These included
antireflux therapy or surgical interventions. In a nonrandomized
fashion, antireflux therapy was initiated at the discretion of the
author or another care provider on the basis of clinical symptoms
and findings. This included the use of proton pump inhibitor (PPI)
therapy (omeprazole 1 mg/kg/day) or histamine-2 receptor antag-
onist (H2RA) therapy (ranitidine 3 mg/kg/dose, 3 times a day).
Parents were queried whether they noted overall improvement in
symptoms after reflux treatment. Fundoplication was reserved
for severe or refractory cases of reflux disease thought to be
contributing to airway or feeding complications. Changes or dis-
continuance of antireflux therapies were recorded at each visit.
Infants with life-threatening complications required sur-
gery as determined by the author or colleagues of the author.
Indications for surgery included failure to thrive, weight loss,
apnea, cyanosis, pulmonary hypertension, cor pulmonale, severe
respiratory distress, pectus excavatum, hypoxia/hypercarbia, and
failed medical intervention. Supraglottoplasty (and revision su-
praglottoplasty if needed) was performed under spontaneous
breathing anesthesia with an operating microscope through a
Benjamin-Lindholm suspension laryngoscope without an endo-
tracheal tube. The supraglottoplasty was performed using micro-
laryngeal instruments. Areas addressed were determined by the
operating surgeon and recorded at the time of surgery. Standard
pediatric tracheotomy techniques were used in those who re-
quired tracheotomy. All medical records were retrospectively re-
viewed for diagnostic test of GERD and medical comorbidities of
neurologic disease, congenital cardiac disease, and genetic disor-
ders or syndromes.
Statistical Analysis
Data parameters were summarized using standard descrip-
tive statistics and by laryngomalacia disease severity group at
the time of presentation. To determine whether there were
unique demographic or patient presentation characteristics or
medical comorbidities that correlate with disease severity, com-
parisons were made between those who presented with symptoms
of mild (group 1), moderate (group 2), and severe laryngomalacia
(group 3). Comparisons of dichotomous or categorical parameters
between the groups were made using the chi-square test or Fish-
er’s exact test, as appropriate. Comparisons of ordinal or contin-
uously scaled parameters were made between the groups using
the Kruskal-Wallis test or an F test from a one-way analysis of
variance model if the distribution was normally distributed.
The cumulative incidence of resolution was calculated sep-
arately for four major presenting symptoms. Calculations were
made using the Kaplan-Meier method to take into account vary-
ing durations of follow-up. Duration of follow-up was calculated
from the date of symptom onset to the date of resolution or last
follow-up. Associations between laryngomalacia disease severity
group and time until resolution were made using the log-rank test.
Thompson: Laryngomalacia, a New Theory of Etiology
 TABLE I.
Laryngopharyngeal Sensory Testing (LPST) Thresholds in Congenital Laryngomalacia.
Mean (SD) LPST, mm Hg

Time Mild (n ⫽ 66) Moderate (n ⫽ 50) Severe (n ⫽ 18) P Value*

Baseline 4.1 (1.2), n ⫽ 66 6.8 (1.6), n ⫽ 50 7.4 (2.5), n ⫽ 18 ⬍.001

1 month 4.2 (1.5), n ⫽ 54 6.2 (1.9), n ⫽ 45 6.5 (1.9), n ⫽ 11 ⬍.001
3 months 3.7 (1.1), n ⫽ 66 4.7 (1.6), n ⫽ 49 5.7 (2.3), n ⫽ 18 ⬍.001
6 months 3.4 (0.9), n ⫽ 65 3.9 (0.9), n ⫽ 47 4.4 (1.2), n ⫽ 16 ⬍.001
9 months 3.1 (0.6), n ⫽ 54 3.5 (0.8), n ⫽ 43 3.5 (0.9), n ⫽ 12 .14
P value for LPST ⬍.001 ⬍.001 ⬍.001
change over time
*P values for mild disease versus moderate or severe disease.

All calculated P values were two-sided, and P values less
than .05 were considered statistically significant. All statistical
analyses were performed using the SAS software package (SAS
Institute, Cary, NC).
RESULTS
Laryngopharyngeal Sensory Testing of
Laryngeal Adductor Reflex Results
The median LPST threshold to induce the LAR at the
time of diagnosis in the 134 infants tested was 5.3 mm Hg.
As seen in Table I and Figure 2, higher mean thresholds
(P ⬍ .001) were required to induce the LAR in children
with moderate (6.8 ⫾ 1.6 mm Hg) and severe disease
(7.4 ⫾ 1.6 mm Hg) when compared with those with mild
disease (4.1 ⫾ 1.2 mm Hg), implying a greater alteration
in either the afferent, central, or efferent control of the
LAR in those with moderate and severe disease.
At 1, 3, and 6 months, those with moderate and
severe disease continued to have significantly higher
thresholds compared with those with mild disease, imply-
ing a longer time duration of alteration in either the
afferent, central, or efferent limb of the LAR. It was not
until 9 months that there was no difference in the LPST
thresholds.
Over time, the LPST thresholds decreased in each
group (P ⬍ .001); however, the decreases were signifi-
cantly greater in those with moderate and severe disease,
implying that maturation of the reflex occurs in all, but
greater changes are required in those with moderate and
severe disease. As seen in Table II, the mean LPST was
significantly higher (P ⬍ .001) among patients with
GERD, both with (7.3 ⫾ 2.1 mm Hg) and without neuro-
logic disease (6.2 ⫾ 2.1 mm Hg) compared with patients
without either comorbidity (3.9 ⫾ 1.3 mm Hg), demon-
strating that these comorbidities may affect the sensori-
motor function of the larynx in infants with laryngomala-
cia (Tables I and II) (Fig. 2).
Patient demographic characteristics and dis-
ease severity. The demographic description of 201 infants
who met the criteria is presented in Table III. At the time
of the first presentation to a physician (86% to primary
care provider; 14% to an otolaryngologist) for the symp-
toms of laryngomalacia, 39.8% had mild disease (group 1),
41.3% had moderate disease (group 2), and 18.9% had
severe disease (group 3). Boy infants were more commonly
affected than were girl infants, demonstrating a ratio of
1.4 to 1 that was not statistically different between the
disease severity groups. This study showed that laryngo-
malacia was a disease of term infants with a mean gesta-
tional age of 38 weeks that was not different between the
groups and, thereby, not influenced by disease severity.
The type of delivery was not different between the groups,
with 71% born by vaginal delivery and 22.9% born by cesar-
ean section. The birth weight ranged from 800 to 5,450 g,
with a median of 3,270 g that likewise was not influenced by
disease severity. The median Apgar scores were significantly

TABLE II.
Baseline Laryngopharyngeal Sensory Testing (LPST) Thresholds in
Those With Neurologic and Gastroesophageal Reflux Disease
(GERD) Comorbidities Compared With Those With No
Medical Comorbidity.
Baseline LPST
No. With (mm Hg),
Baseline LPST Mean (SD)

Neurologic disease and GERD 12 7.3 (2.1)

GERD comorbidity only 75 6.2 (2.0)
Fig. 2. Line plot graph showing decrease in laryngopharyngeal Neurologic disease only 1 3
sensory testing (LPST) threshold (mm Hg) means over time based No medical comorbidity 46 3.9 (1.3)
on disease severity.

Laryngoscope 117: June 2007 Supplement Thompson: Laryngomalacia, a New Theory of Etiology
5
 TABLE III.
Demographic Description of Infants With Congenital Laryngomalacia.
Total Mild Moderate Severe
Characteristic (n ⫽ 201) (n ⫽ 80) (n ⫽ 83) (n ⫽ 38) P Value*

Sex (%) .27

Boy 116 (58) 41 (51) 50 (60) 25 (66)
Girl 85 (42) 39 (49) 33 (40) 13 (34)
Race (%) .014†
White 154 (77) 57 (71) 72 (87) 25 (66)
Black 35 (17) 18 (22) 9 (11) 8 (21)
Asian 1 (1) 0 (0) 0 (0) 1 (3)
Hispanic 7 (3) 3 (4) 1 (1) 3 (8)
Other 4 (2) 2 (3) 1 (1) 1 (3)
Gestational age (wk) .11‡
No. 198 79 82 37
Mean (SD) 38.0 (2.6) 38.5 (1.9) 37.9 (2.7) 37.1 (3.2)
Median 39 39 39 38
IQR 37, 40 37, 40 37, 40 36, 40
Range (26–42) (32–42) (26–42) (28–40)
Type of delivery (%) .23§
Vaginal 142 (71) 58 (72) 63 (76) 21 (55)
Cesarean 46 (23) 18 (22) 17 (20) 11 (29)
Unknown 13 (6) 4 (5) 3 (4) 6 (16)
Birth weight (g) .17
No. 188 79 75 34
Mean (SD) 3,227.7 (679.1) 3,341.3 (638.1) 3,177.0 (726.1) 3,075.8 (639.1)
Median 3,270 3,295 3,270 3,000
IQR 2,865, 3,738 3,000, 3,790 2,780, 3,780 2,730, 3,636
Range (800–5,450) (1,650–5,450) (800–4,545) (1,720–4,090)
1 minute Apgar score (1–10) ⬍.001储
No. 183 79 75 29
Mean (SD) 7.3 (1.4) 7.6 (1.1) 7.3 (1.3) 6.1 (1.9)
Median 8 8 8 6
IQR 6, 8 7, 8 6, 8 5, 7
Range (1–9) (5–9) (3–9) (1–9)
5 minute Apgar score (1–10) .005§
No. 183 79 75 29
Mean (SD) 8.4 (1.2) 8.7 (0.9) 8.4 (1.4) 7.8 (1.4)
Median 9 9 9 8
IQR 8, 9 8, 9 8, 9 7, 9
Range (1–10) (6–10) (1–10) (3–10)
Age at onset (%) .063
Birth 151 (75) 64 (80) 55 (66) 32 (84)
1–7 days 19 (9) 7 (9) 12 (15) 0 (0)
8–14 days 11 (5) 3 (4) 5 (6) 3 (8)
2 weeks⫹ 20 (10) 6 (7) 11 (13) 3 (8)
Age at presentation to health care provider (days) .34
Mean (SD) 67.3 (63.6) 63.1 (63.4) 61.7 (51.9) 88.5 (82.0)
Median 49 47 47 72.5
IQR 27, 89 18.5, 84.5 32, 73 14, 145
Range (0–344) (0–344) (2–284) (0–307.0)
(Continues)

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6
 TABLE III.
(Continued).
Total Mild Moderate Severe
Characteristic (n ⫽ 201) (n ⫽ 80) (n ⫽ 83) (n ⫽ 38) P Value*

Age at diagnosis (days) ⬍.001储

Mean (SD) 102.8 (121.5) 81.3 (71.6) 83.1 (59.9) 191.0 (225.8)
Median 72 64.5 70 147
IQR 40, 125 32.5, 114 47, 91 70, 242
Range (2–1173) (2–385) (9–298) (2–173)
*P value based on chi-square test for comparing nominal variables or based on Kruskal-Wallis test for comparing ordinal or continuously scaled variables
between three groups.
†Upon collapsing race into white versus all others, race was significantly different between the three groups (P ⫽ .014). Evaluation of pair-wise comparisons
identified that patients with moderate disease were more likely to be white compared with patients with mild disease (P ⫽ .015) or severe disease (P ⫽ .007).
‡Patients with an unknown type of delivery were ignored in statistical comparison.
§Apgar scores were significantly different between three groups. Evaluation of pair-wise comparisons identified that patients with severe disease had
significantly lower Apgar scores than patients with either mild disease (P ⬍ .001for 1 min, P ⫽ .001 for 5 min) or with moderate disease (P ⫽ .001 for 1 min, P ⫽
.012 for 5 min).
储Although age on onset and presentation were not significantly different between three groups, age at diagnosis was significant. In particular, patients with
severe disease were diagnosed at a significantly later age than were patients with either mild (P ⬍ .001) or moderate (P ⫽ .001) disease.
IQR ⫽ interquartile range, 25th and 75th percentiles.

lower in those with severe disease when compared with
those with mild disease or with moderate disease.
Seventy-five percent had stridor present at birth,
15% within the first 2 weeks of life and 10% after 2 weeks.
The median age at first evaluation by a physician for a
laryngomalacia-associated symptom was 49 days and was
not significantly different between the groups; however,
the age at diagnosis was. The median age at time of diagno-
sis for patients with severe disease was 147 days, showing
that they were diagnosed at a significantly later age than
were patients with mild or moderate disease (Table III).
Symptom presentation and progression and dis-
ease severity. Stridor was the most common symptom of
congenital laryngomalacia and was present in 100% of the
infants at the time of presentation to a physician and at
the time of diagnosis. Stridor and feeding problems were
common in all groups. After stridor, feeding symptoms of
coughing, choking, and regurgitation were most common
and were seen in the majority of those with moderate and
severe disease (P ⬍ .001). Seventy-one percent were de-
scribed as difficult to feed; however, the proportion was
significantly higher in those with moderate or severe dis-
ease when compared with those with mild disease (P ⬍
.001). Table IV lists all symptoms present at the time of
presentation from most common to least common. As an-
ticipated, as based on group assignment, poor weight gain,
cyanosis, and apnea were more common in those with mod-
erate and severe disease. Pulmonary hypertension and cor
pulmonale were seen only in those with moderate and severe
disease.
Of the 80 infants who presented with mild laryngo-
malacia, 30% (n ⫽ 24) progressed to moderate disease over
a median of 61.5 (range, 17– 400) days, and 0.025% (n ⫽ 2)
infants progressed to severe at 45 and 54 days. Of the 83
infants who had moderate laryngomalacia, 27% (n ⫽ 23)
progressed to severe over a median of 55 (range, 7–210)
days. The median follow-up for all infants was 11.4
months (Table IV).
Medical comorbidities and disease severity.
Table V summarizes the medical comorbidities present at
time of diagnosis and comparisons between the disease
severity groups. When medical records were queried,
65.7% of the infants had a physician-recorded or -reported
medical diagnosis of GERD. The proportion of those with
GERD was higher in infants with moderate (93%) and
severe disease (84%) when compared with those with mild
disease (P ⬍ .001), but it was not different in those with
moderate compared with those with severe disease. Neu-
rologic disease was present in 13.9% of the infants and
was more commonly seen in those with severe disease
(34%) when compared with those with mild (8%, P ⬍ .001)
or moderate disease (11%, P ⫽ .004). Congenital heart
disease was present in 10.4% and was more commonly
seen in those with severe disease (34%) when compared
with those with mild (1%, P ⬍ .001) or moderate disease
(8%, P ⬍ .001). The proportion of those with a congenital
anomaly or genetic syndrome was highest in those with
severe disease (40%) when compared with those with
mild disease (3%, P ⬍ .001) or moderate disease (12%,
P ⫽ .001). Those with moderate laryngomalacia were
also more likely to have an anomaly when compared
with those with mild disease (P ⫽ .032). In those who
presented with mild (n ⫽ 2) or moderate disease (n ⫽
23) that progressed to severe disease requiring surgery,
60% had greater than two medical comorbidities
(Table V).
Symptom resolution. Of the 201 patients, 83.6%
had achieved complete resolution of all symptoms present
at the time of presentation, and an additional 13.4% had
achieved partial resolution. Six (3.0%) patients had not
yet achieved partial resolution of their symptoms at the
time of their last follow-up; five of these had severe dis-
ease at presentation. Calculations were made using the
Kaplan-Meier method to take into account varying dura-
tions of follow-up. Among the patients presenting with
coughing and choking symptoms, patients with mild or
moderate disease were more likely to achieve resolution
within 12 months of follow-up compared with patients
with severe disease (P ⬍ .001). The cumulative incidence
of resolution of stridor, regurgitation, or failure to thrive/
poor weight gain was not significantly different among the
three groups.

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7
 TABLE IV.
Symptoms of Congenital Laryngomalacia Present at Presentation and Diagnosis.
Total Mild Moderate Severe
Symptom (n ⫽ 201) (n ⫽ 80) (n ⫽ 83) (n ⫽ 38) P Value*

Chokes/coughs while eating (%) ⬍.001†

Yes 158 (80.2) 43 (55.1) 82 (100) 33 (89.2)
No 39 (19.8) 35 (44.9) 0 (0) 4 (10.8)
Unknown 4 2 1 1
Clinical regurgitation (%) ⬍.001‡
Yes 145 (73.2) 38 (47.5) 80 (97.6) 27 (75)
No 53 (26.8) 42 (52.5) 2 (2.4) 9 (25)
Unknown 3 0 1 2
Feeding difficulty (%) ⬍.001§
Yes 138 (71.5) 31 (39.7) 74 (93.7) 33 (91.7)
No 55 (28.5) 47 (60.3) 5 (6.3) 3 (8.3)
Unknown 8 2 4 2
Cyanotic spells (%) ⬍.001储
Yes 61 (30.5) 3 (3.8) 27 (32.9) 31 (81.6)
No 139 (69.5) 77 (96.3) 55 (67.1) 7 (18.4)
Unknown 1 0 1 0
Apnea (%) ⬍.001储
Yes 57 (28.5) 3 (3.8) 23 (28) 31 (81.6)
No 143 (71.5) 77 (96.3) 59 (72) 7 (18.4)
Unknown 1 0 1 0
Poor weight gain (%) ⬍.001储
Yes 53 (26.8) 2 (2.5) 18 (22) 33 (91.7)
No 145 (73.2) 78 (97.5) 64 (78) 3 (8.3)
Unknown 3 0 1 2
Pulmonary hypertension (%) ⬍.001¶
Yes 14 (7.1) 0 (0) 5 (6.1) 9 (24.3)
No 184 (92.9) 79 (100) 77 (93.9) 28 (75.7)
Unknown 3 1 1 1
Cor pulmonale (%) .005#
Yes 5 (2.5) 0 (0) 1 (1.2) 4 (10.8)
No 194 (97.5) 80 (100) 81 (98.8) 33 (89.2)
Unknown 2 0 1 1
*P value based on Fisher’s exact test for comparing nominal variables between groups.
†Proportion of patients with chokes/coughs while eating was significantly different between patients with mild versus moderate disease (P ⬍ .001), mild
versus severe disease (P ⬍ .001), and moderate versus severe disease (P ⬍ .01).
‡Proportion of patients with clinical regurgitation was significantly different between patients with mild versus moderate disease (P ⬍ .001), mild versus
severe disease (P ⬍ .01), and moderate versus severe disease (P ⬍ .001).
§Proportion of patients who were difficult to feed was significantly different between patients with mild versus moderate disease (P ⬍ .001) and mild versus
severe disease (P ⬍ .001) but not moderate versus severe disease (P ⫽ .70).
储Proportion of patients with each of these symptoms was significantly different between patients with mild versus moderate disease (P ⬍ .001), mild versus
severe disease (P ⬍ .001), and moderate versus severe disease (P ⬍ .001).
¶Proportion of patients with pulmonary hypertension was significantly different between patients with mild versus severe disease (P ⬍ .001) and moderate
versus vs. severe disease (P ⫽ .011) but not mild versus moderate disease (P ⫽ .06).
#Proportion of patients with cor pulmonale was significantly different between patients with mild versus severe disease (P ⫽ .009) and moderate versus
severe disease (P ⫽ .032) but not mild versus moderate disease (P ⫽ 1.00).

Medical and Surgical Interventions and
Their Outcomes
GERD and reflux treatment. GERD was tested for
in 169 patients, and 80% (n ⫽ 141) of those tested had a
positive test. This is higher than the 65.7% physician-
recorded diagnosis of GERD. Of the 141 patients with test
positive for GERD, 89.4% were diagnosed by contrast
esophagram with reflux, 42.6% by pH-metry, and 14.2%
by esophageal endoscopy with biopsy and histologic con-
firmation of GERD. Esophageal pH monitoring was posi-
tive in 100% of those tested. Contrast esophagram was
positive in 80%, and esophagoscopy with biopsy was pos-
itive in 48.8% of those tested by each modality.
Of the 201 patients, 157 (78.1%) received GERD
treatment on the basis of symptoms. All those who did not
receive therapy had mild disease. The median duration of
pharmacotherapy treatment was 7.3 months; longer
treatment courses were required in those with moderate

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8
 TABLE V.
Medical Comorbidities Present at Diagnosis of Congenital Laryngomalacia.
Total, Mild, Moderate, Severe,
Comorbidity n ⫽ 201 (%) n ⫽ 80 (%) n ⫽ 83 (%) n ⫽ 38 (%) P Value*

Gastroesophageal reflux disease 132 (65.7) 23 (29) 77 (93) 32 (84) ⬍.001†

Neurologic disease 28 (13.9) 6 (8) 9 (11) 13 (34) ⬍.001‡
Congenital heart disease 21 (10.4) 1 (1) 7 (8) 13 (34) ⬍.001§
Any cardiac surgery 5 (2.5) 1 (1) 1 (1) 3 (8)
Any genetic syndrome 27 (13.4) 2 (3) 10 (12) 15 (40) ⬍.001储
Down syndrome 7 (3.5) 0 (0) 4 (5) 3 (8)
Other 20 (10.0) 2 (2) 6 (7) 12 (32)
*P value based on Fisher’s exact test for comparing nominal variables between the groups.
†Proportion of patients with gastroesophageal reflux disease was significantly different between patients with mild versus moderate disease (P ⬍ .001) and
mild versus severe disease (P ⬍ .001) but not moderate versus severe disease (P ⫽ .19).
‡Proportion of patients with any neurologic disease was significantly different between patients with mild versus severe disease (P ⬍ .001) and moderate
versus severe disease (P ⫽ .004) but not mild versus moderate (P ⫽ .59).
§Proportion of patients with any cardiac disease (or specifically congenital cardiac disease) was significantly different between patients with mild versus
severe disease (P ⬍ .001) and moderate versus severe disease (P ⬍ .001) but not mild versus moderate (P ⫽ .064).
储Proportion of patients with any genetic syndrome was significantly different between patients with mild versus moderate disease (P ⫽ .032), mild versus
severe disease (P ⬍ .001), and moderate versus severe disease (P ⫽ .001).

disease (P ⫽ .025). Within 2 weeks of initiation of therapy,
parents perceived that coughing and choking symptoms
improved in 59.9%, and regurgitation symptoms improved
in 54.1%. This initial improvement was noted significantly
more often among patients with mild disease compared
with those with moderate or severe (P ⬍ .001). After 3
months of reflux therapy, parents perceived that coughing
and choking symptoms improved in 72.4% in all patients,
and regurgitation improved in 62.2% but was noted to be
significantly more improved in patients with mild disease
when compared with those with moderate and severe (P ⬍
.001) disease. After 6 months of therapy, parents per-
ceived that coughing and choking symptoms were im-
proved in 88.7% of patients, and regurgitation improved in
69.3% but was noted to be significantly more improved in
patients with mild and severe disease when compared
with those with moderate (P ⬍ .001) disease.
Surgical intervention. Thirty-one percent of the
infants required airway surgical intervention regardless
of disease severity at the time of the first evaluation by a
physician. Of those who presented with less severe dis-
ease, 2.5% with mild and 27.7% with moderate disease
went on to need surgical intervention. Of the patients with
severe disease, 97% required airway intervention. The
single patient with severe disease who did not have air-
way surgery had improvement in airway and feeding
symptoms after Nissen fundoplication and gastrostomy
tube placement. The most common indication for surgical
intervention regardless of status at initial presentation
was feeding difficulty with failure to thrive (82%) followed
by cyanosis (79%), apnea (77%), respiratory distress
(68%), and hypoxia (65%).
Of the 62 infants who required surgery, the primary
operation was a supraglottoplasty (92%) or tracheotomy
(8%), and the median age at the time of surgery was 4.5
months. Patient characteristics are summarized by the
type of primary surgery in Table VI. Five (8%) patients
had isolated laryngomalacia (all 5 presented with mild
disease). The majority had GERD, and nearly half had two
or more comorbidities.
The overall complication rate after supraglottoplasty
was low, with the more frequent complications being tran-
sient dysphagia (11%) and aspiration (14%). At the time of
last follow-up, in those who had a primary supraglotto-
plasty as the only surgical intervention, 81% had complete
resolution of stridor, 71% had complete resolution of cough
and choking symptoms, and 43% had resolution of regur-
gitation symptoms. Among the 57 patients who had a
supraglottoplasty as the initial surgical procedure, 11
(19%) patients required another procedure within a me-
dian of 39 (range, 5–242) days. Six had a second supra-
glottoplasty with success, two had a second supraglotto-
plasty followed by a tracheotomy, and three required a
tracheotomy. Of the five who ultimately required trache-
otomy, all had GERD and a neurologic diagnosis, and
three had a congenital anomaly or genetic disorder in
addition.
A total of 10 patients required a tracheotomy, 5 as the
initial procedure and 5 as a salvage procedure. All had
severe disease at the time of presentation and comorbidi-
ties of GERD and neurologic disease. Seven of the 10 had
a congenital anomaly or genetic disorder.
Retrospective review identified three deaths in this
patient group. One had a supraglottoplasty only, one had
a supraglottoplasty followed by tracheotomy, and one with
Down syndrome had a primary tracheotomy. All three had
congenital heart disease and died of nonrespiratory com-
plications. There were no deaths found in any patients
who presented with mild or moderate disease (Table VI).
DISCUSSION
Abnormal Sensorimotor Integration in Etiology
of Laryngomalacia
By demonstrating elevated LPST thresholds, this
study shows that the sensorimotor integrative function of
the larynx is altered, thereby providing a plausible expla-
nation for the weak laryngeal tone seen in infants with
laryngomalacia. The initial LPST threshold was higher in
infants with moderate and severe disease, indicating that

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9
 TABLE VI.
Summary of Patient and Surgical Characteristics by Type of Primary Operation for
Severe Laryngomalacia.
Total Supraglottoplasty Tracheotomy
(n ⫽ 62) (n ⫽ 57) (n ⫽ 5)

Mean age at time of surgery (days)

Mean (SD) 179.6 (203.8) 167.0 (162.8) 323.2 (483.9)
Median 128 136 114
IQR 78, 179 78, 179 89, 154
Range (9–1,187) (9–815) (72–1,187)
Patients with isolated laryngomalacia (%) 5 (8) 5 (9) 0
Patients with laryngomalacia and a 57 (92) 52 (91) 5 (100)
comorbidity* (%)
GERD (%) 53 (85) 48 (84) 5 (100)
Neurologic disease (%) 16 (26) 11 (19) 5 (100)
Cardiac disease (%) 19 (31) 18 (32) 1 (20)
Genetic disorder (%) 21 (34) 17 (30) 4 (80)
*Numbers exceed 100% because many patients had multiple comorbidities. Among the 57 patients who had
primary supraglottoplasty, 27 (47%) had comorbidities from two or more of categories. All five of patients who had
primary tracheotomy had comorbidities from two or more categories.
IQR ⫽ interquartile range, 25th and 75th percentiles; GERD ⫽ gastroesophageal reflux disease.

the degree of alteration sensorimotor integrative function
of the larynx predisposes the infant to more severe symp-
toms. These data indicate why there is a broad spectrum
of disease presentation. When compared with infants with
mild disease, those with moderate and severe disease also
had higher LPST thresholds over a longer time period,
implying that their laryngeal reflexes take longer to ma-
ture. These data indicate a broad spectrum of disease
presentation and provide a reason as to why infants with
more severe disease may have symptoms for a longer
period of time. This maturational effect is conceptually
similar to the report of reversal and resolution of
laryngomalacia-like symptoms and findings seen after re-
moval of CNS sedation in infants.50
Even though it took longer for the LPST thresholds to
decrease in those with moderate and severe disease, at
more than 9 months, all had similar LPST thresholds. The
decrease in LPST thresholds paralleled improvement and
resolution of the symptoms of the disease. This implies
that maturation of the reflexes occurs in all but at differ-
ent rates, which may play a role the severity and ulti-
mately the disease course of laryngomalacia symptoms.
The concept that sensorimotor alteration improves as
symptoms improve in infants with laryngomalacia is sim-
ilar to that in adults with acquired laryngomalacia after
CNS insult in whom the length of time to recovery is
dependent on the degree of the initial insult.51–54
Although this study does not determine the specific
cause or location of alteration of the sensorimotor integra-
tive function of the larynx in infants with laryngomalacia,
this study and the literature support the notion that sen-
sorimotor integrative function alterations occur at the
brainstem and the peripheral sensory afferent and mo-
tor efferent reflexes. By demonstrating elevated LPST
thresholds, this study indicates that peripheral afferent
function of laryngeal sensation is altered in infants with
laryngomalacia. LPST thresholds were higher in infants
with GERD compared with those without, providing the
most compelling explanation for altered laryngeal sensa-
tion. Although the association of GERD and laryngomala-
cia is well accepted, the mechanism of how GERD poten-
tiates the signs and symptoms of laryngomalacia has been
poorly understood. In combining the LPST data and what
is known about GERD effects on the larynx, a plausible
explanation is that acid exposure causes excessive local-
ized laryngeal tissue edema, particularly in the supra-
arytenoid mucosa and aryepiglottic fold regions. The ex-
cessive edematous tissue prolapses into the airway during
inspiration and leads to airway obstruction, a diagnostic
finding in laryngomalacia. Airway obstruction increases
negative intrathoracic pressure, which promotes more
acid reflux into the larynx, thereby creating a vicious cycle
of laryngeal tissue edema. Prolonged laryngeal acid expo-
sure causes altered sensation and a functional denerva-
tion of the larynx. The resultant functional denervation
blunts the afferent reflexes, thereby making it harder for
an infant to sense that secretions are present and thus to
initiate a swallow for clearance. The resultant pooling of
secretions further blocks the airway and leads to coughing
and choking symptoms and swallowing difficulty; these
are all symptoms seen in those with moderate and severe
laryngomalacia, in whom the incidence of GERD was high
in this study and others.11,14,18,27,31 The concept of an
anesthetic-like functional denervation of the larynx lead-
ing to a broader spectrum of symptoms and signs of laryn-
gomalacia is supported by previously published work that
demonstrated worsening stridor, airway edema, and ob-
struction after the application of lidocaine solution on the
larynx through a bronchoscope in infants with laryngoma-
lacia.74 That study also shows that lidocaine affected the
function and position of the arytenoids more than the
epiglottis. This is similar to our study in which the sensa-
tion at the aryepiglottic fold regions was altered, and the
degree of alteration correlated with disease severity.

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10
 The impact of reflux treatment or surgical interven-
tion on laryngeal sensation could not be statistically eval-
uated because of limitations of study design. Possibilities
are therefore offered. GERD treatment may improve la-
ryngeal sensation, as demonstrated by other investiga-
tors.71,72 However, even in the groups that received GERD
treatment, those with severe disease had longer periods of
elevated thresholds, further supporting a maturational
effect in addition to the possible role of acid on laryngeal
sensation and integration of the LAR. Likewise, surgical
removal of supraglottic edematous tissue may result in
improved laryngeal sensation by removal of the redun-
dant tissue that covers neurosensory receptors at the
aryepiglottic folds, thereby increasing the sensitivity of
the area to a stimulus and subsequently triggering the
LAR.
The central and efferent motor response of laryngeal
function may also be altered as a result of a peripheral
sensory afferent deficit. In laryngomalacia, functional de-
nervation of the larynx could lead to a down-graded neu-
ronal response of the sensory afferent information that is
sent to the brainstem. This ultimately causes dysfunction
of sensorimotor integration of the LAR at the brainstem
and efferent motor response. Peripheral sensory alter-
ation also effects central control of breathing and modu-
lation of central neural transmitters and their influences
on the efferent motor responses of airway patency75– 82
and may influence laryngeal tone and position of the su-
praglottic tissues, further potentiating airway obstruc-
tion. This concept is supported by the study of Thomson
and Turner,46 which demonstrated prolapse of supraglot-
tic structures and laryngeal obstruction that mimicked
laryngomalacia after vagal denervation.
There are additional findings in this study in support
of an alteration of sensorimotor integration of the LAR
and laryngeal function at the central and brainstem level.
Neurologic disease was more common in infants with se-
vere laryngomalacia. LPST thresholds were higher in in-
fants with comorbidities of neurologic disease and GERD
than in those with GERD only. In addition, those with
severe laryngomalacia had higher LPST thresholds than
did those with moderate disease despite having a similar
incidence of GERD and its potential affects on laryngeal
sensation. This suggests that those with neurologic dis-
ease have further compromise in the sensorimotor inte-
grative function that influences laryngeal tone than what
GERD alone would cause. Low Apgar scores were more
common in infants with severe disease. LPST thresholds
were higher in infants with low Apgar scores. Apgar
scores are a reflection of an underdeveloped CNS and
developmental delay. This important finding provides
more support of a central mechanism as part of the
etiology and contribution to the spectrum of disease
presentation.
One of the great enigmas about laryngomalacia is
why infants who do not have the symptoms of laryngoma-
lacia may have the same visual appearance of the larynx
as those with symptoms of laryngomalacia. Abnormal sen-
sorimotor integration in patients with laryngomalacia
demonstrates why the symptoms occur in some and not in
others.
Laryngoscope 117: June 2007 Supplement
Laryngomalacia: Demographics and
Disease Outcomes
This study provides the first full demographic de-
scription of congenital laryngomalacia. Similar to others,
this study shows that laryngomalacia is a disease more
commonly found in term infants11,83 and affects males
more than females.4,5,8,20,26,28,47,84 This study is compara-
ble, showing that neither gestational age nor birth
weight11,28,83 influence disease severity. This is the first
study that statistically evaluated racial demographics.
Laryngomalacia is more common and more severe in
white infants; however, the potential infant population
bias of the two institutions was not explored, and neither
could the rates of health care seeking between the races be
evaluated. The correlation of low postnatal Apgar scores,
stridor, and the development of compromised respiratory
function is recognized85 but until now has not been exam-
ined in infants with laryngomalacia. Both 1 and 5 minute
Apgar scores were lower in those with severe laryngoma-
lacia compared with mild and moderate disease, which
indicates and supports an underlying developmental de-
lay86,87 as an influential factor in the disease etiology and
severity.
Laryngomalacia is usually diagnosed within the first
4 months of life.4,11,19 The majority of the infants in this
study were diagnosed by 3.5 months of age, similar to the
reported overall literature; however, this study found
those with severe disease were diagnosed later, closer to 6
months of age. The specific factors that account for this
late diagnosis were not evaluated. On the basis of the
experience of the author and nonstatistical review of these
infants, several reasons for this are postulated. Many
infants with severe disease had complications from other
medical comorbidities that required treatment that was
prioritized over the airway issues, and the airway symp-
toms were observed until a significant complication of
airway obstruction or hypoxia occurred. Some were mis-
diagnosed with tracheomalacia and observed until other
complications occurred. Others were misdiagnosed and
treated for asthma, bronchiolitis, and reactive airway dis-
ease until a referral was made to the otolaryngologist.
Symptoms
In concordance with the existing literature, this
study shows that inspiratory stridor is the most common
symptom of laryngomalacia.1,9,88 Birth was the most com-
mon time of stridor onset, which is different from the 7 to
14 day onset reported in other studies with statistical
evaluation.4,11,19,89 This study found that 75% had stri-
dor at birth and 90% at 2 weeks of age, which is com-
parable with the nonstatistical descriptive reports in
the literature.40,45– 47,83,90 –93
This study likewise agrees that feeding problems are
the second most common symptom.4,11,19,89 The most com-
mon feeding symptoms of laryngomalacia were coughing,
choking, and regurgitation. Coughing and choking occur
in any condition of infant airway obstruction because of
the difficulty the infant has with coordinating the suck-
swallow breath sequence. Significant airway obstruction
causes air hunger during feeding, leading to aerophagia,
which causes gastric distension and stimulates gastric
Thompson: Laryngomalacia, a New Theory of Etiology
11
vagal reflexes that lead to postprandial vomiting and re-
gurgitation of gastric contents, also a common symptom in
those with moderate and severe laryngomalacia, particu-
larly in those with documented GERD.
Medical Comorbidities
The existing literature that examines the influence
of comorbidities on the symptoms of laryngomalacia is
mostly limited to series of infants with severe disease
and who required surgery, so overall comparisons are
difficult. GERD and neurologic diseases are the most
commonly reported comorbidities. Similar to other stud-
ies,11,14,18,27,31 GERD was the most common comorbidity
and was present in 70% of patients. The presence of GERD
should be considered in all patients with laryngomalacia.
There are two distinct reasons why GERD is more com-
mon in infants with laryngomalacia. First, airway ob-
struction generates large negative intrathoracic pressure
gradients from breathing against a fixed obstruction,
thereby promoting reflux of stomach contents into the
esophagus and upper airway.94 Second, the same central
and efferent vagal function that is responsible for laryn-
geal tone is responsible for lower esophageal sphincter
tone and esophageal motility.94 Alteration in central and
efferent vagal function as demonstrated by elevated LPST
thresholds likely has a negative effect on esophageal mo-
tility and lower esophageal tone, with the resultant out-
come of increased transient lower esophageal relaxation
events, reflux of acid, and poor motility of the esophagus
for clearance. Esophageal motility and lower esophageal
tone improve as vagal related reflexes mature, further
supporting a maturational influence on the signs and
symptoms of laryngomalacia. Contrast esophagram was
the most commonly used modality of diagnosis, showing
80% specificity, followed by pH-metry, which had 100%
sensitivity for GERD. This study suggests that contrast
esophagram is a good initial study when correlated with
clinical symptoms and examination. GERD treatment
should be initiated in all with laryngomalacia and any
feeding symptoms. There is a significant parental percep-
tion that symptoms improve with treatment, with most
noting worsening of the child’s behavior, symptoms, and
ease of feeding if reflux medication is forgotten or omitted.
Parental perception also suggest that GERD treatment
also shortens the time span in which an infant is afflicted
with the laryngomalacia symptoms compared with those
not treated, regardless of disease severity at presentation.
Determining efficacy of the dose and type of therapy was
not directly studied and would require a controlled, pro-
spective study. On the basis of the experience of the au-
thor and nonstatistical review of the infants presented in
this study, it is suggested that most GERD-related symp-
toms in infants with laryngomalacia are improved with
high-dose H2RA therapy (ranitidine 3 mg/kg, 3 times a
day). PPI therapy should be considered for refractory
symptoms and breakthrough symptoms and for those who
undergo surgical therapy for the immediate perioperative
and postoperative period until complete healing has oc-
curred. Those with refractory symptoms may benefit from
combined daytime PPI therapy and nighttime H2RA ther-
Laryngoscope 117: June 2007 Supplement
12
apy for suppression of breakthrough nighttime acid
events, as recommended in the adult reflux literature.95,96
Neurologic disease is a well-acknowledged comorbid-
ity in laryngomalacia. The high association of the two is
the primary reason why neurologic dysfunction had been
implicated in disease etiology. This study found that neu-
rologic disease, although more common in those with se-
vere disease, was present in all degrees of severity. The
34% incidence of neurologic disorders in infants who re-
quired surgery in this study is similar to the higher inci-
dence reports in the literature.20,84 Nearly all with a neu-
rologic disease also had GERD. Those with neurologic
disease likely have poor esophageal motility that can fur-
ther facilitate retrograde reflux. The same vagal efferent
response that is responsible for laryngeal tone is also
responsible for the vagal efferent function of esophageal
motility, so the two are likely interrelated and contribute
to the findings in laryngomalacia and may partially ex-
plain why those with neurologic disease and GERD have
more severe disease.
The presence of genetic disorders and cardiac disease
has been under-explored in the existing laryngomalacia
literature. They were infrequent in infants with mild dis-
ease and moderate disease, but, when present, these in-
fants appear to progress in their symptoms to develop
moderate or severe disease. These comorbidities were
more common in those with severe disease who required
surgical intervention. The 40% incidence of congenital
anomalies and genetic disorders found in surgical patients
in this study is higher than the reported literature.4,30,97
Similar to the report of Denoyelle et al.,30 this study found
that medical comorbidities negatively influenced supra-
glottoplasty outcomes. This study found a higher rate of
supraglottoplasty failures and tracheotomy placement
and incomplete resolution of symptoms in those with med-
ical comorbidities compared with those with isolated la-
ryngomalacia. In summary, the presence of medical co-
morbidities does correlate with disease severity and are
found more commonly in those with moderate and severe
disease, and their presence influences the degree and pro-
gression of symptoms. Comorbidity should prompt careful
consideration of treatment recommendations but not pre-
clude consideration of supraglottoplasty as the first opera-
tion for severe disease. Those with multiple comorbidities
have worse outcomes, particularly after supraglottoplasty,
and have a higher chance of needing a tracheotomy.
Surgical Intervention for
Severe Laryngomalacia
Similar to other series in the literature, this study
shows that supraglottoplasty is a successful operation
with a low complication rate and that tracheotomy is
generally reserved for those with multiple comorbidi-
ties.30 A higher percentage of patients with laryngoma-
lacia needed surgery in this study compared with oth-
ers.10,14,18 –20 Influencing factors of this inclination could
be the referral patterns to the two tertiary care facilities in
which these patients were seen. Another factor to consider
is that during the course of the study, the author and
associates recognized the benefit of surgery on feeding
problems. There were no long-term surgical complications
Thompson: Laryngomalacia, a New Theory of Etiology
of supraglottoplasty in this series. Supraglottic stenosis,
although rare, is the most commonly reported severe or
long-term complication. There were none in this study,
likely because of aggressive GERD treatment in the peri-
operative and postoperative period. Of those who under-
went supraglottoplasty as the initial procedure, 19% re-
quired a second procedure. Fifty-five percent had successful
outcomes from a revision supraglottoplasty, and 45% ulti-
mately required a tracheotomy, all of whom had multiple
medical comorbidities (⬎3), as previously discussed.
Characteristics of Mild Laryngomalacia
Eighty percent of infants with mild disease had in-
spiratory stridor present at birth, and nearly all developed
stridor by 2 weeks of life. Most infants had inconsequen-
tial stridor without complications or progression of symp-
toms because less than 8% have a nonreflux-related med-
ical comorbidity. Up to half of the patients developed a
feeding symptom and had GERD, in whom reflux medica-
tions were beneficial in improving the symptoms of cough-
ing, choking, and regurgitation. Infants who presented
with mild laryngomalacia and had more than two medical
comorbidities had progression of their symptoms to mod-
erate or severe disease. On the basis of projected statistics,
those with mild disease will likely have resolution of all
related symptoms by 12 months of age. Experimental ev-
idence shows that the initial LPST was lower in those with
mild disease. These infants have fewer factors that influ-
ence stimulation thresholds. They had a lower incidence of
GERD, and few had neurologic comorbidities. Therefore, if
LPST is a measure of laryngeal tone and integrative func-
tion, this suggests that it is minimally altered in those with
mild disease, which may limit the degree of airway obstruc-
tion and obstructive symptoms and their consequences.
Characteristics of Moderate Laryngomalacia
Sixty-six percent of infants with moderate disease
had stridor onset at birth, but more had stridor onset after
birth and after the 3 weeks of life when compared with
those with mild or severe disease. This finding suggests
that feeding problems, regurgitation, and resultant GERD
and LPR impact symptom exacerbation and disease pro-
gression. Those with moderate disease had the highest
percentage of feeding symptoms, particularly regurgita-
tion. In addition, they were as difficult to feed as those
were with severe disease. GERD was as common as in
those with moderate and severe disease. Symptoms of
coughing and choking improved with GERD treatment,
and those with moderate disease required longer treat-
ment courses than those with mild or severe disease. The
perception of regurgitation symptoms improved with
GERD therapy but less so when compared with those with
similar symptoms and mild or severe disease. Multimo-
dality treatment reflux therapy may be required more in
those with moderate disease and refractory symptoms. On
the basis of projected statistics, those with moderate dis-
ease will likely have resolution of all related symptoms by
12 months of age. Because most infants with moderate
disease were treated for GERD, it is unknown whether
these infants would have experienced longer durations of
Laryngoscope 117: June 2007 Supplement
symptoms compared with those with mild disease had
they not been treated.
Up to 28% of infants required surgical intervention,
most commonly for consequences of feeding problems.
Half of these patients had GERD and an additional med-
ical comorbidity. Surgery was successful in this group,
with no complications or need for a second procedure or
tracheotomy. Because such a high percentage of those
with moderate disease went on to have surgical interven-
tion, the next question is, should supraglottoplasty be
performed more frequently for those who are difficult to
feed but do not have life-threatening symptoms, thereby
intervening before feeding difficulty leads to failure to
thrive? Prospective studies comparing those with moder-
ate disease and feeding difficulty who receive GERD treat-
ment or surgical therapy may show early benefits of sur-
gical therapy in relieving airway obstruction, thereby
improving GERD. Quality of life may be enhanced, and
parental anxiety may diminish.
The experimental data in this study showed elevated
LPST thresholds when compared with those with mild
disease. This suggests that GERD and LPR lead to a
functional denervation of the larynx that influences laryn-
geal tone and integrative function. It is likely that GERD
and LPR cause more feeding problems and swallowing
problems because of difficulty in clearing secretions,
which then creates a vicious cycle of laryngeal edema,
prolapse, and worsening airway obstruction. It may be
that those with under-treated or inadequately treated
GERD who have no other medical comorbidities are the
infants who go on to be at higher risk for needing surgical
intervention.
Characteristics of Severe Laryngomalacia
Eighty-four percent of the infants with severe disease
had stridor onset at birth, and nearly all developed stridor
by 2 weeks of life. This group had earlier onset of stridor
when compared with those with moderate disease, sug-
gesting the influence of an additional CNS component
that impacts symptom presentation and disease progres-
sion. This group had a higher incidence of neurologic dis-
ease and lower Apgar scores, suggesting developmental
delay compared with those with mild or moderate disease.
Infants with severe disease were more likely to have all
four comorbidities evaluated in this study. This higher
incidence of medical comorbidities may lead to disease
exacerbation or worsening of the degree of symptoms.
Although the infants sought medical care around the
same time as those with mild and moderate disease, most
were not diagnosed until 6 months of age, suggesting that
the symptoms that were mistaken for other conditions
such as reactive airway disease or that treatment of the
other comorbidities took precedence.
Most infants benefited and had symptom resolution
after supraglottoplasty. Complications are rare. GERD
treatment in addition to surgery resulted in improvement
and resolution of most feeding problems. Those with re-
sidual feeding problems had refractory GERD and were
still on medication at the time of last follow-up or required
Nissen fundoplication. Those who required a tracheotomy
as a primary or secondary operation were sicker and had
Thompson: Laryngomalacia, a New Theory of Etiology
13
more comorbidities (⬎3), in particular, neurologic disease
and genetic disorders. Those who died had severe disease
and cardiac disease, and all died from complications re-
lated to the underlying congenital heart disease and not
laryngomalacia.
The experimental data in this study showed elevated
LPST thresholds when compared with those with mild
and moderate disease. GERD was prevalent in those with
severe disease. GERD and LPR likely create the same
effect on laryngeal tone and obstruction, as seen in those
with moderate disease, but when combined with a poten-
tial delay in CNS function, as demonstrated by lower
Apgar scores and higher percentages of neurologic dis-
ease, these infants had worse symptoms that required
intervention. These may be the same reasons why those
with severe disease had higher initial LPST thresholds
than did those with mild and moderate disease.
CONCLUSION
The sensorimotor integrative function and tone of the
larynx is altered in infants with laryngomalacia. Changes
in the peripheral afferent sensory function of the larynx
combined with some underlying delay at the CNS level
may be what predispose an infant to laryngomalacia com-
pared with nondiseased infants. This may explain why
both nondiseased and infants with laryngomalacia may
have the same visual appearance of the larynx but with
different clinical outcomes. In combining the experimental
data from LPST testing and the clinical findings, this
study provides a logical explanation of the relationship of
alteration in the peripheral reflexes and CNS sensorimo-
tor integration and the causation of the signs and symp-
toms and clinical examination findings of congenital la-
ryngomalacia and supports the concept of a new theory of
etiology: abnormal sensorimotor integrative function of
the larynx. The magnitude and duration of alteration is
greater in those with more severe forms of the disease
combined with the additional presence of medical comor-
bidities, particularly low Apgar scores, GERD, or neuro-
logic disease, and this explains why there is such a vari-
ation in the disease spectrum. With maturation of
laryngeal reflexes and the CNS, the symptoms of laryngo-
malacia resolve. Those without medical comorbidities
have resolution of their symptoms without complications
or consequences, whereas those with medical comorbidi-
ties have more symptoms, a more difficult clinical course,
and may develop complications of airway obstruction.
GERD with LPR is probably the most potentiating factor
that influences the symptoms of laryngomalacia, whereas
other medical comorbidities influence the overall severity.
Acknowledgments
The author thanks the following people and organi-
zations: the Triological Society for funding of this project
through the 1999 Research Training Award; Dr. Michael
Rutter for assistance with patient follow-up and data col-
lection; Marsha Foote, RN, BSN, for patient education and
data collection at Cincinnati Children’s Hospital; Wendy
Kochevar, MSN, CNS, PNP, for patient education at Mayo
Clinic; Drs. Robin Cotton, Charles Myer, Paul Willging,
Laryngoscope 117: June 2007 Supplement
14
Sally Shott, and Glen Bratcher for patient referrals at
Cincinnati Children’s Hospital; Amy Weaver, MS, for bio-
statics assistance at Mayo Clinic; Jamie Bartel at Mayo
Clinic for her work in preparing the paper; and Dr. Kerry
Olsen and Dr. Robin Cotton for years of mentorship and
endorsement of this thesis.
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yngol Head Neck Surg 2001;127:694 – 699.
85. Issel EP, Eggers H, Plath C, et al. The apgar value of the
newborn and its prognostic value for the course of the
neonatal period. Zentralbl Gynakol 1976;98:1618 –1625.
86. Nelson KB, Ellenberg JH. Apgar scores as predictors of
chronic neurologic disability. Pediatrics 1981;68:36 – 44.
87. Kamper J, Moller J. Long-term prognosis of infants with
idiopathic respiratory distress syndrome. Follow-up stud-
ies in infants surviving after the introduction of continuous
positive airway pressure. Acta Paediatr Scand 1979;68:
149 –154.
88. Zeitouni A, Manoukian J. Epiglottoplasty in the treatment of
laryngomalacia. J Otolaryngol 1993;22:29 –33.
89. Smith GJ, Cooper DM. Laryngomalacia and inspiratory ob-
struction in later childhood. Arch Dis Child 1981;56:
345–349.
90. Lees D. larynx from an infant with a peculiar form of ob-
structed respiration. Trans Pathol Soc Lond 1883;34:19.
91. Variot G. Un cas de respiration stridoreuse des nouveau-nes
avec autopsie. Soc Med Hop 1898;27:490 – 495.
92. Iglauer S. Epiglottidectomy for the relief of congenital laryn-
geal stridor. Laryngoscope 1922;32:56 –59.
93. Hasslinger F. Diagnostik and therapie des stridor congeni-
tus. Z Hals Nasen Ohrenheilkd 1928;21:223–35.
94. Rudolph CD, Mazur LJ, Liptak GS, et al. Guidelines for
evaluation and treatment of gastroesophageal reflux in
infants and children: recommendations of the North Amer-
ican Society for Pediatric Gastroenterology and Nutrition
[see comment]. J Pediatr Gastroenterol Nutr 2001;32:
S1–S31.
95. Khoury RM, Katz PO, Hammod R, Castell DO. Bedtime ra-
nitidine does not eliminate the need for a second daily dose
of omeprazole to suppress nocturnal gastric pH. Aliment
Pharmacol Ther 1999;13:675– 678.
96. Peghini PL, Katz PO, Castell DO. Ranitidine controls noctur-
nal gastric acid breakthrough on omeprazole: a controlled
study in normal subjects. Gastroenterology 1998;115:
1335–1339.
97. Masters IB, Chang AB, Patterson L, et al. Series of laryngo-
malacia, tracheomalacia, and bronchomalacia disorders
and their associations with other conditions in children.
Pediatr Pulmonol 2002;34:189 –195.
Laryngoscope 117: June 2007 Supplement
16
APPENDIX I
The goals of Appendix I are to
● Provide a historic overview of congenital
laryngomalacia
● Provide a thorough review of the published
literature
● Provide demographic description
● Provide signs, symptoms, and complications
● Discuss GERD and laryngomalacia
● Discuss comorbidities and their influence on dis-
ease severity
● Discuss evolution of diagnosis and management
● Discuss evolution of surgical management for
severe laryngomalacia and outcomes of surgical
intervention
● Discuss the proposed theories of etiology and re-
view of the literature that supports a new theory of
etiology: abnormal sensorimotor integrative func-
tion of the larynx
Historic Evolution of the Terminology of
“Laryngomalacia”
The term laryngomalacia was first coined in 1942 by
Jackson and Jackson.A1 The first description of congenital
stridor that is historically consistent with laryngomalacia
is found in an 1853 French textbook of pediatrics by
Barthez and Rilliet.A2 They describe an infant with in-
spiratory stridor at birth made worse by agitation and
that resolved at age 10 months. These physicians sur-
mised that the symptoms were caused by compression of
the larynx from either the thymus or thyroid gland. In
1883, LeesA3 was the first to report the “peculiar” shape of
the larynx in a child with obstructed respiration. In 1897,
Sutherland and LackA4 were the first to describe supra-
glottic collapse in infants with inspiratory stridor by ex-
amining the larynges of 18 infants. They called the condi-
tion “congenital laryngeal stridor,” failing to recognize the
multiple other causes of stridor in infants. In a similar
description of infants with inspiratory stridor and laryn-
geal collapse, Thomson and TurnerA5 only added to the
confusion by calling the condition “congenital stridor of
infants.” Jackson and Jackson’s stated that the term of
“laryngomalacia” was derived from the Greek word mala-
cia, which translates to a morbid softening of an organ,
the larynx. This has remained the most commonly used
and uniformly accepted term for this condition because of
its descriptive quality and differentiation from other
causes of congenital stridor. “Exaggerated infantile lar-
ynx,”A6 “inspiratory laryngeal collapse,”A7 and “hyper-
spoudastric stridor”A8 are other poorly accepted contem-
porary descriptive terms.
Incidence of Laryngomalacia
Congenital laryngomalacia is the most frequent cause
of stridor in infants and children and the most common
congenital laryngeal anomaly. Large series of infants and
children with congenital laryngeal anomalies cite a 45% to
75% reported incidence of laryngomalacia.A6,A9 –A13
Thompson: Laryngomalacia, a New Theory of Etiology
Demographics
A complete demographic description of infants with
congenital laryngomalacia does not exist. Demographic
characteristics are gleaned from case reports and series.
There is a reported male predominance,A9,A11,A14 –A19 with
an averaged reported 1.6 to 1 male to female ratio. The
importance of this is not known and likely insignificant.
Congenital laryngomalacia is thought to occur in
term or near term birth infants. Most descriptions of ges-
tational age are vague and suggest that this is not a
disease of prematurity but occasionally afflicts the prema-
ture infant.A20 Only one study evaluated gestational age,
reporting a mean age of 38.6 weeks in 79% of the infants
in their cohort of 33 infants. Twenty-one percent of the
infants in this cohort were premature, but the mean ges-
tational age was not reported. In this study, prematurity
was not associated with laryngomalacia, but the trend
presented suggests that if a larger patient population
were studied, there may have been a statistically signifi-
cant association of prematurity and disease severity.A21
The only two studies of gestational age are also the only
studies that evaluate birth weight in infants with laryn-
gomalacia. McSwiney et al.A20 reported a mean birth
weight of 3.4 kg in the 21 infants in their series. Giannoni
et al.A21 reported a mean birth weight of 5.48 lb (2.5 kg).
Similar to gestational age, these authors did not find birth
weight to correlate with disease severity. The 1953 report
of ApleyA14 showed that infants with congenital stridor
had a significantly higher birth weight when compared
with nonstridulous infants. His series did not report a
mean birth weight, and neither did it separate those with
laryngomalacia from those with other causes of congenital
stridor.
The current literature lacks any comment or report of
Apgar scores in children with laryngomalacia. Reports that
evaluate the method of delivery are brief, vague, and descrip-
tive and show no specific trends or significance.A14,A20 Al-
though there are many reports that describe the age at
onset of symptoms of laryngomalacia, only a few reports
determine the mean age at diagnosis of the condition.
Three available series that have statistically evaluated
this show a mean age at the time of diagnosis of 3.8
months,A15 3.2 months,A21 and 2.5 months.A22 There are
no reports that determine the mean age at which a parent
seeks care for the condition, and therefore the time be-
tween the initial presentation to a health care provider
and diagnosis is also unknown.
Signs, Symptoms, Diagnosis, and Complications
of Laryngomalacia
Clinical presentation of laryngomalacia. The
classic textbook presentation of laryngomalacia is inter-
mittent inspiratory stridor that worsens with feeding, ex-
citement, agitation, crying, or positioning in the supine
position. The intensity, pitch, and character vary with the
degree of obstruction.A7 Inspiratory stridor is often
present at birthA7 or within the perinatal period; however,
it may be delayed by several months.A20 Symptoms peak
at 6 to 8 months and usually resolve by 18 to 24
months;A10 however, they may persist for years.A20,A23 The
Laryngoscope 117: June 2007 Supplement
documentation of this well-established presentation of la-
ryngomalacia has evolved over the past 165 years. The
best early documentation of the typical symptoms of la-
ryngomalacia is found in the 1897 report of Sutherland
and Lack,A4 in which they describe 18 patients who had
the condition at birth, associated with intermittent in-
spiratory stridor that worsened with positional changes
and activity. Their initial description has been supported
by many authors since.A1,A9,A24 As physicians became
more aware of the condition, reports reflected a better
understanding of the broad spectrum of disease presenta-
tion, its sequela, and the complications that can occur as a
result of hypoxia and chronic airway obstruction.
Stridor is by far the most common symptom of laryn-
gomalacia. Anything that increases respiration, including
crying, nursing, agitation, excitement, activity, or strug-
gling, also makes the stridor worse.A6,A7,A25,A26 Stridor is
increased by supination and head flexion and decreased
by pronation and head extension.A6,A25–A27 Sleep is vari-
ably affected by laryngomalacia, with the observation of a
decrease with quiet respiration and prone positioning and
an increase with a supine position.A6,A20 Upper respira-
tory tract infections exacerbate the existing symptoms of
laryngomalacia and may prove fatal. This association was
noted as early as in the 1883 report of Lees.A3 The stridor
of laryngomalacia has also been described as precipitated
by an upper respiratory tract infectionA14 in an infant who
had no prior history of stridor. Social factors such as
exposure to second hand smoke also worsen stridor.A21
Early reports are descriptive and note that stridor
is present at birth or within a few days of
birth.A3–A5,A7,A14,A25,A28,A29 Later reports show that the
other common time of onset is 2 weeks of age and that
the majority of infants afflicted have stridor by 4
months of age.A6,A20,A23 More recent series with statis-
tical evaluation report means of 2.2 weeks,A15 14
days,A23 11.82 days,A21 and 7 days.A22 Giannoni et al.A21
found that age of onset of symptoms was not influenced
by gradations of GERD-associated laryngomalacia or
disease severity.
Without intervention, most reports agree that the
natural course history is for stridor to worsen during the
first 8 months of life, reach a plateau between 9 to 12
months, and then spontaneously begin to resolve, with
most children being symptom free by 2 years of
age.A4,A6,A9,A10,A26 The length of time until resolution,
however, is variable, with reports of stridor resolution
given to be as short as 2 to 3 monthsA27 and other reports
of persistent stridor showing resolution from 4 to 12 years
of age.A20,A23 Infants with persistent stridor tend to have
other medical comorbidities, most commonly neurologic
disease.A20
Diagnosis of laryngomalacia. Although the symp-
toms of laryngomalacia fascinated physicians of the mid
19th century, LeesA3 was the first to describe laryngeal
examination findings in his 1883 presentation to the Lon-
don Pathological Society. He performed a laryngoscopic
examination on an infant with “a peculiar form of ob-
structed inspiration,” demonstrating the classic findings
Thompson: Laryngomalacia, a New Theory of Etiology
17
we know today as congenital laryngomalacia. As he
described,
“The upper aperture of the larynx was in the form of a
narrow median slit, extending from above downwards,
the epiglottis being folded on itself, so that the posterior
surfaces of its lateral halves were almost in contact, and
the aryepiglottic folds close together and almost over-
lapping.”
This infant died a month after the laryngoscopic ex-
amination from complications of diphtheria. Lees con-
firmed his clinical findings at the time of the postmortem
examination. From this examination, he was able to cre-
ate a remarkably accurate woodcut replication of the lar-
ynx, which is the first published visual representation of
the laryngeal findings of congenital laryngomalacia and
remained the only published visual for physicians to refer
to for many years.A3 Improvement in methods, equipment,
and skill in direct laryngoscopy facilitated examination,
description, and publication of the characteristics of the
collapsing supraglottic tissues of the condition.A1,A7,A25
The 1944 report of SchwartzA7 is the first with serial
photographs demonstrating the collapse observed
laryngoscopically.
Although the diagnosis of laryngomalacia is sug-
gested by its typical history, it is confirmed by direct
examination of the larynx because other conditions may
mimic its clinical presentation. Introduction of flexible
laryngoscopy has revolutionized the ability to examine
the larynx of an infant in an awake, dynamic state.
Flexible laryngoscopy has allowed for precise descriptions
of the variants in the laryngeal anatomy. The distinct
clinical appearance includes six abnormalities that may
be seen either alone or in combination. These include 1) a
long, tubular, omega-shaped epiglottis that curls on itself;
2) prolapse of the cuneiform cartilages; 3) prolapse of the
arytenoid cartilages; 4) an epiglottis that falls forward,
obstructing the airway; 5) shortened aryepiglottic folds; or
an 6) overly acute angle of the epiglottis at the laryngeal
inlet. These abnormalities result in airway occlusion and
thus the characteristic inspiratory stridor that is often
described.A30 –A33 Several reports agree that there are
three predominant types of supraglottic collapse involving
a combination of the above-mentioned sites. Posterior-
lateral involvement includes arytenoid prolapse and in-
folding of the aryepiglottic folds. This presentation most
commonly has an associated “omega epiglottis.” Posterior
involvement includes prolapse of the arytenoid cartilage,
cuneiform cartilage, the supra-arytenoid mucosa, or a
combination of all three. Anterior involvement is posterior
displacement of the epiglottis.A15,A34 –A36 Correlation of the
anatomic features along with the associated stridor con-
firms the diagnosis. It is these anatomic orientations that
provide for the mechanism for the sound of stridor. These
anatomic considerations are also the elements that form
the basis of the anatomic theory of the disease etiology.
The underlying etiologic factors that give rise to the po-
sitioning of the supraglottic tissue and its collapse into
the glottic airway are unknown and poorly understood
and are thereby challenges to the anatomic theory of
disease etiology.
Laryngoscope 117: June 2007 Supplement
18
Sequela and complications of laryngomalacia.
Multiple reports recognize the link between upper air-
way obstruction from laryngomalacia and its sequela,
with these leading to a broader spectrum of disease
severity, symptom presentation, and complications. Most
reported sequela and complications are respiratory.
ApneaA22,A31,A37–A45 and cyanosisA31,A44,A46 –A48 are well-
described complications in those with severe airway ob-
struction from laryngomalacia. Severe upper airway ob-
struction may lead to use of accessory muscles of
respiration including the intercostal and abdominal
musclesA3,A4 with xiphoid retractions and can in some
cases lead to pectus excavatum. Pectus excavatum was
described as early as 1897 in the report of Sutherland and
Lack.A4 IglauerA25 reported performing an epiglottidec-
tomy for the relief of congenital laryngeal stridor in an
infant with a clinical description that matches pectus ex-
cavatum. Holinger and JohnsonA49 and AtkinsA50 pub-
lished reports on the correlation between chronic upper
airway obstruction and pectus in children with laryngeal
anomalies, some of whom had laryngomalacia. In 1984,
Lane et al.A51 were the first to publish information on the
reversal of pectus excavatum and cor pulmonale in a child
with severe laryngomalacia in whom they performed a
supraglottoplasty. Since this publication, the presence of
pectus or cor pulmonale has become an accepted criterion
for surgical intervention.A19,A31,A33,A42 Cor pulmonale can
develop by two different mechanisms. Chronic hypoxia
can lead to polycythemia and increased blood volume and
viscosity. Chronic hypercapnia can lead to increased pul-
monary artery vascular resistance, which is known as
pulmonary hypertension. If not recognized, cor pulmonale
may prove fatal.A31,A52 McSwiney et al.A20 were the first to
report the increased risk of aspiration in children with
laryngomalacia, particularly when the stridor is aggra-
vated by an upper respiratory tract infection. Polonovski
et al.A17 verified this association in their report of four
patients with pulmonary infections and upper respiratory
tract infections who eventually required aryepiglottic fold
excision for treatment. The etiology of aspiration is not
described in these reports but is likely related to the in-
creased work of breathing and airway obstruction that leads
to a discoordinate suck-swallow breath sequence, thus alter-
ing airway protection and resultant aspiration.A51
Feeding difficulty is another sequela of chronic air-
way obstruction and tachypnea in some infants with la-
ryngomalacia. Feeding difficulty is the second most com-
monly reported symptom of laryngomalacia.A12,A35,A42
Signs of a feeding disorder in laryngomalacia include dys-
phagia, aspiration, lack of oral continence, impaired oral
motor skills, oxygen desaturation with feeding, and slow
or laborious feeding.A14,A53 Feeding difficulty can lead to
poor nutritional status and weight loss and postprandial
vomiting because infants are unable to nurse or feed
comfortably.A7,A20,A35,A49,A51,A54 It can be so severe that it
leads to failure to thrive, another commonly accepted cri-
terion for surgical intervention.A16,A31,A32,A36,A38,A42–A45
Even though feeding difficulty and dysphagia are
well-recognized symptoms of laryngomalacia, very little is
reported about the pathophysiology. The etiology of feed-
ing problems is likely multifactorial. The correlation of
Thompson: Laryngomalacia, a New Theory of Etiology
laryngomalacia and airway obstruction causing an incoor-
dinated suck-swallow breath sequence and feeding diffi-
culty with inability to breast feed is well illustrated in the
case report of Glass and Wolf.A54 There are several indirect
associations and reports of infants with laryngomalacia,
GERD, and feeding disorders, but the cause and effect
relationships have not been described or substantiated in
the literature.A32,A55–A60 There are other reports of infants
with laryngomalacia and neuromuscular disease,A38,A61
with a postulated pathophysiologic mechanism of neuro-
muscular weakness of the muscles of swallowing and air-
way patency. Feeding difficulty has also been described in
children with laryngomalacia or “laryngeal stridor” and
brainstem dysfunction,A62,A63 with a postulated mecha-
nism of compression of the medulla at the level of the
nucleus tractus solitarius and nucleus ambiguus, the nu-
clei for swallowing and respiration. Reported outcomes of
feeding problems are only known in those with failure to
thrive who require surgical intervention. Feeding diffi-
culty improves and usually resolves after surgical inter-
vention, in most cases, with the highest reported resolu-
tion of 77%.A16,A17,A19,A35,A46 Those who have co-existing
neurologic disease are more likely to have persistent feed-
ing problems.A16
Symptoms of regurgitation during feeding in infants
with laryngomalacia include recurrent emesis, postpran-
dial vomiting, coughing, and choking. The pathophysiol-
ogy of regurgitation during feeding and its resultant con-
sequence of vomiting, coughing, and choking in relation to
laryngomalacia are not well described. However, in any
condition of airway obstruction, air hunger during feeding
can lead to aerophagia. Aerophagia causes gastric disten-
sion and stimulates gastric vagal reflexes that lead to
postprandial vomiting of gastric contents. When the gas-
tric contents enter the hypopharynx and laryngeal inlet, a
reflexive cough follows to protect from aspiration into the
tracheobronchial tree.
Medical comorbidities. Laryngomalacia affects
the full spectrum of infants from premature and term
infants, to healthy infants, to those with medical comor-
bidities. GERD, the most commonly associated medical
comorbidity, will be reviewed in the next section of this
thesis appendix. Neurologic disease is the second most
commonly reported medical comorbidity, with an inci-
dence of 8% to 50%.A14,A15,A18,A19,A36,A38,A43,A45,A64 Neuro-
logic conditions include hypotonia, developmental delay,
cerebral palsy, mental retardation, microcephaly, and
quadriparesis.A14,A15,A19,A38,A61 The precise relationship of
co-existing neurologic conditions and laryngomalacia is
poorly understood. However, it is this high incidence that
suggests a cause and effect relation between the two that
is the primary reason neurologic dysfunction is a proposed
theory of disease etiology. The literature contains insuffi-
cient convincing experimental evidence to support this
hypothesis.
Congenital anomalies and genetic disorders occur in
infants with laryngomalacia, with an estimated incidence
of 8% to 20%.A15,A65 Down syndrome appears to be the
most commonly reported associated genetic disorder.
Laryngomalacia publications mention a few isolated
cases of Down syndrome, usually one to two in each
Laryngoscope 117: June 2007 Supplement
series.A14,A15,A19,A43,A44 However, review of the Down syn-
drome literature shows that up to 50% of those who have
respiratory symptoms have laryngomalacia, and it is the
most common airway anomaly seen during endoscopy of
these children.A66 –A68
Micrognathia and its two commonly associated ge-
netic disorders, CHARGE association (choanal atresia,
posterior coloboma, heart defect, choanal atresia, retarda-
tion, genital, and ear anomalies) and Pierre Robin Se-
quence, also randomly appear in the laryngomalacia lit-
erature, with incidence as high as 13% in one surgical
series.A45 The cumulative laryngomalacia literature men-
tions only a few cases with associated micrognathia, so the
incidence of these genetic disorders in infants with laryngo-
malacia is difficult to discern.A7,A14,A15,A65,A69,A70 Other syn-
dromes associated with laryngomalacia in which more
than one report appear in the literature include di
George syndrome,A69,A71 Larsen syndrome,A72–A75 and
arthrogryposis.A65,A76
Congential heart disease can coexist withA14,A21 and
can exacerbate cyanosis, apnea, and stridor symptoms of
laryngomalacia. Cardiovascular disease is a reported co-
morbidity in 31% of infants with laryngomalacia in the
series of Reddy and Matt;A18 however, the specific type of
disease is not delineated. Masters et al.A65 report a 13.7%
incidence of congenital heart disease in their series of
infants with malactic airway disorders; however, the
specific incidence of those with laryngomalacia was not
differentiated from those with tracheomalacia or
bronchomalacia.
Outside of clinical presentation, no studies to date
establish whether medical comorbidities correlate with
disease severity irrespective of the symptoms at presen-
tation. Most of what is known about the influence of co-
morbidities is limited to the surgical literature and is
reviewed in a surgical outcomes section of this thesis
appendix. Very little is known about the influence of med-
ical comorbidities and disease outcomes in those with less
severe disease. Twenty percent of the 58 infants in the
study of Olney et al.A15 had severe neurologic compromise
or multiple congenital anomalies. They found that those
with congenital anomalies had longer durations of symp-
toms and a longer time to symptom resolution compared
with those with isolated laryngomalacia. This finding is
difficult to interpret because the time frame to resolution
was not statistically different between those with isolated
disease and those with a medical comorbidity, and neither
did this study evaluate the potential impact of GERD
treatment or surgical therapy on symptom duration and
resolution. Most surgical series suggest that comorbidities
negatively influence supraglottoplasty success, and symp-
tom resolution occurs less frequently, particularly in those
with underlying neurologic disease.A17,A36,A45
Gastroesophageal Reflux Disease,
Laryngopharyngeal Reflux,
and Laryngomalacia
Gastroesophageal reflux is a common physiologic
occurrence in neonates and infants. The classic symp-
toms of pathologic GERD are emesis, dysphagia, belch-
ing, choking, gagging, and failure to thriveA77 and are
Thompson: Laryngomalacia, a New Theory of Etiology
19
well-recognized symptoms in some infants with laryn-
gomalacia. The association of GERD and laryngomalacia
is well established, with an incidence range of 23% to
100%.A15,A21,A35,A38,A43,A78,A79 The pathophysiology of
GERD in laryngomalacia is caused by the negative pres-
sure generated in the intrathoracic esophagus during ob-
structed inspiration from supraglottic collapse. This neg-
ative pressure acts as a vacuum, drawing the stomach
contents into the esophagusA80 and overcoming the anti-
reflux barrier of the lower esophageal sphincter. Once the
refluxate leaves the esophagus beyond the upper esopha-
geal sphincter, it enters the hypopharynx and larynx and
becomes LPR.A79,A81–A84 LPR occurs in laryngomalacia.
Frequent LPR events result in inflammation and edema of
the laryngeal tissues, potentially leading to airway
compromise.A79,A82 GERD has been implicated as a caus-
ative factor in laryngomalacia because of a high associa-
tion between the two,A21 but the mechanism is unknown.
It is plausible that the GERD- and LPR-induced edema-
tous changes of the larynx are partially or fully responsi-
ble for the prolapse of the supra-arytenoid into the glottic
inlet, as seen in variants of laryngomalacia.
There are a variety of tests used to evaluate and
diagnose GERD in infants. Traditional testing modalities
include a barium esophagram study, 24 hour esophageal
pH monitoring (pH-metry), esophageal endoscopy with
histologic evaluation of biopsies, and bronchoalveolar la-
vage for lipid-laden macrophages. There is no single “gold
standard” test, nor is one single test always diagnostic in
infants, and thereby the clinical picture and testing mo-
dalities are combined to determine whether pathologic
GERD occurs and whether it requires therapy.A85 Tests to
evaluate and diagnose LPR are still evolving and include
24 hour dual and triple probe pH-metryA79,A82,A86,A87 and
LPST.A83,A84 The detection of acid at a proximal pH sensor
located in the upper esophageal sphincter or esophageal
inlet is sensitive and specific for LPR.A81,A86,A88 LPST
testing likewise shows a correlation with LPR.A83,A84 The
technical aspects of LPST testing will be discussed in a
later section of this thesis. Similar to GERD, there is no
single “gold standard” test for LPR to determine its sig-
nificance, and thereby the clinical picture, laryngoscopic
findings, and testing modalities are combined to deter-
mine the need for therapy.A82,A89 –A91
Barium esophagram is the oldest existing test of
GERD. The test is helpful in the diagnosis of reflux; how-
ever, its usefulness is limited. The presence of reflux dur-
ing the limited short testing time suggests that GERD
occurs. It is unknown whether the refluxate is acidic or
nonacidic and may result in false-positive results. The
brief duration of the testing time may result in false-
negative results. These factors make it difficult to de-
termine whether the barium swallow alone has any
positive predictive value of GERD in laryngomalacia.
Several authors have used the documentation of reflux
into the upper esophagus during barium swallow to
determine the presence of GERD in infants with
laryngomalacia.A15,A21,A36,A38,A43,A55,A92,A93
Esophageal pH monitoring is a valid and reliable
measure of acid reflux. Although it is considered the “gold
standard” in the determination of GERD in adults, the
Laryngoscope 117: June 2007 Supplement
20
criteria to determine a positive test in infants and children
are still evolving.A85 The sensitivity (31%– 86%), specific-
ity (21%– 83%), and positive predictive value (80%– 82%)
of esophageal pH monitoring are superior to barium swal-
low.A85 Several authors have used esophageal pH monitor-
ing as a method of determining pathologic GERD in infants
with laryngomalacia.A15,A21,A36,A38,A43,A59,A79,A92,A94 Re-
view of these series indicates that all children have esoph-
ageal acid exposure, and most have laryngeal acid expo-
sure on a regular basis.
Esophageal endoscopy enables both visualization and
biopsy of the esophageal epithelium. Endoscopy and bi-
opsy can determine the presence and severity of esophagi-
tis, which is the end-organ damage from chronic acid
exposure. A normal appearance of the esophagus during
endoscopy does not preclude histopathologic esophagitis.
Likewise, subtle mucosal changes of erythema and pallor
may be observed in the absence of histopathologic esoph-
agitis. Because there is a poor correlation between endo-
scopic appearance and histopathology, esophageal biopsy
is recommended when diagnostic endoscopy is performed.
The available pediatric data suggest that intraepithelial
eosinophils or neutrophils as well as morphometric mea-
sures of basal cell layer thickness and papillary height
are valid indicators of reflux esophagitisA85. It is sug-
gested that esophageal endoscopy with biopsy is an
excellent means of establishing the diagnosis of patho-
logic refluxA56,A78,A85 in infants and children. However, no
study to date has used biopsy data as the determinant of
GERD in infants with laryngomalacia, and therefore its
role in the evaluation of infants with laryngomalacia is yet
to be determined.
Bronchoalveolar lavage with quantification of lipid-
laden macrophages is a nonspecific test for GERD. Its use
in the evaluation of GERD is based on the correlation of
increased lipid-laden macrophages in children with other
documented positive test for GERD compared with those
without GERD.A95 Its role in otolaryngologic diseases and
laryngomalacia is adjunctive.
In consideration of the high incidence of GERD and
GERD-related symptoms in infants with laryngomala-
cia, it is intuitive to the otolaryngologist that antireflux
therapy is beneficial.A21,A79,A96 Multiple modalities of
antireflux therapy for infants are used in those with
laryngomalacia and may include feeding modifications,
upright positioning, pharmacotherapy, and surgical
fundoplication.A15,A53,A78,A85,A92,A96 Whether antireflux
therapy influences the severity or duration of laryngoma-
lacia and its symptoms is unknown. Three studies suggest
that laryngomalacia and its symptoms improve with an-
tireflux therapy. Modalities of therapy, disease endpoints
to determine improvement, and statistical analysis are
lacking in these studiesA36,A78,A92,A96 and in the collective
laryngomalacia literature.
Surgical Management of
Severe Laryngomalacia
A common misconception about laryngomalacia is
that it is rarely severe enough to warrant surgical inter-
vention. In a primary care practice setting, it is believed
that approximately 5% of patients have serious enough
Thompson: Laryngomalacia, a New Theory of Etiology
 TABLE AI. TABLE AIII.
Literature Summary of Percentage of Infants With Congenital Literature Summary of Incidence of GERD and Neurologic
Laryngomalacia Requiring Surgical Intervention. Disease in Infants Who Require Surgical Intervention for
Congenital Laryngomalacia.
No. Patients Requiring
Percentage Surgical Intervention Author GERD* (%) Neurologic Disease (%)
of Infants of Total Number
Requiring Diagnosed With Holinger and KoniorA35 23 Data not provided
Author Surgery Laryngomalacia PrescottA19 Data not provided 30
Roger et al.A36 11.6 115 of 985 Polonovski et al.A17 43.6 Data not provided
Garabedian et al.A58 11.6 115 of 985 Jani et al.A99 75
Olney et al.A15 15.5 9 of 58 McClurg and EvansA43 42 16
Milczuk and JohnsonA22 16 7 of 44 Kelly and GrayA44 44 Data not provided
PrescottA19 18 40 of 213 Roger et al.A36 68 8.8
Friedman et al.A13 22 — Loke et al.A46 6.4 Data not provided
Toynton et al.A16 28 14
Garabedian et al.A58 68 Data not provided
Olney et al.A15 13 8
sequelae to warrant intervention.A97 As seen in Table AI,
Reddy and MattA18 56 45
the percentages in an otolaryngology practice, particularly
Denoyelle et al.A45 Data not provided 20
in a tertiary care facility, range from 11.6% to 22% (Tables
AI and AII).A13,A15,A19,A22,A36,A58 *Gastroesophageal reflux disease (GERD) determined by positive test,
Barium swallow, or pH-metry.
As seen in Table AII, those infants with congenital
laryngomalacia who require surgical intervention have a
reported onset of stridor that is similar to all patients with erate disease, residual stridor, or feeding difficulty who
laryngomalacia.A15,A17,A22,A98 The mean age at time of su- had resolution of the other complicating factors.A18
praglottoplasty ranges from 2.5 to 38.3 months, with the
Medical comorbidities occur in infants who require
most commonly reported age being approximately 3
surgical therapy. To date, there are no studies that sta-
months.A15,A17,A18,A22,A36,A43–A46,A98 Because the symptoms
tistically determine whether the incidence of medical co-
of laryngomalacia usually resolve by 24 months, the re- morbidities is higher in those who require surgery com-
port with the outlier mean ages of 27.1 months and 38.3 pared with those with less severe disease. In addition,
months is difficult to interpret. Review of this reportA18 medical comorbidities are defined differently by different
suggests that the age may be skewed because the authors authors and include GERD, neurologic disease, and ge-
operated on several patients over the age of 24 months, netic disorders. Because GERD and neurologic disease are
with the oldest being 18 years of age. In addition, the the most commonly reported comorbidities in those who
specific criteria for surgical intervention were not given, require surgery, the literature is summarized in Table AIII.
so it is difficult to know whether this series included those As shown in Table AIV, two surgical series have separated
with acquired laryngomalacia or older children with mod- those with isolated laryngomalacia from those with dis-
ease complicated laryngomalacia; however, the diseases
and comorbidities are defined differently in each study
TABLE AII. (Tables AIII and AIV).
Literature Summary of Surgical Patients: Age of Onset of Stridor Indications for surgical intervention are defined
and Age at Time of Supraglottoplasty. differently by authors and are based on severity of the
Age Mean Age disease and associated symptoms. The most commonly
of Onset of at Time of published indications for surgical intervention are life-
Author Stridor Supraglottoplasty (mo) threatening apnea, recurrent cyanosis, dyspnea with re-
Milczuk and JohnsonA22 Mean, 1 wk 2.5 tractions, feeding difficulties resulting in failure to thrive,
Median, 1 day hypoxia, cor pulmonale, and right heart failure. Of these
Denoyelle et al.A45 Not reported 3.6 indications, stridor with respiratory compromise is the most
Polonovski et al.A17 1 wk* 3.7 common indication followed by feeding difficulty and fail-
Olney et al.A15 2.2 wk 3.8 ure to thrive.A17,A19,A22,A31–A33,A35,A36,A42–A45,A58,A64,A98,A99
Roger et al.A36 Not reported 5.5
Loke et al.A46 Not reported 6.5
Kelly and GrayA48 Not reported 7.0 TABLE AIV.
Literature Summary of Infants Who Require Surgical Intervention
McClurg and EvansA43 Not reported 9.0 Who Have Isolated Laryngomalacia Compared With
Marcus et al.A98 Birth* 10.3 Disease-Complicated Laryngomalacia.
Reddy and MattA18 Not reported 27.1† Isolated Disease-Complicated
Reddy and MattA18 Not reported 38.2‡ Author Laryngomalacia (%) Laryngomalacia (%)

*Median or mean not reported. Denoyelle et al.A45 75 25

†Bilateral supraglottoplasty. Toynton et al.A16 53 47
‡Unilateral supraglottoplasty.

Laryngoscope 117: June 2007 Supplement Thompson: Laryngomalacia, a New Theory of Etiology
21
Surgical options are tracheotomy or suspension laryngos-
copy with microsurgical modification of the collapsing su-
praglottic tissues to improve air passage into the trachea,
known as “supraglottoplasty.” Tracheotomy was the gold
standard for treatment of severe life-threatening laryngo-
malacia until the 1980s, when modern techniques of
supraglottoplasty were introduced.A31,A33,A35,A51,A64,A100
Because of the excellent surgical outcomes and the sig-
nificant mortality and complications associated with
tracheotomy,A101,A102 supraglottoplasty is the procedure
of choice, and tracheotomy is now reserved for supra-
glottoplasty failures or when supraglottoplasty is not
possible either because of significant medical comorbidi-
ties or anatomic factors preventing adequate laryngo-
scopic exposure.
Historic Evolution of Surgical Management
of Laryngomalacia
The concept of endoscopic surgical correction of col-
lapsing supraglottic tissues has evolved over the past 107
years. In 1898, VariotA28 proposed that the condition could
be treated by surgery after reviewing a postmortem exam-
ination of a tracheotomized child with laryngomalacia
who died from accidental decannulation. He suggested in
retrospect that division of the aryepiglottic folds could
have treated the problem. In 1922, IglauerA25 pioneered
the endoscopic surgical treatment of stridor by performing
epiglottectomy with a nasal snare, achieving resolution of
a child’s stridor. In 1928, HasslingerA29 treated three
cases of laryngomalacia by dividing the aryepiglottic folds
with excellent results. In 1944, SchwartzA7 achieved im-
provement of symptoms of laryngomalacia by removal of a
V-shaped wedge from the lateral boarders of the epiglottis.
Laryngeal and epiglottic suspension techniques were
introduced in the early 1970s, with many modifications
reported as recently as 2002.A70 Hyomandibulopexy was
introduced by NarcyA103 in 1970, but it was later aban-
doned in 1976A104 because it was “not always successful.”
In 1971, Cagnol et al.A105 performed a modified hyoman-
dibulopexy by suspending the hyoid to the mandible with
a nylon suture. This technique was reported to relieve
stridor in children with pulmonary hypertension by pull-
ing the hyoepiglottic ligament toward the mandible, re-
sulting in elevation of the epiglottis and aryepiglottic folds
and thereby opening the supraglottic area. Fearon and
EllisA106 reported decannulation of a child with severe
laryngomalacia after suturing the epiglottis to the tongue.
In 1987, Solomons and PrescottA64 combined resection of
the aryepiglottic folds with glossoepiglottopexy in 11 pa-
tients with severe laryngomalacia.
The concept of endoscopic removal of prolapsing
supraglottic tissue was reintroduced in 1984 by Lane et
al.A51 They successfully treated a patient with severe
laryngomalacia and pectus excavatum by removing the
supra-arytenoid prolapsing tissue with otologic instru-
ments and trimming the lateral edges of the epiglottis.
Stridor and feeding problems resolved immediately, and
the pectus reversed by 13 months. Since then, many
authors have used and evaluated the efficacy of this tech-
nique with excellent outcomes and minimal complicat-
ions.A15,A16,A18,A19,A31,A33,A35,A42–A46,A53,A58,A64,A98,A99,A101,A107
Laryngoscope 117: June 2007 Supplement
22
Several names have been given to describe this procedure,
including laser laryngoplasty,A43 epiglottoplasty,A31 arye-
piglottoplasty,A16,A99 and supraglottoplasty.A35 Supraglot-
toplasty is most appropriate because it encompasses any
area of the supraglottic larynx that is modified to alleviate
the flaccid obstructing supraglottic tissues.
Supraglottoplasty techniques have evolved over the
past 20 years. Before surgical intervention, flexible laryn-
goscopy of the larynx while the infant was awake facili-
tated judgment of the key flaccid areas of the larynx.
Surgical approaches are aimed at reducing the redundant
flaccid tissue to minimize the obstruction at the laryngeal
inlet. General inhalational anesthesia is administered
through a mask, and spontaneous inhalational respiration
anesthesia is maintained through a nasopharyngeal
tube.A31,A35 Spontaneous respiration optimizes visualiza-
tion of the larynx in its dynamic state, giving the surgeon
an additional opportunity to judge which areas of the
larynx to modify. The suction test described by Polonovski
et al.A17 may be a dependable guide for the amount and
localization of tissue to be trimmed. This is accomplished
by placing a rigid laryngeal suction into the glottis and
observing the areas of most prominent collapse. Before the
surgical procedure itself, a full endoscopy of the airway is
warranted to avoid overlooking a second airway lesion.
Supraglottoplasty is performed with microscopic suspen-
sion laryngoscopy. Variants of the procedure have evolved.
Aryepiglottic fold lengthening is achieved either by
aryepiglottic fold wedge resection or aryepiglottic fold di-
vision. Reduction of the prolapsing posterior glottic tissue
is achieved by removal of supra-arytenoid mucosa with or
without corniculate cartilage removal. Trimming of the
lateral edges of the epiglottis has also been described.
These variants are performed alone or in combinations.
Ultimately, areas of tissue removal are determined by the
surgeon and are based on his or her assessment of the
areas of most severe collapse and obstruction. Excision is
conservative to avoid complications of stenosis. To mini-
mize chances of stenosis, some even advocate removal of
tissue on one side only, known as “unilateral supraglotto-
plasty.” If symptom resolution is not achieved with a uni-
lateral procedure, a contralateral procedure can be per-
formed at a later time.A18
The two technical methods of tissue division or re-
moval are the use of conventional microlaryngeal instru-
ments, also known as “cold-knife” technique, or the use of
the CO2 laser. Cold-knife techniques were used in the
earliest description of aryepiglottic fold resection by
HasslingerA108 in 1928. This technique using micro-
otologic instruments was reintroduced by Lane et al.A51
and Zalzal et al.A31 With the evolution of microlaryngeal
surgery over the past 25 years, otologic instruments are no
longer needed because sophisticated microlaryngeal in-
struments exist specifically for this type of surgery. Some
surgeons believe that they get a better feel of the amount
of tissue to resect using microscissors as compared with
lasers.A99
CO2 laser division of the aryepiglottic folds was de-
scribed by Seid et al.A33 in 1985. Since then, many authors
have popularized the laser excision technique.A18,A19,A43–A45
Advocates of the CO2 laser state the advantages of ease of
Thompson: Laryngomalacia, a New Theory of Etiology
use, surgical precision, and hemostasisA33,A36,A43,A45,A53 but TABLE AV.
warn that the excessive vaporization can create postoper- Literature Summary of Percentages of Successful
ative complications because of locally induced edema.A36 Supraglottoplasty Outcomes.
Theoretically, heat dissipated in the tissue from the laser Supraglottoplasty
may provide an environment to facilitate the complication Author Success (%)
of supraglottic stenosis, but there are no statistical com-
Marcus et al.A98 100
parisons to support this theory.
Reddy and MattA18* 95.7†
The patient is left extubated and observed in a mon-
Reddy and MattA18* 93.2‡
itored unit or intubated, usually for less than 24 hours.
The commonly reported average length of hospital stay is Kelly and GrayA44 94
2 days,A31 with reported mean ranges of 2 to 13 days. The Zalzal et al.A31 90§
average length of hospital stay of 13 days is longer in those 100储
with medical comorbidities compared with 5 days in those Solomons and PrescottA64 82
with isolated laryngomalacia.A16 Denoyelle et al.A45 79
Olney et al.A15 78
Complications of Supraglottoplasty Polonovski et al.A17 76.9
Surgical complications after supraglottoplasty occur McClurg and EvansA43 71
in less than 8% of cases.A45 Perioperative and immedi- Holinger and KoniorA35 ⬎70
ate postoperative complications are usually related to Loke et al.A46 68.7
the surgical site itself and include bleeding, infection, Roger et al.A36 53
sepsis, edema, respiratory distress, aspiration, and dys- Remacle et al.A96 38.1
phagia. Intermediate and long-term complications are
*Same 2001 publication by Reddy and Matt.
rare.A16,A20,A35,A99 Minor complications include granu- †Initial unilateral supraglottoplasty procedure, but reported success
loma, edema, or a small web. Major complications include percent includes revision and contralateral procedures performed at later
supraglottic stenosis, and death. Death after supraglotto- surgery.
‡Bilateral supraglottoplasty.
plasty is rare. Because of many confounding medical prob- §Initial supraglottoplasty.
lems and other determinants, it is difficult to discern 储Revision supraglottoplasty.
whether reported deaths are related to the surgical
procedure.A16,A43 The reported complication rate of supra-
glottic stenosis is 4%.A18,A45 Even though the risk is small, most common indications for supraglottoplasty, mostly
the complication can be devastating and difficult to repair. resolve after surgical intervention (Tables AV and AVI).
Stenosis occurs when opposing raw surfaces scar together. The determinants of supraglottoplasty failure, simi-
The presence of untreated GERD is considered to be a lar to success, are defined differently by different authors,
precipitating factor.A45 Unilateral supraglottoplasty pro- so a comparison of surgical series is difficult. Supraglot-
cedures have not been statistically proven to be of any toplasty failures are uncommon. Most infants only require
significant added benefit in avoiding supraglottic one procedure to achieve a successful outcome. If the ini-
stenosis.A18,A44 Most authors agree that conservative ex- tial procedure proves inadequate, revision is possible.A35
cision minimizes the likelihood of this complication. Revision supraglottoplasty occurs in a range of 4.4% to
50% of the time.A16,A18,A44 –A46 As seen in Table AVII, re-
vision procedures were more commonly required in those
Supraglottoplasty Outcomes series in which the initial operation was a unilateral su-
Understanding of supraglottoplasty outcomes and praglottoplasty. The study of Denoyelle et al.A45 evaluated
determining success is limited in retrospective studies in revision rates in those with medical comorbidities com-
which medical records are incomplete or length of pared with those with isolated laryngomalacia and found
follow-up is unknown. In general, most series show that no statistically significant difference. As seen in Table
supraglottoplasty is a successful operation, with resolu- AVIII, supraglottoplasty failures are uncommon, and the
tion of most symptoms as a direct result of the surgical
intervention.A15,A17,A18,A31,A35,A36,A43–A46,A64,A98 However,
it is unknown whether surgical intervention has an influ-
TABLE AVI.
ence on the time to symptom resolution compared with
Stridor and Feeding Symptom Resolution After Supraglottoplasty.
those with less severe presentations of laryngomalacia
who do not require surgical intervention. As seen in Table Feeding
Author Stridor (%) Difficulty (%)
AV, the reported range of supraglottoplasty success is 38%
to 100%. The determinants of supraglottoplasty success Roger et al.A36 67 95
are defined differently by different authors, so a compar- Holinger and KoniorA35 92 70
ison of these surgical series is difficult. Most reports are of Toynton et al.A16 94.5 72
bilateral supraglottoplasty operations, although some re- Polonovski et al.A17 79 97
ports are of unilateral procedures. In addition, some series Jain et al.A99 92 70
have larger numbers, which may also account for the Loke et al.A46 90.6 —
variance in the range of successful outcomes reported. As Kelly and GrayA44 94 —
seen in Table AVI, stridor and feeding problems, the two

Laryngoscope 117: June 2007 Supplement Thompson: Laryngomalacia, a New Theory of Etiology
23
 TABLE AVII.
Literature Summary of Revision Supraglottoplasty Procedures.
Unilateral Bilateral
Author Supraglottoplasty (%) Supraglottoplasty (%)
Denoyelle et al.A45 4.4
Loke et al.A46 6 The etiology of laryngomalacia is perplexing. Many
Kelly and GrayA44 17
Reddy and MattA18 5.1
Reddy and MattA18 25
Toynton et al.A16 50
most common intervention is tracheotomy placement. The
study of Denoyelle et al.A45 also found that supraglotto-
plasty failures exclusively occurred in those with medical
comorbidities. The study of Olney et al.A15 explored the
same statistical comparison by comparing those with and
without medical comorbidity in the nine patients in their
series who required surgical therapy. The number was too
small to determine whether the need for surgery or its
success correlated with the presence nonairway-related
medical comorbidity. The remainder of the literature sug-
gests that those with neurologic disease fail more often
than those with isolated laryngomalacia; however, the low
number of failures in these series makes statistical eval-
uation of difficult.A16,A17,A36 Initial or revision supraglot-
toplasty rarely fails to alleviate or improve symptoms.
Less that 8% of all children who undergo supraglotto-
plasty will require a tracheotomy (Tables AVII and
AVIII).A15,A17,A18,A35,A36,A43,A45
Hypothesized Theories of Laryngomalacia
The mechanism of stridor production is well under-
stood and is the result of turbulent airflow across the
abnormally positioned and collapsing supraglottic tissues.
The question is what underlying etiologic factor gives rise
to the positioning of the supraglottic tissue and its col-
lapse into the glottic airway? This enigmatic question,
raised in the 19th century by those first to describe the
condition, LeesA3 (1883) and Sutherland and LackA4
(1897), remains unsolved to this day. Others have since
suggested that laryngeal collapse seen in laryngomalacia
is caused by a local condition or some variation to or
congenital malformation of the structures of the
larynx.A7,A109 Many have speculated as to what these local
conditions, variations, or congenital malformations of the
laryngeal tissue could be and is the basis for the current
hypothesized theories of disease etiology.
theories have been described without convincing evidence
of support. Proposed etiologies include the anatomic
theory,A4,A6,A7,A30,A32,A35,A109 the cartilaginous theory,A110
the neurologic theory,A111 or a combination of these.A30,A31
In addition, GERDA21 has been implicated in the etiology
of laryngomalacia because of a high association between
the two.
The anatomic theory of laryngomalacia is based on
the abnormal positioning of the supraglottis and was first
proposed by Sutherland and LackA4 in 1897. The suppo-
sition is that the abnormally positioned tissue prolapses
into the laryngeal inlet, leading to obstruction, stridor,
and apnea. The omega-shaped epiglottis is thought to be a
classic finding in laryngomalacia; however, it can occur in
infants without laryngomalacia and can persist despite
resolution of stridor in those with laryngomalacia.A112
This discrepancy challenges the anatomic theory of etiol-
ogy. Exploring potential factors that cause the abnormal
positing of supraglottic tissue may provide better insight
and supporting evidence of an etiology.
This cartilaginous theory of etiologyA51,A110,A113 pos-
its that abnormal, immature, and pliable laryngeal carti-
lage, “chondromalacia,” prolapses into the laryngeal inlet
to cause airway obstruction and stridor. Histologic studies
of laryngeal cartilages have yielded varying results. The
study by Shulman et al.A113 reported five siblings with
laryngomalacia. Histologic evaluation of the cartilage of
two of the patients showed distinct hypercellularity with
histochemical staining abnormalities but no skeletal de-
fects. In addition, dilated lacunae and a relative paucity of
cartilaginous matrix per cell were found. In contrast, a
similar study by KelemenA110 showed no consistent gross
or microscopic abnormality occurring exclusively in spec-
imens of infants with stridor as compared with control
specimens. The theory of cartilage immaturity remains
questionable. Despite the abnormal appearance of the

TABLE AVIII.
Literature Summary of Supraglottoplasty Failures.
No. Supraglottoplasty
Author Failures (%) Management

Denoyelle et al. A45 12/36 (8.8) Tracheotomy; noninvasive ventilation; supplemental

oxygen and nasogastric feeding
Olney et al.A15 2/9 (2.2) Tracheotomy; tracheotomy and Nissen fundoplication
Roger et al.A36 2/115 (1.7) Tracheotomy
Holinger and KoniorA35 1/13 (7.6) Tracheotomy
Toynton et al.A16 8/100 (8) Tracheotomy; Nissen fundoplication; nasogastric
feeding
Polonovski et al.A17 1/39 (2.5) Tracheotomy and fundoplication
McClurg and EvansA43 1/24 (4.1) Tracheotomy
Reddy and MattA18 6/106 (5.6 ) Tracheotomy

Laryngoscope 117: June 2007 Supplement Thompson: Laryngomalacia, a New Theory of Etiology
24
larynx in laryngomalacia, there is little histologic support
for the notion that the cartilage or soft tissues are differ-
ent in this disorder. Therefore, the anatomic and cartilag-
inous theories of laryngomalacia have little supportive
evidence.
A number of reports have suggested a neurologic
rather than an anatomic or structural cause for laryngo-
malacia. A variety of different neurologic mechanisms
have been proposed. These include delay in the develop-
ment of neurologic or neuromuscular control of airway
patency, denervation of the larynx, and neuromuscular
hypotonia. The first suggestion of a neurologic mechanism
was reported by PollitzerA114 in 1884. He noted the fre-
quency of “nerve imbalance” in infants with stridor without
“pathological accompaniment.” He explained the stridor as a
“disturbance of innervation within the physiological range.”
The first publication with an experimental study to support
a neurologic cause over an anatomic cause was published in
1900 by Thomson and Turner.A5 They used denervated
larynges in an ex vivo model and applied suction to repro-
duce the flaccidity seen in laryngomalacia. They found
that infants who were not afflicted with congenital stridor
had some of the same laryngeal anatomic characteristics
as infants who were afflicted with laryngomalacia, con-
cluding that the anatomic form found in those with stridor
is merely an exaggeration of the normal infantile type
larynx. From this experimental anatomic model, they con-
cluded that laryngomalacia is the result of “ill-coordinated
stammering breathing” and that the disturbance of the
coordination of the respiratory movements was caused by
“developmental backwardness of the cortical structures
which control them.”A5
Neuromuscular hypotonia of the dilatory muscles
of the laryngeal inlet is the proposed etiologic theory of
Belmont and Grundfast.A38 Through anatomic dissection
of adult cadaveric larynges, they concluded that there are
multiple muscles of the supraglottic larynx whose vectors
of force could interact to result in dilation of the laryngeal
inlet. They concluded that there may be hypotonia of these
muscles in patients with laryngomalacia that would result
in collapse of the laryngeal inlet. These investigators de-
duced a neuromuscular hypotonia theory based on this
anatomic dissection and the circumstantial finding that
23% of patients with laryngomalacia in their clinical se-
ries had an underlying neurologic disorder. The relevance
of this theory should be questioned because it was not
studied in a dynamic state, the dissection was performed
on adult larynges, and there was no histopathologic cor-
relation of the implicated muscles. Muscle tissue is
thought to be absent in the laryngeal inlet of infants with
laryngomalacia. This suggests that an active muscular
mechanism at the laryngeal level is not responsible for the
laryngeal supraglottic tissue collapse. Rather, an abnor-
mal or immature neuromuscular or neurologic control of
airway patency may have a more significant role.
A delay in the development of neurologic function and
tone of laryngeal tissue may play a more important role in
the etiology of laryngomalacia. As previously mentioned,
Thomson and TurnerA5 at the turn of the century demon-
strated that a laryngomalacia-like passive medial pro-
lapse of supraglottic structures occurred with denervation
Laryngoscope 117: June 2007 Supplement
in an infant animal model. The classic laryngomalacia
signs have been seen during CNS sedation in infants.A115
CNS insults from sedative drugs, seizures, strokes, or
hypoxic brain injury have resulted in acquired
laryngomalacia.A111,A116 –A118 The location of the CNS in-
sult is at the brainstem nuclei for swallowing, respiration,
and vagal laryngeal function and tone.A111,A116 –A118 Many
of these cases of acquired laryngomalacia resolved with
improvement or reversal of the underlying neurologic con-
dition.A116 This model provides a cogent argument that
congenital laryngomalacia findings and symptoms are a
consequence of altered, immature, or underdeveloped con-
trol neurologic function and tone of laryngeal tissue, akin
to a CNS insult. With use of acquired laryngomalacia as a
model for congenital disease, it can be seen as plausible
that the symptoms resolve as the brainstem nuclei and
their sensorimotor reflexes mature in a process similar to
symptom resolution after improvement or reversal of the
underlying CNS condition. It is also possible that there is
an abnormality of the neurologic control of airway patency
in laryngomalacia and that the abnormality physiologi-
cally behaves similar to denervationA119 and may cause
airway collapse, as seen with laryngomalacia.
The association of GERD has been reported to be as
high as 80% to 100% in infants with laryngomalacia.A21,A87
In GERD-associated laryngomalacia, tissue edema with
erythema of the posterior glottic arytenoid region is seen
on flexible laryngoscopy. Symptoms of laryngomalacia of-
ten improve after a course of antireflux therapy.A96 Al-
though the association between GERD and laryngomala-
cia is established, the proposed mechanism is uncertain. A
plausible mechanism of GERD-complicated laryngomala-
cia is that the gastric acid refluxes into the larynx and
injures the posterior glottis. This injury causes edema of
the tissues, which subsequently prolapse into the air-
way.A79 Gastric acid injury also causes a sensory deficit of
the larynx by decreasing the sensitivity of the nerve end-
ings of the SLN. The SLN regulates the afferent limb of
neurologically controlled reflexes of laryngeal function
and patency. There is experimental and clinical evidence
in adults and children with GERD and LPR that the
afferent limb of laryngeal function is altered.A84,A120 –A122
It is possible that GERD may cause a partial functional
denervation of the afferent response of the larynx. This
association may have a contributing role in the etiology of
laryngomalacia and is explored in this thesis.
Neurologic Control of Laryngeal Function:
Laryngeal Adductor Reflex
Laryngeal patency and function is complex and reg-
ulated through a peripheral and central neurologic mech-
anism. These laryngeal reflexes play an important role in
respiration, laryngeal function, swallowing, and airway
protection from aspiration. Mechanical or chemical stim-
ulation of the supraglottic mucosa or direct stimulation of
the SLN activates the LAR. The phylogenetic purpose of
this reflex is to protect the airway from aspiration and
asphyxiation of secretions and food. The precise sequence
of events from laryngeal stimulation allows for an infan-
tile suck-swallow breath sequence without significant as-
piration or airway complications. Stimulation of the
Thompson: Laryngomalacia, a New Theory of Etiology
25
supraglottic mucosa induces a complex sequence of reflex-
ive events, resulting in adduction of the vocal cords and
closure of the laryngeal inlet and a swallow response. The
stimulus activates the chemosensory and mechanosensory
corpuscles located in the region of the aryepiglottic
fold,A123–A126 which is richly innervated by the SLN. The
SLN then transmits sensory information by way of the spe-
cial visceral afferent fibers of the vagus nerve to the inferior
(nodose) ganglion. From there, information is sent to the
nucleus solitarius, the brain-stem nucleus responsible for
regulation of swallowing and respiration. The efferent
response initiated at the nucleus is ambiguous. From
here, an involuntary efferent response travels by the va-
gus nerve, resulting in a reflexive adduction of the vocal
folds and a swallow response. This same efferent vagal
response influences the tonicity of laryngeal tissues. The
tonicity of laryngeal tissues is altered in laryngomalacia,
leading to the abnormal prolapse into the glottic inlet. It is
plausible that any alteration in the afferent, brainstem, or
efferent neurologic pathway of the LAR results in an al-
teration in the vagal tone of the larynx that could be
responsible for the local tissue prolapse seen in laryngo-
malacia. SchwartzA7 presented this etiologic hypothesis in
1944, but it remains untested (Fig. 1).
Higher stimulus thresholds may be required to elicit
the LAR response of glottic closure and swallow.A120,A127–A130
It is these alterations in the LAR that lead to pathology.
The LAR is implicated in infant apnea and breathing
disorders by two mechanisms. Prolonged or excessive
stimulation can induce prolonged glottic closure or laryn-
gospasm and apnea.A131–A135 Alternatively, if the process
of LAR is interrupted, inefficient coordination of airway
protection may result. The clinical symptoms of interrup-
tion of the LAR include aspiration, choking, apnea, and an
inability to swallow to clear the stimulus. Sustained ap-
nea and death can occur unless swallowing intervenes to
remove the stimulus.A127,A136 –A140 Inability to swallow to
clear stimulus can lead to a vicious cycle of tissue aggrava-
tion, localized edema, prolapse of tissue, and apnea. This
cycle of edema and prolapse of tissue into the glottic inlet has
been proposed as a causative factor in laryngomalacia.A79
Until recently, testing of the LAR has been limited
to stimulation through the instillation of water, saline,
acid, or air into the laryngeal vestibule, with indirect
methods of determining airway closure or a swallow
response.A127,A131,A132,A141–A145 LPST provides a quanti-
fiable method of testing the LAR and direct visualiza-
tion of the laryngeal response.
Laryngopharyngeal Sensory Stimulation
Testing: A Test of Laryngeal Adductor Reflex
LPST was developed as a clinical test of laryngopha-
ryngeal sensation in the adult population.A128,A146 This
test provides invaluable information about laryngopha-
ryngeal sensation and ability to protect the airway from
aspiration by way of the LAR. In the adult setting, the test
can be used as a psychophysical test of laryngopharyngeal
sensation or as a test of the LAR.A128,A129,A146 –A154
As a psychophysical test, a calibrated air pulse stim-
ulation (intensity range between 2 and 10 mm Hg for 50
ms) is delivered to different parts of the laryngopharynx.
Laryngoscope 117: June 2007 Supplement
26
The subject is asked to acknowledge when he/she feels the
delivery of the air pulse. A higher intensity (⬎5 mm Hg)
required to elicit a subjective acknowledgment of the air
pulse is an indicator of a sensory deficit of the larynx.
Subjects who have no sensation or only feel the stimula-
tion at higher levels have been shown to have higher rates
of aspiration and loss of the laryngeal protective function
of glottic closure.A128,A129,A146 –A151,A153 This psychophysi-
cal test of laryngeal sensation is not practical in the
infant.
Application of the same technique can be used to test
the LAR. The integrative function of the LAR is tested by
applying a duration- (50 ms) and intensity- (2.5–10 mm
Hg) controlled airpulse to the aryepiglottic fold and ob-
serving a response of glottic closure and swallow. This
testing modality, LPST,A128,A130,A147,A151,A153,A154 is a test
of the sensorimotor function of the larynx. The advan-
tage of this test is that it does not require a subjective
response or cognitive functional ability for evaluation. It
is intuitive that this would be a more reliable test in
infants because it does not require a subjective response.
The aryepiglottic fold region is chosen because of its
rich innervation by the sensory portion of the SLN. Coin-
cidentally, the aryepiglottic fold is also a common area of
supraglottic collapse in laryngomalacia. It is plausible
that alteration in the sensation of the aryepiglottic fold
region may abate the function of the neurologic reflex of
the LAR at the brainstem or efferent level, thereby result-
ing in alteration in the vagal function and tonicity of
laryngeal tissues. There is clinical evidence to support this
finding. Through flexible bronchoscopy, Nielson et al.A155
found markedly exaggerated prolapse of the arytenoid and
aryepiglottic folds after application of lidocaine to the
region in infants with laryngomalacia. Modulation in the
sensory response of the larynx specifically at the aryepi-
glottic fold could be a contributing factor in the etiology of
laryngomalacia, as proposed by SchwartzA7 in 1944, and is
explored in this thesis. Nielson et al.A155 also noted that
sensory denervation after lidocaine application affected
the position of the posterior supra-arytenoid tissue but not
the epiglottis. The omega-shaped epiglottis can occur in
laryngomalacia and nonlaryngomalacic infants, so its role
in an etiologic cause of laryngomalacia is challenged.A112
Likewise, not all children with laryngomalacia have an
omega epiglottis but may have posterior and lateral tissue
prolapse only.A15,A34,A35 Because lidocaine application ap-
pears to exaggerate the abnormal positioning of the pos-
terior and lateral glottis and not the epiglottis, this fur-
ther supports the idea that sensory or sensorimotor
modulation has a role in the etiology of laryngomalacia.
Therefore, testing of the LAR and its sensorimotor inte-
grative function in infants with laryngomalacia may pro-
vide insight into disease etiology.
This testing modality has been successfully used in
infants and children.A121,A154,A156 Normal adult LPST
thresholds average 2.3 mm Hg.A146,A150 Normative data
are not available for infants and children; however, aver-
age thresholds in infants without neurologic disease or
developmental delay who were evaluated as having air-
way obstruction are 4.3 mm Hg.A156 LPST thresholds of
greater than 5 mm Hg correlate with an abnormality or
Thompson: Laryngomalacia, a New Theory of Etiology
pathology somewhere along the afferent, brainstem, or
efferent limb or the reflex arc and are most often impli-
cated in sensory abnormalities of the larynx. Elevated
LPST thresholds of 5.8 mm Hg in adults and 6.3 mm Hg in
infants and children are seen in the setting of chronic
GERD that results in LPR.A84,A121,A122,A130,A154,A157
Thresholds greater than 6 mm Hg are seen in children and
adults with neurologic disease that includes CNS and
brainstem pathology. Studies have also shown that adults
and infants who receive antireflux treatment for LPR
show a reversal in the elevated LPST thresholds (a de-
creased threshold), indicating increased sensation and
greater response of the sensorimotor reflex after GERD
treatment.A84,A122 Elevated LPST thresholds have been
demonstrated in adults and children with CNS and brain-
stem pathology.A146,A147,A149,A151,A154 Elevated sensory
thresholds are also seen in premature infants with ap-
nea,A156 some of whom have GERD, suggesting a com-
bined peripheral afferent sensory abnormality and central
brainstem abnormality.
Before the development of the flexible laryngoscope
with LPST capability, sensation in adults, children, and
infants was determined by random tapping of the laryn-
geal tissues with the tip of the flexible laryngoscope. This
method, although successful, is less precise, with far less
control, and ultimately delivers a greater stimulus and
does not provide an objective or quantifiable measure.
LPST provides a quantifiable measure of sensorimotor
function of the larynx.
Application of Testing LAR in Laryngomalacia
It may be that neurologically regulated mechanisms
of the LAR are altered in patients with laryngomalacia.
This study proposes that there is a sensorimotor alter-
ation in infants with laryngomalacia that contributes to
the signs and symptoms seen in these infants and there-
fore is an etiologic factor. There are a variety of reasons
why a functional alteration of the LAR and its sensorimo-
tor function exist in patients with laryngomalacia. It is
possible that infants with laryngomalacia have an imma-
ture peripheral nervous system and CNS that contributes
to altered laryngeal function, tonicity, and patency, as
previously theorized. In consideration of the high asso-
ciation of GERD and laryngomalacia, it is also possible
that chronic exposure to the acidic effects of GERD and
LPR downgrade neuronal response to laryngeal stimu-
lation and result in a functional denervation. Chronic
acid exposure causes excessive localized tissue edema,
which can then prolapse into the glottic inlet. This pro-
lapse may be exaggerated in those with less efferent vagal
tone. Chronic acid exposure also alters laryngeal
sensitivity.A84,A121,A130,A154,A157 Altered laryngeal sensitiv-
ity leads to difficulty in swallowing to clear an acid stim-
ulus, saliva, or secretions. If the stimulus is not cleared
into the esophagus by a reflexive swallow, aspiration into
the larynx occurs, thereby inducing obstruction of the
airway.A138 –A140,A143,A158,A159 This event can be seen clin-
ically as laryngospasm and may be responsible for the
apneic events seen in those with severe laryngomalacia.
Elevated sensory thresholds are also seen in premature
infants with apnea,A156 some of whom have GERD, sug-
Laryngoscope 117: June 2007 Supplement
gesting a combined peripheral afferent sensory abnormal-
ity and central brainstem abnormality.
In consideration of this clinical and experimental ev-
idence that supports the idea that an alteration or dener-
vation anywhere along the path of the LAR alters laryn-
geal function and tone, it is possible that alteration of the
sensorimotor integrative function of the LAR may have a
role in the causation of the signs, symptoms, and clinical
examination findings of “laryngomalacia.” Because the
etiology of laryngomalacia remains elusive, this thesis
provides evidence to support a sensorimotor dysfunction
theory of causation as seen through LPST testing of the
LAR in infants with varying degrees of laryngomalacia.
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TABLE AIX.
Summary of Gastroesophageal Reflux Disease Testing.
Total, Percent With
Testing n ⫽ 201 (%) Positive Test
Contrast esophagram
Positive 126 (62.7) 126/157 ⫽ 80.3%
Negative 31 (15.4)
Not Done 44 (21.9)
Esophagoscopy with
biopsy
Positive 20 (10.0) 20/41 ⫽ 48.8%
Negative 21 (10.4)
Not Done 160 (79.6)
Dual pH-metry
Positive 60 (29.8) 60/60 ⫽ 100%
Not Done 141 (70.2)
Thompson: Laryngomalacia, a New Theory of Etiology
 TABLE AX.
Summary of Treatment for Gastroesophageal Reflux Disease (GERD) Testing.
Total Mild Moderate Severe
Characteristic (n ⫽ 157) (n ⫽ 38) (n ⫽ 83) (n ⫽ 36) P Value

Age at initiation of GERD treatment (days) .013

Mean (SD) 108.0 (132.4) 116.1 (76.4) 77.4 (55.0) 169.9 (242.0)
Median 73.0 99.5 65.0 92.0
IQR 46, 124 66, 156 46, 89 24, 180.5
Range (2–1,173) (7–360) (3–288) (2–1,173)
Nissen fundoplication (%) 19 (12.1) 1 (3) 6 (7) 12 (33) ⬍.001
H2 therapy, ranitidine 3 mg/kg 3 ⫻ day (%) 149 (95.5) 38 (100) 80 (96) 31 (89) .017
PPI therapy, omeprazole 1 mg/kg 4 ⫻ day (%) 32 (20.4) 0 (0) 17 (20) 15 (42) ⬍.001
Duration of pharmacotherapy treatment (days)* .025
Mean (SD) 250.9 (192.4) 199.3 (99.4) 259.7 (140.2) 285.3 (322.9)
Median 222 198 249 159.5
IQR 151, 286 147, 256 180, 301 67.5, 294
Range (10–1,446) (45–611) (10–945) (11–1,446)
*Sixteen patients were still actively on therapy at time of their last follow-up.
IQR ⫽ interquartile range, 25th and 75th percentiles; PPI ⫽ proton pump inhibitor.

APPENDIX II: SUPPLEMENTARY RESULTS
Gastroesophageal Reflux Disease
in Laryngomalacia
Review of the medical records found that 70.2% (n ⫽
141) of the patients had a test that was considered positive
for GERD, which is higher than the 65.7% physician-
recorded diagnosis of GERD. Results of GERD testing are
summarized in Table AIX.
Seventy-eight percent of the patients in this study were
treated for signs and symptoms of GERD. Those with mod-
erate and severe disease were more frequently treated than
were those with mild disease. Treatment modalities included
ranitidine, omeprazole, and Nissen fundoplication. Some in-
fants required multimodality therapy; however, this factor
was not statistically addressed. Those with severe disease
were more likely to need PPI therapy or fundoplication when
compared with those with mild or moderate disease. Those
with moderate disease required longer durations of therapy
compared with those with mild or severe disease. A sum-
mary of GERD treatment is presented in Table AX.
Surgical Management: Supraglottoplasty
and Tracheotomy
Surgical intervention was required in 30.8% of the in-
fants in this study, regardless of disease severity at time of
presentation. Of those who presented with less severe dis-
ease, 3% with mild and 28% with moderate disease required
surgical intervention. Of the patients with severe disease,
97% required surgical intervention. The most common indi-
cation for surgical intervention, regardless of status at initial
presentation, was feeding difficulty with failure to thrive
(82%), followed by cyanosis (79%), apnea (77%), respiratory
distress (68%), and hypoxia (65%). Table AXI list all of the
surgical indications from most to least common.
Of the 62 infants who required surgery, the pri-
mary operation was a supraglottoplasty (92%) or

TABLE AXI.
Indications for Surgical Intervention in Congenital Laryngomalacia.
Total, Mild, Moderate, Severe,
Surgical Indication n ⫽ 62 (%) n ⫽ 2 (%) n ⫽ 23 (%) n ⫽ 37 (%)

Feeding difficulty/failure to thrive 51 (82) 1 17 (74) 33 (89)

Cyanosis 49 (79) 1 18 (78) 30 (81)
Apnea 48 (77) 1 19 (83) 28 (76)
Severe respiratory distress 42 (68) 2 14 (61) 26 (70)
Hypoxia 40 (65) 2 14 (61) 24 (65)
Failed medical intervention 28 (45) 0 18 (78) 10 (27)
Right heart failure 17 (27) 0 4 (17) 13 (35)
Cor pulmonale 8 (13) 0 2 (9) 6 (16)
Other 7 (11) 0 2 (9) 5 (14)
Only one of surgical indications was significantly different between three groups based on comparisons made
using Fisher’s exact test. However, there was limited statistical power given the number of patients in each group.
Patients in moderate disease group were more likely to have failed medical intervention than were patients in severe
disease group (P ⬍ .001).

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31
 TABLE AXII.
Summary of Patient and Surgical Characteristics by Type of Primary Operation for
Severe Laryngomalacia.
Total Supraglottoplasty Tracheotomy
(n ⫽ 62) (n ⫽ 57) (n ⫽ 5)

Mean age at time of surgery (days)

Mean (SD) 179.6 (203.8) 167.0 (162.8) 323.2 (483.9)
Median 128 136 114
IQR 78, 179 78, 179 89, 154
Range (9–1,187) (9–815) (72–1,187)
Time between presentation and surgery (days)
Mean (SD) 105.3 (190.1) 88.0 (134.1) 302.6 (496.5)
Median 51.5 46 95
IQR 21, 99 21, 91 68, 144
Range (0–1,187) (0–732) (19–1,187)
Time between diagnosis and surgery (days)
Mean (SD) 34.9 (75.81) 37.2 (78.7) 8.2 (6.9)
Median 11 11 10
IQR 3, 35 4, 37 2, 14
Range (0–536) (0–536) (0–15)
Patients with isolated laryngomalacia (%) 5 (8%) 5 (9%) 0
Patients with laryngomalacia and 57 (92%) 52 (91%) 5 (100%)
comorbidity* (%)
GERD (%) 53 (85%) 48 (84%) 5 (100%)
Neurologic disease (%) 16 (26%) 11 (19%) 5 (100%)
Cardiac disease (%) 19 (31%) 18 (32%) 1 (20%)
Genetic disorder (%) 21 (34%) 17 (30%) 4 (80%)
*Numbers exceed 100% because many patients had multiple comorbidities. Among 57 patients who had a
primary supraglottoplasty, 27 (47%) had comorbidities from two or more categories. All five of patients who had
primary tracheotomy had comorbidities from two or more categories.
IQR ⫽ interquartile range, 25th and 75th percentiles; GERD ⫽ gastroesophageal reflux disease.

tracheotomy (8%). Patient characteristics are summa-
rized by the type of primary surgery in Table AXII. The
median age at surgery was 4.5 months. The time be-
tween initial presentation and surgery was longer in
those who had a primary tracheotomy (median, 95 vs.
46 days); however, the number of patients limited the
power to assess for statistical significance. These pa-
tients were sicker and had more comorbidities. Of those
who had surgery, 5 (8%) patients had isolated laryngo-
malacia (all 5 had mild or moderate disease), 53 (86%)
patients had GERD in combination with another comor-
bidity, and 4 (6%) had a non-GERD comorbidity. As seen
in Table AXII, the complication rate after supraglotto-
plasty was low, with the more frequent complication
being immediate postoperative aspiration (Tables AXII
and AXIII).

TABLE AXIII.
Complications of Supraglottoplasty in Congenital Laryngomalacia Among 57 Patients Who had
Primary Supraglottoplasty.
Total, Mild, Moderate, Severe,
Complication n ⫽ 57 (%) n ⫽ 2 (%) n ⫽ 23 (%) n ⫽ 32 (%)

Bleeding 0 0 0 0
Infection 0 0 0 0
Aspiration 8 (14) 0 3 (13) 5 (16)
Dysphagia 6 (11) 0 1 (4) 5 (16)
Supraglottic stenosis 0 0 0 0
Granulation tissue 2 (4) 0 1 (4) 1 (3)
Transient Respiratory Distress 6 (11) 0 3 (13) 3 (9)
Other 3 (5) 0 2 (9) 1 (3)
None of complication rates were significantly different between three groups based on comparisons made
using Fisher’s exact test. However, there was limited statistical power given the number of patients in each group.

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32
 TABLE AXIV.
Symptom Resolution in Infants With Congenital Laryngomalacia.
Log-Rank Test,
Total Mild Moderate Severe Two-Sided
Symptom (n ⫽ 201) (n ⫽ 80) (n ⫽ 83) (n ⫽ 38) P Value

Stridor .13
No. present at baseline 201 80 83 38
No. resolved (%) 184 (92) 78 (98) 77 (93) 29 (76)
Cumulative percent of incidence of resolution 16.5 12.5 15.7 27.0
by 6 mo
Cumulative percent of incidence of resolution 79.4 87.5 75.8 68.1
by 12 mo
Cough/choke while eating ⬍.001
No. present at baseline 155 43 82 30
No. resolved (%) 128 (83) 41 (95) 67 (82) 20 (67)
Cumulative percent of incidence of resolution 21.4 41.9 17.1 3.4
by 6 mo
Cumulative percent of incidence of resolution 73.0 89.2 73.3 49.7
by 12 mo
Regurgitation .080
No. present at baseline 145 38 80 27
No. resolved (%) 120 (83) 35 (92) 62 (78) 23 (85)
Cumulative percent of incidence of resolution 12.5 26.9 7.5 7.4
by 6 mo
Cumulative percent of incidence of resolution 71.5 79.7 69.3 67.3
by 12 mo
Failure to thrive/poor weight gain .14
No. present at baseline 53 2 18 33
No. resolved (%) 45 (85) 1 (50) 17 (94) 27 (82)
Cumulative percent of incidence of resolution 28.5 * 38.9 21.4
by 6 mo
Cumulative percent of incidence of resolution 74 † † 67.2
by 12 mo
*By 6 months, there were less than 10 patients who had not yet resolved and had more than 6 months of follow-up.
†By 12 months, there were less than 10 patients who had not yet resolved and had more than 12 months of follow-up.

Symptom Outcomes in
Congenital Laryngomalacia
Of the 201 patients, 83.6% had achieved complete res-
olution of all symptoms present at the time of presentation,
and an additional 13.4% had achieved partial resolution. Six
(3.0%) patients had not yet achieved partial resolution of
their symptoms at the time of their last follow-up; five of
these had severe disease at presentation. Table AXIV sum-
marizes the frequency of symptoms present at baseline and
the cumulative incidence of resolution of these symptoms
separately for four major symptoms. Calculations were made
using the Kaplan-Meier method to take into account varying
durations of follow-up. Among the patients presenting with
coughing and choking symptoms, patients with mild or mod-
erate disease were more likely to achieve resolution within
12 months of follow-up compared with patients with severe
disease (P ⬍ .001). The cumulative incidence of resolution of
either stridor, regurgitation, or failure to thrive/poor weight
gain was not significantly different among the three groups
(Table AXIV).

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