Reprinted in the IVIS website with the permission of the AAEP Close window to return to IVIS

MILNE LECTURE: LOWER AIRWAY OF THE HORSE

Pathogenesis and Management of Airway Disease

N. Edward Robinson, B. Vet. Med., PhD, MRCVS

Inflammation of the equine tracheobronchial tree is a result of infection, allergy, and environmental
contamination. Acute bouts of inflammation cause mucus secretion, airway wall thickening, and
increased responsiveness of reflexes that initiate cough and bronchospasm. Recurrent bouts of
inflammation lead to structural changes in the mucosa and the smooth muscle so that the airway wall
is thickened. Prevention of inflammation is at the heart of therapy. This can be done by
environmental management and use of anti-inflammatory drugs, the latter preferably delivered by
inhalation. Bronchodilators are used to relieve acute distress or when inflammation cannot be totally
controlled. Author’s address: Dept. of Large Animal Clinical Sciences, G-321 Veterinary Medical
Center, Michigan State University, East Lansing, MI 48824-1314. r 1997 AAEP.

1. Introduction airway disease is common. These horses are gener-

Airway disease is recognized in several forms. Vi-
ral infections, especially equine influenza, cause
acute inflammation and severe disruption of the
airway epithelium, but their effects are generally
transient. Viral diseases are not discussed further
in this paper; rather, I focus on the more chronic
inflammatory airway diseases.
The most severe form of chronic airway disease is
heaves (chronic obstructive pulmonary disease, or
COPD). In this condition, middle-aged to older
horses develop airway obstruction, usually when
stabled. Obstruction is the result of neutrophilic
inflammation, which is associated with broncho-
spasm and the accumulation of mucus and exudates
in the airway lumen. There is evidence that this
condition is a hypersensitivity response to molds in
hay, but it is also likely that other factors contribute
to the airway inflammation. The condition is pro-
gressive, with respiratory distress becoming more
severe over the years.
In younger horses, 2- to 3-year olds, inflammatory
ally presented for poor performance, and an in-
creased amount of mucopus in the trachea is the
consistent finding. The name inflammatory airway
disease (IAD) has been applied to this condition in
order to distinguish it from COPD.1 IAD has been
suggested to be the consequence of bacterial respira-
tory infections, but the quality of the horse’s environ-
ment plays a role in the severity and duration of the
problem.2
Inflammation of small airways has also been de-
scribed in association with exercise-induced pulmo-
nary hemorrhage (EIPH). It is not clear if this is a
result of hemorrhage into the air spaces or is a factor
contributing to the hemorrhage.
2. Incidence
Lower airway disease is reported to be second only to
musculoskeletal disease as a cause of wastage among
performance horses.3 In necropsy surveys, the inci-
dence of chronic inflammatory disease of the airways
has been reported as 37% in Switzerland4 and 12% in

NOTES

106 1997 @ Vol. 43 @ AAEP PROCEEDINGS

Proceedings of the Annual Convention of the AAEP 1997

 Reprinted in the IVIS website with the permission of the AAEP
MILNE LECTURE:
Minnesota.5 Based on a clinical diagnosis, airway
inflammation coupled with mucus accumulation was
found in 54% of Swiss horses.4 Dixon et al.6 re-
ported on 300 horses referred to the Edinburgh
veterinary college for suspected respiratory prob-
lems. Of these, 55% were said to have COPD, based
on more than 5% neutrophils in bronchoalveolar
lavage fluid (BALF) at the time of examination and a
history of chronic neutrophilic inflammation in asso-
ciation with exposure to hay and straw.
IAD is common in racehorses in training. Swee-
ney et al.7 reported that 27% of Thoroughbreds in
training had more than 20% neutrophils in their
respiratory secretions. Burrell et al.2 followed
horses in two training yards for 2 years and found
that horses spent 33% of their time in training with a
degree of inflammatory lower airway disease. This
tracheobronchial inflammation has been associated
with poor performance in racehorses.8
3. Clinical Signs of Lower Airway Disease
Horses with lower airway disease are presented to
the veterinarian either because they cough, have
respiratory distress, or are exercise intolerant.
Cough is a result of activation of irritant receptors
located in the epithelium of the trachea and large
bronchi. These receptors are activated by material
such as mucus on the epithelial surface, by contrac-
tion of smooth muscle and by release of sensory
neuropeptides such as substance P. The sensitivity
of the cough reflex is increased when the epithelium
is damaged, e.g., by viral infections, and by some
mediators such as histamine and prostaglandins
released during the inflammatory response. Two
recent studies have reported on the usefulness of
cough as a sign of lower airway disease. Cough is a
specific sign, i.e., when it is present, horses have
airway disease. However, it is not a very sensitive
sign: many horses with airway inflammation do
not cough.2 Burrell et al.2 reported that cough is
more prevalent when airway disease has been pre-
sent for more than 1 month. This probably explains
why Dixon et al.9 found coughing in 71% of horses
referred for respiratory problems.
Respiratory distress in the resting animal is a sign
of severe airway obstruction. Under these condi-
tions, the horse adopts a breathing strategy that
allows it to exhale most of its tidal volume early in
exhalation. As the airways become obstructed later
in exhalation, the horse uses an abdominal push to
force a small volume of air through the obstructed air
passages.10 When judging the severity of respira-
tory distress, it is this change in breathing strategy
that is noted by the clinician.11 Although, in gen-
eral the magnitude of airway obstruction is associ-
ated with the severity of clinical signs, some horses
with quite severe airway obstructions will not adopt
the characteristic breathing strategy. Consequently,
there is not a particularly tight correlation between
the magnitude of airway resistance and the clini-
cian’s ability to detect signs of respiratory distress.
Proceedings of the Annual Convention of the AAEP 1997
Close window to return to IVIS
LOWER AIRWAY OF THE HORSE
The majority of horses with inflammatory airway
disease do not exhibit respiratory distress nor do
they have measurable alterations in lung function.12
It is most likely that any effect of inflammatory
airway disease on performance is due to uneven
distribution of ventilation that accentuates exercise-
induced hypoxemia.
Findings on auscultation are dependent on the
degree of airway obstruction and the minute ventila-
tion of the horse. If obstruction is slight and the
horse is at rest, abnormal sounds usually are not
heard.9 The likelihood of hearing abnormal sounds
is increased when minute ventilation is increased by
exercising the horse, by placing a rebreathing bag
over the muzzle, or after temporarily occluding the
nares. As obstruction becomes more severe, two
types of abnormal sounds can occur: increased
sound in the trachea and bronchi, or wheezes that
originate in the peripheral airways but may also be
heard in the trachea. Because the airways are
narrowest at end exhalation, wheezes are most
obvious at this point in the respiratory cycle.
4. Diagnostic Procedures
Endoscopic examination is an essential part of the
evaluation of the horse’s airways. It should include
evaluation of the upper airway as well as the tracheo-
bronchial tree. Inflammation of the lower airway is
indicated by varying amounts of secretions and
exudates in the airway lumen. Horses with mild
disease will have a small amount of mucus that may
be white because it contains inflammatory cells.
Horses with severe COPD may have copious mucopu-
rulent exudate. In some cases, mucus may be thick
and tenacious so that it plugs the peripheral airways
and may not be particularly evident in the larger
airways. Other findings on endoscopy can include
hyperemia and edema of the airway wall and an
increased tendency of the airway to bleed when
traumatized by the endoscope.
The cellular composition within airway secretions
has been examined in tracheal mucus, in tracheal
washes, and in BALF. For a diagnosis of diffuse
airway disease, bronchoalveolar lavage is preferable
to examination of tracheal secretions because there
can be a wide variation in the number of neutrophils
in the tracheal secretions of normal horses.12 The
percentage of neutrophils in the BALF of control
horses is much less variable and usually less than
5%. In addition, tracheal secretions are richer in
neutrophils and have fewer lymphocytes than BALF
and are therefore not a good reflection of the status of
the more peripheral airways.13 Bronchoalveolar la-
vage (BAL) can be conducted with the endoscope if it
is long enough (at least 2 m). Otherwise a BAL
tubea can be used. The endoscope or lavage tube is
wedged in an airway. The location of the wedge is
unimportant because chronic airway disease is usu-
ally diffuse.14 Three hundred ml of sterile saline is
instilled and withdrawn in 100-ml aliquots. About
half of the volume infused is usually recovered. The
AAEP PROCEEDINGS @ Vol. 43 / 1997 107
 Reprinted in the IVIS website with the permission of the AAEP
MILNE LECTURE: LOWER AIRWAY OF THE HORSE
recovered BALF is examined grossly for the presence
of mucuopurulent exudate or blood (sometimes the
result of trauma by the tube). Total and differential
cell counts are made from BALF.15 In normal horses,
macrophages and lymphocytes constitute the major-
ity of cells in BALF; neutrophils make up less than
5% [Fig. 1(a)]. The majority of horses with airway
inflammation have an increase in the number and
percentage of neutrophils. This can be as few as
10% in horses with IAD and up to 90% in some horses
with COPD [Fig. 1(b)]. Occasionally there will be an
increased number of eosinophils16 or mast cells17 in
young horses. In the former, one should rule out
lungworms or migrating strongyles before conclud-
ing that there is an eosinophilic pulmonary disease.
Radiographic examination of the lungs is usually
unrewarding in horses with diffuse airway disease
unless the condition is advanced, when there may be
increased linear densities. The latter, however, is
very dependent on radiographic technique and on
the state of inflation of the lung when the radiograph
is taken. Radiography should be done to rule out
other problems such as lung abscess or pleuropneu-
monia. Scintigraphy will reveal uneven distribu-
tion of ventilation and ventilation–perfusion
mismatching.
(a)
(b)
Fig. 1. Cells in BALF. (a) Normal horse: L, lymphocyte; M,
inactive macrophage; AM, active macrophage. (b) Horse with
COPD [note the massive number of neutrophils (N)]. M, macro-
phage, which appears to be engulfing a neutrophil.
108 1997 @ Vol. 43 @ AAEP PROCEEDINGS
Proceedings of the Annual Convention of the AAEP 1997
Close window to return to IVIS
A measurement of blood gas tensions detects
hypoxemia, the magnitude of which depends on the
severity of disease. In the horse with mild disease,
arterial oxygen tension may be normal at rest, but
the exercise-induced hypoxemia normally seen in
strenuously exercising horses will be more severe or
develop earlier in the course of exercise. It is
important to remember that changes in blood gas
tensions simply reflect the magnitude of lung dysfunc-
tion; they are not specific for a particular problem.
5. Functional Consequences of Airway Obstruction
The changes in lung function associated with airway
disease have been extensively studied in horses with
COPD.18 Diffuse airway obstruction results in in-
creased pulmonary resistance (RL) and decreased
dynamic compliance (Cdyn). These changes necessi-
tate that the horse use a greater effort, i.e., change in
pleural pressure, to generate its tidal volume.
When COPD-susceptible animals are pastured or
bedded on shredded paper and fed a cubed diet for
several weeks, RL and Cdyn usually are not different
from those of control animals, but when the suscep-
tible animals are returned to the hay and straw
environment, RL increases and Cdyn decreases as
obstruction redevelops.
Airway obstruction of COPD is a result of broncho-
spasm, mucus accumulation, and probably also in-
flammatory changes in the airway wall. The rapid
decrease in RL following administration of broncho-
dilators results from the relaxation of airway smooth
muscle. After administration of bronchodilators,
some obstruction persists, particularly in the periph-
eral airways, probably as a result of mucus plugging
and inflammation.
The diffuse airway obstruction results in abnormal
distribution of ventilation that causes ventilation–
perfusion mismatching and hypoxemia, a low PaO2.
Despite the increased work of breathing necessitated
by airway obstruction, hypoventilation, i.e., an in-
crease in PaCO2, is not a consistent finding. The
magnitude of ventilation–perfusion mismatching and
hypoxemia correlates with the clinical signs and
severity of bronchiolitis.
Hypoxemia provides increased respiratory drive,
which results in an increased frequency of breathing
without a change in tidal volume. For the horse to
inhale or exhale the tidal volume in a shorter period
of time, airflow rates must increase even though the
airways are obstructed. The horse solves this di-
lemma by having higher than normal flow rates
toward the end of inspiration and at the beginning of
exhalation. These are the points in the respiratory
cycle when lung volume is greatest and therefore the
airway lumens have the greatest diameter. The
breathing strategy chosen by the horse with airway
obstruction gives rise to the counterintuitive observa-
tion that peak flow rates increase as the airways
narrow.
Increased pulmonary arterial pressure has been
consistently described in COPD-affected horses, the
 Reprinted in the IVIS website with the permission of the AAEP
MILNE LECTURE:
magnitude of hypertension increasing with the sever-
ity of the disease. The increased pressure results
from increased vascular resistance that is probably
due to a combination of hypoxic vasoconstriction of
pulmonary arteries, alveolar hyperinflation that com-
presses capillaries, and inflammatory mediator-
induced vasospasm. Even though COPD is
associated with pulmonary hypertension, right heart
failure is not a consistent finding in horses with
severe airway disease.
6. Pathogenesis of Lower Airway Disease
Lower airway disease can be the result of unresolved
viral or bacterial infections that are due to a specific
hypersensitivity, i.e., an antigen–antibody reaction,
the result of inhalation of dusts, endotoxins, or
irritating gases, or as part of the EIPH complex.
Very often the initiating cause of the problem is
unknown, and it is quite likely that many cases of
equine airway disease have a multifactorial etiology.
A. Inflammation is at the Core
It is now very clear that inflammation is the basis of
almost all the changes that occur in chronic airway
diseases. During the inflammatory cascade, cyto-
kines and mediators are released that have a variety
of effects in the airways. These events have been
most extensively studied in horses with COPD18 and
are summarized here. Within 7 h of exposing a COPD-
susceptible animal to stable dusts, there is an influx of
neutrophils into the lung19 and the airway lumen,
whence they can be recovered by BAL. Even though
COPD is thought to have an allergic etiology, eosinophils
do not seem to be involved except in the recovery phase,
when there can be an increase in eosinophil numbers.20
Associated with the inflammatory response is the re-
lease of proinflammatory mediators that induce broncho-
spasm. Of the proinflammatory mediators known to
be released during the inflammation associated with
heaves, histamine contracts airway smooth muscle,21
increases the sensitivity of airway sensory receptors,22
facilitates neurotransmission at airway autonomic gan-
glia,23 and augments the response of smooth muscle to
acetylcholine that is released from parasympathetic
nerves (Fig. 2).b However, histamine H1 antagonists
have little therapeutic benefit in the treatment of equine
COPD, so it is likely that mediators in addition to
histamine also are operative. Levels of thromboxane
and 15-hydroxyeicosatetraenoic acid (15-HETE) are in-
creased in horses with heaves,24–26 but these mediators
are unlikely to be important in bronchospasm because
they have no direct effect on smooth muscle. Prelimi-
nary evidence suggests that there is increased produc-
tion of leukotrienes (LT’s) in heaves.27 Because
leukotrienes LTC4, D4, and E4 contract peripheral air-
way smooth muscle in vitro,21 augment the response of
peripheral airways to parasympathetic nerve activa-
tion,b and cause respiratory distress when adminis-
Proceedings of the Annual Convention of the AAEP 1997
Close window to return to IVIS
LOWER AIRWAY OF THE HORSE
Fig. 2. Sites at which inflammation can facilitate the reflex that
leads to smooth muscle contraction and bronchospasm (CNS,
central nervous system).
tered to horses,28 LT’s may be important mediators of
bronchospasm.
Although the increased production of bronchospas-
tic mediators is one possible mechanism of broncho-
spasm, a reduced availability of inhibitory mediators
and neurotransmitters could also contribute to it.
Prostaglandin E2 (PGE2) is a potent inhibitor of
smooth muscle contraction,29 and its production by
airway mucosa is reduced in heaves-affected ani-
mals.25 This deficiency of PGE2 may potentiate the
contractile effect of acetylcholine on smooth muscle.
The inhibitory nonadrenergic–noncholinergic ner-
vous system also is dysfunctional.30,31 There is no
evidence for downregulation of b2 adrenoceptors.
Rather, b2 adrenoceptors appear to be activated in
heaves-affected animals because the administration
of a b-blocker worsens the airway obstruction.32
Smooth muscle contraction is normally inhibited to a
small degree by a nonprostanoid inhibitory factor
released by the airway epithelium.31,33 Although
there are major structural changes in the airway
epithelium of heaves-affected horses,34,35 there is no
evidence to support a deficiency of this epithelium-
derived inhibitory factor.31,36 Rather, its production
appears to be increased in heaves-affected horses.31
In addition to effects on smooth muscle, inflamma-
tory cells and mediators also increase the production
and secretion of mucus (Fig. 3) and increase bron-
chial blood flow and vascular permeability. The
latter events contribute to obstruction by increasing
the mucus in the airway lumen and by causing
edema of the airway wall. All in all, the acute
inflammatory response leads to the signs of airway
disease, including cough, increased mucopus in the
airways, and varying degrees of respiratory distress
and exercise intolerance, which are a result of air-
way obstruction.
A single inflammatory event may resolve without
complications, but if the animal is continuously or
repeatedly exposed to agents that injure the air-
ways, some changes may become chronic. Under
this situation, structural changes occur in the air-
AAEP PROCEEDINGS @ Vol. 43 / 1997 109
 Reprinted in the IVIS website with the permission of the AAEP
MILNE LECTURE: LOWER AIRWAY OF THE HORSE
Fig. 3. Airway wall from a horse with COPD. Note the numer-
ous goblet cells in the epithelium. The plexus of bronchial
vessels (V) beneath the epithelium is clearly visible.
way wall. There is proliferation of the mucus appa-
ratus so that overproduction of mucus occurs, and
there is proliferation of both the mucosa and airway
smooth muscle, which contribute to airway hyperre-
sponsiveness.
B. What is Airway Hyperresponsiveness?
Airway hyperresponsiveness is a term used to de-
scribe an overreaction of the airways to a stimulus
that is usually inconsequential. For example, nor-
mal horses do not develop bronchospasm when they
inhale a solution containing 0.1 mg/ml of histamine,
but a horse with an exacerbation of COPD develops
quite severe airway obstruction when it inhales such
a solution. The latter horse is said to have hyperre-
sponsive airways. Airway hyperresponsiveness is
usually nonspecific, that is, the airways narrow more
vigorously in response to all agents that can cause
bronchospasm. This list of agents includes inflam-
matory mediators and the neurotransmitter acetyl-
choline, which is released from parasympathetic
nerves when irritant receptors are activated by
inhaled irritants. Airway hyperresponsiveness is
associated with airway inflammation and is due to
the actions of mediators on neuromuscular regula-
tion and to structural changes in the airway wall
that amplify the effects of bronchospasm.
From a clinical viewpoint, airway hyperresponsive-
ness is important because it contributes to a vicious
cycle that perpetuates airway obstruction. A horse
may have a mild inflammatory response but little
evidence of respiratory distress or poor performance.
If this animal is then exposed to a stimulus that
irritates the airways or releases mediators, the
effects of these agents will be exaggerated so that the
horse develops more severe airway obstruction.
Owners of horses with chronic airway disease will
frequently be diligent about protecting their animal
from dusts by keeping it outside. They will, how-
ever, bring it into the stable for grooming or other
activities. This brief exposure may be enough to
initiate an inflammatory response that leads to
110 1997 @ Vol. 43 @ AAEP PROCEEDINGS
Proceedings of the Annual Convention of the AAEP 1997
Close window to return to IVIS
hyperresponsiveness that can persist for several
days. Owners will then erroneously conclude that
their attempts to improve the horse by environmen-
tal management are of no use.
In horses, airway hyperresponsiveness has been
well documented in association with COPD.37,38
The minimal exposure to stable dusts necessary to
induce hyperresponsiveness is unknown, but after the
horse has been stabled for 7 h, hyperresponsiveness
persists for at least 72 h.39 Hyperresponsiveness
wanes when the environment is changed and inflam-
mation resolves. Hyperresponsiveness has also been
documented following equine influenza infection.40
Although it is likely that hyperresponsiveness is also
present in horses with IAD, it has not been confirmed.
C. Role of Airway Wall Thickening
In asthmatics, increased responsiveness to a broncho-
constricting stimulus can be explained partly or
wholly by a reduction in airway caliber that is the
result of airway wall thickening.41 Moderate
amounts of airway wall thickening, which have little
effect on baseline caliber, can have marked effects on
the degree of airway narrowing caused when the
smooth muscle shortens. These effects are greater
when the airway wall thickening is localized to the
peripheral rather than the central airways. Broad-
stone et al.42 reported that, compared with controls,
horses with COPD have significantly increased pul-
monary resistance and significantly decreased dy-
namic compliance immediately before being
euthanized. Quantitative assessment of airway
morphology in lung tissue samples collected at this
time showed that airway smooth muscle area and
wall thickness were significantly increased in af-
fected horses compared with controls. Similar struc-
tural changes in the airways in cases of fatal asthma
can account for excessive airway narrowing, even in
the presence of normal smooth muscle shortening.43
Changes leading to increases in wall thickness are
the result of inflammatory responses. During acute
COPD, edema fluid increases wall thickness, and
during chronic inflammation, release of growth fac-
tors could result in smooth muscle or connective
tissue proliferation.
D. Importance of the Environment
The importance of environmental factors in equine
lower airway disease has been recognized for several
hundred years. In the late 1800’s, it was thought
that bad hay contributed to airway disease because
toxins were absorbed from the gastrointestinal sys-
tem.44 Now we are just as convinced that it is the
inhaled dust in the environment that is the cause of
airway inflammation.
The dusts to which horses are exposed most com-
monly are those found in stables. Even though
horses may inhale dusts generated on the racetrack
or in arenas, animals are exposed to these dusts for a
matter of minutes per day, whereas they inhale
stable dusts for many hours per day. Agricultural
Reprinted in the IVIS website with the permission of the AAEP
MILNE LECTURE:
dusts contain a variety of materials that can be
inhaled, including bacteria and bacterial endotoxins;
animal-derived components, e.g., dander, hair, urine,
and feces; parts of feed grains and plants; pollens;
insect parts and feces; and fungal parts, e.g., spores,
hyphae, sporangia, and mycotoxins.45 The actual
constituents of dust in a stable depend on what is
being fed and what is used for bedding, when and
how it was grown and harvested, and the conditions
under which it was stored.46 Hays can be classified
as good, moldy, or very moldy, based on the number
and types of spores that they contain. Hay stored
above 40% water is rich in spores of thermophilic
actinomycetes such as Aspergillus fumigatus, Ther-
moactinomyces vulgaris, and Faeni rectivirgula, the
species thought to be important in the induction of
COPD.
Several investigators have measured dust levels
in stables.47–50 When dust levels are measured in
the corridor or in the air of the stall itself, the
concentration is in the range of 0.25 to 2.5 mg/m3;
higher values are obtained during feeding and bed-
ding and when horses are receiving particularly
moldy feed. Dust levels tend to decrease at night
when there is less activity, and in general, the larger
particles sediment out at night, whereas respirable
particles, less than 5 µm in diameter, remain sus-
pended in the air.
Particulate concentrations in air depend on the
content of particulates in the source material, gener-
ally hay, the agitation of the material, and the rate of
removal of dusts by the ventilation system. The
veterinarian’s ability to detect environmental qual-
ity depends on all these factors. In a well-venti-
lated stable, there can be very high local con-
centrations of dust around the feed source but dust
levels in the corridors may be quite low, and so one
may conclude, incorrectly, that there is not a dust
problem. Woods et al.50 demonstrated very clearly
that dust levels in the stall do not reflect dust levels
in the breathing zone of the horse, i.e., close to the
nostrils, especially when there is a point source of
dust. When horses eat hay, they toss the material
and release dusts. Under these conditions, the dust
concentration in the breathing zone can be 30 to 40
times higher than that a few feet away in the stall.
When the point dust source is eliminated by feeding
a pelleted diet, dust concentrations in the breathing
zone decrease to 3% of those recorded when hay is
fed and are identical to those in the stall.
Because of the complexity of agricultural dusts, it
is difficult to identify responses to individual
agents.45,51 Total airborne dust is what is impor-
tant, and industrial bronchitis in humans is more
prevalent when workers breathe greater than 10
mg/m3 of dust for an 8-h period, regardless of whether
it is organic or inorganic. Dust levels in the breath-
ing zone of horses being fed poor hay average 20
mg/m3 over a 24-h period.50 Little wonder then that
stabled horses develop chronic airway disease and
some become respiratory cripples. The importance
Proceedings of the Annual Convention of the AAEP 1997
Close window to return to IVIS
LOWER AIRWAY OF THE HORSE
of stable management in equine respiratory disease
was demonstrated in several studies. Burrell et al.2
reported that horses kept on shredded paper in
American barns suffered less lower airway disease
than horses on straw in loose boxes. The episodes
of lower airway disease were of shorter duration in
the former group. In the same study, horses bedded
on paper coughed less than those on straw. Clarke
and Madelin52 reported that recovery from equid
herpesvirus infection was delayed in horses in badly
ventilated stables with high fungal contamination.
When veterinarians and horse owners think of
dusts, they tend to think of antigenic material that
can initiate an allergic reaction. However, some of
the components of dusts, e.g., endotoxin, can initiate
inflammation without invoking a specific hypersensi-
tivity reaction.53 It is now becoming clear that
simply depositing small particles on the epithelium
of the airways can initiate the production of cyto-
kines that contribute to an inflammatory response.54
Because acute bouts of airway inflammation lead to
airway hyperresponsiveness and to mucus secretion
and recurrent bouts lead to proliferation of the
mucus apparatus and smooth muscle in the airway
wall, it is vital to reduce stable dust levels as much
possible.
E. Role of Allergy
It is widely believed that COPD is a hypersensitivity
disease. In stabled horses, the responsible agents
are thought to be thermophilic molds and fungi such
as A. fumigatus, T. vulgaris, and F. rectivirgula, but
other antigens may be involved. A similar syn-
drome, summer-pasture-associated obstructive air-
way disease (SPOAD), which occurs primarily in the
south of the U.S.,55 is thought to be a hypersensitiv-
ity to molds in pastures. The evidence to support
an allergic etiology for COPD includes higher levels
of mold-specific immunoglobulins IgA, IgG, and IgE
in the BALF of COPD-affected horses,56 increased
numbers of IgA- and IgG(Fc)-containing cells and
even free IgA and IgG(Fc) in interepithelial clefts of
COPD-affected horses,57,58 and mast cells in bron-
chial and intracellular clefts of COPD-affected
horses.34 Despite evidence in favor of an allergic
basis for COPD, the challenge of COPD-susceptible
horses with F. rectivirgula, the etiological agent most
frequently implicated, induces airway inflammation
but does not reproduce the characteristic total syn-
drome of airway obstruction.59 The duration of
exposure, a combination of antigens, or other factors
may also be important.
Recently, lymphocyte populations have been stud-
ied in BALF from horses with COPD and IAD. Mc-
Gorum et al.60 showed an increase in the percentage
of CD51 CD82 (presumably CD41) T-lymphocytes
and a concurrent decrease in CD81 lymphocytes in
BALF from COPD-susceptible animals exposed to
hay and straw. Presumably these cells recognize
antigen and orchestrate the inflammatory response.
Because inflammation and clinical signs are appar-
AAEP PROCEEDINGS @ Vol. 43 / 1997 111
 Reprinted in the IVIS website with the permission of the AAEP
MILNE LECTURE: LOWER AIRWAY OF THE HORSE
ent 5–7 h after antigen exposure, COPD is character-
istic of a delayed hypersensitivity.
The changes in inflammatory cell populations and
lymphocyte subpopulations of BALF in IAD differs
from that in COPD. In IAD, there is an increase in
populations of neutrophils, lymphocytes, and macro-
phages, whereas in COPD only neutrophils increase.
There is a low population of CD41 lymphocytes and
a greater proportion of non-B non-T cells (null cells)
in IAD. For this reason, Moore et al.1 concluded
that IAD does not have an allergic etiology, is not an
early stage of COPD, and is probably a response to
infection or environmental factors. With regard to
the latter, we recently demonstrated that stabling
control horses for 1 week and feeding moldy hay
induces airway inflammation.c
F. Role of Viral and Bacterial Infections
Acute infections with respiratory viruses, especially
influenza, cause inflammation and disruption of the
epithelium. These changes are associated with in-
creased mucus secretion, airway hyperresponsive-
ness,40 and airway obstruction. Airway hyper-
responsiveness persists for several weeks following
the resolution of clinical signs of acute infection, and
during this period horses are more likely to develop
airway obstruction in response to irritants in their
environment. There is also evidence that it is easier
to sensitize animals to inhaled antigens during an
acute viral infection.
The difference in inflammatory response in la-
vages from horses with IAD and COPD led Moore et
al.1 to conclude that the etiopathogenesis of IAD and
COPD differs and that infection may be a cause of
IAD. This is in agreement with the results of
studies by workers in England. Wood et al.62 stud-
ied 551 tracheal washes from 278 horses with respi-
ratory disease or poor performance. The likelihood
of finding inflammation increased with the number
of bacterial colony-forming units per milliliter of
wash and lower airway inflammation was particu-
larly associated with bacteria in horses less than 3
years old. The aerobic bacteria Streptococcus zooepi-
demicus, Pasteurella–Actinobacillus-like species, and
S. pneumoniae were significantly associated with
lower airway inflammation. Mycoplasma infec-
tions, especially Mycoplasma felis and M. equirhinis,
may work synergistically with other bacteria.63
Burrell et al.2 have reported on the importance of
bacterial infection as a cause of IAD in British
racehorse training yards. In these animals there
was a positive correlation between the severity of the
inflammatory response and the number of bacterial-
colony-forming units in tracheal washes. The au-
thors state that 2-year-old horses are 7 times more
likely than 3-year olds to have lower respiratory
tract disease. The number of colony-forming units
reported in this study (.3000/ml of tracheal wash)
suggests that some of the horses had pneumonia or
that there was contamination from the upper airway.
In the latter study, there was no association between
112 1997 @ Vol. 43 @ AAEP PROCEEDINGS
Proceedings of the Annual Convention of the AAEP 1997
Close window to return to IVIS
the onset of IAD and viral seroconversion. It is
difficult to judge the significance of the association
between bacterial counts and inflammation, and one
should not assume a cause-and-effect relationship.
If the tracheobronchial tree is inflamed for other
reasons, e.g., environmental insult, it may be more
easily colonized by bacteria.
Even though, clinically, the onset of COPD may
follow an acute infectious disease, the relationship
between bacterial and viral infections in the young
horse and the development of COPD in the older
horse is virtually unknown. COPD-affected ani-
mals have been reported to have higher levels of
influenza A hemagglutination-inhibiting activity
than control animals.64
G. Interactions with Exercise-Induced
Pulmonary Hemorrhage
Airway inflammation and plugging of small airways
with mucopurulent exudate have been described in
association with regions of EIPH.65 There are two
possible cases to explain this finding. The small
airway obstruction may have contributed to the
rupture of pulmonary capillaries by accentuating the
decrease in alveolar pressure that normally occurs
during inhalation. This greater decrease in alveo-
lar pressure increases the pressure gradient across
the alveolar capillary wall, tending to cause stress
failure. Alternatively, the airway inflammation
could be a consequence of the presence of blood in the
airspaces.66 Whatever the reason for airway inflam-
mation, neovascularization of inflamed airways by
the bronchial circulation68 may provide a network of
fragile capillaries that contribute to episodes of
EIPH.
7. Management of Lower Airway Disease
A. Reducing Dust and Aeroallergen Concentrations
Improving air quality in the horse’s environment is
the most important step in the prevention and
treatment of equine lower airway disease. This can
be done in several ways: by removing point sources
of dust, by instituting a low-dust management
scheme, and by improving overall ventilation.
Although measurements of dust levels in the
breathing zone of horses have clearly demonstrated
that feed is the prime dust source,50 this fact has
been suspected since at least 1656, when Markham67
stated that ‘‘the best diet for a horse in this cause is
grasse in summer and hay sprinkled with water in
winter.’’ Ideally, horses should be kept outdoors on
pasture and fed a dust-free diet when there is
insufficient pasture. In our experience, following
this regimen can improve horses with severe COPD
to the extent that it is difficult to induce the disease
again. If it is not possible to keep horses at pasture,
reducing dust levels in feed can be accomplished by
use of low-dust feed such as a complete pelleted diet
or grass silage. High-quality hay is less dusty than
poorly cured hay. Dampening the feed has been
 Reprinted in the IVIS website with the permission of the AAEP
MILNE LECTURE:
used to reduce dust, but Dixon et al.69 reported that
this was not associated with success in treating
COPD. Unless the source of dust in the feed is
removed, all other attempts to improve the environ-
ment are useless.
Overall, dust levels in stables can be reduced by a
low-dust management scheme. Bedding horses on
shredded paper or shavings will reduce dust expo-
sure. Preferably, hay should not be stored in the
same barn as the horses and certainly not above the
horses from where it can be dropped down into the
stalls to create the maximum dust levels. In large
stables, it is wise to keep horses that are dust
sensitive together so that one is not feeding hay next
door to a horse that is on a pelleted diet. Dampen-
ing aisles during the busy times and before sweeping
also helps to reduce dust levels. Remember that
these measures are good not only for the horse but
for stable personnel.
Improving stable ventilation will decrease not only
dust levels but also concentrations of gases such as
ammonia that may be irritating to the respiratory
system. Ideally, stables should be constructed with
the advice of an agricultural engineer who has
experience with animal housing. In older stables,
windows and doors should be open as much as
possible. Dixon et al.69 recommends at least 3 square
feet of opening in the rear wall of the stall and an
open half-door in the front. In the north, stables
are often closed in winter. This is for the comfort of
personnel; horses do not need to be kept warm.
B. Use of Bronchodilators
Because airway obstruction is primarily a result of
bronchospasm, bronchodilators provide relief from
respiratory distress. However, this is symptomatic
relief and it does not attack the underlying problem
of airway inflammation. Bronchodilators should be
considered as an adjunct to the primary aim of
therapy, which is the relief of inflammation. Ide-
ally, bronchodilators should be administered by inha-
lation, and devices are becoming available for such
treatment. In this way, high concentrations of drugs
can be delivered locally without significant side
effects. The bronchodilator drugs available, doses
to be used, and routes of administration are dis-
cussed in a different paper in this proceedings (see
page 95).
C. Use of Anti-Inflammatory Drugs
When airway inflammation cannot be resolved by
changes in management, anti-inflammatory therapy
is indicated. Frequently this therapy is combined
with a change in the horse’s environment. Cortico-
steroids are still the drug of choice. The treatment
of human asthma has been revolutionized by the use
of inhaled steroids. Asthmatics monitor their own
lung function and adjust their steroid dose accord-
ingly. A similar treatment modality should be our
goal in veterinary medicine. The use of inhaled
steroids for treatment of horses is becoming practical
Proceedings of the Annual Convention of the AAEP 1997
Close window to return to IVIS
LOWER AIRWAY OF THE HORSE
as convenient devices for aerosol delivery reach the
market. In the absence of a convenient inhalation
therapy device, systemic steroid administration will
continue to be the mainstay of treatment for inflam-
matory airway disease. Corticosteroid treatment is
described in a different paper in this proceedings
(see page 95).
Cromolyn sodium, a mast cell stabilizer, can also
be classified as an anti-inflammatory therapy. This
drug has been shown to prevent airway obstruction
in COPD-affected horses and to alleviate clinical
signs and decrease airway reactivity in young horses
with an increased number of metachromatic cells
(mast cells) in the BALF (see page 95 in this
proceedings).17
Newer anti-inflammatory agents such as LT syn-
thesis inhibitors, COX-2 inhibitors, and phosphodies-
terase isoenzymes are being tested in models of
airway disease. A LT synthesis inhibitor (Zileu-
tond) is available for the treatment of asthma. Some
of these compounds may be tried in horses, but
practitioners must realize that the small size of the
equine drug market deters companies from develop-
ing compounds specifically for the treatment of horse
airway diseases.
D. Other Treatments
The use of nonspecific immune stimulation in the
treatment of equine respiratory disease was recently
reviewed by Moore et al.70 Several types of agents
are available. Inactivated Propionibacterium acnes
(Eqstime) and purified mycobacterial cell wall ex-
tract (Equimune IVf) have been approved for the
treatment of equine respiratory disease complex and
are reported to hasten recovery. Acemannan and
levamisole are also reported to be useful in treat-
ment of equine airway disease.
Oral administration of a low dose of human inter-
feron-a (50 U) has been reported to lower the total
cell count in BALF from horses with IAD and to
make the cell profile noninflammatory.70 Higher
doses are less effective. Interferon has several ac-
tions on the immune system that may explain its
beneficial effects in horses with IAD.
Hyposensitization is being used to treat chronic
airway disease based on the results of enzyme-linked
immunosorbent assay tests for antigen-specific IgE
in blood. In people, hyposensitization is a useful
therapy for IgE-mediated allergic diseases, espe-
cially allergic rhinitis, and has been shown to be of
benefit in allergic asthma, particularly allergy to
house dust mites in children. The role of IgE in
horse airway disease is still in debate. COPD is not
an immediate hypersensitivity,71 and there is no
strong evidence of mast cell involvement except in a
few horses.17 Using skin tests to identify antigens
responsible for an allergic response in the airways is
not useful because positive skin tests to molds occur
frequently in all horses.72 Identification of antigens
by means of IgE may be preferable. Despite these
questions, Beech and Merryman73 reported a posi-
AAEP PROCEEDINGS @ Vol. 43 / 1997 113
 Reprinted in the IVIS website with the permission of the AAEP
MILNE LECTURE: LOWER AIRWAY OF THE HORSE
tive response of the majority of COPD-affected horses
to hyposensitization therapy. Large-scale clinical
trials will be necessary to judge the value of this
treatment in horses.
This research was supported by grants from 3M
Animal Care Products and Bayer AG.
References and Footnotes
1. Moore BR, Krakowka S, Robertson JT, et al. Cytologic
evaluation of bronchoalveolar lavage fluid obtained from
Standardbred racehorses with inflammatory airway disease.
Am J Vet Res 1995;56:562–567.
2. Burrell MH, Wood JLN, Whitwell KE, et al. Respiratory
disease in thoroughbred horses in training: the relationship
between disease and viruses, bacteria and environment. Vet
Rec 1996;139:308–313.
3. Rossdale PD, Hopes R, Wingfield Digby NJ, et al. Epidemio-
logical study of wastage among racehorses 1982 and 1983. Vet
Rec 1985;116:66–69.
4. Bracher V, von Fellenberg R, Winder CN, et al. An investiga-
tion of the incidence of chronic obstructive pulmonary disease
(COPD) in random populations of Swiss horses. Equine Vet
J 1991;23:136–141.
5. Larson VL, Busch RH. Equine tracheobronchial lavage:
comparison of lavage cytologic and pulmonary histopatho-
logic findings. Am J Vet Res 1985;46:144–146.
6. Dixon PM, Railton DI, McGorum BC. Equine pulmonary
disease: a case control study of 300 referred cases. Part 1:
examination techniques, diagnostic criteria and diag-
noses. Equine Vet J 1995;27:416–421.
7. Sweeney CR, Humber KA, Roby KAW. Cytologic findings of
tracheobronchial aspirates from 66 Thoroughbred race-
horses. Am J Vet Res 1992;53a:1172–1175.
8. Fogarty U, Buckley T. Bronchoalveolar lavage findings
in horses with exercise intolerance. Equine Vet J
1991;23:434–437.
9. Dixon PM, Railton DI, McGorum BC. Equine pulmonary
disease: a case control study of 300 referred cases. Part 2:
details of animals and of historical and clinical findings.
Equine Vet J 1995;27:422–427.
10. Petsche VM, Derksen FJ, Robinson NE. Tidal breathing
flow-volume loops in horses with recurrent airway obstruc-
tion (heaves). Am J Vet Res 1994;55:885–891.
11. Robinson NE, Olszewski M, Berney C, et al. Are clinical
signs an indicator of the severity of airway obstruction?, in
Proceedings. 13th Vet Respir Symp 1994;A–11.
12. Dixon PM, Railton DI, McGorum BC. Equine pulmonary
disease: a case control study of 300 referred cases. Part 3:
ancillary diagnostic findings. Equine Vet J 1995;27:428–435.
13. Derksen FJ, Brown CM, Sonea I, et al. Comparison of
transtracheal aspirate and bronchoalveolar lavage cytology
in 50 horses with chronic lung disease. Equine Vet J 1989;21:
23–26.
14. Sweeney CR, Rossier Y, Ziemer EL, et al. Effects of lung site
and fluid volume on results of bronchoalveolar lavage fluid
analysis in horses. Am J Vet Res 1992;53:1376–1379.
15. Moore BR. Lower respiratory tract disease. Vet Clin North
Am [Equine Pract] 1996;12:457–472.
16. Hare JE, Viel L. Pulmonary eosinophilia associated with
increased airways responsiveness in young racing
horses. Am J Vet Res (in press).
17. Hare JE, Viel L, O’Byrne PM, et al. Effect of sodium
cromoglycate on light racehorses with elevated metachromatic
cell numbers on bronchoalveolar lavage and reduced exercise
intolerance. J Vet Pharmacol Therap 1994;17:237–244.
18. Robinson NE, Derksen FJ, Olszewski MA, et al. The patho-
114 1997 @ Vol. 43 @ AAEP PROCEEDINGS
Proceedings of the Annual Convention of the AAEP 1997
Close window to return to IVIS
genesis of chronic obstructive pulmonary disease of
horses. Br Vet J 1996;152:283–306.
19. Fairbairn SM, Page CP, Lees P, et al. Early neutrophil but
not eosinophil or platelet recruitment to the lungs of allergic
horses following antigen exposure. Clin Exper Allergy 1993;
23:821–828.
20. Derksen FJ, Scott JS, Miller DC, et al. Bronchoalveolar
lavage in ponies with recurrent airway obstruction (heaves).
Am Rev Respir Dis 1985;132:1066–1070.
21. Doucet MY, Jones TR, Ford-Hutchinson AW. Responses of
equine trachealis and lung parenchyma to methacholine,
histamine, serotonin, prostanoids, and leukotrienes in vitro.
Can J Physiol Pharmacol 1990;68:279–383.
22. Undem BJ, Hubbard W, Weinreich D. Immunologically in-
duced neuromodulation of guinea pig nodose ganglion nerves.
J Auton Nerv Syst 1993;44:34–44.
23. Myers A, Undem BJ. Antigen depolarizes guinea pig bron-
chial parasympathetic ganglion neurons by activation of
histamine H1 receptors. Am J Physiol 1995;268:L879–L884.
24. Gray PR, Derksen FJ, Robinson NE, et al. The role of
cyclooxygenase products in the acute airway obstruction and
airway hyperreactivity of ponies with heaves. Am Rev Respir
Dis 1989;140:154–160.
25. Gray PR, Derksen FJ, Broadstone RV, et al. Decreased
airway mucosal prostaglandin E2 production during airway
obstruction in an animal model of asthma. Am Rev Respir
Dis 1992;146:586–591.
26. Gray PR, Derksen FJ, Broadstone RV, et al. Increased
pulmonary production of immunoreactive 15-hydroxyeico-
satetraenoic acid in an animal model of asthma. Am Rev
Respir Dis 1992;145:1092–1097.
27. Doucet MY, Vrins AA, Ford-Hutchinson AW. Histamine inha-
lation challenge in normal horses and in horses with small
airway disease. Can J Vet Res 1991;55:285–293.
28. Marr KA, Lees P, Page CP, et al. Effects of inhaled LTD4 and
LTB4 on bronchoconstriction and radiolabelled neutrophil
accumulation in the horse. Am J Respir Crit Care Med
1995;151:A825.
29. Wang Z, Yu M, Robinson NE, et al. Exogenous but not
endogenous PGE2 modulates pony tracheal smooth muscle
contractions. Pulm Pharmacol 1992;5:225–231.
30. Broadstone RV, LeBlanc PH, Derksen FJ, et al. In vitro
responses of airway smooth muscle from horses with recur-
rent airway obstruction. Pulm Pharmacol 1991;4:191–202.
31. Yu MF, Wang ZW, Robinson NE, et al. Modulation of bron-
chial smooth muscle function in horses with heaves. J Appl
Physiol 1994;77:2149–2154.
32. Scott JS, Broadstone RV, Derksen FJ, et al. b-Adrenergic
blockade in ponies with recurrent obstructive pulmonary
disease. J Appl Physiol 1988;64:2324–2328.
33. Tessier GJ, Lackner PA, O’Grady SM, et al. Modulation of
equine tracheal smooth muscle contractility by epithelial-
derived and cyclooxygenase metabolites. Respir Physiol 1991;
84:105–114.
34. Kaup F-J, Drommer W, Damsch S, et al. Ultrastructural
findings in horses with chronic obstructive pulmonary disease
(COPD) II: pathomorphological changes of the terminal air-
ways and the alveolar region. Equine Vet J 1990;22:349–355.
35. Kaup F-J, Drommer W, Deegen E. Ultrastructural findings
in horses with chronic obstructive pulmonary disease (COPD)
I: alterations of the larger conducting airways. Equine Vet
J 1990b;22:343–348.
36. Loschner E, Wilkens JH, Deegen E. Epithelium-dependent
modulation of equine smooth muscle tone in horses with
obstructive airway disease, in Proceedings. 12th Vet Respir
Symp, 1993.
37. Derksen FJ, Robinson NE, Armstrong PJ, et al. Airway
 Reprinted in the IVIS website with the permission of the AAEP
MILNE LECTURE:
reactivity in ponies with recurrent airway obstruction (heaves).
J Appl Physiol 1985;58:598–604.
38. Klein H-J, Deegen E. Histamine inhalation provocation
test: method to identify nonspecific airway reactivity in
equids. Am J Vet Res 1986;47:1796–1800.
39. Fairbairn SM, Lees P, Page CP. Duration of antigen-induced
hyperresponsiveness in horses with allergic respiratory dis-
ease and possible links with early airway obstruction. J Vet
Pharmacol Ther 1993;16:469–476.
40. Hoffman AM, Viel L, McDonell WN, et al. Airway hyperre-
sponsiveness in ponies following a naturally-acquired influ-
enza infection. Am Rev Respir Dis 1992;145:A432.
41. Wiggs BR, Bosken C, Pare PD, et al. A model of airway
narrowing in asthma and in chronic obstructive pulmonary
disease. Am Rev Respir Dis 1992;145:1251–1258.
42. Broadstone R, Carroll N, James A, et al. Altered airway
morphometry but inconsistent inflammatory changes in horses
with recurrent airway obstruction. Am Rev Respir Dis 1996;
153:A618.
43. James AL, Pare PD, Hogg JC. The mechanics of airway nar-
rowing in asthma. Am Rev Respir Dis 1989;139:242–246.
44. Gresswell A, Gresswell JB. Diseases and disorders of the
horse: a treatise on equine medicine and surgery. York-
shire Conservative Newspaper, 1886.
45. Donham KJ. Hazardous agents in agricultural dusts and
methods of evaluation. J Ind Med 1986;10:205–220.
46. Lacey J, Dutkiewicz J. Methods of examining the microflora
of mouldy hay. J Appl Bact 1976;41:13–27.
47. Crichlow EC, Yoshida K, Wallace K. Dust levels in a riding
stable. Equine Vet J 1980;12:185–188.
48. Zeitler MH. Konzentration and Korngrössenverteilung von
luftgetragenen Staubpartikeln in Pferdeställen. Berl Münch
Tierärztl Wschr 1985;98:241–246.
49. Clarke AF. A review of environmental and host factors in
relation to equine respiratory disease. Equine Vet J 1987;19:
435–441.
50. Woods PSA, Robinson NE, Swanson MC, et al. Airborne
dust and aeroallergen concentration in a horse stable under
two different management systems. Equine Vet J 1993;25:
208–213.
51. Flaherty DK. Mechanisms of host response to grain dust.
Ann Am Conf Gov Ind Hyg 1982;2:197–205.
52. Clarke AF, Madelin TM. The relationship of air hygiene in
stables to lower airway disease and pharyngeal lymphoid
hyperplasia in two groups of Thoroughbred horses. Equine
Vet J 1987;19:524–530.
53. Jagielo PJ, Thorne PS, Kern JA, et al. Role of endotoxin in
grain dust-induced lung inflammation in mice. Am J Physiol
1996;270:L1052–L1059.
54. Borm PJ, Driscoll K. Particles of inflammation and respira-
tory tract carcinogenesis. Toxicol Lett 1996;88:109–113.
55. Seahorn TL, Beadle RE. Summer pasture-associated obstruc-
tive pulmonary disease in horses: 21 cases (1983–1991). J
Am Vet Med Assoc 1993;202:779–782.
56. Halliwell REW, McGorum BC, Irving P, et al. Local and
systemic antibody production in horses affected with chronic
obstructive pulmonary disease. Vet Immunol Immuno-
pathol 1993;38:201–215.
57. Winder NC, von Fellenberg R. Immunofluorescent evalua-
tion of the lower respiratory tract of healthy horses and of
horses with chronic bronchiolitis. Am J Vet Res 1986;47:
1271–1274.
58. Winder NC, von Fellenberg R. Chronic small airway
disease in the horse: immunohistochemical evaluation of
lungs with mild, moderate and severe lesions. Vet Rec
1988;122:181–183.
Proceedings of the Annual Convention of the AAEP 1997
Close window to return to IVIS
LOWER AIRWAY OF THE HORSE
59. McGorum BC, Dixon PM, Halliwell REW. Responses of
horses affected with chronic obstructive pulmonary disease to
inhalation challenges with mould antigens. Equine Vet J
1993;25:261–267.
60. McGorum BC, Dixon PM, Halliwell REW. Phenotypic analy-
sis of peripheral blood and bronchoalveolar lavage fluid
lymphocytes in control and chronic obstructive pulmonary
disease affected horses, before and after ‘‘natural (hay and
straw) challenges.’’ Vet Immunol Immunopathol 1993;36:
207–222.
61. Sutton GA, Viel L, Carman PS, et al. Study of the duration
and distribution of equine influenza virus subtype 2 (H3N8)
antigens in experimentally infected ponies in vivo. Can J
Vet Res 1997;61:113–120.
62. Wood JLN, Burrell MH, Roberts CA, et al. Streptococci and
Pasteurella spp. associated with disease of the equine lower
respiratory tract. Equine Vet J 1993;25:314–318.
63. Wood JLN, Newton JR, Windsor GD, et al. Epidemiological
studies of the role of mycoplasma infections in equine respira-
tory disease. Int Org Mycoplasmol Lett 1994;3:115.
64. Thorsen J, Willoughby RA, McDonell W, et al. Influenza
hemagglutination inhibiting activity in respiratory mucus
from horses with chronic obstructive pulmonary disorders
(heaves syndrome). Can J Compar Med 1983;47:332–335.
65. O’Callaghan M, Pascoe J, Tyler W, et al. Exercise-induced
pulmonary hemorrhage in the horse: results of a detailed
clinical, post-mortem, and imaging study, V: microscopic
observations. Equine Vet J 1987;19:411–418.
66. Tyler WS, Pascoe JR, Aguilera-Tejero E, et al. Morphologi-
cal effects of autologous blood or saline in airspaces of equine
lungs. Int EIPH Conf 1993;1:16.
67. Markham G. Markham’s maister-peece. London: Nicho-
las Okes, 1631;113.
68. O’Callaghan M, Pascoe J, Tyler W, et al. Exercise-induced
pulmonary hemorrhage in the horse: results of a detailed
clinical, post-mortem, and imaging study, III: subgross find-
ings in lungs subjected to latex perfusions of the bronchial
and pulmonary arteries. Equine Vet J 1987;19:394–404.
69. Dixon PM, Railton DI, McGorum BC. Equine pulmonary
disease: a case control study of 300 referred cases. Part 4:
treatments and re-examination findings. Equine Vet J 1995;
27:436–439.
70. Moore BR, Krakowka S, Cummins JJ, et al. Changes in
airway inflammatory cell populations in Standardbred race-
horses after interferon-alpha administration. Vet Immunol
Immunopath 1996;49:347–358.
71. McGorum BC, Dixon PM, Halliwell REW. Quantification of
histamine in plasma and pulmonary fluids from horses with
chronic obstructive pulmonary disease before and after ‘‘natu-
ral’’ (hay and straw) challenges. Vet Immunol Immuno-
pathol 1993;36:223–237.
72. McGorum BC, Dixon PM, Halliwell REW. Evaluation of
intradermal mould antigen testing in the diagnosis of equine
chronic obstructive pulmonary disease. Equine Vet J 1993;
25:273–275.
73. Beech J, Merryman GS. Immunotherapy for equine respira-
tory disease. Equine Vet Sci 1986;6:6–10.
aBivona, Gary, IN 46406.
bOlszewski MA. Unpublished data. July 1997.
cRobinson NE, Berney C. Unpublished data. January 1997.
dZyflo, Abbott Laboratories, Abbott Park, IL 60064.
eEqstim, ImmunoVet Inc., Tampa, FL 33610.
fEquimune IV, Vetrapharm Inc., Athens, GA 30601.
AAEP PROCEEDINGS @ Vol. 43 / 1997 115