Pulmonary Disease

Examination and
Board Review

Edited by
Ronaldo Collo Go, MD
Faculty
Division of Pulmonary, Critical Care, and Sleep Medicine
Mount Sinai Beth Israel
New York, New York
and
Crystal Run Health Care
Middletown, New York

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Pulmonary Disease Examination and Board Review

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Pulmonary disease examination and board review / edited by Ronaldo Collo Go.
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   I. Go, Ronaldo Collo, editor.
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 Contents

Contributors  xi
Preface  xv

1. THE CELL AND IMMUNOLOGY

Ronaldo Collo Go
Page 1
2. PULMONARY FUNCTION TESTS
Ronald Evans, Ronaldo Collo Go, Andrew Matragrano, and
Paul Simonelli
Page 9
3. CHEST RADIOLOGY
Mary Salvatore, Lea Azour, Adam Jacobi, Matthew Cham,
Corey Eber, and Joseph Marchione
Page 33
4. CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Jason Filopei, Lisa Bajpayee, and Ronaldo Collo Go
Page 66
5. ASTHMA
Sarun Thomas and Alfred Astua
Page 86
6. BRONCHIECTASIS
Daniel Greenblatt Fein, Stacy Verzosa, and Patricia Walker
Page 101
7. DIFFUSE PARENCHYMAL LUNG DISEASES
Ronaldo Collo Go
Page 121
8. CYSTIC LUNG DISEASES
Daniel Greenblatt Fein, Stacey Verzosa, and Patricia Walker
Page 157
9. TRACHEAL DISEASES
Omar Ibrahim and Erik Folch
Page 166

vii
viii Contents

10. MEDIASTINAL DISEASES

George Cheng and Colleen Keyes
Page 179
11. PLEURAL DISEASES
Oleg Epelbaum and Irene Galperin
Page 193
12. PULMONARY VASCULAR DISEASES
Luis D. Quintero and Roxana Sulica
Page 215
13. LUNG CANCER
Ronaldo Collo Go
Page 241
14. OCCUPATIONAL LUNG DISEASES
Brian M Walsh and Paul Simonelli
Page 264
15. SLEEP MEDICINE
Michael Marino, Ronaldo Collo Go,
Evelyn Mai, and Alfred Astua
Page 274
16. INTERVENTIONAL PULMONOLOGY
Amit Mahajan and Adnan Majid
Page 293
17. LUNG TRANSPLANTATION
Irene Louh, Hilary Robbins, and Lori Shah
Page 307
18. BACTERIAL AND VIRAL DISEASES
Navitha Ramesh, Aloke Chakravarti,
and Ronaldo Collo Go
Page 315
19. MYCOBACTERIAL DISEASES
Michael Bergman and Ronaldo Collo Go
Page 327
20. FUNGAL DISEASES
Jimmy Johannes, Tessy Paul, and Tisha Wang
Page 343
21. HIV-ASSOCIATED PULMONARY DISEASES
Anthony F. Arredondo, Richard H. Huynh, and Steven Y. Chang
Page 366
 Contents ix

22. CRITICAL CARE

Ronaldo Collo Go, Michael Silverberg, Rafael Yunen,
Amar Anantdeep Singh Sarao, Charanya Sivaramamkrishnan,
Vikram Dhawan, and Roopa Kohli-Seth
Page 386
23. BIOSTATISTICS
Michael Elias and Roopa Kohli-Seth
Page 431
24. HYPERBARIC MEDICINE
Nagendra Madisi, Ronaldo Collo Go, and Roopa Kohli-Seth
Page 447
25. CARDIOTHORACIC SURGERY
Stephen Spindel and Dong-Seok Lee
Page 459
26. PULMONARY PATHOLOGY
Abul Ala Syed Rifat Mannan and Songyang Yuan
Page 475
 2
Pulmonary Function Tests

Ronald Evans DO, Ronaldo Collo Go MD, Andrew Matragrano MD, and
Paul Simonelli MD, PhD

CASE 1 Question 2: Which of the following is part of the

reproducibility criteria?
A 24-year-old woman is being evaluated for chronic cough
with a pulmonary function test. A. No artifacts
B. Exhalation >6 seconds
** C. Two largest values of FVC are within 0.150 L from
Volume versus Time and Flow versus Time is seen below. each other
D. The start is <5% extrapolated volume of FVC
4 E. Plateau in volume-time curve
Volume (Liters)

3
CASE 2
2 A 30-year-old woman, 34 weeks age of gestation with
history of asthma comes in for routine follow-up.
1

0 1 2 3 4 5 6
IRV
Time (seconds) IC

IVC
4 VT
TLC
Flow (Second)

3
ERV
2
1 FRC
RV

0 1 2 3 4 5 6
Reproduced with permission from Wanger J, Clausen JL, Coates
Time (seconds) A, et al. Standardisation of the measurement of lung volumes.
Eur Respir J. 2005;26(3):511–522.
Question 1: What kind of artifact do you see?
A. Cough Question 1: Which of the following are increased
B. Hesitation during the third trimester of pregnancy?
C. Early termination A. TV and IC
D. Air leak B. VC
E. Glottis closure C. FRC, ER, RV

9
10 Pulmonary Disease Examination and Board Review

D. TLC Question 2: The patient had a single breath nitrogen

E. ER, IR test and the graph is below. Which portion of the graph
illustrate the nonuniform ventilation secondary to his
Question 2: Which of the following is primarily mea- disease?
sured by body plethysmography and gas dilution
­techniques?
A. TV
B. VC
C. RV IV

% of N2
D. TLC
E. FRC III

II
CASE 3 I

A 50-year-old man with COPD was referred to your

clinic for his pulmonary disease. Pulmonary function Volume in liters
tests were ordered as part of the initial evaluation.
A. I
B. II
C. III
Absolute Lung Volume in Liters

D. IV
E. All of the above
A
B
CASE 4
C
A 24-year-old man who was clinically diagnosed with
childhood asthma arrives in clinic for asthma evalua-
tion. He is asymptomatic and has no complaints.
Static Pleural Pressure or Elastic Recoil Pressure cm H20 **
Modified with permission from Hyatt RE, Scanlon PD, On physical examination, his vital signs are within nor-
Nakamura M. Interpretation of Pulmonary Function Tests. 3rd mal limits, including pulse oximetry of 97% on room air.
ed. Philadelphia, PA: Wolters-Kluwer/Lipincott Williams & He appears fit and muscular. His heart and lung exami-
Wilkins; 2008. nation is normal. Chest x-ray is also normal.

Question 1: In the static pleural pressure versus lung

volume graph above, which is more likely to represent
this patient?
A. A
B. B
C. C
D. A and C
E. All of the above
 chapter 2 Pulmonary Function Tests 11

**
Spirometry performed by his primary care physician
prior to specialty consultation is as follows:

Flow PULMONARY FUNCTION ANALYSIS

16

12 Ref Pre Pre Post Post Post

Meas % Ref Meas % Ref % Chg
8
FVC Liters 5.09 5.40 106 5.38 106 -0
4 FEV1 Liters 4.39 3.80 87 3.87 88 2
FEV1/FVC % 85 70 72
0 FEF25–75% L/sec 4.92 2.82 57 2.86 58 1
PEF L/sec 9.39 7.90 84 7.70 82 -2
-4 FET100% Sec 10.46 9.62 -8
FIVC Liters 5.09 5.28 104 5.40 106 2
-8 FIF50% Liters 5.13 4.70 -8
MVV L/min 179
-12
-2 0 2 4 6 8
Volume

**
He is sent for a methacholine challenge test as there is
a strong need to clarify if he truly has a diagnosis of
asthma. Results of the methacholine challenge test are
as follows:

BASELINE MAX RESPONSE Post-BD

Pred Actual % Pred Actual % Chng Actual % Chng
— SPIROMETRY —
FVC (L) 5.05 5.20 102 4.38 -15 5.30 +2
FEV1 (L) 4.20 3.69  87 2.86 -22 3.79 +2
FEF 25–75% (L/sec) 4.45 2.67  59 1.06 -60 2.85 +6
FEF max (L/sec) 9.52 8.73  91 6.34 -27 8.30 -4

12 12
12 10 10
10 8 8
8 6 6
6
4 4
4
2 2
2
0 0 0
-2 2 4 6 -2 1 2 3 4 5 6
-2 1 2 3 4 5 6
-4 -4 -4
-6 -6 -6
-8 -8 -8
-10 -10 -10
-12 -12 -12

Pred Pred
Pred Pre Pre
Pre Chlg Post
12 Pulmonary Disease Examination and Board Review

Stage BASELINE 0.031 MG/ML 0.0625 MG/ML 0.125 MG/ML

Dose 0.00000 0.03100 0.06250 0.12500
Does Units 0.00000 0.15500 0.31250 0.62500
C.D.U.s 0.00000 0.15500 0.46750 1.09250
— SPIROMETRY —
FVC (L) 5.20 5.24 5.15 5.13
% Change +0 +0 +0 -1
FEV1 (L) 3.69 3.65 3.58 3.49
% Change +0 +0 -2 -5
FEF 25–75% (L/sec) 2.67 2.62 2.47 2.28
% Change +0 -1 -7 -14
FEF max (L/sec) 8.73 8.19 7.69 7.74
% Change +0 -6 -11 -11

Stage 0.25 MG/ML 0.5 MG/ML 1 MG/ML 2 MG/ML

Dose 0.25000 0.50000 1.00000 2.00000
Dose units 1.25000 2.50000 3.00000 10.00000
C.D.U.s 2.34250 4.84250 9.842S0 19.84250
— SPIROMETRY —
FVC (L) 5.05 4.93 4.74 4.84
% Change -2 -5 -8 -6
FEV1 (L) 3.44 3.28 3.18 3.27
% Change -6 -10 -13 -11
FEF 25–75% (L/sec) 2.15 1.87 1.68 1.81
% Change -19 -30 -37 -31
FEF max (L/sec) 7.23 7.55 7.08 7.29
% Change -17 -13 -18 -16

Stage 4 MG/ML 8 MG/ML POST-BRONCH

Dose 4.00000 8.00000 0.00000
Dose Units 20.00000 40.00000 0.00000
C.D.U.s 39.84250 79.84250 79.84250
— SPIROMETRY —
FVC (L) 4.74 4.38 5.30
% Change -8 -15 +2
FEV1 (L) 3.13 2.86 3.79
% Change -15 -22 +2
FEF 25–75% (L/sec) 1.59 1.06 2.85
% Change -40 -60 +6
FEF max (L/sec) 7.05 6.34 8.30
% Change -19 -27 -4
 chapter 2 Pulmonary Function Tests 13

Question 1: What can be said about this patient having
a diagnosis of asthma?
A. The patient absolutely has asthma as evidenced by
the >20% decrease in FEV1 during methacholine
testing
B. The patient absolutely does not have a diagnosis of
asthma as his FEV1 did not fall below 20% until a
concentration on 8 mg/mL methacholine
C. The probability of the patient having asthma is border-
line due to the methacholine concentration needed to
induce a 20% or greater decrease in FEV1, but his lack
of asthmatic symptoms give him a low pre-test proba-
bility for a diagnosis of asthma
D. PFTs prior to methacholine testing showed a 2%
improvement in FEV1 following bronchodilator. This
alone shows bronchial responsiveness and proves
enough evidence for the diagnosis of asthma in this
patient
E. He has asthma as evidenced by the diagnosis he car-
ries from childhood
Question 2: Which of the following may have inter-
fered with the methacholine challenge testing?
A. The patient used albuterol inhaler 1 day prior to
methacholine testing
B. The patient came to clinic after eating milk and oat
cereal for breakfast prior to methacholine testing
C. The patient drank a cup of regular coffee on the way
to his methacholine test
D. The patient took 1,000 mg acetaminophen on the
morning of his methacholine test
E. He also takes lisinopril for hypertension
CASE 5
A 73-year-old man has recently been diagnosed with
COPD and has smoked 1 pack per day for 50 years. He
notes his shortness of breath is not limiting his daily
activities and he continues doing strenuous manual
labor around his home daily. He notes daily symptoms of
cough productive of yellow-brown sputum and states he
has one to two bouts of “bronchitis” per year, for which
he sees his primary care physician and is typically treated
with a course of oral antibiotics and oral corticosteroids.
**
His physical examination is otherwise unremarkable
except for a BMI 32 and occasional expiratory wheeze.
**
Pulmonary function tests are shown below:

Pre-Bronch Post-Bronch
Actual Pred % Pred SD LLN Actual % Chng
— SPIROMETRY —
FVC (L) 2.86 3.97 72 0.54 3.08
FEV1 (L) 1.42 2.88 49 0.45 2.14
FEV1/FVC (%) 50 73 67 6 63
FEF 25% (L/sec) 1.61
FEF 75% (L/sec) 0.27
FEF 25–75% (L/sec) 0.58 2.12 27 0.92 0.60
FEF max (L/sec) 3.75 7.56 49 1.33 5.37
FIVC (L) 2.22
FIF max (L/sec) 2.71

(continued)
14 Pulmonary Disease Examination and Board Review

(Continued)
Pre-Bronch Post-Bronch
Actual Pred % Pred SD LLN Actual % Chng
— LUNG VOLUMES —
SVC (L) 3.22 3.97 81 0.54 3.08
IC (L) 2.43 3.12 77
ERV (L) 0.79 0.85 92
TGV (L) 5.25 3.54 148 0.72 2.10
RV (Pleth) (L) 4.46 2.42 184 0.37 1.68
TLC (Pleth) (L) 7.68 6.66 115 0.79 5.08
RV/TLC (Pleth)(%) 58 37 157 4 29
Trapped gas (L)
— DIFFUSION —
DLCOunc (mL/min/mm Hg) 15.09 29.49 51 4.83 19.83
DLCOcor (mL/min/mm Hg) 29.49 4.83 19.83
DL/VA (mL/min/mm Hg/L) 2.76 4.43 62
VA (L) 5.47 6.66 82 0.79 5.36
— AIRWAYS RESISTANCE —
Raw (cmH2O/L/s) 1.45 0.48 0.66
Gaw (L/s/cmH2O) 1.03

0
1 2 3 4
-8

-8

-6

-8

Pred Pre
 chapter 2 Pulmonary Function Tests 15

Six-minute walk test results: Walked 372 m in 6 minutes C. His COPD is severe, lung volumes are not suggestive
of air trapping, his DLCO is moderately decreased,
Heart Borg and there is no evidence of hypoxemia with exertion
SpO2 (%) Rate Scale O2 (L/min) D. His COPD is very severe, lung volumes are suggestive
of air trapping, his DLCO is moderately decreased,
Baseline 94  94 2 Room air
and there is no evidence of hypoxemia with exertion
1 minute 93  99 2 Room air E. His COPD is severe, lung volumes are suggestive of
2 minutes 93 102 3 Room air air trapping, his DLCO is severely decreased, and
3 minutes 93 100 3 Room air there is no evidence of hypoxemia with exertion
4 minutes 94 104 4 Room air
5 minutes 94 103 4 Room air CASE 6
6 minutes 93 103 4 Room air A 68-year-old man with 50 pack-years and quit 11 years
Recovery ago, obstructive sleep apnea on CPAP, hypertension,
1 minute 94  98 3 Room air GERD, and hypothyroidism presents for evaluation of
2 minutes 96  93 3 Room air increasing dyspnea on exertion. He can presently climb
less than one flight of stairs before having to rest due to
3 minutes 96  95 2 Room air
breathlessness. He also notes dyspnea when dressing
4 minutes 95  92 2 Room air himself. However, he has no shortness of breath at rest
5 minutes 95  92 2 Room air or when lying flat. He denies any occupational, environ-
mental, or chemical exposures.

Question 1: What does his pulmonary function test- **

ing and 6-minute walk test indicate about his lung
­disease?
A. His COPD persists but is likely unchanged since pre-
vious testing 12 years earlier when the severity was
moderate
B. His COPD is severe, lung volumes are suggestive of
air trapping, his DLCO is moderately decreased, and
there is no evidence of hypoxemia with exertion
His physical examination is remarkable for body mass
index is 36 kg/m², Mallampati score of II, and bilateral
crackles.
**
His pulmonary function tests, including spirometry,
lung volumes, DLCO, and 6-minute walk testing are per-
formed. The results are below:

Actual Pred % Pred SD LLN Actual % Chng

— SPIROMETRY —
FVC (L) 2.32 4.12 56 0.53 3.25 2.25 -3
FEV1 (L) 2.00 3.04 65 0.45 2.30 1.96 -2
FEV1/FVC (%) 86 74 116 6 64 87 +1
FEF 25% (L/sec) 5.59 6.90 +23
FEF 75% (L/sec) 0.94 0.75 -20
FEF 25–75% (L/sec) 2.78 2.36 117 0.91 0.86 2.57 -7
FEF max (L/sec) 5.92 8.04 73 1.32 5.86 6.87 +16
FIVC (L) 1.73 1.81 +4
FIF max (L/sec) 3.73 4.10 +10

(continued)
16 Pulmonary Disease Examination and Board Review

(Continued)
Actual Pred % Pred SD LLN Actual % Chng
— LUNG VOLUMES —
SVC (L) 2.29 4.12 55 0.53 3.25
IC (L) 1.79 3.12 57
ERV (L) 0.50 1.00 50
TGV (L) 2.70 3.44 78 0.72 2.00
RV (Pleth) (L) 2.20 2.28 96 0.37 1.54
TLC (Pleth) (L) 4.48 6.56 68 0.79 4.98
RV/TLC (Pleth) (%) 49 35 139 4 27
Trapped gas (L)
— DIFFUSION —
DLCOunc (mL/min/mm Hg) 10.76 30.32 35 4.83 20.66
DLCOcor (mL/min/mm Hg) 30.32 4.83 20.66
DL/VA (mL/min/mm Hg/L) 3.45 4.62 74
VA (L) 3.12 6.56 47 0.79 5.26
— AIRWAYS RESISTANCE —
Raw (cmH2O/L/s) 1.45 0.48 0.66
Gaw (L/s/cmH2O) 1.03
sRaw (cmH2O*s) <4.76
sGaw (1/cmH2O*s) 0.20 0.07 0.08

10
8
6
4
2
0
-2 1 2 3 4 5
-4
-6
-8
-10

Pred Pre Post

A 6-minute walk test: Walked 305 m in 6 minutes

Heart Borg Heart Borg

SpO2 (%) Rate Scale O2 (L/min) SpO2 (%) Rate Scale O2 (L/min)
Baseline 95  83 2 Room air Recovery
1 minute 87  99 3 Room air 1 minute 85  73 2 Room air
2 minutes 79 105 4 Room air 2 minutes 93  77 1 Room air
3 minutes 81  95 4 Room air 3 minutes 95  78 0 Room air
4 minutes 80  91 3 Room air 4 minutes 96  74 0 Room air
5 minutes 78 113 4 Room air 5 minutes 95  73 0 Room air
6 minutes 82  99 3 Room air
 chapter 2 Pulmonary Function Tests 17

Question 1: What is the major finding in the spirome- evaluation of shortness of breath. Until recently, she has
try and lung volumes? felt that her asthma symptoms were under control and
A. Restrictive physiology but not true restriction due to had not used her albuterol inhaler for months. She notes
the preserved total lung capacity an insidious onset of dyspnea on exertion over the past
B. Obstructive lung disease due to the FEV1 being less 1 to 2 years. She mainly has noted difficulty performing
than the lower limit of normal her daily aerobic exercise routine due to dyspnea. She
C. True restrictive disease notes she has tried her albuterol inhaler with only mild
D. Emphysema due to the low DLCO relief of her symptoms. She feels her symptoms only
E. Normal spirometry occur with physical exertion and feel different than her
previous asthma symptoms.

CASE 7 **
A 20-year-old woman with a past medical history signif- Physical examination is remarkable for BMI is 24 kg/m²
icant for tobacco use (half pack of cigarettes per day for and fixed split S2.
4 years—quit 1 month prior to presentation), atrial sep- **
tal defect, and mild intermittent asthma diagnosed clin-
Pulmonary function testing is performed and the results
ically (without PFTs) when she was a child presents for
follow.

Pre-Bronch Post-Bronch
Actual Pred % Pred SD LLN Actual % Pred % Chng
— SPIROMETRY —
FVC (L) 4.03 3.97 101 0.44 3.24 4.23 106 +4
FEV1 (L) 2.51 3.45  72 0.37 2.84 3.14 91 +25
FEV1/FVC (%) 62 86  72 6 76 74 86 +19
FEF 25% (L/sec) 2.60 6.08  42 1.30 3.94 3.32 54 +27
FEF 75% (L/sw) 1.79 2.11  84 0.58 1.15 2.17 102 +21
FEF 25–75% (L/sec) 2.35 3.81  61 0.79 2.51 3.05 79 +29
FEF max (L/sec) 2.70 7.08  38 1.09 5.28 3.42 48 +26
FIVC (L) 2.17 2.17 +0
FIF max (L/sec) 2.58 3.89 +50
FEV6(L) 4.03 3.97 101 0.43 3.26 4.23 106 +4
Time to FEF max (sec) 0.355 0.465 +30

10
8
6
4
2
0
-2 1 2 3 4 5
-4
-6
-8
-10

Pred Pre Post

18 Pulmonary Disease Examination and Board Review

Question 1: What does the flow-volume loop indicate? CASE 8

A. Classic obstructive lung disease. Most likely asthma
B. Restrictive physiology with likely “Fingerprinting” in
the expiratory limb of the flow-volume loop
C. Variable extrathoracic obstruction
D. Variable intrathoracic obstruction
E. Fixed obstruction
CPET:
A 50-year-old man with history of COPD and Conges-
tive Heart Failure is sent for cardiopulmonary exercise
testing to evaluate his dyspnea. His medications consist
of tiotropium, furosemide, metoprolol, lisinopril, and
albuterol as needed. Review of prior chest computed
tomography shows upper-lobe emphysematous changes
with fibrotic changes in the lower lobes. The CPET is
aborted for dyspnea.

Work Rate 80 65% predicted SaO2% 93 Rest 84 Peak

VO2 1.10 65% predicted SpO2% 90 Rest 84 Peak
AT 0.80 N PaO2 67 Rest 50 Peak
HR 135 85% predicted PaCO2 40 Rest 50 Peak
O2 pulse 8 80% predicted PO2 (A–a) 20 Rest 35 Peak
BP 170/80 VD/VT 0.45 0.43
VE 50 120% predicted
FR 39 N
VE/VCO2
at AT 44
RER 1

Max Predicted HR

Max Predicted O2 Pulse

HR

O2 Pulse
VO2

WR VO2

(continued)
 chapter 2 Pulmonary Function Tests 19

(Continued)

MVV
VCO2

VE
WR VCO2

VC

VE/VCO2

PETCO2
F (Breaths per minute)
VT

PETO2
VE/VO2

VO2 VO2
PAO2

VD/VT

PaCO2
SaO2
PaO2

VO2 VO2

Modified with permission from American Thoracic Society; American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise
testing. Am J Respir Crit Care Med. 2003;167(2):211–277.

Question 1: What contributes to his exercise intoler- C. Interstitial lung disease

ance? D. Psychogenic
A. COPD E. None of the above
B. CHF
 Answers

CASE 1

Flow (Liters/Second)
4

3
Question 1: A. Cough
2
An acceptable effort is devoid of any artifacts, which
can include abnormalities in the volume-time curve and 1
flow-volume curve secondary to cough or variable effort,
0 1 2 3 4 5 6
early termination (<6 seconds with no plateau reached
Time (seconds)
in volume-time curve and low total volume in flow-
volume curve), leak (volume-time curve drops instead Hesitation
of plateaus and flow-volume backtracks), glottis closure
(an abrupt stop in both curves), and hesitation (the ini- 4
tial exhalation is delayed or not forceful).
Volume (Liters)

3
Glottis closure
2

4 1
Volume (Liters)

3
2 0 1 2 3 4 5 6
1 Time (seconds)

0 1 2 3 4 5 6 4
Flow (Liters/Second)

Time (seconds)
3
Flow (Liters/Second)

4
2
3
1
2

1 0 1 2 3 4 5 6
Time (seconds)
0 1 2 3 4 5 6
Time (seconds)
Leak

Early termination 4
Volume (Liters)

3
4
2
Volume (Liters)

3
1
2

1 0 1 2 3 4 5 6 7 8
Time (seconds)

0 1 2 3 4 5 6
Time (seconds)

20

6 exhaled]/[concentration of alveolar nitrogen]) with
5
Flow (Liters/Second)
4
0 1 2 3 4 5
Time (seconds)
Question 2: C. Two largest values of FVC are within
0.150 L from each other
The acceptable criteria for individual spirograms consists
of (1) free of artifacts; (2) good starts as defined by extra­
polated volume <5% of FVC or 0.15 L, whichever is
greater; and 3) satisfactory exhalation defined as ≥6 sec­
onds, a plateau in volume time curve or patient cannot or
should not continue to exhale.1
**
The reproducibility criteria involves at least three indi-
vidual spirograms which adhere to the acceptability cri-
teria with the two largest FEV1 and FVC within 0.150 L
from each other.1 If this is achieved, the examination can
be concluded. If not, it can be repeated 8 times.
CASE 2
Question 1: A. TV and IC
During pregnancy there is a progressive decrease in
expiratory reserve, residual volume, functional residual
capacity, and total lung capacity secondary to the grow-
ing uterus. TV and IC increase. The TV increases up to
600 mL secondary to progesterone-mediated respiration
and enhancement of hypercapnic ventilatory drive. VC
does not change.
Question 2: E. FRC
Lung volumes can be calculated by initially determin-
ing the FRC.2 There are two approaches. One is to use
gas dilution technique which works on the derivative
of Boyle’s law (P1V1 = P2V2). Nitrogen and helium dilu-
tion techniques only measure airways of communicat-
ing conducting airways.2 With the nitrogen washout
method, 100% oxygen for 3 to 7 minutes is employed
or until three consecutive breaths have <1.5% nitrogen.
FRC has a nitrogen concentration of 0.75 and the calcu-
lation (VFRC = [Concentration of exhaled N2] [volume
chapter 2 Pulmonary Function Tests 21
small corrections for remaining concentration of alve-
olar nitrogen and nitrogen produced by body tissues.2
Nitrogen %
6
Volume
Modified with permission from Wanger J, Clausen JL, Coates
A, et al; ATS/ERS Task Force. Standardisation of the measure-
ment of lung volumes. Eur Respir Jl. 2005;26(3):511–522.
**
Another gas dilution technique is the closed circuit
helium dilution. Spirometer is filled with 20% to 30%
oxygen, air and helium is added until 10% is achieved.2
Patient rebreathes the spirometer until the He con-
centration is in equilibrium. The calculation is FRC =
(% Heliuminitial – % Heliumfinal) × system volume%
Heliumfinal.2 Adjustments are made for 100 mL for helium
lost in the blood and dead-space volume from breathing
valve and filter.
**
In body plethysmography, volume from both communi-
cating and noncommunicating airways is accounted for.
The patient is placed in a box and pants with hands on
cheek, against a closed shutter. Decreases in cabinet vol-
ume are indirectly related to thoracic volume increase.2
CASE 3
Question 1: A. A
Resistance is the pressure required to flow 1 L/S in and
out of the lung.3 It has a reciprocal relationship with con-
ductance and is less in larger airways compared to smaller
airways. It is measured in two ways: (1) obtaining the
pleural pressure indirectly via a small balloon catheter at
the distal esophagus and comparing it with the pressure .
at the mouth divided by flow (Rpulm = Ppl – Pao/V )
22 Pulmonary Disease Examination and Board Review

or (2) via body plethysmograph . by measuring airway
resistance (Raw = Palv – Pao/V ). Raw is less than Rpulm
because there is no tissue resistance.
**
Compliance (CL = ΔV/ΔPpl) is the change in volume
secondary from a change in elastic pressure of the lung.
There are two types: (1) static compliance, where there is
no flow measured during total lung capacity (TLC); and
(2) dynamic compliance which is Ppl measured during
end inspiration and minus end expiration.3 Normal CL is
0.150 to 0.250 L/cmH2O.
**
Hysteresis defines the major contribution of elastic recoil
pressure is secondary to the surface tensions at the alve-
olar air–fluid interface. This elastic recoil pressure is the
main determinant of maximal expiratory flow.
patient inhales 100% of oxygen. The patient then slowly
exhales through a one way valve as a nitrogen meter
records the nitrogen concentration of expired air. Phase
I is the anatomical dead space with no nitrogen.3 Phase
II consists of mixed concentrations of alveolar air and
washing out of air from dead space.3 Phase III consists
of alveolar air, initially from dependent regions where
nitrogen concentrations are lowest.3 The slope is nor-
mally 1% to 2.5% per liter. This slope is increased in
pathologic conditions where there is increased heter-
ogeneous ventilation such as in COPD. Phase IV illus-
trates the end of nitrogen emptying from dependent
regions and the increase reflect the abundant nitrogen
concentration in the apical regions.3 Phase IV’s onset
also illustrates the airway closure of the dependent
areas, usually 80% to 90% of VC. Phase IV ends at the
residual volume.

**
Compliance is reduced in pulmonary fibrosis. In COPD,
the static compliance is increased but the dynamic
­compliance maybe normal due to the heterogeneous
ventilation.
**
Choice A refers to COPD where the lung parenchyma
cannot distend the airways to the extent of a nondis-
eased lung, Choice B is the normal range. Choice C
refers to reduced ability of expiratory muscles because
of reduced lung volume and increased recoil as seen in
pulmonary fibrosis.
Question 2: C. III
Single breath nitrogen (SBN2) tests the distribution
of ventilation. After exhaling to residual volume the
CASE 4
Question 1: C. The probability of the patient having
asthma is borderline due to the methacholine concen-
tration needed to induce a 20% or greater decrease in
FEV1, but his lack of asthmatic symptoms give him a
low pre-test probability for a diagnosis of asthma.
**
Methacholine challenge test maybe used to provide more
evidence for an asthma diagnosis only if baseline spirom-
etry does not show significant airway obstruction (FEV1
should be ≥50% of predicted [ideally ≥60% or 70%] and
≥1 L [ideally ≥1.5 L] and there is no significant broncho-
dilator response).4 The table below lists the indications
and contraindications for methacholine challenge test.

Indications Absolute Contraindications Relative Contraindications

Assessing for a diagnosis of asthma, risk of
developing asthma, response to asthma
treatments
Chronic cough evaluation
Bronchial hyperresponsiveness assessment in
patients with bronchoconstriction
FEV1 <50% predicted, or <1 L
CVA or MI in the last 3 months
Uncontrolled HTN (SBP >200 or
DBP >100)
Aortic aneurysm
FEV1 <60% predicted or <1.5 L or
FEV1
Inability to follow directions
Pregnancy or location
Cholinesterase inhibitor use
Respiratory infection within 2 weeks
Epilepsy

**
The change in FEV1 is primarily what is monitored dur-
ing a methacholine challenge test. A fall in FEV1 by ≥20%
defines the PC20 and this is considered a significant
marker of bronchial responsiveness.4 Lowest dose of meth-
acholine which results in a decrease in FEV1 by ≥20% from
baseline is known as the PC20. Typically, methacholine is
introduced in a series of increasing concentrations until a
dose of 16 mg/mL is reached or until FEV1 decreases ≥20%
from pre-test spirometry. During testing, spirometry is
performed 30 and 90 seconds after each dose of diluted
methacholine. If a concentration of 16 mg methacholine
per mL does not result in a decrease in FEV1 by 20% or
more, then the PC20 should be reported as “greater than
16 mg/mL.” If the FEV1 is decreased by 20% or more prior
to the dose reaching 16 mg methacholine per mL, then the
test is terminated at that dose and the PC20 is reported as
the lowest methacholine concentration which resulted in
the FEV1 falling by ≥20% from baseline. Following testing,
albuterol should be administered and spirometry repeated
until pre-test spirometry results are duplicated.
% Fall in FEV 1
20%
10%
PC 20
0 value of approximately 90%.4 Thus a negative mannitol
Dilvent 0.125 0.25 0.5 1 2 4 8 16
Concentration in mg/cc
**
The PC20 can be interpreted as below. As can be seen, in
the correct clinical context, extremes in PC20 may result
in more straight forward interpretation of methacho-
line challenge testing while intermediate dose responses
become more challenging.4
PC20 (mg/mL) Interpretation
Greater than 16 Normal bronchial responsiveness
4–16 Borderline bronchial hyperresponsiveness
1–4 Mild bronchial hyperresponsiveness
Less than 1 Moderate to severe bronchial hyperres-
ponsiveness
Source: Crapo RO, Casaburi R, Coates AL, et al. Guidelines for methacho-
line and exercise testing-1999. This official state­ment of the American
Thoracic Society was adopted by the ATS Board of Directors, July 1999.
Am J Respir Crit Care Med. 2000;161:309–329.
chapter 2 Pulmonary Function Tests 23
**
Bronchoprovocation tests, which also includes hista-
mine, mannitol, and exercise, help identify patients with
asthma, exercise-induced bronchoconstriction (EIB) or
other diseases with bronchial hyperresponsiveness, gauge
the severity of their disease, identify triggers of their dis-
ease, and determine if there is a clinic response.4 They can
act directly (methacholine and histamine) by stimulation
of airway smooth muscle receptors or indirectly (manni-
tol, adenosine monophosphate, and eucapnic hyperventi-
lation) via the release of inflammatory mediators.
**
With mannitol challenge, the subject is asked to exhale
completely before taking a series of controlled deep
breaths from a device containing 0 mg and then increas-
ing doses of mannitol. The patient holds his/her breath
for 5 seconds and then exhales through the mouth. At
each dose level, spirometry is performed in duplicate,
60 seconds after inhalation of the dose. Consecutive
doses are administered until the target is achieved, which
is a 15% fall the FEV1 or cumulative dose <635 mg.
Bronchoconstriction is then reversed with albuterol.
**
When compared to methacholine, the data is less robust
for mannitol challenge. In those with symptoms of
asthma, the test is 58% sensitive and a 98% specific with a
positive predictive value of 91% and a negative predicted
challenge in a patient with symptoms of asthma (and
thus a high pre-test probability) makes the diagnosis of
asthma unlikely but does not exclude it.
**
Bronchoprovocation challenge test with exercise begins
with pre-testing inhalation of dry air (<10 mg H2O)
from a gas cylinder with a reservoir bag and a one
way valve apparatus. The exercise test should allow the
patient to reach 80% to 90% of predicted maximum vol-
untary ventilation (MVV ≈40 × FEV1). Spirometry is
performed prior to and at 5, 10, 15, 20, and 30 minutes
after the exercise test is complete. A fall in FEV1 of 10%
is suggestive but 15% is more diagnostic.
**
Bronchoprovocation challenge test via eucapnic volun-
tary hypercapnia (EVH) involves inhalation of chilled
hypercapnic air to a rate 80% to 85% of MVV. Two
reproducible spirometries are performed at 5, 10, and