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Pulmonary Disease
Examination and
Board Review
 NO ICE

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Pulmonary Disease
Examination and
Board Review

Edited by
Ronaldo Collo Go, MD
F ly
Dv P lm y, C l C , d Sl p M d
M S B hI l
N w Y k, N w Y k
d
C y lR H l hC
M ddl w , N w Y k

N w Y k Ch g S F Ah L d M d d Mx C y
N w D lh S J S gp Syd y
Pulmonary Disease Examination and Board Review

C py gh © 2016 y M G w H ll Ed . All gh v d. P d Ch . Ex p p m d d h U dS
C py gh A 1976, p h p l m y p d d d d y m y ym , d
d v l y m, w h h p w p m h p l h .

1 2 3 4 5 6 7 8 9 0 C P/C P 19 18 17 16

ISBN 978 0 07 184529 8

MHID 0 07 184529 1

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ISBN 978 0 07 184529 8 (p k. : lk. p p )—ISBN 0 07 184529 1 (p k. : lk. p p )
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[DNLM: 1. R p y D —Ex m Q .
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2015011040

M G w H ll Ed k v l l p lq yd p m m d l p m p
gp g m . p v , pl v h C U p g www.mhp l. m
 T is book is dedicated to:

Evangeline and Benjamin Go

Anna Go, Jean Go, and Juan ruyol
Natalio Collo and Brigida Zapanta Collo
Jose Go and Rosalina Go
Sabina, Esther and the Bediones Family
ruyol Family
Lydia, Rodolfo, Imelda, and the Jovellanos Family
Rosa, Fortunato, and the Garces Family
Go Family
Collo Family
abobo Family
May Martin
Our patients
 Contents

Cont r ibu t or s x
Pr efa ce xv

1. HE CELL AND IMMUNOLOGY

Ronaldo Collo Go
Page 1
2. PULMONARY FUNC ION ES S
Ronald Evans, Ronaldo Collo Go, Andrew Matragrano, and
Paul Simonelli
Page 9
3. CHES RADIOLOGY
Mary Salvatore, Lea Azour, Adam Jacobi, Matthew Cham,
Corey Eber, and Joseph Marchione
Page 33
4. CHRONIC OBS RUC IVE PULMONARY DISEASE
Jason Filopei, Lisa Bajpayee, and Ronaldo Collo Go
Page 66
5. AS HMA
Sarun T omas and Alfred Astua
Page 86
6. BRONCHIEC ASIS
Daniel Greenblatt Fein, Stacy Verzosa, and Patricia Walker
Page 101
7. DIFFUSE PARENCHYMAL LUNG DISEASES
Ronaldo Collo Go
Page 121
8. CYS IC LUNG DISEASES
Daniel Greenblatt Fein, Stacey Verzosa, and Patricia Walker
Page 157
9. RACHEAL DISEASES
Omar Ibrahim and Erik Folch
Page 166

vii
viii Co n t e n t s

10. MEDIAS INAL 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. OCCUPA IONAL 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. IN ERVEN IONAL PULMONOLOGY
Amit Mahajan and Adnan Majid
Page 293
17. LUNG RANSPLAN A ION
Irene Louh, Hilary Robbins, and Lori Shah
Page 307
18. BAC ERIAL AND VIRAL DISEASES
Navitha Ramesh, Aloke Chakravarti,
and Ronaldo Collo Go
Page 315
19. MYCOBAC ERIAL DISEASES
Michael Bergman and Ronaldo Collo Go
Page 327
20. FUNGAL DISEASES
Jimmy Johannes, essy Paul, and isha Wang
Page 343
21. HIV-ASSOCIA ED PULMONARY DISEASES
Anthony F. Arredondo, Richard H. Huynh, and Steven Y. Chang
Page 366
 Co n t e n t s ix

22. CRI ICAL CARE

Ronaldo Collo Go, Michael Silverberg, Rafael Yunen,
Amar Anantdeep Singh Sarao, Charanya Sivaramamkrishnan,
Vikram Dhawan, and Roopa Kohli-Seth
Page 386
23. BIOS A IS ICS
Michael Elias and Roopa Kohli-Seth
Page 431
24. HYPERBARIC MEDICINE
Nagendra Madisi, Ronaldo Collo Go, and Roopa Kohli-Seth
Page 447
25. CARDIO HORACIC SURGERY
Stephen Spindel and Dong-Seok Lee
Page 459
26. PULMONARY PA HOLOGY
Abul Ala Syed Rifat Mannan and Songyang Yuan
Page 475
 Contributors

Anthony F. Arredondo, MD Matthew Cham, MD

Fellow Associate Professor of Radiology and Medicine
Dv P lm y, C lC , d I h Sh l M d M S
Sl p M d D p m R d l gy
R ld R g UCLA M d lC M S H p l
L A gl ,C l N w Y k, N w Y k

Alfredo Astua, MD Steven Y. Chang, MD, PhD

Assistant Professor of Medicine Associate Clinical Professor of Medicine
Dv P lm y, C lC , d Dv P lm y, C lC , d
Sl p M d Sl p M d
M S B hI l D vdG Sh l M d UCLA
N w Y k, N w Y k R ld R g UCLA M d l C
L A g l ,C l
Lea Azour, MD
Resident George Cheng, MD, PhD
D p m R d l gy Fellow
M S H p l Dv P lm y dC lC M d
N w Y k, N w Y k M h G lH p l
B ,M h
Lisa Bajpayee, MD
Resident Dong-Seok Daniel Lee, MD
D p m I lM d Assistant Professor of Surgery
B U v yM d lC D p m T S g y
B ,M h I h Sh l M d M S
M S H p l
Michael P. Bergman, MD N w Y k, N w Y k
Fellow
Dv P lm y, C lC , d Vikram Dhawan, MD
Sl p M d Fellow
M S B hI l Dv S g lC lC
N w Y k, N w Y k M S H p l
N w Y k, N w Y k
Aloke Chakravarti, MD
Fellow Corey Eber, MD
Dv P lm y, C lC , d Assistant Professor of Radiology
Sl p M d I h Sh l M d M S
M S B hI lM d lC D p m R d l gy
N w Y k, N w Y k M S H p l
N w Y k, N w Y k

xi
xii Co n t r ib u t o r s

Michael Elias, MD Daniel Greenblatt Fein, MD

Fellow Fellow
Dv S g lC lC Dv P lm y, C lC , d
M S H p l Sl p M d
N w Y k, N w Y k M S B hI l
N w Y k, N w Y k
Oleg Epelbaum, MD
Director Richard Huynh, MD
Bronchoscopy and Interventional Pulmonology Fellow
Elmh H p lC Dv P lm y, C lC , d
Assistant Professor of Medicine Sl p M d
I h Sh l M d M S R ld R g UCLA M d lC
N w Y k, N w Y k L A gl ,C l

Ronald Evans, DO Omar Ibrahim, MD

Fellow Assistant Professor of Medicine
Dv P lm y dC lC M d Director of Interventional Pulmonary
G g M d lC Dv P lm y dC lC M d
D v ll , P ylv U v y C Sh l M d
F m g ,C
Jason Filopei, MD
Fellow Adam Jacobi, MD
Dv P lm y, C lC , d Sl p M d Assistant Professor of Radiology
M S B hI l I h Sh l M d M S
N w Y k, N w Y k D p m R d l gy
M S H p l
Erik Folch, MD N w Y k, N w Y k
Assistant Professor of Medicine
Associate Director of Interventional Pulmonology Jimmy Johannes, MD
B hI lD M d lC Fellow
H v dM d lS h l Dv P lm y, C lC , d
B ,M h Sl p M d
R ld R g UCLA M d lC
Irene Galperin, MD L A gl ,C l
Director, Pleural Disease Service
Dv P lm y dC lC M d Colleen Keyes, MD, MPH
L x H ll H p l – NSLIJ Associate Program Director, C m d BIDMC MGH
Assistant Professor of Medicine I v l P lm y F ll w h p
Al E C ll g M d Dv P lm y, C lC , d
N w Y k, N w Y k Sl p M d
M h G lH p l
Ronaldo Collo Go, MD I ,H v d M d l S h l
Faculty B ,M h
Dv P lm y, C lC , d
Sl p M d Irene K. Louh, MD, PhD
M S B hI l Fellow
N w Y k, N w Y k Dv P lm y, All gy, d
A d C lC M d
C y lR H l h C C l m U v yM d lC
M ddl w , N w Y k N w Y k, N w Y k
 Co n t r ib u t o r s xiii

Nagendra Madisi, MD essy Paul, MD

Fellow Fellow
Dv S g lC lC Dv P lm y, C lC , d
M S H p l Sl p M d
N w Y k, N w Y k R ld R g UCLA M d lC
L A gl ,C l
Amit Mahajan, MD
C d ,V l , d S g lA Luis D. Quintero, DO, MPH
I v l P lm l gy INOVA F xH p l Resident
F ll Ch h, V g D p m I lM d
M S B hI l
Evelyn Mai, MD N w Y k, N w Y k
Faculty
Dv P lm y, C lC , d Navitha Ramesh, MD
Sl p M d Fellow
G g M d lC Dv P lm y, C lC , d
D v ll , P ylv Sl p M d
M S B hI lM d lC
Adnan Majid, MD N w Y k, N w Y k
Director, Section of Interventional Pulmonology
Director, Combined BIDMC-MGH Interventional Abul Ala Syed Rifat Mannan, MD
Pulmonology Fellowship Resident
Dv T S g y dI v l D p m P h l gy
P lm l gy M S S .L k ’ R vl H p lC
B hI lD M d lC N w Y k, N w Y k
A P M d
H v dM d lS h l Hilary Robbins, MD
B ,M h Assistant Professor of Clinical Medicine
L g pl P g m
Joseph Marchione, MD Dv P lm y, All gy, d
Resident C lC M d
D p m R d l gy N wY k P y C l m
M S H p l N w Y k, N w Y k
N w Y k, N w Y k
Mary Salvatore, MD
Michael Marino, DO Assistant Professor of Radiology
Faculty I h Sh l M d M S
Dv P lm y, C lC , d D p m R d l gy
Sl p M d M S H p l
G g M d lC N w Y k, N w Y k
D v ll , P ylv
Amar Anantdeep Singh Sarao, MD
Andrew Matragrano, MD Fellow
Director of Pulmonary Function Lab Dv S g lC lC
G g M d lC M S H p l
D v ll , P ylv N w Y k, N w Y k
xiv Co n t r ib u t o r s

Lori Shah, MD Brian M. Walsh, DO

Assistant Professor of Clinical Medicine Fellow
L g pl P g m Dv P lm y, C lC , d
Dv P lm y, All gy, d C lM d Sl p M d
N wY k P y C l m G g M d lC
M d lC D v ll , P ylv
N w Y k, N w Y k
isha Wang, MD
Michael Silverberg, MD Assistant Clinical Professor of Medicine
Faculty Fellowship Program Director
Dv P lm y, C lC , d Associate Chief of Inpatient Services and raining
Sl p M d Dv P lm y, C lC , d
H k kU v yM d lC Sl p M d
H k k, N w J y D vdG Sh l M d UCLA
R ld R g UCLA M d l C
Stephen Spindel, MD L A g l ,C l
Resident
D p m C d h S g y Stacey Verzosa Weisman, MD
M S H p l Associate Professor of Radiology
N w Y k, N w Y k M S H l h Sy m – B h I l,
S .L k ’, d R vl H p l
Roxana Sulica, MD N w Y k, N w Y k
Director of Pulmonary Hypertension Program
Assistant Professor of Medicine Songyang Yuan, MD, PhD
I h Sh l M d M S Faculty
Dv P lm y, C lC , d D p m P h l gy
Sl p M d M S B hI lM d lC
M S B hI l N w Y k, N w Y k
N w Y k, N w Y k
Rafael Alba Yunen, MD
Sarun T omas, DO Fellow
Fellow Dv S g lC lC
Dv P lm y, C lC , d M S H p l
Sl p M d N w Y k, N w Y k
M S B hI l
N w Y k, N w Y k

Patricia Walker, MD
Co-director of Adult Cystic Fibrosis Center
Acting Chief
Dv P lm y, C lC , d
Sl p M d
M S B hI l
N w Y k, N w Y k
 Preface

M G w H ll’ Pulmonary Disease Examination and I mh p l h h k w ll h

Board Review d d h d w h y k wl dg p lm yd d h lp y p
p lm yd , h p lm y ll w, d h h p lm y d.
p lm y d g dy g h d .T d
h k g w h d ly p h Ronaldo Collo Go, MD
d d p d d g p lm y Editor
d .F h ,I h v k d phy m Faculty
h d p m d l gy, p h l gy, d h Division of Pulmonary, Critical Care, and
g y, p lm y d l p vd m l Sleep Medicine
d pl yp p v .T Mount Sinai Beth Israel
d g d h p pp h w ll h New York, New York
d m l m d h phy l gy, m and
l gy, d ll l mm l gy. T v g m l Crystal Run Health Care
l l d l mm h m y v lv v m ll Middletown, New York
h l l h p lm yd , dp March 2015
d g d d m d
mpl .

xv
 1
he Cell and Immunology

Ronaldo Collo Go MD

CASE 1 D. P85 a mutation

E. 790 point mutation

G0
CASE 2
G1 S Human immune system consists o two parts: innate
immunity which recognizes pathogen receptor moti s in
many microbes and adaptive immunity which involves
Mitos is G2 generation o speci c antigen receptors on and B cells.

Question 1: Which o the ollowing have azurophilic

granules?
Question 1: What stage o the cell cycle is the rst A. Macrophages
checkpoint or aberrant DNA? B. Dendritic cells
C. Natural killer cells
A. G0
D. Neutrophils
B. Mitosis
E. Eosinophils
C. G1
D. S Question 2: An important component o the innate
E. G2 immunity is the complement system. Which comple-
ment component is responsible or the membrane
Question 2: Which o the ollowing is responsible or
attack complex?
senescence?
A. C4 a
A. elomere
B. C3 a
B. Mitochondria
C. C3 b
C. Cytokine
D. C5 a
D. Integrin
E. C5–9
E. tRNA
Question 3: Cytokines are proteins that are critical in
Question 3: Which o the ollowing con ers resistance
both innate and adaptive immunity. T ey unction to
to tyrosine kinase inhibitors in patients with EGFR
promote active immune cells and mediate the in am-
mutations?
matory response. Di erent cytokines have similar
A. Deletions on exon 19 unctions and each cytokine may have di erent actions
B. Point mutation in L858R in exon 21 on di erent cells. T eir actions can be autocrine,
C. V600 mutation

1
2 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

paracrine, or endocrine. Which cytokine is responsi- Question 6: What type o hypersensitivity involves
ble or the release o eosinophils? arthus reaction?
A. IL-5 A. ype I hypersensitivity reaction
B. IL-1, IL-6, NF-alpha B. ype II hypersensitivity reaction
C. IL-2 C. ype III hypersensitivity reaction
D. Il-17 D. ype IV hypersensitivity reaction
E. IL-10 E. ype V hypersensitivity reaction

Question 4: Adaptive immunity requires an initial con- Question 7: Which inter eron is prominent in granu-
tact with the antigen ollowed by a more vigorous loma ormation in sarcoidosis?
in ammatory response af er re-exposure to the antigen. A. Inter eron alpha
Bone marrow is the major site or B cells and thymus is B. Inter eron beta
the major site or cells. In the lymph nodes, the cells C. Inter eron gamma
are in the deep paracortical areas around B-cell germi- D. Inter eron alpha and beta
nal centers. wo important subsets o cells include E. All o the above
the cytotoxic CD8+ /MHC Class I and helper CD4+ /
MHC Class II. Which o the ollowing is not true Question 8: Which oll-like receptor proteins are
regarding the -cell recognition o an antigen? associated with gram-negative septic shock?
A. It is a heterodimer with CD3 subunits. A. LR1
B. It closely resembles the immunoglobulin heavy and B. LR3
light chains. C. LR4
C. Diversity is determined by rearrangements o V D. LR5
(variable), D (diversity), and J (joining) regions. E. LR6
D. CR recognizes protein antigen peptides which have
been “processed” by antigen presenting cells. Question 9: Anti-IgE therapy in asthma involves which
E. None o the above. type o antibody?
A. IgG
Question 5: B cells express immunoglobulins on their B. IgA
sur ace which can recognize unprocessed native anti- C. IgM
gens, and components o activated complement. D. IgD
Which immunoglobulin is ound as either a monomer E. IgE
or dimer, with J chain, and has secretory properties?
A. IgG Question 10: Which o the ollowing is pro brotic?
B. IgA A. GF-beta
C. IgM B. Plate-derived growth actor
D. IgD C. Insulin-derived growth actor
E. IgE D. Connective tissue growth actor
E. All o the above
 Answers
CASE 1
Question 1: C. G1
T e cell cycle leads to duplication and division o one
cell into two daughter cells. It consists o two phases:
interphase and mitosis. Interphase consists o three
events: G1 is the biosynthetic and growth stage, S phase
is where DNA is replicated, and G2 is continued growth
and preparation or karyokinesis, or mitosis. Mitosis is
urther subdivided into: prophase, metaphase, anaphase,
telophase, and cytokinesis. G0 is a state o senescence
where cells stop dividing, sometimes due to nonviable
progeny. Progression o the cell cycle is dependent on
a heterodimer which consists o cyclin, which is the
regulatory unit and a catalytic unit, cyclin-dependent
kinases (CDK). Once activated by cyclins, the CDK
phosphorylates and activates or inactivates a target
protein.
**
T ere are three checkpoints: G1, G2, and the metaphase
o mitosis. In the G1 and G2 phase, P53 acts as a gate
keeper and prevents urther replication and synthesis o
aberrant DNA.1
**
arget cells in lung cancer are the basal bronchial cells
and clara cells. umor growth is enhanced by evasion
o apoptosis through death cell dysregulation via FAS
ligand and E2F (Figs. 1–1 and 1–2), cell immortaliza-
tion via telomerase, epigenetic modi cation via DNA
methylation, and miRNA.2
**
One o the most well-studied risk actors, tobacco, with
polycyclic aromatic hydrocarbons and nitrosamines,
cause genetic mutations via DNA adducts. Excision o
these adducts occurs via nucleotide repair amily which
includes ERCC1 and XRCC. Persistence o adducts
lead to mutations such as in either P53, which is usu-
ally not seen in immunohistochemistry because o the
short hal -li e, 14,ARF RAS, or INKa amily. Less than 20%
3
smokers develop cancer suggesting a genetic predispo-
sition. Polymorphisms in cytochrome P450 1A1 gene,
GS M1 homozygous deletion, polymorphisms in DNA
repair gene, nicotinic receptor polymorphism at chro-
mosome locus 15q25 can predispose a person to lung
cancer risk.
Question 2: A. elomere
elomeres are repetitive nucleotide sequences, usu-
ally AGGG, and acts as bu ers rom chromosomal
deterioration. elomeres shorten a er each cell divi-
sion. elomerase, the enzyme responsible or addition
o this nucleotide sequence, has two subunits: h ER ,
the reverse transcriptase, and h R, an RNA that con-
tains telomere template repeat. Stability is dependent on
X-chromosome DKC1 gene. Shortened telomeres are
perceived as damaged DNA and undergo apoptosis or
senescence via P53/A M pathway.
**
elomeres are important in lung diseases. Idiopathic
pulmonary brosis is the most commonly associated
mani estation o telomerase mutations, particularly with
involving h ER , h R, and DKC1.3 Besides lung diseases,
shortened telomeres cause accelerated aging as seen in
aplastic anemia and dyskeratosis congenital (DC). In
lung carcinogenesis, these shortened telomeres continue
to proli erate because P53 pathway is inactivated. COPD
is ound as early mani estations in telomerase mutation
carriers.
Question 3: E. 790 point mutation
Due to its association with carcinogenesis, one o the
most studied growth signaling pathways is EGFR. Lig-
ands bind to the extracellular domains which result in
heterodimer or homodimer ormation and transphos-
phorylation. T is leads to activation o two sets o down-
stream signaling: RAS/mitogen-activated protein kinase
and P13 K/AK pathways. Mutations or dysregulation on
any component o the pathway cause them to be onco-
genes. One o the most common mutations is deletions
4 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

CELL MEMBRANE CELL MEMBRANE CELL MEMBRANE CELL MEMBRANE CELL MEMBRANE CELL MEMBRANE CELL MEMBRANE CELL MEMBRANE

CD95 Extrins ic pathway Intrins ic pathway

Pro-cas pas e 8

STRESS SIGNALS VIA DNA DAMAGE,

ONCOGENE, HYPOXIA

Cas pas e 8

P53

Bax bcl2 Bax bcl2

Cytochrome C

Cas pas e 9

Cas pas e 3

APOPTOSIS

Figure 1–1 T ere are two pathways leading to apoptosis. T e intrinsic pathway involves the P53 system which detects stress signals
via DNA damage, oncogene, and hypoxia. T is activates the BAX to proceed to increased permeability and release o cytochrome
C. T e extrinsic pathway involves binding o Fas Ligand and entering the apoptosis pathway via Caspase 3.

on exon 19 and point mutation in L858R in exon 21. CASE 2

KRAS can have missense mutations; BRAF has V600
mutation; and PI3 K has mutations in p85a subunit.
Some mutations are sensitive to certain chemotherapies
while others render them resistant. For example, pri-
mary resistance to KI to EGFR is secondary to exon 20
insertion mutations and secondary resistance to 790M
point mutation.
Question 1: D. Neutrophils
Azurophilic granules contain antimicrobial elements such
as myeloperoxidase, phospholipase A2, acid hydrolases,
elastase, de ensins, proteases, lysozymes, and cathepsin G.
T ey are most closely associated with neutrophils.
**

P53
P16
P21 P27 INK
CDK2
Cyclin E2
Rb Rb
CDK2
Cyclin D1
E2F E2F
Figure 1–2 RB Pathway. T e retinoblastoma pathway is the
downstream pathway or P53 and disrupts G1 entry to S phase.
T is is highlighted by phosphorylation o RB/E2 F product,
causing dissociation o E2 F rom RB. (Reproduced with per-
mission o Brambilla E, Gazdar A. Pathogenesis o lung cancer
signalling pathways: roadmap or therapies. Eur Respir J. 2009;
33(6):1485–1497.)
T e ve phases o host de ense include: (1) migration o
leukocytes to antigen; (2) antigen recognition by innate
immunity; (3) antigen recognition by adaptive immu-
nity; (4) in ammatory response; and (5) destruction and
removal o particles.
**
Migration o the leukocyte, such as a neutrophil, involves
interaction with endothelial cells and con ormational
change with their adhesion molecules. T e rst stage,
called attachment and rolling, involves leukocyte leav-
ing the blood stream through the post-capillary venule,
mediated by L-selectin molecule. T e second stage, rm
adhesion with activation-dependent stable arrest, is
attachment o leukocyte to high endothelial venules via
cytokines. T e third stage is the migration o leukocyte to
endothelial cells and release o matrix metalloprotenases
which digest the subendothelial basement membrane.
Question 2: E. C5–9
T e complement system is a cascading series o reactions
which results in cell lysis. T ere are three pathways which
include classic activation pathway via immune com-
plex, mannose-binding lectin pathway, and alternative
c h a Pt e r 1 t h e c e l l a n D im m u n o l o g y 5
E ector Cells
Macrophages First line o de ense o innate immunity
Binding LPS
APC to lymphocytes
Secretions o IL-1, NF-a, IL-12, IL-6
Dendritic cells APC
CD83, MHC II, multiple thin membrane
projectile
Most potent producers o IFN-alpha
Natural killer Sur ace receptors or Fc o IgG, NCAM-I
cells (CD56), CD8
Dual role: Antibody-dependent cytotoxicity
and nonimmune killing o target cells
Killing ability is inversely related to levels
o MHC I
Granulocytes:
Neutrophils Fc receptors or IgG (CD16) and or com-
plement components (C3b and CD35)
Secretes azurophilic granules into the sur-
ace generating superoxide radicals a er
stimulation rom immune complexes or
opsonized bacteria
Eosinophils Fc receptors o IgG (CD32)
Cytotoxic to parasitic in ections
Contents include major basic protein,
eosinophilic cationic protein, neurotoxin
and Anti-in ammatory enzymes such as
histaminase, arylsul ase, phospholipase D
Basophils IL-4
High af nity or IgE (FCRI)
Release histaminine, eosinophlic chemo-
tactic actor, neutral protease
Expresses C3a and C5b receptors
pathway. C4a, C3a, and C5a release histamine rom
basophils and mast cells.4 C3b and C3bi participate in
the phagocytosis by neutrophils and macrophages and
participate in the ormation o immune complex. C5–9
is the membrane attack complex.
Question 3: A. IL-5
Recognition interleukins and their roles might have
therapeutic implications such as in asthma. T e normal
airway is rich with T 1 cells. In an asthmatic airway, they
are rich in T 2 cells.8 Below is a table that lists selected
interleukins, their mechanisms, and associated drugs.8
Question 4: E. None o the above
MHC-peptide- CR is the initiation o an antigen
driven immune response. T e major histocompatibility
complex (MHC), also called human leukocyte antigen
6 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

Interleukin Mechanism Drugs

IL-1 • Stimulates IL-5 release rom smooth muscles and in uences eosinophilic • Anakinra–inhaled IL-1R
recruitment and activation antagonist
IL-2 • Promotes e ector -cell and -reg responses • Daclizumab–antibody against
• Secreted by malignancies and its antibodies have been used to suppress a subunit o IL-2 receptor
rejection in organ transplants
IL-5 • Promotes proli eration, di erentiation and survival o eosinophils and • Mepolizumab and reslizumab
development o basophils and mast cells are IL-5 antibodies
• Benralizumab–antibody
against alpha chain o IL-R5
IL-4 • Highly involved in allergic reaction and ollowing signaling via S A 6 • Lebrikizumab—IL-13 antibody
IL-13 • Produce IgE • Pascolizumab—anti-IL-4
• Associated with subepithelial brosis and airway remodeling antibody
• Fibroblastic • Altrakincept and nuvance–
inhaled
IL-6 • Promotes T 2 and T 17 di erentiation and T 1 suppression

IL-8 • Induces migration o neutrophils, monocytes and eosinophils to sites o

in ammation
IL-9 • Role in airway hyperresponsiveness, eosinophilia, and IgE

IL-10 • Anti-in ammatory and inhibits release o IL-1,IL-6,IL-12, and NF-alpha • Corticosteroids
• Deactivates macrophages, mast cells, and eosinophils • Vitamin D

IL-12 • Suppress allergies and eosinophilia

IL-17 • Proin ammatory and released by IL-23 • Secukinumab

• Secreted by T 17
• Role in neutrophilic asthma and corticosteroid insensitive

IL-22 • Acts on nonhematopoietic tissue to secret antimicrobial peptides and

maintain cellular integrity
IL-25 • Causes eosinophilia indirectly by increasing secretion o IL-5

IL-33 • Released rom necrotic cells and leads to T 2 response

(HLA) complex, is located on chromosome 6 and has a
role on antigen speci city and presentation. T ey have
roles in pathogen resistance and autoimmune disease.
T ere are two classes. Class I, HLA-A,-B, and -C, appear
to have particular characteristics such as polymorphism
and linkage disequilibrium. Recognized by CD8 cells,
class I allele has a heavy chain and a nonpolymorphic
B2-microglobulin light chain. Recognized by CD4 cells,
class II consists o a heterodimer with amino-terminal
domains representing antigen-binding regions.
**
T e association o HLA and sarcoidosis has been well
documented, initially with Class I HLA-B8 but more
so with Class II HLA, with variable implications.13
HLA-DQB1*0201 and HLA-DRB1-301 are associated
with good prognosis in British and Dutch and in Swish
respectively.14,15 HLA-DRB1*01 and HLA-DQB1*0501
have been shown to be protective against sarcoidosis.14
Other groups o HLA are organ speci c such as: HLA-
DRB1*12 and HLA-DRB1*14 are associated with lung
involvement, HLA-DRB1*04-BQB1*0301 are associated
with uveitis, and HLA-DQB1*0601 are associated with
cardiac involvement.13–18
**
CD4 helper cells produce cytokines. T 1 CD4+ aide
in cellular killing and help generate opsonizing antibod-
ies that lead to a delayed hypersensitivity response. T ey
secrete IL-2, IFN-gamma, IL-3, NF-alpha, GM-CSF, and
NF-beta. T 2 CD4+ produce IL3-6, IL-10, and IL-13
regulate humoral immunity and isotype switching.
**
CD4 and CD8 regulatory cells are produced by den-
dritic cells and suppress immune response, particularly
those rom sel -antigens.
 c h a Pt e r 1 t h e c e l l a n D im m u n o l o g y 7

Question 5: B. IgA IFN-alpha and IFN-beta, is produced by nucleated cells

Immunoglobulins are products o B cells and mediate and ype II IFN-gamma is produced by NK cells and
humoral response by binding to antigen and promote inac- lymphocytes.
tivation or removal o an o ending substance. T e basic
structure consists o two heavy chains, which determine **
the subtype, and two light chains. Each chain has a con- Granulomas orm to contain pathogen and limit in am-
stant and variable region. Disul de bridges link the heavy mation. Inter eron alpha promotes overexpression o
chains together and the heavy chain to the light chain. T e major histocompatibility complex (MHC) II on antigen
variable regions are also the antibody-binding sites. presenting cell. T is leads to increased cytokine release
rom dendritic cells, IL-12 rom monocytes, and inter-
IgG Monomer eron gamma rom natural killer cells. reatment with
Mass = 150 kDa inter eron therapy has led to inter eron-induced sar-
75–85% total Serum Ig coidosis.5 T is can be seen in inter eron alpha therapy
Binding Macrophages, neutrophils, lymphocytes or hepatitis C but case reports have suggested the devel-
Crosses placenta, secondary response
opment o sarcoidosis rom inter eron beta therapy
IgA Monomer, dimer in patient with multiple sclerosis and renal cell carci-
J chain
Mass = 150-600 kDa
noma.6 T e dependence o sarcoidosis on CD4 counts
7–15% total Serum Ig are observed in a retrospective study HIV that showed
Binding o lymphocytes patients with CD4> 200 were more likely to have sar-
Secretory coidosis than those with CD4< 200.7
IgM Pentamer, hexamer
J chain Question 8: C. LR4
Mass = 950–1150 kDa oll-like receptors initiate the adaptive immune
5–10% total Serum Ig response and have also had roles in the development o
Binding o lymphocytes septic shock.12 T ey are associated with CD14 and are
Primary response, Autoimmune diseases
expressed on macrophages, dendritic cells, and B cells.
IgD Monomer T ey activate intracellular signaling that lead to bacterial
Mass = 175 kDa and viral killing. LR2 and LR4 have been studied in
0.3 % o total Serum Ig
Mature B Cell Marker
their role in gram-negative septic shock.
IgE Monomer Question 9: B. IgG
Mass = 190 kDa Anti-IgE therapy, such as omalizumab, is an IgG antibody
0.019% total Serum Ig
that binds to IgE.9,11 It is recommended or patients with
Binding o Mast cells, Basophils, and B cells
Allergic response, antiparasitic response moderate to severe asthma, a total serum IgE 30 to 700 IU/
mL, inadequately controlled on high dose–inhaled corti-
costeroids, and positive skin testing and in vitro testing.11
Question 6: C. ype III Hypersensitivity Reaction
Question 10: E. All o the above
ype I: immediate Anaphylaxis Pulmonary brosis consists o an in ammatory state
hypersensitivity with IgE
that results in excessive extracellular matrix accumu-
ype II: cytotoxic Hemolytic anemia lation and lung architecture distortion. T is is a conse-
hypersensitivity with IgG or IgM
quence o abnormal re-epithelization and an imbalance
ype III: circulating antigen– Serum sickness, between in ammatory molecules, brogenetic and anti-
antibody immune complexes arthus reaction
brogenic molecules, oxidants and antioxidants, and
ype IV: delayed hypersensitivity Contact dermatitis antivascular and provascular molecules. Sites o epithe-
lial injury show migration and organization o bro-
Question 7: C. Inter eron gamma blasts and myo broblasts into brotic oci. Fibroblasts
Inter erons are glycoproteins with immunomodula- di erentiate into myo broblasts and perpetuate collagen
tory properties and act primarily as a response to viral synthesis, and decreased synthesis o tissue inhibitor o
in ections but have roles in response to tumor cells, metalloproteinase. T e table below lists the cells or mol-
parasites, and bacteria. ype I IFN, which consists o ecules and their mechanisms in pulmonary brosis.10
8 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

Cells or Molecules Mechanisms

rans orming growth actor beta • Stimulates broblast production, myo broblast di erentiation, resistance to apoptosis,
and ROS production
Connective tissue growth actor • Stimulates broblast production and ECM production

Platelet growth actor • Stimulates broblast production and chemotaxis

Insulin-like growth actor • Stimulates broblast production

cells • Pro brotic via LR -beta and PDGF

• CD8+ cells associated with worse prognosis
Macrophages • Overexpression o reactive oxygen species
• Pro brotic
• Receptors to proteinase

B Cells • Autoantibodies against periplakin, a component o desmosomes

• Overexpression o CD19
• May have some “protective” e ects although this remains unclear

Fibrocytes • Bone marrow derived, they produce collagen and express CD45 (leukocytes) and CD34
(stem cells)
• Di erentiate to myo broblasts and contribute to ECM or di erentiate into mesenchy-
mal cells
• Recruitment dependent on CXCL12, CCL2, CCL3, and IL-10

CD40–CD40 L • Co-stimulators in the activation o CD4+ cells via CD40L and antigen presenting cell
(APC) via CD40
• With IL-4, promotes broblasts

Fas–FasL • Inherent resistance to apoptosis

• Cells within broblastic oci have minimal or absent expression o Fas

Integrins • Cell sur ace molecules involve in adhesion between cell to cell and cell to ECM
• Roles in cell migration, growth, and survival

REFERENCES 10. odd NW, Lyzina IG, Atamas SP. Molecular and cellular
mechanisms o pulmonary brosis. Fibrogenesis Tissue
1. Rom WN, Hay JG, Lee C, et al. Molecular and genetic
Repair. 2012;5(11):1–24.
aspects o lung cancer. Am J Respir Crit Care Med. 2000;
11. Strunk RC, Bloomberg GR. Omalizumab or asthma.
161:1355–1367.
N Engl J Med. 2006;354:2689–2695.
2. Brambilla E, Gazdar A. Pathogenesis o lung cancer signal-
12. Abbas AK, Lichtman AH. Basic Immunology. New York,
ing pathways: roadway to therapies. Eur Respir J. 2009;33(6):
NY: Saunders; 2010.
1485–1497.
13. Inannuzzi MC, Rybicki BA, eirstein AS. Sarcoidoisis. N
3. Armanios, M. elomerase and idiopathic pulmonary
Engl J Med. 2007;357:2153–2165.
brosis. Mutat Res. 2012;730:52–58.
14. Grunewald J, Eklund A. Lo gren’s Syndrome. Human Leu-
4. Stone KD, Prussin C, Metcal e DD. IgE, mast cells, basophils
kocyte Antigen Strongly In uences the Disease. Course.
and eosinophils. J Allergic Clin Immunol. 2010;125:S73–S80.
Am J Respir Crit Care Med. 2009;179:307–312.
5. Marzouk K, Saleh S, Kannass M, et al. Inter eron-induced
15. Sato H, Grutters JC, Pantelidis P, et al. HLA-DQB1*0201.
granulomatous lung disease. Curr Opin Pulm Med. 2004;
Am J Respir Cell Mol Biol. 2002;27:406–412.
10(5):435–440.
16. Sato H, Woodhead FA, Ahmad , et al. Sarcoidosis HLA
6. Petousi N, T omas EC. Inter eron-B-induced pulmonary
Class II genotype distinguishes di erences o clinical phe-
sarcoidosis in a 30-year-old woman treated or multiple
notype across ethnic groups. Hum Mol Gen. 2012;19:
sclerosis. J Med Case Reports. 2012;6:344.
4100–4111.
7. Morris DG, Jasmer RM, Huang L, et al. Sarcoidosis
17. Iannuzzi MC, Maliarik MJ, Poisson LM, et al. Sarcoidosis
ollowing HIV In ection: Evidence or CD4+ lymphocyte
susceptibility and resistance HLA-DQB1 alleles in A rican
dependence. Chest. 2003;124:929–935.
Americans. Am J Respir Crit Care Med. 2003;167:1225–
8. Garcia G, aille C, Pierantonio L, et al. Anti-interleukin-5
1231.
therapy in severe asthma. Eur Respir Rev. 2013;22:251–257.
18. Ayyala US, Nair AP, Padilla ML. Cardiac Sarcoidosis. Clin
9. Gibeon D, Menzies-Gow AN. argeting interleukins to treat
Chest Med. 2008;29:493–508.
severe asthma. Expert Rev Respir Med. 2012;6(4):423–429.
 2
Pulmon ry Func ion ss

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

CASE 1 Question 2: Which o the ollowing is part o the

reproducibility criteria?
A 24-y r-ol wom n is b ing v lu or chronic cough
wi h pulmon ry unc ion s . A. No r i c s
B. Exh l ion > 6 s con s
** C. wo l rg s v lu s o FVC r wi hin 0.150 L rom
Volum v rsus im n Flow v rsus im is s n b low. ch o h r
D. T s r is < 5% x r pol volum o FVC
4 E. Pl u in volum - im curv
)
s
3
r
CASE 2
e
t
i
L
(
A 30-y r-ol wom n, 34 w ks g o g s ion wi h
e
2
m
u
his ory o s hm com s in or rou in ollow-up.
l
o
V
1

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

IVC
4 VT
)
TLC
d
3
n
o
ERV
c
e
2
S
(
FRC
w
1
o
l
F
RV

0 1 2 3 4 5 6
R pro uc wi h p rmission rom W ng r J, Cl us n JL, Co s
Time (s econds ) A, l. S n r is ion o h m sur m n o lung volum s.
Eur Respir J. 2005;26(3):511–522.
Question 1: What kind o arti act do you see?
A. Cough Question 1: Which o the ollowing are increased
B. H si ion during the third trimester o pregnancy?
C. E rly rmin ion A. V n IC
D. Air l k B. VC
E. Glo is closur C. FRC, ER, RV

9
10 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

D. LC Question 2: T e patient had a single breath nitrogen

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

2
D. LC

N
f
o
E. FRC III

%
II
CASE 3 I

A 50-y r-ol m n wi h COPD w s r rr o your

clinic or his pulmon ry is s . Pulmon ry unc ion Volume in liters
s s w r or r s p r o h ini i l v lu ion.
A. I
B. II
C. III
s
r
D. IV
e
t
i
L
E. All o h bov
n
i
e
A
m
u
l
B
o
V
CASE 4
g
n
C
u
L
A 24-y r-ol m n who w s clinic lly i gnos wi h
e
t
u
l
o
chil hoo s hm rriv s in clinic or s hm v lu -
s
b
A
ion. H is symp om ic n h s no compl in s.
Static Pleural Pres s ure or Elas tic Recoil Pres s ure cm H2 0 **
Mo i wi h p rmission rom Hy RE, Sc nlon PD, On physic l x min ion, his vi l signs r wi hin nor-
N k mur M. Interpretation of Pulmonary Function Tests. 3r m l limi s, inclu ing puls oxim ry o 97% on room ir.
. Phil lphi , PA: Wol rs-Kluw r/Lipinco Willi ms & H pp rs n muscul r. His h r n lung x mi-
Wilkins; 2008. n ion is norm l. Ch s x-r y is lso norm l.

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 n C
E. All o h bov
 c h a Pt e r 2 Pu l m o n a r y Fu n c t io n t e s t s 11

**
Spirom ry p r orm by his prim ry c r physici n
prior o sp ci l y consul ion is s ollows:

Flow P ULMONARY FUNCTION ANALYSIS

16

12 Re f P re P re P o s t Pos t Pos t
Me a s % Re f Me a s % Re f % 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/s ec 4.92 2.82 57 2.86 58 1
PEF L/s ec 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

**
H is s n or m h cholin ch ll ng s s h r is
s rong n o cl ri y i h ruly h s i gnosis o
s hm . R sul s o h m h cholin ch ll ng s r
s ollows:

BASELINE MAX RESPONSE Post-BD

Pred Actual %Pred Actual %Chng Actual %Chng
— SPIROME RY —
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/s c) 4.45 2.67 59 1.06 - 60 2.85 +6
FEF m x (L/s c) 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 Pos t
12 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

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

Dos 0.00000 0.03100 0.06250 0.12500
Do s Uni s 0.00000 0.15500 0.31250 0.62500
C.D.U.s 0.00000 0.15500 0.46750 1.09250
— SPIROME RY —
FVC (L) 5.20 5.24 5.15 5.13
% Ch ng +0 +0 +0 - 1
FEV1 (L) 3.69 3.65 3.58 3.49
% Ch ng +0 +0 - 2 - 5
FEF 25–75% (L/s c) 2.67 2.62 2.47 2.28
% Ch ng +0 - 1 - 7 - 14
FEF m x (L/s c) 8.73 8.19 7.69 7.74
% Ch ng +0 - 6 - 11 - 11

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

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

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

Dos 4.00000 8.00000 0.00000
Dos Uni s 20.00000 40.00000 0.00000
C.D.U.s 39.84250 79.84250 79.84250
— SPIROME RY —
FVC (L) 4.74 4.38 5.30
% Ch ng - 8 - 15 +2
FEV1 (L) 3.13 2.86 3.79
% Ch ng - 15 - 22 +2
FEF 25–75% (L/s c) 1.59 1.06 2.85
% Ch ng - 40 - 60 +6
FEF m x (L/s c) 7.05 6.34 8.30
% Ch ng - 19 - 27 - 4
 c h a Pt e r 2 Pu l m o n a r y Fu n c t io n t e s t s 13

Question 1: What can be said about this patient having C. T p i n r nk cup o r gul r co on h w y
a diagnosis o asthma? o his m h cholin s
A. T p i n bsolu ly h s s hm s vi nc by D. T p i n ook 1,000 mg c minoph n on h
h > 20% cr s in FEV1 uring m h cholin morning o his m h cholin s
s ing E. H lso k s lisinopril or hyp r nsion
B. T p i n bsolu ly o s no h v i gnosis o
s hm s his FEV1 i no ll b low 20% un il CASE 5
conc n r ion on 8 mg/mL m h cholin
C. T prob bili y o h p i n h ving s hm is bor r- A 73-y r-ol m n h s r c n ly b n i gnos wi h
lin u o h m h cholin conc n r ion n o COPD n h s smok 1 p ck p r y or 50 y rs. H
in uc 20% or gr r cr s in FEV1, bu his l ck no s his shor n ss o br h is no limi ing his ily
o s hm ic symp oms giv him low pr - s prob - c ivi i s n h con inu s oing s r nuous m nu l
bili y or i gnosis o s hm l bor roun his hom ily. H no s ily symp oms o
D. PF s prior o m h cholin s ing show 2% cough pro uc iv o y llow-brown spu um n s s h
improv m n in FEV1 ollowing broncho il or. T is h s on o wo bou s o “bronchi is” p r y r, or which
lon shows bronchi l r sponsiv n ss n prov s h s s his prim ry c r physici n n is ypic lly r
nough vi nc or h i gnosis o s hm in his wi h cours o or l n ibio ics n or l cor icos roi s.
p i n
**
E. H h s s hm s vi nc by h i gnosis h c r-
ri s rom chil hoo His physic l x min ion is o h rwis unr m rk bl
xc p or BMI 32 n occ sion l xpir ory wh z .
Question 2: Which o the ollowing may have inter-
ered with the methacholine challenge testing? **
Pulmon ry unc ion s s r shown b low:
A. T p i n us lbu rol inh l r 1 y prior o
m h cholin s ing
B. T p i n c m o clinic r ing milk n o
c r l or br k s prior o m h cholin s ing

Pre-Bronch Post-Bronch
Actual Pred %Pred SD LLN Actual %Chng
— SPIROME RY —
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/s c) 1.61
FEF 75% (L/s c) 0.27
FEF 25–75% (L/s c) 0.58 2.12 27 0.92 0.60
FEF m x (L/s c) 3.75 7.56 49 1.33 5.37
FIVC (L) 2.22
FIF m x (L/s c) 2.71

(continued)
14 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

(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
GV (L) 5.25 3.54 148 0.72 2.10
RV (Pl h) (L) 4.46 2.42 184 0.37 1.68
LC (Pl h) (L) 7.68 6.66 115 0.79 5.08
RV/ LC (Pl h)(%) 58 37 157 4 29
r pp g s (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 RESIS ANCE —
R w (cmH 2O/L/s) 1.45 0.48 0.66
G w (L/s/cmH 2O) 1.03

0
1 2 3 4
- 8

- 8

- 6

- 8

Pred Pre
 c h a Pt e r 2 Pu l m o n a r y Fu n c t io n t e s t s 15

Six-minute walk test results: W lk 372 m in 6 minu s C. His COPD is s v r , lung volum s r no sugg s iv
o ir r pping, his DLCO is mo r ly cr s ,
Heart Borg n h r is no vi nc o hypox mi wi h x r ion
SpO2 (%) Rate Scale O2 (L/min) D. His COPD is v ry s v r , lung volum s r sugg s iv
o ir r pping, his DLCO is mo r ly cr s ,
B s lin 94 94 2 Room ir
n h r is no vi nc o hypox mi wi h x r ion
1 minu 93 99 2 Room ir E. His COPD is s v r , lung volum s r sugg s iv o
2 minu s 93 102 3 Room ir ir r pping, his DLCO is s v r ly cr s , n
3 minu s 93 100 3 Room ir h r is no vi nc o hypox mi wi h x r ion
4 minu s 94 104 4 Room ir
5 minu s 94 103 4 Room ir CASE 6
6 minu s 93 103 4 Room ir A 68-y r-ol m n wi h 50 p ck-y rs n qui 11 y rs
R cov ry go, obs ruc iv sl p pn on CPAP, hyp r nsion,
1 minu 94 98 3 Room ir GERD, n hypo hyroi ism pr s n s or v lu ion o
2 minu s 96 93 3 Room ir incr sing yspn on x r ion. H c n pr s n ly climb
l ss h n on igh o s irs b or h ving o r s u o
3 minu s 96 95 2 Room ir
br hl ssn ss. H lso no s yspn wh n r ssing
4 minu s 95 92 2 Room ir hims l . How v r, h h s no shor n ss o br h r s
5 minu s 95 92 2 Room ir or wh n lying . H ni s ny occup ion l, nviron-
m n l, or ch mic l xposur s.

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

ing and 6-minute walk test indicate about his lung
disease?
A. His COPD p rsis s bu is lik ly unch ng sinc pr -
vious s ing 12 y rs rli r wh n h s v ri y w s
mo r
B. His COPD is s v r , lung volum s r sugg s iv o
ir r pping, his DLCO is mo r ly cr s , n
h r is no vi nc o hypox mi wi h x r ion
His physic l x min ion is r m rk bl or bo y m ss
in x is 36 kg/m², M ll mp i scor o II, n bil r l
cr ckl s.
**
His pulmon ry unc ion s s, inclu ing spirom ry,
lung volum s, DLCO, n 6-minu w lk s ing r p r-
orm . T r sul s r b low:

Actual Pred %Pred SD LLN Actual %Chng

— SPIROME RY —
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/s c) 5.59 6.90 + 23
FEF 75% (L/s c) 0.94 0.75 - 20
FEF 25–75% (L/s c) 2.78 2.36 117 0.91 0.86 2.57 - 7
FEF m x (L/s c) 5.92 8.04 73 1.32 5.86 6.87 + 16
FIVC (L) 1.73 1.81 +4
FIF m x (L/s c) 3.73 4.10 + 10

(continued)
16 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

(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
GV (L) 2.70 3.44 78 0.72 2.00
RV (Pl h) (L) 2.20 2.28 96 0.37 1.54
LC (Pl h) (L) 4.48 6.56 68 0.79 4.98
RV/ LC (Pl h) (%) 49 35 139 4 27
r pp g s (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 RESIS ANCE —
R w (cmH 2O/L/s) 1.45 0.48 0.66
G w (L/s/cmH 2O) 1.03
sR w (cmH 2O*s) < 4.76
sG w (1/cmH 2O*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 Pos t

A 6-minute walk test: W lk 305 m in 6 minu s

Heart Borg Heart Borg

SpO2 (%) Rate Scale O2 (L/min) SpO2 (%) Rate Scale O2 (L/min)
B s lin 95 83 2 Room ir R cov ry
1 minu 87 99 3 Room ir 1 minu 85 73 2 Room ir
2 minu s 79 105 4 Room ir 2 minu s 93 77 1 Room ir
3 minu s 81 95 4 Room ir 3 minu s 95 78 0 Room ir
4 minu s 80 91 3 Room ir 4 minu s 96 74 0 Room ir
5 minu s 78 113 4 Room ir 5 minu s 95 73 0 Room ir
6 minu s 82 99 3 Room ir
 c h a Pt e r 2 Pu l m o n a r y Fu n c t io n t e s t s 17

Question 1: What is the major nding in the spirome- v lu ion o shor n ss o br h. Un il r c n ly, sh h s
try and lung volumes? l h h r s hm symp oms w r un r con rol n
A. R s ric iv physiology bu no ru r s ric ion u o h no us h r lbu rol inh l r or mon hs. Sh no s
h pr s rv o l lung c p ci y n insi ious ons o yspn on x r ion ov r h p s
B. Obs ruc iv lung is s u o h FEV1 b ing l ss 1 o 2 y rs. Sh m inly h s no if cul y p r orming
h n h low r limi o norm l h r ily robic x rcis rou in u o yspn . Sh
C. ru r s ric iv is s no s sh h s ri h r lbu rol inh l r wi h only mil
D. Emphys m u o h low DLCO r li o h r symp oms. Sh ls h r symp oms only
E. Norm l spirom ry occur wi h physic l x r ion n l i r n h nh r
pr vious s hm symp oms.

CASE 7 **
A 20-y r-ol wom n wi h p s m ic l his ory signi - Physic l x min ion is r m rk bl or BMI is 24 kg/m²
ic n or ob cco us (h l p ck o cig r s p r y or n x spli S2.
4 y rs—qui 1 mon h prior o pr s n ion), ri l s p- **
l c , n mil in rmi n s hm i gnos clin-
Pulmon ry unc ion s ing is p r orm n h r sul s
ic lly (wi hou PF s) wh n sh w s chil pr s n s or
ollow.

Pre-Bronch Post-Bronch
Actual Pred %Pred SD LLN Actual %Pred %Chng
— SPIROME RY —
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/s c) 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/s c) 2.35 3.81 61 0.79 2.51 3.05 79 + 29
FEF m x (L/s c) 2.70 7.08 38 1.09 5.28 3.42 48 + 26
FIVC (L) 2.17 2.17 +0
FIF m x (L/s c) 2.58 3.89 + 50
FEV6(L) 4.03 3.97 101 0.43 3.26 4.23 106 +4
im o FEF m x (s c) 0.355 0.465 + 30

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

Pred Pre Pos t

18 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

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

A. Cl ssic obs ruc iv lung is s . Mos lik ly s hm A 50-y r-ol m n wi h his ory o COPD n Cong s-
B. R s ric iv physiology wi h lik ly “Fing rprin ing” in iv H r F ilur is s n or c r iopulmon ry x rcis
h xpir ory limb o h ow-volum loop s ing o v lu his yspn . His m ic ions consis
C. V ri bl x r hor cic obs ruc ion o io ropium, uros mi , m oprolol, lisinopril, n
D. V ri bl in r hor cic obs ruc ion lbu rol s n . R vi w o prior ch s compu
E. Fix obs ruc ion omogr phy shows upp r-lob mphys m ous ch ng s
wi h bro ic ch ng s in h low r lob s. T CPE is
bor or yspn .
CPET:

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

VO2 1.10 65% pr ic SpO2% 90 R s 84 P k
A 0.80 N P O2 67 R s 50 P k
HR 135 85% pr ic P CO2 40 R s 50 P k
O2 puls 8 80% pr ic PO2 (A– ) 20 R s 35 P k
BP 170/80 VD/V 0.45 0.43
VE 50 120% pr ic
FR 39 N
VE/VCO2
A 44
RER 1

Max Predicted HR

Max Predicted O 2 Puls e

R
O
2
O
H
2
V
P
u
l
s
e
WR VO 2

(continued)
 c h a Pt e r 2 Pu l m o n a r y Fu n c t io n t e s t s 19

(Continued)

MVV
2
E
O
V
C
V
WR VCO 2

VC

2
P
O
E
C
T
V
C
F
/
E
O
(
V
B
2
r
e
a
t
T
h
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s
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P
r
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m
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T
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V
O
n
/
u
2
E
t
V
e
)
VO 2 VO 2
2
O
A
P
T
V
P
/
a
D
C
V
S
O
a
O
2
2
2
O
a
P
VO 2 VO 2

Mo i wi h p rmission rom Am ric n T or cic Soci y; Am ric n Coll g o Ch s Physici ns. A S/ACCP S m n on c r iopulmon ry x rcis
s ing. Am J Respir Crit Care Med. 2003;167(2):211–277.

Question 1: What contributes to his exercise intoler- C. In rs i i l lung is s

ance? D. Psychog nic
A. COPD E. Non o h bov
B. CHF
 Answers

CASE 1

)
4

d
n
o
c
3

e
S
Question 1: A. Cough

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s
2

r
An cc p bl or is voi o ny r i c s, which

e
t
i
L
(
c n inclu bnorm li i s in h volum - im curv n 1

w
o
ow-volum curv s con ry o cough or v ri bl or ,

l
F
0 1 2 3 4 5 6
rly rmin ion (< 6 s con s wi h no pl u r ch
Time (s econds )
in volum - im curv n low o l volum in ow-
volum curv ), l k (volum - im curv rops ins Hesitation
o pl us n ow-volum b ck r cks), glo is closur
( n brup s op in bo h curv s), n h si ion ( h ini- 4
i l xh l ion is l y or no orc ul).
)
s
3
r
e
t
i
L
Glottis closure
(
2
e
m
u
l
4
o
1
)
V
s
r
e
3
t
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(
2 0 1 2 3 4 5 6
e
m
u
Time (s econds )
l
1
o
V
0 1 2 3 4 5 6 4
)
d
n
Time (s econds )
o
c
3
e
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/
)
4
s
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t
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w
1
/
o
s
l
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t
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1 0 1 2 3 4 5 6
w
o
Time (s econds )
l
F
0 1 2 3 4 5 6
Time (s econds )
Leak

Early termination 4
)
s
r
3
e
t
i
4
L
(
2
)
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s
m
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o
1
V
Time (s econds )

0 1 2 3 4 5 6
Time (s econds )

20
 c h a Pt e r 2 Pu l m o n a r y Fu n c t io n t e s t s 21

6 xh l ]/[conc n r ion o lv ol r ni rog n]) wi h

sm ll corr c ions or r m ining conc n r ion o lv -
)
5
d
n
o
c
ol r ni rog n n ni rog n pro uc by bo y issu s.2
4
e
S
/
s
3
r
e
t
i
L
2
(
w
o
l
1
F
%
0 1 2 3 4 5 6

n
e
Time (s econds )

g
o
r
t
i
N
Question 2: C. wo largest values o FVC are within
0.150 L rom each other
T cc p bl cri ri or in ivi u l spirogr ms consis s
o (1) r o r i c s; (2) goo s r s s n by x r -
pol volum < 5% o FVC or 0.15 L, which v r is Volume
gr r; n 3) s is c ory xh l ion n s ≥ 6 s c-
Mo i wi h p rmission rom W ng r J, Cl us n JL, Co s
on s, pl u in volum im curv or p i n c nno or
A, l; A S/ERS sk Forc . S n r is ion o h m sur -
shoul no con inu o xh l .1 m n o lung volum s. Eur Respir Jl. 2005;26(3):511–522.
**
T r pro ucibili y cri ri involv s l s hr in i- **
vi u l spirogr ms which h r o h cc p bili y cri- Ano h r g s ilu ion chniqu is h clos circui
ri wi h h wo l rg s FEV1 n FVC wi hin 0.150 L h lium ilu ion. Spirom r is ll wi h 20% o 30%
rom ch o h r.1 I his is chi v , h x min ion c n oxyg n, ir n h lium is un il 10% is chi v .2
b conclu . I no , i c n b r p 8 im s. P i n r br h s h spirom r un il h H con-
c n r ion is in quilibrium. T c lcul ion is FRC =
(% H lium ini i l – % H lium n l) × sys m volum %
CASE 2 H lium n l.2 A jus m n s r m or 100 mL or h lium
los in h bloo n -sp c volum rom br hing
Question 1: A. V and IC v lv n l r.
During pr gn ncy h r is progr ssiv cr s in
xpir ory r s rv , r si u l volum , unc ion l r si u l **
c p ci y, n o l lung c p ci y s con ry o h grow- In bo y pl hysmogr phy, volum rom bo h communi-
ing u rus. V n IC incr s . T V incr s s up o c ing n noncommunic ing irw ys is ccoun or.
600 mL s con ry o prog s ron -m i r spir ion T p i n is pl c in box n p n s wi h h n s on
n nh nc m n o hyp rc pnic v n il ory riv . VC ch k, g ins clos shu r. D cr s s in c bin vol-
o s no ch ng . um r in ir c ly r l o hor cic volum incr s .2

Question 2: E. FRC
Lung volum s c n b c lcul by ini i lly rmin- CASE 3
ing h FRC.2 T r r wo ppro ch s. On is o us
g s ilu ion chniqu which works on h riv iv Question 1: A. A
o Boyl ’s l w (P1V1 = P2V2). Ni rog n n h lium ilu- R sis nc is h pr ssur r quir o ow 1 L/S in n
ion chniqu s only m sur irw ys o communic - ou o h lung.3 I h s r ciproc l r l ionship wi h con-
ing con uc ing irw ys.2 Wi h h ni rog n w shou uc nc n is l ss in l rg r irw ys comp r o sm ll r
m ho , 100% oxyg n or 3 o 7 minu s is mploy irw ys. I is m sur in wo w ys: (1) ob ining h
or un il hr cons cu iv br hs h v < 1.5% ni rog n. pl ur l pr ssur in ir c ly vi sm ll b lloon c h r
FRC h s ni rog n conc n r ion o 0.75 n h c lcu- h is l soph gus n comp ring i wi h h pr ssur.
l ion (VFRC = [Conc n r ion o xh l N2] [volum h mou h ivi by ow (Rpulm = Ppl – P o/V)
22 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

or (2) vi bo y pl hysmogr .ph by m suring irw y p i n inh l s 100% o oxyg n. T p i n h n slowly

r sis nc (R w = P lv – P o/V). R w is l ss h n Rpulm xh l s hrough on w y v lv s ni rog n m r
b c us h r is no issu r sis nc . r cor s h ni rog n conc n r ion o xpir ir. Ph s
I is h n omic l sp c wi h no ni rog n.3 Ph s
** II consis s o mix conc n r ions o lv ol r ir n
Compli nc (CL = ΔV/ΔPpl) is h ch ng in volum w shing ou o ir rom sp c .3 Ph s III consis s
s con ry rom ch ng in l s ic pr ssur o h lung. o lv ol r ir, ini i lly rom p n n r gions wh r
T r r wo yp s: (1) s ic compli nc , wh r h r is ni rog n conc n r ions r low s .3 T slop is nor-
no ow m sur uring o l lung c p ci y ( LC); n m lly 1% o 2.5% p r li r. T is slop is incr s in
(2) yn mic compli nc which is Ppl m sur uring p hologic con i ions wh r h r is incr s h r-
n inspir ion n minus n xpir ion.3 Norm l CL is og n ous v n il ion such s in COPD. Ph s IV illus-
0.150 o 0.250 L/cmH 2O. r s h n o ni rog n mp ying rom p n n
r gions n h incr s r c h bun n ni rog n
** conc n r ion in h pic l r gions.3 Ph s IV’s ons
Hys r sis n s h m jor con ribu ion o l s ic r coil lso illus r s h irw y closur o h p n n
pr ssur is s con ry o h sur c nsions h lv - r s, usu lly 80% o 90% o VC. Ph s IV n s h
ol r ir– ui in r c . T is l s ic r coil pr ssur is h r si u l volum .
m in rmin n o m xim l xpir ory ow.

**
CASE 4
Compli nc is r uc in pulmon ry brosis. In COPD,
h s ic compli nc is incr s bu h yn mic
compli nc m yb norm l u o h h rog n ous Question 1: C. T e probability o the patient having
v n il ion. asthma is borderline due to the methacholine concen-
tration needed to induce a 20%or greater decrease in
** FEV1, but his lack o asthmatic symptoms give him a
Choic A r rs o COPD wh r h lung p r nchym low pre-test probability or a diagnosis o asthma.
c nno is n h irw ys o h x n o non is-
**
s lung, Choic B is h norm l r ng . Choic C
r rs o r uc bili y o xpir ory muscl s b c us M h cholin ch ll ng s m yb us o provi mor
o r uc lung volum n incr s r coil s s n in vi nc or n s hm i gnosis only i b s lin spirom-
pulmon ry brosis. ry o s no show signi c n irw y obs ruc ion (FEV1
shoul b ≥ 50% o pr ic [i lly ≥ 60% or 70%] n
Question 2: C. III ≥ 1 L [i lly ≥ 1.5 L] n h r is no signi c n broncho-
Singl br h ni rog n (SBN2) s s h is ribu ion il or r spons ).4 T bl b low lis s h in ic ions
o v n il ion. A r xh ling o r si u l volum h n con r in ic ions or m h cholin ch ll ng s .

Indications Absolute Contraindications Relative Contraindications

Ass ssing or i gnosis o s hm , risk o FEV1 < 50% pr ic , or < 1 L FEV1 < 60% pr ic or < 1.5 L or
v loping s hm , r spons o s hm CVA or MI in h l s 3 mon hs FEV1
r m ns Uncon roll H N (SBP > 200 or In bili y o ollow ir c ions
Chronic cough v lu ion DBP > 100) Pr gn ncy or loc ion
Bronchi l hyp rr sponsiv n ss ss ssm n in Aor ic n urysm Cholin s r s inhibi or us
p i n s wi h bronchocons ric ion R spir ory in c ion wi hin 2 w ks
Epil psy
 c h a Pt e r 2 Pu l m o n a r y Fu n c t io n t e s t s 23

** **
T ch ng in FEV1 is prim rily wh is moni or ur- Bronchoprovoc ion s s, which lso inclu s his -
ing m h cholin ch ll ng s . A ll in FEV1 by ≥20% min , m nni ol, n x rcis , h lp i n i y p i n s wi h
n s h PC20 n his is consi r signi c n s hm , x rcis -in uc bronchocons ric ion (EIB) or
m rk r o bronchi l r sponsiv n ss.4 Low s os o m h- o h r is s s wi h bronchi l hyp rr sponsiv n ss, g ug
cholin which r sul s in cr s in FEV1 by ≥20% rom h s v ri y o h ir is s , i n i y rigg rs o h ir is-
b s lin is known s h PC20. ypic lly, m h cholin is s, n rmin i h r is clinic r spons .4 T y c n
in ro uc in s ri s o incr sing conc n r ions un il c ir c ly (m h cholin n his min ) by s imul ion
os o 16 mg/mL is r ch or un il FEV1 cr s s ≥20% o irw y smoo h muscl r c p ors or in ir c ly (m nni-
rom pr - s spirom ry. During s ing, spirom ry is ol, nosin monophosph , n uc pnic hyp rv n i-
p r orm 30 n 90 s con s r ch os o ilu l ion) vi h r l s o in mm ory m i ors.
m h cholin . I conc n r ion o 16 mg m h cholin
p r mL o s no r sul in cr s in FEV1 by 20% or **
mor , h n h PC20 shoul b r por s “gr r h n Wi h m nni ol ch ll ng , h subj c is sk o xh l
16 mg/mL.” I h FEV1 is cr s by 20% or mor prior compl ly b or king s ri s o con roll p
o h os r ching 16 mg m h cholin p r mL, h n h br hs rom vic con ining 0 mg n h n incr s-
s is rmin h os n h PC20 is r por s ing os s o m nni ol. T p i n hol s his/h r br h
h low s m h cholin conc n r ion which r sul in or 5 s con s n h n xh l s hrough h mou h. A
h FEV1 lling by ≥20% rom b s lin . Following s ing, ch os l v l, spirom ry is p r orm in uplic ,
lbu rol shoul b minis r n spirom ry r p 60 s con s r inh l ion o h os . Cons cu iv
un il pr - s spirom ry r sul s r uplic . os s r minis r un il h rg is chi v , which
is 15% ll h FEV1 or cumul iv os < 635 mg.
Bronchocons ric ion is h n r v rs wi h lbu rol.
% Fall in FEV 1

20% **
Wh n comp r o m h cholin , h is l ss robus
or m nni ol ch ll ng . In hos wi h symp oms o
10%
PC 20
s hm , h s is 58% s nsi iv n 98% sp ci c wi h
posi iv pr ic iv v lu o 91% n n g iv pr ic
0 v lu o pproxim ly 90%.4 T us n g iv m nni ol
Dilvent 0.125 0.25 0.5 1 2 4 8 16 ch ll ng in p i n wi h symp oms o s hm ( n
Conc entration in mg/cc
hus high pr - s prob bili y) m k s h i gnosis o
s hm unlik ly bu o s no xclu i .
**
T PC20 c n b in rpr s b low. As c n b s n, in **
h corr c clinic l con x , x r m s in PC20 m y r sul Bronchoprovoc ion ch ll ng s wi h x rcis b gins
in mor s r igh orw r in rpr ion o m h cho- wi h pr - s ing inh l ion o ry ir (< 10 mg H 2O)
lin ch ll ng s ing whil in rm i os r spons s rom g s cylin r wi h r s rvoir b g n on
b com mor ch ll nging.4 w y v lv pp r us. T x rcis s shoul llow h
p i n o r ch 80% o 90% o pr ic m ximum vol-
PC20 (mg/mL) Interpretation un ry v n il ion (MVV ≈ 40 × FEV1). Spirom ry is
Gr r h n 16 Norm l bronchi l r sponsiv n ss p r orm prior o n 5, 10, 15, 20, n 30 minu s
r h x rcis s is compl . A ll in FEV1 o 10%
4–16 Bor rlin bronchi l hyp rr sponsiv n ss
is sugg s iv bu 15% is mor i gnos ic.
1–4 Mil bronchi l hyp rr sponsiv n ss
L ss h n 1 Mo r o s v r bronchi l hyp rr s- **
ponsiv n ss Bronchoprovoc ion ch ll ng s vi uc pnic volun-
Source: Cr po RO, C s buri R, Co s AL, l. Gui lin s or m h cho- ry hyp rc pni (EVH) involv s inh l ion o chill
lin n x rcis s ing-1999. T is of ci l s m n o h Am ric n hyp rc pnic ir o r 80% o 85% o MVV. wo
T or cic Soci y w s op by h A S Bo r o Dir c ors, July 1999.
Am J Respir Crit Care Med. 2000;161:309–329. r pro ucibl spirom ri s r p r orm 5, 10, n
24 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

15 minu s n h s is consi r posi iv i FEV1 decreased, and there is no evidence o hypoxemia with
cr s s by ≤ 10%. exertion
Question 2: C. T e patient drank a cup o regular co - **
ee on the way to his methacholine test T h llm rk o obs ruc ion is h ispropor ion
Drugs which c bronchi l r sponsiv n ss shoul b cr s in FEV1 wh n comp r o h FVC. T us h
s opp prior o h s .5 T im r m r comm n FEV1/FVC r io will ll (unl ss h FVC lso is signi -
c n b oun in s n r pro ocols. In i ion, n ihis- c n ly iminish , i. ., in c s s o s v r ir r pping).1
min s n o b s opp b c us o h n icholin rgic T low FEV1 is r c ion o xpir ory ir ow slow-
c o m h cholin . No , h c o inh l cor icos- ing n r sul s in h cl ssic conc v sh p o h xpir-
roi s on bronchi l hyp rr sponsiv n ss p rsis s or up ory limb o h ow-volum loop. Abnorm li i s in
o 3 w ks r h rug is s opp . A “n g iv ” bronch- h xpir ory ow uring xh l ion 75% FVC o
oprovoc ion s whil h p i n is using inh l cor- 25% FVC (FEF 25–75) r lso ypic lly s n ( s in his
icos roi n is symp om ic impli s h h p i n ’s x mpl ) bu r no sp ci c or sm ll irw ys is s .1
symp oms r no u o s hm . o xclu irw ys How v r, som u hori i s l h r uc ion in FEF
hyp rr sponsiv n ss, h ch ll ng shoul b p r orm 25–75 c n b sign o rly obs ruc iv physiology.
3 w ks r h iscon inu ion o inh l cor icos roi s.
**
**
As xpir ory ow con inu s o cr s , h FVC lso
M h cholin , riv iv o c ylcholin , is cholin rgic
cr s s s llu o bov . T is r c s h in bili y o
gonis h c us s bronchocons ric ion by ir c s imu-
h p i n o ully xh l uring h orc ul m n uv r.
l ion o cholin rgic r c p ors. B or s ing, qu s ion-
T r l iv ly high ows which occur in h FVC ( orc
n ir r vi wing pr vious s hm his ory, r c n in c ion,
vi l c p ci y) m n uv r c n c us xc ssiv n rrowing
o h r p r in n m ic l con i ions, n m ic ion is
o h in r hor cic irw ys, r sul ing in obs ruc ion.
minis r . Also n in orm cons n is ob in .
T SVC (slow vi l c p ci y, lso r rr o s VC [vi l
Minimum time between c p ci y]) is slow xpir ory m n uv r h c n lim-
Agent last exposure and testing in som o h in r hor cic irw y coll ps in uc
uring orc xh l ion. T i r nc in SVC n FVC
Shor c ing inh l 8 hours r c s r pp ir. In s v r COPD, h FVC m y b sig-
broncho il ors
ni c n ly low r h n h SVC. A signi c n i r nc in
M ium c ing inh l 24 hours SVC n FVC is consi r o b 200 mL or mor .
broncho il ors
Long c ing inh l 48 hours (Up o 1 w k or **
broncho il ors io ropium) T r io o FEV1 o FVC (or VC [slow vi l c p ci y, lso
Or l broncho il ors 12–48 hours known s SVC]) s blish s h pr s nc o obs ruc iv
Cromolyn so ium 8 hours is s . T b s r pro ucibl r sul o spirom ry r
Hy roxyzin 3 ys
s vr l mp s n r h minis r ion o bron-
cho il or shoul b us o cl ssi y h s v ri y o
L uko ri n inhibi ors 24 hours
ir ow obs ruc ion. Un or un ly, h r w s no pos -
Inh l cor icos roi s Up o 3 w ks broncho il or r sul r por or his p i n so “ h
C in con ining oo s Hol on h yo su y b s ” r sul is h only r sul lis . I h r or c n
b rgu h his s is in qu or cl ssi ying h
Source: Cr po RO, C s buri R, Co s AL, l. Gui lin s or m h cho-
lin n x rcis s ing-1999. T is of ci l s m n o h Am ric n s v ri y o his COPD.
T or cic Soci y w s op by h A S Bo r o Dir c ors, July 1999.
Am J Respir Crit Care Med. 2000;161:309–329. **
As bov , i FEV1/FVC is us , s v r obs ruc ion wi h
ir r pping m y r sul in norm l r io (“ps u onor-
CASE 5
m liz ion”) u o h yn mic cr s in FVC long
wi h h xp c cr s in FEV1. I FEV1/VC is us ,
Question 1: B. His COPD is severe, lung volumes are h r io will b mor s nsi iv bu l ss sp ci c or
suggestive o air trapping, his DLCO is moderately c ing obs ruc iv ci s. A subs n i l i r nc
 c h a Pt e r 2 Pu l m o n a r y Fu n c t io n t e s t s 25

b w n SVC n FVC (SVC – FVC > 200 mL) is **

vi nc o ir r pping. As p r h 1991 A S gui lin s, I h p i n c rri s clinic l i gnosis o COPD, h r
h FEV1/VC shoul b us or c ing obs ruc iv r GOLD (glob l ini i iv or chronic obs ruc iv lung
ci s n obs ruc ion is consi r pr s n wh n h is s ) cri ri or qu n i ying h s v ri y o COPD
FEV1/VC r io is l ss h n h p rc n il o h pr ic h sligh ly i rs rom h A S cri ri cl ssi ying h
v lu . How v r, p r mor r c n A S/ERS gui lin s on gr o obs ruc ion.1 Pl s no h h b s r pro uc-
COPD n h Glob l Ini i iv or Chronic Obs ruc iv ibl FEV1 (Pr - or pos broncho il or) shoul b us in
Lung Dis s (GOLD), FEV1/FVC shoul b us o or r o limi v ri bili y b w n s s.
scr n or h pr s nc o obs ruc iv physiology n ,
p r GOLD cri ri , x v lu o 0.7 or l ss is con-
FEV1 (%Predicted. Using the
si r signi c n or obs ruc ion.5 T i ring cri ri
GOLD Criteria or best reproducible FEV1
or i gnosing obs ruc ion c n obviously l o i r- Classi cation o obtained during the testing
ing ccur cy o i gnos ics mong in rpr ing physi- Severity o COPD 6 [Pre- or Postbronchodilator])
ci ns. T r or , i m y b wis o no h cri ri us
wh n i gnosing such issu s. Mil : GOLD 1 80 or gr r
Mo r : GOLD 2 50–79
** S v r : GOLD 3 30–49
On c n s h c lcul v lu s or r si u l volum
V ry s v r : GOLD 4 L ss h n 30
(RV) will i r i h FVC or VC (SVC) is us o m k
his c lcul ion in p i n s wi h signi c n COPD. I
h FVC is signi c n ly l ss h n h SVC n h RV is **
c lcul by sub r c ing FVC rom LC ( o l lung c p c- T ch ng in lung unc ion ov r im m y lso b
i y), h r si u l volum will s m high r h n i h RV is ss ss i h is v il bl . T r m y b v ri bili y
c lcul by sub r c ing SVC rom LC. Mos US c n rs in s ing minu o minu , y o y, w k o w k, c.
us SVC r h r h n FVC in c lcul ions o s ic lung T r or , i is impor n o rmin i ch ng s in PF s
volum s. How v r, or h obs ruc iv in x in h Uni r u o s v ri ion or v n h xp c ch ng s wi h
S s, h FEV1/FVC r io is us wh r s in Europ , h g . T ollowing ispl ys ch ng s l o b signi c n .
FEV1/SVC ( i n u in x) is commonly us .

** MEF (Mid
Signi cant Expiratory
Air ow r sis nc is r r ly us o c obs ruc iv
Changes Over Flow)
ci s. How v r, ir ow r sis nc m y h v rol in
ime FVC FEV1 25–75% DLCO
c ing x r hor cic or l rg c n r l irw y n rrowing.
D y o y
** Norm l subj c s ≥5 ≥5 ≥ 13 > 7%
Cl ssi c ion o h s v ri y o ir ow obs ruc ion is COPD p i n s ≥ 11 ≥ 13 ≥ 23
lso impor n . T is shoul b rmin by h b s
W k ow k
r pro ucibl FEV1 ( i h r pr - or pos broncho il or,
bu ypic lly pos broncho il or) m sur uring h Norm l p i n s ≥ 11 ≥ 12 ≥ 21 > 6 uni s
spirom ry m n uv rs.1 COPD p i n s ≥ 20 ≥ 20 ≥ 30 > 4 uni s
Y r oy r ≥ 15 ≥ 15 > 10%
A S Criteria or Severity o
Any Spirometric Abnormality FEV1 (%Predicted) Flow-Volume Loop
Mil 70 or gr r T ow-volum loop mus lso b ss ss . As b low, h
Mo r 60–69 ow-volum loop m y llu o h pr s nc o x or
v ri bl obs ruc ion, obs ruc iv physiology, r s ric iv
Mo r ly s v r 50–59
physiology, or o h r irw ys obs ruc ion. T ov r ll sh p
Svr 35–49
o h ow-volum loop mus b ss ss n mos im s
V ry s v r L ss h n 35 is s r v ling s h spirom ric numb rs h ms lv s.
26 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

Normal Flow-Volume Loop Restrictive Loops

PEF

FEF25

FEF50
PEF

FEF75 FEF25

FEF50
TLC FVC FEV RV

FEF75

RV
TLC FEV
Obstructive Loops FVC

PEF

FEF25

FEF50
Mixed Loop
FEF75

PEF

FEF25
TLC FVC FEV RV

FEF50

FEF75

TLC FVC FEV RV

PEF

FEF25

FEF50
Lung Volumes
FEF75
Exp c (or “Norm l”) lung volum s r rmin
prim rily by g n r n bo y siz (s n ing h igh b ing
h mos impor n siz v lu ) n hnici y. In chil-
RV
FVC FEV r n n ol sc n s, lung grow h n s o l g b hin
TLC
bo y grow h uring grow h spur s. T us, xp c lung
volum s or chil r n n ol sc n s r l ss r li bl .
 c h a Pt e r 2 Pu l m o n a r y Fu n c t io n t e s t s 27

Di r n hnici i s h v sligh ly i r n propor ions o lung volum n cr s in DLCO is nonlin r u

o hor cic siz s comp r os n ing h igh . T is is o h nonuni ormi y o v n il ion n p r usion in h
lso ru in h i r n s x s. T in rpr r mus b lungs. Corr c ion mo ls h v b n consi r bu no
sur h r r nc v lu s us in h s u y ruly r c y v li clinic lly.
h p i n b ing s .
Six-Minu W lk s
** T 6-minu w lk s (6-MW ) is clinic l ool us
Slow vi l c p ci y (SVC or VC) is m sur long wi h o obj c iv ly v lu unc ion l x rcis c p ci y. As p r
orc vi l c p ci y (FVC) in mos US pulmon ry unc- h A S, h 6-MW is sy o p r orm, w ll- ol r ,
ion l bor ori s. In obs ruc iv lung is s wi h ir r p- n w ll r c s c ivi i s o ily living.8 T r is lso
ping, h FVC m y b consi r bly sm ll r h n h SVC vi nc h h 6-MW is nc corr l s w ll wi h
u o irw y coll psibili y in uc uring h orc orm l s m n s o qu li y o li . In p i n s wi h s v r
vi l c p ci y m n uv r. A subs n i l i r nc b w n COPD, r pro ucibili y o 6-MW is nc is b r h n
SVC n FVC (SVC – FVC > 200 mL) is vi nc o ir r pro ucibili y o FEV1. Fur h rmor , ch ng s in 6-MW
r pping. In obs ruc iv lung is s wi h “ps u onor- is nc r l w ll o subj c iv ch ng s in yspn ol-
m liz ion” o h FEV1/FVC in x, i m y b b n ci l o lowing h r p u ic in rv n ions.
c lcul n FEV1/SVC in x s scrib bov .
**
T prim ry m sur m n in h 6-MW is h is nc
DLCO
on c n quickly w lk on h r , sur c or l s
T i usion c p ci y or c rbon monoxi (DLCO) is n 100 in 6-minu im r m . P i n s r p rmi
imp r c s bu is o n im s h lp ul wh n in rpr ing o slow own or s op s n . P rio s o r s r lso
PF s n mp ing o m k i gnosis. T DLCO is cc p bl i sir by h p i n .
highly p n n on h circul ing h moglobin in h lung.7
T r or , i h p i n ’s h moglobin is known h corr c **
DLCO (DLCOcor) shoul b r por n us or in r- A S r comm n s h us o bsolu ch ng in 6-MW
pr ion. I h p i n ’s DLCO is no known, h uncor- is nc un il ur h r s u i s r on o comp r h
r c DLCO is o n r por (DLCOunc). T conv n ion mos r li bl in ic or o physiologic ch ng v rsus v ri-
or cl ssi ying h s v ri y o cr s in DLCO is r por bili y b w n mp s.6 A norm l p rson shoul b bl
in h bl b low. No , i h DLCO is bov h low r l v l o w lk b w n 400 n 700 m uring 6-MW . In pr -
o norm l (LLN), h n h DLCO is consi r norm l. vious s u i s o p i n s wi h pulmon ry hyp r nsion,
h is nc w lk in 6 minu s corr l v ry s rongly
Severity o Decrease in wi h VO2 s rmin by c r io pulmon ry x rcis
DLCO i Below the LLN %o predicted DLCO s ing. A is nc < 332 m w s in p n n ly ssoci-
wi h incr s mor li y. T minim lly impor n
Mil > 60% bu < low r limi o
i r nc ( h sm ll s ch ng in n ou com m sur s
norm l
p rc iv s b n ci l n woul jus i y ch ng in
Mo r 40–60% m ic l m n g m n ) w s pproxim ly 33 m.
Svr < 40%

**
T r c n lso b n incr s in DLCO. T is c n b s n in
c r in con i ions such s x rcis , s hm , ob si y, supin
posi ion, polycy h mi , l o righ in r c r i c shun ,
rly pulmon ry m , n in r pulmon ry h morrh g .
**
A jus ing DLCO or lung volum (DLCO/V or DLCO/
LC) is con rov rsi l.7 Conc p u lly, corr c ing h
DLCO or lung volum loss (such s in pn umon c-
omy) s ms o m k s ns . How v r, h r l ion o loss
CASE 6
Question 1: C. rue restrictive disease
His spirom ry shows r s ric iv physiology u o low
FVC n FEV1 wi h norm l FEV1/FVC r io. No
r s ric iv lung is s c nno b con rm un il lung
volum s r m sur n con rm low o l lung vol-
um ( LC < h p rc n il o h pr ic v lu or
< low r limi o norm l [LLN]) s is ru in his c s .2
T r is no signi c n ch ng ollowing h minis r -
ion o broncho il or. Lung volum s show low o l
28 Pu l m o n a r y Dis e a s e e x a m in a t io n a n D Bo a r D r e v ie w

lung c p ci y. T is con rms h pr s nc o r s ric iv broncho il or is n s n FEV1, FVC, or bo h

lung is s . T gr o r s ric ion is mo r b s h improv ≥ 12% and ≥ 200 mL ollowing broncho-
on FEV1, hough i is mil b s on LC con nc il or. T is m y in ic gr o r v rsibl bron-
in rv ls ( LC pr ic – LC m sur = 2.08). chocons ric ion.
Qu n i c ion o h gr o r s ric ion: **
How v r, h ow-volum loop mus no b ov rlook .
A S Criteria or Severity o Any T ow-volum loop in his c s pp rs o show pl -
Spirometric Abnormality1 FEV1 (%Predicted) u in h xpir ory limb. T is is s n in bo h h pr -
n pos broncho il or loops. T inspir ory limb o
Mil 70 or gr r
h ow-volum loop is lso bnorm l, bu his n ing
Mo r 60–69 is lik ly m ni s ion o s chniqu r h r h n
Mo r ly s v r 50–59 physiologic con i ion in h p i n .
Svr 35–49
**
V ry s v r L ss h n 35
An irr gul ri y in h xpir ory limb m y no b n c s-
s rily p hologic, bu m y b r pr s n iv o mil sm ll
** irw y coll ps h occurs wi h orc xh l ion. T is
Al rn iv ly, h s v ri y o r s ric ion c n b r- is sp ci lly ru i h r sul is con inu lly r pro uc
min by o l lung c p ci y con nc in rv ls s r c- in subs qu n mp s. Such n ing is commonly
omm n by h In rmoun in T or cic Soci y. T is r rr o s “Fing rprin ing” or “Sign ur ” which
is on by sub r c ing h m sur o l lung c p ci y ims o illus r h h sub l sh p o h ow-vol-
rom h pr ic o l lung c p ci y ( LC pr ic um loop is uniqu o v ry p i n . Fing rprin ing/
– LC m sur ) i h o l lung c p ci y is b low h Sign ur s o no usu lly ch ng ov r im . I h irr g-
low r limi o norm l or h in ivi u l p i n . ul ri y is no r pro uc in ll subs qu n mp s, h
c lik ly r pr s n s n r i c , n or -r l n -
LC predicted – LC predicted –
ing, cough uring s ing, c.
LC measured LC measured
**
Severity o Restriction Women Men A pl u in h xpir ory loop, such s s n h r ,
Based on Con - shoul m k on consi r h possibili y o v ri bl
dence Intervals
in r hor cic irw y obs ruc ion. Common c us s o
Norm l (< 1 CI) < 1.08 < 1.61 v ri bl in r hor cic irw y obs ruc ion inclu r -
Mil (≥ 1–1.5 CI) 1.08–1.16 1.61–2.41 ch om l ci n umor.
Mo r (≥ 1.5–2 CI) 1.62–2.15 2.42–3.21 Fixed upper airway obstruction
S v r (≥ 2 CI) > 2.15 > 3.21
PEF
T r or , in his p i n , his r s ric ion is mo r p r A S cri ri
(b s FEV1 = 65% pr ic ) n is mil p r con nc in rv ls ( LC FEF25
pr ic – LC m sur = 6.56 – 4.48 = 2.08).

FEF50

CASE 7
FEF75

Question 1: D. Variable intrathoracic obstruction

In his c s , h pr -broncho il or spirom ry v l-
u s r consis n wi h obs ruc ion (FEV1/FVC r io TLC FVC FEV RV
< LLN) wi h signi c n r spons o broncho il or
(FEV1 incr s s by 25% [> 12%] n 0.23 L [> 0.2 L]).
As pr viously iscuss , signi c n r spons o
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eat. It maddened him to hear these old ladies chattering over tiny
pulsations of monotony as it they were events; to hear them
discussing the paltry British weather under an impervious roof; to
hear them talk of burglars in the next parish as if they were tigers on
the lower branches; to learn that Julia’s quarrel with Mrs. Armstrong
had ended in changing her doctor, when he had pictured her tearing
handfuls of fur out of Mrs. Armstrong’s back. He longed to throttle
the smug butcher who brought the daily tray of meat, robbing life of
all the pleasure of desire.
When he first arrived the Prince had been so easily amused. It was
enough for him to sit at a window and watch the men mending the
road; to follow the housemaid from room to room and see her make
the beds; to help to screw a leaf into the dining-room table; to dust
Mr. Cato’s books. It was, therefore, a great surprise to his host when
he blurted this out one evening. Had it been one of his nephews from
the country—his youngest sister married the Rector of Woolcombing
—Mr. Cato would have known what to do; he would have treated him
to some of those amusements which are provided for country
nephews; taken him to the British Museum, South Kensington, the
Tower of London, or the College of Mining in Jermyn Street; he
would have contrived little outings on omnibuses, ending with tea at
an Aërated Bread shop. But the Prince seemed too old for these
things; the weather was bad; Mr. Cato was busy, and he had
determined to keep him at Hampstead till things had settled down
and he knew his proper social value.
 IX
That was one of Mr. Cato’s chief preoccupations. What was the
Prince’s social station in England? How much deference might be
demanded of the world? Who were the people to whose company he
had a natural right? One must neither prejudice his future by
assuming too low a value for him, nor expose him to any rebuff by
claiming too much.
The question was one beyond Mr. Cato’s own competence. His
thoughts turned to his nephew Pendred. Not a country nephew this,
with any implication of humbleness. Quite the contrary; Pendred
Lillico, ex-Lieutenant of the Grenadiers, son of Mr. Cato’s half-sister,
who had married a hitherto obscure baronet in the days of her
beauty. Pendred was a dancing man, a well-known man, a pattern of
manners, an arbiter of fashions. They rarely met: Mr. Cato was
secretly afraid of his nephew; Pendred seldom had occasion to boast
of his uncle.
He arrived on his motor-car—small, fair, translucent, admirable. The
occasion suited him. Appreciation was his métier—appreciation of
frocks, laces, china, women, men. He knew hallmarks, pottery-
marks, marks of breeding, marks of coming success. Mr. Cato
passed the morning before his arrival in a restless state; he was
nervous as to the verdict.
‘How much a year, do you say?’ asked Pendred, in his touching little
glass voice.
‘Two thousand.’
‘H’m ... Borneo.... Can I see him?’
‘But that makes no difference, does it?’
‘It’s everything.’
‘But, surely dukes and millionaires aren’t estimated on their personal
value?’
‘Oh, once you get into big figures!’
‘But a man’s social value....’
‘Social value, my dear uncle, is human value.’
‘Well, I’m delighted to hear it.’
‘On two thousand a year, that is.... Well, let’s see your man. I think I
shall be able to give you an opinion.’
Prince Dwala was seated in an armchair in the library—nursing the
fire, remote, abstracted. So abstracted that he took no notice of their
entrance. Pendred put his head on one side and tried to sketch a
rough estimate; he was puzzled. He put his head on the other side
and attempted a new valuation. Mr. Cato touched the Prince on the
shoulder.
‘I’ve brought you my nephew to make your acquaintance.’
Dwala gave a long sigh and looked up.
‘Nephew ... what’s a nephew?’
‘This is my nephew,’ said Mr. Cato, presenting Pendred, who
stepped delicately forward, smiling, with hand extended.
The Prince drew him towards himself. Then suddenly, without any
warning, as if it were the most natural thing in the world, he took him
up in his arms and carried him to the light to make a better
examination. Mr. Cato stood petrified. Pendred lay perfectly still,
looking up with frightened blue eyes. Dwala seated himself on the
edge of the table by the window, and put Pendred on his knee. It was
the first finished product of civilisation that he had seen, perfect at
every point. He smelt him; he stroked his hair and ears; he felt the
fineness of his clothes; and growled a deep guttural growl of delight.
‘I should like to have a nephew, too.’
‘Put him down, put him down,’ cried Mr. Cato, finding voice: ‘you
mustn’t treat Pendred like that!’
Dwala glided obediently off the table, set Pendred on a chair, and
crouched at his feet looking up.
‘Does it talk?’ he asked.
‘That’s right. Of course he does. Pendred’s a terrible chatterbox. He’ll
talk your head off.’
‘Please make it talk.’
‘How can he talk when you frighten him to death like that?’
‘Don’t be absurd, Uncle Wyndham,’ said Pendred plaintively: ‘I’m not
at all frightened, thank you.’ He pulled out his case of gold-tipped
cigarettes, and lighted one, at which Dwala growled again and
clapped his hands.
‘Did you have a jolly voyage? I hear you were quite a lion on board.
Terrible long journey. Awful bore travellin’. What do you think of
England?’
‘Pretty voice! pretty voice!’ said the Prince, stroking one of his little
boots. ‘Will it eat? He pulled a biscuit out of his pocket and put it up
to Pendred’s lips. Pendred slipped his legs away and jumped up.
‘No, thanks awfully. I must be gettin’ home. People to tea. Awful
bore.’ And with this he bolted straight out of the door and through the
house to his motor-car, which was snorting and jumping up and
down outside, in charge of a man in shiny black surrounded by a
crowd of ragamuffins. He was half-way down the road when Mr. Cato
emerged in pursuit.
The Prince sat by the fire, nodding his head in high spirits, and
ejaculating: ‘Awful bore! Awful bore!’
‘How dare you?’ said Mr. Cato, coming in a moment later, and
shutting the door behind him.
‘Dare what?’
‘How dare you treat my nephew like that? Pendred! A gentleman! A
future baronet! Here am I, working my fingers to the bone to get
justice done to you—at it night and day, spending my substance,
sacrificing everything—and then, when I invite my nephew out here,
who might have helped you in your London career, you treat him like
that! You drive him out of the house—he even forgot his gloves.’
‘I liked him. I wanted to keep him.’
‘You treat him like a child, like a plaything, a doll. You forget that he
is a man.’
‘Is he a man?’
‘He was twenty-eight in June. Of course he’s a man.’
‘I didn’t know. He has no eye.’
‘No eye? What do you mean?’
‘Nothing here.’ The Prince moved his hand over his eyes. ‘Nothing
behind.’
‘I don’t know what you mean. Eye or no eye, I’ll beg you for the
future to be respectful to everybody, mind you—everybody, high or
low. Social position makes no difference. Now you’ve spoilt
everything. Pendred’s offended. He won’t come back. How can you
get on if you behave like that?’
Mr. Cato had heard of a man ‘having a leg,’ but never of a man
having ‘no eye.’ It conveyed nothing to him. But the idea was clear
and even elementary to Dwala. Being a beast, endowed with no
reason, having only instinct and that μονὴ αἰσθήματος, or
persistence of impressions, which takes the place of reason in the
lower animals, he was incapable of the rational classification of
natural things which characterises the human outlook. His criteria of
species were distinct but illogical; his categories did not tally with
human categories; they fell short of them and they overlapped them.
Species was defined for him, not by the grouping of attributes, but by
an abstract something—a spiritual essence inherent in the attributes.
He was guided, to put it in philosophical terms, not by ‘phenomena,’
but by ‘noumena.’ For instance, he knew a horse from a donkey, not
by its size, its ears, or its coat, not on consideration, but abruptly,
instinctively, round the corner, by an effluence of individuality; in
short, by its ‘equinity.’ So too, in the forest, he had always known a
venomous cobra from a harmless grass-snake at any distance, not
by considerations of form or colour—considerations which might
often have led to too late a conclusion—but merely by its ‘cobrinity.’
But this attitude is liable to error; and Prince Dwala had been led
astray by it. His notion of the essence of humanity was formed from
the men he had first met; it was limited and imperfect. It included an
element not essential to humanity, this ‘eye’ of which he spoke: a
thing difficult to define; something revealed in the bodily eye; not
exactly strength of will or power to command; not entirely dignity or
courage; some reflection rather of the spirit of the universe, a self-
completeness and responsibility, a consciousness of individual
independence. This he had known and felt in the American, in the
Soochings, in Mr. Cato, in the housemaid—it was the basis of his
respect and obedience; but it was wanting in Pendred Lillico.
It was fortunate that he was disabused of error so early in his career.
He could afford to laugh at his foolishness later—he saw what
mistakes of behaviour it would have led him into; for when he came
to know London better, he found that the mass of people, both in
drawing-rooms and slums, indubitably men, altogether lacked the
‘eye’ which he had thought essential.
 X
At breakfast next morning Mr. Cato groaned a good deal over his
letters.
‘Well, Wyndham, what does Pendred say?’ asked sister Emily.
Mr. Cato frowned, and shook his head in a menacing aside,
enjoining discretion.
‘I was afraid so,’ he said, after breakfast, when Dwala had retired to
the study fire. ‘Pendred is very pessimistic. Oh dear, oh dear! And
yet, who can say he is not right after the way he was treated? “I am
afraid that the same thing cannot be said of your protégé. Quite
apart from his rudeness to me—of which I will say nothing, if you will
do the same—it is evident that Prince Dwala is not a gentleman. Not
at present, at any rate. There is a brusquerie about him which would
do very well in a Hapsburg or a Hohenzollern, but not in a deposed
Borneo Prince. He doesn’t know how to sit down; nor in fact what to
sit on. He doesn’t know what to do with his hands; all his movements
are too large, and, as Lady Hamish would say, ‘too conclusive.’”
Pendred won’t come to lunch on Tuesday—I was afraid not; he
leaves town on Monday. However, there is a ray of hope. It is really
very generous of Pendred, considering. It is certainly worth trying.
“Gentlemen are made as well as born. Captain Howland-Bowser
acquired it because he was determined to succeed; and now nobody
would know he was not a gentleman, and in fact a very fine
gentleman, and received everywhere. Of course it is a secret. I
should never have known if Warbeck Wemyss had not told me
himself. Present the letter I enclose, and let him see that you mean
perfect discretion.”’
‘Who is Warbeck Wemyss? Not the ...’
‘Of course.’
‘The actor?’
‘Gives lessons in manners, do you mean?’
‘But won’t it be very expensive?’
‘Of course Wyndham means the Prince to pay himself.’
‘Now Clara, once for all, let me hear no more of these hints. The
Prince shall not pay. We have no right to expect it, poor fellow. We
have done very well without going to the country this year, and surely
we can manage to do it again. If the worst comes to the worst we
can move into a smaller house when the Prince leaves us. You must
try to be more economical; the bills come to far more than they ought
to.’ He closed the discussion by leaving the room.
Warbeck Wemyss consented, on terms. It was a ‘wrench,’ as
Traddles would have said; but surely it was worth while. The lessons
were a great amusement for the Prince. The going out into the
passage; the entering the library, hat in hand; the surprise on Mr.
Wemyss’s part; the little interchange on health and weather; the play
with his monstrous gloves: the more elaborate lessons;
introductions; forgetfulnesses; the assumption of grave interest while
a humble Wemyss endeavoured to recall to him where they had met
before; the pretended dinners; the new words; the manner of
gallantry; the manner of confidence; the gestures and ejaculations of
patience under a long anecdote—a thousand situations which
pictured a new and delightful universe before his eyes. Dwala had
the imitative faculty in perfection; he almost cried with humble joy
when Wemyss clapped him on the shoulder, and assured him that
he would make a gentleman of him in no time. Mr. Cato was
delighted with the teacher’s reports: a little slapdash at first; rather
random in the use of ‘rippin’’ and ‘awful bore,’ but quicker progress
than he had ever seen.
 XI
Meanwhile there were other things to raise Mr. Cato’s spirits.
Parliament was back. The Government still held good, it is true, in
spite of all rumours to the contrary; but opposition is exhilarating.
Best of all, the Privy Council was in session. The Crown Officers,
worn out with long obstructive sittings, made a poor fight of it: a
dispute about a bit of land in Borneo was a small matter compared
with the fate of a historic party. The judges were favourably
impressed by the brusque appositeness of Mr. Cato’s counsel.
When Mr. Cato came back one day in a four-wheeler instead of the
omnibus, his sisters knew that something extraordinary had
happened.
‘We’ve won!’ he cried, sinking, smiling and exhausted, into an
armchair.
Everybody shook hands with Dwala.
‘Thank you, thank you,’ he said, pressing each hand delicately, and
laying his left hand on the top of it, in a graceful and engaging way
which Mr. Wemyss had taught him. ‘You’re very kind.’ But he had no
understanding of the news. Only at dinner, when a gold-necked
bottle of Christmas champagne was produced and they all drank his
health, he began to realise that it was something solemn and
important.
 XII
It was more solemn than anybody suspected. The news from the
mines had been good; but it was nothing to what it was going to be.
When Mr. Cato came home in the afternoon, two days later, he found
a smart brougham at the door. On the hall table lay a card: ‘Baron
Blumenstrauss.’ The famous Baron in his house! The drawing-room
was empty. He went into the library. There he beheld an elderly bald-
headed Jewish gentleman in a white waistcoat, with fat little purple
hands clasping his spread knees, gazing with baggy eyes through
dishevelled gold pince-nez at Prince Dwala, who lay back in an
armchair, lids down, breathing heavily. At Mr. Cato’s entrance, the
visitor took off his pince-nez and looked up.
‘It iss an extra-ordinary ting,’ he said: ‘de shendlemann ’as gone to
sleep!’
The Prince awoke at this and leaned forward blinking.
‘Pray continue. It is most interesting.’
‘I am not used to ’ave my beesness bropositions receift in soch a
way. I am Baron Blumenstrauss,’ he said, turning to Mr. Cato, with
gurgling guttural r’s.
‘Yes?... I am Mr. Cato—Mr. Wyndham Cato ... I ... I live here, you
know.’
‘Ah—sit down, Mister Cato. I ’ave read your speeches. You are
cleffer man; you ’ave ideas; wrong ideas, bot cleffer. What can I do
wid a shendlemann dat go to sleep when I make him beesness
bropositions? I offer to make him very rich man, he say “rippin’”; I
say four hunderd tousand pount a year, he shut his eye; I say fife
hunderd tousand pount, he go to sleep.’
‘Five, hundred ... thousand ... pounds!’ ejaculated Mr. Cato faintly,
overwhelmed.
‘Effery year.’
‘Why?’
The Baron winked ponderously, with an effort, and smiled with
exquisite penetration of Mr. Cato’s labyrinthine slyness.
‘Nod for nussing!’
‘What is the proposition?’
‘Are you de shendlemann’s guardian?’ returned the Baron abruptly.
‘Why no,’ reflected Mr. Cato: ‘I suppose I am not. But I’m his principal
adviser.’
‘Ah! I know.’
The Baron rose suddenly, snatching up his white-lined hat and
lavender gloves.
‘Well, goot-bye, shendlemen. I haf laties wait for me at home. Adieu,
mon Prince.’
‘Good-bye, good-bye,’ said Dwala, with careful intonations: ‘I hope
you’ll look in again some time.’
‘Goot-bye, I leaf you to your books, your studies. Goot-bye ... Dis
vay?’ he appealed to Mr. Cato, moving towards the door.
‘I’ll see you out.’
‘Goot! You haf charming leetle house. Man can see dat Madame haf
excellent taste.’
He stopped at the hat-rack, took down a hat and put it into Mr. Cato’s
hand, nodding and smiling.
‘Put him on. You come wid me.’
‘I wasn’t going out.’
‘Come alonk. I make you beesness broposition.’ He hurried him
down the steps. ‘Leedle flower’s all dead,’ he said, half glancing at
the wintry garden. ‘Half-past seex,’ he added, looking at his watch.
As they bowled along in the smooth brougham, night fell. The Baron
talked; Mr. Cato began to see dimly the gigantic outline of the thing
that he had done. His mind was still numbed with the vastness of big
figures; he hardly perceived the order in which things happened. The
Baron had drawn a paper from some recess of the carriage and put
it in his hand; he was fascinated by the purple unconscious
forefinger striding about it, and the continuous voice in his ear. It was
a map, a copy of the map of the Sooching forest made by the
lawyers: ‘As shown in the map appended hereto, and marked C,’ he
repeated to himself. Yellow squares, and circles and figures in black
had grown on the bare centre since he last saw it. The purple blood-
gorged finger was running rapidly from pit to pit; they were all full of
gold, and the finger was peeping and gloating and chuckling,
planning schemes of union and division, conquest and annihilation.
The coachman’s steady back looked in with its two silver eyes from
the box, like the face of a giant Fate, rumbling and gliding them to
inevitable ends.
The burst of a barrel organ brought him to everyday consciousness.
The Baron was still talking.
‘“Are de Government mad?” said my friends to me. “Dey might haf
taken de whole ting wid deir retchiment of men; and dey let it all go
to one shendlemann. An’ now dere can neffer be a war for it; it is
brivate broperty. Dey leaf it to de Soochinks? Goot! Someday de
Soochinks rebel; dey oppose de Ettucation law, de Tynamite law, de
Church law: de Government take it away from dem. Goot! Dat is
Bolitics. But dey have made it Broperty: dere is no Bolitics wid
Broperty. We shall see big row. De Government will fall.”’
‘They have many things to answer for.’
‘It is solid gold!’
‘Ten thousand butchered Bulgarians lie at their door.’
‘Polgarrians? What are your ten tousand Polgarrians to me, ten
hunderd tousand Polgarrians, ten million Polgarrians? A tousand
tons of solid gold, I tell you. Dey know nussing, your Government. All
de land is one big reef. I haf known it tree munt, you haf known it,
efferybody haf known it; but de Government knows nussing, de Brivy
Gouncil knows nussing.’
‘Do you mean that the gold runs right across this map, where these
marks are?’
‘Natürlich.’
‘I never even guessed it.’
‘Is it a choke? Bah! Den why haf you made soch friends of de
Brince?’
‘What’s your proposal?’
‘Wait!’ He put his head out of window and shouted to the driver:
‘Kvicker! Kvicker!’.... ‘I tell you at home. Haf a smoke?’ He held out a
fat cigar-case.
‘No thank you.’
‘Take it! take it! Fifty pount a box.’ Mr. Cato still refused.
Gates opened before them; they drove over a gravel court, and
ascended broad steps on a red carpet rolled down by footmen.
‘To de English room.’
They flew through a monstrous hall, with three footmen after them;
fountains, palms, mosaics, tiles, pillars, galleries, lights; a card-table,
dwarfed by the vastness; card-players, lounging men, thin
contemptuous women smoking cigarettes. As they bowled rapidly by,
the Baron waved flickering red fingers:
‘My exguses laties. Come along Max: beesness!’
A young Jew arose from the table, threw down his cards, made
apologies, and followed quickly.
In the English room the Baron cast rapid gestures at the pictures on
the walls:
‘Reynolds, Cainsborough, Dicksee, Constable, Leader, Freeth.
Come along, Max. Bring champagne,’ he said to the footmen.
‘Not for me, thank you,’ said Mr. Cato.
‘Goot! I will drink it mysailfe.’
They sat in a blaze of electric light, velvet, gold, Venetian glasses;
everything exhaled a fat smell of luxury. This was the stunning
atmosphere in which the Baron preferred to make his ‘broposition.’
Papers flitted about the table; champagne and diamond rings
flickered before Mr. Cato’s eyes.
The Baron planned an amalgamation, a monopoly; harmony and
understanding; big handling and cheap production; the sales
regulated; the market chosen; the rate of exchange manipulated. A
mass of companies, with different names, different directorates, even
different supposititious localities.
‘If I call him Cato Deeps, and say he is in Mexico, who knows? who
cares? De enchineer? I pay him. De public? De diffidends are all in
Treadneedle Street.’
An oscillation of good reports and bad reports, share-prices going up
and down, with the Baron and his friends in the middle of the see-
saw, and money rolling to them from alternate ends of the plank.
‘Gold is goot, but gompanies are better,’ he said.
But the Baron must have a free hand; it amounted to a purchase, a
right to exploit. Everything depended on the Prince, and evidently the
Prince depended on Mr. Cato. For the one there waited the 500,000l.
a year in perpetuity, guaranteed on his own property; for the other,
directorships, fees, shares, pickings at every corner; a safe income
of at least ten thousand to be had for the asking. He had only to get
the Prince’s consent to the bargain.
Mr. Cato flipped aside the personal question without a word. But for
the Prince? 500,000l. a year. No one could reasonably ask more of
life. Had he a right to refuse it? But these companies! tricks of
promotion! all the garbage of the money market. Had he a right to
accept it? He hesitated.
The butler came in, and murmured in the Baron’s ear.
‘Where?’
‘Just outside, sir.’
‘Gif him a smoke, and tell him to vait.’
‘Can I come in?’ said a voice at the door.
‘Aha, cher Duc!’ cried the Baron with brazen-voiced, brutal
bonhomie: ‘go to de pilliard room and vait.’
‘Can’t you spare a moment?’
‘Ne voyez-vous pas?’ The bonhomie passed to imperial fierceness. ‘I
am peezy!’
‘Well?’ he said, as Mr. Cato still sat plunged in thought. ‘For you it is
leetle question—for de Brince, leetle question: it is me or somebody
else. Fife hunderd tousand pount, effery year.’
Mr. Cato still pondered. He thought he saw his duty clearing before
him.
‘Well? De Duke vaits; I vait. You impoverish de world: you widdraw
me from circulation. Is it Yes?’
‘No!’ said Mr. Cato, pushing back his chair. ‘It is No.’
‘Ah?... Who will manage de mines?’
‘The Prince will manage the mines. I will manage the mines.’
‘Goot! You hear, Max? Dis shendlemann will manage de mines.’
Max only stared palely at Mr. Cato. The irony was too great for
laughter. He saw a man putting to sea on a plank, unconscious of
the deep voice of the gathering tornado; a child going out with a
wooden gun to make sport of an angry crowd of sans-culottes.
‘Can I get a copy of the corrected map anywhere?’ asked the Child.
‘Gif him de map, Max,’ said the Baron, with a short, indulgent laugh.
‘My secret achents haf brepared it, Mr. Cato. Gif him de figures, all
de papers. Let him haf efferyting. Goot-bye, Mr. Cato. See him to de
carriage, Max.’
‘I’ll walk, thank you.’
‘Better drive. Goot-bye.’
‘Good-bye.’
‘You will haf deeficulties, Mr. Cato.’
Mr. Cato went home by omnibus. His heart sank as he looked at the
map, divorced from the purple finger.
There is lightheartedness in great conflict: we see the larger outline;
our forces are fed by the consciousness of it. A field of gold, still in
possession; a thing still to sell, if need be: it was an impregnable
position. But courage is needed after the battle; we see partially, at
short range. To have rejected a magnificent offer, to have so little in
its place—some papers, an idea, a consciousness that needed an
atlas to explain it. To have rejected the proposals of confident
authority creates a helpless mid-air terror; that is the power of
religions. Mr. Cato felt like a heretic of the Middle Ages, wondering,
on the way to the stake, if after all the Pope were not right.
He went straight to his bedroom; walked up and down in his slippers,
lay awake for hours in long moods of elation and depression, and fell
asleep at last very cold.
 XIII
The wheel had begun to turn. Nothing could stop it now. Next
morning came a fresh-looking elderly gentleman in grey, who
announced himself as ‘of the Colonial Office.’ He looked about him
as if he meant to buy the place; but modestly, as if for someone else.
Mr. Cato received him in the drawing-room. He hoped the Prince
was well. The Colonial Office had heard of the Prince’s improving
fortunes. His business concerned the Prince, but it could most
conveniently be broached to Mr. Cato. He would see the Prince
afterwards.
It had probably struck Mr. Cato that the time had now arrived for the
Prince to set up a separate establishment. The Colonial Office,
which was ultimately responsible for him, felt that Mr. Cato’s
kindness must not be trespassed on. He must not be allowed to
monopolise the Prince.
Mr. Cato had probably noticed that native potentates always had,
what you might call, for want of a better word, ‘keepers’ attached to
their persons while they were in England. The actual title varied. As
a rule it was some tall muscular military man who was said to be ‘in
attendance on His Majesty the So-and-so.’ It was this functionary’s
duty to keep him generally out of mischief; for these Oriental fellows
would play the very deuce if left alone. Well, as far as Prince Dwala
was concerned, the Colonial Office had decided that a Private
Secretary would meet the case, and they had in fact selected the
man.
‘Who is it?’ asked Mr. Cato, repressing a pang of jealousy.
‘One of the Huxtables—John Huxtable, a son of the Bishop.’
This again smelt of large success. Mr. Cato knew nothing of this
particular John; but he was a Huxtable, and Huxtables are, like
Napoleon, not men but institutions. Nature has such caprices. Out of
many million wild rough briars, one rougher and crabbeder than all
the rest is chosen by her for a fathering stock; whatever is grafted on
it thrives. Another is richer, larger, better-flowered, the pride of the
field—it is wise, courteous, a soldier, a leader of men; it is made a
Duke; it is grafted with the delicatest buds of Paestum. But the bloom
is frail and mean; shelter and fine feeding avail not, it has a good
place in the garden, but it is fragrant only in its name. The Huxtables
came of a rough and crabbed stock. Their great-grandfather was
somebody’s gamekeeper. His sons throve in business. His
grandsons were great men—soldiers, lawyers, priests. His great-
grandsons, an innumerable rising generation, were destined for
greater greatness. It had become an English custom to see large
futures before them. They were big and bony, they played at Lord’s,
they abounded in clubs and country houses; their handsome, strong-
toothed sisters married well, breeding powerful broad-browed babies
that frowned and pinched.
This particular Huxtable had tutored a Prince of the blood. He had
been secretary to a philanthropic commission; he would be a
Cabinet Minister, a Viceroy—anything he pleased. For the present
he would be private secretary to Dwala: he would manage him,
regulate him, assert him, protect him, establish him, marry him
perhaps, and pass on to another broad stage in the regal staircase
of his career.
As for the mines, the gentleman in grey had no advice to offer. It was
a private affair of Prince Dwala’s; no concern of the Colonial Office.
Why not consult some big financier? Baron Blumenstrauss, for
instance.
Mr. Cato made no reply.
‘Well, after all,’ the grey gentleman concluded, ‘it had better be left to
Mr. Huxtable.’
 XIV
The Huxtable came later—a terrifying young man, who said little, but
listened with a tolerant smile—and after him a host of others,
entailed by his plans for Dwala. A house had been found in Park
Lane. The owner, who was travelling in the East, had left the thing
intact; his creditors wished to sell it as it stood. The appointments
were passable; he had been a rather random collector of good things
—some rubbish must be weeded out and replaced, but there was
nothing to delay possession.
However, it must be paid for. If Mr. Cato would produce his accounts,
the Huxtable would be glad to go through them with him.
‘Oh, I have no accounts to show.’
‘Why not?’
‘Dwala has been my guest. There is nothing to account for.’
‘But the property in Borneo—you have an account of that?’
‘No.’
‘This is all very curious. A man has a fortune of some hundreds of
thousands a year, and no account is kept of it!’
‘But he hasn’t got it yet. It lies buried in the earth in Borneo.’
‘Yes; it consists of mines, I know. But, of course, the fortune was
realisable as soon as the Privy Council gave their decision.’
‘Well, it hasn’t been realised.’
‘But the decision was given a week ago. Do you mean to say it has
been neglected all this time?’
‘“Neglected” is a piece of impertinence, Mr. Huxtable.’
‘A week’s income lost means something like 10,000l.’
‘How dare you come to me—me, who has been toiling night and day
in the Prince’s interest—in this authoritative, censorious way—I, who
am old enough to be your grandfather—talking of neglect?’
‘You regard it as an aspersion? Well, and what are the results of all
your labour?’
‘I have secured him justice.’
‘Justice is a matter of law, Mr. Cato: the Privy Council has attended
to that. If you were incapable of realising his fortune yourself, why
not have applied to some big financier—Baron Blumenstrauss, for
instance?’
‘I have seen Baron Blumenstrauss.’
‘Well, what did he say?’
‘He made an offer. He volunteered to buy all the Prince’s rights for
500,000l. a year.’
‘Then, surely, you have realised it?’
‘No, sir, I have not.’
‘You don’t mean that you refused his offer? You weren’t expecting
anyone to offer more, I suppose?’
‘I refused his offer.’
‘On what ground?’
‘I regard Baron Blumenstrauss as an immoral man. I regard his
business methods as immoral. If I had accepted the offer on the
Prince’s behalf, I should have been advising him to lend himself to a
vile system of exploitation, which I regard as one of the most
infamous curses of our modern civilisation. I would rather see Dwala
starve.’
‘You have taken a very great responsibility on yourself, Mr. Cato.’
‘I am quite willing to bear it.’
A smile flickered round the Huxtable’s nose, and Mr. Cato felt that he
was being betrayed into melodrama. Silence ensued.