2017 making sense of lung function tests

MAKING SENSE of

Lung Function Tests
Second edition

A hands-on guide



MAKING SENSE of

Lung Function Tests
Second edition

A hands-on guide
Jonathan Dakin, MD FRCP BSc Hons
Consultant Respiratory Physician
Royal Surrey County Hospital NHS Foundation Trust
Surrey, UK
Honorary Consultant Respiratory Physician
Portsmouth Hospitals NHS Trust
Hampshire, UK

Mark Mottershaw, BSc Hons MSc
Chief Respiratory Physiologist
Queen Alexandra Hospital
Portsmouth Hospitals NHS Trust
Hampshire, UK

Elena Kourteli, FRCA

Consultant Anaesthetist
St George’s University Hospitals Foundation NHS Trust
London, UK


CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2017 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Printed on acid-free paper
International Standard Book Number-13: 978-1-4822-4968-2 (Paperback)
This book contains information obtained from authentic and highly regarded sources. Reasonable
efforts have been made to publish reliable data and information, but the author and publisher cannot
assume responsibility for the validity of all materials or the consequences of their use. The authors and
publishers have attempted to trace the copyright holders of all material reproduced in this publication
and apologize to copyright holders if permission to publish in this form has not been obtained. If any
copyright material has not been acknowledged please write and let us know so we may rectify in any
future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced,
transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or
hereafter invented, including photocopying, microfilming, and recording, or in any information
storage or retrieval system, without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access
www.copyright.com ( or contact the Copyright Clearance Center, Inc.
(CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization
that provides licenses and registration for a variety of users. For organizations that have been granted
a photocopy license by the CCC, a separate system of payment has been arranged.

Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are
used only for identification and explanation without intent to infringe.
Library of Congress Cataloging-in-Publication Data
A catalog record of this book is on file with the Library of Congress.

Visit the Taylor & Francis Web site at

and the CRC Press Web site at



Ὁ μεν βίος βραχὺς, ἡ δὲ τέχνη μακρὴ, ὁ δὲ καιρὸς ὀξὺς, ἡ δὲ πεῖρα σφαλερὴ,
ἡ δὲ κρίσις χαλεπή.
Ἱπποκράτης
Life is short, science is long; opportunity is elusive, experiment is dangerous,
judgement is difficult.
Hippocrates



Contents

Preface

xv

Acknowledgement

xv

Abbreviations
1 Expressions of normality
PART 1

TESTS OF AIRWAY FUNCTION AND MECHANICAL
PROPERTIES

2 Peak expiratory flow
Introduction
Test description and technique
Pitfalls
Physiology of test
Normal values
Peak flow variability in the diagnosis of asthma
Assessment and management of asthma
Pitfall
3 Spirometry and the flow–volume loop
Introduction
Measured indices and key definitions
Test description and technique
Physiology of tests
Restrictive and obstructive defects
Restrictive defects
Obstructive defects
Maximum expiratory flows
Normal values
Assessment of severity of obstruction
Mid-expiratory flows

xvii

1

5
7
7
7
7
8
8
8
11
12
13
13
13
13
16
16
16
18
18
20
21
22
vii


viii Contents

FVC versus VC

Patterns of abnormality
Obstructive spirometry
Restrictive spirometry
Reduction of FEV1 and FVC
Mixed obstructive/restrictive defect
Non-specific ventilatory defect
Large airways obstruction
Fixed upper airway obstruction
Variable extrathoracic obstruction
Variable intrathoracic obstruction
Clinical pearls
4 Airway responsiveness
Introduction
Test physiology
Test descriptions
Reversibility
Challenge testing
Interpretation of results
Reversibility
Challenge testing
5 Fractional concentration of expired nitric oxide
Introduction
Test description/technique
Physiology of test
Normal values and interpretation
Specific considerations
6 Gas transfer
Introduction
Measured indices/key definitions
Alveolar volume

K CO
Test description
Physiology of gas exchange
Normal values
Patterns of abnormality
Incomplete lung expansion
Discrete loss of lung units
Diffuse loss of lung units

23
23
23
25
27
27
28
29
29
29
31
31
35
35
35
36
36
37
37
37
38

41
41
41
42
43
44
45
45
45
46
46
47
48
48
49
49
51
52


Contents ix

Pulmonary emphysema
Pulmonary vascular disease
Causes of increased gas transfer
Clinical pearls
Interstitial lung disease
Obstructive disease
Acute disease
7 Static lung volumes and lung volume subdivisions

Introduction
Measured indices/key definitions
Test descriptions/techniques
Helium dilution
Nitrogen washout
Whole-body plethysmography
Comparison of methods
Physiology of lung volumes
Total lung capacity
Residual volume
Functional residual capacity
Closing capacity
Normal values
Patterns of abnormality
Relationship between VC and TLC
Obstructive lung disease
Interstitial lung disease
Miscellaneous
Specific considerations
Anaesthesia
FRC in patients receiving ventilatory support: PEEP
and CPAP
Clinical pearls
8 Airway resistance
Introduction
Physiology of airway resistance tests
Plethysmography technique
Test description/technique
Measured indices/key definitions
Normal values

Patterns of abnormality

52
53
54
54
54
55
56
57
57
57
59
59
61
61
63
64
64
64
64
65
65
66
67
67
67
68
68
68

68
70
73
73
74
75
75
76
76
76


x Contents

Oscillometry techniques
Test description/technique
Measured indices/key definitions
Normal values
Patterns of abnormality
Assessment of severity
Specific and clinical considerations
9 Respiratory muscle strength
Introduction
Test descriptions/techniques
Upright and supine vital capacity
Static lung volumes
Maximal expiratory pressure
Maximal inspiratory pressure
Sniff nasal inspiratory pressure
Sniff trans-diaphragmatic pressure

Direct electromagnetic phrenic nerve stimulation
Cough peak flow
Arterial blood gases
Radiological assessment of muscle strength
Clinical interpretation of tests of muscle strength
Forced vital capacity
Sniff nasal inspiratory pressure
MIP and MEP
The twitch PDI
Sleep, ventilatory failure, and VC
Clinical pearls
PART 2

BLOOD GAS INTERPRETATION

10 Assessment of ventilation
Introduction
Measured indices/key definitions
Physiology of ventilation in relation to CO2
Normal values
Measurement of venous blood gases
Causes of hypercapnia
Chronic obstructive pulmonary disease
Obesity hypoventilation syndrome

79
79
79
82
82

84
84
87
87
87
87
90
90
90
90
91
91
91
92
92
93
93
94
94
95
95
99
103
105
105
105
105
108
109
109

110
111


Contents xi

Exhaustion
Increased CO2 production
Causes of low PCO2
Hypoxaemia
Metabolic acidosis
Central nervous system disorders
Drugs
Anxiety
Clinical pearls
11 Assessment of haemoglobin saturation
Introduction
Measured indices
Measurement of oxygen saturation
Pulse oximetry
Waveform
Accuracy
Specific sources of error
Pros and cons of pulse oximetry
Physiology – oxygen dissociation curve
What determines the amount of oxygen carried in
blood?
Normal values
Carbon monoxide poisoning
Clinical pearls

12 Assessment of oxygenation
Introduction
Normal values
Measurement of PaO2
Measurement of arterialised capillary PO2
The oxygen cascade
Humidification of dry air
Alveolar gas
Arterial blood
A–a partial pressure PO2 difference
Tissue
Relationship between alveolar PO2 and arterial PCO2
Clinical pearls
Specific clinical considerations
Hypoxaemia

111
112
112
112
112
112
112
113
113
115
115
115
116
117

117
118
119
120
120
121
122
122
123
125
125
125
125
126
127
128
128
129
129
132
132
133
133
133


xii Contents

Apnoeic respiration
Chronic respiratory failure

13 Assessment of acid–base balance
Introduction
Measured indices/key definitions
Physiology of acid–base balance
Compensation
Classification of acid–base disorders
Respiratory disorder
Metabolic disorder
Evaluating compensation of acid–base disturbance
Respiratory compensation for metabolic disorder
Metabolic compensation for respiratory disorder
Time course of compensation
Summary: Evaluation of acid–base disorders

134
135
137
137
137
138
139
140
140
140
141
142
142
143
143

PART 3 EXERCISE TESTING

145

14 Field exercise tests
Introduction
Measurement indices
Description of tests
Six-minute walk test
Incremental shuttle walk test
Endurance shuttle walk test
Choice of field-walking test
Physiology of field exercise tests
Normal values
Six-minute walk test
Incremental shuttle walk test
Endurance shuttle walk test
Clinical pearls
15 Cardiopulmonary exercise testing
Introduction
Measured indices/key definitions
Test description/technique
Physiology of exercise testing
Normal physiological responses
Normal values

147
147
147
148

148
149
149
149
150
151
151
151
151
152
155
155
155
155
159
159
164


Contents xiii

Patterns of abnormality
Exercise tolerance
Lung disease
Heart disease – ischaemic heart disease
Heart disease – cardiomyopathy
Pulmonary vascular disease
Summary
Assessment of severity
Specific considerations

PART 4 INTERPRETATION

165
165
165
166
168
168
169
169
171
173

16 A strategy for interpretation of pulmonary function tests 175
Introduction
175
17 Characteristic pulmonary function abnormalities
183
Airway diseases
183
Asthma
183
Chronic obstructive pulmonary disease
183
Bronchiolitis
184
Bronchiectasis
184
Large airway obstruction – variable extrathoracic
184

Large airway obstruction – variable intrathoracic
184
Fixed upper airway obstruction
185
Restrictive diseases interstitial lung disease
185
Pleural disease
185
Chest wall deformity
186
Muscle weakness
186
Post-pulmonary resection surgery
186
Pulmonary vascular disease
187
Pulmonary arterial hypertension
187
Recurrent pulmonary emboli
187
Chronic pulmonary venous congestion
187
Carbon monoxide poisoning
187
References

189

Index

197



Preface

Every doctor involved in acute medicine deals with blood gas or lung function data. Although a wealth of information lies therein, much of the content
may be lost on the non-specialist. Frequently the information necessary for
interpretation of basic data is buried deep in heavy specialist texts. This book
sets out to unearth these gems and present them in a context and format useful to the frontline doctor. We accompany the clinical content with underlying physiology because we believe that for a little effort it offers worthwhile
enlightenment. However, as life in clinical medicine is busy, we have placed
the physiology in separate sections, so that those who want to get to the bottom line first can do so.
This book is not a technical manual, and details of performing laboratory
test are kept to minimum to outline the physical requirements for successful compliance. Nor is it a reference manual for the specialist. The aim is to
present information in an accessible way, suitable for those seeking a basic
grounding in spirometry or blood gases, but also sufficiently comprehensive
for readers completing specialist training in general or respiratory medicine.

ACKNOWLEDGEMENT
We wish to thank Warwick Hampden-Woodfall for essential IT backup.

xv



Abbreviations

LUNG FUNCTION PARAMETERS
Ax
ERV

FEF
FeNO
FEV1
FRC
Fres
FVC
Gaw
IC
IRV
IVC
KCO
MEP
MIP
MVV
PEF
PIF
R5
R 5−R 20
R 20
Raw
RV
sGaw
Sniff Pdi
SNIP
sRaw
TLC
TLCO

capacitance reactance area (Goldman triangle)
expiratory reserve volume

forced expiratory flow
fractional exhaled nitric oxide
forced expiratory volume within the first second
functional residual volume
resonant frequency
forced vital capacity
airway conductance
inspiratory capacity
inspiratory reserve volume
inspiratory vital capacity
transfer coefficient (measured using carbon monoxide)
maximal expiratory pressure
maximal inspiratory pressure
maximum voluntary ventilation
peak expiratory flow
peak inspiratory flow
total airway resistance
peripheral airway resistance
large airway resistance
airway resistance
residual volume
specific airway conductance
sniff transdiaphragmatic pressure
sniff inspiratory pressure
specific airway resistance
total lung capacity
transfer factor (measured using carbon monoxide)
xvii

xviii Abbreviations

VA
VA
VC
 2
VCO
VD
VE
VT
X5

alveolar volume
minute volume of alveolar ventilation
vital capacity
volume of CO2 produced by the body per minute
dead space
minute volume of ventilation
tidal volume
reactance

EXERCISE TESTING
6MWD
6MWT
AT
Borg
BR
 2
Do
ESWT

ISWT
MVV

RER
RPE
 2
VCO
VE
VE /V CO 2
VE /VO 2
VE cap
VO 2
VO 2MAX
VO 2 @ AT
VO 2 /HR
WR

6 minute walk distance
6 minute walking test
anaerobic threshold
type of dyspnoea scale
breathing reserve
rate of oxygen delivery to the tissues
endurance shuttle walk test
incremental shuttle walk test
maximum voluntary ventilation per minute, usually
extrapolated from a 15-second period of forced maximal
breathing
respiratory exchange ratio, given by VCO 2 /VCO2
rating of perceived exertion

rate of oxygen carbon dioxide elimination by the lungs
minute volume of ventilation
ratio of minute ventilation to carbon dioxide elimination by
the lungs (ventilatory equivalent for CO2)
ratio of minute ventilation to oxygen uptake by the lungs
(ventilatory equivalent for oxygen)
maximum ventilatory capacity, usually derived from predictive
equation using FEV1
rate of oxygen consumption
peak rate of oxygen consumption achieved during a maximal
exercise test
oxygen consumption measured at the anaerobic threshold
oxygen consumption per heart beat (oxygen pulse)
work rate (measured in watts, W)


Abbreviations xix

RESPIRATORY GAS PARAMETERS
A–a
ABG
D O 2
HCO3−
PACO2
PaCO2
PAo2
Pao2
PIo2
P vCO2
Sao2

SpO2
Sv O 2
 2
VCO

alveolar–arterial difference
arterial blood gas
rate of oxygen delivery to the tissues
bicarbonate
partial pressure of carbon dioxide within alveoli
partial pressure of carbon dioxide within blood
partial pressure of oxygen within alveoli
partial pressure of oxygen within blood
partial pressure of oxygen in inspired air
partial pressure of carbon dioxide within venous blood
oxyhaemoglobin saturation, measured directly by blood
gas analysis
oxyhaemoglobin saturation, measured by peripheral
pulse oximetry
mixed venous oxygen saturation, measured in blood from the
pulmonary artery
rate of production of CO2

GASES
CO
CO2
He
NO
O2
ppb

carbon monoxide
carbon dioxide
helium
nitric oxide
oxygen
parts per billion

STATISTICS
LLN
SD
SR
ULN

lower limit of normality
standard deviation
standard residual
upper limit of normality

SOCIETIES/GUIDELINES
ATS
BTS

American Thoracic Society
British Thoracic Society


xx Abbreviations

ERS

GINA
GOLD
mMRC
MRC
NICE
SIGN

European Respiratory Society
Global Initiative for Asthma
Global Initiative for Chronic Obstructive Lung Disease
Modified Medical Research Council (Dyspnoea Scale)
Medical Research Council (UK)
National Institute for Health and Care Excellence (UK)
Scottish Intercollegiate Guidelines Network

DISEASES
ALS
COPD
ILD
MND
OHS
OSA
RTA

amyotrophic lateral sclerosis
chronic obstructive pulmonary disease
interstitial lung disease
motor neurone disease
obesity hypoventilation syndrome
obstructive sleep apnoea

renal tubular acidosis

UNITS
L
min
mmol
mM
s
SI

litre
minute
millimoles
millimoles per litre
second
standard international (units)

MISCELLANEOUS
BODE
CK
CPAP
CSF
CT
ICS
PEEP
REM

BMI, Obstruction, Dyspnoea and Exercise (index)
creatinine kinase
continuous positive airway pressure

cerebrospinal fluid
computed tomography
inhaled corticosteroid
positive end expiratory pressure
rapid eye movement (sleep)


1
Expressions of normality
The percentage predicted has long been the favoured method of expressing
lung function results amongst clinicians. It has the advantages of being easy
to calculate and intuitive to understand. A test result which falls below 80% of
the predicted value is often considered to be outside the range of natural variability and therefore abnormal, for a number of pulmonary function indices.
The percentage predicted is also used to grade severity of disease by
comparing test results with a table of cut-off ranges. The number of categories and exact cut-offs are fairly arbitrary and vary between different
respiratory societies. For example, one such table for identifying abnormal
spirometry based on the FEV1% predicted is shown in Table 1.1, modified
from the American Thoracic Society (ATS)/European Respiratory Society
(ERS) taskforce guidelines on interpretative strategies for lung function
testing.1 A similar classification is in common usage for peak flow readings
in asthma (Table 2.1).
However, different lung function tests and indices have different degrees
of natural variation within the population. For example, the transfer factor
for carbon monoxide (TLCO) has a wider inter-individual variability than
many other lung function test values, and therefore a result which is 75%
predicted may be well within the normal range. Moreover, this normal range
may alter with age, so a value which is 75% of that predicted may be normal
in the elderly, but warrant further investigation in the young.
This shortcoming has led clinical physiologists to favour the concept of the
standard residual as a statistically more valid approach to identifying normal

ranges. This method involves using standard deviations (SDs) to identify the
upper and lower limits of normality (ULN and LLN respectively). Figure 1.1
shows a typical bell-shaped normal distribution curve and includes the percentage of values which lie within each SD (or Z score) and the mean. In a
normal distribution, 95% of the population will record values within two SDs
above or below the mean value.
The convention amongst physiologists is to use a value of 1.64 SDs to identify the ULN and LLN. This value is chosen because in a normal distribution
1


2 Expressions of normality

Table 1.1 Severity of airflow obstruction by FEV1
Degree of severity

FEV1% predicted

Normal

>80

Mild

70–79

Moderate

60–69

Moderately severe

50–59

Severe

35–49

Very severe

<35

Mean

–2 –1.64
2.5%
5%

–1

0

+1

Standard deviations (Z score)

+1.64 +2
2.5%
5%

Figure 1.1 Normal distribution curve showing the percentage of a normal
population who would fall 1.64 standard residuals beneath the mean. If  the

limit of normality is placed at 1.64 SDs below the mean, the healthy range
encompasses 95% of the population.

90% of the population will fall within ±1.64 SDs of the mean, with 5% having
‘supranormal’ values above this range and 5% having ‘abnormal’ results below
this range. However, there is no pathology associated with a supranormal


Expressions of normality 3

value (with few exceptions such as measurements of airway resistances – see
Chapter 8) and those fortunate individuals may be placed within the normal
range, from a medical point of view. Therefore, the limit of –1.64 SDs below
the mean identifies a 95% confidence limit, below which measurements are
abnormal. The standard residual may be used to express the distance a result
lies from the mean, and thereby grade the severity of abnormality, as shown
in Table 1.2.
Table 1.2 Grade of severity by standard residual
Standard residual
–1.64 or greater

Grade of severity
Normal

–1.65 to –2.50

Mild

–2.50 to –3.50

Moderate

<–3.50

Severe

KEY POINTS
●

●

The percentage of predicted is the most commonly used expression
of normality, which is simple to calculate and intuitively
understood. However, the cut-off for normality (e.g. <80%) is
chosen arbitrarily and may result in under- or overdiagnosis of
pathology.
The use of standard residuals is more robust and provides a
statistically valid method to identify values that fall below the limits of normal physiological variability. Usage of standard residuals
is increasing and may ultimately replace the percentage predicted.