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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
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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 xvii

1 Expressions of normality 1

PART 1 TESTS OF AIRWAY FUNCTION AND MECHANICAL

PROPERTIES 5

2 Peak expiratory flow 7

Introduction 7
Test description and technique 7
Pitfalls 7
Physiology of test 8
Normal values 8
Peak flow variability in the diagnosis of asthma 8
Assessment and management of asthma 11
Pitfall 12
3 Spirometry and the flow–volume loop 13
Introduction 13
Measured indices and key definitions 13
Test description and technique 13
Physiology of tests 16
Restrictive and obstructive defects 16
Restrictive defects 16
Obstructive defects 18
Maximum expiratory flows 18
Normal values 20
Assessment of severity of obstruction 21
Mid-expiratory flows 22

vii
viii Contents

FVC versus VC 23
Patterns of abnormality 23
Obstructive spirometry 23
Restrictive spirometry 25
Reduction of FEV1 and FVC 27
Mixed obstructive/restrictive defect 27
Non-specific ventilatory defect 28
Large airways obstruction 29
Fixed upper airway obstruction 29
Variable extrathoracic obstruction 29
Variable intrathoracic obstruction 31
Clinical pearls 31
4 Airway responsiveness 35
Introduction 35
Test physiology 35
Test descriptions 36
Reversibility 36
Challenge testing 37
Interpretation of results 37
Reversibility 37
Challenge testing 38
5 Fractional concentration of expired nitric oxide 41
Introduction 41
Test description/technique 41
Physiology of test 42
Normal values and interpretation 43
Specific considerations 44
6 Gas transfer 45
Introduction 45
Measured indices/key definitions 45
Alveolar volume 46
K CO 46
Test description 47
Physiology of gas exchange 48
Normal values 48
Patterns of abnormality 49
Incomplete lung expansion 49
Discrete loss of lung units 51
Diffuse loss of lung units 52
 Contents ix

Pulmonary emphysema 52
Pulmonary vascular disease 53
Causes of increased gas transfer 54
Clinical pearls 54
Interstitial lung disease 54
Obstructive disease 55
Acute disease 56
7 Static lung volumes and lung volume subdivisions 57
Introduction 57
Measured indices/key definitions 57
Test descriptions/techniques 59
Helium dilution 59
Nitrogen washout 61
Whole-body plethysmography 61
Comparison of methods 63
Physiology of lung volumes 64
Total lung capacity 64
Residual volume 64
Functional residual capacity 64
Closing capacity 65
Normal values 65
Patterns of abnormality 66
Relationship between VC and TLC 67
Obstructive lung disease 67
Interstitial lung disease 67
Miscellaneous 68
Specific considerations 68
Anaesthesia 68
FRC in patients receiving ventilatory support: PEEP
and CPAP 68
Clinical pearls 70
8 Airway resistance 73
Introduction 73
Physiology of airway resistance tests 74
Plethysmography technique 75
Test description/technique 75
Measured indices/key definitions 76
Normal values 76
Patterns of abnormality 76
x Contents

Oscillometry techniques 79
Test description/technique 79
Measured indices/key definitions 79
Normal values 82
Patterns of abnormality 82
Assessment of severity 84
Specific and clinical considerations 84
9 Respiratory muscle strength 87
Introduction 87
Test descriptions/techniques 87
Upright and supine vital capacity 87
Static lung volumes 90
Maximal expiratory pressure 90
Maximal inspiratory pressure 90
Sniff nasal inspiratory pressure 90
Sniff trans-diaphragmatic pressure 91
Direct electromagnetic phrenic nerve stimulation 91
Cough peak flow 91
Arterial blood gases 92
Radiological assessment of muscle strength 92
Clinical interpretation of tests of muscle strength 93
Forced vital capacity 93
Sniff nasal inspiratory pressure 94
MIP and MEP 94
The twitch PDI 95
Sleep, ventilatory failure, and VC 95
Clinical pearls 99

PART 2 BLOOD GAS INTERPRETATION 103

10 Assessment of ventilation 105

Introduction 105
Measured indices/key definitions 105
Physiology of ventilation in relation to CO2 105
Normal values 108
Measurement of venous blood gases 109
Causes of hypercapnia 109
Chronic obstructive pulmonary disease 110
Obesity hypoventilation syndrome 111
 Contents xi

Exhaustion 111
Increased CO2 production 112
Causes of low PCO2 112
Hypoxaemia 112
Metabolic acidosis 112
Central nervous system disorders 112
Drugs 112
Anxiety 113
Clinical pearls 113
11 Assessment of haemoglobin saturation 115
Introduction 115
Measured indices 115
Measurement of oxygen saturation 116
Pulse oximetry 117
Waveform 117
Accuracy 118
Specific sources of error 119
Pros and cons of pulse oximetry 120
Physiology – oxygen dissociation curve 120
What determines the amount of oxygen carried in
blood? 121
Normal values 122
Carbon monoxide poisoning 122
Clinical pearls 123
12 Assessment of oxygenation 125
Introduction 125
Normal values 125
Measurement of PaO2 125
Measurement of arterialised capillary PO2 126
The oxygen cascade 127
Humidification of dry air 128
Alveolar gas 128
Arterial blood 129
A–a partial pressure PO2 difference 129
Tissue 132
Relationship between alveolar PO2 and arterial PCO2 132
Clinical pearls 133
Specific clinical considerations 133
Hypoxaemia 133
xii Contents

Apnoeic respiration 134

Chronic respiratory failure 135
13 Assessment of acid–base balance 137
Introduction 137
Measured indices/key definitions 137
Physiology of acid–base balance 138
Compensation 139
Classification of acid–base disorders 140
Respiratory disorder 140
Metabolic disorder 140
Evaluating compensation of acid–base disturbance 141
Respiratory compensation for metabolic disorder 142
Metabolic compensation for respiratory disorder 142
Time course of compensation 143
Summary: Evaluation of acid–base disorders 143

PART 3 EXERCISE TESTING 145

14 Field exercise tests 147

Introduction 147
Measurement indices 147
Description of tests 148
Six-minute walk test 148
Incremental shuttle walk test 149
Endurance shuttle walk test 149
Choice of field-walking test 149
Physiology of field exercise tests 150
Normal values 151
Six-minute walk test 151
Incremental shuttle walk test 151
Endurance shuttle walk test 151
Clinical pearls 152
15 Cardiopulmonary exercise testing 155
Introduction 155
Measured indices/key definitions 155
Test description/technique 155
Physiology of exercise testing 159
Normal physiological responses 159
Normal values 164
 Contents xiii

Patterns of abnormality 165

Exercise tolerance 165
Lung disease 165
Heart disease – ischaemic heart disease 166
Heart disease – cardiomyopathy 168
Pulmonary vascular disease 168
Summary 169
Assessment of severity 169
Specific considerations 171

PART 4 INTERPRETATION 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 func-
tion 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 use-
ful to the frontline doctor. We accompany the clinical content with underly-
ing 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 bot-
tom 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 success-
ful 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 capacitance reactance area (Goldman triangle)
ERV expiratory reserve volume
FEF forced expiratory flow
FeNO fractional exhaled nitric oxide
FEV1 forced expiratory volume within the first second
FRC functional residual volume
Fres resonant frequency
FVC forced vital capacity
Gaw airway conductance
IC inspiratory capacity
IRV inspiratory reserve volume
IVC inspiratory vital capacity
KCO transfer coefficient (measured using carbon monoxide)
MEP maximal expiratory pressure
MIP maximal inspiratory pressure
MVV maximum voluntary ventilation
PEF peak expiratory flow
PIF peak inspiratory flow
R5 total airway resistance
R 5−R 20 peripheral airway resistance
R 20 large airway resistance
Raw airway resistance
RV residual volume
sGaw specific airway conductance
Sniff Pdi sniff transdiaphragmatic pressure
SNIP sniff inspiratory pressure
sRaw specific airway resistance
TLC total lung capacity
TLCO transfer factor (measured using carbon monoxide)

xvii
xviii Abbreviations

VA alveolar volume
VA minute volume of alveolar ventilation
VC vital capacity
 2
VCO volume of CO2 produced by the body per minute
VD dead space
VE minute volume of ventilation
VT tidal volume
X5 reactance

EXERCISE TESTING
6MWD 6 minute walk distance
6MWT 6 minute walking test
AT anaerobic threshold
Borg type of dyspnoea scale
BR breathing reserve
 2
Do rate of oxygen delivery to the tissues
ESWT endurance shuttle walk test
ISWT incremental shuttle walk test
MVV maximum voluntary ventilation per minute, usually
extrapolated from a 15-second period of forced maximal
breathing
RER respiratory exchange ratio, given by VCO 2 /VCO2
RPE rating of perceived exertion
 2
VCO rate of oxygen carbon dioxide elimination by the lungs
VE minute volume of ventilation
VE /V CO 2 ratio of minute ventilation to carbon dioxide elimination by
the lungs (ventilatory equivalent for CO2)
VE /VO 2 ratio of minute ventilation to oxygen uptake by the lungs
(ventilatory equivalent for oxygen)
VE cap maximum ventilatory capacity, usually derived from predictive
equation using FEV1
VO 2 rate of oxygen consumption
VO 2MAX peak rate of oxygen consumption achieved during a maximal
exercise test
VO 2 @ AT oxygen consumption measured at the anaerobic threshold
VO 2 /HR oxygen consumption per heart beat (oxygen pulse)
WR work rate (measured in watts, W)
 Abbreviations xix

RESPIRATORY GAS PARAMETERS

A–a alveolar–arterial difference
ABG arterial blood gas
D O 2 rate of oxygen delivery to the tissues
HCO3− bicarbonate
PACO2 partial pressure of carbon dioxide within alveoli
PaCO2 partial pressure of carbon dioxide within blood
PAo2 partial pressure of oxygen within alveoli
Pao2 partial pressure of oxygen within blood
PIo2 partial pressure of oxygen in inspired air
P vCO2 partial pressure of carbon dioxide within venous blood
Sao2 oxyhaemoglobin saturation, measured directly by blood
gas analysis
SpO2 oxyhaemoglobin saturation, measured by peripheral
pulse oximetry
Sv O 2 mixed venous oxygen saturation, measured in blood from the
pulmonary artery
 2
VCO rate of production of CO2

GASES
CO carbon monoxide
CO2 carbon dioxide
He helium
NO nitric oxide
O2 oxygen
ppb parts per billion

STATISTICS
LLN lower limit of normality
SD standard deviation
SR standard residual
ULN upper limit of normality

SOCIETIES/GUIDELINES
ATS American Thoracic Society
BTS British Thoracic Society
xx Abbreviations

ERS European Respiratory Society

GINA Global Initiative for Asthma
GOLD Global Initiative for Chronic Obstructive Lung Disease
mMRC Modified Medical Research Council (Dyspnoea Scale)
MRC Medical Research Council (UK)
NICE National Institute for Health and Care Excellence (UK)
SIGN Scottish Intercollegiate Guidelines Network

DISEASES
ALS amyotrophic lateral sclerosis
COPD chronic obstructive pulmonary disease
ILD interstitial lung disease
MND motor neurone disease
OHS obesity hypoventilation syndrome
OSA obstructive sleep apnoea
RTA renal tubular acidosis

UNITS
L litre
min minute
mmol millimoles
mM millimoles per litre
s second
SI standard international (units)

MISCELLANEOUS
BODE BMI, Obstruction, Dyspnoea and Exercise (index)
CK creatinine kinase
CPAP continuous positive airway pressure
CSF cerebrospinal fluid
CT computed tomography
ICS inhaled corticosteroid
PEEP positive end expiratory pressure
REM 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 vari-
ability 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 cat-
egories 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 per-
centage 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 iden-
tify 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 –1 0 +1 +1.64 +2
2.5% Standard deviations (Z score) 2.5%
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 Grade of severity

–1.64 or greater 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 lim-
its of normal physiological variability. Usage of standard residuals
is increasing and may ultimately replace the percentage predicted.
 PART
1

TESTS OF AIRWAY
FUNCTION AND
MECHANICAL
PROPERTIES

2 Peak expiratory flow 07

3 Spirometry and the flow–volume loop 13
4 Airway responsiveness 35
5 Fractional concentration of exhaled nitric oxide 41
6 Gas transfer 45
7 Static lung volumes and lung volume subdivisions 57
8 Airway resistance 73
9 Respiratory muscle strength 87
 2
Peak expiratory flow

INTRODUCTION

Measurement of the peak expiratory flow (PEF) is one of the most convenient,
economical, and commonly performed tests in the management of asthma.
The test requires the simplest of measurement equipment and is straightfor-
ward to teach and perform.

TEST DESCRIPTION AND TECHNIQUE

The PEF is an easy test for most individuals to master but is dependent upon
maximal effort, and so requires cooperation, coordination, and comprehen-
sion to produce repeatable and reliable results.
The test involves taking a forceful, full inspiration, immediately followed
by short, maximal, explosive expiratory effort into the PEF meter. Expiration
does not need to continue past the initial ‘blast’, as flow will quickly decline
beyond this point.
The value recorded is usually the best of three efforts, each of which should
be made with acceptable technique.

PITFALLS
● An isolated peak flow reading has limited value in diagnosing the cause
of respiratory insufficiency, though it is helpful for monitoring known
cases of asthma.
● The PEF can be ‘cheated’ by spitting into the meter like a blowpipe or
pea-shooter. With practice, it is easy to blow the meter to the end of its
scale with moderate effort using this technique.

7
8 Peak expiratory flow

PHYSIOLOGY OF TEST

PEF is the highest velocity of airflow that can be transiently achieved during
a maximal expiration from total lung capacity. Because flow is a function of
resistance, and the majority of resistance is encountered in the upper airways,
the peak flow is an excellent indicator of large airway function.
In addition to airway resistance and effort, the PEF is also a function
of lung volume and recoil, both of which increase as the lung is inflated.
Therefore, measurements should be made after a full inspiration.

NORMAL VALUES

Normal values for PEF are commonly read from a nomogram, similar to that
shown in Figure 2.1.2 Note that values at all ages are directly related to height,
but that males have higher values than females of the same height and age.
These nomograms are constructed from regression equations derived
from large population studies. The most commonly used regression equa-
tions in Europe are those calculated from the European Community of Coal
and Steelworkers (ECCS) study.3 The equations for calculation of predicted
normal values for PEF for males and females are as follows:
Males: PEF (L·s−1) = (6.14 × height) – (0.043 × age) + 0.15
Females: PEF (L·s−1) = (5.50 × height) – (0.030 × age) – 1.11

PEAK FLOW VARIABILITY IN THE

DIAGNOSIS OF ASTHMA
The key to assessment of asthma is a careful history, which in many cases will
allow a reasonably certain clinical diagnosis. Nonetheless, as treatment may
be required over many years, it is important even in relatively clear cases to
try to obtain objective support for the diagnosis where possible.4
Confirmation of a diagnosis of asthma hinges upon demonstration of air-
flow obstruction, varying over short periods of time.
A period of monitoring may be helpful by identifying diurnal variation,
which is a hallmark of asthma, to add weight to a diagnosis in uncertain
cases. During a period of monitoring, peak flow should be measured at
least twice per day, morning and night, and recorded on a peak flow chart
similar to that shown in Figure 2.2.
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