Download An Atlas of Induced Sputum - An Aid for Research, Diag. - R. Djukanovic, et. al., (Parthenon, 2003) WW PDF

TitleAn Atlas of Induced Sputum - An Aid for Research, Diag. - R. Djukanovic, et. al., (Parthenon, 2003) WW
TagsMedical
LanguageEnglish
File Size3.5 MB
Total Pages204
Table of Contents
                            Book Cover
Half-Title
Title
Copyright
Contents
List of principal contributors
Introduction
Chapter 1 Sputum induction: methods and safety
Chapter 2 Analysis of sputum cells: cytology, immunocytochemistry and in situ hybridization
Chapter 3 Analysis of soluble mediators in the sputum fluid phase
Chapter 4 Induced sputum studies in asthma
Chapter 5 Induced sputum studies in chronic obstructive pulmonary disease
Chapter 6 Induced sputum studies in children
Chapter 7 Induced sputum studies in cystic fibrosis
Chapter 8 The use of induced sputum in clinical trials
Chapter 9 The use of induced sputum in clinical practice
Chapter 10 Induced sputum in interstitial and occupational lung diseases
Subject index
                        
Document Text Contents
Page 102

Figure 4.29 Receiver operator characteristic (ROC) curves showing the
sensitivity and specificity over a range of cut-points for dose-
response ratio mannitol (DRR mannitol), a measure of
responsiveness to mannitol, defined as the percentage fall in FEV1 at
the last dose of mannitol, divided by the total dose administered and
percent sputum eosinophils for predicting failure to reduce inhaled
corticosteroid treatment. The solid line indicates no discrimination.
Plots that lie farthest to the ‘northwest’ indicate more accurate values.
Reproduced with permission from Leuppi JD, Salome CM,
Woolcock AJ, et al. Predictive markers of asthma exacerbation
during stepwise dose reduction of inhaled corticosteroids. Am J
Respir Crit Care Med 2001; 163:406–12

An atlas of induced sputum 94

Page 103

CHAPTER 5
Induced sputum studies in chronic obstructive

pulmonary disease
Piero Maestrelli and Cristina E. Mapp

Induced sputum has been widely used to study the inflammatory mechanisms of chronic
obstructive pulmonary disease (COPD). There remains a question as to the extent to
which sampling the airways reflects changes in small airways and the parenchyma, sites
where the disease processes are most active in COPD. These issues notwithstanding, the
application of induced sputum has been very informative, helping to define some unique
features of COPD.

It has long been appreciated that smoking is the most important risk factor for COPD;
however, it is equally recognized that only a proportion of smokers develop a clinically
overt disease. The mechanisms of the increased susceptibility in these smokers remain
unknown. A longitudinal study of smokers has applied sputum induction to examine
whether the airway inflammatory process is different in smokers susceptible to COPD
development compared with smokers who are ‘resistant’, i.e. do not develop clinically
relevant disease. The percentages of sputum neutrophils were greater in smokers with
COPD than in asymptomatic smokers; these correlated with the annual decline in forced
expiratory volume (FEV1) observed over the 15-year follow-up (Figure 5.1). These
results strongly suggest that neutrophils are important in the pathogenesis of COPD.

It is likely that neutrophils accumulate in the airway lumen of smoking individuals as a
consequence of recruitment from the circulation, a process that involves cell adherence
and chemotactic factors which together recruit inflammatory cells into the lungs.
Cigarette smoke stimulates alveolar macrophages and possibly epithelial cells to release
inflammatory mediators. Examples of such mediators are interleukin-8 (IL-8) and tumor
necrosis factor-alpha (TNF- ), whose concentrations are increased in the sputum of
asymptomatic smokers and COPD patients (Figures 5.2 and 5.3). These cytokines may;
in turn, induce an influx of neutrophils into the lung. TNF- promotes expression of
adhesion molecules, whereas IL-8 is a potent neutrophil chemoattractant and activator of
these cells. Increased expression of adhesion molecule CDllb/CD18, the intracellular
adhesion molecule-1 (ICAM-1) ligand, has been observed in COPD, and this expression
is related to the degree of airway obstruction (Figure 5.4).

An imbalance between cytokines with different properties has been suggested as
playing a role in cigarette smoke-induced lung damage. While the pro-inflammatory
cytokines IL-8 and TNF- may be increased in COPD, theanti-inflammatory cytokine IL-
10 has been shown to be reduced in sputum of healthy smokers and, to a greater extent, in
smokers with COPD (Figure 5.5). These data suggest that there is not a clear qualitative
difference in the inflammatory process detected in the airway lumen between COPD and

Page 203

advantages 23
ECP levels 53
soluble mediators, effect on 42, 48–51, 50, 53, 55
temperature effects 51, 59
unacceptable 40

sputum samples 8
abnormal findings 27–33
cell analysis see cell analysis
composition 41
cystic fibrosis 137–8
evaluation 25
fluid phase analysis 41–65
normal findings 26
processing see sputum processing
quality control 25
squamous epithelial cell contamination 136–7
unacceptable 40
see also cytospin preparations

squamous epithelial cell contamination 136–7
standard operating procedure (SOP) protocols 24
steroid treatment

asthma 82, 163
clinical trials 163, 142, 145
eosinophil counts 87–95
methacholine hyperresponsiveness 95
symptom scores 95
COPD 100, 107, 109, 166
clinical trials 166, 149, 173
eosinophilic bronchitis 171

Streptococcus pneumoniae, secretory IgA 68–71, 73
surfactant protein A 18


T
T-helper cells, asthma 68
theophylline, COPD effects 105, 109, 111
thunderstorm asthma 121
T-lymphocytes, asthma 68
total cell count (TCC) 23

asthma, acute exacerbations 79
cystic fibrosis 129, 135, 137
induced sputum vs. bronchoalveolar lavage 135
manual 25

total elastase activity, in COPD 149
tryptase

asthma 52
sample size estimates 153

tumour necrosis factor-alpha (TNF-α) 98, 100
asthma 100

Subject index 195

Page 204

COPD 98, 100, 114
acute exacerbations 109, 113
reproducibility of assay 65
in situ hybridization 39
smokers 98, 102


U
ultrasonic nebulizers 9
uveitis 179, 180

differential diagnosis 179


V
viral infections, asthma 118–9, 121, 122


W
Wright's stain 20

immunocytochemistry vs. 34–5, 36


Z
zymography, asthma 70, 78

Subject index 196

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