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Queen Elizabeth Hospital Birmingham, UK
Correspondence to: Robert A. Stockley, DSc, MD, Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, United Kingdom
To the Editor:
We read with interest both the editorial comment by Dr.
Watanakunakorn1
and the article it was referring to by
Sethi et al2
(December 2000). This article does indeed
represent a further move forward in trying to facilitate antibiotic
prescribing. However, the measurements of neutrophil elastase,
interleukin-8, and other inflammatory cytokines in the airway are
subject to many individual factors. In general, for instance, all of
these measurements are higher for patients who have
1-antitrypsin deficiency, even during the
stable clinical state, and they merely represent of the neutrophilic
influx associated with that condition. In addition, the presence of
bronchiectasis, often detected only by high-resolution CT scan, is also
associated with an increase in lung inflammatory markers.3
There is increasing evidence of bacterial colonization and its association with increased airway inflammation. However, most of these studies, including that by Dr. Sethi, reflect heterogeneity (ie, some subjects in whom inflammation is clearly increased and others where it is not). In his editorial, Dr. Watanakunakorn was clearly cautious about the use of inflammatory markers as a way of differentiating situations in which antibiotics may be important, and we would endorse this view.
Based on theoretical reasons, we have always argued that airway colonization that is not associated with a secondary inflammatory response of the lung host defenses is less likely to be a problem clinically than the situation where such a response occurs. In our study,4 we chose the clinical observation of sputum purulence as being a clear indicator of a neutrophilic response. During exacerbations, these patients nearly always had pure growths of a bacterial species thought to be involved in the exacerbation. More important, the number of bacteria isolated during these episodes increased compared with the number of bacteria isolated in the stable clinical state, or during exacerbations where the sputum had not become purulent. More recently, we expanded this work5 and demonstrated quite clearly that the presence of bacteria alone does not influence airway inflammation in COPD. Specifically, it is the number of bacteria that lead to an inflammatory response. Thus, interpretation of the influence of bacteria on airway inflammation in COPD is dependent on quantitative bacterial culture, as well as on the microorganism involved. For instance, Pseudomonas aeruginosa is associated with more inflammation than Haemophilus influenzae when secretions from patients are matched for the bacterial load.5 On the other hand, Moraxella catarrhalis and H influenzae are associated with a similar degree of inflammation, providing the bacterial load is also matched.
In summary, the nature of acute exacerbation has been poorly defined in the past. The presence of bacterial colonization per se does not necessarily lead to airway inflammation in patients, and the release of enzymes like elastase is not, by itself, a requirement for antibiotic therapy. Such patients may have the same colonizing organism, the same bacterial load, and the same lack of airway inflammation during the stable clinical state. On the other hand, an increase in the bacterial load of > 106 cfu/mL is associated with increasing airway neutrophilia and inflammation.5 This is reasonably well identified by carefully assessing the color of the sputum (ie, its myeloperoxidase content), and the increased bacterial load resolves with the exacerbation itself.4
We hope these comments will assist research workers as they continue to refine their techniques in addressing these important issues.
References
SUNY at Buffalo Buffalo, NY
Correspondence to: Sanjay Sethi, MD, VA WNY Healthcare System 151, 3495 Bailey Ave, Buffalo, NY 14215; e-mail: sethi.sanjay{at}buffalo.va.gov
To the Editor:
We appreciate Dr. Stockley’s comments regarding our
article.1
The intention of our study was not to establish
the usefulness of inflammatory cytokines measurement as a diagnostic
test to determine the use of antibiotics. However, we did find that
elastase activity in sputum is reasonably discriminatory between
bacterial and nonbacterial exacerbations; therefore, we suggested that
this elastase activity be explored further as a diagnostic test.
Obviously, further studies are required. We screened the first 50
patients enrolled in our study for 1-antitrypsin and
found none to be deficient. In addition, none of our patients had
clinical and chest radiographic features of idiopathic bronchiectasis.
We did not do high-resolution CT scans in these patients. However,
finding an area of bronchiectasis with a high-resolution CT in patients
with advanced COPD could simply be a part of the natural history of
disease.
In our study, the bacterial pathogen concentration in sputum did correlate with the level of inflammatory markers, which agrees with the data cited by Dr. Stockley.1 2 However, to conclude from this that bacterial load in the airways is the only determinant of the inflammatory state of the airways and of the clinical status of the patient ignores other potentially important factors. Virulence determinants may differ among the strains of the infecting bacterial pathogen. Infection by a pathogen in these patients may be a dynamic process where acquisition of a new strain, to which the host lacks immunity, may determine the inflammatory and clinical state. Different bacterial species and different strains between the same species may induce qualitatively and quantitatively different inflammatory responses.3 Dr. Stockley states that a bacterial load > 106 cfu/mL is associated with increasing airway inflammation and sputum purulence. However, bacterial load of this level has been reported, by several investigators including Dr. Stockley himself,4 5 6 in patients with stable COPD with mucoid sputum.
We are encouraged by the increasing attention being paid to the role of bacterial infection in COPD, and we hope that such discussion would augment this interest so that we can have more definitive answers.
References
1-antitrypsin deficiency (PiZ). Am J Respir Crit Care Med 160,1968-1975
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