REBUTTAL FROM DR. MACNEE

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Dr. Wedzicha concludes that the evidence is now compelling that "airway infection, especially with bacteria, is associated with . . . susceptibility to decline in lung function." However, only circumstantial or in some instances no evidence is provided to support this view.

It does not follow that the heterogeneity in the decline in FEV₁ in smokers suggests a role for infection in the natural history of COPD; rather, it might suggest that genetic factors have a role as at least there are some supportive studies in this area.

The presence of bacterial colonization in a proportion of patients with COPD is not disputed, and there is increasing evidence that this is associated with increased airway inflammation. However, there is no longitudinal study that directly links bacterial colonization, or increased airway inflammation, to the decline in lung function.

The role of bacteria in exacerbations of COPD is still controversial and it does not follow, as suggested by Dr. Wedzicha, that the presence of higher levels of airspace inflammation, in limited studies, in bacterial exacerbations, leads to decline in lung function.

Further controversies are the effect of exacerbations on lung function decline and the evidence for lack of recovery in lung function, which is not universal in all studies. The associations of Haemophilus influenzae, increased airway inflammation, health status, and frequent exacerbations are not relevant to the argument for accelerated decline in lung function.

Furthermore, the association between latent adenoviral infection and COPD is irrelevant because it does not relate to the decline in lung function. In any case this hypothesis, although interesting, remains a hypothesis until it has been replicated in other studies, as does the contention that viral colonization has any relevance to COPD.

In short, there is no direct evidence of a role for infection in accelerating the decline in lung function in COPD. My only point of agreement with Dr. Wedzicha is that definitive studies have not been done and require to be done to prove or refute this hypothesis, but the evidence at present provides no support for this contention.