Interactions of airway pathogens and inflammatory processes

The clinical history of chronic obstructive pulmonary disease (COPD) is punctuated by recurrent episodes of increases in dyspnea, cough, or sputum production named exacer- bations. In addition to increasing COPD-associated morbidity and mortality, exacerbations contribute to loss of lung function and impaired health status in COPD patients (1). Although it is often assumed that exacerbations are associated with increased airway inflammation, there is little information on the nature of the acute-on-chronic inflammation that characterizes these episodes. Most of the data currently available refer to soluble indirect markers of airway inflammation rather than inflammatory cell infiltration per se (2). Infections of the tracheobronchial tree, together with air pollution, are considered the most common causes of COPD exacerbations (1). Whether different patterns of airway inflammation correspond to different etiologies is largely unknown. Better understanding of these relationships and of the underlying pathophysiological mechanisms would give the opportunity to identify relevant targets (pathogens and inflammation) for the treatment and prevention of COPD exacerbations. Many exacerbations are associated with symptoms of infection of the tracheobron- chial tree, and bacteria have been considered the main infective cause of exacerbations (1). Determining the contribution of bacteria to exacerbations is difficult, as COPD patients are often colonized with bacteria even when clinically stable (3). The proportion of patients with positive bacterial cultures and a high bacterial load increases during exacerbations in most, although not in all, studies (4–6). Newer molecular techniques have recently shown that colonization is not a static condition and there is a frequent turnover of different strains of bacteria evoking specific host responses (7). Thus, it is likely that a change in the strain but not the organism may be responsible for the exacerbations. Therefore, previous studies lacking in the molecular characterization of bacterial strains may have missed evidence of a new infection. Indeed, it has been documented that the acquisition of a new strain of colonizing bacteria increases the risk of an exacerbation (8). In the last few decades, the use of highly sensitive diagnostic methods, such as polymerase chain reaction (PCR), to evaluate the association between respiratory virus infections and COPD exacerbations has shown that viruses are responsible for a much higher proportion of exacerbations than was previously realized. In a study of the East London COPD cohort, respiratory viruses were detected in 39% of exacerbations, the most common being rhinoviruses that accounted for 58% of viruses (9). A respiratory virus was detected in around 50% of patients with severe COPD exacerbation admitted to hospitals in Germany and Italy, with rhinovirus again being the most common (5,10). In patients with very severe COPD exacerbations requiring intubation and mechanical ventilation, viruses were identified in 47% of patients (11). At variance with bacterial infections, the respiratory viruses more commonly found at exacerbations were virtually absent in stable state (5,12), suggesting that they play a relevant role in the etiology of the acute episodes.