Legionella spp. in acute exacerbations of chronic obstructive pulmonary disease: what is the evidence?

Acute exacerbations are a frequent complication during the clinical course of chronic obstructive pulmonary disease (COPD). A recent monograph dealing with COPD exacerbations demonstrated that virtually all issues related to the management of acute exacerbations remain unsettled and controversial, including the definition, aetiology, microbial patterns, and antimicrobial treatment of this condition [1]. This is of particular concern in view of the high burden of this complication on public health resources. With regards to microbial patterns and their possible involvement in the aetiology of acute exacerbations, it is a common view that Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis are the leading pathogens. Viruses have also been shown to cause acute exacerbations, frequently working as copathogens together with bacterial pathogens [2–4]. Only recently, important extensions of this concept have been provided. Firstly, evidence has grown that microbial patterns may move towards an increasing incidence of Gram-negative enterobacteriaceae and Pseudomonas aeruginosa in more advanced stages of COPD [5]. Similar observations were made in severe exacerbations requiring ventilatory support [6, 7]. Secondly, several studies found evidence of Chlamydia pneumoniae playing a role as a pathogen or copathogen in acute exacerbations [7–10]. Finally, new challenges emerge from drug-resistant micro-organisms [11]. Overall, bacterial pathogens were found to be present in approximately 50%, and atypical bacterial and viral pathogens in an additional 25% of cases. The presumptive aetiology in the remaining 25% of cases remained unclear [12]. In this issue of the European Respiratory Journal, LIEBERMAN et al. [13] present data on a large population, hospitalized with acute exacerbations of COPD, which provides evidence for the first time for Legionella spp. infection as a potential underlying pathogen in as many as 16.7% of cases [13]. These pathogens were detected serologically by an indirect immunofluorescence method using an in-house kit and applying strict criteria of seroconversion in paired samples. What is the meaning of these findings: should Legionella spp. be included in the list of potential pathogens of acute exacerbations of COPD and should antimicrobial treatment regimens, targeted against these pathogens be designed? Up to now, Legionella spp. have not been reported to form part of the microbial patterns of acute exacerbations. This may simply reflect the principal methodological problems of diagnosing such infections. Legionella spp. can only rarely be cultured from sputum, and bronchoalveolar lavage fluid is usually not suitable in COPD patients with acute exacerbations. In fact, performing bronchoalveolar may prove harmful in these patients. Antigen detection, although highly specific and sensitive, exclusively covers infections by Legionella pneumophila serogroup 1. A paired serum for serology is only rarely obtained, mainly because hospitalization is not usually required forw2 weeks. Moreover, usual serology only covers Legionella pneumophila serogroup 1. Using this approach, LIEBERMANN et al. [13] would only have detected Legionella infections in 4% of cases. Thus, the study confirmed that a vigorous search usually results in unexpected findings. In fact, they provided much indirect evidence that these findings are truely valid. Legionellosis is known to cause not only pneumonia but also an acute illness, that of Pontiac fever. Fever and chills associated with myalgia, malaise, and headache are the leading symptoms. The symptoms develop progressively. A dry cough may occur as well as minor respiratory symptoms such as sore throat, coryza, and sore eyes. In addition, neurological symptoms have been reported [14]. These clinical features of Pontiac fever are compatible with those described in the report here. No patient had an abrupt onset of exacerbation, and all systemic symptoms were more prevalent in patients with evidence of Legionella infections, however due to the limited number of patients studied the difference was only significant for myalgia/arthralgia. Thus, there is considerable evidence that the group seroconverted for Legionella spp. truely forms a clinically distinguishable group of its own. Conversely, serology as an indirect diagnostic tool does not provide irrefutable evidence for the involvement of a microbial pathogen. This is particularly true for an in-house kit which is not externally validated. Nevertheless, there are several hints which point at the validity of the serological kits as explained by LIEBERMAN et al. [13] in the discussion. One of the most important is the low rate of false-positive results Dept of Internal Medicine, University of Bonn, Bonn, Germany.