Diagnostic criteria for invasive pulmonary aspergillosis in chronic obstructive pulmonary disease patients

Over 400 million people have chronic obstructive pulmonary disease (COPD), with exacerbations representing a major health burden. Although the overall incidence of invasive pulmonary aspergillosis (IPA) in patients with COPD with hospitalised exacerbation is only 1 to 4%, certain factors substantially increase this frequency. Risk factors compromising defences against Aspergillus spp in COPD patients include systemic or high-dose inhaled corticosteroids, comorbidities including bronchiectasis, diabetes, and cardiovascular disease, and prolonged courses of antibiotics. An international group of experts met to develop criteria for diagnosing IPA based on existing literature and consensus in non-ventilated COPD patients. The preliminary diagnostic recommendations were further evaluated by additional experts using the Delphi methodology. A hospitalized exacerbation of COPD with two or more of the above clinical risk factors should prompt 1) a CT scan of the chest, 2) sending a respiratory sample (sputum, induced sputum or bronchoscopy sample) for direct microscopy for fungi, high volume fungal culture and preferably Aspergillus PCR, and if a bronchoscopy sample is obtained then also Aspergillus antigen (galactomannan), 3) a serum sample for galactomannan and Aspergillus IgG. The combination of a high-risk COPD patient, with compatible imaging abnormalities and any two positive tests (two samples or different tests on the same respiratory sample) for Aspergillus is sufficient to establish the diagnosis of IPA with enough confidence to initiate antifungal therapy and/or enroll the patient in a clinical or epidemiological study of IPA in COPD. Additional studies are required to augment performance data for most assays in COPD and validate the proposed diagnostic criteria.