Chronic Bronchopulmonary aspergillosis patients with underlying chronic obstructive pulmonary disease: providing grounds for biomarkers search through clinical phenotyping

Abstract

Objective: In this work, we aim to clinically characterize patients with chronic obstructive lung disease (COPD) and chronic bronchopulmonary aspergillosis (CBPA) in order to better understand how these conditions interact, and open way to further studies aiming to improve diagnostic and therapeutic tools of CBPA in COPD patients. Methods/Design: This study was carried out using a database of patients from pulmonology department of Hospital São João, who have at least one isolation of Aspergillus spp in the last ten years. We selected those with obstructive lung disease, defined as FEV1/FVC <0.7, and chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA), or Aspergillus bronchitis (AB), studying their demographic characteristics, comorbidities, lung function, smoking status, immunosuppression, mortality and other clinical outcomes. We did the same for patients who had Aspergillus spp. colonization. Results: From 260 patients who had COPD and Aspergillus spp in the sputum(A. fumigatus (131), A. niger (111), A. terreus (3), A. flavus (11), A.versicolor (3), A.nidulans (1), A.glacus (1) ), 19 were diagnosed with CPA, 8 with ABPA, 12 with AB. At the same time, 221 were considered to be colonized based on clinical judgment. The most frequent phenotype of obstructive disease was bronchiectasis (51.5%), followed by"pure" COPD (21.5%) and post-TB sequelae (10.0%). Among the patients with CBPA, bronchiectasis was also the most frequent phenotype (53.8%), median (IQR) age was 66 (50-74) years, and most were female (59%). Obstruction severity GOLD 2 and 3 were predominant. There were no statistically significant differences when comparing the underlying pathology and other clinical characteristics of the colonized and CBPA groups. The mortality was higher in the CBPA group (vs. the colonization group; p=0.004), with a mean overall survival of 9.6 years (total population). Median survival was not reached. Conclusions: This sample population shows a high level of bronchiectasis patients in the CPBA group and in the simple colonization group, which confirms the importance of this phenotype. There were no clear distinctive characteristics in the CBPA group, and that makes us question if the criteria for colonization are clear enough, and if the impact of Aspergillus spp is not being underestimated. Aspergillosis should be taken into account when COPD patients have clinical deterioration, especially if they have bronchiectasis