Influence of the Lung Microbiota Dysbiosis in Chronic Obstructive Pulmonary Disease Exacerbations: The Controversial Use of Corticosteroid and Antibiotic Treatments and the Role of Eosinophils as a Disease Marker

Abstract

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease associated with loss of lung function, poorer quality of life, co-morbidities, significant mortality, and higher health care costs. Frequent acute exacerbations of COPD are sudden worsening of symptoms, the nature of which is associated with bacterial or viral infections. However, one-third of exacerbations remain of undetermined origin. Although it is largely discussed and controversial, current guidelines recommend treatment of exacerbations with bronchodilators, antibiotics, and systemic corticosteroids; this is despite being associated with limited benefits in term of reducing mortality, side effects and without paying attention to the heterogeneity of these exacerbations. Increasing evidence suggests that the lung microbiota plays an important role in COPD and numerous studies have reported differences in the microbiota between healthy and disease states, as well as between exacerbations and stable COPD, leading to the hypothesis that frequent acute exacerbation is more likely to experience significant changes in lung microbiota composition. These findings will need further examination to explain the causes of lung dysbiosis, namely microbial composition, the host response, including the recruitment of eosinophils, lifestyle, diet, cigarette smoking and the use of antibiotics and corticosteroids. It is now important to assess: 1) Whether alterations in the lung microbiota contribute to disease pathogenesis, especially in exacerbations of unknown origin; 2) The role of eosinophils; and 3) Whether the microbiota of the lung can be manipulated therapeutically to improve COPD exacerbation event and disease progression. In summary, we hypothesize that the alterations of the lung microbiota may explain the undetermined origins of exacerbations and that there is an urgent need to facilitate the design of intervention studies that aim at conserving the lung microbial flora.

Keywords: Antibiotics; Chronic obstructive pulmonary disease; Corticosteroids; Eosinophils; Lung microbiota dysbiosis; Probiotics.