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.

Microbial burden and viral exacerbations in a longitudinal multicenter COPD cohort

“…This observational study included a variety of standard-ofcare medications, doses and timings precluding precise treatment effect modeling on the microbiota. Clinical trials exploring current and novel treatment modalities will lead to better patient management and antibiotics stewardship as reviewed elsewhere [55].…”

May nutrients and dietary supplements influence the gut-lung microbiota axis in chronic obstructive pulmonary disease and exacerbations?

“…In particular, Hemo philus influenzae increased [3] whereas the relative abundance of Streptococcus pneumonia species decreased. Other reports have determined colonization by Pseudomonas aeruginosa during exacer bations [33,59,60]. Also, a significant increase of Moraxella catarrhalis was seen between exacerbation versus non-exacerbation samples [58].…”

“…Personalized treatments based on risk stratification by the dominant organism in the microbiota may be beneficial [63]. As we have already described [33], differences in the microbiota composition between healthy and exacerbation are illustrated in Figure 1.…”

“…A very recent study [61] provided further evidence that some microbial species, potentially those dominated by Moraxella, may be associated with an increased risk of future lung disease as well as an abundance of the Proteobacteria class in general, which seems to be correlated also with the presence of disorders such as ulcerative colitis and Chron's disease [62]. Notably, there was a sig-nificant positive correlation between Moraxella catarrhalis and the percentage of sputum neutrophils [58], suggesting the possible involvement of the host immune response [33].…”

“…Their direct communication is perhaps not surprising as these two mucosal sites have the same embryonic origin and are anatomically and functionally similar [31]. The composition of the lung micro biota is determined by the balance of migration of the bacteria from inhalation, mucosal dispersion or micro-aspiration and the microbial elimination by innate and adaptive host defenses, cough and mucociliary clearance [32,33]. Unlike the gut, the lung is oxygen-rich and it contains numerous lipid-rich surfactants that have bacteriostatic effects on selected bacterial species [34].…”