Sputum Microbiota and the Association With Clinical Parameters in Steady-state Acute Exacerbation and Convalescence of Bronchiectasis

Description

Bronchiectasis is a chronic airway disease characterized by airway infection, inflammation and destruction [1]. Bacteria are frequently responsible for the vicious cycle seen in bronchiectasis. Clinically, potentially pathogenic microorganisms (PPMs) primarily consisted of Hemophilus influenzae, Hemophilus parainfluenzae, Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae and Moraxella catarrhalis [1]. These PPMs elicit airway inflammation [2-5] and biofilm formation [6] leading to and oxidative stress [7,8]. However, different PPMs harbor varying effects on bronchiectasis. For instance, P. aeruginosa has been linked to more pronounced airway inflammation and poorer lung function [9,10].

However, it should be recognized that routine sputum bacterial culture techniques could only effectively identify a small proportion of PPMs. The assay sensitivity and specificity could be significantly affected by the duration from sampling to culture, the culture media and environment. Pyrosequencing of the bacterial 16srRNA might offer more comprehensive assessment of the airway microbiota. Based on this technique, Goleva and associates [11] identified an abundance of gram-negative microbiota (predominantly the phylum proteobacteria) which might be responsible for corticosteroid insensitivity. The microbiome of airways in patients with asthma [11,12], idiopathic pulmonary fibrosis [13] and bronchiectasis [14,15] has also been characterized. Furthermore, the association between the "core microbiota" and clinical parameters (i.e., FEV1) has been demonstrated. However, previous studies suffered from relatively small sample size and lack of comprehensive sets of clinical parameters for further analyses.

Bronchiectasis exacerbations (BEs) are characterized by significantly worsened symptoms and (or) signs that warrant antibiotics therapy. The precise mechanisms responsible for triggering BEs have not been fully elucidated, but could be related to virus infection and increased bacterial virulence. However, it should be recognized that antibiotics, despite extensive bacterial resistance, remain effective for most BEs. This at least partially suggested that bacterial infection might have played a major role in the pathogenesis of BEs. Therefore, the assessment of sputum microbiota during steady-state, BEs and convalescence may unravel more insights into the dynamic variation in microbiota compositions and the principal microbiota phylum or species that account for BEs.

In the this study, the investigators seek to perform 16srRNA pyrosequencing to determine: 1) the differences in microbiota compositions between bronchiectasis patients and healthy subjects; 2) association between sputum microbiota compositions and clinical parameters, including systemic/airway inflammation, spirometry, disease severity, airway oxidative stress biomarkers and matrix metalloproteinase; 3) the microbiota compositions in patients who yielded "normal flora (commensals)", in particular those who produced massive sputum daily (>50ml/d); 4) dynamic changes in microbiota compositions during BEs and convalescence as compared with baseline levels; 5) the utility of predominant microbiota taxa in predicting lung function decline and future risks of BEs during 1-year follow-up.

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