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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Guangzhou Institute of Respiratory Disease

Brief Summary:

Study 1 is a cross-sectional investigation. Patients with clinically stable bronchiectasis (symptoms, including cough frequency, sputum volume and purulence, within normal daily variations) will undergo baseline assessment consisting of history taking, routine sputum culture, 16srRNA pyrosequencing, measurement of sputum inflammatory markers, oxidative stress biomarkers and MMPs, and spirometry. Microbiota taxa will be compared between bronchiectasis patients and healthy subjects.

In study 2, patients inform investigators upon symptom deterioration. Following diagnosis of BEs, patients will undergo the aforementioned assessments as soon as possible. This entails antibiotic treatment, with slightly modified protocol, based on British Thoracic Society guidelines [16]. At 1 week after completion of 14-day antibiotic therapy, patients will undergo convalescence visit.

Study 3 is a prospective 1-year follow-up scheme in which patients participated in telephone or hospital visits every 3 months. For individual visit, spirometry and sputum culture will be performed, and BEs will be meticulously captured from clinical charts and history inquiry, with the final decisions adjudicated following group discussion.


Detailed Summary:

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
Sponsor: Guangzhou Institute of Respiratory Disease

Current Primary Outcome: relative abundance, diversity and richness of microbiota taxa [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]

Sputum microbiota taxa compositions (at phylum and species levels, respectively), including the relative abundance, diversity and richness


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Serum inflammatory indices [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
    IL-8, TNF-α, WBC and CRP
  • Sputum sol phase inflammatory biomarkers [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
    IL-8 and TNF-α
  • Sputum sol phase oxidative stress biomarkers or parameters [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
    CAT, hydrogen peroxide, superoxide dismutase, MDA
  • Sputum sol phase matrix metalloproteinases [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
    MMP-8, MMP-9, TIMP-1, MMP-9/TIMP-1 ratio
  • 24-hour sputum volume [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
    24-hour sputum volume, measured to the nearest 5 ml
  • Spirometry [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
    FEV1, FVC, FEV1/FVC, MMEF
  • Bronchiectasis Severity Index [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
  • Sputum culture findings [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
    normally reported as growth of a predominant potentially pathogenic microorganism or no bacterial growth
  • Sputum purulence [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
    scale 1 to 8
  • SGRQ total score and the scores of individual domains [ Time Frame: Jan 2015 to Dec 2017, up to 3 years ]
    SGRQ total score and the scores of individual domains


Original Secondary Outcome: Same as current

Information By: Guangzhou Institute of Respiratory Disease

Dates:
Date Received: December 8, 2014
Date Started: January 2015
Date Completion: December 2017
Last Updated: August 8, 2016
Last Verified: August 2016