An interventional study of Antibiotics in Bronchiectasis, sponsored by Guangzhou Institute of Respiratory Disease. Status unknown at 1 site in China. Open to participants aged 18 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-08-01.
Sponsored by Guangzhou Institute of Respiratory Disease · Not applicable, Interventional, and Diagnostic
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.
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.
373 studies on the registry are indexed under Bronchiectasis; 104 are open to participants now.
This study's planned enrollment of 120 is above the median of 59 across 238 interventional studies indexed under Bronchiectasis.
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Exclusion Criteria:
Inclusion criteria for healthy subjects include all of the above criteria except for known respiratory diseases
It is estimated that 120 patients will be recruited in the study. Some of the patients in the BISER study (currently still ongoing, No.: NCT01761214) who are eligible for the current study will undergo assessments de novo, with the index date deemed as the the date of recruitment
Patients will be given antibiotics based on sputum microbiology during steady-state bronchiectasis. The methodology has been described in the British Thoracic Society guideline \[16\]. Briefly, for first-line therapy, patients isolated with Hemophilus influenzae, Hemophilus parainfluenzae, Streptoccus pneumoniae and Moraxella catarrhalis at baseline will be treated with amoxicillin clavulanate potassium (625mg bid); patients isolated with Klebsela pneumonae or Pseudomonas aeruginosa at baseline will be treated with fluoroquinolones. Levofloxacin (500mg qd) will be empirically employed for antibiotic treatment in those who tested negative to sputum microbiology. Severe BEs could be prescribed with intravenous antibiotics therapy at the discretion of study investigators, either in the out-patient department or hospitalized for intensive systemic treatment. Hospitalized patients will not be included in the exacerbation cohort.
Drug: Antibiotics
Patients will be given antibiotics based on sputum microbiology during steady-state bronchiectasis. The methodology has been described in the British Thoracic Society guideline \[16\]. Briefly, for first-line therapy, patients isolated with Hemophilus influenzae, Hemophilus parainfluenzae, Streptoccus pneumoniae and Moraxella catarrhalis at baseline will be treated with amoxicillin clavulanate potassium (625mg bid); patients isolated with Klebsela pneumonae or Pseudomonas aeruginosa at baseline will be treated with fluoroquinolones. Levofloxacin (500mg qd) will be empirically employed for antibiotic treatment in those who tested negative to sputum microbiology. Severe BEs could be prescribed with intravenous antibiotics therapy at the discretion of study investigators, either in the out-patient department or hospitalized for intensive systemic treatment. Hospitalized patients will not be included in the exacerbation cohort.
relative abundance, diversity and richness of microbiota taxa
Sputum microbiota taxa compositions (at phylum and species levels, respectively), including the relative abundance, diversity and richness
Time frame: Jan 2015 to Dec 2017, up to 3 years
Serum inflammatory indices
IL-8, TNF-α, WBC and CRP
Time frame: Jan 2015 to Dec 2017, up to 3 years
Sputum sol phase inflammatory biomarkers
IL-8 and TNF-α
Time frame: Jan 2015 to Dec 2017, up to 3 years
Sputum sol phase oxidative stress biomarkers or parameters
CAT, hydrogen peroxide, superoxide dismutase, MDA
Time frame: Jan 2015 to Dec 2017, up to 3 years
Sputum sol phase matrix metalloproteinases
MMP-8, MMP-9, TIMP-1, MMP-9/TIMP-1 ratio
Time frame: Jan 2015 to Dec 2017, up to 3 years
24-hour sputum volume
24-hour sputum volume, measured to the nearest 5 ml
Time frame: Jan 2015 to Dec 2017, up to 3 years
Spirometry
FEV1, FVC, FEV1/FVC, MMEF
Time frame: Jan 2015 to Dec 2017, up to 3 years
Bronchiectasis Severity Index
Time frame: Jan 2015 to Dec 2017, up to 3 years
Sputum culture findings
normally reported as growth of a predominant potentially pathogenic microorganism or no bacterial growth
Time frame: Jan 2015 to Dec 2017, up to 3 years
Sputum purulence
scale 1 to 8
Time frame: Jan 2015 to Dec 2017, up to 3 years
SGRQ total score and the scores of individual domains
SGRQ total score and the scores of individual domains
Time frame: Jan 2015 to Dec 2017, up to 3 years
This study is status unknown, as verified in Jul 2019. You cannot join it, but the record below documents what was studied.
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Guangzhou Institute of Respiratory Disease