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

NCT02315547 | Unknown

• 1 other identifier: GIRD-20141208-GWJ
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Bronchiectasis

Keywords

Microbiota; Airway infection; Bronchiectasis; Airway inflammation; Oxidative stress; Matrix metalloproteinase

Outcome Measures

Primary Outcomes (1)

• 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

  Jan 2015 to Dec 2017, up to 3 years

Secondary Outcomes (10)

• Serum inflammatory indices

  Jan 2015 to Dec 2017, up to 3 years

• Sputum sol phase inflammatory biomarkers

  Jan 2015 to Dec 2017, up to 3 years

• Sputum sol phase oxidative stress biomarkers or parameters

  Jan 2015 to Dec 2017, up to 3 years

• Sputum sol phase matrix metalloproteinases

  Jan 2015 to Dec 2017, up to 3 years

• 24-hour sputum volume

  Jan 2015 to Dec 2017, up to 3 years

Study Arms (1)

Antibiotics

OTHER

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

Interventions

Antibiotics DRUG

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.

Antibiotics

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of either sex and age between 18 and 85 years

You may not qualify if:

• Patient judged to have poor compliance
• Female patient who is lactating or pregnant
• Patients having concomitant severe systemic illnesses (i.e. coronary heart disease, cerebral stroke, uncontrolled hypertension, active gastric ulcer, malignant tumor, hepatic dysfunction, renal dysfunction)
• Miscellaneous conditions that would potentially influence efficacy assessment, as judged by the investigators
• Participation in another clinical trial within the preceding 3 months
• 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

Sponsors & Collaborators

• Guangzhou Institute of Respiratory Disease: lead

Study Sites (1)

Guangzhou Institute of Respiratory Disease

Guangzhou, Guangdong, 510120, China

RECRUITING

Related Publications (20)

• Pasteur MC, Helliwell SM, Houghton SJ, Webb SC, Foweraker JE, Coulden RA, Flower CD, Bilton D, Keogan MT. An investigation into causative factors in patients with bronchiectasis. Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1277-84. doi: 10.1164/ajrccm.162.4.9906120.

  PMID: 11029331 BACKGROUND

• Davies G, Wells AU, Doffman S, Watanabe S, Wilson R. The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis. Eur Respir J. 2006 Nov;28(5):974-9. doi: 10.1183/09031936.06.00074605. Epub 2006 Aug 9.

  PMID: 16899482 BACKGROUND

• Chmiel JF, Davis PB. State of the art: why do the lungs of patients with cystic fibrosis become infected and why can't they clear the infection? Respir Res. 2003;4(1):8. doi: 10.1186/1465-9921-4-8. Epub 2003 Aug 27.

  PMID: 14511398 BACKGROUND

• King PT, Hutchinson PE, Johnson PD, Holmes PW, Freezer NJ, Holdsworth SR. Adaptive immunity to nontypeable Haemophilus influenzae. Am J Respir Crit Care Med. 2003 Feb 15;167(4):587-92. doi: 10.1164/rccm.200207-728OC. Epub 2002 Nov 14.

  PMID: 12433671 BACKGROUND

• Sadikot RT, Blackwell TS, Christman JW, Prince AS. Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med. 2005 Jun 1;171(11):1209-23. doi: 10.1164/rccm.200408-1044SO. Epub 2005 Feb 1.

  PMID: 15695491 BACKGROUND

• Starner TD, Zhang N, Kim G, Apicella MA, McCray PB Jr. Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am J Respir Crit Care Med. 2006 Jul 15;174(2):213-20. doi: 10.1164/rccm.200509-1459OC. Epub 2006 May 4.

  PMID: 16675778 BACKGROUND

• Horvath I, Loukides S, Wodehouse T, Kharitonov SA, Cole PJ, Barnes PJ. Increased levels of exhaled carbon monoxide in bronchiectasis: a new marker of oxidative stress. Thorax. 1998 Oct;53(10):867-70. doi: 10.1136/thx.53.10.867.

  PMID: 10193374 BACKGROUND

• Angrill J, Agusti C, De Celis R, Filella X, Rano A, Elena M, De La Bellacasa JP, Xaubet A, Torres A. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am J Respir Crit Care Med. 2001 Nov 1;164(9):1628-32. doi: 10.1164/ajrccm.164.9.2105083.

  PMID: 11719301 BACKGROUND

• Ryall B, Davies JC, Wilson R, Shoemark A, Williams HD. Pseudomonas aeruginosa, cyanide accumulation and lung function in CF and non-CF bronchiectasis patients. Eur Respir J. 2008 Sep;32(3):740-7. doi: 10.1183/09031936.00159607. Epub 2008 May 14.

  PMID: 18480102 BACKGROUND

• Evans SA, Turner SM, Bosch BJ, Hardy CC, Woodhead MA. Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa. Eur Respir J. 1996 Aug;9(8):1601-4. doi: 10.1183/09031936.96.09081601.

  PMID: 8866579 BACKGROUND

• Goleva E, Jackson LP, Harris JK, Robertson CE, Sutherland ER, Hall CF, Good JT Jr, Gelfand EW, Martin RJ, Leung DY. The effects of airway microbiome on corticosteroid responsiveness in asthma. Am J Respir Crit Care Med. 2013 Nov 15;188(10):1193-201. doi: 10.1164/rccm.201304-0775OC.

  PMID: 24024497 BACKGROUND

• Marri PR, Stern DA, Wright AL, Billheimer D, Martinez FD. Asthma-associated differences in microbial composition of induced sputum. J Allergy Clin Immunol. 2013 Feb;131(2):346-52.e1-3. doi: 10.1016/j.jaci.2012.11.013. Epub 2012 Dec 23.

  PMID: 23265859 BACKGROUND

• Garzoni C, Brugger SD, Qi W, Wasmer S, Cusini A, Dumont P, Gorgievski-Hrisoho M, Muhlemann K, von Garnier C, Hilty M. Microbial communities in the respiratory tract of patients with interstitial lung disease. Thorax. 2013 Dec;68(12):1150-6. doi: 10.1136/thoraxjnl-2012-202917. Epub 2013 Aug 14.

  PMID: 23945167 BACKGROUND

• Rogers GB, van der Gast CJ, Cuthbertson L, Thomson SK, Bruce KD, Martin ML, Serisier DJ. Clinical measures of disease in adult non-CF bronchiectasis correlate with airway microbiota composition. Thorax. 2013 Aug;68(8):731-7. doi: 10.1136/thoraxjnl-2012-203105. Epub 2013 Apr 6.

  PMID: 23564400 BACKGROUND

• Tunney MM, Einarsson GG, Wei L, Drain M, Klem ER, Cardwell C, Ennis M, Boucher RC, Wolfgang MC, Elborn JS. Lung microbiota and bacterial abundance in patients with bronchiectasis when clinically stable and during exacerbation. Am J Respir Crit Care Med. 2013 May 15;187(10):1118-26. doi: 10.1164/rccm.201210-1937OC.

  PMID: 23348972 BACKGROUND

• Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58. doi: 10.1136/thx.2010.136119.

  PMID: 20627931 BACKGROUND

• Chalmers JD, Goeminne P, Aliberti S, McDonnell MJ, Lonni S, Davidson J, Poppelwell L, Salih W, Pesci A, Dupont LJ, Fardon TC, De Soyza A, Hill AT. The bronchiectasis severity index. An international derivation and validation study. Am J Respir Crit Care Med. 2014 Mar 1;189(5):576-85. doi: 10.1164/rccm.201309-1575OC.

  PMID: 24328736 BACKGROUND

• Laszlo G. Standardisation of lung function testing: helpful guidance from the ATS/ERS Task Force. Thorax. 2006 Sep;61(9):744-6. doi: 10.1136/thx.2006.061648.

  PMID: 16936234 BACKGROUND

• Zheng J, Zhong N. Normative values of pulmonary function testing in Chinese adults. Chin Med J (Engl). 2002 Jan;115(1):50-4.

  PMID: 11930658 BACKGROUND

• Fodor AA, Klem ER, Gilpin DF, Elborn JS, Boucher RC, Tunney MM, Wolfgang MC. The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations. PLoS One. 2012;7(9):e45001. doi: 10.1371/journal.pone.0045001. Epub 2012 Sep 26.

  PMID: 23049765 BACKGROUND

MeSH Terms

Conditions

Bronchiectasis

Interventions

Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Nan-shan Zhong, MD

  State Key Laboraotry of Respiratory Disease

  STUDY CHAIR

Central Study Contacts

Wei-jie Guan, Ph.D.

CONTACT

+86-13826042052; battery203@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: physician

Study Record Dates

• First Submitted: December 8, 2014
• First Posted: December 12, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: August 1, 2019

Record last verified: 2019-07

Locations

CN (1)