Bacteriology and Inflammation in Bronchiectasis

Bronchiectasis Clinical Trial

— BISER  

Official title:

Bacteriology and Sputum and Systemic Inflammation in Steady-state, Acute Exacerbation and Recovery of Bronchiectasis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01761214
• Other study ID #: SKLRD-2013-GWJ
• Status: Recruiting
• Phase: N/A
• Start date: September 2012
• Est. completion date: December 2023

Study information

• Verified date: February 2020
• Source: Guangzhou Institute of Respiratory Disease
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Bronchiectasis is a chronic disease arises from progressive airway inflammation and infection. It has been postulated that bacterial infection triggers intense airway inflammation leading to acute exacerbation of bronchiectasis. Antibiotics have been the most potent medications for the treatment of bronchiectasis, however, the sputum bacterial load and inflammatory indices at steady-state and exacerbation remain largely unknown. The investigation might shed light on the roles that antibiotics play in acute exacerbation of bronchiectasis and uncover the mechanisms on why a subgroup of individuals do not respond satisfactorily.

Description:

Bronchiectasis is a chronic disease arises from progressive airway inflammation and infection. Pro-inflammatory mediators, the products of activated neutrophils recruited to the inflamed sites, are released in bronchiectatic airways and mediate cascades of neutrophil infiltration. This suggests that bacterial infection plays a pivotal role in the neutrophil-derived inflammation leading to the vicious cycle that perpetuates the development of airway destruction and might result in acute exacerbation. Treatments targeting at bacterial infection is therefore necessary, particularly for those with acute exacerbation of bronchiectasis.

Although short- and long-term administration of antibiotics have been evidenced to markedly suppress bacterial colonization and inflammatory indices, the roles that potent antibiotics play in patients with exacerbation of bronchiectasis are unclear. The assessment of bacterial infection and sputum and systemic inflammation during steady-state, acute exacerbation and recovery from exacerbation of bronchiectasis may clinically shed light on and indicate the efficacy of antibiotic treatments.

Furthermore, a subgroup of patients may experience the acute exacerbation that may stem from non-bacterial pathogens. There has been a dire need to compare the changes in sputum bacterial load and inflammatory indices based on sputum bacteriology. This may help uncover the mechanism of different responses to antibiotic treatment in patients who had varying bacteriologic profiles.

Unlike assessment of chronic obstructive pulmonary disease, few clinical indices for appraisal of onset of exacerbation and efficacy of treatments are available. Of these, the 24-hour sputum volume, microbial clearance, C-reactive protein (CRP) and St George's Respiratory Questionnaire have been validated. In the present study, we employed sputum bacteriology and inflammatory indices, including the aforementioned parameters, for assessment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients of either sex and age between 18 and 70 years

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Bronchiectasis
• Inflammation

Intervention

Drug:
• Fluroquinolones
All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis
• Beta-lactamase inhibitor
All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis.

Locations

Country	Name	City	State
China	State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Institute of Respiratory Disease

Country where clinical trial is conducted

China, 

References & Publications (11)

Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. Review. — View Citation

Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012 Oct 1;186(7):657-65. doi: 10.1164/rcc — View Citation

Fuschillo S, De Felice A, Balzano G. Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms. Eur Respir J. 2008 Feb;31(2):396-406. doi: 10.1183/09031936.00069007. Review. — View Citation

Kapur N, Masters IB, Chang AB. Exacerbations in noncystic fibrosis bronchiectasis: Clinical features and investigations. Respir Med. 2009 Nov;103(11):1681-7. doi: 10.1016/j.rmed.2009.05.007. Epub 2009 Jun 6. — View Citation

Laszlo G. Standardisation of lung function testing: helpful guidance from the ATS/ERS Task Force. Thorax. 2006 Sep;61(9):744-6. — View Citation

Murray MP, Turnbull K, Macquarrie S, Hill AT. Assessing response to treatment of exacerbations of bronchiectasis in adults. Eur Respir J. 2009 Feb;33(2):312-8. doi: 10.1183/09031936.00122508. Epub 2008 Oct 1. — View Citation

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. Review. — View Citation

Tsang KW, Chan K, Ho P, Zheng L, Ooi GC, Ho JC, Lam W. Sputum elastase in steady-state bronchiectasis. Chest. 2000 Feb;117(2):420-6. — View Citation

Tsang KW, Ho PL, Lam WK, Ip MS, Chan KN, Ho CS, Ooi CC, Yuen KY. Inhaled fluticasone reduces sputum inflammatory indices in severe bronchiectasis. Am J Respir Crit Care Med. 1998 Sep;158(3):723-7. — View Citation

Tsang KW, Tan KC, Ho PL, Ooi GC, Ho JC, Mak J, Tipoe GL, Ko C, Yan C, Lam WK, Chan-Yeung M. Inhaled fluticasone in bronchiectasis: a 12 month study. Thorax. 2005 Mar;60(3):239-43. — View Citation

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

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sputum microbiology	type of bacterial infection, also referred to as potentially pathogenic organisms, and bacterial load, as expressed in cfu per mililiter	1 year
Secondary	Sputum sol phase inflammatory indices	sputum sol phase interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), leukotriene B4 (LTB4), myeloperoxidase (MPO) and C-reactive protein (CRP)	1 year
Secondary	24-hour sputum volume	Eligible patients with bronchiectasis, following recruitment, will be instructed to record the condition of expectoration in the patient diary card. This includes recording of 24-hour sputum volume, sputum purulence and changes in the symptoms per day. A minimum of 3 daily records between two neighboring visits are required. The 24-hour sputum volume will be recorded as the mean of 3 records.; The volume of 24-hour sputum was recorded as the mean of the nearest 3 consecutive days. Sputum volume was scored for 1, 2, 3, 4, 5 and 6 points corresponding to 0-10ml, 10-20ml, 20-30ml, 30-40ml, 40-50ml and >50ml, respectively.	1 year
Secondary	Spirometry	Spirometric indices in the present study is referred to as FEV1, FVC, FEV1/FVC and MMEF.; Spirometry tests are carried out using a spirometer (COSMED, QUARK PFT, Italy). All operation procedures meet the joint recommendation by ATS and ERS. A total of at least 3 (not more than 8) spirometric maneuvers are performed, with the variation between the best two maneuvers of <5% or 200ml in FVC and FEV1. The maximal values of FVC and FEV1 are reported. MMEF is chosen from the maneuver with the highest sum of FVC and FEV1. The predicted values are selected based on the reference regression model established by Zheng JP and Zhong NS.	1 year
Secondary	Sputum purulence	Patients receive chest physical therapy 15 minutes upon arrival at the hospital till expectoration complete. Patients are instructed to be seated and remove contents in the oral cavity followed by sputum collection using a sterile container between 10:00 a.m. and 12:00 a.m., an hour after physical therapy.; Sputum purulence is scored for 1, 2, 3, 4, 5, 6 and 7 points corresponding to complete absence, almost translucent, half translucent, translucent but colorless, opaque and white, grey and green, moderately green and dark green, respectively. The specimen with highest score is selected for reports.	1 year
Secondary	Sputum viscosity	Sputum viscosity is assessed by using a stick to randomly pick up the sputum from the center of the specimen. Sputum viscosity is scored for 1, 2 and 3 corresponding to mildly, moderately and severely sticky, respectively.	1 year
Secondary	SGRQ total score and the score of each domain		1 year
Secondary	Time to recovery of respective symptom	The symptoms of bronchiectasis include cough, expectoration (referred to as 24-hour sputum volume, purulence and viscosity), chest pain, chest distress, wheezing, febrile, malaise, fatigue, tachypnea and hemoptysis. A significant amelioration (>20%) in the respective symptom during antibiotic treatment when compared with that of acute exacerbation is deemed as recovery. The time of recovery is mainly determined by patient self-reporting.	1 year
Secondary	Sputum bacterial clearance rate	Sputum bacterial clearance rate is defined as the proportion of subjects who test negatively to sputum microbiology following a 14-day antibiotic therapy, with exception of those who showed a negative sputum culture profile during the steady-state bronchiectasis.	1 year