Bacteriology and Inflammation in Bronchiectasis (BISER)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Bacteriology and Sputum and Systemic Inflammation in Steady-state, Acute Exacerbation and Recovery of Bronchiectasis|
- Sputum microbiology [ Time Frame: 1 year ] [ Designated as safety issue: No ]type of bacterial infection, also referred to as potentially pathogenic organisms, and bacterial load, as expressed in cfu per mililiter
- Sputum sol phase inflammatory indices [ Time Frame: 1 year ] [ Designated as safety issue: No ]sputum sol phase interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leukotriene B4 (LTB4), myeloperoxidase (MPO) and C-reactive protein (CRP)
- 24-hour sputum volume [ Time Frame: 1 year ] [ Designated as safety issue: No ]
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.
- Spirometry [ Time Frame: 1 year ] [ Designated as safety issue: No ]
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.
- Sputum purulence [ Time Frame: 1 year ] [ Designated as safety issue: No ]
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.
- Sputum viscosity [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
- SGRQ total score and the score of each domain [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Time to recovery of respective symptom [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
- Sputum bacterial clearance rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Active Comparator: Fluroquinolones
The fluroquinolones employed in the present study are referred to as oral levofloxacin (500mg q.d.), moxifloxacin (400mg, q.d.) and ciprofloxacin (500mg, b.i.d.). All medications are administered based on the bronchiectasis guideline issued by British Thoracic Society.
All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis
Active Comparator: Beta-lactamase inhibitor
In the present study, amoxicillin and amoxicillin clavulanate potassium compound are employed, based on the British Thoracic Society guideline for bronchietasis, as mainly determined by sputum microbiology during steady-state bronchiectasis.
Drug: Beta-lactamase inhibitor
All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis.
Other Name: amoxicillin clavulanate potassium compound (Junerqing)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01761214
|State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College||Recruiting|
|Guangzhou, Guangdong, China, 510120|
|Contact: Nan-shan Zhong, M. D. 020-83062718 firstname.lastname@example.org|
|Contact: Rong-chang Chen, M. D. 020-83062718 email@example.com|
|Sub-Investigator: Wei-jie Guan, Ph. D.|
|Sub-Investigator: Zhi-ya Lin, Ph. D.|
|Principal Investigator: Nan-shan Zhong, M. D.|
|Principal Investigator: Rong-chang Chen, M. D.|
|Sub-Investigator: Yong-hua Gao, Ph. D.|
|Sub-Investigator: Gang Xu, Ph. D.|
|Principal Investigator:||Nan-shan Zhong, M. D.||Sate Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College|
|Principal Investigator:||Rong-chang Chen, M. D.||Sate Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College|