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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fluroquinolones | Active Comparator | 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. |
|
| Beta-lactamase inhibitor | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluroquinolones | Drug | All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis |
|
| Measure | Description | Time Frame |
|---|---|---|
| Sputum microbiology | type of bacterial infection, also referred to as potentially pathogenic organisms, and bacterial load, as expressed in cfu per mililiter | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Sputum sol phase inflammatory indices | sputum sol phase interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leukotriene B4 (LTB4), myeloperoxidase (MPO) and C-reactive protein (CRP) | 1 year |
| 24-hour sputum volume |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College | Recruiting | Guangzhou | Guangdong | 510120 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11986413 | Background | Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. doi: 10.1056/NEJMra012519. No abstract available. | |
| 18238949 | Background | 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. |
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| ID | Term |
|---|---|
| D001987 | Bronchiectasis |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077266 | Moxifloxacin |
| D002939 | Ciprofloxacin |
| C093087 | cifran |
| D065093 | beta-Lactamase Inhibitors |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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| Beta-lactamase inhibitor | Drug | All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis. |
|
|
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 |
| 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 |
| 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 |
| 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 |
| SGRQ total score and the score of each domain | 1 year |
| 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 |
| 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 |
| 18829674 | Background | 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. |
| 15741443 | Background | 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. doi: 10.1136/thx.2002.003236. |
| 20627931 | 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. |
| 9730996 | Background | 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. doi: 10.1164/ajrccm.158.3.9710090. |
| 10669685 | Background | 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. doi: 10.1378/chest.117.2.420. |
| 16936234 | 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. |
| 11930658 | Background | Zheng J, Zhong N. Normative values of pulmonary function testing in Chinese adults. Chin Med J (Engl). 2002 Jan;115(1):50-4. |
| 22744718 | Result | 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/rccm.201203-0487OC. Epub 2012 Jun 28. |
| 19501498 | Result | 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. |
| 27339787 | Derived | Guan WJ, Yuan JJ, Gao YH, Li HM, Zheng JP, Chen RC, Zhong NS. Maximal mid-expiratory flow is a surrogate marker of lung clearance index for assessment of adults with bronchiectasis. Sci Rep. 2016 Jun 24;6:28467. doi: 10.1038/srep28467. |
| 26904207 | Derived | Guan WJ, Gao YH, Xu G, Li HM, Yuan JJ, Zheng JP, Chen RC, Zhong NS. Bronchodilator response in adults with bronchiectasis: correlation with clinical parameters and prognostic implications. J Thorac Dis. 2016 Jan;8(1):14-23. doi: 10.3978/j.issn.2072-1439.2016.01.05. |
| 26060319 | Derived | Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Jiang M, Zheng JP, Chen RC, Zhong NS. Inflammatory Responses, Spirometry, and Quality of Life in Subjects With Bronchiectasis Exacerbations. Respir Care. 2015 Aug;60(8):1180-9. doi: 10.4187/respcare.04004. Epub 2015 Jun 9. |
| 25654540 | Derived | Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Zheng JP, Chen RC, Zhong NS. Impulse oscillometry in adults with bronchiectasis. Ann Am Thorac Soc. 2015 May;12(5):657-65. doi: 10.1513/AnnalsATS.201406-280OC. |
| 25405614 | Derived | Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Zheng JP, Chen RC, Zhong NS. Characterization of lung function impairment in adults with bronchiectasis. PLoS One. 2014 Nov 18;9(11):e113373. doi: 10.1371/journal.pone.0113373. eCollection 2014. |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000900 | Anti-Bacterial Agents |
| D000890 | Anti-Infective Agents |
| D045506 | Therapeutic Uses |