Clinical trial NCT04215172: Macrolides in COPD- Bronchiectasis Overlap
Official title: Safety and Efficacy of Long-Term Macrolide Therapy in Patients With COPD-Bronchiectasis Overlap Syndrome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bronchiectasis
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-01-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients who are admittted toChest department of Assiut University Hospitals or visit its outpatients' clinic

Brief summary: To assess safety of long-term macrolide therapy in patients with COPD-bronchiectasis overlap syndrome And evaluate its efficacy in treating COPD-bronchiectasis overlap syndrome regarding change in clinical, functional and microbiological profile.

To define the, clinical, radiological, functional and microbiological patterns of patients with COPD-bronchiectasis overlap syndrome

Detailed description: COPD and bronchiectasis share common symptoms of cough with sputum production and susceptibility to recurrent exacerbations driven by new or persistent infection The overlap between chronic obstructive pulmonary disease (COPD) and bronchiectasis is a neglected area of research, and it is not covered by guidelines for clinical practice COPD is diagnosed on the basis of poorly reversible airflow obstruction and is therefore a physiological diagnosis. It is defined when an objective measure of airflow obstruction is associated with an abnormal inflammatory response of the lung to noxious stimuli, with cigarette smoke being the most common exposure in the developed world. Operationally, this implies that patients with any sufficient exposure and fixed airflow obstruction are labelled as having COPD.

Bronchiectasis is diagnosed in the presence of airway dilatation and airway wall thickening on imaging (usually computed tomography (CT)), and is therefore a structural diagnosis. Clinically significant disease is present when imaging abnormalities are associated with symptoms of persistent or recurrent bronchial infection.

in the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD.

The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages. The identification of bronchiectasis in COPD has been defined as a different clinical COPD phenotype with greater symptomatic severity, more frequent chronic bronchial infection and exacerbations, and poor prognosis.

A recent meta-analysis by Du et al, of 5,329 COPD patients found a greatly increased exacerbation risk due to comorbid COPD with bronchiectasis compared to COPD alone.18 Moreover, the risk of exacerbations rose almost two times higher, colonization of the lungs four times higher, severe airway obstruction 30 percent higher, and mortality two times higher. It is not surprising that such elevated risks are also associated with higher healthcare costs.

Treatments useful in COPD may not be widely effective in bronchiectasis and vice versa. Inhaled corticosteroids provide perhaps the best example of this: they are widely used in COPD but not recommended for most patients with bronchiectasis . The reasons for this are unclear but probably reflect, in part, the diverse aetiology underlying bronchiectasis. In contrast, inhaled antibiotics, including antipseudomonal agents in appropriate patients, are of benefit and appear in current bronchiectasis guidelines ,but are not used routinely in stable COPD Macrolides, in addition to their antimicrobial effects, have decreased neutrophil chemotaxis and infiltration into the respiratory epithelium, inhibition of transcription factors leading to decreased proinflammatory cytokine production, down-regulation of adhesion molecule expression, inhibition of microbial virulence factors including biofilm formation, reduced generation of oxygen-free radicals, enhanced neutrophil apoptosis, and decreased mucus hypersecretion with improved mucociliary clearance.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or above, male or female.
* Non / Ex-smokers.
* Confirmed diagnosis of bronchiectasis based on high-resolution computed tomography scan.
* Confirmed diagnosis of COPD based on pulmonary function test.

Exclusion Criteria:

* Active smokers.
* Moderate to severe liver impairment (Child-Pugh B or C) and/or sever renal impairment (c. clearance less than 30ml/min).
* Patients who are known to be hypersensitive to macrolide.
* Patient with known or susceptible to have rhythm problems

Primary outcomes:
measure: long-term macrolides therapy in patients with COPD-bronchiectasis overlap syndrome regarding ototoxicity, hepatotoxicity and cardiac toxicity
timeFrame: two years
measure: evaluate macrolides in treating COPD-bronchiectasis overlap syndrome regarding improvement of symptoms, frequency of exacerbations, systemic inflammatory response and pulmonary function tests.
timeFrame: two years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Hurst JR, Elborn JS, De Soyza A; BRONCH-UK Consortium. COPD-bronchiectasis overlap syndrome. Eur Respir J. 2015 Feb;45(2):310-3. doi: 10.1183/09031936.00170014. No abstract available.
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.
citation: Martinez-Garcia MA, Miravitlles M. Bronchiectasis in COPD patients: more than a comorbidity? Int J Chron Obstruct Pulmon Dis. 2017 May 11;12:1401-1411. doi: 10.2147/COPD.S132961. eCollection 2017.
citation: Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DM, Lopez Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017 Mar 1;195(5):557-582. doi: 10.1164/rccm.201701-0218PP.
citation: Ni Y, Shi G, Yu Y, Hao J, Chen T, Song H. Clinical characteristics of patients with chronic obstructive pulmonary disease with comorbid bronchiectasis: a systemic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015 Jul 28;10:1465-75. doi: 10.2147/COPD.S83910. eCollection 2015.
citation: Figueiredo Bde C, Ibiapina Cda C. The role of macrolides in noncystic fibrosis bronchiectasis. Pulm Med. 2011;2011:751982. doi: 10.1155/2011/751982. Epub 2011 Sep 5.
citation: Chalmers JD. Bronchiectasis and COPD Overlap: A Case of Mistaken Identity? Chest. 2017 Jun;151(6):1204-1206. doi: 10.1016/j.chest.2016.12.027. No abstract available.