Bronchiectasis Clinical Trial
Official title:
Safety and Efficacy of Long-Term Macrolide Therapy in Patients With COPD-Bronchiectasis Overlap Syndrome
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
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.
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