Macrolides in COPD- Bronchiectasis Overlap

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.