Evaluating the impact of angiotensin receptor blocker use on the response to Icenticaftor.

Evaluating the impact of angiotensin receptor blocker use on the response to Icenticaftor.

Chronic obstructive pulmonary disease (COPD) is the most common smoking-related lung disease and affects just over 5% of the adult population in the United States (US).COPD, refers to a group of diseases that cause airflow blockage and breathing-related problems. It includes emphysema and chronic bronchitis. Currently approved therapies are aimed at slowing lung function decline and decreasing frequency of exacerbations. Despite measures aimed at prevention and therapeutic advances it remains the sixth leading cause of death in the US and accounts for a great degree of morbidity as well for those affected with COPD. One of the key clinical features of COPD is chronic bronchitis, which is caused by inflammatory in the lungs leading to increased mucus production and dysfunction of the airway lining. Laboratory studies have shown that a specific protein in the airway lining, one that controls the thickness of mucus in the airways, is dysfunctional in chronic bronchitis. This protein, called cystic fibrosis transmembrane conductance regulator (CFTR), has been studied extensively for treatment of cystic fibrosis, a closely related lung disease. Borrowing from a treatment approach from CF, it is through that therapies which improve CFTR function could improve outcomes in chronic bronchitis. A recently reported large clinical trial found that icenticaftor, which is a modulator of CFTR, did not improve lung function in those with chronic bronchitis. However, it is known that ongoing inflammation in the airway can hinder the ability of therapies like icenticaftor to work properly. Additionally, our research group found that this effect can be reversed by losartan, a common blood pressure medication with anti-inflammatory properties. The goal of this study is to determine if, in this large clinical trial of icenticaftor, if those on losartan or similar medications had more benefit from treatment with icenticaftor than those that were not.

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