Antitussive Use in Patients with Inadequately Controlled Moderate-to-Severe Asthma: A Post Hoc Analysis of the Omalizumab EXTRA Trial.

Acute and chronic cough are common symptoms in patients with severe allergic asthma. Although asthma-related cough can be controlled by asthma-specific medications, both prescription and over-the-counter antitussives are often also necessary. The anti-immunoglobulin E monoclonal antibody omalizumab is an effective treatment for patients with moderate-to-severe asthma, but little is known about subsequent antitussive use patterns. This post hoc analysis examined data from the Phase 3 EXTRA study that included patients aged 12-75 years with inadequately controlled moderate-to-severe asthma. Baseline antitussive use was low overall (16/427, 3.7% for omalizumab and 18/421, 4.3% for placebo). Among patients with no baseline antitussive use (n = 411 omalizumab, n = 403 placebo), most patients (88.3% omalizumab, 83.4% placebo) reported not using antitussives during the 48-week treatment period. The percentage of patients using 1 antitussive was lower for patients treated with omalizumab than placebo (7.1% vs 13.2%), although the adjusted rate of antitussive use during the treatment period was similar for omalizumab and placebo (0.22 and 0.25). Non-narcotics were used more often than narcotics. In conclusion, this analysis found low use of antitussives in patients with severe asthma and suggests that omalizumab may have the potential to decrease antitussive use.

Abundant DNase I-sensitive bacterial DNA in healthy porcine lungs and its implications for the lung microbiome.

Human lungs are constantly exposed to bacteria in the environment, yet the prevailing dogma is that healthy lungs are sterile. DNA sequencing-based studies of pulmonary bacterial diversity challenge this notion. However, DNA-based microbial analysis currently fails to distinguish between DNA from live bacteria and that from bacteria that have been killed by lung immune mechanisms, potentially causing overestimation of bacterial abundance and diversity. We investigated whether bacterial DNA recovered from lungs represents live or dead bacteria in bronchoalveolar lavage (BAL) fluid and lung samples in young healthy pigs. Live bacterial DNA was DNase I resistant and became DNase I sensitive upon human antimicrobial-mediated killing in vitro. We determined live and total bacterial DNA loads in porcine BAL fluid and lung tissue by comparing DNase I-treated versus untreated samples. In contrast to the case for BAL fluid, we were unable to culture bacteria from most lung homogenates. Surprisingly, total bacterial DNA was abundant in both BAL fluid and lung homogenates. In BAL fluid, 63% was DNase I sensitive. In 6 out of 11 lung homogenates, all bacterial DNA was DNase I sensitive, suggesting a predominance of dead bacteria; in the remaining homogenates, 94% was DNase I sensitive, and bacterial diversity determined by 16S rRNA gene sequencing was similar in DNase I-treated and untreated samples. Healthy pig lungs are mostly sterile yet contain abundant DNase I-sensitive DNA from inhaled and aspirated bacteria killed by pulmonary host defense mechanisms. This approach and conceptual framework will improve analysis of the lung microbiome in disease.