Long acting muscarinic receptor antagonists (LAMA) reverse airflow obstruction by antagonizing para-sympathetic bronchoconstricting effects within the airways. For years, tiotropium, has been the cornerstone LAMA for chronic obstructive pulmonary disease (COPD) management. Recently, new agents, aclidinium bromide, glycopyrronium bromide, and umeclidinium bromide, have been developed and introduced into clinical practice. Areas covered: This article reviews the clinical efficacy and adverse effects of currently available LAMAs in COPD treatment as well as developing LAMAs in early clinical trials and preclinical studies (V0162, TD-4208, CHF 5407, AZD9164, AZD8683, bencycloquidium). In addition, a new class of molecule that combines muscarinic antagonist and β2-adrenergic properties (MABA) is described and current developmental progress discussed (GSK-961081, THRX-200495). Expert opinion: Future key areas for developing drugs for the management of COPD include prolonged duration of action, optimal delivery systems, synergistic combinations with other drugs, maximization of benefits and minimization of adverse effects. The development of new LAMA and MABA molecules provides exciting progress towards simpler and more effective COPD management.
e20719 Background: Genomic profiling of advanced non-squamous lung cancer is integral for appropriate management. Appropriate testing and timeliness in getting the results often pose a challenge in a community setting. We share our experience in a community setting and the importance of an integrated approach to improve outcomes. Methods: Retrospective review of the charts of patients with stage- III-B/IV was conducted to gather data. Effect of Multi-disciplinary meetings to improving coordination among treating physicians and Incorporation of reflex testing for complete mutational profiling on diagnosis was studied. Results: Between 04/2016 and 10/2018, 127 patients charts were reviewed. 83% were stage-IV and 17% stage-III-B. Males (61%), Females (49%). Median age was 62 yrs. 76% had smoking history.There were 53% core biopsies, 42% FNAs and 5% resections. Mutational profiling panel was based on the NCCN guidelines. Adequate specimen for complete profiling was available in 111/127 (87%) of the patients. Two/16 (12%) of pts with in-adequate sample had a repeat biopsy and 12/16 ( 75%) had liquid biopsies done. Remaining 2 pts didnot have further w/u due to declining PS. Complete mutational profile (EGFR/ALK/ROS-1/MET/RET/BRAF/PDL-1) was available in 100% of pts. after re-biopsy/liquid bx. Incorporation of reflex testing decreased the reporting time from an average of 11.6 days to 6.9 days. The results of mutational profiling were available in 94% of pts. before starting the treatment. Prevalence of mutations were, EGFR:14%, ALk:3%, BRAF:1%, MET:0%, RET:1%, ROS-1:2%. Conclusions: Multi-disciplinary integrated approach and reflex testing upon diagnosis is essential for appropriate and timely genomic profiling of locally advanced/ metastatic non-squamous lung cancer patients to deliver appropriate treatment in a community setting.
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