Safety and Tolerability of Systemic Beta-2-Adrenergic Agonist[Albuterol] as Pharmacological Therapy in Non-Invasive Ventilation[ NIV ]-supported Amyotrophic Lateral Sclerosis[ALS]Patients with Chronic Respiratory Failure (P4.079)

OBJECTIVE: Clinical audit of use of systemic albuterol in NIV-supported ALS patients at an ALS Multidisciplinary Clinic. BACKGROUND: NIV decreases the rate of respiratory function decline in ALS patients[Kleopa,1999;Bourke,2006]. Few clinical trials have addressed improving respiratory function or extending time before NIV daytime-dependency in these patients[Yi,2012]. Beta-2-adrenergic agonists[albuterol/clenbuterol]have increased vital capacity and neck strength short-term in ALS and spinal muscular atrophy patients[Brooks,2000; Soraru,2006, Querin,2013]. DESIGN/METHODS: Retrospective audit of albuterol utilization in NIV-supported ALS patients from 2010-2013. Vital signs[pulse rate, respiratory rate, blood pressure, vital capacity[%predicted-Knudsen(adult), ALSFRS-R individual or combined bulbar-and respiratory-subscores]were reviewed in 108 NIV-supported ALS patients[55M;52F]at start of NIV or at start of albuterol on NIV and then at 3 and 6 months subsequently. Albuterol was started at median systemic dose[tablet/liquid]of 6 + 3[SD] mg/day in NIV-supported ALS patients with difficulty maintaining breathing capacity associated with bulbar and respiratory dysfunction. RESULTS: Albuterol was tolerated for 6 months in 49/52 [31M;18F]NIV-supported ALS patients but not in 3 patients[1M;2F][94.2% tolerability]with no further VC reduction for 3 months. More M patients(P=0.0262)with VC below 70% predicted [VC=61.0% predicted(95%CI=53.9-68.2]were given albuterol compared with NIV-supported ALS patients[23M;32F]not receiving albuterol[VC=77.3%(95%CI=70.7-83.9)]. ALSFRS-R respiratory-, but not bulbar-sub-score was significantly[P=0.0006] decreased in albuterol-treated[6.4(95%CI=5.4-7.3)}compared with patients not receiving albuterol[9.2(95%CI=8.0-10.6)]. Pulse rate increased 10% from baseline but the population variability of this change within the normal pulse rate range was not significant. VC remained unchanged at 3 months[VC=57.7%(95%CI=49.8-65.5)]but declined at 6 months on albuterol[VC=50.0%(95%CI=35.8-58.5)]. CONCLUSIONS: Systemic albuterol is 94.2% tolerable when used in NIV-supported ALS patients. M NIV-supported ALS patients more commonly required albuterol. VC was maintained at 3 months without change but not at 6 months in albuterol-treated NIV-supported ALS patients. Further studies are required on pharmacologically enhancing the treatment of NIV-supported ALS patients. Study Supported by: Carolinas ALS Research Fund/Pinstripes Fund/Carolinas Garden of Hope/Carolinas Healthcare Foundation Disclosure: Dr. Brooks has received personal compensation for activities with Biogen Idec, Avanir Pharmaceuticals, Acorda Therapeutics, Cytokinetics, Synapse, and the National Institute of Neurological Disorders and Stroke. Dr. Brooks has received research support from Biogen Idec, Avanir Pharmaceuticals, Cytokinetics, Neuraltus Pharmaceuticals, GlaxoSmithKline, Inc., and the National Institute of Neurological Disorders and Stroke. Dr. Kandinov has nothing to disclose. Dr. Langford has nothing to disclose. Dr. Lindblom has nothing to disclose. Dr. Sanjak has nothing to disclose. Dr. Wright has nothing to disclose. Dr. Ward has nothing to disclose. Dr. Holsten has nothing to disclose. Dr. Fischer has nothing to disclose. Dr. Lucas has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Nichols has nothing to disclose. Dr. Lary has nothing to disclose. Dr. Nemeth has nothing to disclose. Dr. Russo has received personal compensation for activities with Teva Neuroscience and Biogen Idec as a consultant. Dr. Bockenek has nothing to disclose. Dr. Bravver has received research support from Biogen Idec, Avanier, Cytokinetics Pharmaceuticals, Neuraltus Pharmaceuticals, GlaxoSmithKline Inc., the National Institute of Neurological Disorders and Stroke, and the Clinical Research Consortium. Dr. Desai has received personal compensation for activities with Purdue Pharma and UCB Pharma as a speaker. Dr. Story has nothing to disclose. Dr. Pacicco has nothing to disclose.