Amyotrophic Lateral Sclerosis and the Respiratory System Andrew T. Braun, MD, MHS a,b , Candelaria Caballero-Eraso, MD, PhD a,c , Noah Lechtzin, MD, MHS a, * INTRODUCTION Amyotrophic lateral sclerosis (ALS) is a progres- sive neurodegenerative disorder that always af- fects the respiratory muscles. It is characterized by degeneration of motor neurons in the brain and spinal cord. 1 Respiratory complications, including pneumonia and progressive respiratory failure, are the most common causes of death in ALS and typically occur within 3 to 5 years of diag- nosis. 2,3 Because ALS affects both upper and lower motor neurons, it causes hyperreflexia, spasticity, muscle fasciculations, muscle atrophy, and weakness. It ultimately progresses to func- tional quadriplegia. ALS most commonly begins in the limbs, but in about one-third of cases it be- gins in the bulbar muscles responsible for speech and swallowing. 4 A small proportion of cases begin with respiratory muscle weakness and can present as unexplained hypercarbic respiratory failure. 5 Most cases of ALS are idiopathic, but approx- imately 10% of cases are due to identifiable genetic mutations and are inherited in an auto- somal dominant manner. 6 The incidence of ALS in the United States is 1 to 2 cases per 100,000 people, and the average age of onset is in the mid-fifties. There is a male predominance of spo- radic cases with a male to female ratio of almost 2:1. 7 There are now 2 medications approved by the US Food and Drug Administration for the treatment of ALS, riluzole and edaravone 8 ; but in spite of therapeutic developments, the disease is uniformly fatal and the treatment is largely Disclosures: Dr N. Lechtzin has served as a consultant with Hill-Rom, Inc, Dr A. Braun and Dr C. Caballero-Eraso have no relevant conflicts of interest or financial disclosures. a Division of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Johns Hopkins Univer- sity School of Medicine, 1830 East Monument Street, Baltimore, MD 21205, USA; b Division of Allergy, Pulmo- nary, and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA; c Medical-Surgical Unit of Respiratory Diseases, Institute of Biomedicine of Seville (IBiS), Centre for Biomedical Research in Respiratory Diseases Network (CIBERES), Uni- versity Hospital Virgen del Rocı ´o, University of Seville, Avenida Dr. Fedriani, 41009 Sevilla, Spain * Corresponding author. E-mail address: nlechtz@jhmi.edu KEYWORDS  Noninvasive ventilation  Diaphragm  Secretion clearance KEY POINTS  Amyotrophic lateral sclerosis (ALS) is an incurable disease whereby patients most commonly die of respiratory complications.  It is important for pulmonary physicians to be aware of this and understand management options, including noninvasive and invasive ventilation and assisted cough techniques.  Because ALS affects both upper and lower motor neurons, it causes hyperreflexia, spasticity, mus- cle fasciculations, muscle atrophy, and weakness. Clin Chest Med 39 (2018) 391–400 https://doi.org/10.1016/j.ccm.2018.01.003 0272-5231/18/Ó 2018 Elsevier Inc. All rights reserved. chestmed.theclinics.com