Obesity and sleep: a growing concern Purpose of review The ‘obesity epidemic’ is a growing concern globally, and obesity trends are projected to continue increasing in both prevalence and overall mean BMI. Cardiovascular and metabolic comorbidities have historically been well described; however, obesity-related respiratory disease is now increasingly prevalent, in particular, sleep disordered breathing. The surge in clinically significant obstructive sleep apnoea and obesity hypoventilation syndrome is associated with increased cardiopulmonary morbidity, quality-of-life impairment, and a potential rise in the frequency of road traffic accidents. Recent findings We discuss recent trends in obesity and obesity-related sleep disordered breathing. We also discuss recently published international guidelines regarding the diagnosis and management of sleep disordered breathing, and in particular, the role of weight management interventions, such as bariatric surgery, in this area. We discuss possible approaches to meet the growing demand for sleep assessment and management in the future. Summary Obesity-related respiratory disease reflects an increasing proportion of patients in both inpatient and outpatient settings. It is important to recognize the impact of obesity on pulmonary physiology in order to appropriately care for this population, as well as plan for the future. Correspondence to Dr John F. Garvey, MB BCh, BAO, PhD, Department of Respiratory Medicine, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. Tel: +353 221 3702; fax: +353 221 3576; e-mail: j.garvey@svhg.ie Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A contemporary review of obstructive sleep apnea with emphasis on definitions, epidemiology, and consequences Purpose of review This review provides a contemporary review of sleep apnea with emphasis on definitions, epidemiology, and consequences. Recent findings Amyloid β-42 is one of the main peptides forming amyloid plaques in the brains of Alzheimer patients. Poorer sleep quality and shorter sleep duration have been associated with a higher amyloid burden. Decreased sleep time in the elderly is a precipitating factor in amyloid retention. Studies have shown that the dysregulation of the homeostatic balance of the major inhibitory and excitatory amino acid neurotransmitter systems of gamma-aminobutyric acid (GABA) and glutamate play a role in sleep disordered breathing (SDB). Summary Untreated sleep disordered breathing (obstructive sleep apnea and/or central sleep apnea) are an important cause of medical mortality and morbidity. OSA is characterized by recurrent episodes of partial or complete collapse of the upper airway during sleep followed by hypoxia and sympathetic activation. Apneic events are terminated by arousal, followed by increases in pulse and blood pressure, and re-oxygenation and the release of inflammatory factors. Individuals with OSA have an increased risk of developing atrial fibrillation. Hypoxemia and poor sleep quality because of OSA increase the risk of cognitive decline in the elderly. Correspondence to Frank Ralls, MD, Associate Professor of Internal Medicine, University of New Mexico, Program Director: UNM Sleep Medicine Fellowship, Medical Director, University Hospital Sleep Disorders Center, 1101 Medical Arts Avenue NE, Building 2, Albuquerque, NM 87102, USA. Tel: +1 505 272 6110; fax: +1 505 272 6112; e-mail: FRalls@salud.unm.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Prevention of drug-related complications in cystic fibrosis Purpose of review Due to continuous development of new drugs and better treatment strategies, survival of patients with cystic fibrosis has changed dramatically. Recently, targeted therapy of cystic fibrosis transmembrane conductance regulator (CFTR) modulators have become available. Despite these promising developments, treatment of this complex multiorgan disease constitutes a high and variable amount of other drugs. Complications of pharmacotherapeutic treatment are, therefore, expected to become more prevalent. This gives cause to review drug-related side effects in this new era in cystic fibrosis treatment. Recent findings We will discuss cystic fibrosis-related pharmacotherapies with a focus on indication of treatment, side effects and their complications, drug--drug interactions, and options to monitor and prevent drug-induced toxicity. Many recent publications about pharmacotherapy in cystic fibrosis, focus on antifungal therapy and CFTR modulators. We will give an overview of the most important studies. Summary With increased life expectancy which is, in part, because of better treatment options, the burden of pharmacotherapy in cystic fibrosis patients will increase. This has a high impact on quality of life as pharmacotherapy is time consuming and may cause side effects. Therefore, it is very important to be aware of possible pharmacotherapy-related side effects and their complications, drug--drug interactions, and options to monitor and prevent drug-induced toxicity. Correspondence to Renske van der Meer, Haga Ziekenhuis, Els Borst-Eilersplein 275, 2545 AA Den Haag, The Netherlands. Tel: +31 641319642; e-mail: r.vandermeer@hagaziekenhuis.nl Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Phenotypic approach to pharmacotherapy in the management of obstructive sleep apnoea Purpose of review To provide a concise synthesis of the current knowledge of obstructive sleep apnoea (OSA) phenotyping concepts and how this information is being used to develop and direct targeted pharmacotherapy for OSA. Recent findings The causes of OSA vary between patients and therefore so too does the optimal therapy or therapies. Key phenotypic causes include impaired upper airway anatomy and non-anatomical contributors such as ineffective pharyngeal dilator muscles during sleep, waking up too easily to minor airway narrowing (low arousal threshold) and unstable respiratory control (high loop gain). Traditionally, heterogeneity of OSA pathophysiology was not considered in pharmacotherapy approaches for OSA. However, recent study has focussed on targeted pharmacotherapies directed towards specific OSA phenotypes. This, combined with advances in knowledge of the neurobiology of pharyngeal muscle control from animal studies that have recently been translated to human proof-of-concept studies by repurposing existing drugs that target the desired mechanisms, have opened up exciting new lines of investigation for OSA pharmacotherapy. Summary There have been major recent advances in the development of new targeted approaches to pharmacotherapy for OSA. This study shows considerable promise for a viable and much needed pathway to drug therapy for this common chronic health condition. Correspondence to Danny J. Eckert, AISH, Flinders University, Box 6, Mark Oliphant Building, 5 Laffer Drive, Bedford Park, South Australia 5042, Australia. E-mail: danny.eckert@flinders.edu.au Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Sleep and interstitial lung disease Purpose of review There is an increasing recognition of the impact of sleep and sleep disorders on respiratory disease. Recent years have seen a new focus on the relationship between sleep and outcomes in patients interstitial lung disease (ILD). Recent findings Recent studies suggest a high prevalence of sleep issues in ILD cohorts, which seem to have a meaningful negative impact on quality of life, disease progression, and survival. Summary Sleep disordered breathing is common in ILD patients: obstructive sleep apnoea (OSA) is found in 44–72% of ILD patients, and nocturnal hypoxemia is relatively common even in the absence of OSA. Sleep disorders are associated with worse quality of life in ILD, and may also predict more rapid disease progression and increased mortality. It remains unknown if nocturnal hypoxemia may itself cause progression of ILD. Uncontrolled and retrospective studies have suggested that treating OSA may improve ILD-related outcomes, but prospective studies are lacking in this field. Correspondence to Dr Brian D. Kent, Sleep Disorders Centre, Guy's Hospital, London SE1 9RT, United Kingdom. E-mail: briankent@physicians.ie Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A contemporary review of obstructive sleep apnea Purpose of review The current review provides a contemporary review of sleep apnea with emphasis on definitions, epidemiology, and consequences. Recent findings Amyloid β-42 is one of the main peptides forming amyloid plaques in the brains of Alzheimer patients. Poorer sleep quality and shorter sleep duration have been associated with a higher amyloid burden. Decreased sleep time in the elderly is a precipitating factor in amyloid retention. Studies have shown that the dysregulation of the homeostatic balance of the major inhibitory and excitatory amino acid neurotransmitter systems of gamma-aminobutyric acid and glutamate play a role in sleep disordered breathing (SDB). Summary Untreated SDB [obstructive sleep apnea (OSA) and/or central sleep apnea] are an important cause of medical mortality and morbidity. OSA is characterized by recurrent episodes of partial or complete collapse of the upper airway during sleep followed by hypoxia and sympathetic activation. Apneic events are terminated by arousal, followed by increases in pulse and blood pressure, and reoxygenation and the release of inflammatory factors. Individuals with OSA have an increased risk of developing atrial fibrillation. Hypoxemia and poor sleep quality due to OSA increase the risk of cognitive decline in the elderly. Correspondence to Frank Ralls, MD, Associate Professor of Internal Medicine, University of New Mexico; Program Director, UNM Sleep Medicine Fellowship; Medical Director, University Hospital Sleep Disorders Center, 1101 Medical Arts Avenue NE, Building 2, Albuquerque, NM 87102, USA. Tel: +1 505 272 6110; fax: +1 505 272 6112; e-mail: FRalls@salud.unm.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Prevention of transmission of Mycobacterium abscessus among patients with cystic fibrosis Purpose of review Pulmonary nontuberculous mycobacterial (NTM) infection is recognized as one of the most challenging infections to treat among cystic fibrosis patients. The source of NTM infection, modes of transmission, and exposure risks are poorly understood. Healthcare-associated transmission of Mycobacterium abscessus among cystic fibrosis patients has been suspected and is a growing concern for cystic fibrosis centers worldwide. This review describes our current understanding of prevention of healthcare-associated transmission of M. abscessus among patients with cystic fibrosis. Recent findings Multiple healthcare-associated outbreaks of M. abscessus among cystic fibrosis patients within cystic fibrosis care centers have been reported. The percentage of patients involved in the reported outbreaks, as well as the perceived impact of patient-to-patient transmission varies dramatically between the reporting centers and population surveys. Several groups have now proposed M. abscessus-specific measures to limit future outbreaks. Summary Improved NTM surveillance combined with a standardized, systematic approach to epidemiologic investigation of potential episodes of healthcare-associated transmission will help to reveal risk factors for NTM acquisition and inform future evidence-based infection prevention and control measures for patients with cystic fibrosis. Correspondence to Jane E. Gross, MD, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. E-mail: grossjane@njhealth.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Cardiovascular consequences of obstructive sleep apnea in different study models and novel perspectives Purpose of review Obstructive sleep apnea (OSA) is heterogeneous in terms of contributing pathophysiological mechanisms, clinical presentation, and consequences. Different study models from animal models of intermittent hypoxia over case-control, cohort, and population-based observational studies to uncontrolled interventional and randomized controlled interventional trials have contributed to the knowledge base. Controversial findings on underlying mechanisms and consequences of untreated OSA have challenged the field and resulted in uncertainty in treatment recommendations. Recent findings The heterogeneity of OSA in pathogenesis and clinical outcomes and strengths and limitations of different study models and designs used for studying OSA pathophysiology and cardiovascular consequences are discussed on the background of controversial findings on cardiovascular outcomes in OSA. In addition, recent findings from randomized controlled continuous positive airway pressure therapy withdrawal trials, an efficient and controlled study model, are highlighted. Summary Novel designs for clinical trials on long-term outcomes in the highly prevalent patient group with OSA addressing the heterogeneity in underlying mechanisms, different phenotypes in terms of cardiovascular risk, and new treatment concepts are needed to improve clinical practice standards. Correspondence to Esther I. Schwarz, Department of Pulmonology and Sleep Disorders Centre, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland. Tel: +41 44 255 38 28; fax: +41/44 255 44 51; e-mail: estherirene.schwarz@usz.ch Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Diagnosis and management of nonrapid eye movement-parasomnias Purpose of review Nonrapid eye movement (NREM) parasomnias are common sleep disorders that potentially have significant personal, social and forensic implications. They represent a unique opportunity in nature to explore the coexistence of sleep and wake-state in the human brain. Recent findings Neuroimaging and electroencephalography have advanced our understanding of NREM-parasomnia pathophysiology, and the interplay between wakefulness and sleep. These disorders are increasingly viewed as resulting from an evolutionary process with a basis in uni-hemispheric brain activity in sleep seen in some animals, maintaining consciousness and ability to act against life-threatening situations. Although current classification of NREM parasomnia phenotypes distinguishes between disorders of arousal and other types of behaviours, evidence increasingly points to there being a significant overlap between the various phenotypes. Treatment practice appears more standardized nowadays based on larger case series, but randomized control trials are still needed. Summary NREM-parasomnia is a very common disorder of uncertain pathogenesis but of known pathophysiology, the diagnosis of which remains primarily clinical. Correspondence to Panagis Drakatos, Sleep Disorders Centre, Guy's Hospital, 1st Floor, Nuffield House, Great Maze Pond, London SE1 9RT, UK. Tel: +44 2071853390; fax: +44 2071886114; e-mail: panagis.drakatos@gstt.nhs.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Anti-alarmin approaches entering clinical trials Purpose of review The alarmins, thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33, are upstream regulators of T2 (type 2) inflammation and found to be expressed at high levels in airway epithelium of patients with T2 asthma. This review will summarize how alarmins regulate the inflamed asthmatic airways through previously described and newly identified mechanisms. Recent findings Alarmins drive allergic and nonallergic asthma through activation of innate lymphoid cell 2 (ILC2), which are a rich source of cytokines such as IL-5 and IL-13, with resulting effects on eosinophilopoeisis and remodelling, respectively. Findings from bronchial allergen challenges have illustrated widespread expression of alarmins and their receptors across many effector cells in airways, and recent studies have emphasized alarmin regulation of CD4+ T lymphocytes, eosinophils and basophils, and their progenitors. Furthermore, a link between alarmins and lipid mediators is being uncovered. Summary Alarmins can drive well defined inflammatory pathways through activation of dendritic cells and polarizing T cells to produce type 2 cytokines, as well as they can directly activate many other effector cells that play a central role in allergic and nonallergic asthma. Clinical trials support a central role for TSLP in driving airway inflammation and asthma exacerbations, while ongoing trials blocking IL-33 and IL-25 will help to define their respective role in asthma. Correspondence to Gail M. Gauvreau, McMaster University, 1200 Main St W., HSC 3U26, Hamilton, ON L8N 3Z5, Canada. Tel: +1 905 525 9140 x22791; e-mail: gauvreau@mcmaster.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.