Asthma and air pollution: recent insights in pathogenesis and clinical implications Purpose of review Air pollution has adverse effects on the onset and morbidity of respiratory diseases, including asthma. In this review, we discuss recent insights into the effects of air pollution on the incidence and exacerbation of asthma. We focus on epidemiological studies that describe the association between air pollution exposure and development, mortality, persistence and exacerbations of asthma among different age groups. Moreover, we also provide an update on translational studies describing the mechanisms behind this association. Recent findings Mechanisms linking air pollutants such as particulate matter, nitrogen dioxide (NO2) and ozone to the development and exacerbation of asthma include the induction of both eosinophilic and neutrophilic inflammation driven by stimulation of airway epithelium and increase of pro-inflammatory cytokine production, oxidative stress and DNA methylation changes. Although exposure during foetal development is often reported as a crucial timeframe, exposure to air pollution is detrimental in people of all ages, thus influencing asthma onset as well as increase in asthma prevalence, mortality, persistence and exacerbation. Summary In conclusion, this review highlights the importance of reducing air pollution levels to avert the progressive increase in asthma incidence and morbidity. Correspondence to Guy Joos, Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Medical Research Building (MRBII), 2nd Floor, Corneel Heymanslaan 10, 9000, Ghent, Belgium. Tel: +32 93322611; e-mail: guy.joos@ugent.be Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Can training induce inflammatory control in asthma, or is it symptom control only? Purpose of review Exercise has shown to reduce asthma symptoms; however, the underlying mechanism for this improvement remains unclear. Improvement in inflammatory control could be the reason for this reduction in symptoms. This review discusses recent studies evaluating the effect of exercise on inflammatory control in patients with asthma. Recent findings New studies support that exercise is well tolerated and feasible regardless of intensity. Exercise seems to improve systemic low-grade inflammation, but consistency lacks when it comes to reduction in airway inflammation. Summary Physical exercise as an adjuvant therapy leads to improvement in asthma symptoms and asthma-related quality of life and should be recommended for all patients with asthma. Correspondence to Anders Pitzner-Fabricius, MD, Centre for Physical Activity Research, Rigshospitalet, Section 7641, Blegdamsvej 9, 2100 Copenhagen, Denmark. Tel: +45 2163 0502; e-mail: Anders.Pitzner-Fabricius@regionh.dk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Asthma: a modifiable disease on a crossroad No abstract available

Household air pollution in India and respiratory diseases: current status and future directions Purpose of review Combustion of solid cooking fuels employed by more than3 billion people globally, contributes to approximately one third of ambient air pollution. In the recent past, the issue has drawn global attention because of its threat to the health of rural communities, particularly women and children. This review is focused on the evidence from India on effects of household air pollution (HAP) on respiratory health and interventions to replace the solid fuels. Recent findings HAP exposure is a major risk factor for increased respiratory symptoms, respiratory infections, and chronic obstructive pulmonary disease. In most studies, the odds ratio for the risk of development of respiratory disorders is more than one in HAP exposed individuals. HAP is also associated with increased risk of tuberculosis, asthma, mortality from cardio-respiratory illnesses, and nonrespiratory problems such as adverse pregnancy outcomes, prematurity, and low birth weight. Summary Household air pollution is a common but preventable risk factor for respiratory diseases. Replacement of solid cooking fuels with clean fuels such as LPG gas as exemplified by the ‘Ujjwala’ program of India is likely to be most effective intervention to reduce the HAP related disease burden. Correspondence to Surinder K. Jindal, Medical Director, Jindal Clinics, SCO 21, Sector 20 D, Chandigarh, India 160020. Tel: +9172 4911000; e-mail: dr.skjindal@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The role of genomic profiling in identifying molecular phenotypes in obstructive lung diseases Purpose of review The biology underlying asthma and chronic obstructive pulmonary disease (COPD) is heterogeneous. Targeting therapies to patient subgroups, or ‘molecular phenotypes’, based on their underlying biology is emerging as an efficacious treatment strategy. This review summarizes the role of airway sample gene expression profiling in understanding molecular phenotypes in obstructive lung disease. Recent findings Recent gene expression studies have reinforced the importance of Type two (T2) inflammation in asthma and COPD subgroups. Studies in asthma also suggest that the molecular phenotype with enhanced T2 inflammation is itself heterogeneous with a subgroup that has steroid-refractory inflammation. Other inflammatory pathways are also emerging as implicated in asthma and COPD molecular phenotypes, including Type one and Type 17 adaptive immune responses and proinflammatory cytokines, such as interleukin-6. Summary Genomic profiling studies are advancing our understanding of the complex biology contributing to asthma and COPD molecular phenotypes. Recent studies suggest that asthma and COPD subgroups may benefit from different treatment strategies than those currently in practice. Correspondence to Stephanie A. Christenson, Assistant Professor, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, 505 Parnassus Ave, M1292, San Francisco, CA 94118, USA. E-mail: Stephanie.christenson@ucsf.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Asthma–COPD overlap: review of diagnosis and management Purpose of review Asthma and chronic obstructive pulmonary disease are both commonly encountered respiratory conditions. The term asthma--COPD overlap (ACO) has been used to identify patients presenting with features of both conditions. Controversy exists regarding its definition, approach to diagnosis and management. In this publication, recent evidence has been reviewed that provides insight into diagnosis and management of this condition. Recent findings Previously, multiple criteria were used to define Asthma--COPD overlap. In this publication, the most recent guidelines to identify this condition have been reviewed. This publication provides a summary of the recent evidence with regard to the role of various diagnostic modalities including the use of biomarkers, such as exhaled nitric oxide, serum IgE and provides updated evidence on available treatment choices for this condition. Summary ACO is a commonly encountered clinical condition with patients experiencing frequent exacerbations and resulting in increased healthcare resource utilization. Recent interest in ACO has led to development of a framework towards diagnosis and management of this condition. Therapeutic choices for ACO range from bronchodilator therapy to immunomodulatory therapy, highlighting the heterogeneity of this condition. Additional research is required to improve understanding of pathogenesis and improve outcomes in ACO. Correspondence to Anand N. Venkata, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301W. Markham Street #555, Little Rock, AR 72205, USA. Tel: +1 501 686 5525; e-mail: Avenkata@uams.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The different faces of the macrophage in asthma Purpose of review Asthma is a chronic inflammatory disease in which changes in macrophage polarization have been shown to contribute to the pathogenesis. The present review discusses the contribution of changes in macrophage function to asthma related to polarization changes and elaborates on possible therapeutic strategies targeting macrophage function and polarization. Recent findings Macrophage function alterations were shown to contribute to asthma pathology in several ways. One is by impaired phagocytosis and efferocytosis. Another is by changing inflammation, by altered (anti)inflammatory cytokine production and induction of the inflammasome. Finally, macrophages can contribute to remodeling in asthma, although little evidence is present in humans yet. Novel therapeutic strategies targeting macrophages include dampening inflammation by changing polarization or by inhibiting the NLRP3 inflammasome, and by targeting efferocytosis. However, many of these studies were performed in animal models leaving their translation to the clinic for future research. Summary The present review emphasizes the contribution of altered macrophage function to asthma, gives insight in possible new therapeutic strategies targeting macrophages, and indicates which knowledge gaps remain open. Correspondence to Barbro N. Melgert, Department of Molecular Pharmacology, Groningen Research Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. Tel: +31-50-3632947; e-mail: b.n.melgert@rug.nl This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Long and winding road: from infant wheeze to adult asthma Purpose of review This review aims to recognize the multifactorial cause of asthma, from the influence of mother until adulthood, highlight the main characteristics of the disease at different ages and summarize the evidence of potential prevention strategies. Recent findings To date, regarding the prenatal period, the presence of specific genes, maternal asthma, drugs, and tobacco exposure are the most relevant predisposing features for an asthmatic offspring. For newborns, preterm, bronchopulmonary dysplasia, and low birth weight has been associated with low lung function. Among young children, atopic dermatitis, lower respiratory tract infections, and increased levels of total Immunoglobulin E (IgE) and allergen-specific IgE are important determinants. Breastfeeding has been demonstrated being protective for the onset of asthma. Allergen immunotherapy has also been shown to have significant preventive effect decreasing asthma development. Inhaled corticosteroids use in early childhood prevents exacerbations but does not alter the natural history of asthma. Other interventions, such as the use of palivizumab, probiotics, vitamin D supplementation, and fish consumption presented controversial results. Summary A good knowledge of risk factors for asthma development, from prenatal period to adulthood, may lead to efficacious preventive strategies. Further data of long-term follow-up in population-based studies according to different phenotypes are needed. Correspondence to Silvia Sánchez-García, MD, PhD, Allergy Department, Hospital Infantil Universitario Niño Jesús, Avda Menendez Pelayo 65, 28009 Madrid, Spain. Tel: +34 91 503 59 35; e-mail: ssanchez@salud.madrid.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Epithelial dysfunction in chronic respiratory diseases, a shared endotype? Purpose of review Epithelial barrier defects are being appreciated in various inflammatory disorders; however, causal underlying mechanisms are lacking. In this review, we describe the disruption of the airway epithelium with regard to upper and lower airway diseases, the role of epigenetic alterations underlying this process, and potential novel ways of interfering with dysfunctional epithelial barriers as a novel therapeutic approach. Recent findings A defective epithelial barrier, impaired innate defence mechanisms or hampered epithelial cell renewal are found in upper and lower airway diseases. Barrier dysfunction might facilitate the entrance of foreign substances, initiating and facilitating the onset of disease. Latest data provided novel insights for possible involvement of epigenetic alterations induced by inflammation or other unknown mechanisms as a potential mechanism responsible for epithelial defects. Additionally, these mechanisms might precede disease development, and represent a novel therapeutic approach for restoring epithelial defects. Summary A better understanding of the role of epigenetics in driving and maintaining epithelial defects in various inflammatory diseases, using state-of-the-art biology tools will be crucial in designing novel therapies to protect or reconstitute a defective airway epithelial barrier. Correspondence to Brecht Steelant, PhD, KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, Herestraat 49, box 811, 3000 Leuven, Belgium. Tel: +32 16 34 61 65; fax: +32 16 34 60 35; e-mail: brecht.steelant@kuleuven.be Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Small airway disease in chronic obstructive pulmonary disease: insights and implications for the clinician Purpose of review Small airway disease (SAD) is a common feature in chronic obstructive pulmonary disease (COPD) patients. Chronic exposure to cigarette smoking causes inflammation, damage, tissue remodelling and eventually airway loss. These features lead to airflow limitation and defective alveolar ventilation. The aim of this review is to provide clinicians with an up-to-date perspective of SAD in COPD. Recent findings In this review, we will discuss the key pathological features of SAD. We also review state-of-the-art techniques for measuring SAD, including impulse oscillometry and lung imaging methods. We discuss emerging concepts such as SAD in the earlier stages of COPD and the relationship between SAD and emphysema. Summary The current review highlights the importance of targeting small airways early in the course of COPD to tackle disease progression. Correspondence to Dave Singh, The University of Manchester, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, UK. Tel: +44 161 946 4050; e-mail: DSingh@meu.org.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.