Portal de Periódicos da CAPES

Obesity and asthma

2018; Elsevier BV; Volume: 141; Issue: 4 Linguagem: Inglês

10.1016/j.jaci.2018.02.004

1097-6825

Ubong Peters, Anne E. Dixon, Erick Forno,

IL-33, ST2, and ILC Pathways

Information for Category 1 CME CreditCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted.Date of Original Release: April 2018. Credit may be obtained for these courses until March 31, 2019.Copyright Statement: Copyright © 2018-2019. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Ubong Peters, PhD, Anne E. Dixon, MA, BM, BCh, and Erick Forno, MD, MPH (authors); Andrea Apter, MD, MA, MSc (editor)Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: A. E. Dixon has received grants from the National Institutes of Health, the American Lung Association, and Pfizer and has received personal fees from Vitaeris. The rest of the authors declare that they have no relevant conflicts of interest. A. Apter (editor) declares that she has no relevant conflicts of interest.Activity Objectives:1.To understand the role that obesity plays as a risk factor for and disease modifier of asthma.2.To identify the mechanisms involved in asthma pathogenesis.3.To understand the evidence supporting lifestyle changes in influencing disease progression.4.To identify the clinical characteristics of obese asthma in children and adults.Recognition of Commercial Support: This CME activity has not received external commercial support.List of CME Exam Authors: Gagandeep Cheema, MD, Erica Ridley, MD, Eliane Abou-Jaoude, MD, and Christian Nageotte, MD.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The exam authors disclosed no relevant financial relationships.Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk, and obese asthmatic patients have more symptoms, more frequent and severe exacerbations, reduced response to several asthma medications, and decreased quality of life. Obese asthma is a complex syndrome, including different phenotypes of disease that are just beginning to be understood. We examine the epidemiology and characteristics of this syndrome in children and adults, as well as the changes in lung function seen in each age group. We then discuss the better recognized factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, and the genetics/genomics of obese asthma. Finally, we describe current evidence on the effect of weight loss and mention some important future directions for research in the field. Information for Category 1 CME CreditCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted.Date of Original Release: April 2018. Credit may be obtained for these courses until March 31, 2019.Copyright Statement: Copyright © 2018-2019. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Ubong Peters, PhD, Anne E. Dixon, MA, BM, BCh, and Erick Forno, MD, MPH (authors); Andrea Apter, MD, MA, MSc (editor)Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: A. E. Dixon has received grants from the National Institutes of Health, the American Lung Association, and Pfizer and has received personal fees from Vitaeris. The rest of the authors declare that they have no relevant conflicts of interest. A. Apter (editor) declares that she has no relevant conflicts of interest.Activity Objectives:1.To understand the role that obesity plays as a risk factor for and disease modifier of asthma.2.To identify the mechanisms involved in asthma pathogenesis.3.To understand the evidence supporting lifestyle changes in influencing disease progression.4.To identify the clinical characteristics of obese asthma in children and adults.Recognition of Commercial Support: This CME activity has not received external commercial support.List of CME Exam Authors: Gagandeep Cheema, MD, Erica Ridley, MD, Eliane Abou-Jaoude, MD, and Christian Nageotte, MD.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The exam authors disclosed no relevant financial relationships.Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk, and obese asthmatic patients have more symptoms, more frequent and severe exacerbations, reduced response to several asthma medications, and decreased quality of life. Obese asthma is a complex syndrome, including different phenotypes of disease that are just beginning to be understood. We examine the epidemiology and characteristics of this syndrome in children and adults, as well as the changes in lung function seen in each age group. We then discuss the better recognized factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, and the genetics/genomics of obese asthma. Finally, we describe current evidence on the effect of weight loss and mention some important future directions for research in the field. Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions. Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted. Date of Original Release: April 2018. Credit may be obtained for these courses until March 31, 2019. Copyright Statement: Copyright © 2018-2019. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Ubong Peters, PhD, Anne E. Dixon, MA, BM, BCh, and Erick Forno, MD, MPH (authors); Andrea Apter, MD, MA, MSc (editor) Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: A. E. Dixon has received grants from the National Institutes of Health, the American Lung Association, and Pfizer and has received personal fees from Vitaeris. The rest of the authors declare that they have no relevant conflicts of interest. A. Apter (editor) declares that she has no relevant conflicts of interest. Activity Objectives:1.To understand the role that obesity plays as a risk factor for and disease modifier of asthma.2.To identify the mechanisms involved in asthma pathogenesis.3.To understand the evidence supporting lifestyle changes in influencing disease progression.4.To identify the clinical characteristics of obese asthma in children and adults. Recognition of Commercial Support: This CME activity has not received external commercial support. List of CME Exam Authors: Gagandeep Cheema, MD, Erica Ridley, MD, Eliane Abou-Jaoude, MD, and Christian Nageotte, MD. Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: The exam authors disclosed no relevant financial relationships. Obesity is both a major risk factor and a disease modifier of asthma in children and adults. Although obesity is defined according to a threshold body mass index (BMI), recent studies suggest that BMI z scores might be unreliable, particularly among children and adolescents with severe obesity.1Freedman D.S. Butte N.F. Taveras E.M. Lundeen E.A. Blanck H.M. Goodman A.B. et al.BMI z-scores are a poor indicator of adiposity among 2- to 19-year-olds with very high BMIs, NHANES 1999-2000 to 2013-2014.Obesity (Silver Spring). 2017; 25: 739-746Crossref PubMed Scopus (66) Google Scholar, 2Freedman D.S. Butte N.F. Taveras E.M. Goodman A.B. Ogden C.L. Blanck H.M. The limitations of transforming very high body mass indexes into z-scores among 8.7 million 2- to 4-year-old children.J Pediatr. 2017; 188: 50-56.e1Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 3Peterson C.M. Su H. Thomas D.M. Heo M. Golnabi A.H. Pietrobelli A. et al.Tri-ponderal mass index vs body mass index in estimating body fat during adolescence.JAMA Pediatr. 2017; 171: 629-636Crossref PubMed Scopus (2) Google Scholar In adults obesity is defined as a BMI of 30 kg/m2 or greater, yet a given BMI might reflect vastly differing physiology and metabolic health. This distinction is likely important for asthma. Although serum IL-6 (produced by macrophages in adipose tissue and a marker of metabolic health) is a marker of asthma severity, some subjects with BMIs in the nonobese range have increased IL-6 levels4Peters M.C. McGrath K.W. Hawkins G.A. Hastie A.T. Levy B.D. Israel E. et al.Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts.Lancet Respir Med. 2016; 4: 574-584Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar; Sideleva et al5Sideleva O. Suratt B.T. Black K.E. Tharp W.G. Pratley R.E. Forgione P. et al.Obesity and asthma: an inflammatory disease of adipose tissue not the airway.Am J Respir Crit Care Med. 2012; 186: 598-605Crossref PubMed Scopus (141) Google Scholar found that adipose tissue inflammation is increased in obese patients with asthma compared with obese control subjects. Metabolic dysfunction is more important than fat mass for asthma in obesity; however, most asthma studies have used BMI and metabolic dysfunction related to obesity synonymously. In this article we will report data on metabolic dysfunction, where available, but will otherwise use obesity as a marker of both fat mass and metabolic dysfunction. Asthma affects approximately 6.5 million children (approximately 9% prevalence) in the United States.6Asthma data, statistics, and surveillance. 2016. Available at: http://www.cdc.gov/asthma/most_recent_data.htm. Accessed December 14, 2017.Google Scholar Likewise, 17% of children in this country are obese, and another 15% are overweight.7Childhood Obesity. 2016. Available at: https://www.cdc.gov/obesity/childhood/index.html. Accessed December 14, 2017.Google Scholar Obesity is now recognized as a major risk factor for asthma: several longitudinal epidemiologic studies show that obesity or increased adiposity often precedes incident asthma.8Gilliland F.D. Berhane K. Islam T. McConnell R. Gauderman W.J. Gilliland S.S. et al.Obesity and the risk of newly diagnosed asthma in school-age children.Am J Epidemiol. 2003; 158: 406-415Crossref PubMed Scopus (300) Google Scholar, 9Gold D.R. Damokosh A.I. Dockery D.W. Berkey C.S. Body-mass index as a predictor of incident asthma in a prospective cohort of children.Pediatr Pulmonol. 2003; 36: 514-521Crossref PubMed Scopus (181) Google Scholar, 10Mannino D.M. Mott J. Ferdinands J.M. Camargo C.A. Friedman M. Greves H.M. et al.Boys with high body masses have an increased risk of developing asthma: findings from the National Longitudinal Survey of Youth (NLSY).Int J Obes (Lond). 2006; 30: 6-13Crossref PubMed Scopus (128) Google Scholar, 11Mamun A.A. Lawlor D.A. Alati R. O'Callaghan M.J. Williams G.M. Najman J.M. Increasing body mass index from age 5 to 14 years predicts asthma among adolescents: evidence from a birth cohort study.Int J Obes (Lond). 2007; 31: 578-583Crossref PubMed Scopus (0) Google Scholar, 12Zhang Z. Lai H.J. Roberg K.A. Gangnon R.E. Evans M.D. Anderson E.L. et al.Early childhood weight status in relation to asthma development in high-risk children.J Allergy Clin Immunol. 2010; 126: 1157-1162Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 13Weinmayr G. Forastiere F. Buchele G. Jaensch A. Strachan D.P. Nagel G. et al.Overweight/obesity and respiratory and allergic disease in children: international study of asthma and allergies in childhood (ISAAC) phase two.PLoS One. 2014; 9: e113996Crossref PubMed Scopus (50) Google Scholar, 14Mebrahtu T.F. Feltbower R.G. Greenwood D.C. Parslow R.C. Childhood body mass index and wheezing disorders: a systematic review and meta-analysis.Pediatr Allergy Immunol. 2015; 26: 62-72Crossref PubMed Scopus (16) Google Scholar, 15Ho W.C. Lin Y.S. Caffrey J.L. Lin M.H. Hsu H.T. Myers L. et al.Higher body mass index may induce asthma among adolescents with pre-asthmatic symptoms: a prospective cohort study.BMC Public Health. 2011; 11: 542Crossref PubMed Scopus (30) Google Scholar, 16Flaherman V. Rutherford G.W. A meta-analysis of the effect of high weight on asthma.Arch Dis Child. 2006; 91: 334-339Crossref PubMed Scopus (209) Google Scholar Many studies have reported differing obesity-asthma associations by sex,10Mannino D.M. Mott J. Ferdinands J.M. Camargo C.A. Friedman M. Greves H.M. et al.Boys with high body masses have an increased risk of developing asthma: findings from the National Longitudinal Survey of Youth (NLSY).Int J Obes (Lond). 2006; 30: 6-13Crossref PubMed Scopus (128) Google Scholar, 17Willeboordse M. van den Bersselaar D.L. van de Kant K.D. Muris J.W. van Schayck O.C. Dompeling E. Sex differences in the relationship between asthma and overweight in Dutch children: a survey study.PLoS One. 2013; 8: e77574Crossref PubMed Google Scholar, 18Lu K.D. Billimek J. Bar-Yoseph R. Radom-Aizik S. Cooper D.M. Anton-Culver H. Sex differences in the relationship between fitness and obesity on risk for asthma in adolescents.J Pediatr. 2016; 176: 36-42Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar, 19Maltz L. Matz E.L. Gordish-Dressman H. Pillai D.K. Teach S.J. Camargo Jr., C.A. et al.Sex differences in the association between neck circumference and asthma.Pediatr Pulmonol. 2016; 51: 893-900Crossref PubMed Scopus (3) Google Scholar, 20Castro-Rodriguez J.A. A new childhood asthma phenotype: obese with early menarche.Paediatr Respir Rev. 2016; 18: 85-89Crossref PubMed Google Scholar although results on which sex is more affected have been conflicting. Obesity is also associated with increased asthma severity. Obesity-induced increases in asthma risk can start in utero. In a meta-analysis of more than 108,000 participants, we found that maternal obesity and weight gain during pregnancy are independently associated with approximately 15% to 30% increased risk of asthma in the offspring, and others have reported very similar findings.21Forno E. Young O.M. Kumar R. Simhan H. Celedon J.C. Maternal obesity in pregnancy, gestational weight gain, and risk of childhood asthma.Pediatrics. 2014; 134: e535-e546Crossref PubMed Scopus (79) Google Scholar, 22Dumas O. Varraso R. Gillman M.W. Field A.E. Camargo Jr., C.A. Longitudinal study of maternal body mass index, gestational weight gain, and offspring asthma.Allergy. 2016; 71: 1295-1304Crossref PubMed Scopus (18) Google Scholar This risk is not merely mediated by the child's own obesity.23Harskamp-van Ginkel M.W. London S.J. Magnus M.C. Gademan M.G. Vrijkotte T.G. A study on mediation by offspring BMI in the association between maternal obesity and child respiratory outcomes in the Amsterdam Born and Their Development study cohort.PLoS One. 2015; 10: e0140641Crossref PubMed Google Scholar Mechanisms involved can include inflammatory or other changes during pregnancy or early postnatal life,24Malti N. Merzouk H. Merzouk S.A. Loukidi B. Karaouzene N. 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De Marco L. et al.Infant weight trajectories and early childhood wheezing: the NINFEA birth cohort study.Thorax. 2016; 71: 1091-1096Crossref PubMed Scopus (4) Google Scholar, 28Casas M. den Dekker H.T. Kruithof C.J. Reiss I.K. Vrijheid M. de Jongste J.C. et al.Early childhood growth patterns and school-age respiratory resistance, fractional exhaled nitric oxide and asthma.Pediatr Allergy Immunol. 2016; 27: 854-860Crossref PubMed Scopus (4) Google Scholar A meta-analysis of several prospective studies involving more than 300,000 adults found a dose-response relationship between obesity and asthma: the odds ratio of incident asthma was 1.5 in the overweight and 1.9 in the obese groups compared with the lean group; in effect, 250,000 new asthma cases per year in the United States are related to obesity.29Beuther D.A. Sutherland E.R. Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies.Am J Respir Crit Care Med. 2007; 175: 661-666Crossref PubMed Scopus (654) Google Scholar This relationship has radically changed the demographics of asthma in the United States: the prevalence of asthma in lean adults is 7.1%, and that in obese adults is 11.1%. The relationship is more striking in women; the prevalence of asthma in lean versus obese women is 7.9% and 14.6%, respectively.30Akinbami L.J. Fryar C.D. Asthma prevalence by weight status among adults: United States, 2001-2014. NCHS data brief, no 239. National Center for Health Statistics, Hyattsville (MD)2016Google Scholar On occasion, asthma can predispose to obesity,31Chen Z. Salam M.T. Alderete T.L. Habre R. Bastain T.M. Berhane K. et al.Effects of childhood asthma on the development of obesity among school-aged children.Am J Respir Crit Care Med. 2017; 195: 1181-1188Crossref PubMed Scopus (36) Google Scholar obesity can confound its diagnosis,32Lang J.E. Hossain J. Holbrook J.T. Teague W.G. Gold B.D. Wise R.A. et al.Gastro-oesophageal reflux and worse asthma control in obese children: a case of symptom misattribution?.Thorax. 2016; 71: 238-246Crossref PubMed Scopus (7) Google Scholar, 33Lang J.E. Hossain M.J. Lima J.J. Overweight children report qualitatively distinct asthma symptoms: analysis of validated symptom measures.J Allergy Clin Immunol. 2015; 135: 886-893.e3Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar or both can simply co-occur. However, the majority of observational and experimental evidence points to an “obese asthma” phenotype in which obesity modifies asthma.34Lang J.E. Hossain J. Dixon A.E. Shade D. Wise R.A. 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Sen S. et al.Childhood obesity and asthma control in the GALA II and SAGE II studies.Am J Respir Crit Care Med. 2013; 187: 697-702Crossref PubMed Scopus (77) Google Scholar Many obese children with asthma tend to have TH1-skewed responses, particularly in response to inflammatory stimuli, with at least part of these responses mediated by systemic inflammation, insulin resistance, and/or alterations in lipid metabolism.41Eising J.B. Uiterwaal C.S. Evelein A.M. Visseren F.L. van der Ent C.K. Relationship between leptin and lung function in young healthy children.Eur Respir J. 2014; 43: 1189-1192Crossref PubMed Google Scholar, 42Rastogi D. Fraser S. Oh J. Huber A.M. Schulman Y. Bhagtani R.H. et al.Inflammation, metabolic dysregulation, and pulmonary function among obese urban adolescents with asthma.Am J Respir Crit Care Med. 2015; 191: 149-160Crossref PubMed Scopus (66) Google Scholar, 43Vinding R.K. Stokholm J. Chawes B.L. Bisgaard H. Blood lipid levels associate with childhood asthma, airway obstruction, bronchial hyperresponsiveness, and aeroallergen sensitization.J Allergy Clin Immunol. 2016; 137: 68-74.e4Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar These children and adolescents also tend to have a decreased response to asthma medications. Using data from the Childhood Asthma Management Program (CAMP), we described that overweight and obese children with asthma had a reduced response to inhaled corticosteroids (ICSs), leading to increased prednisone courses and moderate-to-severe exacerbations.44Forno E. Lescher R. Strunk R. Weiss S. Fuhlbrigge A. Celedon J.C. et al.Decreased response to inhaled steroids in overweight and obese asthmatic children.J Allergy Clin Immunol. 2011; 127: 741-749Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar More recently, McGarry et al45McGarry M.E. Castellanos E. Thakur N. Oh S.S. Eng C. Davis A. et al.Obesity and bronchodilator response in black and Hispanic children and adolescents with asthma.Chest. 2015; 147: 1591-1598Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar reported that obese black and Latino adolescents were 24% more likely to be bronchodilator unresponsive than their nonobese peers. Moreover, among children hospitalized for asthma, obesity is associated with longer length of stay and higher risk of mechanical ventilation.37Okubo Y. Nochioka K. Hataya H. Sakakibara H. Terakawa T. Testa M. Burden of obesity on pediatric in patients with acute asthma exacerbation in the United States.J Allergy Clin Immunol Pract. 2016; 4: 1227-1231Abstract Full Text Full Text PDF PubMed Google Scholar Obese children with asthma might also be more susceptible to having increased symptoms with exposure to indoor pollutants.46Lu K.D. Breysse P.N. Diette G.B. Curtin-Brosnan J. Aloe C. Williams D.L. et al.Being overweight increases susceptibility to indoor pollutants among urban children with asthma.J Allergy Clin Immunol. 2013; 131 (e1-3): 1017-1023Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Much like children, obese adults tend to have more severe asthma than lean adults, with a 4- to 6-fold higher risk of being hospitalized compared with lean adults with asthma.47Holguin F. Bleecker E.R. Busse W.W. Calhoun W.J. Castro M. Erzurum S.C. et al.Obesity and asthma: an association modified by age of asthma onset.J Allergy Clin Immunol. 2011; 127: 1486-1493.e2Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar Nearly 60% of adults with severe asthma in the United States are obese.48Schatz M. Hsu J.W. Zeiger R.S. Chen W. Dorenbaum A. Chipps B.E. et al.Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma.J Allergy Clin Immunol. 2014; 133: 1549-1556Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar Obese patients also have worse asthma control and lower quality of life.49Vortmann M. Eisner M.D. BMI and health status among adults with asthma.Obesity (Silver Spring). 2008; 16: 146-152Crossref PubMed Scopus (54) Google Scholar Obese asthmatic patients do not respond as well to standard controller medications, such as ICSs and ICS/long-acting β-agonist combination.50Boulet L.P. Franssen E. Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma.Respir Med. 2007; 101: 2240-2247Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar The mechanisms behind the impaired ICS response are likely related to increased production of inflammatory cytokines in obesity, which reduce induction of mitogen-activated kinase phosphatase 1 by glucocorticoid, a signaling protein that plays an important role in steroid responses.51Sutherland E.R. Goleva E. Strand M. Beuther D.A. Leung D.Y. Body mass and glucocorticoid response in asthma.Am J Respir Crit Care Med. 2008; 178: 682-687Crossref PubMed Scopus (204) Google Scholar Impaired response to asthma therapy in obesity is also due to the altered pathogenesis of disease, which does not respond well to medications developed to treat conventional allergic asthma. There are likely several phenotypes within the obese asthma syndrome (Fig 1). Holguin et al47Holguin F. Bleecker E.R. Busse W.W. Calhoun W.J. Castro M. Erzurum S.C. et al.Obesity and asthma: an association modified by age of asthma onset.J Allergy Clin Immunol. 2011; 127: 1486-1493.e2Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar reported that obese asthmatic patients with earlier-onset disease (who tended to have higher markers of TH2 inflammation) had the most severe disease among obese asthmatic patients. There is also a group with later-onset disease, most often female, with little in the way of airway inflammation but significant inflammation in adipose tissue and increased airway oxidative stress.5Sideleva O. Suratt B.T. Black K.E. Tharp W.G. Pratley R.E. Forgione P. et al.Obesity and asthma: an inflammatory disease of adipose tissue not the airway.Am J Respir Crit Care Med. 2012; 186: 598-605Crossref PubMed Scopus (141) Google Scholar Some have described a phenotype with neutrophilic airway inflammation,52Scott H.A. Gibson P.G. Garg M.L. Wood L.G. Airway inflammation is augmented by obesity and fatty acids in asthma.Eur Respir J. 2011; 38: 594-602Crossref PubMed Scopus (153) Google Scholar which improves with weight loss in women.53Scott H.A. Gibson P.G. Garg M.L. Pretto J.J. Morgan P.J. Callister R. et al.Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial.Clin Exp Allergy. 2013; 43: 36-49Crossref PubMed Scopus (117) Google Scholar Obese subjects appear to have increased susceptibility to air pollutants,54Dong G.H. Qian Z. Liu M.M. Wang D. Ren W.H. Fu Q. et al.Obesity enhanced respiratory health effects of ambient air pollution in Chinese children: the Seven Northeastern Cities study.Int J Obes (Lond). 2013;