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Overweight children report qualitatively distinct asthma symptoms: Analysis of validated symptom measures

Published:October 14, 2014DOI:https://doi.org/10.1016/j.jaci.2014.08.029

      Background

      Past studies of asthma in overweight/obese children have been inconsistent. The reason overweight/obese children commonly report worse asthma control remains unclear.

      Objective

      To determine qualitative differences in symptoms between lean and overweight/obese children with early-onset, atopic asthma.

      Methods

      We conducted a cross-sectional analytic study of lean (20% to 65% body mass index) and overweight/obese (≥85% body mass index) 10- to 17-year-old children with persistent, early-onset asthma. Participants completed 2 to 3 visits to provide a complete history, qualitative and quantitative asthma symptom characterization, and lung function testing. We determined associations between weight status and symptoms using multivariable linear and logistic regression methods.

      Results

      Overweight/obese and lean asthmatic children displayed similar lung function. Despite lower fraction of exhaled nitric oxide (30.0 vs 62.6 ppb; P = .037) and reduced methacholine responsiveness (PC20FEV1 1.87 vs 0.45 mg/mL; P < .012), overweight/obese children reported more than thrice frequent rescue treatments (3.7 vs 1.1 treatments/wk; P = .0002) than did lean children. Weight status affected the child's primary symptom reported with loss of asthma control (Fisher exact test; P = .003); overweight/obese children more often reported shortness of breath (odds ratio = 11.8; 95% CI, 1.41-98.7) and less often reported cough (odds ratio = 0.26; 95% CI, 0.08-0.82). Gastroesophageal reflux scores were higher in overweight/obese children (9.6 vs 23.2; P = .003) and appear to mediate overweight/obesity-related asthma symptoms.

      Conclusions

      Overweight/obese children with early-onset asthma display poorer asthma control and a distinct pattern of symptoms. Greater shortness of breath and β-agonist use appears to be partially mediated via esophageal reflux symptoms. Overweight children with asthma may falsely attribute exertional dyspnea and esophageal reflux to asthma, leading to excess rescue medication use.

      Key words

      Abbreviations used:

      ACQ6 (6-Item Asthma Control Questionnaire without the FEV1 component), ACT (Asthma Control Test), ASUI (Asthma Symptom Utility Index), BMI (Body mass index), Feno (Fraction of exhaled nitric oxide), GERD (Gastroesophageal reflux disease), MID (Minimally important difference), PAQLQ (Pediatric Asthma Quality of Life Questionnaire), SABA (Short-acting β-agonist)
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      References

        • Mannino 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 Obesity. 2006; 30: 6-13
        • Gold 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: 514-521
        • Black M.H.
        • Zhou H.
        • Takayanagi M.
        • Jacobsen S.J.
        • Koebnick C.
        Increased asthma risk and asthma-related health care complications associated with childhood obesity.
        Am J Epidemiol. 2013; 178: 1120-1128
        • Taylor B.
        • Mannino D.
        • Brown C.
        • Crocker D.
        • Twum-Baah N.
        • Holguin F.
        Body mass index and asthma severity in the National Asthma Survey.
        Thorax. 2008; 63: 14-20
        • Quinto K.B.
        • Zuraw B.L.
        • Poon K.Y.
        • Chen W.
        • Schatz M.
        • Christiansen S.C.
        The association of obesity and asthma severity and control in children.
        J Allergy Clin Immunol. 2011; 128: 964-969
        • Borrell L.N.
        • Nguyen E.A.
        • Roth L.A.
        • Oh S.S.
        • Tcheurekdjian H.
        • 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: 697-702
        • Forno E.
        • Lescher R.
        • Strunk R.
        • Weiss S.
        • Fuhlbrigge A.
        • Celedon J.C.
        Decreased response to inhaled steroids in overweight and obese asthmatic children.
        J Allergy Clin Immunol. 2011; 127: 741-749
        • Sideleva O.
        • Black K.
        • Dixon A.E.
        Effects of obesity and weight loss on airway physiology and inflammation in asthma.
        Pulm Pharmacol Ther. 2013; 26: 455-458
        • Schachter L.M.
        • Salome C.M.
        • Peat J.K.
        • Woolcock A.J.
        Obesity is a risk for asthma and wheeze but not airway hyperresponsiveness.
        Thorax. 2001; 56: 4-8
        • Ross K.R.
        • Hart M.A.
        • Storfer-Isser A.
        • Kibler A.M.
        • Johnson N.L.
        • Rosen C.L.
        • et al.
        Obesity and obesity related co-morbidities in a referral population of children with asthma.
        Pediatr Pulmonol. 2009; 44: 877-884
        • Tantisira K.G.
        • Litonjua A.A.
        • Weiss S.T.
        • Fuhlbrigge A.L.
        Association of body mass with pulmonary function in the Childhood Asthma Management Program (CAMP).
        Thorax. 2003; 58: 1036-1041
        • Dixon A.E.
        • Shade D.M.
        • Cohen R.I.
        • Skloot G.S.
        • Holbrook J.T.
        • Smith L.J.
        • et al.
        Effect of obesity on clinical presentation and response to treatment in asthma.
        J Asthma. 2006; 43: 553-558
        • Sah P.K.
        • Gerald Teague W.
        • Demuth K.A.
        • Whitlock D.R.
        • Brown S.D.
        • Fitzpatrick A.M.
        Poor asthma control in obese children may be overestimated because of enhanced perception of dyspnea.
        J Allergy Clin Immunol Pract. 2013; 1: 39-45
        • Tsai S.Y.
        • Ward T.
        • Lentz M.J.
        • Kieckhefer G.M.
        Daytime physical activity levels in school-age children with and without asthma.
        Nurs Res. 2012; 61: 252-259
        • Gennuso J.
        • Epstein L.H.
        • Paluch R.A.
        • Cerny F.
        The relationship between asthma and obesity in urban minority children and adolescents.
        Arch Pediatr Adolesc Med. 1998; 152: 1197-1200
        • Koenig K.
        Pilot study of low-income parents' perspectives of managing asthma in high-risk infants and toddlers.
        Pediatr Nurs. 2007; 33 (242): 223-228
        • van den Bemt L.
        • Kooijman S.
        • Linssen V.
        • Lucassen P.
        • Muris J.
        • Slabbers G.
        • et al.
        How does asthma influence the daily life of children? Results of focus group interviews.
        Health Qual Life Outcomes. 2010; 8: 5
        • Meng A.
        • McConnell S.
        Symptom perception and respiratory sensation: clinical applications.
        Nurs Clin N Am. 2003; 38: 737-748
        • Scano G.
        • Stendardi L.
        Dyspnea and asthma.
        Curr Opin Pulm Med. 2006; 12: 18-22
        • Lang J.E.
        • Hossain J.
        • Dixon A.E.
        • Shade D.
        • Wise R.A.
        • Peters S.P.
        • et al.
        Does age impact the obese asthma phenotype? Longitudinal asthma control, airway function, and airflow perception among mild persistent asthmatics.
        Chest. 2011; 140: 1524-1533
        • Krishnan J.A.
        • Lemanske Jr., R.F.
        • Canino G.J.
        • Elward K.S.
        • Kattan M.
        • Matsui E.C.
        • et al.
        Asthma outcomes: symptoms.
        J Allergy Clin Immunol. 2012; 129: S124-S135
        • Juniper E.F.
        Assessing asthma control.
        Curr Allergy Asthma Rep. 2007; 7: 390-394
        • Juniper E.F.
        • O'Byrne P.M.
        • Guyatt G.H.
        • Ferrie P.J.
        • King D.R.
        Development and validation of a questionnaire to measure asthma control.
        Eur Respir J. 1999; 14: 902-907
        • Juniper E.F.
        • Guyatt G.H.
        • Feeny D.H.
        • Ferrie P.J.
        • Griffith L.E.
        • Townsend M.
        Measuring quality of life in children with asthma.
        Qual Life Res. 1996; 5: 35-46
        • Bime C.
        • Wei C.Y.
        • Holbrook J.T.
        • Sockrider M.M.
        • Revicki D.A.
        • Wise R.A.
        Asthma symptom utility index: reliability, validity, responsiveness, and the minimal important difference in adult asthmatic patients.
        J Allergy Clin Immunol. 2012; 130: 1078-1084
        • Schatz M.
        • Sorkness C.A.
        • Li J.T.
        • Marcus P.
        • Murray J.J.
        • Nathan R.A.
        • et al.
        Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists.
        J Allergy Clin Immunol. 2006; 117: 549-556
        • Revicki D.A.
        • Leidy N.K.
        • Brennan-Diemer F.
        • Sorensen S.
        • Togias A.
        Integrating patient preferences into health outcomes assessment: the multiattribute Asthma Symptom Utility Index.
        Chest. 1998; 114: 998-1007
        • Parshall M.B.
        • Schwartzstein R.M.
        • Adams L.
        • Banzett R.B.
        • Manning H.L.
        • Bourbeau J.
        • et al.
        An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea.
        Am J Respir Crit Care Med. 2012; 185: 435-452
        • Troiano R.P.
        • Flegal K.M.
        • Kuczmarski R.J.
        • Campbell S.M.
        • Johnson C.L.
        Overweight prevalence and trends for children and adolescents. The National Health and Nutrition Examination Surveys, 1963 to 1991.
        Arch Pediatr Adolesc Med. 1995; 149: 1085-1091
      1. Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. 2000 CDC growth charts for the United States: methods and development. DHHS Publication No. (PHS) 2002-1696, 01–0617, National Center for Health Statistics, Hyattsville, MD: Vital Health Stat 2002;11:1-190.

        • Holbrook J.T.
        • Wise R.A.
        • Gold B.D.
        • Blake K.
        • Brown E.D.
        • Castro M.
        • et al.
        Lansoprazole for children with poorly controlled asthma: a randomized controlled trial.
        JAMA. 2012; 307: 373-381
        • Castro M.
        • King T.S.
        • Kunselman S.J.
        • Cabana M.D.
        • Denlinger L.
        • Holguin F.
        • et al.
        Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial.
        JAMA. 2014; 311: 2083-2091
        • National Asthma Education and Prevention Program
        Expert Panel Report 3: guidelines for the diagnosis and management of asthma.
        National Heart, Lung, and Blood Institute, Bethesda, Md2007
        • Crapo R.O.
        • Casaburi R.
        • Coates A.L.
        • Enright P.L.
        • Hankinson J.L.
        • Irvin C.G.
        • et al.
        Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999.
        Am J Respir Crit Care Med. 2000; 161: 309-329
        • Dweik R.A.
        • Boggs P.B.
        • Erzurum S.C.
        • Irvin C.G.
        • Leigh M.W.
        • Lundberg J.O.
        • et al.
        An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications.
        Am J Respir Crit Care Med. 2011; 184: 602-615
        • Nathan R.A.
        • Sorkness C.A.
        • Kosinski M.
        • Schatz M.
        • Li J.T.
        • Marcus P.
        • et al.
        Development of the asthma control test: a survey for assessing asthma control.
        J Allergy Clin Immunol. 2004; 113: 59-65
        • Schatz M.
        • Kosinski M.
        • Yarlas A.S.
        • Hanlon J.
        • Watson M.E.
        • Jhingran P.
        The minimally important difference of the Asthma Control Test.
        J Allergy Clin Immunol. 2009; 124: 719-723.e1
        • Juniper E.F.
        • Guyatt G.H.
        • Willan A.
        • Griffith L.E.
        Determining a minimal important change in a disease-specific Quality of Life Questionnaire.
        J Clin Epidemiol. 1994; 47: 81-87
        • Juniper E.F.
        • Guyatt G.H.
        • Feeny D.H.
        • Ferrie P.J.
        • Griffith L.E.
        • Townsend M.
        Measuring quality of life in the parents of children with asthma.
        Qual Life Res. 1996; 5: 27-34
        • Deal L.
        • Gold B.D.
        • Gremse D.A.
        • Winter H.S.
        • Peters S.B.
        • Fraga P.D.
        • et al.
        Age-specific questionnaires distinguish GERD symptom frequency and severity in infants and young children: development and initial validation.
        J Pediatr Gastroenterol Nutr. 2005; 41: 178-185
        • Miller M.R.
        • Hankinson J.
        • Brusasco V.
        • Burgos F.
        • Casaburi R.
        • Coates A.
        • et al.
        Standardisation of spirometry.
        Eur Respir J. 2005; 26: 319-338
        • Wanger J.
        • Clausen J.L.
        • Coates A.
        • Pedersen O.F.
        • Brusasco V.
        • Burgos F.
        • et al.
        Standardisation of the measurement of lung volumes.
        Eur Respir J. 2005; 26: 511-522
        • ATS/ERS
        ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005.
        Am J Respir Crit Care Med. 2005; 171: 912-930
        • Moore W.C.
        • Meyers D.A.
        • Wenzel S.E.
        • Teague W.G.
        • Li H.
        • Li X.
        • et al.
        Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program.
        Am J Respir Crit Care Med. 2010; 181: 315-323
        • Scott 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: 594-602
        • Cloutier M.M.
        • Schatz M.
        • Castro M.
        • Clark N.
        • Kelly H.W.
        • Mangione-Smith R.
        • et al.
        Asthma outcomes: composite scores of asthma control.
        J Allergy Clin Immunol. 2012; 129: S24-33
        • Lang J.E.
        • Holbrook J.T.
        • Wise R.A.
        • Dixon A.E.
        • Teague W.G.
        • Wei C.Y.
        • et al.
        Obesity in children with poorly controlled asthma: sex differences.
        Pediatr Pulmonol. 2013; 48: 847-856
        • Juniper E.F.
        • Svensson K.
        • Mork A.C.
        • Stahl E.
        Measurement properties and interpretation of three shortened versions of the asthma control questionnaire.
        Respir Med. 2005; 99: 553-558
        • National Asthma Education and Prevention Program
        Expert Panel Report 3: guidelines for the diagnosis and management of asthma (full report 2007).
        NHLBI/NIH, US Department of Health and Human Services; Bethesda, MD, 2007
      2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention (revised 2014), Available at www.ginasthma.org.

        • Richter J.E.
        Gastroesophageal reflux disease and asthma: the two are directly related.
        Am J Med. 2000; 108: 153S-158S
        • Harding S.M.
        • Richter J.E.
        The role of gastroesophageal reflux in chronic cough and asthma.
        Chest. 1997; 111: 1389-1402
        • Wu D.N.
        • Tanifuji Y.
        • Kobayashi H.
        • Yamauchi K.
        • Kato C.
        • Suzuki K.
        • et al.
        Effects of esophageal acid perfusion on airway hyperresponsiveness in patients with bronchial asthma.
        Chest. 2000; 118: 1553-1556
        • Laviolette L.
        • Laveneziana P.
        Dyspnoea: a multidimensional and multidisciplinary approach.
        Eur Respir J. 2014; 43: 1750-1762
        • Davenport P.W.
        • Vovk A.
        Cortical and subcortical central neural pathways in respiratory sensations.
        Respir Physiol Neurobiol. 2009; 167: 72-86
        • Patterson R.N.
        • Johnston B.T.
        • Ardill J.E.
        • Heaney L.G.
        • McGarvey L.P.
        Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux.
        Thorax. 2007; 62: 491-495
        • Sin D.D.
        • Jones R.L.
        • Man S.F.
        Obesity is a risk factor for dyspnea but not for airflow obstruction.
        Arch Intern Med. 2002; 162: 1477-1481
        • Zutler M.
        • Singer J.P.
        • Omachi T.A.
        • Eisner M.
        • Iribarren C.
        • Katz P.
        • et al.
        Relationship of obesity with respiratory symptoms and decreased functional capacity in adults without established COPD.
        Prim Care Respir J. 2012; 21: 194-201
        • Bajwah S.
        • Ross J.R.
        • Peacock J.L.
        • Higginson I.J.
        • Wells A.U.
        • Patel A.S.
        • et al.
        Interventions to improve symptoms and quality of life of patients with fibrotic interstitial lung disease: a systematic review of the literature.
        Thorax. 2012; 68: 867-879
        • King G.G.
        • Brown N.J.
        • Diba C.
        • Thorpe C.W.
        • Munoz P.
        • Marks G.B.
        • et al.
        The effects of body weight on airway calibre.
        Eur Respir J. 2005; 25: 896-901
        • Salome C.M.
        • Munoz P.A.
        • Berend N.
        • Thorpe C.W.
        • Schachter L.M.
        • King G.G.
        Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects.
        Int J Obesity. 2008; 32: 502-509
        • Naimark A.
        • Cherniack R.M.
        Compliance of the respiratory system and its components in health and obesity.
        J Appl Physiol. 1960; 15: 377-382
        • Pankow W.
        • Podszus T.
        • Gutheil T.
        • Penzel T.
        • Peter J.
        • Von Wichert P.
        Expiratory flow limitation and intrinsic positive end-expiratory pressure in obesity.
        J Appl Physiol (1985). 1998; 85: 1236-1243
        • Jones R.L.
        • Nzekwu M.M.
        The effects of body mass index on lung volumes.
        Chest. 2006; 130: 827-833
        • Chlif M.
        • Keochkerian D.
        • Feki Y.
        • Vaidie A.
        • Choquet D.
        • Ahmaidi S.
        Inspiratory muscle activity during incremental exercise in obese men.
        Int J Obes (Lond). 2007; 31: 1456-1463
        • Zavorsky G.S.
        • Hoffman S.L.
        Pulmonary gas exchange in the morbidly obese.
        Obes Rev. 2008; 9: 326-339
        • Sharp J.T.
        • Henry J.P.
        • Sweany S.K.
        • Meadows W.R.
        • Pietras R.J.
        The total work of breathing in normal and obese men.
        J Clin Investig. 1964; 43: 728-739
        • Kress J.P.
        • Pohlman A.S.
        • Alverdy J.
        • Hall J.B.
        The impact of morbid obesity on oxygen cost of breathing (VO(2RESP)) at rest.
        Am J Respir Crit Care Med. 1999; 160: 883-886
        • Ofir D.
        • Laveneziana P.
        • Webb K.A.
        • O'Donnell D.E.
        Ventilatory and perceptual responses to cycle exercise in obese women.
        J Appl Physiol (1985). 2007; 102: 2217-2226
        • Narkiewicz K.
        • Kato M.
        • Pesek C.A.
        • Somers V.K.
        Human obesity is characterized by a selective potentiation of central chemoreflex sensitivity.
        Hypertension. 1999; 33: 1153-1158
        • Steier J.
        • Jolley C.J.
        • Seymour J.
        • Roughton M.
        • Polkey M.I.
        • Moxham J.
        Neural respiratory drive in obesity.
        Thorax. 2009; 64: 719-725
        • Roussos C.
        • Macklem P.T.
        The respiratory muscles.
        N Engl J Med. 1982; 307: 786-797

      References

        • Juniper E.F.
        • O'Byrne P.M.
        • Guyatt G.H.
        • Ferrie P.J.
        • King D.R.
        Development and validation of a questionnaire to measure asthma control.
        Eur Respir J. 1999; 14: 902-907
        • Schatz M.
        • Sorkness C.A.
        • Li J.T.
        • Marcus P.
        • Murray J.J.
        • Nathan R.A.
        • et al.
        Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists.
        J Allergy Clin Immunol. 2006; 117: 549-556
        • Nathan R.A.
        • Sorkness C.A.
        • Kosinski M.
        • Schatz M.
        • Li J.T.
        • Marcus P.
        • et al.
        Development of the asthma control test: a survey for assessing asthma control.
        J Allergy Clin Immunol. 2004; 113: 59-65
        • Schatz M.
        • Kosinski M.
        • Yarlas A.S.
        • Hanlon J.
        • Watson M.E.
        • Jhingran P.
        The minimally important difference of the Asthma Control Test.
        J Allergy Clin Immunol. 2009; 124: 719-723.e1
        • Revicki D.A.
        • Leidy N.K.
        • Brennan-Diemer F.
        • Sorensen S.
        • Togias A.
        Integrating patient preferences into health outcomes assessment: the multiattribute Asthma Symptom Utility Index.
        Chest. 1998; 114: 998-1007
        • Juniper E.F.
        • Guyatt G.H.
        • Willan A.
        • Griffith L.E.
        Determining a minimal important change in a disease-specific Quality of Life Questionnaire.
        J Clin Epidemiol. 1994; 47: 81-87
        • Juniper E.F.
        • Guyatt G.H.
        • Feeny D.H.
        • Ferrie P.J.
        • Griffith L.E.
        • Townsend M.
        Measuring quality of life in the parents of children with asthma.
        Qual Life Res. 1996; 5: 27-34