All Title Author
Keywords Abstract

Role of Obesity in Asthma Control, the Obesity-Asthma Phenotype

DOI: 10.1155/2013/538642

Full-Text   Cite this paper   Add to My Lib


Asthma is a disease with distinct phenotypes that have implications for both prognosis and therapy. Epidemiologic studies have demonstrated an association between asthma and obesity. Further studies have shown that obese asthmatics have poor asthma control and more severe asthma. This obese-asthma group may represent a unique phenotype. The mechanisms behind poor asthma control in obese subjects remain unclear, but recent research has focused on adipokines and their effects on the airways as well as the role of oxidative stress. Both surgical and nonsurgical weight loss therapy have shown promising results with improvements in asthma control and decreased asthma severity. Comorbid conditions such as gastroesophageal reflux disease and obstructive sleep apnea may also have a role in poor asthma control in obese asthmatics. Further research is needed to define the mechanisms behind this phenotype which will guide the development of targeted therapies. 1. Introduction to the Obese-Asthma Phenotype Obesity and asthma are major public health problems affecting large numbers of individuals across the globe. Obesity is often classified using body mass index (BMI) (Table 1) [1]. Worldwide obesity has more than doubled since 1980. In 2008, more than 1.4 billion adults, ≥20 years, were overweight. Of these, over 200 million men and nearly 300 million women were obese. It is estimated that at least 2.8 million adults die each year as a result of being overweight or obese [2]. Table 1: WHO body mass index (BMI) Classification [ 1]. The World Health Organization estimates that 235 million people currently suffer from asthma and that asthma is under diagnosed and undertreated [3]. Asthma prevalence (the percentage of people who have ever been diagnosed with asthma and still have asthma) increased from 7.3% in 2001 to 8.4% in 2010 in the United States [4]. In 2010, an estimated 25.7 million people had asthma: 18.7 million adults aged 18 and over, and 7.0 million children aged 0–17 years [4]. Both cross-sectional epidemiologic investigations and prospective studies have shown an association between asthma and obesity with a relative risk (RR) of up to 3.0 [5–8]. A meta-analysis of seven prospective studies showed an increased odds ratio (OR) for incident asthma of 1.92 (1.43–2.59) in those with obesity versus normal weight and concluded that the odds of incident asthma increased by 50% in overweight/obese individuals [9]. There was a dose-response relationship between body weight and asthma with increasing odds of incident asthma as BMI increased ( for trend) [9].


[1]  “Classification of Overweight and Obesity by BMI, Waist Circumference, and Associated Disease Risks,” 2012,
[2]  “Obesity and Overweight,” Fact sheet no. 311, 2012,
[3]  “Asthma,” Fact sheet no. 307, 2011,
[4]  L. J. Akinbami, J. E. Moorman, C. Bailey, H. S. Zahran, M. King, and X. Liu, “Trends in asthma prevalence, health care use, and mortality in the United States, 2001–2010,” NCHS Data Brief, no. 94, pp. 1–8, 2012.
[5]  C. A. Camargo, S. T. Weiss, S. Zhang, W. C. Willett, and F. E. Speizer, “Prospective study of body mass index, weight change, and risk of adult- onset asthma in women,” Archives of Internal Medicine, vol. 159, no. 21, pp. 2582–2588, 1999.
[6]  S. Guerra, D. L. Sherrill, A. Bobadilla, F. D. Martinez, and R. A. Barbee, “The relation of body mass index to asthma, chronic bronchitis, and emphysema,” Chest, vol. 122, no. 4, pp. 1256–1263, 2002.
[7]  E. Huovinen, J. Kaprio, and M. Koskenvuo, “Factors associated to lifestyle and risk of adult onset asthma,” Respiratory Medicine, vol. 97, no. 3, pp. 273–280, 2003.
[8]  E. S. Ford, “The epidemiology of obesity and asthma,” Journal of Allergy and Clinical Immunology, vol. 115, no. 5, pp. 897–910, 2005.
[9]  D. A. Beuther and E. R. Sutherland, “Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies,” American Journal of Respiratory and Critical Care Medicine, vol. 175, no. 7, pp. 661–666, 2007.
[10]  V. Hjellvik, A. Tverdal, and K. Furu, “Body mass index as predictor for asthma: a cohort study of 118,723 males and females,” European Respiratory Journal, vol. 35, no. 6, pp. 1235–1242, 2010.
[11]  W. S. Beckett, D. R. Jacobs, Y. U. Xinhua, C. Iribarren, and O. Dale Williams, “Asthma is associated with weight gain in females but not males, independent of physical activity,” American Journal of Respiratory and Critical Care Medicine, vol. 164, no. 11, pp. 2045–2050, 2001.
[12]  Y. Chen, D. Rennie, Y. Cormier, and J. Dosman, “Sex specificity of asthma associated with objectively measured body mass index and waist circumference: the Humboldt study,” Chest, vol. 128, no. 4, pp. 3048–3054, 2005.
[13]  A. E. Dixon, F. Holguin, A. Sood et al., “An official American Thoracic Society Workshop report: obesity and asthma,” Proceedings of the American Thoracic Society, vol. 7, no. 5, pp. 325–335, 2010.
[14]  A. Fuhlbrigge, M. L. Reed, D. A. Stempel, H. O. Ortega, K. Fanning, and R. H. Stanford, “The status of asthma control in the U.S. adult population,” Allergy and Asthma Proceedings, vol. 30, no. 5, pp. 529–533, 2009.
[15]  T. Haselkorn, H. Chen, D. P. Miller et al., “Asthma control and activity limitations: insights from the Real-world Evaluation of Asthma Control and Treatment (REACT) Study,” Annals of Allergy, Asthma and Immunology, vol. 104, no. 6, pp. 471–477, 2010.
[16]  National Asthma Education and Prevention Program, “Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007,” The Journal of Allergy and Clinical Immunology, vol. 120, no. 5, pp. S94–S138, 2007.
[17]  M. M. Cloutier, M. Schatz, M. Castro et al., “Asthma outcomes: composite scores of asthma control,” Journal of Allergy and Clinical Immunology, vol. 129, no. 3, supplement, pp. S24–S33, 2012.
[18]  R. H. Stanford, A. W. Gilsenan, R. Ziemiecki, X. Zhou, W. R. Lincourt, and H. Ortega, “Predictors of uncontrolled asthma in adult and pediatric patients: analysis of the asthma control characteristics and prevalence survey studies (ACCESS),” Journal of Asthma, vol. 47, no. 3, pp. 257–262, 2010.
[19]  M. Schatz, D. M. Mosen, M. Kosinski et al., “Predictors of asthma control in a random sample of asthmatic patients,” Journal of Asthma, vol. 44, no. 4, pp. 341–345, 2007.
[20]  P. Demoly, P. Paggiaro, V. Plaza et al., “Prevalence of asthma control among adults in France, Germany, Italy, Spain and the UK,” European Respiratory Review, vol. 18, no. 112, pp. 105–112, 2009.
[21]  L. Laforest, E. Van Ganse, G. Devouassoux et al., “Influence of patients' characteristics and disease management on asthma control,” Journal of Allergy and Clinical Immunology, vol. 117, no. 6, pp. 1404–1410, 2006.
[22]  L. L. Barros, A. Souza-Machado, L. B. Corrêa et al., “Obesity and poor asthma control in patients with severe asthma,” Journal of Asthma, vol. 48, no. 2, Article ID 554940, pp. 171–176, 2011.
[23]  K. L. Lavoie, S. L. Bacon, M. Labrecque, A. Cartier, and B. Ditto, “Higher BMI is associated with worse asthma control and quality of life but not asthma severity,” Respiratory Medicine, vol. 100, no. 4, pp. 648–657, 2006.
[24]  A. Lessard, H. Turcotte, Y. Cormier, and L. P. Boulet, “Obesity and asthma: a specific phenotype?” Chest, vol. 134, no. 2, pp. 317–323, 2008.
[25]  D. M. Mosen, M. Schatz, D. J. Magid, and C. A. Camargo, “The relationship between obesity and asthma severity and control in adults,” Journal of Allergy and Clinical Immunology, vol. 122, no. 3, p. 507, 2008.
[26]  P. Saint-Pierre, A. Bourdin, P. Chanez, J. P. Daures, and P. Godard, “Are overweight asthmatics more difficult to control?” Allergy, vol. 61, no. 1, pp. 79–84, 2006.
[27]  J. I. Peters, J. M. McKinney, B. Smith, P. Wood, E. Forkner, and A. D. Galbreath, “Impact of obesity in asthma: evidence from a large prospective disease management study,” Annals of Allergy, Asthma and Immunology, vol. 106, no. 1, pp. 30–35, 2011.
[28]  M. J. H. Akerman, C. M. Calacanis, and M. K. Madsen, “Relationship between asthma severity and obesity,” Journal of Asthma, vol. 41, no. 5, pp. 521–526, 2004.
[29]  B. Taylor, D. Mannino, C. Brown, D. Crocker, N. Twum-Baah, and F. Holguin, “Body mass index and asthma severity in the National Asthma Survey,” Thorax, vol. 63, no. 1, pp. 14–20, 2008.
[30]  A. Youkou, T. Hasegawa, K. Suzuki et al., “Influence of obesity on control in asthmatic Japanese patients defined by the Japanese definition of obesity,” Internal Medicine, vol. 50, no. 18, pp. 1911–1916, 2011.
[31]  T. Haselkorn, J. E. Fish, B. E. Chipps, D. P. Miller, H. Chen, and S. T. Weiss, “Effect of weight change on asthma-related health outcomes in patients with severe or difficult-to-treat asthma,” Respiratory Medicine, vol. 103, no. 2, pp. 274–283, 2009.
[32]  J. Sastre, J. M. Olaguíbe, A. L. Vi?a, J. M. Vega, V. Del Pozo, and C. Picado, “Increased body mass index does not lead to a worsening of asthma control in a large adult asthmatic population in spain,” Journal of Investigational Allergology and Clinical Immunology, vol. 20, no. 7, pp. 551–555, 2010.
[33]  E. M. Clerisme-Beaty, S. Karam, C. Rand et al., “Does higher body mass index contribute to worse asthma control in an urban population?” Journal of Allergy and Clinical Immunology, vol. 124, no. 2, pp. 207–212, 2009.
[34]  M. Peters-Golden, A. Swern, S. S. Bird, C. M. Hustad, E. Grant, and J. M. Edelman, “Influence of body mass index on the response to asthma controller agents,” European Respiratory Journal, vol. 27, no. 3, pp. 495–503, 2006.
[35]  L. P. Boulet and E. Franssen, “Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma,” Respiratory Medicine, vol. 101, no. 11, pp. 2240–2247, 2007.
[36]  C. S. Farah, J. A. Kermode, S. R. Downie et al., “Obesity is a determinant of asthma control independent of inflammation and lung mechanics,” Chest, vol. 140, no. 3, pp. 659–666, 2011.
[37]  E. R. Sutherland, E. Goleva, M. Strand, D. A. Beuther, and D. Y. M. Leung, “Body mass and glucocorticoid response in asthma,” American Journal of Respiratory and Critical Care Medicine, vol. 178, no. 7, pp. 682–687, 2008.
[38]  A. E. Dixon, D. M. Shade, R. I. Cohen et al., “Effect of obesity on clinical presentation and response to treatment in asthma,” Journal of Asthma, vol. 43, no. 7, pp. 553–558, 2006.
[39]  C. T. Juel -B, Z. Ali, L. Nilas, and C. S. Ulrik, “Asthma and obesity: does weight loss improve asthma control? A systematic review,” Journal of Asthma and Allergy, no. 5, pp. 21–26, 2012.
[40]  B. Stenius-Aarniala, T. Poussa, J. Kvarnstr?m, E. L. Gr?nlund, M. Ylikahri, and P. Mustajoki, “Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study,” British Medical Journal, vol. 320, no. 7238, pp. 827–832, 2000.
[41]  S. D. Aaron, D. Fergusson, R. Dent, Y. Chen, K. L. Vandemheen, and R. E. Dales, “Effect of weight reduction on respiratory function and airway reactivity in obese women,” Chest, vol. 125, no. 6, pp. 2046–2052, 2004.
[42]  F. B. Adeniyi and T. Young, “Weight loss interventions for chronic asthma,” Cochrane Database of Systematic Reviews, vol. 7, Article ID CD009339, 2012.
[43]  J. B. Dixon, L. Chapman, and P. O'Brien, “Marked improvement in asthma after Lap-Band surgery for morbid obesity,” Obesity Surgery, vol. 9, no. 4, pp. 385–389, 1999.
[44]  M. Maniscalco, A. Zedda, S. Faraone et al., “Weight loss and asthma control in severely obese asthmatic females,” Respiratory Medicine, vol. 102, no. 1, pp. 102–108, 2008.
[45]  A. E. Dixon, R. E. Pratley, P. M. Forgione et al., “Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation,” Journal of Allergy and Clinical Immunology, vol. 128, no. 3, pp. 508.e2–515.e2, 2011.
[46]  E. R. Sutherland, C. A. Camargo, W. W. Busse et al., “Comparative effect of body mass index on response to asthma controller therapy,” Allergy and Asthma Proceedings, vol. 31, no. 1, pp. 20–25, 2010.
[47]  D. Jarvis, S. Chinn, J. Potts, and P. Burney, “Association of body mass index with respiratory symptoms and atopy: results from the European Community Respiratory Health Survey,” Clinical and Experimental Allergy, vol. 32, no. 6, pp. 831–837, 2002.
[48]  S. L. Appleton, R. J. Adams, D. H. Wilson, A. W. Taylor, and R. E. Ruffin, “Central obesity is associated with nonatopic but not atopic asthma in a representative population sample,” Journal of Allergy and Clinical Immunology, vol. 118, no. 6, pp. 1284–1291, 2006.
[49]  Y. Chen, D. Rennie, Y. Cormier, and J. Dosman, “Atopy, obesity, and asthma in adults: the Humboldt study,” Journal of Agromedicine, vol. 14, no. 2, pp. 222–227, 2009.
[50]  R. V. Fenger, A. Gonzalez-Quintela, C. Vidal et al., “Exploring the obesity-asthma link: do all types of adiposity increase the risk of asthma?” Clinical and Experimental Allergy, vol. 42, no. 8, pp. 1237–1245, 2012.
[51]  A. M. Fortuna, T. Feixas, M. González, and P. Casan, “Diagnostic utility of inflammatory biomarkers in asthma: exhaled nitric oxide and induced sputum eosinophil count,” Respiratory Medicine, vol. 101, no. 11, pp. 2416–2421, 2007.
[52]  A. Jatakanon, S. Lim, S. A. Kharitonov, K. F. Chung, and P. J. Barnes, “Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma,” Thorax, vol. 53, no. 2, pp. 91–95, 1998.
[53]  S. H. Kim, T. H. Kim, J. S. Lee et al., “Adiposity, adipokines, and exhaled nitric oxide in healthy adults without asthma,” Journal of Asthma, vol. 48, no. 2, Article ID 529223, pp. 177–182, 2011.
[54]  D. C. Todd, S. Armstrong, L. D'Silva, C. J. Allen, F. E. Hargreave, and K. Parameswaran, “Effect of obesity on airway inflammation: a cross-sectional analysis of body mass index and sputum cell counts,” Clinical and Experimental Allergy, vol. 37, no. 7, pp. 1049–1054, 2007.
[55]  C. M. Berg, D. S. Thelle, A. Rosengren, L. Lissner, K. Torén, and A. C. Olin, “Decreased fraction of exhaled nitric oxide in obese subjects with asthma symptoms: data from the population study INTERGENE/ADONIX,” Chest, vol. 139, no. 5, pp. 1109–1116, 2011.
[56]  H. A. Scott, P. G. Gibson, M. L. Garg, and L. G. Wood, “Airway inflammation is augmented by obesity and fatty acids in asthma,” European Respiratory Journal, vol. 38, no. 3, pp. 594–602, 2011.
[57]  K. E. Wellen and G. S. Hotamisligil, “Obesity-induced inflammatory changes in adipose tissue,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1785–1788, 2003.
[58]  M. Can?z, F. Erdenen, H. Uzun, C. Müderriso?lu, and S. Aydin, “The relationship of inflammatory cytokines with asthma and obesity,” Clinical and Investigative Medicine, vol. 31, no. 6, pp. E373–E379, 2008.
[59]  N. Ali Assad and A. Sood, “Leptin, adiponectin and pulmonary diseases,” Biochimie, vol. 94, no. 10, pp. 2180–2189, 2012.
[60]  S. A. Shore, I. N. Schwartzman, M. S. Mellema, L. Flynt, A. Imrich, and R. A. Johnston, “Effect of leptin on allergic airway responses in mice,” Journal of Allergy and Clinical Immunology, vol. 115, no. 1, pp. 103–109, 2005.
[61]  N. L. Lugogo, J. W. Hollingsworth, L. G. Que et al., “Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype,” American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 5, pp. 404–411, 2012.
[62]  O. Sideleva, B. T. Suratt, K. E. Black et al., “Obesity and asthma: an inflammatory disease of adipose tissue not the airway,” American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 7, pp. 598–605, 2012.
[63]  A. Sood, X. Cui, C. Quails et al., “Association between asthma and serum adiponectin concentration in women,” Thorax, vol. 63, no. 10, pp. 877–882, 2008.
[64]  A. Sood, C. Qualls, M. Schuyler et al., “Low serum adiponectin predicts future risk for asthma in women,” American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 1, pp. 41–47, 2012.
[65]  T. J. T. Sutherland, M. R. Sears, C. R. McLachlan, R. Poulton, and R. J. Hancox, “Leptin, adiponectin, and asthma: findings from a population-based cohort study,” Annals of Allergy, Asthma and Immunology, vol. 103, no. 2, pp. 101–107, 2009.
[66]  R. L. Jones and M. M. U. Nzekwu, “The effects of body mass index on lung volumes,” Chest, vol. 130, no. 3, pp. 827–833, 2006.
[67]  W. Ladosky, M. A. M. Botelho, and J. P. Albuquerque, “Chest mechanics in morbidly obese non-hypoventilated patients,” Respiratory Medicine, vol. 95, no. 4, pp. 281–286, 2001.
[68]  I. Rubinstein, N. Zamel, L. DuBarry, and V. Hoffstein, “Airflow limitation in morbidly obese, nonsmoking men,” Annals of Internal Medicine, vol. 112, no. 11, pp. 828–832, 1990.
[69]  D. D. Sin, R. L. Jones, and S. F. Paul Man, “Obesity is a risk factor for dyspnea but not for airflow obstruction,” Archives of Internal Medicine, vol. 162, no. 13, pp. 1477–1481, 2002.
[70]  R. A. Watson and N. B. Pride, “Postural changes in lung volumes and respiratory resistance in subjects with obesity,” Journal of Applied Physiology, vol. 98, no. 2, pp. 512–517, 2005.
[71]  L. C. Collins, P. D. Hoberty, J. F. Walker, E. C. Fletcher, and A. N. Peiris, “The effect of body fat distribution on pulmonary function tests,” Chest, vol. 107, no. 5, pp. 1298–1302, 1995.
[72]  D. J. Ding, J. G. Martin, and P. T. Macklem, “Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans,” Journal of Applied Physiology, vol. 62, no. 3, pp. 1324–1330, 1987.
[73]  C. M. Salome, P. A. Munoz, N. Berend, C. W. Thorpe, L. M. Schachter, and G. G. King, “Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects,” International Journal of Obesity, vol. 32, no. 3, pp. 502–509, 2008.
[74]  T. J. T. Sutherland, J. O. Cowan, and D. R. Taylor, “Dynamic hyperinflation with bronchoconstriction: differences between obese and nonobese women with asthma,” American Journal of Respiratory and Critical Care Medicine, vol. 177, no. 9, pp. 970–975, 2008.
[75]  A. Sood, C. Qualls, A. Arynchyn et al., “Obesity-asthma association: is it explained by systemic oxidant stress?” Chest, vol. 136, no. 4, pp. 1055–1062, 2009.
[76]  S. Komakula, S. Khatri, J. Mermis et al., “Body mass index is associated with reduced exhaled nitric oxide and higher exhaled 8-isoprostanes in asthmatics,” Respiratory Research, vol. 8, article 32, 2007.
[77]  F. Holguin and A. Fitzpatrick, “Obesity, asthma, and oxidative stress,” Journal of Applied Physiology, vol. 108, no. 3, pp. 754–759, 2010.
[78]  W. W. Chan, M. E. Chiou, K. L. Obstein, A. S. Tignor, and T. L. Whitlock, “The efficacy of proton pump inhibitors for the treatment of asthma in adults: a meta-analysis,” Archives of Internal Medicine, vol. 171, no. 7, pp. 620–629, 2011.
[79]  J. Y. Julien, J. G. Martin, P. Ernst et al., “Prevalence of obstructive sleep apnea-hypopnea in severe versus moderate asthma,” Journal of Allergy and Clinical Immunology, vol. 124, no. 2, pp. 371–376, 2009.
[80]  A. E. Dixon, E. M. Clerisme-Beaty, E. A. Sugar et al., “Effects of obstructive sleep apnea and gastroesophageal reflux disease on asthma control in obesity,” Journal of Asthma, vol. 48, no. 7, pp. 707–713, 2011.
[81]  M. Teodorescu, D. A. Polomis, S. V. Hall et al., “Association of obstructive sleep apnea risk with asthma control in adults,” Chest, vol. 138, no. 3, pp. 543–550, 2010.
[82]  C. Shu Chan, A. J. Woolcock, and C. E. Sullivan, “Nocturnal asthma: role of snoring and obstructive sleep apnea,” American Review of Respiratory Disease, vol. 137, no. 6, pp. 1502–1504, 1988.
[83]  M. Teodorescu, D. A. Polomis, M. C. Teodorescu et al., “Association of obstructive sleep apnea risk or diagnosis with daytime asthma in adults,” Journal of Asthma, vol. 49, no. 6, pp. 620–628, 2012.


comments powered by Disqus