A major problem in studying asthma is that there is no universally accepted unambiguous definition of asthma. How asthma is defined may have a great impact on any apparent association with obesity . Most epidemiological reports of this association have used self-report questionnaires asking about typical symptoms and/or doctor-diagnosed asthma; few studies have used objective measures to confirm the diagnosis. A lot of self-reported asthma may be overdiagnosed , and some studies  suggest that asthma may be overdiagnosed in obese patients as they found associations between BMI and respiratory symptoms but not with the markers of airway inflammation such as exhaled nitric oxide or bronchial responsiveness that are typically found in asthma [16,26,27]. In a cross-sectional analysis of 1922 men and women , who completed questionnaires from the European Community Respiratory Health Survey, and underwent spirometry and a bronchial challenge test, a reported diagnosis of asthma was associated with BMI, waist-to-height ratio, and waist circumference, but there was no association with asthma confirmed by bronchial responsiveness for any of these obesity measures. However, Aaron et al.  found that although about one in three patients with asthma appeared to be overdiagnosed when they were tested with a range of objective measures, overdiagnosis was not more likely to occur in obese patients. Moore et al.  used cluster analysis to explore asthma phenotypes in patients with severe asthma and found a distinct group of mostly older obese women with late-onset nonatopic asthma, moderate reductions in forced expiratory volume in 1 s (FEV1), and frequent requirement for oral corticosteroids to manage exacerbations. Hence, in adults, the obese phenotype of asthma seems to be different from the classical atopic asthma type. Another cluster analysis identified two groups of predominantly obese individuals that differed in bronchial responsiveness and exhaled nitric oxide, but both clusters demonstrated evidence of reduced expression of glucocorticoid receptor alpha, a finding that could mediate glucocorticoid insensitivity . This may explain why obese patients have more persistent asthma symptoms, higher use of inhaled corticosteroids, lower discharge rates from emergency departments, and more frequent hospitalization than nonobese patients with asthma in spite of higher initial FEV1 and peak expiratory flows [30,31]. In a small study by Shim et al. , obese asthmatic and nonasthmatic adolescents had significantly reduced physical fitness compared with healthy controls, but similar pulmonary reserve at the peak of exercise. They concluded that breathlessness was primarily due to cardiopulmonary deconditioning in the majority of obese adolescents with or without a diagnosis of asthma. In severely obese women referred for bariatric surgery, resting dyspnea complaints were observed in association with asthma or gastroesophageal reflux, whereas activity-related dyspnea was mainly related to obesity . Consequently, neither asthma nor obesity could explain all of the respiratory symptoms among these obese patients.
Many other conditions affecting breathing, including obesity hypoventilation syndrome, obstructive sleep apnea, chronic obstructive pulmonary disease, pulmonary embolism, and aspiration pneumonia, are more common in obesity . In addition to these, a physical or mechanical effect of obesity on the respiratory system seems likely to play a role in the obesity–asthma association. Adipose tissue that impinges on the volume of the chest cavity or airways may reduce lung volumes and have a direct mechanical effect. Hence, it may not only be the extent of adiposity but also the body distribution that is important [10,37]. BMI underestimates the prevalence of obesity, especially in men in whom BMI actually correlates better with lean mass than with body fat percentage. This may help to explain why the association between asthma and obesity has often been observed to be weaker in men than women [16,27,38]. In most obese individuals, there is a relative reduction of the functional residual capacity (FRC) and lower tidal volumes . Spirometric values of FEV1 and forced vital capacity (FVC) are inversely proportional to BMI , although no correlation between BMI and spirometric values was found in elderly patients over 60 years of age . Sutherland et al.  found an inverse correlation between FRC and abdominal obesity, whereas there was no correlation with BMI. Obesity-related reductions in FEV1 may also be related to waist circumference more than BMI . The distribution of fat tissue seems to be important because abdominal obesity increases the risk of incident asthma in women in addition to BMI, indicating that using both measures of BMI and waist circumference may provide a better clinical assessment for asthma risk than either measure alone [43,44], although measurement of total body fat, trunk fat, and BMI all appear to have similar associations with asthma in women . Increasing adiposity is associated with lower lung function independently of atopic status . Airway hyperresponsiveness in nonasthmatic individuals also seems to increase with increasing BMI. Badier et al. [45▪] used specific airway resistance to compare responses to methacholine challenge in nonasthmatic lean, overweight, and obese individuals and found asymptomatic airway hyperresponsiveness in 17, 26, and 50% of individuals, respectively. Deep inspirations, which naturally occur during exercise, may be the first line of defence against bronchospasm. A deep inspiration can partially reverse bronchoconstriction once it is established because of its effect of disrupting actin–myosin cross-bridges and reducing airway smooth muscle tone [46,47]. A decrease in the number of sighs or periodic expansions of the lungs while sedentary may contribute to nonspecific bronchial hyperresponsiveness in children . A reduction in deep inspirations due to reduced physical activity may increase actin-myosin cross-bridging in obese patients making the lungs less flexible and increasing airway narrowing and hyperresponsiveness. Expiratory flow limitation during tidal breathing is more likely to develop in obese asthmatic and nonasthmatic individuals during bronchoconstriction than those who are not obese, despite similar changes in FEV1 . In the same study, expiratory flow limitation was a significant determinant of the severity of breathlessness during challenge in nonasthmatic individuals, and of asthma symptom control in asthmatic patients following anti-inflammatory treatment.
Obesity has a number of immunological effects that could plausibly mediate the association between asthma and obesity.
Both airways disease and obesity are associated with inflammation. Adipose tissue is known to have pro-inflammatory effects and reduced lung function is also known to be associated with systemic inflammation [57–59]. One study  found that both asthma and obesity were independently and synergistically associated with systemic inflammation and this suggests that obesity may modulate airway inflammation to increase the risk and the expression of asthma. However, another study [61,62] found no association between either systemic inflammation measured by blood CRP or adipokine levels and exhaled nitric oxide, suggesting that obesity-related systemic inflammation per se does not induce airway inflammation. Desai et al.  found that the number of airway submucosal eosinophils and levels of sputum IL-5, but not blood or sputum eosinophils, were higher in obese than lean patients with severe asthma. In a study of children , obesity-associated asthma differed from atopic asthma with a Th1 polarization as well as with lower spirometric values. In children aged 8–17 years, obese asthma was not associated with increased airway or systemic inflammation (measured by exhaled nitric oxide, sputum eosinophils, blood CRP, and IL-6), although it was noted that obese asthmatic girls were more likely to have noneosinophilic asthma than boys, again suggesting that there may be sex differences in the inflammatory mechanisms . In a mouse model of obesity and asthma, obesity was shown to be related to allergic asthma through neurogenic inflammation by acting through the selective substance P receptor antagonist (NK1-R) receptor NK1-R . In the same model, they also demonstrated that obesity lowers the sensitization threshold . This finding may help to explain why, under certain circumstances, obesity may be a risk factor for the development of allergic asthma. In another mouse model, it was shown that obesity induced by a high-fat diet exacerbates pulmonary eosinophilic inflammation after ovalbumin challenge [68▪]. Taken together, these studies indicate that there may be immunologic pathways by which obesity induces or exacerbates atopic asthma. However, several studies [69▪,70] have found neutrophilic, rather than eosinophilic, airway inflammation in obese asthmatic patients, suggesting that there are also nonallergic mechanisms.
Adiponectin is an adiposity-related cytokine (adipokine) that is secreted inversely in relation to obesity. Low levels have been associated with nonatopic asthma mainly in girls  and high levels have been linked to a lower asthma risk in one study, but not another . In men, higher levels of adiponectin have been linked to lower levels of nitric oxide (indicating less airway inflammation), but paradoxically more responsiveness to bronchodilator . Adiponectin-deficient mice have more airway eosinophilia and airway remodeling . Leptin is another adipokine. Unlike adiponectin, leptin is secreted directly proportionally to the level of obesity and acts as an appetite suppressant. In one study , leptin levels were not associated with any phenotypic characteristics of asthma. In a study of obese women undergoing bariatric surgery, those with low Th2 asthma (defined as low IgE levels) had increased leptin levels and low adiponectin in visceral adipose tissue, but although visceral fat and bronchoalveolar lavage fluid leptin levels were correlated with airway reactivity, there was no evidence of increased airway inflammation. This suggests that leptin may act directly on the airway through noninflammatory mechanism . Lugogo et al. [75▪] also found that leptin levels in bronchoalveolar lavage fluid were increased in overweight/obese individuals, and were significantly higher in overweight/obese women (but not men) with asthma. In this study, leptin was also shown to enhance production of proinflammatory cytokines from macrophages derived from overweight/obese individuals with asthma, but not among nonasthmatic individuals. As leptin stimulated Th1 cytokine production (e.g. TNF-α, IL-2, and interferon-γ), it seems likely that leptin does not act solely via the classical Th2 pathway of asthma. In accordance with this in a pediatric population, obesity-associated asthma differed from atopic asthma and was characterized by Th1 polarization . The altered immune environment was associated with lower lung function in obese asthmatic children. However, another study  found no differences in either leptin or adiponectin levels among obese asthmatic compared with nonobese asthmatic children.
Dyslipidemia is common comorbidity of obesity and could potentially help to explain the link between asthma and obesity. In mouse models of asthma, a high-cholesterol diet promotes, whereas cholesterol-lowering drugs reduce, Th2 inflammation . One study  found a higher prevalence of asthma in children with high serum cholesterol, but an association between lipoproteins and airway hyperresponsiveness in another cohort was not independent of obesity . Paradoxically, another study  found lower total cholesterol against asthma, but only among Mexican Americans and not among other ethic/racial groups. A recent small pilot study  found associations between different subclasses of low-density lipoproteins and asthma, and aspects of lung function. Although this study only included normal weight adults without the metabolic syndrome, these preliminary findings suggest that alterations in these lipoproteins in obesity could plausibly help to explain the association with asthma. The metabolic syndrome itself has also been suggested to play a role in the asthma–obesity association. A prospective study  found that the metabolic syndrome predicted incident asthma in both men and women over 11 years of follow-up. However, when broken down by its component parts, only waist circumference and high glucose or diabetes were significant independent predictors of asthma onset, whereas low high-density lipoprotein (HDL) and raised triglycerides were not. In a large cross-sectional study , low levels of HDL and high levels of triglyceride were associated with self-reported wheeze among young adults, but these associations were independent of BMI or waist circumference, indicating that they are not likely to mediate the association between obesity and asthma.
It is possible that local factors in lung tissue explain different pulmonary responses to obesity: obesity results in both pulmonary and systemic inflammation in mice, but whereas tumor necrosis factor receptor 1-deficient mice have systemic inflammation, they have less pulmonary inflammation and are protected against obesity-associated airway hyperresponsiveness [83▪▪]. Hallstrand et al.  estimated from a twin study that 8% of the genetic components of asthma and obesity are shared and phenotypic variation could be a result of genetic effects and co-variation effects. This relatively low concordance combined with heterogeneity in the samples and exposures may explain different outcomes when genome-wide analyses are done. Melen et al.  initially found evidence for an interaction between asthma and obesity with a polymorphism on locus 1q31, which is responsible for interacting with tumor necrosis factor alpha receptor variants, but this finding could not be shown in a replication analysis. It is also possible that epigenetic changes may alter the risk for different phenotypes of asthma and that they may also affect the risk for developing other diseases. For example, Neuropeptide Y gene polymorphisms are important in the development of atherosclerosis . Neuropeptide Y has also been shown to be involved as an immunomodulator in asthma. Jaakkola et al. [87▪] investigated the role of two functional Neuropeptide Y polymorphisms, NPY-Leu7Pro and NPY-399C, and obesity for the development of asthma as well as atherosclerosis in asthmatic and nonasthmatic individuals. Being overweight together with the NPY-399T allele without NPY7Pro allele was associated with an increased risk for asthma. Atherosclerosis was lower in patients with asthma depending on the Neuropeptide Y genotype. Epigenetic mechanisms are also suggested by the finding that maternal obesity during pregnancy is associated with an increased risk of asthma and wheezing in offspring, but with a lower risk of atopy and hay fever, suggesting that these pathways may be mainly nonallergic [8,11,88,89▪,90▪]. One study [90▪] showed that low birth weight predisposes to the development of asthma and that excess body mass amplifies the risk. Data from eight European birth cohorts on asthma and allergies showed that rapid growth in BMI during the first 2 years of life increases the risk of asthma up to age 6 years, but not rapid BMI increase after 2 years . Taken together, the outcome of a specific genetic disposition seems to depend on the timing, amount of external exposures such as diet , pollution , and lifestyle intervention .
In addition to the mechanisms considered above, obesity may also influence the risk of asthma through its effect on other disease processes like gastroesophageal reflux, obesity hypoventilation syndrome, and obstructive sleep apnea, which are also associated with obesity. However, in a large epidemiological study , these associations were not significant. Behavioral changes during the past 50 years may also contribute to the asthma–obesity association. A sedentary lifestyle itself may contribute to both obesity and asthma for a broad range of reasons including low physical fitness , inactivity [94,95], and inadequate sleep . A Mediterranean diet, which is associated with lower rates of cardiovascular disease and obesity , has also been associated with protection against childhood asthma and wheeze , particularly higher consumption of vegetables, fruits, legumes, and fish during pregnancy. However, a clinical trial of one dietary supplement (n-3 long chain polyunsaturated fatty acid) in pregnancy did not reduce the overall incidence of asthma [98▪▪]. It is possible that environmental toxins may also contribute to the obesity–asthma association: for example, biphenyl A, which is used in the plastics industry and in food packaging has estrogenic effects, is associated with obesity , and increases allergic inflammation in mouse models . It has also been associated with increased wheezing and asthma in children . In the study by Perzanowski et al. [101▪▪], prenatal exposure to cockroach allergen was associated with a greater risk of allergic sensitization, a risk that was augmented in children if exposed to polycyclic aromatic hydrocarbons having a certain glutathione-S-transferase mu 1 gene polymorphisms.
Current evidence suggests that there are two major phenotypes and three important pathways of asthma in the obese: one group characterized by early onset of asthma that is made worse by obesity and, to some extent, connected with allergy; a second group primarily comprising late-onset disease with nonatopic asthma. This is more often seen in women and may be connected with the inflammatory effects of obesity in lungs. The pathways seem to be a mechanical effect of reduced deep breathing leading to more airway hyperresponsiveness. This is present to some extent in most obese individuals, but is more obvious in those predisposed to asthma. There is some evidence for an inflammatory pathway in which adipokines play a key role in creating a pro-inflammatory state in the lungs that progresses to asthma in predisposed individuals. On top of all of these – like an umbrella – environmental and lifestyle changes over the past 50 years may have altered the occurrence and expression of asthma and obesity, with these effects moderated by the timing of exposures and the presence of genetic susceptibilities.
Papers of particular interest, published within the annual period of review, have been highlighted as:
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25. Aaron SD, Vandemheen KL, Boulet LP, et al. Overdiagnosis of asthma in obese and nonobese adults. CMAJ 2008; 179:1121–1131.
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30. Rodrigo GJ, Plaza V. Body mass index and response to emergency department treatment in adults with severe asthma exacerbations: a prospective cohort study. Chest 2007; 132:1513–1519.
31. Borrell LN, Nguyen EA, Roth LA, 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.
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33. Castro-Rodriguez JA, Holberg CJ, Morgan WJ, et al. Increased incidence of asthmalike symptoms in girls who become overweight or obese during the school years. Am J Respir Crit Care Med 2001; 163:1344–1349.
34. Nystad W, Meyer HE, Nafstad P, et al. Body mass index in relation to adult asthma among 135 000 Norwegian men and women. Am J Epidemiol 2004; 160:969–976.
35. Takeda M, Tanabe M, Ito W, et al. Gender difference in allergic airway remodeling and immunoglobulin production in mouse model of asthma. Respirology 2013; 18:797–806.
36. Murugan AT, Sharma G. Obesity and respiratory diseases. Chron Respir Dis 2008; 5:233–242.
37. Fenger RV, Gonzalez-Quintela A, Vidal C, et al. Exploring the obesity-asthma link: do all types of adiposity increase the risk of asthma? Clin Exp Allergy 2012; 42:1237–1245.
38. Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond) 2008; 32:959–966.
39. Jones RL, Nzekwu MM. The effects of body mass index on lung volumes. Chest 2006; 130:827–833.
40. Agondi RC, Bisaccioni C, Aun MV, et al. Spirometric values in elderly asthmatic patients are not influenced by obesity. Clin Exp Allergy 2012; 42:1183–1189.
41. Sutherland TJ, Goulding A, Grant AM, et al. The effect of adiposity measured by dual-energy X-ray absorptiometry on lung function. Eur Respir J 2008; 32:85–91.
42. Leone N, Courbon D, Thomas F, et al. Lung function impairment and metabolic syndrome: the critical role of abdominal obesity. Am J Respir Crit Care Med 2009; 179:509–516.
43. Brumpton B, Langhammer A, Romundstad P, et al. General and abdominal obesity and incident asthma in adults: the HUNT study. Eur Respir J 2013; 41:323–329.
44. Von Behren J, Lipsett M, Horn-Ross PL, et al. Obesity, waist size and prevalence of current asthma in the California Teachers Study cohort. Thorax 2009; 64:889–893.
45▪. Badier M, Guillot C, Delpierre S. Increased asymptomatic airway hyper-responsiveness in obese individuals. J Asthma 2013; 50:573–578.
The study measured baseline-specific airway conductance (SGaw) and compared it to the methacholine challenge testing in lean and obese as a measure of airway hyperresponsiveness. They found that the SGaw seem to better in obese to show the presence of airway hyperresponsiveness.
46. Skloot G, Togias A. Bronchodilation and bronchoprotection by deep inspiration and their relationship to bronchial hyperresponsiveness. Clin Rev Allergy Immunol 2003; 24:55–72.
47. Scichilone N, Permutt S, Bellia V, Togias A. Inhaled corticosteroids and the beneficial effect of deep inspiration in asthma. Am J Respir Crit Care Med 2005; 172:693–699.
48. Hark WT, Thompson WM, McLaughlin TE, et al. Spontaneous sigh rates during sedentary activity: watching television vs reading. Ann Allergy Asthma Immunol 2005; 94:247–250.
49. Mahadev S, Farah CS, King GG, Salome CM. Obesity, expiratory flow limitation and asthma symptoms. Pulm Pharmacol Ther 2012; 26:438–443.
50. Stenius-Aarniala B, Poussa T, Kvarnstrom J, et al. Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study. BMJ 2000; 320:827–832.
51. Hakala K, Stenius-Aarniala B, Sovijarvi A. Effects of weight loss on peak flow variability, airways obstruction, and lung volumes in obese patients with asthma. Chest 2000; 118:1315–1321.
52. Boulet LP, Turcotte H, Martin J, Poirier P. Effect of bariatric surgery on airway response and lung function in obese subjects with asthma. Respir Med 2012; 106:651–660.
53▪. Scott HA, Gibson PG, Garg ML, et al. Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial. Clin Exp Allergy 2013; 43:36–49.
A randomized trial showing the beneficial effects of weight loss and exercise on symptoms and inflammatory markers for asthma.
54. Jensen ME, Gibson PG, Collins CE, et al. Diet-induced weight loss in obese children with asthma: a randomized controlled trial. Clin Exp Allergy 2013; 43:775–784.
55. da Silva PL, de Mello MT, Cheik NC, et al. Interdisciplinary therapy improves biomarkers profile and lung function in asthmatic obese adolescents. Pediatr Pulmonol 2012; 47:8–17.
56. da Silva PL, de Mello MT, Cheik NC, et al. The role of pro-inflammatory and anti-inflammatory adipokines on exercise-induced bronchospasm in obese adolescents undergoing treatment. Respir Care 2012; 57:572–582.
57. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005; 115:911–919.
58. Rasmussen F, Mikkelsen D, Hancox RJ, et al. High-sensitive C-reactive protein is associated with reduced lung function in young adults. Eur Respir J 2009; 33:382–388.
59. Hancox RJ, Poulton R, Greene JM, et al. Systemic inflammation and lung function in young adults. Thorax 2007; 62:1064–1068.
60. Khan UI, Rastogi D, Isasi CR, Coupey SM. Independent and synergistic associations of asthma and obesity with systemic inflammation in adolescents. J Asthma 2012; 49:1044–1050.
61. Sutherland TJ, Sears MR, McLachlan CR, et al. Leptin, adiponectin, and asthma: findings from a population-based cohort study. Ann Allergy Asthma Immunol 2009; 103:101–107.
62. Sutherland TJ, Taylor DR, Sears MR, et al. Association between exhaled nitric oxide and systemic inflammatory markers. Ann Allergy Asthma Immunol 2007; 99:334–339.
63. Desai D, Newby C, Symon FA, et al. Elevated sputum interleukin-5 and submucosal eosinophilia in obese severe asthmatics. Am J Respir Crit Care Med 2013; 188:657–663.
64. Jensen ME, Gibson PG, Collins CE, Wood LG. Airway and systemic inflammation in obese children with asthma. Eur Respir J 2013; 42:1012–1019.
65. Rastogi D, Canfield SM, Andrade A, et al. Obesity-associated asthma in children: a distinct entity. Chest 2012; 141:895–905.
66. Ramalho R, Almeida J, Beltrao M, et al. Substance P antagonist improves both obesity and asthma in a mouse model. Allergy 2013; 68:48–54.
67. Ramalho R, Almeida J, Beltrao M, et al. Neurogenic inflammation in allergen-challenged obese mice: a missing link in the obesity-asthma association? Exp Lung Res 2012; 38:316–324.
68▪. Dietze J, Bocking C, Heverhagen JT, et al. Obesity lowers the threshold of allergic sensitization and augments airway eosinophilia in a mouse model of asthma. Allergy 2012; 67:1519–1529.
A mice study showing that high-fat diet may lower the allergic threshold.
69▪. Lintomen L, Calixto MC, Schenka A, Antunes E. Allergen-induced bone marrow eosinophilopoiesis and airways eosinophilic inflammation in leptin-deficient ob/ob mice. Obesity (Silver Spring) 2012; 20:1959–1965.
A mice study showing that high-fat diet may lower the allergic threshold.
70. Scott HA, Gibson PG, Garg ML, Wood LG. Airway inflammation is augmented by obesity and fatty acids in asthma. Eur Respir J 2011; 38:594–602.
71. Nagel G, Koenig W, Rapp K, et al. Associations of adipokines with asthma, rhinoconjunctivitis, and eczema in German schoolchildren. Pediatr Allergy Immunol 2009; 20:81–88.
72. Sood A, Cui X, Qualls C, et al. Association between asthma and serum adiponectin concentration in women. Thorax 2008; 63:877–882.
73. Medoff BD, Okamoto Y, Leyton P, et al. Adiponectin deficiency increases allergic airway inflammation and pulmonary vascular remodeling. Am J Respir Cell Mol Biol 2009; 41:397–406.
74. Sideleva O, Suratt BT, Black KE, et al. Obesity and asthma: an inflammatory disease of adipose tissue not the airway. Am J Respir Crit Care Med 2012; 186:598–605.
75▪. Lugogo NL, Hollingsworth JW, Howell DL, et al. Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype. Am J Respir Crit Care Med 2012; 186:404–411.
One of few studies with actual samples from the lung showing enhanced pro-inflammatory response of leptin in obese asthmatic patients.
76. McKay A, Leung BP, McInnes IB, et al. A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma. J Immunol 2004; 172:2903–2908.
77. Al-Shawwa B, Al-Huniti N, Titus G, Abu-Hasan M. Hypercholesterolemia is a potential risk factor for asthma. J Asthma 2006; 43:231–233.
78. Rasmussen F, Hancox RJ, Nair P, et al. Associations between airway hyperresponsiveness, obesity and lipoproteins in a longitudinal cohort. Clin Respir J 2013; 7:268–275.
79. Fessler MB, Massing MW, Spruell B, et al. Novel relationship of serum cholesterol with asthma and wheeze in the United States. J Allergy Clin Immunol 2009; 124:967–974.e1-15.
80. Scichilone N, Rizzo M, Benfante A, et al. Serum low density lipoprotein subclasses in asthma. Respir Med 2013; . [Epub ahead of print].
81. Brumpton BM, Camargo CA, Romundstad PR, et al. Metabolic syndrome and incidence of asthma in adults: the HUNT study. Eur Respir J 2013; . [Epub ahead of print].
82. Fenger RV, Gonzalez-Quintela A, Vidal C, et al. Exploring the obesity-asthma link: do all types of adiposity increase the risk of asthma? Clin Exp Allergy 2012; 42:1237–1245.
83▪▪. Zhu M, Williams AS, Chen L, et al. Role of TNFR1 in the innate airway hyperresponsiveness of obese mice. J Appl Physiol 2012; 113:1476–1485.
Study demonstrating that the TNF receptor 1 protects the lungs against obesity-related systemic inflammation and reduces obesity-related airway hyperresponsiveness in mice.
84. Hallstrand TS, Fischer ME, Wurfel MM, et al. Genetic pleiotropy between asthma and obesity in a community-based sample of twins. J Allergy Clin Immunol 2005; 116:1235–1241.
85. Melen E, Granell R, Kogevinas M, et al. Genome-wide association study of body mass index in 23 000 individuals with and without asthma. Clin Exp Allergy 2013; 43:463–474.
86. Shah SH, Freedman NJ, Zhang L, et al. Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis. PLoS Genet 2009; 5:e1000318.
87▪. Jaakkola U, Kakko T, Juonala M, et al. Neuropeptide Y polymorphism increases the risk for asthma in overweight subjects; protection from atherosclerosis in asthmatic subjects: the cardiovascular risk in young Finns study. Neuropeptides 2012; 46:321–328.
A study showing that the same polymorphisms can affect different diseases such as asthma and atherosclerosis. Interestingly, here some were associated with increased risk for asthma and at the same time decreased risk for atherosclerosis.
88. Harpsoe MC, Basit S, Bager P, et al. Maternal obesity, gestational weight gain, and risk of asthma and atopic disease in offspring: a study within the Danish National Birth Cohort. J Allergy Clin Immunol 2013; 131:1033–1040.
89▪. Guerra S, Sartini C, Mendez M, et al. Maternal prepregnancy obesity is an independent risk factor for frequent wheezing in infants by age 14 months. Paediatr Perinat Epidemiol 2013; 27:100–108.
A study showing effect of prepregnancy obesity on asthma-related phenotypes.
90▪. Lu FL, Hsieh CJ, Caffrey JL, et al. Body mass index may modify asthma prevalence among low-birth-weight children. Am J Epidemiol 2012; 176:32–42.
A large study from Taiwan showing that low birth weight combined with a high body mass in adolescence amplifies the risk of developing asthma.
91. Curti ML, Pires MM, Barros CR, et al. Associations of the TNF-alpha -308 G/A, IL6-174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk. Diabetol Metab Syndr 2012; 4:49–54.
92. Gunnbjornsdottir MI, Omenaas E, Gislason T, et al. Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms. Eur Respir J 2004; 24:116–121.
93. Rasmussen F, Lambrechtsen J, Siersted HC, et al. Low physical fitness in childhood is associated with the development of asthma in young adulthood: the Odense schoolchild study. Eur Respir J 2000; 16:866–870.
94. Landhuis CE, Poulton R, Welch D, Hancox RJ. Programming obesity and poor fitness: the long-term impact of childhood television. Obesity (Silver Spring) 2008; 16:1457–1459.
95. Jakes RW, Day NE, Patel B, et al. Physical inactivity is associated with lower forced expiratory volume in 1 s: European Prospective Investigation into Cancer-Norfolk Prospective Population Study. Am J Epidemiol 2002; 156:139–147.
96. Landhuis CE, Poulton R, Welch D, Hancox RJ. Childhood sleep time and long-term risk for obesity: a 32-year prospective birth cohort study. Pediatrics 2008; 122:955–960.
97. Bonaccio M, Iacoviello L, de Gaetano G. Moli-Sani InvestigatorsThe Mediterranean diet: the reasons for a success. Thromb Res 2012; 129:401–404.
98▪▪. Palmer DJ, Sullivan T, Gold MS, et al. Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants’ allergies in first year of life: randomised controlled trial. BMJ 2012; 344:e184
A randomized controlled trial looking at the effects of dietary supplementary products on allergy development – a negative study – but nevertheless important.
99. Li DK, Miao M, Zhou Z, et al. Urine bisphenol-A level in relation to obesity and overweight in school-age children. PLoS One 2013; 8:e65399.
100. Midoro-Horiuti T, Tiwari R, Watson CS, Goldblum RM. Maternal bisphenol A exposure promotes the development of experimental asthma in mouse pups. Environ Health Perspect 2010; 118:273–277.
101▪▪. Perzanowski MS, Chew GL, Divjan A, et al. Early-life cockroach allergen and polycyclic aromatic hydrocarbon exposures predict cockroach sensitization among inner-city children. J Allergy Clin Immunol 2013; 131:886–893.