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Mechanisms of obesity in asthma

Rasmussen, Finn; Hancox, Robert J.

Current Opinion in Allergy and Clinical Immunology: February 2014 - Volume 14 - Issue 1 - p 35–43
doi: 10.1097/ACI.0000000000000024
MECHANISMS OF ALLERGY AND ADULT ASTHMA: Edited by Jean Bousquet and J. Andrew Grant
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Purpose of review Obesity and asthma are chronic conditions affecting millions of people worldwide. The two conditions also appear to be linked with an increased risk of asthma in people who are obese. The purpose of this review is to describe mechanism(s) that may explain the association between asthma and obesity.

Recent findings Current evidence suggests that the association between asthma and obesity is linked by two major phenotypes and three important pathways of obesity-related asthma: one phenotype with primary (often atopic) asthma that is aggravated by obesity and a second phenotype with late-onset nonatopic asthma, which predominantly affects women and primarily seems to be associated with neutrophilic inflammation. Proposed pathways include the mechanical effects of obesity (fewer deep inspirations leading to increased airway hyperresponsiveness), an inflammatory pathway driven by obesity-related cytokines (adipokines), and finally environment and lifestyle changes that have led to an increasing prevalence of obesity over the past 50 years (including exposures in utero, physical activity, and diet) may also result in asthma in predisposed individuals. How these environmental changes influence the occurrence and expression of asthma may depend on the age of exposure and on interactions with genetic susceptibilities.

Summary Future research should be directed to shed light on the associations between obesity and asthma phenotypes, modern lifestyles and environmental exposures and genetic susceptibilities.

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aDepartment of Allergy and Respiratory Medicine, Near East University Hospital, North Cyprus, Mersin, Turkey

bDepartment of Preventive & Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

Correspondence to Finn Rasmussen, MD, PhD, DMSc, Department of Allergy and Respiratory Medicine, Near East University Hospital, Near East Avenue, Nicosia, 99138 Northern Cyprus, Mersin 10, Turkey. Tel: +90 392 675 1000; fax: +90 392 223 6461; e-mail:

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Obesity and asthma are chronic conditions affecting millions of people worldwide. Over the past 50 years, there has been a rapid increase in the prevalence of both conditions. Whereas the prevalence of asthma may have reached a plateau in western countries [1,2], obesity is expected to rise further [3]. The rapid increase in the rates of these conditions cannot be due to changes in genetics and are unlikely to be due to changes in diagnostic criteria [4]. Changes in lifestyle such as diet, physical activity, and early life exposures are likely to be important factors contributing to the increase in prevalence of both conditions. Moreover, numerous epidemiological studies show that the two conditions are linked: people who are obese have a 1.5 to three times higher risk of asthma than those who are not, although the reasons for this remain uncertain [5] and are the topic of this review.

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Asthma and obesity both result from a mix of genetic risk and environmental exposures. Hence, asthma and obesity are likely to be connected in a multifactorial fashion with modern lifestyles creating new environmental interactions with existing genetic susceptibilities. The causes of obesity seem more straightforward than for asthma: if energy expenditure is less than intake, obesity will develop, but simple measures of diet and physical activity actually explain only a small part of the variance in adiposity and there may be many less obvious environmental pathways that lead to obesity [6]. The environmental causes of asthma are even harder to determine. Identifying the mechanisms that link obesity and asthma will require a holistic approach as it seems unlikely that a single pathway is responsible [7,8]. There is little evidence that asthma increases the risk for obesity, but obesity has been found to increase the risk for developing asthma in meta-analyses of prospective studies in both children and adults [9,10]. Obesity probably has an effect on asthma development through several different mechanisms. These mechanisms could plausibly either inhibit or promote the disease depending on the age of exposure, including before birth [11], infancy [12], or childhood [13], differences in diet [14], sex [15,16], levels of hormones or cytokines [17–19], environmental exposures [20,21], comorbidities [22], and even climate change [23] (Fig. 1).



Box 1

Box 1

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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 [24]. 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 [25], and some studies [26] 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 [24], 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. [25] 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. [28] 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 [29]. 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. [32], 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 [22]. Consequently, neither asthma nor obesity could explain all of the respiratory symptoms among these obese patients.

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Several studies such as that by Castro-Rodriguez et al. [33] point toward a sex difference in the association between weight gain and asthma as weight gain in girls but not boys was associated with asthma. In fact, the association between obesity and asthma has often been found to be greater in females than males [15,16], although some of the largest studies have not shown a sex difference [34] and sex differences were not observed in meta-analyses of prospective studies [9,10] of obesity and incident asthma in children and adults. It is plausible that an increased association in women could be due to female sex hormones [17,35]. It is also possible that the effects of adiposity are greater in women simply because they have a higher proportion of body fat than men, but the reasons for the apparent sex difference observed in many studies is not yet known [27].

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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 [36]. 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 [39]. Spirometric values of FEV1 and forced vital capacity (FVC) are inversely proportional to BMI [37], although no correlation between BMI and spirometric values was found in elderly patients over 60 years of age [40]. Sutherland et al. [41] 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 [42]. 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 [27]. Increasing adiposity is associated with lower lung function independently of atopic status [37]. 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 [48]. 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 [49]. 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.

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The effects of weight loss

The first randomized study [50] on obese asthmatic patients showed that weight reduction improved lung function, symptoms, morbidity, and health status. These effects can be achieved by dietary weight reduction [51] or by surgery [52]. Boulet et al. [52] showed that bariatric surgery improved airway responsiveness, lung volumes, systemic inflammatory markers (C-reactive protein, CRP), and asthma severity/control after a follow-up period of 12 months. These weight loss studies support the notion that, at the very least, obesity worsens the symptoms associated with asthma. In a randomized study of a 10-week dietary, exercise, or combined intervention, Scott et al. [53▪] found that a 5–10% weight loss resulted in clinically important improvements in asthma control. Adipose tissue reduction was also associated with reduced neutrophilic airway inflammation, whereas reducing dietary saturated fat was associated with less neutrophilic airway inflammation in men. The exercise intervention resulted in significant reductions in sputum eosinophils in both sexes. Diet-induced weight loss in children has also been shown to improve asthma control, but without significant changes in airway inflammation [54]. A Brazilian study [55] using interdisciplinary weight loss therapy for 1 year in obese adolescents found improvements in inflammatory biomarkers and lung function in both asthmatic and nonasthmatic patients. In their study, the change in adiponectin was an independent predictor of the improvement in lung function after therapy in both groups. In a smaller group of patients, they also demonstrated that 1 year of interdisciplinary obesity therapy decreased exercise-induced bronchospasm in obese adolescents, with parallel increases in lung function and improvements in pro-inflammatory/anti-inflammatory adipokines [56]. However, it is also important to note that the participants in these studies were not cured of their asthma despite their weight loss.

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Obesity has a number of immunological effects that could plausibly mediate the association between asthma and obesity.

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Systemic inflammation

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 [60] 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. [63] 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 [64], 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 [65]. 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 [66]. In the same model, they also demonstrated that obesity lowers the sensitization threshold [67]. 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.

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Obesity-related cytokines

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 [71] and high levels have been linked to a lower asthma risk in one study, but not another [72]. 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 [62]. Adiponectin-deficient mice have more airway eosinophilia and airway remodeling [73]. 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 [62], 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 [74]. 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 [65]. The altered immune environment was associated with lower lung function in obese asthmatic children. However, another study [63] found no differences in either leptin or adiponectin levels among obese asthmatic compared with nonobese asthmatic children.

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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 [76]. One study [77] 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 [78]. Paradoxically, another study [79] found lower total cholesterol against asthma, but only among Mexican Americans and not among other ethic/racial groups. A recent small pilot study [80] 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 [81] 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 [82], 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.

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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. [84] 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. [85] 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 [86]. 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 [13]. Taken together, the outcome of a specific genetic disposition seems to depend on the timing, amount of external exposures such as diet [14], pollution [21], and lifestyle intervention [91].

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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 [92], 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 [93], inactivity [94,95], and inadequate sleep [96]. A Mediterranean diet, which is associated with lower rates of cardiovascular disease and obesity [97], has also been associated with protection against childhood asthma and wheeze [14], 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 [99], and increases allergic inflammation in mouse models [100]. It has also been associated with increased wheezing and asthma in children [21]. 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.

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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.

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Conflicts of interest

There are no conflicts of interest.

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Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest
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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.

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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.
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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.
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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.
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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.
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72. Sood A, Cui X, Qualls C, et al. Association between asthma and serum adiponectin concentration in women. Thorax 2008; 63:877–882.
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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].
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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.
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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.
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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.

asthma; cytokines; environment and lifestyle changes; mechanical effects; obesity; phenotypes

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