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Tuesday, November 19, 2013

Obesity and Asthma

 Posted by Chantel Martiromo,  Article By Kyle J. Norton
 Obesity is defined as a medical condition of excess body fat has accumulated overtime, while overweight is a condition of excess body weight relatively to the height. According to the Body Mass Index(BMI), a BMI between 25 to 29.9 is considered over weight, while a BMI of over 30 is an indication of obesity. According to the statistic, 68% of American population are either overweight or obese.
Asthma effects over 300 million people word wide and causes as many as 250,000 death a year. The rate has increased rapidly over last 10 year as a result of "industrial revolution" of countries in the South East Asia. Contrary to general believe, most cases of asthma are caused by allergic effects and many people suffer their first asthma attack after the age of 70.
In conventional medicine, asthma is defined as a condition of chronic airway inflammatory disease, including symptoms of airway obstruction, sudden constriction of the muscles in the walls of the bronchioles, tight chest, wheezing, coughing, etc.

1. The joint association of anxiety, depression and obesity with incident asthma
In the study to assess the association of anxiety or depression symptoms and the joint association of these symptoms and obesity with incident asthma, found that having anxiety or depression symptoms was associated with incident asthma [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.09-1.78). Obese participants with anxiety or depression symptoms had a substantially higher risk of incident asthma (OR 2.93, 95% CI 2.20-3.91) than any other group (non-obese participants without anxiety or depression symptoms [reference], non-obese participants with anxiety or depression symptoms (OR 1.20, 95% CI 1.00-1.45) and obese participants without anxiety or depression symptoms (OR 1.47, 95% CI 1.19-1.82)]. The relative excess risk for incident asthma due to interaction between anxiety or depression symptoms and obesity was 1.26 (95% CI 0.39-2.12)(1).

2. Metabolic syndrome and incidence of asthma
Obesity is a risk factor for incident asthma in adults, and obesity is a major component of metabolic syndrome. In the study, conducted a prospective cohort study of participants who were asthma-free at baseline (n=23 191) in the Nord-Trøndelag Health Study from 1995 to 2008 to explore the associations of metabolic syndrome and its components with the cumulative incidence of asthma in adults, found that metabolic syndrome was a risk factor for incident asthma (adjusted OR 1.57, 95% CI 1.31 to 1.87). This association was consistent in sensitivity analyses using a stricter asthma definition (adjusted OR 1.42, 95% CI 1.13 to 1.79). Among the components of metabolic syndrome, two remained associated with incident asthma after mutual adjustment for the other metabolic components; high waist circumference (adjusted OR 1.62, 95% CI 1.36 to 1.94), and elevated glucose or diabetes (adjusted OR 1.43, 95% CI 1.01 to 2.04).Metabolic syndrome and two of its components (high waist circumference, and elevated glucose or diabetes) were associated with an increased risk of incident asthma in adults(2).

3. General and abdominal obesity and incident asthma in adults
Measures of body mass index (BMI) and waist circumference define general obesity and abdominal obesity respectively. In the study to determine the association between BMI, waist circumference and incident asthma in adults, we conducted a prospective study (n=23,245) in a population living in Nord-Trøndelag, Norway in 1995-2008, showed that odds ratios for asthma associated with obesity were calculated using multivariable logistic regression. General obesity was a risk factor for asthma in females (OR 1.96, 95% CI 1.52-2.52) and males (OR 1.84, 95% CI 1.30-2.59). In females, after additional adjustment for BMI, abdominal obesity remained a risk factor for asthma development (OR 1.46, 95% CI 1.04-2.05). Abdominal obesity seems to increase the risk of incident asthma in females in addition to BMI, indicating that using both measures of BMI and waist circumference in females may be a superior clinical assessment for asthma risk than any measure alone(3).

4. Atopy, obesity, and asthma in adults
Obesity appears more strongly associated with asthma in women than in men. It is hypothesized that a stronger linkage of obesity with nonatopic asthma than with atopic asthma may explain the sex difference. In the study to examine the association between obesity and asthma in atopic and nonatopic people separately with a total of 1997 residents aged 18 to 79 years who participated in the 2003-2004 Humboldt study were included in the analysis, found that overall, 8% reported having asthma, 30% had atopic sensitization as determined by allergy skin tests, 31% reported a history of respiratory allergy, and 35% were obese defined as BMI equal to or larger than 30 kg/m(2). Compared to those with a BMI <25 kg/m(2), the odds ratio for asthma for the nonatopic subjects of those with a BMI of at least 30.0 kg/m(2) was 2.01 (95% confidence interval [CI]: 1.13, 3.59] after adjustment for sex and age. The association between obesity and asthma was not statistically significant in atopic subjects. The adjusted odds ratios for obesity versus normal weight were 2.56 (95% CI: 1.07, 6.12) and 1.76 (95% CI: 1.04, 3.01) for those without and with a history of respiratory allergy, respectively. The association of asthma with waist circumference was not statistically significant in all the subgroups defined by atopy and respiratory allergy. The data suggested a stronger association between obesity and asthma among nonatopic people than among atopic people(4).

5. Association of obesity in adults with allergic asthma
Obesity and asthma are diseases of high prevalence around the world. The increment in their incidence constitutes a challenge to public health. Asthma can be worse in patients with obesity. In the study to know the prevalence of obesity in a group of Mexican allergic asthmatic adults, showed that according to the BMI, 112 (70.9%) patients had a weight above normal; 76 (67.9%) were women and 36 (32.1%) were men. The highest number of patients with weight above normal corresponded to the overweight group. Mild persistent asthma presented in two-thirds of the patients with overweight and obesity. Women with overweight and obesity showed a higher severity of asthma than men. Women had more positive skin tests than men. Half of the patients had IgE levels above normal(5).

6. Childhood overweight/obesity and asthma
Asthma and overweight/obesity prevalence are both increasing worldwide. Overweight/obesity has been suggested as a risk factor for developing asthma. In the study to present and evaluate recent publications that help answer the question: "Is increased body weight (at least overweight status) related to asthma in children?, found that current evidence supports a weak yet significant association between high body weight and asthma. New information indicates that central obesity in children increases asthma risk. Also, the link between high body weight and asthma may be stronger in nonallergic asthma. There are mixed results about the importance of sex. Although the nature of the association between overweight/obese status and asthma remains unclear, prospective studies point that high body weight precedes asthma symptoms. These data add weight to the importance of preventing and treating a high body weight against asthma outcomes. Available research in children has not studied adequately the influence of weight change (either gain or loss) on asthma symptoms, an area of clinical importance. Beyond energy control, the role of diet as a possible inflammatory stimulus warrants further investigation(6).

7. Obesity and asthma: physiological perspective
Obesity induces some pertinent physiological changes which are conducive to either development of asthma or cause of poorly controlled asthma state. According to the study by the Chest Research Foundation, Marigold Complex, Kalyani Nagar, obesity related mechanical stress forces induced by abdominal and thoracic fat generate stiffening of the lungs and diaphragmatic movements to result in reduction of resting lung volumes such as functional residual capacity (FRC). Reduced FRC is primarily an outcome of decreased expiratory reserve volume, which pushes the tidal breathing more towards smaller high resistance airways, and consequentially results in expiratory flow limitation during normal breathing in obesity. Reduced FRC also induces plastic alteration in the small collapsible airways, which may generate smooth muscle contraction resulting in increased small airway resistance, which, however, is not picked up by spirometric lung volumes. There is also a possibility that chronically reduced FRC may generate permanent adaptation in the very small airways; therefore, the airway calibres may not change despite weight reduction. Obesity may also induce bronchodilator reversibility and diurnal lung functional variability. Obesity is also associated with airway hyperresponsiveness; however, the mechanism of this is not clear. Thus, obesity has effects on lung function that can generate respiratory distress similar to asthma and may also exaggerate the effects of preexisting asthma(7).

8. Childhood body mass index and subsequent physician-diagnosed asthma
In the study to examine the association between overweight/obesity, defined by body mass index (BMI) >18 years of age, and subsequent physician-diagnosed incident asthma at least one year after BMI assessment. We sought to explore potential effect modification by sex, found that six prospective cohort studies which focused on children >18 years of age met criteria for inclusion. The combined risk ratio (RR) of overweight was associated with asthma (RR = 1.35; 95% CI = 1.15, 1.58). In boys, the combined RR of overweight on asthma was significant (RR = 1.41; 95% CI = 1.05, 1.88). For girls, when BMI was defined by Z-score, the combined RR of overweight on asthma was also significant (RR = 1.19; 95% CI = 1.06, 1.34). The combined risk ratio (RR) of obesity was associated with asthma in both boys and girls (RR = 1.50; 95% CI = 1.22, 1.83), in boys only (RR = 1.40; 95% CI = 1.01, 1.93) and in girls only (RR = 1.53; 95% CI = 1.09, 2.14)(8).

9. Obesity and the risk of newly diagnosed asthma in school-age children
In the study to determine the relation between obesity and new-onset asthma among school-age children,  by examining longitudinal data from 3,792 participants in the Children's Health Study (Southern California) who were asthma-free at enrollment, showed that the risk of new-onset asthma was higher among children who were overweight (relative risk (RR) = 1.52, 95% confidence interval (CI): 1.14, 2.03) or obese (RR = 1.60, 95% CI: 1.08, 2.36). Boys had an increased risk associated with being overweight (RR = 2.06, 95% 1.33, 3.18) in comparison with girls (RR = 1.25, 95% CI: 0.83, 1.88). The effect of being overweight was greater in nonallergic children (RR = 1.77, 95% CI: 1.26, 2.49) than in allergic children (RR = 1.16, 95% CI: 0.63, 2.15). The authors conclude that being overweight is associated with an increased risk of new-onset asthma in boys and in nonallergic children(9).

10. The relation of body mass index to asthma, chronic bronchitis, and emphysema
In the study to determine whether a relation of body mass index (BMI) to asthma, chronic bronchitis (CB), or emphysema exists (analysis 1), and, if so, whether the association between obesity and asthma is modified by gender (analysis 2), showed that adiagnosis of emphysema was significantly associated with a BMI < 18.5 (odds ratio [OR], 2.97; 95% confidence interval [CI], 1.33 to 6.68, when compared to healthy control subjects). A BMI >/= 28 increased the risk of receiving a diagnosis of asthma (OR, 2.10; 95% CI, 1.31 to 3.36) and CB (OR, 1.80; 95% CI, 1.32 to 2.46). About 30% of the patients with asthma and 25% of the patients with CB (vs 16% of the control subjects, p < 0.001) were preobese or obese, regardless whether BMI was assessed before the diagnosis or before the onset of respiratory symptoms. The relation of elevated BMI to asthma was significant only among women(10).

11. The incidence of asthma in young adults
 In the study to determine the incidence of asthma and to establish the risk factors for the development of asthma in subjects who were 12 to 41 years old over an 8-year period, found that there is a continuing high incidence of asthma past childhood that is most pronounced among female subjects. Increasing levels of BMI are associated with a greater likelihood of developing asthma for both sexes. A substantial portion of cases of adult asthma is preceded by upper airway allergic symptoms and/or eczema, thus indicating a shared pathogenesis(11).

12. Risk factors for asthma in young adults
The liability to asthma is influenced both by genetic and environmental factors. In the study to identify risk factors for asthma in young adult twin pairs during an 8-year period, from the birth cohorts 1953-1982 of the Danish Twin Registry, 6,090 twin pairs who were initially unaffected with respect to asthma at a nationwide questionnaire-based study in 1994 participated in a similar follow-up study in 2002, showed that hay fever, eczema, female sex, exercise and increasing levels of BMI were risk factors for asthma in young adults. The different risk profile observed in MZ twins compared with DZ twins may reflect an underlying genetic vulnerability shared between those risk factors and asthma(12).

13. Simple obesity in children. A study on the role of nutritional factors
In the study to examine the effectiveness of dietary treatment in children with simple obesity on the basis of thorough analysis of their state of nutrition, method of nutrition and eating habits and the impact of other environmental factors,. found that
1) Simple obesity in children aged 3-15 yrs is connected with familial and environmental factors, including incorrect eating habits.
2) Dietary treatment consisting in the lowering of energetic value of the diet through the reduction of fat consumption and quantity and quality changes with respect to carbohydrates consumption decreased the children's obesity, and was more effective in the older age group (7-15 yrs). Dietary treatment normalizes the lipid profile in children.
3) Significant body mass loss has been observed in children in whose diet the amount of proteins and their share in the total energy value only slightly differs from the level before the dietary treatment. The amount of proteins in the children's diet was within the range of physiological recommendations(13).

14. Sleep duration, asthma and obesity
Obesity is more prevalent in asthmatics. Short sleep duration is a novel risk factor for obesity in general populations. In the study to test the association of sleep duration and asthma characteristics with obesity. Methods: Adults at tertiary clinics were surveyed on asthma symptoms and habitual sleep duration, indicated that obesity in asthmatics is associated with shorter and very long sleep duration, worse asthma severity, psychopathology, and high dose inhaled corticosteroids. Although this cross-sectional study cannot prove causality, we speculate that further investigation of sleep may provide new opportunities to reduce the rising prevalence of obesity among asthmatics(14).

15. The Effect of Obesity on the Level of Fractional Exhaled Nitric Oxide in Children with Asthma
In the study to to evaluate the association of FeNO with obesity and obesity-related metabolic complications in asthmatic and nonasthmatic children, included children aged between 6 and 17 years and consisted of 4 groups: obese asthmatics (n = 52), normal-weight asthmatics (n = 49), obese nonasthmatics (n = 51) and normal-weight nonasthmatics (n = 42), showed that the FeNO level of asthma patients with MS was not different from those without MS (14.5 ± 8.0 and 16.7 ± 8.7, respectively, p = 0.449). In the nonasthmatic group, subjects with MS had a higher FeNO level than subjects without MS (12.5 ± 5.1 and 17.3 ± 8.3, respectively, p = 0.014). Spearman's rank correlation coefficients revealed a positive correlation between FeNO and body mass index (BMI; p = 0.049, r2: 0.204) in the nonasthmatic group and after multivariate regression analysis, BMI still persisted as an independent risk factor for FeNO and conclude that a positive correlation between BMI and FeNO level which suggests a link between obesity and increased airway inflammation in nonasthmatic children(15).

16. The asthma phenotype in the obese
According to the study by the North Shore-Long Island Jewish Health System, asthma is a heterogenous disorder that can be classified into several different phenotypes. Recent cluster analyses have identified an "obese-asthma" phenotype which is characterized by late onset, female predominance and lack of atopy. In addition, obesity among early-onset asthmatics clearly exists and heightens the clinical presentation. Observational studies have demonstrated that asthma among the obese has a clinical presentation that is more severe, harder to control, and is not as responsive to standard controller therapies. While weight loss studies have demonstrated improvement in asthma outcomes, further studies need to be performed. The current knowledge of the existence of two obesity-asthma phenotypes (early- versus late-onset asthma) should encourage investigators to study these entities separately since just as they have distinct presentations, their course, response to therapies, and weight loss strategies may be different as well(16).

17. Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma
In the study to examine the DNA methylation epigenome-wide in peripheral blood mononuclear cells (PBMCs) from 8 obese asthmatic pre-adolescent children and compare it to methylation in PBMCs from 8 children with asthma alone, obesity alone and healthy controls, showed that PBMCs from obese asthmatic children had distinctive DNA methylation patterns, with decreased promoter methylation of CCL5, IL2RA and TBX21, genes encoding proteins linked with Th1 polarization, and increased promoter methylation of FCER2, a low-affinity receptor for IgE, and of TGFB1, inhibitor of Th cell activation. T-cell signaling and macrophage activation were the two primary pathways that were selectively hypomethylated in obese asthmatics. These findings suggest that dysregulated DNA methylation is associated with non-atopic inflammation observed in pediatric obesity-associated asthma(17).

18. Obesity-associated asthma in children: a distinct entity
Obesity-associated asthma has been proposed to be a distinct entity, differing in immune pathogenesis from atopic asthma. Both obesity-mediated inflammation and increase in adiposity are potential mechanistic factors that are poorly defined among children.  In the study of recruited 120 children, with 30 in each of the four study groups: obese asthmatic children, nonobese asthmatic children, obese nonasthmatic children, and nonobese nonasthmatic children, showed that obese asthmatic children had significantly higher Th1 responses to PMA (P < .01) and tetanus toxoid (P < .05) and lower Th2 responses to PMA (P < .05) and D farinae (P < .01) compared with nonobese asthmatic children. Th-cell patterns did not differ between obese asthmatic children and obese nonasthmatic children. Obese asthmatic children had lower FEV(1)/FVC (P < .01) and residual volume/total lung capacity ratios (P < .005) compared with the other study groups, which negatively correlated with serum interferon-inducible protein 10 and IFN-γ levels, respectively. PFTs, however, did not correlate with BMI z score or waist to hip ratio(18).

19. Mitochondrial dysfunction in metabolic syndrome and asthma
According to the study by the CSIR-Institute of Genomics and Integrative Biolog, severe asthma does not fell in the routine definition of asthma and requires alternative treatment strategies. It has been observed that asthma severity increases with higher body mass index. The obese-asthmatics, in general, have the features of metabolic syndrome and are progressively causing a significant burden for both developed and developing countries thanks to the westernization of the world. As most of the features of metabolic syndrome seem to be originated from central obesity, the underlying mechanisms for metabolic syndrome could help us to understand the pathobiology of obese-asthma condition. While mitochondrial dysfunction is the common factor for most of the risk factors of metabolic syndrome, such as central obesity, dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, the involvement of mitochondria in obese-asthma pathogenesis seems to be important as mitochondrial dysfunction has recently been shown to be involved in airway epithelial injury and asthma pathogenesis(19).

20.  Emerging interface between metabolic syndrome and asthma
There is growing epidemiological evidence that obesity increases the risk of developing asthma. In some studies, insulin resistance or metabolic syndrome is a stronger risk factor than body mass. The obese-asthma subphenotype is marked by a paucity of inflammation but also by marked symptoms, poor response to glucocorticoids, and peripheral airway dysfunction. According to the study by the Institute of Genomics & Integrative Biology, there is growing evidence of the influence of hyperglycemia, hyperinsulinemia, and insulin-like growth factors on airway structure and function. Also, studies from mouse models of asthma have highlighted the importance of nitric oxide-arginine metabolism abnormalities and oxonitrosative stress in lungs. Such changes are well established features of the metabolic syndrome and may represent an interface between these diseases that can be therapeutically targeted. Such therapies, including administration of l-arginine or statins, increasing endothelial nitric oxide synthase, or the use of arginase inhibitors, have been successful in experimental models but have not yet translated to the clinical arena(20).

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