Vol. 14 •Issue 2 • Page 16
Allergy & Asthma
Researchers Have Their Appetite Whetted About Link Between Asthma and Obesity
The growing prevalence of obesity has been accompanied by rapidly rising asthma rates worldwide in children and adults.
The first reports to describe such an association date back to the 1980s.1,2 However, the nature of this relationship has been a controversial topic in medicine.
While a detailed review of the epidemiologic literature is beyond the scope of this piece, it’s important to note that several studies have presented conflicting statistics in describing a possible connection between asthma and obesity.
Cross-sectional diagnosis of asthma has been noted in obese children and adults.3-6 The Growing Up Today study found that being overweight was an independent risk of incident asthma in boys and girls, suggesting that increasing prevalence of obesity may partly explain the rising asthma prevalence in children.7
Similarly, the Children’s Health Study in Southern California concluded that being overweight and obese were associated with new-onset asthma in boys and girls.8 The study examined 3,792 school-age children who were free of asthma upon enrollment.
After a six-year follow-up, the risk of new-onset asthma was higher among children who were overweight (relative risk [RR] = 1.52) or obese (RR = 1.60) compared to their non-obese counterparts.
Similar findings also were derived from the adult population. The Canadian National Health Survey tracked new cases of asthma among 4,266 men and 4,883 women over a two-year period. During the study, 1.6 percent of the men and 2.9 percent of the women developed asthma. The adjusted odds ratio (OR) for asthma was 1.52 in obese women compared to non-obese ones.9
Also, a recent prospective study of adult twins in Finland followed for nine years found obesity (body mass index = 30) to be associated with a significant risk of adult-onset asthma (OR = 3.0) compared to those with normal weight.10
Several of these studies have noted a linear dose-relationship between BMI and asthma prevalence. This relationship was reported to be only in women, while others exclusively in men.1,9,11,12
These findings were first documented in the Nurses’ Health Study II.13 After controlling for age, race, smoking, physical activity and energy intake, the evidence pointed to a dose-response relationship between BMI and the relative risk of adult-onset asthma.
Women who had gained 10 to 20 kg since the age of 18 had a RR of 1.4 of developing asthma compared with women whose weight remained stable; while those who had gained more than 25 kg since the age of 18 had a 2.7 higher relative risk of developing asthma. Conversely, data from the Normative Aging Study supported a dose relationship in men with BMI ranging between 24 and 29 kg/m2.14
The most compelling evidence of a causal link between obesity and asthma in adults is provided by studies linking weight loss to reduced severity and frequency of asthma symptoms. Using a non-blinded, randomized clinical trial, 38 obese subjects with asthma were assigned to either an intensive dietary program or a control group.15 At the end of dieting, there was a statistically significant increase in both FEV1 and FVC of the study group compared to the control group. Even after one year, the differences in FEV1 and FVC remained statistically significant.
Two other studies that focused on asthma therapy usage post-gastric bypass surgery reported 50 percent and 100 percent decrease in medication, respectively.16,17 The improvement encompassed all aspects of asthma.18
Several authors have looked into what could be causing the increased incidence of asthma in the obese.
The evidence suggesting an epidemiological linkage between asthma and obesity raises the paradigm of “the chicken and the egg” question. Is it the development of obesity that predisposes to asthma, or is it actually asthma leading to obesity?
It’s conceivable that subclinical or exercise-induced asthma may lead to exercise limitation, which in turn would decrease caloric expenditure causing increased body weight. This hypothesis was tested in a community-based cohort of urban young adults aged 18 to 30 years old followed prospectively for up to 10 years.19
Although a significant association between asthma and BMI was observed, this association wasn’t explained by a lower physical activity. A similar conclusion was reached by a previous population-based study that demonstrated that leisure-time energy expenditure wasn’t lower in asthmatic patients compared to non-asthmatic patients.20
It was suggested instead that the obesity-related sedentary lifestyle may be a precursor of increased airway responsiveness.4,21
A cross-sectional study of 7,019 rural Chinese lend support to a linkage between asthma (defined by airway hyperresponsiveness to methacholine challenge testing) and overweight conditions.22
Furthermore, increased physical activity has been correlated with decreases in the relative risk of incident asthma in schoolchildren and in twins discordant for the same diagnosis.23,25
This concept, however, was challenged by a recent trial of obese women with asthma who were enrolled in an intensive weight loss program. The study didn’t show any significant effect of weight loss on airway reactivity despite improvement in lung function. These findings suggest that the improvements occurred due to a reduction in mass loading on the respiratory system, rather than improvements in asthma per se.25
Obesity has several mechanical effects on respiratory function. It has been long known to decrease tidal volume, leading to a reduction in functional residual capacity due to the effects of the abdominal contents on the position of the diaphragm.26
The decrements in FRC and tidal volume infer small cycling rates resulting in conversion of airway smooth muscle from rapidly cycling actin-myosin cross-bridges to slowly cycling “latch bridges.”27 This change in airway smooth muscle compliance has been postulated to lead to an increased airway resistance and responsiveness to methacholine.28
A common clinical entity shared between asthma and obesity is the occurrence of gastroesophageal reflux. The increased pressure gradient across the gastroesophageal junction in obese individuals is thought to be responsible for acid-induced bronchoconstriction.
Mechanically, this effect may occur either secondary to microaspiration or vagally mediated reflex.29 Although a direct cause/effect relationship is lacking, both medical and surgical weight loss regimens have yielded significant improvement in obese patients with GER-related asthma symptoms, pointing to an association between these two entities.16
A notable observation from a recently conducted cross-sectional study suggests a significant association between obesity and asthma in post-pubertal girls and adult females. These findings, however, weren’t universal as the association between symptoms and obesity were almost identical in men and women.30
Part of the explanation for this heterogeneity in the findings may be in study size and methodology. A number of studies haven’t reported a test of interaction but analyzed data for men and women separately on a priori grounds because of the previous reports of differing associations.
Others have reported a combined effect, so the evaluation of the evidence for and against a sex difference is quite difficult. Nonetheless, women appear to have a higher prevalence of airway hyperresponsiveness than men that persists after adjusting for airway size.31
Moreover, postmenopausal hormonal replacement therapy has been implicated in a significant rise in the incidence of asthma in women.32 These associations led investigators to suspect a role for the sex hormones in the pathogenesis of obesity-related asthma.
Because estrogen amplification is reported to occur in the stroma of adipose tissue of obese subjects through aromatization of testosterone and androstenedione, it has been suggested that the excess female sex hormones may alter smooth muscle beta2-adrenergic receptor function.
During the menstrual cycle, peak estrogen levels have been correlated with decreased pulmonary function in asthmatic women.33 Moreover, estrogen administration has been shown to cause a shift in the T lymphocytes subpopulation from Th1 to a Th2 type and to drive an increase in eosinophil recruitment and degranulation.34,35
These potential associations between asthma and obesity beg the question of whether asthma behaves differently in the obese patient.
A multicenter prospective cohort study that looked at 572 patients between the ages of 18 and 54 presenting to the emergency department with acute asthma exacerbation found no difference between the groups with respect to severity, duration of symptoms, treatment response, hospital admissions or length of stay.36 One intervention in the obese asthmatic that showed consistently positive response is weight loss.
A Finnish study reported decreased dyspnea, reduced rescue medication usage and number of exacerbations, and increased quality of life when these patients lost a mean of 14.5 percent of their pretreatment weight.15
More recently, a prospective study of 58 obese women with asthma showed that for every 10-percent relative reduction in body weight, FVC increased by 92 mL and FEV1 increased by 73 mL. There also was an increase in health status.25
While far from being definitive, these studies suggest that weight reduction is of benefit in the obese asthmatic and should be an important treatment intervention.
Dr. Krause is a fellow in pulmonary and critical care medicine at the University at Buffalo, New York. Dr. El Solh is an associate professor of medicine and the director of the medical intensive care unit at the same facility.
For a list of references, please call Mike Bederka at (610) 278-1400, ext. 1128, or visit www.advanceweb.com/respmanager.