Obesity alters lung function, can cause symptoms suggesting asthma, and may worsen preexisting asthma. The precise mechanisms on how obesity leads to or worsens asthma are not well elucidated. A combination of mechanical factors, adipose-released inflammatory mediators, and immune system activation appears likely responsible for the “obese-asthma” phenotype.

Pregnancy has a variable and unpredictable effect on asthma. Studies suggest maternal obesity may be a risk factor for the development of asthma in offspring.

In this chapter, we discuss the evidence linking asthma to obesity, review the proposed mechanisms, and discuss the clinical care of obese individuals with asthma (see Box 7-1 for key clinical points).

Asthma prevalence has increased in parallel with obesity.^1,2 Of US adults, 8% have asthma—an increase from the 1980 value of 3.1%.² In the bariatric surgery population with body mass index (BMI) greater than 60 kg/m², the asthma prevalence is estimated to be 33%.³

Obesity is defined as BMI greater than 30 kg/m². While simple to calculate and commonly used, BMI is not the best measure of assessing body fat influence on respiratory diseases. BMI does not capture fat distribution patterns or assess metabolically active adipose. The android pattern (abdominal fat distribution), rather than a gynoid (gluteofemoral) pattern, is associated with higher asthma risk.^4,5 The metabolically more active ectopic fat present in muscles and viscera, as measured by computed tomography (CT) or magnetic resonance imaging (MRI), may predict asthma risk more accurately.⁶

A meta-analysis involving 333,000 adults showed a modest risk of developing asthma (odds ratio [OR] 1.5; 95% confidence interval [CI] 1.27–1.80) in overweight or obese (BMI ≥25) compared to normal-weight adults (p < .0001). When the analysis was restricted to obese (BMI >30), the risk doubled.⁷ A positive dose-response relationship exists between obesity and asthma. Several limitations to epidemiological asthma-obesity studies exist. Many studies relied on patient-reported asthma diagnosis and so could overestimate risk by overdiagnosing asthma. Also, a U-shaped relationship between weight and risk of asthma could lead investigators to underestimate the risk. Asthma prevalence increases among individuals with either low BMI or high BMI, forming a U-shaped curve.⁸ Studies that include individuals with low BMI among those with normal BMI may underestimate the obesity effect on asthma.

Studies that have assessed the effect of weight loss on asthma support the obesity and asthma association. Weight loss of at least 10% has been shown to improve lung function in obese individuals with asthma.⁹ A randomized, controlled trial of bariatric surgery in patients with asthma and without asthma found significant improvement in clinical and physiological parameters. Twelve months after surgery, individuals with asthma experienced significant improvement in asthma control, quality of life, and the need for rescue β₂-agonists.¹⁰

Several confounding factors may be responsible for the association of asthma with obesity. For example, poor diet, lack of physical activity, and shared genes and environment may affect the incidence of both asthma and obesity independently as well as via complex interactions. In addition, patients with asthma may become overweight from the side effects of corticosteroids and lack of physical activity.

Lack of physical activity could promote asthma. Vigorous physical exercise is known to augment bronchodilation, hyperinflation, and cyclical smooth muscle stretch. Lack of these protective physiological events, in the absence of physical exercise, may lead to increased airway hyperresponsiveness (AHR) and asthma.¹¹

The relationship between diet and obesity seems obvious. However, obese patients may consume no more calories than lean individuals.¹² In regard to asthma risk, types of food consumed appear more important than the total calorie intake. Lack of dietary antioxidants, such as omega-3 fatty acid, has been associated with asthma in children.¹³ A high-fat diet has been shown to lead to increased airway inflammation and to impair bronchodilator recovery.¹⁴ Obese individuals tend to have diets high in fat and low in antioxidants.¹² Despite these observations, when adjusted for diet and level of physical activity, the asthma-obesity association persists in patients who already have developed asthma. Results from prospective intervention studies, however, are conflicting.¹⁵ Pregnancy creates a unique situation to prospectively assess the effects of dietary manipulation on the risk of asthma and obesity in children. Some cohort studies and few intervention studies suggested an advantageous effect of maternal dietary modification, especially a diet high in omega-3 polyunsaturated fatty acids (PUFAs; found in fish oil) content, on the risk of asthma in children.^16,17,18 Little is known about the role of maternal dietary constituents and the risk of obese asthma in the offspring. Maternal diet could alter both asthma and obesity risk by influencing fetal programming of genes in utero.

Common environmental factors and shared genes may influence the association between asthma and obesity. Studies suggested a shared genetic makeup in asthma and obesity.¹⁹ The probability (genetic liability) of this sharing to lead to the development of asthma and obesity appears to be significantly correlated with female gender.²⁰ Joint asthma-obesity candidate genes, such as β₂-receptor and tumor necrosis factor alpha (TNF-α) have been identified, but not confirmed.²¹ Asthma and obesity are more common in minorities and groups with low socioeconomic status. Future studies examining epigenetic mechanisms and gene-by-gene and gene-by-environment interaction are needed.

Sex Effect on Obesity and Asthma

While an asthma-obesity association has been found in both men and women, some epidemiological studies noted the association was much stronger in women. Several potential explanations for this stronger association in women exist. Studies have shown that obese women are more likely to be diagnosed with asthma as compared to obese men when they have respiratory symptoms.²² This may be partly because women tend to seek medical care more readily for respiratory symptoms than men. This leads to misclassification when the asthma diagnosis is not verified with spirometry or challenge testing. Hormonal differences may contribute to differences in gender effect on asthma prevalence. Prepubertal boys are more often affected with asthma than prepubertal girls and the risk reverses after puberty.²³ Similarly, early menarche in school-aged obese girls increases the risk of asthma, possibly from extended estrogen exposure.²⁴ Women frequently report worsening of asthma symptoms around menstrual periods.²⁵ Multiple prospective studies of hormone replacement therapy suggested increased asthma risk in postmenopausal women (OR 1.38 to 1.57).^26,27,28

Pregnancy, Asthma, and Obesity

Asthma affects 4%–6% of pregnant women. The course of asthma in pregnancy is unpredictable. One-third of pregnant women will have worsening, one-third will have no change, and one-third will have improvement in asthma symptoms during pregnancy.²⁹ Women with mild disease are less likely to experience problems, whereas those with severe asthma are at high risk of deterioration, especially during the period of significant weight gain in late second and third trimesters, between the 25th and the 32nd weeks of gestation. Asthma control usually reverts to the prepregnancy level within 3 months of delivery, but the severity of asthma remains consistent in subsequent pregnancies. Progesterone-mediated bronchodilation and anti-inflammatory effects of increased free cortisol might explain the improvement seen in some women.

Factors that tend to worsen asthma control are decreased functional residual capacity (FRC), increased oxidative stress, altered immune regulation in pregnancy, and increased prevalence of gastroesophageal reflux disease (GERD). Some experience worsening of symptoms because of reduction or stopping of medication secondary to fear of adverse effects to the fetus. Prepregnancy factors associated with increased risk of worsening include severe disease, poor asthma-related quality of life, and cigarette smoking.³⁰ Maternal obesity, after adjusting for confounders, has also been recognized as a risk factor for poor asthma control and asthma exacerbation during pregnancy.³⁰ Similarly, pregnant women with asthma tend to be obese compared to pregnant women without asthma.

Studies suggest an increased risk of asthma in offspring of obese pregnant women. In a population-based cohort study, pre-pregnancy birth weight and gestational weight gain were independently associated with asthma in the offspring during 7-year follow-up. This association was independent of the child’s BMI.³¹ Another observational study demonstrated that maternal weight gain during pregnancy can predict asthma and low lung function at 9 years of age among children who exhibited persistently elevated serum TNF-α level (lipopolysaccharide induced) at birth and 3 month.³² A prospective randomized controlled trial of weight management in pregnancy and asthma risk in offspring is needed.

Altered Respiratory Physiology

Obesity alters respiratory function, particularly lung volumes (Figure 7-1). The effect of obesity on the respiratory system depends on the pattern of fat distribution. Central obesity (abdominal and visceral adiposity) exerts greater respiratory load than peripheral obesity (femur-gluteal adiposity) (Figure 7-2).

Functional residual capacity, the resting lung volume at the end of a tidal breath, is determined by the balance between inflationary forces due to chest wall recoil and deflationary forces due to lung parenchymal elastic recoil and collapse. Adipose tissue decreases chest wall recoil by mass loading. Increased abdominal pressure from central obesity increases the deflationary forces. Additional factors leading to a decrease in FRC include atelectasis, redistribution of blood flow, and changes in alveolar surfactant. Pregnancy further exaggerates the deflation as the size of the uterus increases in late pregnancy.

The FRC is partitioned into two volumes (Figure 7-1): expiratory reserve volume (ERV), the air that can be forcefully exhaled after the end of a tidal breath; and residual volume (RV), the air left in the lung after the ERV has been expired. Decreased ERV out of proportion to decreased FRC is the most common finding on pulmonary function testing. Total lung capacity (TLC) is usually preserved in obesity except at extreme obesity. Diffusion capacity of the lungs for carbon monoxide (DLCO), a measure of gas transfer across the capillary surface, is normal or increased.

Airway hyperresponsiveness measured by bronchial challenge testing is the cardinal feature of asthma. Human and animal studies suggested obesity can lead to AHR.^33,34 In a study of 1725 adults with respiratory symptoms and without previous asthma diagnosis, Sood et al. showed that AHR increased with increasing BMI.³³ Surgical weight loss studies have demonstrated improvement in AHR 12 months after surgery but only in individuals with nonatopic asthma.¹⁰ Proposed mechanisms for hyperresponsiveness in obesity are (1) increased airway smooth muscle contractility secondary to breathing at low lung volume and (2) enhanced inflammation.

Low lung volumes decrease the retractive forces on airways and decrease airway caliber. Persistent decrease in airway caliber induces changes in airway smooth muscles to shorter length and alters the actin myosin cross-bridging cycle. These changes make airway smooth muscles more reactive and contract at higher velocity.³⁵ Breathing at low lung volumes promotes dynamic hyperinflation and air trapping with mild bronchospasm and during tidal breathing during exertion. Hyperinflation and air trapping adds to the load that respiratory muscles need to overcome to breathe. This can give rise to an exaggerated sensation of dyspnea.