Obesity and asthma

INTRODUCTION — 

Obesity is a risk factor for both incident and prevalent asthma. The interrelationship between obesity and asthma derives from a complex interplay of biologic, physiologic, and environmental factors. Asthma in patients with obesity is often severe and difficult to control [1].

The epidemiology, potential contributing factors, clinical features, diagnosis, and management of coexistent asthma and obesity will be reviewed here. Overviews of obesity and asthma are provided separately.

●(See "Obesity in adults: Prevalence, screening, and evaluation".)

●(See "Obesity in adults: Overview of management".)

●(See "Definition, epidemiology, and etiology of obesity in children and adolescents".)

●(See "Overview of the health consequences of obesity in children and adolescents".)

●(See "Asthma in adolescents and adults: Evaluation and diagnosis".)

●(See "Asthma in children younger than 12 years: Initial evaluation and diagnosis".)

●(See "An overview of asthma management in children and adults".)

EPIDEMIOLOGY — 

The prevalence of asthma is increased in those with concomitant obesity, particularly in the adult female population [1]. In the United States, asthma is significantly more prevalent in patients with obesity compared with the remainder of the population (14.6 versus 7.9 percent prevalence in females, 7.1 versus 6.1 percent prevalence in males) (figure 1) [2]. Children with obesity are also more likely to have asthma (adjusted odds ratio 1.29, 95% CI 1.16-1.42) [3].

Over the past several decades, obesity and asthma have increased in parallel in the United States (figure 2) [4]. Among adults with severe asthma in the United States, nearly 60 percent are obese [1].

There is a dose-dependent effect of obesity on the risk of asthma, such that the greater the body mass index (BMI), the greater the risk of asthma. In adults, the relative risk of asthma increases by 1.32 (95% CI 1.21-1.44) for every 5 kg/m² increase in BMI [5].

In some individuals, the development of obesity precedes asthma, with obesity a risk factor for later asthma development [6,7]. In other individuals, asthma precedes obesity, suggesting that asthma or asthma treatment may be a risk factor for the development of obesity [8,9]. Asthma at the age of three to four years increases the risk of obesity nearly twofold by age eight [10].

POTENTIAL CONTRIBUTING RISK FACTORS — 

Several factors related to obesity likely contribute to the increased risk and severity of asthma in obesity, but the exact pathogenesis is not known.

The pathogenesis of asthma that develops in a patient with obesity may differ from asthma complicated by obesity; obesity and associated metabolic changes may cause airway disease in the first scenario, while they may contribute to asthma severity in the latter.

●Genetic factors – Studies in monozygotic and dizygotic twins suggest that 8 percent of the genetic component of obesity is shared with asthma [11]. In one study, children with a genetic predisposition to adult obesity demonstrated increased risk of lower respiratory tract infections and severe wheeze in early childhood independent of childhood BMI [12].

●Environmental exposures – Observational studies suggest that exposure to air pollution and parental smoking are independent risk factors for the development of both obesity [13-15] and asthma [16,17] in children.

●Dietary factors – Poor dietary quality (eg, diets high in sugar or saturated fatty acids, or low in antioxidants or fiber) is associated with increased respiratory symptoms [18] and contributes to the development of obesity. A meal high in saturated fatty acids can acutely increase airway inflammation [19] and decrease lung function [20]; conversely, a high-fiber supplement has the opposite effect [21]. Low levels of micronutrients such as vitamin D may also contribute to the risk of asthma [1]. At the population level, a tax on sugar-sweetened beverages, which significantly reduced consumption of such drinks, was also associated with significantly reduced admissions for asthma exacerbations [22] in children in the United Kingdom.

●Lung growth – Children with obesity have increased lung volume relative to airway caliber ("dysanapsis"), reflected by a lower than normal ratio of forced expiratory volume in one second to forced vital capacity (FEV₁/FVC) despite normal values for FEV₁ and FVC [23]. Dysanaptic lung growth often manifests as early as infancy [24], and it contributes to airflow limitation in obesity. In addition, dysanapsis is associated with higher insulin levels, increased asthma exacerbations, and use of systemic glucocorticoids in children with asthma [23,25].

●Mechanical factors – Mass loading of the chest wall and abdomen with adipose tissue decreases the functional residual capacity (the lung volume at the end of normal tidal exhalation) (figure 3); breathing at lower functional residual capacity may increase airway reactivity [26]. However, patients with obesity breathe at similarly low lung volumes regardless of asthma status [19], so other factors must also be involved.

●Metabolic dysfunction – Adipose tissue in individuals with obesity releases proinflammatory mediators such as interleukin (IL)-6. High levels of circulating IL-6 are associated with poor asthma control [27], and markers of inflammation in adipose tissue are increased in patients with asthma and obesity compared with those with obesity alone [28,29], implicating metabolic factors in the pathogenesis of asthma in obesity. Thus, the metabolic health of adipose tissue may be more important than the fat mass in terms of asthma severity [1].

Insulin resistance in people with asthma is associated with low lung function, impaired response to bronchodilators, and accelerated lung function decline, illustrating the relationship between metabolic health and asthma [30].

●Immune cell function — Adaptive and innate immune cell function are altered in obesity. One such alteration is suppression of T-helper lymphocyte function involved in allergic responses [28,31-34]. Innate lymphoid cells (ILCs), which respond to intrinsic damage signals rather than antigens, may contribute to asthma airway inflammation in obesity [35]. Interactions between Th1 cells and airway smooth muscle cells may be enhanced in obese asthma [36].

Eosinophil function is also altered by obesity. While submucosal eosinophils are increased in obese patients with asthma relative to overweight and lean subjects, eosinophils in induced sputum and peripheral blood are not increased with obesity [37].

●Increased oxidative stress – Patients with obesity and late-onset (≥12 years) asthma have increased levels of oxidative stress, which is itself associated with impaired lung function [38-40].

●Airway innervation – Animal models of obese asthma suggest that high insulin levels in obesity increase airway innervation and reflex-mediated bronchoconstriction [41].

CLINICAL FEATURES

Asthma symptoms and severity — Symptoms of asthma are the same in those with obesity as in leaner individuals and include wheeze, cough, shortness of breath, and nocturnal symptoms. However, symptom severity may be greater with obesity. The clinical features and biomarkers altered in patients with obesity and asthma are summarized in the figure (figure 4).

Dyspnea is a common symptom in adults with obesity, but not all patients with dyspnea develop asthma. Other etiologies of dyspnea in patients with obesity are uncertain, but increased oxygen cost of breathing, higher rates of perceived exertion, and altered lung physiology likely contribute [42-44].

●Increased severity and worse asthma control in obese adults – Adults with obesity tend to have worse asthma control (increased cough, wheeze, shortness of breath, and nocturnal symptoms) and a greater likelihood of requiring oral glucocorticoids than nonobese individuals [45-47]. In addition, adults with obesity have a two- to four-fold increased risk of being hospitalized for asthma exacerbations compared with lean patients [45,48]; the exacerbation risk increases with increasing BMI in a dose-dependent fashion [49].

●Increased severity in obese children – Children with asthma and obesity also have an increased risk of exacerbations, but the effect on asthma control is not as apparent. While some studies report worse asthma control in the setting of obesity [50], a meta-analysis did not demonstrate a difference [51].

Symptoms of sinonasal disease that are common accompaniments of asthma do not appear to differ among obese and lean patients with asthma [52]. Patients with asthma and obesity are more likely to report symptoms of gastroesophageal reflux and sleep disturbance than nonobese patients [53].

Asthma phenotypes — Among all patients with asthma, a varied spectrum of disease characteristics has been described and sometimes clusters of characteristics, such as age of onset, type of airway inflammation, and physiologic features, are reproducible enough to be considered phenotypes (see "Characterizing severe asthma phenotypes"). Patients with obesity and asthma can be divided into two major categories: (1) asthma complicated by obesity and (2) asthma consequent to obesity; within each group additional phenotypes are still being described [1].

●Asthma complicated by obesity – This phenotype likely includes all asthma phenotypes found in lean patients. The best-recognized phenotype is early-onset allergic asthma complicated by obesity. These patients have early-onset disease (typically <12 years old), elevated markers of allergic inflammation (atopy, allergic symptoms, high serum immunoglobulin E), significant physiologic changes (airway obstruction and hyper-responsiveness), and severe disease [45]. These patients gain weight faster than those with later-onset disease [45].

●Asthma consequent to obesity – Many patients with asthma and obesity have later-onset disease (≥12 years old), less allergic inflammation, and are more likely to be female [45]. Their asthma is typically characterized by less airflow obstruction and hyperresponsiveness measured by spirometry, but some may have significant small airway disease (measured by oscillometry [54,55] or chest CT [56]). There are likely many phenotypes within this population; some patients appear to have neutrophilic airway inflammation, whereas others have little in the way of overt cellular airway inflammation [57].

Physical examination — Apart from obesity, the physical examination may be normal during periods of asthma quiescence, with tachypnea, wheezing, and prolonged expiration appearing only during exacerbations. Stigmata of atopy (eg, allergic rhinitis, atopic dermatitis) may be present, particularly in patients with childhood-onset asthma. (See "The relationship between IgE and allergic disease".)

EVALUATION — 

The evaluation of asthma in patients with obesity is largely the same as in other patients with asthma. It is based on a compatible history and demonstration of variable expiratory airflow limitation (preferably by spirometry). Additional testing may be needed to rule out conditions that might mimic asthma. (See "Asthma in adolescents and adults: Evaluation and diagnosis", section on 'Diagnostic evaluation'.)

History — A detailed history that characterizes the pattern (episodic, continuous), triggers (work, exercise, aeroallergen exposure, smoke exposure) of symptoms, and timing of onset of obesity and asthma is a key part of the evaluation of asthma in all patients (table 1 and figure 5). (See "Trigger control to enhance asthma management".)

Additionally, concomitant symptoms should be explored, particularly those suggestive of comorbid conditions such as rhinosinusitis, obstructive sleep apnea, gastroesophageal reflux disease, metabolic syndrome, and depression, which are more common in obesity and may complicate the disease. (See 'Evaluation of comorbidities' below.)

Identifying the age of onset of asthma and the age of onset of obesity may help distinguish between different phenotypes of obese asthma, which may have implications for disease treatment. (See 'Asthma phenotypes' above.)

Identifying asthma triggers can help distinguish asthma phenotype (allergic versus nonallergic) and identify environmental factors that could be contributing to worsening disease (exposure to tobacco smoke or environmental pollution) (table 1). (See "Trigger control to enhance asthma management".)

Determination of obesity — In general, the determination of obesity is based on the body mass index (BMI). In adults, a BMI ≥30 kg/m² is considered obese; in children, a BMI ≥95^th percentile for age and sex is considered obese (table 2). (See "Obesity in adults: Prevalence, screening, and evaluation" and "Definition, epidemiology, and etiology of obesity in children and adolescents".)

While BMI is commonly used to assess obesity, the actual distribution of fat can influence the effects of adipose tissue on pulmonary and cardiometabolic effects (eg, increased preperitoneal fat mass, but not BMI, is associated with higher fraction of exhaled nitric oxide [FE_NO]), raising the possibility that other measures of fat distribution (eg, waist circumference) might provide a better correlation with clinical effects [58,59]. In general, metabolic dysfunction associated with obesity appears more important than BMI, as measures of metabolic dysfunction are more closely associated with abnormal lung function and asthma exacerbations than BMI itself [30,60].

Pulmonary function testing — Obesity, unless severe or combined with another respiratory disease, has minimal effect on spirometric values and gas transfer. When severe, chest wall and abdominal obesity can cause reduced chest wall and lung compliance with associated restrictive changes in lung volumes and increased work of breathing. These changes are described separately. (See "Chest wall diseases and restrictive physiology", section on 'Obesity'.)

Spirometry with bronchodilator reversibility — Assessment of reversible airflow limitation by spirometry with inhaled bronchodilator reversibility testing is a cornerstone of asthma diagnosis. If airflow obstruction is present, a diagnosis of asthma requires bronchodilator testing to determine reversibility. In contrast, absence of airflow limitation requires bronchoprovocation testing or evidence of reversible airflow limitation over time. (See "Overview of pulmonary function testing in adults" and "Pulmonary function testing in asthma".)

Adults with asthma and obesity often have normal baseline pulmonary function tests without airflow limitation (defined as a ratio of forced expiratory volume in one second to forced vital capacity [FEV₁/FVC] <0.7 or less than the lower limit of normal), or may have a slight decrease in FEV₁ and FVC without a decrease in the ratio [53]. In one study in adults, for every one unit increase in BMI, FEV₁ decreased by 0.47 (95% CI -0.76 to -0.17) percent, and FVC decreased by 0.40 (95% CI -0.66 to -0.14) percent, when corrected for age, sex, and clinic site [53].

In contrast, children with asthma and obesity are more likely to have "dysanapsis" with normal FEV₁ and FVC, but reduced FEV₁/FVC [23]. (See 'Potential contributing risk factors' above.)

Bronchoprovocation testing — Bronchoprovocation testing with pharmacologic agents (eg, methacholine) or physical challenge with eucapnic voluntary ventilation or exercise is useful when patients have symptoms suggestive of asthma, but do not have airflow limitation on spirometry. The techniques for bronchoprovocation testing are described separately. (See "Bronchoprovocation testing".)

Asthma in individuals with obesity is associated with increased airway hyperresponsiveness (AHR; positive bronchoprovocation challenge) whether asthma is early onset (<12 years of age)-allergic or late onset-nonallergic [61]. However, weight loss is associated with decreased AHR in the late onset-nonallergic group, but not the early onset-allergic group. At least a component of the increased AHR in the late onset-nonallergic group appears related to collapsibility of the airways (increased airway elastance) that leads to airway closure at the reduced functional residual capacities found in those with obesity (figure 3).

Fraction of exhaled nitric oxide — FE_NO levels tend to be slightly lower in adults with asthma and obesity than in lean or overweight adults [62,63]. Children with asthma and a low FE_NO are more likely to have increased adiposity indicators (BMI, percent body fat, and waist circumference), while children with asthma and a high FE_NO are likely to have poorly controlled asthma [64]. A FE_NO level of 14.5 parts per billion (ppb) has been suggested as a threshold for identifying eosinophilic disease in patients with obesity, which is substantially lower than the usual cut-point of 25 ppb in adults [62]. (See "Exhaled nitric oxide analysis and applications".)

Laboratory testing — In patients with uncontrolled moderate to severe persistent asthma, we obtain a complete blood count with differential to assess for anemia and eosinophilia, a total serum immunoglobulin E (IgE) level, and allergy testing to environmental allergens (allergy skin tests or immunoassays for allergen-specific serum IgE). In patients with severe asthma, we obtain an alpha-1 antitrypsin level. (See "Asthma in adolescents and adults: Evaluation and diagnosis" and "Asthma in adolescents and adults: Evaluation and diagnosis", section on 'Evaluation'.)

●Thresholds for eosinophilia – Obesity appears to decrease biomarkers of eosinophilic inflammation, but specific thresholds to identify eosinophilic disease in patients with obesity are not well-defined. In a series of 652 patients with asthma, those with obesity were less likely to have evidence of eosinophilic inflammation defined as a sputum eosinophil count >2 percent, blood eosinophil count >300 cells/microL, or FE_NO >25 ppb [62]. While serum IgE and peripheral blood eosinophil levels have a good correlation among patients with obesity [62], peripheral blood and induced sputum eosinophils are likely to underestimate the severity of airway eosinophilia [37]. (See 'Patients with severe asthma' below.)

Evaluation of comorbidities — Patients with asthma and obesity often have multiple comorbidities such as sleep-disordered breathing, gastroesophageal reflux, metabolic syndrome, and depression [65]. These comorbidities may affect asthma control. To evaluate for comorbid conditions that might mimic or contribute to worsening asthma especially in patients with obesity, we consider the following:

●Obstructive sleep apnea (OSA) – Several epidemiologic studies support a strong relationship between OSA and obesity. OSA is associated with worse asthma control, increased health care utilization, and neutrophilic airway inflammation [66,67]. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults".)

Severe or untreated OSA can worsen asthma, reduce functional capacity, and lead to pulmonary hypertension [68-70].

As part of the history, patients should be asked about snoring, sleep quality, nocturnal wakening, and daytime sleepiness; formal documentation using the Epworth Sleepiness Scale may be helpful (calculator 1). Additional studies, such as home sleep apnea testing or in-laboratory polysomnography, may be indicated to evaluate for OSA. (See "Evaluation of suspected obstructive sleep apnea in children" and "Clinical presentation and diagnosis of obstructive sleep apnea in adults" and "Quantifying sleepiness", section on 'Epworth Sleepiness Scale (ESS)'.)

●Gastroesophageal reflux disease – Gastroesophageal reflux disease (GERD) is increased in adults and children with obesity and asthma [71,72]. While the relationship of GERD to asthma is not entirely clear [66,72], GERD may trigger asthma symptoms in some patients. Symptoms of heartburn, regurgitation, sour taste, and chest pain are typical. This topic is discussed in more detail elsewhere. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults" and "Gastroesophageal reflux disease in children and adolescents: Clinical manifestations and diagnosis" and "Gastroesophageal reflux and asthma".)

●Metabolic Syndrome – Metabolic syndrome, characterized by abdominal obesity, insulin resistance, hypertriglyceridemia, and hypertension, is more common in obesity, affecting approximately 60 percent of those who are obese, and may contribute to asthma pathogenesis [39,73,74]. Serum interleukin (IL)-6, a marker of the metabolic syndrome, is increased in patients with poor asthma control [27]. Patients with severe asthma and insulin resistance also show blunted responses to inhaled short-acting beta-agonists and systemic glucocorticoids, as well as greater decline in lung function over time [30]. If not already obtained, glycated hemoglobin A1C may be appropriate to identify diabetes. (See "Metabolic syndrome (insulin resistance syndrome or syndrome X)".)

●Depression – The incidence of depression is increased in patients with obesity and asthma and has been associated with poor asthma control [75,76].

Additional asthma comorbidities not specifically related to obesity are discussed separately. (See "Evaluation of severe asthma in adolescents and adults", section on 'Assessing comorbid conditions'.)

DIAGNOSIS — 

The diagnosis of asthma requires the same criteria in all individuals. It is based on a compatible history of respiratory symptoms (eg, wheeze, shortness of breath, chest tightness, and cough) that vary over time and in intensity, demonstration of variable expiratory airflow limitation (preferably by spirometry), and exclusion of an alternative diagnosis. The key point in patients with obesity is that exclusion of alternative diagnoses becomes more important. (See 'Differential diagnosis' below.)

Concerns about overdiagnosis of asthma have been raised as patients with obesity are more likely to have dyspnea symptoms, although in at least one study overdiagnosis was no greater in obese than nonobese patients [77]. Nonetheless, diagnostic precision is essential to optimal management.

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of asthma in individuals with obesity is similar to other patients. (See "Asthma in adolescents and adults: Evaluation and diagnosis", section on 'Differential diagnosis' and "Asthma in children younger than 12 years: Initial evaluation and diagnosis", section on 'Differential diagnosis'.)

When evaluating patients with obesity for possible asthma, particular attention should be directed to excluding disease processes that are more common in obesity and mimic asthma symptoms (wheezing, dyspnea, cough, and nocturnal symptoms) including the following:

●Goiter with hypothyroidism – Patients with obesity due to hypothyroidism can have cervical or intrathoracic goiter causing tracheal compression (image 1). Patients with tracheal compression typically complain of dyspnea on exertion. Physical examination can identify extrathoracic goiter, but chest imaging is needed to identify intrathoracic goiter. (See "Clinical presentation and evaluation of goiter in adults", section on 'Obstructive symptoms'.)

●Chest wall compression – Class 3 or higher obesity (table 2) in the absence of asthma can cause exertional and nocturnal dyspnea. Chest wall adipose tissue can compress the chest cavity, intra-abdominal adipose tissue can impede diaphragmatic motion, and intrathoracic adipose tissue can (rarely) cause tracheal compression and dyspnea [78,79]. Symptoms may be exacerbated by recumbency. Pulmonary function tests typically show irreversible airflow limitation, but restrictive or mixed defects can also be seen. Imaging is needed for a diagnosis of tracheal compression. (See "Chest wall diseases and restrictive physiology", section on 'Obesity'.)

●Heart failure with preserved ejection fraction (HFpEF) – Obesity is a leading risk factor for HFpEF, and symptoms associated with HFpEF include dyspnea on exertion, paroxysmal nocturnal dyspnea, and orthopnea, which overlap with asthma. It is important to note that natriuretic peptide levels can be normal in patients with obesity and HFpEF, and echocardiography is needed to make the diagnosis. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis", section on 'Evaluation'.)

●Cardiovascular deconditioning – Cardiovascular deconditioning can accompany obesity and cause exertional dyspnea. Cardiopulmonary exercise testing (CPET) can help to assess functional capacity and the physiologic performance of the cardiovascular and respiratory systems in unison. (See "Approach to the patient with dyspnea".)

●Pulmonary hypertension – Among patients with obesity, pulmonary hypertension can develop as a consequence of nocturnal hypoxemia, obstructive sleep apnea, and HFpEF. In addition, the use of some appetite suppressants (generally no longer in use) is associated with pulmonary hypertension. Transthoracic echocardiogram is a first step in diagnosis. (See "The epidemiology and pathogenesis of pulmonary arterial hypertension (group 1)", section on 'Drugs and toxins' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults".)

MANAGEMENT OF ASTHMA IN THE OBESE PATIENT — 

The management of asthma in those with obesity does not generally differ from standard practice. Patients with obesity may have reduced responsiveness to standard controller medications and different thresholds for determination of asthma phenotypes to guide biologic therapy. Evaluation and treatment of common comorbidities, including weight reduction, are also of increased importance. These differences are outlined in the following sections.

Pharmacologic therapy — Pharmacologic treatment is the mainstay of treatment in most patients with asthma; however, treatment of comorbidities and lifestyle interventions are particularly important in patients who also suffer from obesity. Asthma medication guidelines do not differ, although patients with obesity may not be as responsive to standard therapies. (See "An overview of asthma management in children and adults".)

All patients with asthma should have quick relief rescue therapy (see "An overview of asthma management in children and adults") to be used as needed for asthma symptoms and be instructed in the correct inhaler technique. However, a portion of Black or Hispanic adolescents with obesity may be less responsive to inhaled beta-agonists than their leaner peers [80].

Patients who need daily controller medication — Nearly all patients with persistent asthma should be treated with inhaled glucocorticoids according to international guidelines (table 3 and table 4) [65]. (See "Initiating asthma therapy and monitoring in adolescents and adults".)

Inhaled glucocorticoids (also called inhaled corticosteroids [ICS]) reduce the frequency of asthma symptoms, improve asthma-related quality of life, and reduce the risk of severe asthma exacerbations [65,81]. However, studies show attenuated responses to inhaled glucocorticoids in obese patients over the age of five years [82-84], but not among preschool children [85]. Combination therapy with inhaled glucocorticoids and a long-acting beta agonist is more likely to result in asthma control than inhaled glucocorticoids alone, but it is less effective in achieving asthma control in patients with obesity compared with other patients [84].

●Useful add-on therapies – Additional therapies such as long-acting muscarinic antagonists and leukotriene-modifying agents can be added to ICS-LABA therapy if asthma is not well-controlled, or the patient's asthma is more severe. (See "Ongoing monitoring and titration of asthma therapies in adolescents and adults", section on 'Increasing (stepping up) therapy, for persistent poor symptom control'.)

In a randomized trial of tiotropium step-up therapy in 210 patients with asthma, tiotropium improved symptoms and lung function [86]. While obesity was not specifically studied, the mean body mass index (BMI) of study participants was 31.4, suggesting that antimuscarinic agents are effective in patients with asthma and obesity.

Limited data suggest that leukotriene-modifying agents help to maintain asthma control in the obese population [82,87], although a retrospective analysis of four clinical trials found that combination fluticasone-salmeterol was more effective than montelukast even at a high body mass index [88].

●Add-on therapies not helpful in patients with obesity – Theophylline is associated with increased asthma exacerbations among obese patients compared with nonobese patients and is rarely used in this setting [53].

Roflumilast is also associated with an increased risk of asthma exacerbation in individuals with obesity and poorly controlled asthma [89].

Patients with severe asthma — Many patients with obesity and asthma meet criteria for severe asthma. In these patients, we redouble efforts to optimize daily controller medications, asthma education, trigger avoidance, and treatment of comorbidities. We avoid long-term treatment with systemic glucocorticoids if at all possible because the side effects of weight gain and metabolic dysfunction are likely to worsen disease in this patient population in the long term. As an alternative, we evaluate these patients for treatment with biologic agents. (See 'Treatment of comorbidities' below and "Treatment of severe asthma in adolescents and adults", section on 'Persistently uncontrolled severe asthma'.)

When selecting a biologic agent, we consider the following:

●While some studies have reported that patients with obesity have a less favorable response to anti-IgE therapy, the balance of evidence suggests similar effectiveness regardless of body mass [90-93]. However, weight-based dosing precludes omalizumab therapy in patients with a body weight above 150 kg. (See "Anti-IgE therapy".)

●According to meta-analyses, the anti-IL-5 medication mepolizumab reduces asthma exacerbations similarly in patients of all sizes but may have reduced efficacy in improving lung function in people with obesity [94]. Benralizumab, another anti-IL-5 medication, may have slightly less efficacy at reducing exacerbations in those with BMI >35 kg/m² [95].

●Dupilumab, which blocks the receptor for IL-4 and IL-13, appears to have similar efficacy across BMI groups [94]. The same is likely true for tezepelumab, an anti-thymic stromal lymphopoietin antibody [96].

●Traditional thresholds for eosinophilic disease may not be appropriate in patients with asthma and obesity (see 'Laboratory testing' above) [62]. A blood eosinophil count of 96 cells/microL has been suggested as a cutpoint for identifying eosinophilic inflammation in these patients [62], but further research is needed to determine the optimal cutpoints for responsiveness to anti-eosinophilic biologic agents.

Pulmonary rehabilitation — One randomized trial of a pulmonary rehabilitation intervention for people with BMI ≥25 kg/m² found a significant improvement in asthma control scores and decrease in symptoms for those in the pulmonary rehabilitation group compared with those receiving usual care [97].

Treatment of comorbidities — While large studies evaluating whether treatment of most comorbidities improves asthma control in patients with obesity are lacking, conditions such as obstructive sleep apnea, gastroesophageal reflux, metabolic syndrome, type 2 diabetes, and depression warrant treatment in their own right as serious comorbidities [65,81]. Treatment of these comorbid conditions is discussed separately:

●Obstructive sleep apnea (see "Obstructive sleep apnea: Overview of management in adults")

●Gastroesophageal reflux disease (see "Gastroesophageal reflux and asthma")

●Metabolic syndrome (see "Metabolic syndrome (insulin resistance syndrome or syndrome X)", section on 'Therapy')

●Depression (see "Major depressive disorder in adults: Approach to initial management" and "Overview of prevention and treatment for pediatric depression")

●Type 2 diabetes (see "Initial management of hyperglycemia in adults with type 2 diabetes mellitus" and "Management of persistent hyperglycemia in type 2 diabetes mellitus")

In one large retrospective population-based cohort study of patients with asthma, initiation of metformin for type 2 diabetes was associated with an approximately 30 percent reduction in asthma exacerbations in the ensuing 12 months [98]. This was true both for 4278 patients when compared with their exacerbation rates in the year prior to metformin initiation (incident rate ratio 0.68, 95% CI 0.62-0.75) and in a separate group of 8424 patients matched with similar patients who only received metformin after the end of the study period (hazard ratio 0.76, 95% CI 0.67-0.85). Add-on GLP-1 inhibitors demonstrated an additional persistent reduction in asthma attacks over the one-year period (incident rate ratio 0.6, 95% CI 0.5-0.7). Sex, BMI, and hemoglobin A1c level did not modify the effect, suggesting the mechanism of improvement from these agents may not be related directly to their impact on type 2 diabetes or obesity. These results are consistent with prior publications in the United States, using electronic health record data [99] and health claims data [100].

Weight loss interventions — Weight loss interventions include a wide variety of strategies, such as liquid-diet replacement, diet and exercise, GLP-1 inhibitors, and bariatric surgery [62,101-103]. In general, studies of weight loss interventions show improvements in asthma control, asthma-related quality of life, and lung function if a sufficient amount of weight loss (at least 5 percent) is attained [101,103-105]. An approach to weight loss interventions is discussed separately. (See "Obesity in adults: Overview of management".)

●Behavioral lifestyle interventions – Behavioral lifestyle interventions have been successful in achieving and maintaining weight loss in patients with hypertension and diabetes. In asthma, evidence of benefit is accruing with behavioral lifestyle interventions that incorporate diet and exercise with studies showing improvements in spirometry, asthma control, quality of life, airway inflammation, and exacerbation frequency depending on the outcomes examined [1,106-108]. In a systematic review, four randomized trials involving children (n = 246) and adults (n = 502) used various combinations dietary restrictions, exercise, and cognitive behavioral therapy (CBT) and found improvements in asthma-related quality of life and, to some degree, asthma control [106]. Differences in interventions, outcomes, and duration precluded pooled analysis. Effects on airway reactivity are variable [109,110], perhaps due to heterogeneity among patients with asthma and obesity in the studies. (See "Obesity in adults: Behavioral therapy".)

●Drug therapy for obesity – Drug therapy for obesity (eg, glucagon-like peptide 1 agonists, phentermine-topiramate, and others) may be appropriate for some patients who have not lost weight with behavioral lifestyle interventions alone. Individualized discussion of the risks and benefits is advisable. (See "Obesity in adults: Drug therapy".)

In one retrospective database study, 4373 adult patients with asthma who were initiating GLP-1R agonists for type 2 diabetes had fewer asthma exacerbations compared with those starting other agents for treatment intensification [99]. Similar findings were seen in a separate retrospective cohort study [98]. These results were independent of changes in BMI and hemoglobin A1c, suggesting mechanisms in addition to weight loss and glycemic control in this population.

●Bariatric surgery – For patients with asthma and obesity, bariatric surgery is typically reserved for those with a BMI ≥35 kg/m² who have not been able to lose sufficient weight by other methods. As bariatric surgery carries the risk of peri- and postoperative morbidity that may be exacerbated by severe asthma and requires lifelong lifestyle changes, a careful evaluation of the risks and benefits of surgery should be discussed in detail with each patient. (See "Bariatric surgery for management of obesity: Indications and preoperative preparation", section on 'Indications' and "Metabolic and bariatric operations: Early morbidity and mortality" and "Anesthesia for adult patients with asthma".)

Bariatric surgery can produce significant weight loss, and nonrandomized prospective and retrospective data suggest that it can improve asthma control, airway reactivity, and lung function [28,111-116]. Additionally, a self-controlled case series of 2261 patients suggests that bariatric surgery can reduce asthma exacerbations by almost 60 percent [116,117].

Vaccinations — Vaccination strategies against respiratory infections are similar to those suggested for other patients with asthma. However, obesity may further increase the risk of severe respiratory infections, increasing the benefits of vaccination in this population. (See "An overview of asthma management in children and adults", section on 'Immunizations and antiviral strategies'.)

●Patients with obesity and asthma are at increased risk of severe disease from influenza (table 5) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (table 6), so annual administration of influenza and COVID vaccines is appropriate [118-120]. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines".)

●Patients with asthma are likewise at increased risk from pneumococcal disease [121]; pneumococcal vaccination is recommended for obese patients with asthma as described elsewhere (algorithm 1 and algorithm 2 and table 7). (See "Pneumococcal vaccination in adults" and "Pneumococcal vaccination in children".)

●Adults with asthma are also more likely to develop severe respiratory syncytial virus (RSV) infection than the general population. Vaccination is therefore appropriate for many older adults with asthma. (See "Respiratory syncytial virus infection in adults", section on 'Severe disease' and "Respiratory syncytial virus infection in adults", section on 'Vaccination'.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Asthma in children" and "Society guideline links: Asthma in adolescents and adults" and "Society guideline links: Severe asthma in adolescents and adults" and "Society guideline links: Obesity in children" and "Society guideline links: Obesity in adults".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (See "Patient education: Asthma in adults (The Basics)" and "Patient education: Asthma in children (The Basics)" and "Patient education: Avoiding asthma triggers (The Basics)" and "Patient education: Health risks of obesity (The Basics)" and "Patient education: Weight loss treatments (The Basics)" and "Patient education: Shortness of breath (The Basics)" and "Patient education: Cough in adults (The Basics)" and "Patient education: Cough in children (The Basics)".)

●Beyond the Basics topics (See "Patient education: Asthma symptoms and diagnosis in children (Beyond the Basics)" and "Patient education: Trigger avoidance in asthma (Beyond the Basics)" and "Patient education: Asthma treatment in adolescents and adults (Beyond the Basics)" and "Patient education: Chronic cough in adults (Beyond the Basics)" and "Patient education: Shortness of breath (dyspnea) (Beyond the Basics)".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Obesity is a risk factor for the development of asthma, and asthma may increase the risk of developing obesity. Adults and children with obesity have a greater risk of exacerbations than lean adults and children. In adults, but not children, obesity is associated with worse asthma control. (See 'Epidemiology' above and 'Asthma symptoms and severity' above.)

●Clinical manifestations – Symptoms of asthma are the same in all individuals and include wheeze, cough, shortness of breath, and nocturnal symptoms; however, symptom severity, particularly dyspnea, may be greater with obesity. (See 'Clinical features' above.)

●Evaluation and diagnosis

•The evaluation and diagnosis of asthma in patients with obesity is largely the same as in other patients. It is based on a compatible history and demonstration of variable expiratory airflow limitation (preferably by spirometry), along with additional testing to rule out conditions that might mimic asthma. (See 'Evaluation' above.)

•Peripheral blood and induced sputum eosinophils are likely to underestimate the severity of airway eosinophilia in obese patients. (See 'Laboratory testing' above.)

●Pharmacologic management

•Initial pharmacologic therapy for asthma in patients with obesity follows standard guidelines (table 3 and table 4). While some of these patients have reduced response to inhaled glucocorticoids or combination therapy with inhaled glucocorticoid-long-acting beta agonists, these medications generally perform better than leukotriene receptor antagonists, and combination therapy performs better than inhaled glucocorticoid alone. Long-acting muscarinic antagonists added to inhaled glucocorticoids are as effective in all patients with asthma. (See 'Pharmacologic therapy' above.)

•When selecting a biologic agent for patients with severe asthma and obesity, weight-based dosing of anti-IgE agents precludes therapy in patients with a body weight above 150 kg. Obesity appears to decrease biomarkers of eosinophilic inflammation, but specific trials using different eosinophil cut-points for anti-eosinophil agents in obese patients are lacking. (See 'Patients with severe asthma' above.)

•A brief course of oral glucocorticoids may be needed periodically to treat an asthma exacerbation, but every effort should be made to avoid long-term use of oral glucocorticoids in this population. (See 'Pharmacologic therapy' above.)

●Comorbidities – Comorbidities such as obstructive sleep apnea, gastroesophageal reflux disease, metabolic syndrome, type 2 diabetes, and depression, are more common in patients with obesity and are associated with poor asthma control. Screening for and treating these conditions is prudent, especially in patients with poorly controlled asthma. (See 'Evaluation of comorbidities' above.)

●Effect of weight loss on asthma

•Behavioral lifestyle interventions incorporating diet and exercise and achieving weight loss of at least 5 to 10 percent may improve asthma control and quality of life, although data are limited. Similar effects might be expected from weight loss achieved with these interventions and additional pharmacologic assistance. (See 'Weight loss interventions' above.)

•Bariatric surgery is typically reserved for patients with a BMI ≥35 kg/m² and an associated comorbidity, such as severe asthma. It can lead to significant improvements in asthma control and reduce the risk of asthma exacerbations. As severe asthma increases the risk of adverse outcomes from major surgery, a careful evaluation of the risks and benefits of surgery should be discussed in detail with each patient. (See 'Weight loss interventions' above.)

●Preventative health maintenance – Patients with asthma and obesity should receive appropriate vaccinations against respiratory viral infections given the increased risks of severe pulmonary infection. (See 'Vaccinations' above.)