Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk, and obese asthmatic patients have more symptoms, more frequent and severe exacerbations, reduced response to several asthma medications, and decreased quality of life. Obese asthma is a complex syndrome, including different phenotypes of disease that are just beginning to be understood. We examine the epidemiology and characteristics of this syndrome in children and adults, as well as the changes in lung function seen in each age group. We then discuss the better recognized factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, and the genetics/genomics of obese asthma. Finally, we describe current evidence on the effect of weight loss and mention some important future directions for research in the field.

There is a major epidemic of obesity, and many obese patients suffer with respiratory symptoms and disease. The overall impact of obesity on lung function is multifactorial, related to mechanical and inflammatory aspects of obesity. Areas covered: Obesity causes substantial changes to the mechanics of the lungs and chest wall, and these mechanical changes cause asthma and asthma-like symptoms such as dyspnea, wheeze, and airway hyperresponsiveness. Excess adiposity is also associated with increased production of inflammatory cytokines and immune cells that may also lead to disease. This article reviews the literature addressing the relationship between obesity and lung function, and studies addressing how the mechanical and inflammatory effects of obesity might lead to changes in lung mechanics and pulmonary function in obese adults and children. Expert commentary: Obesity has significant effects on respiratory function, which contribute significantly to the burden of respiratory disease. These mechanical effects are not readily quantified with conventional pulmonary function testing and measurement of body mass index. Changes in mediators produced by adipose tissue likely also contribute to altered lung function, though as of yet this is poorly understood.

The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group was coordinated and supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. It is designed to improve patient care and support informed decision making about asthma management in the clinical setting. This update addresses six priority topic areas as determined by the state of the science at the time of a needs assessment, and input from multiple stakeholders: Fractional Exhaled Nitric Oxide Testing Indoor Allergen Mitigation Intermittent Inhaled Corticosteroids Long-Acting Muscarinic Antagonists Immunotherapy in the Treatment of Allergic Asthma Bronchial Thermoplasty A rigorous process was undertaken to develop these evidence-based guidelines. The Agency for Healthcare Research and Quality’s (AHRQ) Evidence-Based Practice Centers conducted systematic reviews on these topics, which were used by the Expert Panel Working Group as a basis for developing recommendations and guidance. The Expert Panel used GRADE (Grading of Recommendations, Assessment, Development and Evaluation), an internationally accepted framework, in consultation with an experienced methodology team for determining the certainty of evidence and the direction and strength of recommendations based on the evidence. Practical implementation guidance for each recommendation incorporates findings from NHLBI-led patient, caregiver, and clinician focus groups. To assist clincians in implementing these recommendations into patient care, the new recommendations have been integrated into the existing Expert Panel Report-3 (EPR-3) asthma management step diagram format.

Background Asthma in obese individuals is poorly understood, these patients are often refractory to standard therapy. Objectives To gain insights into the pathogenesis and treatment of asthma in obese individuals by determining how obesity and bariatric surgery affect asthma control, airway hyperresponsiveness and markers of asthmatic inflammation. Methods A prospective study of (i) asthmatic and non-asthmatic bariatric surgery patients compared at baseline, and (ii) asthmatic patients followed for 12 months after bariatric surgery. Results We studied 23 asthmatic and 21 non-asthmatic patients undergoing bariatric surgery. At baseline, asthmatics had lower FEV1 and FVC, and lower levels of lymphocytes in bronchoalveolar lavage. Following surgery, asthmatic participants experienced significant improvements in asthma control (asthma control score 1.55 to 0.74, p < 0.0001) and asthma quality of life (4.87 to 5.87, p < 0.0001). Airways responsiveness to methacholine improved significantly (PC20 3.9 to 7.28, p = 0.03). There was a statistically significant interaction between IgE status and change in airways responsiveness (p for interaction term = 0.01), improvement in AHR was significantly related to change in BMI in those with normal IgE (p = 0.02, R2 = 0.46). The proportion of lymphocytes in bronchoalveolar lavage and production of cytokines from activated peripheral blood CD4+ T cells increased significantly. Conclusions Bariatric surgery improves airway hyperresponsiveness in obese asthmatics with normal serum IgE. Weight loss has dichotomous effects on airway physiology and T cell function typically involved in the pathogenesis of asthma, suggesting that obesity produces a unique phenotype of asthma that will require a distinct therapeutic approach.

There is an urgent need for research to better understand the mechanisms of asthma in the obese, and to develop new therapies specifically targeted to this unique patient population.

Background The interleukin (IL)-1 family member IL-33 plays a critical role in type-2 innate immune responses to allergens, and is an important mediator of allergic asthma. The mechanisms by which allergens provoke epithelial IL-33 secretion are still poorly understood. Objective Based on previous findings indicating involvement of the NADPH oxidase DUOX1 in epithelial wound responses, we explored the potential involvement of DUOX1 in allergen-induced IL-33 secretion and potential alterations in airways of subjects with asthma. Methods Cultured human or murine airway epithelial cells or mice were subjected to acute challenge with Alternaria alternata or house dust mite (HDM), and secretion of IL-33 and activation of subsequent type 2 responses were determined. The role of DUOX1 was explored using siRNA approaches and DUOX1-deficient mice. Cultured nasal epithelial cells from healthy or asthmatic subjects were evaluated for DUOX1 expression and allergen-induced responses. Results In vitro or in vivo allergen challenge resulted in rapid airway epithelial IL-33 secretion, which critically depended on DUOX1-mediated activation of epithelial epidermal growth factor receptor (EGFR) and the protease calpain-2, via a redox-dependent mechanism involving cysteine oxidation within EGFR and the tyrosine kinase Src. Primary nasal epithelial cells from subjects with allergic asthma were found to express elevated DUOX1 and IL-33, and demonstrated enhanced IL-33 secretion in response to allergen challenge compared to nasal epithelial cells from non-asthmatic subjects. Conclusion Our findings implicate epithelial DUOX1 as a pivotal mediator of IL-33-dependent activation of innate airway type 2 immune responses to common airborne allergens, and indicate that enhanced DUOX1 expression and IL-33 secretion may present important contributing features of allergic asthma.

Rationale: Obesity is a major risk factor for asthma; the reasons for this are poorly understood, although it is thought that inflammatory changes in adipose tissue in obesity could contribute to airway inflammation and airway reactivity in individuals who are obese. Objectives: To determine if inflammation in adipose tissue in obesity is related to late-onset asthma, and associated with increased markers of airway inflammation and reactivity. Methods: We recruited a cohort of obese women with asthma and obese control women. We followed subjects with asthma for 12 months after bariatric surgery. We compared markers in adipose tissue and the airway from subjects with asthma and control subjects, and changes in subjects with asthma over time. Measurements and Main Results: Subjects with asthma had increased macrophage infiltration of visceral adipose tissue (P , 0.01), with increased expression of leptin (P , 0.01) and decreased adiponectin (p , 0.001) when controlled for body mass index. Similar trends were observed in subcutaneous adipose tissue. Airway epithelial cells expressed receptors for leptin and adiponectin, and airway reactivity was significantly related to visceral fat leptin expression (rho ¼ 20.8; P , 0.01). Bronchoalveolar lavage cytokines and cytokine production from alveolar macrophages were similar in subjects with asthma and control subjects at baseline, and tended to increase 12 months after surgery. Conclusions: Obesity is associated with increased markers of inflammation in serum and adipose tissue, and yet decreased airway inflammation in obese people with asthma; these patterns reverse with bariatric surgery. Leptin and other adipokines may be important mediators of airway disease in obesity through direct effects on the airway rather than by enhancing airway inflammation.

Rationale: The pathogenesis of asthma in obesity is poorly understood, but may be related to breathing at low lung volumes.Objectives: To determine if lung function in obese patients with asthma and control subjects would respond differently to weight loss.Methods: Lung function was evaluated by conventional clinical tests and by impulse oscillometry in female late-onset, nonallergic patients with asthma and control subjects before, and 12 months after, bariatric surgery. Measurements and Main Results:Patients with asthma (n = 10) had significantly lower FEV 1 (79.8 6 10.6 vs. 95.5 6 7.0%) and FVC (82.4 6 13.2 vs. 93.7 6 8.9%) compared with control subjects (n = 13). There were no significant differences in FRC or TLC at baseline. Twelve months after surgery, control subjects had significant increases in FEV 1 (95.5 6 7.0 to 100.7 6 5.9), FVC (93.6 6 8.9 to 98.6 6 8.3%), FRC (45.4 6 18.5 to 62.1 6 15.3%), and TLC (84.8 6 15.0 to 103.1 6 15.3%), whereas patients with asthma had improvement only in FEV 1 (79.8 6 10.6 to 87.2 6 11.5). Control subjects and patients with asthma had a significantly different change in respiratory system resistance with weight loss: control subjects exhibited a uniform decrease in respiratory system resistance at all frequencies, whereas patients with asthma exhibited a decrease in frequency dependence of resistance. Fits of a mathematical model of lung mechanics to these impedance spectra suggest that the lung periphery was more collapsed by obesity in patients with asthma compared with control subjects.Conclusions: Weight loss decompresses the lung in both obese control subjects and patients with asthma, but the more pronounced effects of weight loss on lung elastance suggest that the distal lung is inherently more collapsible in people with asthma.