Obesity-Related Asthma: Is Inflammation Driving Severity?

Obesity -associated asthma (OAA) is a distinct asthma phenotype shaped by complex, bidirectional interactions among immunity, metabolism, respiratory mechanics, and microbiome, according to research presented at the Francophone Congress of Allergology (CFA) 2026 . Researchers examined how obesity and asthma may influence one another through multiple immune pathways, offering a new physiopathologic interpretation of this particularly severe and therapeutically challenging phenotype. The prevalence of both obesity and asthma has continued to increase over the past 50 years. “A strong [epidemiologic] correlation is observed between these two diseases,” explained Grégory Bouchaud, PhD, research director at the French National Research Institute for Agriculture, Food and Environment-Biopolymers Interactions Assemblies unit in Nantes, France. “However, this is by no means formal proof of a causal relationship.” Bouchaud noted that clinical observations consistently showed that OAA is more severe, with poor disease control, more frequent exacerbations, impaired quality of life, distinct clinical phenotypes, and different therapeutic responses.

Asthma Endotypes

The pathophysiology of asthma includes two major endotypes. The T2 high endotype involves differentiation of T lymphocytes into T helper type 2 cells, with production of type 2 cytokines, including interleukin (IL)-4, IL-5, and IL-13. This profile is associated with eosinophilia , production of specific immunoglobulin E, bronchial hyperresponsiveness, and characteristic clinical symptoms. It also involves disruption of the bronchial epithelial barrier and production of alarmins, including thymic stromal lymphopoietin, IL-25, and IL-33. The T2 low, or non-T2, endotype instead involves differentiation into T helper type 1 and T helper type 17 cells, with production of cytokines, including IL-6, IL-17A, and TNF. This profile is associated with neutrophilic inflammation and the production of reactive oxygen species, which contribute to bronchial hyperresponsiveness and asthma symptoms. The epithelial barrier is also altered in this endotype, with the additional production of alarmins.

Obesity and Severity

An epidemiologic association between asthma and obesity has been recognized since the late 1990s. One study involving more than 85,000 nurses in North America suggested an increased risk for late-onset asthma among individuals with a BMI ≥ 30, with an odds ratio of 2.7. Subsequent studies, most of which were cross-sectional, confirmed an increased risk for asthma among individuals with obesity — particularly women — along with greater disease severity. “First, obesity affects ventilatory mechanics,” Bouchaud said. “Individuals with obesity breathe at lower tidal lung volumes, which promotes closure of small airways and impaired ventilation.” In addition, a functional reduction in lung volume results from thoracoabdominal compression by the adipose tissue. Lung compliance is also reduced due to an alteration in the lung’s elastic properties resulting from the infiltration of adipose tissue into the chest. Finally, increased contractility of bronchial smooth muscle cells is associated with the presence of adipose tissue.

Innate Immunity

Beyond respiratory mechanics, obesity strongly influences the immune response. “Obesity affects several molecular mediators, particularly IL-4, IL-13, and IL-33 — which are involved in both T2 and non-T2 asthma endotypes.” However, they emphasized that obesity primarily affects innate immunity, especially type 2 innate lymphoid cells (ILC2s). Among individuals with obesity and asthma, researchers observed reduced numbers of ILC2s expressing the CD45RA marker, which is predominantly associated with an anti-inflammatory profile, along with increased numbers of “inflammatory” CD45RO+ ILC2s linked to a proinflammatory phenotype. “This profile suggests reduced sensitivity to corticosteroids because increased CD45RO+ ILC2s are associated with corticosteroid resistance,” Bouchaud said. Animal studies have also shown that obesity in the context of asthma increases IL-17-producing ILC3s, inducing bronchial hyperresponsiveness. An increase in IL-13+ ILC2 and IL-17+ ILC3 has also been observed in mouse models of OAA. “Beyond molecular mediators, obesity also acts on cellular pathways, particularly ILC2s, whose expansion contributes to both T2 and non-T2 asthma phenotypes,” Bouchaud said.

Leptin Effects

Obesity is also associated with the dysregulation of adipokines. Leptin, produced by the adipose tissue and involved in regulating satiety and fat storage through hypothalamic pathways, increases in obesity. In contrast, adiponectin, which is inversely correlated with BMI, decreases. Both molecules directly modulate cytokine production and immune system activity. According to Bouchaud, leptin contributes to the activation of inflammatory pathways at both the molecular and cellular levels, worsening asthma severity in both T2 and non-T2 phenotypes. Conditioned media from adipocytes of patients with obesity and asthma stimulate bronchial epithelial cells to increase the production of proinflammatory cytokines such as IL-8, contributing to severe asthma. “Similar results are observed in bronchial smooth muscle cells,” said Bouchaud, “with increased production of IL-6, IL-8, and cell-derived chemokines such as CCL-4, thereby setting the stage for inflammation.” In these conditioned media, leptin is found in high concentrations, whether in the serum or bronchoalveolar lavage fluid. In culture with epithelial cells , it induced a dose-dependent increase in eotaxin-3. Leptin also acts directly on lymphocytes, leading to a decrease in IL-10 (an anti-inflammatory cytokine) and an increase in IL-13 and IL-17. “Leptin profoundly modulates the adaptive immune system by increasing T helper type 1, T helper type 2, and T helper type 17 lymphocytes while reducing regulatory T lymphocytes,” Bouchaud said. “It also affects innate immunity by increasing production of TNF-alpha and IL-1-beta by dendritic cells and by promoting proliferation of ILC2s.”

Microbiome Changes

The microbiome also appears to play a significant role in the pathogenesis of OAA. “Individuals with asthma show dysbiosis of both the intestinal and pulmonary microbiomes,” Bouchaud said. “In animals, the short-chain fatty acids (SCFAs) produced by microbiota have a protective effect against the development of asthma (as does fecal microbiota transplantation).” However, obesity is associated with a less diverse intestinal microbiome and reduced production of SCFAs, a condition associated with a less stable immune response, which promotes increased lung inflammation. Impairment of the intestinal barrier is also present, with increased permeability allowing toxins to pass into the bloodstream and then to the lungs. The lung microbiota is also altered, resulting in a reduced response to conventional inhaled treatments, such as corticosteroids or bronchodilators. One study identified 27 species of gut microbiota that exert specific effects on OAA. Three genera, Faecalicatena , Prevotella , and Eisenbergiella , were associated with an increased risk for OAA. Two other species belonging to Actinobacteria were associated with lower risk. Animal studies have shown pulmonary microbiota dysbiosis in obese and asthmatic mice, with greater alterations observed when both conditions coexist. Researchers also observed a reduction in the genus Ralstonia . At this stage, in silico analyses suggested that OAA may be associated with a distinct microbial functional profile. Bouchaud reported having no relevant conflicts of interest. This story was translated from Medscape’s French edition .