The Impact of Obesity on Airway Inflammation, Lung Function and Biologic Treatment in Asthma: A Narrative Review

Abstract: Obesity and asthma are two chronic conditions with increasing global prevalence. The interplay between obesity and asthma has created a distinct “obese asthma phenotype” characterized by increased disease severity, poorer symptom control and altered treatment response. This phenotype is driven by complex interactions between mechanical factors, chronic low-grade systemic inflammation and metabolic dysfunction. Since the last decades biologics are used to treat patients with severe asthma. These therapies act on specific inflammatory pathways, so it is plausible that obesity-related metabolic and inflammatory alterations may alter their effectiveness. Obese patients can have both type-2 high and type-2 low (T2-low) endotypes, although there seems to be a shift towards T2-low asthma, with increased airway neutrophils and altered cytokine profiles. Current biologics targeting several cytokines demonstrate varying results in treatment efficacy in obese asthma patients, whereas tezepelumab shows the most benefit. Several mechanisms have been proposed for reduced efficacy of biologics in this population through mechanisms involving pharmacokinetics/dynamics, inflammatory and immunologic pathways. Obese patients frequently exhibit persistent symptoms despite treatment, suggesting incomplete disease control. Understanding the relationship of obesity and asthma is critical in determining optimal management and requires integrated strategies addressing both airway inflammation and metabolic dysfunction. Several emerging therapies, like glucagon-like peptide-1 receptor agonists (GLP-1) show promise through mechanisms extending beyond weight reduction. Future research priorities include trials in obese populations to optimize biologic dosing, improved biomarker research and develop precision medicine treatments to transform this complex interplay of conditions into a manageable multisystem disease. This review aims to assess current evidence regarding the link between asthma and obesity, biologic responsiveness in this population and to explore potential mechanisms, clinical implications, new therapeutic possibilities and areas for future research. Keywords: adiposity, efficacy, pharmacokinetics, immunology