The Unified Airway: Linking Severe Asthma and Sinus Disease

In "The Unified Airway: Linking Severe Asthma and Sinus Disease," our experts turn from the lower airway to the whole of it.

Dr. Chupp notes the discussion has focused on asthma, though sinus disease is a large part of the equation, and asks how each panelist defines the unified airway. Dr. Ross says it is really one airway, artificially separated in the past. Look at the biology at the epithelial surface, she argues, and the two sites look alike: exposed to the same pathogens, allergens, viruses, and occupational irritants, with the same early alarmin responses through TSLP, IL-33, and IL-25. Both show mucus hypersecretion, goblet cell hyperplasia, potential polyp growth, and ciliary dysfunction. She highlights nerve hyper-responsiveness at both sites, producing anosmia above and bronchoconstriction below. Patients with a respiratory complaint usually report an upper airway complaint at the same time, so treatment must run from the sinuses to the lungs.

Dr. Wechsler frames it as a systemic inflammatory process rather than mere anatomical proximity, predominantly type 2, with the same cytokines, the same cells, the same epithelial barrier dysfunction, fibrotic elements, and mucus. Because bad sinuses worsen asthma and bad asthma worsens sinuses, he treats systemically, blocking TSLP or IL-4 and IL-13 to benefit both. Dr. Ross adds that the dual presentations cluster: nasal polyps with asthma, aspirin-exacerbated respiratory disease, allergic rhinitis with asthma. She argues these should be understood as combined phenotypes.

Dr. Hanania supplies the evidence base. The hypothesis was propagated years ago and is supported epidemiologically, pathophysiologically, immunologically, and functionally. About 70% of patients with CRS with nasal polyps have asthma, and about 40% of asthma patients, especially type 2, have CRS with nasal polyps. Compare a nasal polyp cross-section with an airway biopsy, he says, and the infiltration, mucus, and remodeling match. It is a two-way highway.

Our next episode, "Unified Airway Disease Presentation in Clinic," presses Dr. Ross on an assumption about who those polyp patients really are.