Introduction: Asthma is a heterogeneous chronic inflammatory disease involving different underling pathogenetic mechanisms. We aimed to investigate the characteristics of patients with the diagnosis of asthma and primary antibody immunodeficiency (PAD) and the impact of immunoglobulin therapy (IVIg). Methods: Thirty-three patients with severe asthma and PAD (either IgG subclasses deficiency or unclassified hypogammaglobulinemia) were retrospectively recruited. Severe asthma was diagnosed according to GINA recommendations and PAD was diagnosed according to ESID diagnostic criteria; normal immunoglobulins serum levels were defined according to the local laboratory values (IgG 700–1,600 mg/dL; IgA 70–400 mg/dL; IgM 40–230 mg/dL; IgG1 382–929 mg/dL; IgG2 242–700 mg/dL; IgG3 22–176 mg/dL; IgG4 4–88 mg/dL). Clinical and laboratory features were analyzed before and after immunoglobulin therapy (IVIg). Results: We observed a high proportion of patients with low T2 markers (36.4%), with very low blood eosinophils (BE), compared to patients with elevated T2 markers (BE: 80 [range 30–140] vs. 200 [range 50–760] cells/μL, p < 0.001). After IVIg, we observed significant reduction of respiratory infections (4 [range 0–20] vs. 1 [range 0–5], p < 0.001) and exacerbations (6 [range 1–20] vs. 1 [range 0–7], p < 0.001); moreover, in patients with low T2 markers, BE significantly rose (80 [range 30–140] vs. 115 [range 70–520] cells/μL, p < 0.05). Conclusion: IVIg therapy reduces infections and infection-related exacerbations in patients with the diagnosis of asthma and PAD and could modulate asthma phenotype.

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