Background: Mepolizumab, a monoclonal anti–IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor α fusion (F/P)–negative hypereosinophilic syndrome (HES). Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by marked overproduction of IL-5 by dysregulated T cells.

Objective: To determine whether patients with L-HES respond to mepolizumab in terms of corticosteroid tapering and eosinophil depletion to the same extent as corticosteroid-responsive F/P-negative patients with HES and a normal T-cell profile.

Methods: Patients enrolled in the mepolizumab trial were evaluated for L-HES on the basis of T-cell phenotyping and T-cell receptor gene rearrangement patterns, and their serum thymus-and-activation-regulated chemokine (TARC) levels were measured. Response to treatment was compared in patient subgroups based on results of these analyses.

Results: Lymphocytic variant HES was diagnosed in 13 of 63 patients with HES with complete T-cell assessments. The ability to taper corticosteroids on mepolizumab was similar in patients with L-HES and those with a normal T-cell profile, although a lower proportion of patients with L-HES maintained eosinophil levels below 600/μL. Increased serum TARC levels (>1000 pg/mL) had no significant impact on the ability to reduce corticosteroid doses, but a lower proportion of patients with elevated TARC achieved eosinophil control on mepolizumab.

Conclusion: Mepolizumab is an effective corticosteroid-sparing agent for patients with L-HES. In some cases however, eosinophil levels remain above 600/μL, suggesting incomplete neutralization of overproduced IL-5 or involvement of other eosinophilopoietic factors.

Background: Patients with aspirin-exacerbated respiratory disease have been shown to benefit clinically from aspirin desensitization followed by chronic high-dose aspirin therapy. However, the mechanism of this phenomenon is still unclear.

Objective: The aim of this study was to characterize the airway inflammatory response to aspirin desensitization and after treatment with high-dose aspirin for 6 months.

Methods: Twenty-one adult patients with asthma, chronic polypoid sinusitis, and a convincing history of acute respiratory reaction to the ingestion of aspirin or nonsteroidal anti-inflammatory drugs were selected. These patients underwent an oral desensitization to aspirin over a 2-day period, followed by daily ingestion of aspirin 650 mg twice daily. Induced sputum samples and exhaled nitric oxide measurements were taken before the procedure, during the second day of the procedure, and after 6 months of treatment.

Results: There was a significant elevation in both the exhaled nitric oxide level (P = .03) and sputum tryptase level (P = .05) during the desensitization process. After 6 months of aspirin treatment, sputum IL-4 (P = .0007) and matrix metalloproteinase 9 (MMP-9; P = .05) decreased significantly compared with baseline. Predesensitization to postdesensitization changes in MMP-9 and tissue inhibitors of metalloproteinases 1 were highly correlated (r = 0.79; P = .0003). Immediately after the desensitization, MMP-9 and tryptase were correlated (r = 0.82; P = .001), whereas IL-4 was inversely related with FMS-like tyrosine kinase 3 ligand (FLT3-L) (r = –0.79; P = .0008). There was a significant decrease in the average symptom score at 6 months.

Conclusion: Consistent with previous reports, acute aspirin desensitization in patients with aspirin-exacerbated respiratory disease involves mast cell degranulation. In contrast, long-term treatment with aspirin involves suppression of IL-4 as well as downregulation of proinflammatory MMP-9 while Th1 marker FLT3-L increases.