Anti-Interleukin-5 Therapy Is Associated with Attenuated Lung Function Decline in Severe Eosinophilic Asthma Patients From the Belgian Severe Asthma Registry.

BACKGROUND: Asthmatics have accelerated lung function decline over time compared with healthy individuals. OBJECTIVE: To evaluate risk factors for accelerated lung function decline. METHODS: In a longitudinal analysis on severe asthmatics enrolled in the Belgian Severe Asthma Registry with at least 2 visits a minimum of 12 months apart, we compared characteristics of patients with and without decline (loss of post-bronchodilation forced expiratory volume in 1 s [FEV1] (% predicted)/y greater than zero) over time. Multiple linear regression was applied to study the factors independently associated with FEV1 decline. RESULTS: In the overall population (n = 318), median annual FEV1 decline was 0.27 (-4.22 to 3.80) % predicted/y over a period of 23 months (12-41 months). Asthma was less controlled at baseline in nondecliners than in decliners (53%). Lung function and residual volume at baseline were higher in the declining group. Decliners presented with increased bronchial reactivity (ie, a lower provocative concentration of methacholine causing a 20% fall in FEV1) at baseline. Twenty-five percent of nondecliners were started on anti-interleukin-5 (anti-IL-5) for severe eosinophilic asthma during the study compared with 10% of decliners. The multivariable model suggested that Asthma Control Questionnaire score at baseline, late-onset asthma, and addition of anti-IL-5 during follow-up were associated with lower FEV1 decline, independently from other variables such as evolution in exacerbations, smoking status, inhaled corticosteroids or oral corticosteroids dose, or add-on anti-immunoglobulin E over time, whereas reversibility to salbutamol and higher FEV1 were associated with accelerated FEV1 decline. CONCLUSIONS: Add-on therapy with anti-IL-5 in severe eosinophilic asthma was associated with an attenuated FEV1 decline. The causality of this observation should, however, be confirmed in future prospective controlled studies.

Executive dysfunctions as a good predictor of misuse of respiratory inhalers among hospitalized patients: a prospective survey.

The objectives of the study are to determine the prevalence and potential risk factors of misuse of respiratory inhalers among hospitalized patients admitted at the CHU UcL Namur, site Godinne. Using a cross-sectional design, patients using respiratory inhalers since more than 7 days were recruited from a database established by the hospital pharmacy. Inhaler technique was assessed using a standardised check-list and graded misuse as major or minor errors using previously published criteria. Demographic and clinical data were prospectively collected using standardised tools. Among the 100 consecutive patients selected for the study (median of age: 68 years), the prevalence of misuse was 40%. According to univariate analysis, main risk factors of misuse were age, executive dysfunction, a low grip strength, a low level of manual dexterity and the type of inhaler used. The best predictor of misuse according to multivariate analysis was executive dysfunction as assessed by the BREF scale (batterie rapide d'efficience frontale) (adjusted odds ratio: 1.35 [CI95%: 1.11-1.64]; p: 0.002). A BREF score ≤ 12/18 was associated with a six-fold increase of respiratory inhaler misuse risk. We conclude that executive dysfunction is associated with a higher risk of respiratory inhalers misuse. A short screening of executive function, using the BREF scale, before starting respiratory inhaler may improve the selection of inhaler devices and therefore the compliance to treatment.

Presence in sputum of functional dust mite-specific IgE antibodies in intrinsic asthma.

RATIONALE: Intrinsic asthma was described by Rackemann as asthma without allergy. Local IgE production has been documented in intrinsic asthma, but antigen specificity of this response remains elusive. OBJECTIVES: We investigated (1) the presence of dust mite-specific IgE in sputum of patients with intrinsic asthma, (2) their clinical/immunological relevance, and (3) their functionality. METHODS: Specific IgE to Dermatophagoides pteronyssinus (Der p) and to recombinant major allergens (rDer p1 and rDer p2) were assayed by ELISA in sputum samples from patients with intrinsic versus atopic asthma and control subjects. Whole-lung challenge was performed with Der p for clinical and inflammatory readouts. Functionality of local IgE to trigger effector cells was assessed using basophil activation test (surface expression of CD203c). MEASUREMENTS AND MAIN RESULTS: Both total IgE and Der p-specific IgE levels are increased in patients with intrinsic asthma compared with healthy nonatopic patients. However, no immediate asthmatic responses were observed in patients with intrinsic asthma after Der p exposure. These sputum Der p-specific IgE do, however, recognize major allergens Der p1 and Der p2 and are able to trigger activation of blood basophils from atopic donors. CONCLUSIONS: We confirm that IgE production occurs in intrinsic asthma and show that part of this IgE recognizes Der p antigens. However, this IgE reactivity does not translate into clinical responses to Der p exposure, despite specificity to major allergens and functionality to activate effector cells in vitro. We postulate that a second signal that promotes IgE-mediated asthmatic responses through FcεRI is lacking in intrinsic asthma.