Rhinoconjunctivitis severity induced by cat exposure influences early and late asthmatic responses: Evidence from an environmental exposure chamber.

BACKGROUND: The impact of allergic rhinoconjunctivitis on the early (EAR) and late asthmatic response (LAR) has yet to be assessed during optimal allergen exposure conditions. OBJECTIVE: We aimed to assess predictive factors of the EAR and LAR and to evaluate the relation between rhinitis, conjunctivitis and asthma induced by cat allergen exposure in an environmental exposure chamber (EEC). METHODS: Data from two cohort studies involving asthmatic patients with cat allergy who performed a cat allergen exposure challenge in ALYATEC EEC were analysed. Spirometry, visual analogue scale (VAS) for asthma, VAS for rhinitis, Total Nasal Symptoms Score, Total Ocular Symptoms Score (TOSS), Rhinoconjunctivitis Total Symptoms Score and Abelson score were used to assess asthma, rhinitis and conjunctivitis during and after exposure. RESULTS: An EAR occurred in 65.1% of patients, 32.1% of whom had a LAR. The diameter of the prick test to cat allergens and non-specific bronchial hypersensitivity level were independent risk factors for EAR (p < .05). No independent risk factors for LAR were identified. Rhinoconjunctivitis severity during exposure correlated with the asthma VAS during EAR and LAR (p < .05). Allergen exposure time needed to trigger an EAR correlated with the Abelson score during exposure (p < .05). The asthma VAS and TOSS during exposure correlated with faster LAR occurrence (p < .05). CONCLUSION: Prick test size and non-specific bronchial hypersensitivity level were confirmed as independent predictive factors of EAR during allergen exposure in an EEC. This study demonstrated the relation between the severity of rhinitis, conjunctivitis and asthma induced by allergen exposure for both EAR and LAR.

Proof-of-concept study of anti-Fel d 1 IgY antibodies in cat food using the MASK-air® app.

BACKGROUND: An innovation to better manage cat-allergic patients utilises anti-Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no published study showing its clinical efficacy in humans in a home setting. A longitudinal, open-label, proof-of-concept study was carried out to approach clinical efficacy of the cat food in cat-allergic patients. METHODS: After a baseline evaluation, the cats ate only the cat food for the following 4 months. Daily evaluation of efficacy was performed for 2 weeks at baseline and after 1, 2 and 3 months of intervention for periods of 2 weeks. The MASK-air app was used daily to assess symptoms, work productivity and medications. RESULTS: Of the 49 patients screened, 42 were followed up and 33 (78.5%) reported MASK-air data at all 3 evaluation periods. The primary end point (visual analogue scale [VAS] for global allergy symptoms) was significantly improved (p < 0.0001). All symptoms (VAS nose, eye, and asthma), VAS work and the combined symptom-medication score significantly improved after 1 month. The percentage of uncontrolled days (VAS>20/100) decreased from 64% at baseline to 35% at 1 month (p < 0.0001) and 14% at 3 months. A sensitivity analysis in patients with uncontrolled disease at baseline found similar results. DISCUSSION: A cat diet containing anti-Fel d 1 antibodies was able to (i) show decreased allergic symptoms and related outcomes, (ii) inform the design and feasibility of future studies with a control arm and (iii) estimate the sample size of the study. STUDY REGISTRATION NUMBER: clinicaltrials.gov: NCT05656482.

Efficacy of bronchial thermoplasty in patients with severe asthma and frequent severe exacerbations: A randomized controlled study✰.

BACKGROUND: Bronchial thermoplasty (BT) is a bronchoscopic procedure for patients with severe uncontrolled asthma, but randomized controlled studies of its efficacy in severe asthma with frequent exacerbations are lacking. The current aim was to assess BT efficacy in this patient population. METHODS: Thirty patients with asthma (GINA 5) who had experienced at least four severe exacerbations in the preceding year were randomized to BT (n = 15) or control groups (n = 15). All patients had four follow-up visits over the following 15 months, corresponding to 3, 6, 9, and 12 months after the last procedure for the BT group. The primary outcome was number of exacerbations at 15 months after inclusion (i.e. 12 months after bronchial thermoplasty). RESULTS: All but three patients had received an asthma biologic without receiving benefit. In the year preceding enrollment, patients in the BT group had an average of five exacerbations, compared with six among controls. For patients in the BT group, oral steroid intake was 9.3 mg/d, compared with 11.0 mg/d among controls. The BT group had 1.58 fewer severe exacerbations (mean, 6.09) compared with controls (mean, 8.28) in the 12-month period after the therapy (p = 0.047). Oral steroid intake during follow-up after BT was significantly lower in the BT group (ratio vs controls: 0.61; p = 0.0002). Quality-of-life measures between inclusion and the last visit were significantly improved in the BT group, but not among controls. Few mild to moderate adverse events were reported, and all were controlled within days. CONCLUSION: In patients with severe asthma and frequent severe exacerbations, BT significantly decreased the rate of severe exacerbations and oral steroid intake and led to improved quality of life during the 15 months after inclusion. BT appears to offer a therapeutic option for severe asthma with frequent exacerbations.

Clinical benefits with 300 IR HDM SLIT tablet in Europeans with house dust mite allergic rhinitis: Post hoc analysis of a large phase 3 trial.

Background: House dust mite (HDM)-induced allergic rhinitis (AR) is a major cause of allergic respiratory disease. The efficacy and safety of the 300 IR HDM sublingual immunotherapy (SLIT) tablet in patients with moderate-to-severe HDM-AR was confirmed in a large, international, phase 3 randomized controlled trials (RCTs). Here, we analyzed the results in the European population. Methods: Data from 91 European centers that participated in the international, double-blind, RCT (EudraCT 2014-004223-46, NCT02443805) with the 300 IR HDM SLIT tablet versus placebo over 12 months were analyzed post hoc. The treatment effect in European adults and adolescents was notably assessed through the European Academy of Allergy and Clinical Immunology (EAACI)-recommended combined symptom and medication score (CSMS0-6, pre-defined endpoint) and the total combined rhinitis score (TCRS0-24, post hoc endpoint, also balanced) during the primary evaluation period (4 weeks at the end of treatment period) using analysis of covariance (ANCOVA). Results: There were 818 patients who comprised the modified full analysis set in Europe. Over the primary period, the differences in CSMS0-6 and TCRS0-24 between the 300 IR and placebo groups were statistically significant (p < 0.0001): -0.32 (95%CI [-0.46; -0.17]) and -1.28 (95%CI [-1.63; -0.94]), respectively, with relative differences of -20.9% and -21.2%. All post hoc and the rhinoconjunctivitis quality of life endpoints were significantly improved with 300 IR versus placebo. The 300 IR HDM tablet was generally well tolerated. Conclusion: This RCT sub-analysis confirmed the 300 IR HDM SLIT tablet is an effective and safe treatment for European adults and adolescents with HDM-AR with clinically meaningful benefits from the patients' perspective. Trial registration: NCT02443805. Registered on April 29, 2015./EudraCT 2014-004223-46. Registered on September 16, 2015.

Diagnostic Accuracy of Specific IgE Against Wheat and Rye in Flour-Induced Occupational Asthma.

BACKGROUND: Assessment of IgE-mediated sensitization to flour allergens is widely used to investigate flour-induced occupational asthma. The diagnostic efficiency of detecting specific IgE antibodies (sIgEs) against wheat and rye flour, however, has not been thoroughly compared with other diagnostic procedures. OBJECTIVE: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared with specific inhalation challenge (SIC) with flour as the reference standard. METHODS: This retrospective multicenter study included 264 subjects who completed an SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result. RESULTS: Compared with SIC, sIgE levels of 0.35 kUA/L or greater against wheat and rye provided similar sensitivities (84% to 85%, respectively), specificities (71% to 78%), positive predictive values (91% to 93%), and negative predictive values (56% to 61%). Increasing the threshold sIgE value to 5.10 kUA/L for wheat and to 6.20 kUA/L for rye provided a specificity of 95% or greater and further enhanced the positive predictive value to 98%. Among subjects with a positive SIC, those who failed to demonstrate sIgE against wheat and rye (n = 26) had significantly lower total serum IgE level and blood and sputum eosinophil counts and a lesser increase in postchallenge FeNO compared with subjects with a detectable sIgE. CONCLUSION: High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need to perform an SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of TH2 biomarkers.