Effects of CFTR-modulator triple therapy on sinunasal symptoms in children and adults with cystic fibrosis.

PURPOSE: Sinunasal symptoms and chronic rhinusinutitis are common in patients with cystic fibrosis. Cystic fibrosis transmembrane regulator (CFTR) modulators have led to dramatic improvements of respiratory symptoms and quality of life in patients with cystic fibrosis. This study aims to evaluate subjective and objective sinunasal symptoms after start of CFTR-modulator triple therapy. METHODS: 43 patients (n = 6 < 18 years), treated with highly effective CFTR-modulator therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) were included, as were 20 controls with cystic fibrosis but without CFTR-modulator therapy (n = 6 < 18 years). All assessed their sinunasal symptoms retrospectively and the intervention group at a mean of 9.3 (2-16) months after start of ELX/TEZ/IVA. RESULTS: Improvements in SNOT-22 overall score from m = 32.7 to m = 15.7 points (p < 0.0001) as well in the nasal, emotional, otologic, and sleep subdomains could be demonstrated in the intervention group. No changes were found in the control group. Children showed lower SNOT-22 scores than adults and a reduction of SNOT-22 total score from m = 9.4 to m = 2.2 (p = 0.25) was found. 8 patients were evaluated by an otorhinolaryngologist before and after start of ELX/TEZ/IVA and showed pronounced objective clinical improvement. CONCLUSIONS: Highly effective CFTR-modulator therapy has a significant positive impact on both subjective and objective sinunasal symptoms in patients with CF and some improvement could be demonstrated in children < 18 years as well.

Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells.

BACKGROUND: Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. METHODS: This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy. RESULTS: We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects. CONCLUSIONS: To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT.

Symptom Control of Patients With Chronic Rhinosinusitis With Nasal Polyps Under Maintenance Therapy With Daily Acetylsalicylic Acid.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (NERD) is defined by intolerance to cyclooxygenase 1 inhibitors, chronic rhinosinusitis with recurrent nasal polyps, and/or intrinsic bronchial asthma. Long-term administration of acetylsalicylic acid (ASA) after desensitization has been used to mitigate these sequelae, but the optimal dose and balancing symptom relief and side effects remain unsettled. METHODS: Retrospective data analysis of 85 patients with NERD receiving maintenance therapy of 300 mg ASA was followed by questionnaires (our own, not validated and the Sino-Nasal Outcome Test-20). We received responses from 55 patients and examined 30 of them clinically. RESULTS: Patients with no ASA-associated side effects were 56.4% (56 of 85 patients) of the cohort. In this study, 60% (33 of 55 patients) continued prophylaxis of 300 mg ASA daily for an average of 34.7 months. Elective surgery was the most frequent cause of discontinuation of ASA (21.8%; 12 of 55 patients). Rhinomanometry values were significantly improved with ASA (P < .05; Wilcoxon), but there was no significant reduction in nasal polyposis or improvement in olfaction at the time of follow-up examination. CONCLUSIONS: Minor clinical improvements were identified. Side effects were well tolerated by most patients, and no serious sequelae occurred. The indications for long-term ASA therapy in NERD patients remain unsettled.