High Frequency of Specific Polysaccharide Antibody Deficiency in Adults With Unexplained, Recurrent and/or Severe Infections With Encapsulated Bacteria.

BACKGROUND: Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD). METHODS: In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3). Main exclusion criteria were all local and general conditions that could explain infections. If no PID diagnosis was made, response to polysaccharide antigens was assessed using a pneumococcal polysaccharide vaccine. RESULTS: From March 2015 to March 2020, 118 patients were included (37 males, median age of 41 years): 73, 17, and 28 in groups 1, 2, and 3, respectively. Forty-seven PIDs were diagnosed, giving an estimated frequency of 39.8% (95% confidence interval [CI] [30.4, 48.8]). SPAD was the most frequent diagnosis by far (n = 37/47, 78.7%), and was made in 23, 5, and 9 patients from groups 1 to 3, respectively. All SPAD patients received conjugate vaccines and, according to their infectious history, were on surveillance or treated with preventive antibiotics (n = 6) and/or with immunoglobulins replacement therapy (n = 10), the latter being dramatically efficient in all cases. CONCLUSIONS: Considering its high prevalence among adults with unexplained recurrent and/or severe bacterial infections, SPAD should be screened in those patients. CLINICAL TRIALS REGISTRATION: NCT02972281.

Auto bi-level with pressure relief during exhalation as a rescue therapy for optimally treated obstructive sleep apnoea patients with poor compliance to continuous positive airways pressure therapy--a pilot study.

BACKGROUND: Continuous positive airways pressure (CPAP) is the accepted therapy for obstructive sleep apnoea (OSA), but compliance is variable. We hypothesised that an auto bi-level device with pressure relief during exhalation (auto bi-level) would treat OSA as well as CPAP and that transitioning non-compliant CPAP patients without modifiable causes of poor compliance to this device would improve compliance and clinical outcomes. MATERIALS AND METHODS: OSA patient's on positive airways pressure therapy with compliance below 4 h of use on ≥70% of nights over the past 3 months despite having no modifiable causes of poor compliance were transitioned onto an auto bi-level device for 10 weeks. Patients completed an Epworth sleepiness scale and Functional Outcomes of Sleep Questionnaire (FOSQ) at 15 days and 10 weeks and had their compliance and therapy data downloaded. Additionally, patients underwent polysomnography on their auto bi-level device at week 10. RESULTS: Thirty-five patients were included. The apnoea-hypopnoea index, arousal index, sleep efficiency, total sleep time and sleep stage distribution were similar at baseline and week 10. Compliance, excessive daytime sleepiness and several FOSQ domains improved significantly at day 15 and week 10. Patients requiring an effective pressure ≥10 cmH(2)0 during the lead-in period on CPAP experienced greater significant improvements compliance than those requiring an effective pressure <10 cmH(2)0. CONCLUSIONS: Auto bi-level with pressure relief during exhalation treats OSA as effectively as CPAP without inducing additional arousals. Transitioning non-compliant CPAP patients without modifiable causes of poor compliance from their CPAP to this new device improves compliance and clinical outcomes over a 10-week period.

Involvement of IL-9 in the bronchial phenotype of patients with nasal polyposis.

BACKGROUND: Nasal polyposis (NP) is frequently associated with asthma. In this disease, asymptomatic bronchial hyperresponsiveness (BHR) is thought to precede the development of asthma. IL-9 and its receptor have been reported as candidate genes for asthma and to be associated with BHR. OBJECTIVE: The objective of this study was to assess the contribution of 11-9 to the pathogenesis of BHR in NP by comparing the expression of IL-9 and its receptor in bronchial biopsy specimens from three groups of patients with NP: NP without BHR, NP with asymptomatic BHR, and NP with BHR and asthma. METHODS: Bronchial biopsy specimens were examined in terms of cellular infiltration and in terms of expression of IL-9 protein and mRNA as well as of its receptor by using immunohistochemistry and in situ hybridization. RESULTS: Patients with NP with asthma as compared with the two other groups exhibited an increased bronchial infiltration of basophils, eosinophils, and T cells that correlated with the asthma score. The two groups of patients with NP with BHR showed an increased expression in IL-9 protein and mRNA as well as an increase in the expression of IL-9R mRNA at the epithelial level. These modifications were inversely correlated with the airway responsiveness to methacholine, producing a 20% fall in FEV1. There was a close association between IL-9+ cells, IL-5 mRNA expression, and eosinophil infiltration that correlated with each other. CONCLUSIONS: These results suggest an important role for IL-9 in the pathogenesis of BHR and a causal relation between IL-9 and the development of bronchial eosinophilia in asthma.

Cell and cytokine profile in nasal secretions in cystic fibrosis.

BACKGROUND: Nasal polyposis (NP) frequently complicates the course of cystic fibrosis (CF). The aim of this study was to determine the pattern of inflammatory cells and mediators in nasal secretions from patients with or without NP compared to patients with idiopathic NP and healthy controls. METHODS: Eighteen CF patients with NP (NP+ group: 6 untreated, 12 treated with nasal steroids), and 15 without NP (NP- group) were included in this prospective study and compared to 9 patients with idiopathic NP and 12 healthy controls. Differential cell count eosinophil cationic protein (ECP), interleukin-5 (IL-5) and IL-8 were determined in nasal lavage fluids. RESULTS: The total cell count, the number and the percentage of neutrophils and eosinophils, the levels of IL-8, IL-5 and ECP were significantly higher in nasal secretions from both NP+ and NP- as compared with controls. No difference was found between untreated and treated CF patients with NP. No difference was found between NP+ and NP- groups. Compared to idiopathic NP group, both NP+ and NP- groups had higher percentage of neutrophils and lower percentage of eosinophils. There were no differences according to the use of topical steroids, systemic antibiotherapy, or the type of mutation. CF patients with positive nasal culture had a higher percentage of neutrophils than those with negative culture. CF patients with atopy had a higher percentage of eosinophils than non-atopic patients. CONCLUSION: Our results demonstrate that nasal inflammation is a prominent feature in patients with CF and does not differ according to the presence of NP. IL-8 and IL-5 may play crucial roles in recruitment and activation of neutrophils and eosinophils in upper airways of CF patients.