Ivacaftor in Infants Aged 4 to <12 Months with Cystic Fibrosis and a Gating Mutation. Results of a Two-Part Phase 3 Clinical Trial.

Rationale: We previously reported that ivacaftor was safe and well tolerated in cohorts aged 12 to <24 months with cystic fibrosis and gating mutations in the ARRIVAL study; here, we report results for cohorts aged 4 to <12 months.Objectives: To evaluate the safety, pharmacokinetics, and pharmacodynamics of ivacaftor in infants aged 4 to <12 months with one or more gating mutations.Methods: ARRIVAL is a single-arm phase 3 study. Infants received 25 mg or 50 mg ivacaftor every 12 hours on the basis of age and weight for 4 days in part A and 24 weeks in part B.Measurements and Main Results: Primary endpoints were safety (parts A and B) and pharmacokinetics (part A). Secondary/tertiary endpoints (part B) included pharmacokinetics and changes in sweat chloride levels, growth, and markers of pancreatic function. Twenty-five infants received ivacaftor, 12 in part A and 17 in part B (four infants participated in both parts). Pharmacokinetics was consistent with that in older groups. Most adverse events were mild or moderate. In part B, cough was the most common adverse event (n = 10 [58.8%]). Five infants (part A, n = 1 [8.3%]; part B, n = 4 [23.5%]) had serious adverse events, all of which were considered to be not or unlikely related to ivacaftor. No deaths or treatment discontinuations occurred. One infant (5.9%) experienced an alanine transaminase elevation >3 to ≤5× the upper limit of normal at Week 24. No other adverse trends in laboratory tests, vital signs, or ECG parameters were reported. Sweat chloride concentrations and measures of pancreatic obstruction improved.Conclusions: This study of ivacaftor in the first year of life supports treating the underlying cause of cystic fibrosis in children aged ≥4 months with one or more gating mutations.Clinical trial registered with clinicaltrials.gov (NCT02725567).

The association between the reflux symptoms index and nasal symptoms among patients with non-allergic rhinitis.

BACKGROUND: Laryngopharyngeal reflux symptoms assessed with the reflux symptom index can overlap with non-allergic rhinitis symptoms. This study aims to explore the association between the reflux symptom index and nasal symptoms in non-allergic rhinitis patients. METHODS: A cross-sectional study was conducted on consecutive adults with non-allergic rhinitis. The reflux symptom index (score of more than 13 = laryngopharyngeal reflux) and nasal symptoms (categorised as mild (total score of 0-3), moderate (4-7) or severe (8-12)) were assessed. RESULTS: The study included 227 participants (aged 58.64 ± 12.39 years, 59.5 per cent female). The reflux symptom index scores increased with total nasal symptom scores (mild vs moderate vs severe, 8.61 ± 6.27 vs 12.94 ± 7.4 vs 16.40 ± 8.10; p < 0.01). Logistic regression indicated that laryngopharyngeal reflux is more likely in patients with severe nose block (odds ratio 5.47 (95 per cent confidence interval = 2.16-13.87); p < 0.01). CONCLUSION: Laryngopharyngeal reflux symptoms are associated with nasal symptom severity, and nasal symptoms should be primarily treated. Those with predominant nose block and laryngopharyngeal reflux symptoms are more likely to have laryngopharyngeal reflux.

Long-term outcome of concurrent coblator turbinoplasty with adenotonsillectomy in children with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is one of the most prevalent chronic diseases in children. Patients with AR tend to have more persistent symptoms after adenotonsillectomy (T&A). OBJECTIVES: This study was aimed to evaluate the outcome of additional concurrent coblation-assisted turbinoplasty with adenotonsillectomy (T&A + T) in patients with AR. MATERIAL AND METHODS: This study included 104 children who underwent T&A, and 67 who underwent T&A + T. All patients were diagnosed as AR and were aged < 12 years at the time of surgery. Symptoms (snoring, mouth breathing, nasal obstruction, rhinorrhea, itching, and sneezing) were evaluated preoperatively and postoperatively via a questionnaire and a telephone survey. RESULTS: None of the six symptoms investigated differed significantly between the two groups preoperatively, and all evaluated symptoms exhibited dramatic improvements after the surgery in both groups. The T&A + T group showed significantly greater difference of improvement in mouth breathing and nasal obstruction than T&A group. There were no significant difference of improvements in snoring, rhinorrhea, itching and sneezing postoperatively between two groups. In multiple regression analysis, postoperative obstructive symptoms including mouth breathing and nasal obstruction were significantly associated with concurrent turbinoplasty. CONCLUSION: Concurrent turbinoplasty should be considered especially in patients who have AR and adenotonsillar hypertrophy to improve obstructive symptoms.

Respiratory Symptoms of Exposure to Substances in the Workplace among Bulgarian Dental Students: a Self-report Questionnaire Survey.

BACKGROUND: Dental students are at high risk of developing adverse respiratory reactions as a result of their practical work during their dentistry degree program when they come into contact with multiple airborne irritants and allergens. AIM: To estimate the prevalence of respiratory symptoms of exposure to substances in the workplace and associated risk factors in Bulgarian dental students. RESULTS: The prevalence of self-reported respiratory symptoms related to the pre-clinical and clinical training courses of the dentistry program was 12.4%. According to logistic regression analysis, the most important risk factors for work-related respiratory symptoms were a personal history of allergic rhinoconjunctivitis (odds ratio (OR) 6.34, 95% confidence interval (CI): 3.14-12.78), atopic dermatitis (OR 2.81, 95%CI: 1.26-6.26), and exposure to chemicals from dental environment for more than 6 hours a day (OR 3.60, 95%CI: 1.21-10.70). CONCLUSION: The results of this study suggest that work-related respiratory symptoms are frequent among dental students and indicate the need for efforts to establish effective primary preventive programs for occupational respiratory disorders at national level.