Aerosolized lancovutide in adolescents (≥12 years) and adults with cystic fibrosis - a randomized trial.

BACKGROUND: Lancovutide activates a chloride channel (TMEM-16A) other than the cystic fibrosis (CF) transmembrane conductance regulator protein and could benefit CF patients. METHODS: In this randomized, multi-center, double-blind, placebo-controlled, parallel-group trial 161 patients ≥12 years with a confirmed diagnosis of CF were randomized to either placebo (saline) or active drug in 3 different dosing schemes of 2.5mg inhaled lancovutide (once daily, every other day or twice a week) for eight weeks. The primary endpoint was the change in the forced expiratory volume in 1 second (FEV1) percent predicted. Secondary endpoints included further lung function parameters (FEV1 (absolute), functional vital capacity percent predicted, forced expiratory flow percent predicted, pulse oximetry), quality of life assessment, pulmonary exacerbations, hospitalization due to pulmonary exacerbations, time to first pulmonary exacerbation, duration of anti-inflammatory, mucolytic or antibiotic treatment, and safety. RESULTS: There was no significant difference in the change in FEV1 percent predicted, quality of life, other lung function parameters, pulmonary exacerbations or requirement of additional treatment between groups. Overall, the inhalation of lancovutide was safe although a higher rate of adverse events, especially related to the respiratory system, occurred as compared to placebo. CONCLUSIONS: Lancovutide did not improve FEV1 percent predicted when compared to placebo (NCT00671736).

Rhinosinusitis in cystic fibrosis: not a simple story.

OBJECTIVE: Chronic inflammation of sinuses and nasal mucosa is found in 74-100% patients suffering from cystic fibrosis, whereas nasal polyps in 6-44% patients. The aim of this paper is to assess rhinosinusitis types taking into account the forms of cystic fibrosis and the kind of CFTR gene mutation. MATERIAL AND METHODS: The author presents material of 126 cystic fibrosis patients, 90 with typical clinical features and 36 with atypical phenotype. Genetic tests were carried out to determine the genotype of CFTR gene. The sample was divided into four groups according to the genotype effect on the chloride canal function. Cytological examination of nasal mucosa was carried out in all the patients. RESULTS: In 71.5% of patients with cystic fibrosis, infectious chronic non-specific rhinosinusitis was found. Other types of rhinosinusitis--acute infectious, chronic allergic and non-allergic with eosinophilia were found in 21.4% of patients, whereas in 7.1% of patients no clinical symptoms of rhinosinusitis were found. Nasal polyps were found in 23 (18.3%) patients with cystic fibrosis: in 21 patients with a typical form and in 2 patients with an atypical form. Nasal polyps were more frequent in groups with the genotype consisting of both "strong" mutations than in the group with unknown or "mild" mutations. CONCLUSION: Rhinosinusitis in cystic fibrosis patients is not homogenous pathology. Infectious chronic non-specific rhinosinusitis is found the most frequently, but other forms of rhinosinusitis appear quite often and they require proper treatment.

Frequency, consequences and pharmacological treatment of gastroesophageal reflux in children with cystic fibrosis.

BACKGROUND: Gastroesophageal reflux (GER) may aggravate chronic bronchopulmonary diseases. The study evaluated GER frequency and characteristics in children with Cystic Fibrosis (CF) as well as its consequences and pharmacological treatment. MATERIAL/METHODS: 40 CF children aged 1.3 to 20 years were examined. The study methodology involved: medical files analysis, anamnesis, physical examination, growth status estimation, esophageal pH-metry and upper gastrointestinal tract endoscopy with histological examination of esophageal biopsies. RESULTS: Based on pH-metry results, the diagnosis of GER was established in 22 children (55%). Mild GER (Index Reflux - IR 5-10%) was found in 12 children (54.5%), moderate GER (IR 10-20%) in 7 (31.8%) and severe GER (IR>20%) in 3 (13.6%). Ten patients with moderate or severe GER underwent endoscopy, which revealed GER-related esophagitis in 8 cases. There was no statistical difference of GER frequency and degree according to: age, sex, growth status, presence of type DF508 mutation in CFTR genome and typical GERD symptoms. According to the ESPGAN proposition, cisapride or cisapride with ranitidine medication was instituted. Treatment analysis was performed in 19 cases after successful follow-up examinations carried out three months later, indicating a significant decrease in reflux index, the longest episode duration and the number of episodes longer than 5 minutes. Improvement of endoscopic picture was noticed after treatment. CONCLUSIONS: High frequency of gastroesophageal reflux and its consequences among children with cystic fibrosis, as well as the possibility of well-tolerated and efficient treatment of GER, indicate that diagnostics of GER among children with CF should be obligatory.