CFTR Protein: Not Just a Chloride Channel?

Cystic fibrosis (CF) is a recessive genetic disease caused by mutations in a gene encoding a protein called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The CFTR protein is known to acts as a chloride (Cl-) channel expressed in the exocrine glands of several body systems where it also regulates other ion channels, including the epithelial sodium (Na+) channel (ENaC) that plays a key role in salt absorption. This function is crucial to the osmotic balance of the mucus and its viscosity. However, the pathophysiology of CF is more challenging than a mere dysregulation of epithelial ion transport, mainly resulting in impaired mucociliary clearance (MCC) with consecutive bronchiectasis and in exocrine pancreatic insufficiency. This review shows that the CFTR protein is not just a chloride channel. For a long time, research in CF has focused on abnormal Cl- and Na+ transport. Yet, the CFTR protein also regulates numerous other pathways, such as the transport of HCO3-, glutathione and thiocyanate, immune cells, and the metabolism of lipids. It influences the pH homeostasis of airway surface liquid and thus the MCC as well as innate immunity leading to chronic infection and inflammation, all of which are considered as key pathophysiological characteristics of CF.

Immunoglobulin G: A useful outcome marker in the follow-up of cystic fibrosis patients?

BACKGROUND AND METHODS: Hypergammaglobulinemia (hyper-IgG) and hypogammaglobulinemia (hypo-IgG) have been reported in patients with cystic fibrosis (CF). Although the clinical respiratory course is paradoxically different, depending on the IgG status, this association remains elusive. Therefore, we performed a longitudinal study to assess the annual evolution of IgG profiles in a cohort of pediatric patients with CF, from their diagnosis until 2016. We then compared clinical findings with the patients' IgG status to determine whether IgG status could reflect the respiratory clinical course of patients with CF. RESULTS: Among the 66 patients with CF that were aged between 12 months and 18 years in 2016 (mean age: 9.3 years [SD: 5.2]), hypo-IgG was observed in 15.2% and no hyper-IgG was identified. Longitudinal assessment since diagnosis revealed no hyper-IgG but 33.3% of patients had at least one sample showing hypo-IgG, among which two patients displayed persistent hypo-IgG. The number of pulmonary exacerbations, duration of antibiotic therapy, and erythrocyte sedimentation rate were all lower in hypo-IgG patients. No difference was observed for the genotype, chronic Pseudomonas aeruginosa or Staphylococcus aureus infection, and in the parameters of lung function. CONCLUSION: The IgG profile of pediatric patients with CF has changed over recent decades, particularly with regard to hyper-IgG. In a significant portion of the pediatric CF population, hypo-IgG is transient and only identifiable in longitudinal assessments. This study reinforces that hypo-IgG patients paradoxically present a more favorable course of clinical status. Therefore, IgG levels could be a useful outcome marker in the follow-up of patients with CF.

Exhaled nitric oxide in childhood allergic asthma management: a randomised controlled trial.

OBJECTIVE: We investigated the potential yield of incorporating fractional exhaled nitric oxide (FeNO) measurements in childhood allergic asthma management. METHODS: Ninety-nine children with persistent allergic asthma were included in this multicentre, single-blind, randomized controlled trial. Treatment was based on the Global Initiative for Asthma (GINA) guidelines. In the FeNO group, asthma management was also guided by FeNO measurements. Health outcomes were evaluated over a 52-week timeframe. RESULTS: Fewer asthma exacerbations were registered in the FeNO group. 24% of the children in the FeNO group experienced one or more exacerbations per year, compared with 48% in the clinical group (P = 0.017). The proportion of symptom-free days did not differ between groups. In the FeNO group, more months of leukotriene receptor antagonist use (median (interquartile range)) were observed: 12 (9-12) months, compared with 9 (3-12) months in the clinical group (P = 0.019). Next, the evolution of inhaled corticosteroid doses between visits 1 and 5 (median change (interquartile range)) showed a significant increase of +100 µg (0, +400) in the FeNO group and a change of 0 µg (-200, +80) in the clinical group (P = 0.016). CONCLUSIONS: FeNO measurements in childhood asthma management did not improve the proportion of symptom-free days, but did result in fewer asthma exacerbations associated with an increased leukotriene receptor antagonist use and an augmentation of the inhaled corticosteroid doses.

[Prevention and treatment of asthma in child]. / Prévention et traitement de l'asthme chez l'enfant.

Asthma is a chronic inflammatory disorder of the airways with an impact on the life of the patient, his family and the society. Asthma is the most common chronic disease of the childhood. Consequently, prevention and treatment of asthma are real challenges in public health. Treatment includes two levels: prevention and medication treatment. Prevention is to avoid one or several causes of asthma and risk factors of exacerbations particularly in high risk population. Medication treatment includes the reliever treatment and the maintenance treatment. Bronchodilatator treatment will be used in first line treatment in asthma attacks. Inhaled glucocorticosteroids are the most effective controller medications. No treatment is curative for asthma, establishing of therapeutic objectives is necessary. The reliever treatment, the maintenance treatment, the new classification of asthma and the new recommendations of therapeutic management will be discussed.