Cystic Fibrosis and Formes Frustes of CFTR-Related Disease

Abstract

Cystic fibrosis (CF) is the commonest genetic cause of bronchiectasis in the Caucasian population. Since identification of the putative gene in 1989, the molecular basis of the condition has become clearer with characterisation of the unique pathophysiology. The small airways are the primary site of lung disease, with an intense but localised inflammatory picture, dominated by neutrophils. The clinical heterogeneity is explained to some degree by the distinct molecular consequences of the many mutations that have been recognised to affect the CF transmembrane conductance regulator (CFTR) gene; however other genes appear to modify the phenotype as well as environmental exposure. It has become increasingly apparent that certain conditions may result from CFTR dysfunction without fulfilling diagnostic criteria for CF. In some cases this may result in single organ disease for which the term CF (or CFTR)-related disease has been advocated. Congenital bilateral absence of the vas deferens is the most clearly characterised of these. In other cases where a mild CF phenotype is apparent, atypical CF is probably a better term. It remains unclear whether carrier status predisposes to certain conditions such as chronic rhinosinusitis or pancreatitis.

Cystic Fibrosis Carrier Testing in an Ethnically Diverse US Population

“…Cystic fibrosis (CF) 2 is a panethnic autosomal recessive disease characterized by obstructive lung disease with microbial colonization, exocrine pancreatic insufficiency, diabetes, liver disease, and congenital bilateral absence of the vas deferens (CBAVD) in affected males (1,2 ). Advancing medical care has improved the quality of life for patients with CF, yet life expectancy is limited, with a mean life expectancy of 37.4 years in the US (3 ).…”

Ibuprofen Modulates NF-ĸB Activity but Not IL-8 Production in Cystic Fibrosis Respiratory Epithelial Cells

“…We tested this hypothesis in a respiratory epithelial cell line (CFTE29o–) [21] which expresses the most common CF mutation (F508del) [22]. Key experiments were confirmed in another CF respiratory epithelial cell line (CFBE41o–; F508del) [23], as well as in a 1HAEo– respiratory epithelial cell line expressing wild-type CF transmembrane regulator (CFTR) [24].…”

The Genetics of CFTR: Genotype - Phenotype Relationship, Diagnostic Challenge and Therapeutic Implications

“…Not easier is the task of categorizing the even more heterogeneous oligo-and mono-symptomatic CFTR-RD. In this regard CFTR mutations have been linked to a wide series of pathologies: obstructive azoospermia for CBAVD (Claustres, 2005;Cuppens & Cassiman, 2004;Stuhrmann & Dork, 2000); non-obstructive azoospermia, reduced sperm quality and spermatogenesis defects (Boucher et al, 1999;Dohle et al, 2002;Jakubiczka et al, 1999;Jarvi et al, 1998;Mak et al, 2000;Pallares-Ruiz et al, 1999;van der Ven et al, 1996); male hypofertility due to idiopathic seminal hyperviscosity (Elia et al, 2009;Rossi et al, 2004); female hypofertility due to thick cervical mucus (Gervais et al, 1996;Hayslip et al, 1997); neonatal hypertrypsinaemia with normal sweat test (Castellani et al, 2001a;Gomez Lira et al, 2000;Narzi et al, 2007;Padoan et al, 2002); idiopathic pancreatitis (Castellani et al, 2001b;Gomez Lira et al, 2000;Maire et al, 2003;Pallares-Ruiz et al, 2000); pulmonary diseases (Bombieri et al, 1998;Bombieri et al, 2000); disseminated bronchiectasis (Girodon et al, 1997;Pignatti et al, 1995); chronic rhinosinusitis (Raman et al, 2002;Southern, 2007;Wang et al, 2000b); nasal polyposis (Kerem, 2006;Pawankar, 2003); metabolic alkalosis, hypochloremia, hyponatriemia, hypokalemia and dehydration (Augusto et al, 2008;Kerem, 2006;Leoni et al, 1995;…”