BACKGROUND: Abnormal homeostasis of the volume of airway surface liquid in patients with cystic fibrosis is thought to produce defects in mucus clearance and airway defense. Through osmotic forces, hypertonic saline may increase the volume of airway surface liquid, restore mucus clearance, and improve lung function.

METHODS: A total of 24 patients with cystic fibrosis were randomly assigned to receive treatment with inhaled hypertonic saline (5 ml of 7 percent sodium chloride) four times ...

BACKGROUND: Cystic fibrosis is characterized by abnormal electrolyte transport across the epithelia of the airways. In particular, there is excessive sodium absorption and deficient chloride secretion. Drugs that block excessive sodium absorption may provide clinical benefit in cystic fibrosis, but there are no available therapeutic agents to improve chloride secretion. In vitro studies in cultured human-airway epithelia indicate that triphosphate nucleotides (ATP and UTP) induce ...

BACKGROUND: Many patients with chronic pulmonary disease similar to that seen in cystic fibrosis have normal (or nondiagnostic) sweat chloride values. It has been difficult to make the diagnosis of cystic fibrosis in these patients because no associated mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene has been identified.

METHODS: We evaluated 23 patients with pulmonary disease characteristic of cystic fibrosis but with sweat chloride concentrations in the ...

RATIONALE: Primary ciliary dyskinesia (PCD) is an autosomal recessive, genetically heterogeneous disorder characterised by oto-sino-pulmonary disease and situs abnormalities (Kartagener syndrome) due to abnormal structure and/or function of cilia. Most patients currently recognised to have PCD have ultrastructural defects of cilia; however, some patients have clinical manifestations of PCD and low levels of nasal nitric oxide, but normal ultrastructure, including a few patients with ...

RATIONALE: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by recurrent infections of the airways and situs inversus in half of the affected offspring. The most frequent genetic defects comprise recessive mutations of DNAH5 and DNAI1, which encode outer dynein arm (ODA) components. Diagnosis of PCD usually relies on electron microscopy, which is technically demanding and sometimes difficult to interpret.

METHODS: Using specific antibodies, we ...

BACKGROUND: Cystic fibrosis is a monogenic disease that deranges multiple systems of ion transport in the airways, culminating in chronic infection and destruction of the lung. The introduction of a normal copy of the cystic fibrosis transmembrane conductance regulator (CFTR) gene into the airway epithelium through gene transfer is an attractive approach to correcting the underlying defects in patients with cystic fibrosis. We tested the feasibility of gene therapy using adenoviral ...

RATIONALE: Primary ciliary dyskinesia (PCD) is characterized by recurrent airway infections and randomization of left-right body asymmetry. To date, autosomal recessive mutations have only been identified in a small number of patients involving DNAI1 and DNAH5, which encode outer dynein arm components.

METHODS: We screened 109 white PCD families originating from Europe and North America for presence of DNAH5 mutations by haplotype analyses and/or sequencing.

RESULTS: Haplotype analyses ...

BACKGROUND: It is unknown whether genetic factors predispose patients to idiopathic pancreatitis. In patients with cystic fibrosis, mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene typically cause pulmonary and pancreatic insufficiency while rarely causing pancreatitis. We examined whether idiopathic pancreatitis is associated with CFTR mutations in persons who do not have lung disease of cystic fibrosis.

METHODS: We studied 27 patients (mean age at ...

BACKGROUND & AIMS: Nonalcoholic chronic pancreatitis is usually idiopathic and often associated with cystic fibrosis gene (CFTR) mutations. It is unknown whether pancreatitis risk correlates with having 1 or 2 CFTR mutations, abnormal epithelial ion transport, or mutations of other genes.

METHODS: We tested 39 patients with idiopathic chronic pancreatitis (mean age at diagnosis, 33 years) for common mutations of CFTR and of genes encoding a trypsin inhibitor (PSTI) and trypsinogen ...

Cystic fibrosis (CF) is a monogenetic disease that is associated with chronic airways disease and early death. The pulmonary disease reflects mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and associated abnormal epithelial ion transport, including defective cAMP-mediated (CFTR) Cl- secretion and an accelerated rate of basal Na+ transport. With the development of vectors for gene therapy, the airway epithelium of CF patients has been targeted for ...

RATIONALE: Primary ciliary dyskinesia (PCD) is a rare, usually autosomal recessive, genetic disorder characterized by ciliary dysfunction, sino-pulmonary disease, and situs inversus. Disease-causing mutations have been reported in DNAI1 and DNAH5 encoding outer dynein arm (ODA) proteins of cilia.

OBJECTIVES: We analyzed DNAI1 to identify disease-causing mutations in PCD and to determine if the previously reported IVS1+2_3insT (219+3insT) mutation represents a "founder" or "hot spot" ...

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 20 genes, but collectively they account for only ∼65% of all PCDs. To identify mutations in additional genes that cause PCD, we performed exome sequencing on three unrelated probands with ciliary outer and inner dynein arm (ODA+IDA) defects. Mutations in SPAG1 were identified in ...

We studied the change in ion transport function by measuring the basal transepithelial potential difference (PD) across the ciliated epithelium of the nose in 85 term neonates during the first 72 hours of life. Differences in PD associated with the mode of delivery or the presence of respiratory disease and differences in the PD response to the superfusion of amiloride (10(-5) mol/L) were assessed. We also studied term neonates with transient tachypnea of the newborn (TTN) and acute ...

Hemoptysis is common in patients with cystic fibrosis (CF). Bleeding may vary in severity, ranging from minor blood-streaking of sputum to expectoration of significant quantities of blood. Major hemoptysis, defined as bleeding greater than 240 ml/24 h, represents a medical emergency. Bronchial artery embolization (BAE) is one of the treatment options for hemoptysis. We reviewed the 10-yr experience at the University of North Carolina Hospitals in the treatment of hemoptysis by BAE. ...