The answer is e. Cystic fibrosis (CF) is a multisystem disease caused by an abnormally functioning cystic fibrosis transmembrane regu¬lator (CFTR) protein. Abnormal secretions are produced as a result of decreased permeability of ionized chloride in the secretory epithelium of a number of organs. Progressive lung failure is caused by accumulation of viscid secretions that obstruct the airway and lead to infection, bronchiectasis, and inflammatory changes. Survival has improved markedly during the past few decades as a result of prompt recognition of CF and aggressive treatment; the median age at death has increased from less than 10 years to more than 30 years. Therapeutic approaches have included inhalation therapy, chest physical therapy, aggressive antibiotic administration, bronchodilators, oxygen, and nutritional support. Heart-lung transplants have prolonged life and improved qualify of life for some terminal patients. Sev¬eral new approaches to the treatment of CF have been proposed, namely, the use of amiloride, recombinant DNAase, and gene therapy. The rationale for these therapeutic modalities is that they focus directly on ameliorating or correcting the basic deficit: amiloride by inhibiting sodium, and with it water reabsorption, thereby improving airway hydration; DNAase by reacting with DNA released by dead leukocytes to reduce sputum viscosity; and gene therapy by altering genetic material. Lung cancer does not appear to be associated with cystic fibrosis.
Unlike many other tests, there is almost no overlap in chloride values in sweat between patients with cystic fibrosis and normal control partici-pants. A chloride concentration of greater than 60 meq/L is diagnostic, val¬ues less than 40 are normal, and values between 40 and 60 are intermediate. Genetic studies that assay for about 30 of the most common mutations known to cause CF are available. A number of states have included a test for immunoreactive trypsinogen in their newborn screening programs, and when combined with confirmatory testing, the sensitivity has been re¬ported to be as high as 95%.
Conditions other than cystic fibrosis can manifest an elevated sweat chloride, including adrenal insufficiency, ectodermal dysplasia, nephrogenic diabetes insipidus, hypothyroidism. and malnutrition.