AUTONOMIC AND AIRWAY REACTIVITY IN OBLIGATE HETEROZYGOTES FOR CYSTIC-FIBROSIS

Abstract

Obligate heterozygotes for cystic fibrosis [CF], like the patients themselves, have significantly increased pupillary .alpha.-adrenergic and cholinergic sensitivity and significantly decreased lymphocyte .beta.-adrenergic responses. The parents of patients with CF also have a high prevalence of airway reactivity: 1/3 have a fall in forced expiratory vol in 1 s (FEV1) of > 20% (PD20 FEV1) to < 3 mg/ml methacholine, compared with 4% in control subjects (P = 0.01, .chi.2). Airway reactivity (PD20 FEV1) is significantly correlated with the lymphocyte cAMP response to isoproterenol (Rs = 0.54, P < 0.05). Abnormal autonomic and airway reactivity cannot be ascribed to medication usage, preexisting pulmonary disease or atopy in these subjects. The autonomic abnormalities in CF are inherited and may contribute to the development and progression of pulmonary disease by predisposing to increased airway reactivity.