Test for the Concentration of Electrolytes in Cystic Fibrosis of the Pancreas Utilizing Pilocarpine by Iontophoresis, by Lewis E. Gibson and Robert E. Cooke,Pediatrics; 1959;24:545–549
Aim. To develop a method for stimulating sweating that is rapid, painless, and avoids the risk of heat stress.
Background. Since the discovery that there is a high concentration of sodium and chloride in the sweat of patients with cystic fibrosis of the pancreas in 1953, the sweat test has been performed by placing the patient's body in a plastic bag with or without hot water bottles to stimulate sweating. This method is unsatisfactory because of complications such as hyperpyrexia and heat stroke. Direct injection of a cholinergic agent intradermally is painful and therefore not practical.
Methods. A rheostat with a milliampere meter was constructed at a cost of ∼$7 that allowed the iontophoresis of pilocarpine into the skin using negative and positive (2-cm diameter) electrocardiography electrodes. The positive electrode was placed on the flexor surface of the arm over a filter paper soaked in 0.2 mL of 0.2% pilocarpine nitrate. Current (0.2 mA) was applied for 5 minutes and then sweat was collected onto a preweighed filter paper for 30 minutes. Sweat chloride was determined by a polarographic method. Sweat tests were performed on 25 patients with cystic fibrosis (CF), 17 asymptomatic relatives and 27 control patients. Patients with CF had sweat chloride concentration >80 mEq/L; relatives, 32.5 mEq/L (highest 57 mEq/L); and control subjects, 21.1 mEq/L (highest 60 mEq/L).
Conclusions. The iontophoresis of pilocarpine into the skin is a rapid, painless, safe, and reliable method for stimulating sweating and facilitating the determination of sweat chloride concentration.
This article by Gibson and Cooke published inPediatrics in 1959 described a method for stimulating and collecting sweat in infants and children to determine chloride concentration. This methodologic paper provided the basis for the standard sweat collection method that is still being used nearly 40 years later for the diagnosis of CF. Previously, the standard method of inducing sweating was by placing an infant in a plastic bag with or without hot water bottles! This dangerous practice was quickly supplanted by the relatively quick and easy iontophoresis method of Gibson and Cooke.
How did Pete Gibson and Bob Cooke know that sweat chloride concentrations were abnormal in CF. Astute clinical observation and the testing of an hypothesis led to the discovery of high NaCl concentration in sweat of patients with CF. In a seminal paper published in Pediatrics in 1951, Kessler and Anderson1 reported that 5 of 10 children admitted to Babies Hospital in New York as a result of a severe hot spell in August 1948 were children with CF. The children suffered from marked dehydration, fever, and signs of circulatory collapse, and two patients died (both had CF). In subsequent summers, 2 more patients with CF suffered from heat prostration. Note that 7 patients with CF represented 40% of the known CF population in New York at the time! They hypothesized that either sweat glands were not functioning well or that low grade infection and hypermetabolism had made the children with CF more susceptible to heat prostration. They actually favored the latter hypothesis because two of the children with CF were observed to be sweating profusely. This observation led to the hypothesis that there may be an abnormality in the electrolyte composition of sweat in patients with CF, and the same authors published two papers on this subject in 1953. The first was a preliminary communication.2 The second paper again was a seminal paper that first proved that there was elevated sweat NaCl in CF and was published in Pediatrics 6 years before the standard method for collecting sweat was published by Gibson and Cooke. Di Sant'Agnese et al3 studied 43 patients with CF (2 to 16 years of age) and 50 control subjects (40 children and 10 adults). Sweat was collected from the midabdomen on dry gauze patches. Sweating was induced in a hot humid room (32.2°C; 50% humidity), and subjects were covered with a sheet and blanket! There was almost no overlap between CF patients and control in sweat chloride values. These authors also questioned the use of the term mucoviscidosis because both sweat and salivary gland secretions were abnormal in CF, and they suggested that the disease affected all exocrine gland function.
Thus, the three papers published in the 1950s inPediatrics culminated in establishing the standard iontophoresis method of sweat collection for the diagnosis of CF and made it possible to establish reliably the diagnosis earlier and more safely, and allowed for early treatment of the disease. Concomitant with this was an increase in median survival age from ∼3 years in the 1950s to ∼17 years by 1970.
- Copyright © 1998 American Academy of Pediatrics