Paul A. di Sant'Agnese

Cystic fibrosis in adults. 75 cases and a review of 232 cases in the literature.

Abstract Cystic fibrosis is now the most common cause of chronic obstructive pulmonary disease (COPD) and of pancreatic insufficiency in the first three decades of life in the United States. In this report we describe 75 patients with cystic fibrosis aged 18 to 47 years and review another 232 cases reported in the literature. All of these 307 patients had elevated sweat chloride and sodium levels, which proved excellent discriminants for cystic fibrosis even in patients in the older age group. COPD, present in 97 per cent, was the major cause of morbidity and mortality, and differed from COPD of other etiologies. The progressive downhill course in these patients was punctuated by recurrent symptomatic exacerbations of chronic bacterial bronchitis caused by Pseudomonas aeruginosa and Staphyloccocus aureus, and terminated in pulmonary insufficiency, cor pulmonale and death. COPD was complicated by minor hemoptysis in 60 per cent, massive hemoptysis in 7 per cent and pneumothorax in 16 per cent, problems rare in children. Sinusitis was present in all those examined roentgenographically, and 48 per cent had nasal polyposis. Pancreatic insufficiency was present in 95 per cent of the patients, but in contrast to younger patients it was seldom symptomatic although steatorrhea and azotorrhea were still massive. Intussusception and meconium ileus equivalent (fecal accumulation) are frequent in adults (21 per cent) but rare in children, and they require immediate diagnostic and therapeutic intervention with enemas of diatrizoate sodium. Glycosuria, biliary cirrhosis, cholelithiasis and aspermia were among other complications. Height and weight were usually within the lower limits of normal, but 17 per cent of the men were above 180 cm in height and 7 per cent were overweight. Therefore, a high index of suspicion is needed to make the diagnosis, because older patients with cystic fibrosis may look quite well.

A new prognostic score and clinical evaluation system for cystic fibrosis

A new, simple, and comprehensive system for evaluating patients with cystic fibrosis is presented. The system is based primarily on pulmonary parameters of the disease and considers simple pulmonary function tests and certain complications which have been shown to have prognostic significance. Seventy-three patients were evaluated and 3 and 6 year mortality rates were calculated. Based on this data, a curve depicting probability of dying from cystic fibrosis (within 3 years) according to the prognostic scores was determined. The combination of this new scoring system and mortality rate curve allows for rapid, simultaneous assessment of a patients past and current clinical status and provides a numerical prediction of life expectancy.

The Occurrence and Effects of Human Vitamin E Deficiency: A STUDY IN PATIENTS WITH CYSTIC FIBROSIS

The role of vitamin E in human nutrition was studied by investigation of patients with cystic fibrosis (CF) and associated pancreatic insufficiency. Vitamin E status was assessed by measurement of the plasma concentration of the principal circulating isomer, alpha-tocopherol. Results of such determinations in 52 CF patients with pancreatogenic steatorrhea revealed that all were deficient in the vitamin. The extent of decreased plasma tocopherol varied markedly but correlated with indices of intestinal malabsorption, such as the serum carotene concentration and percentage of dietary fat absorbed. Supplementation with 5-10 times the recommended daily allowance of vitamin E in a water-miscible form increased the plasma alpha-tocopherol concentrations to normal in all 19 CF patients so evaluated. Studies on the effects of vitamin E deficiency focused on possible hematologic alterations. An improved technique was developed to measure erythrocyte hemolysis in vitro in the presence of hydrogen peroxide. While erythrocyte suspensions from control subjects demonstrated resistance to hemolysis during a 3-h incubation, all samples from tocopherol-deficient CF patients showed abnormal oxidant susceptibility, evidenced by greater than 5% hemoglobin release. The degree of peroxide-induced hemolysis was related to the plasma alpha-tocopherol concentration in an inverse, sigmoidal manner. The possibility of in vivo hemolysis was assessed by measuring the survival of (51)Cr-labeled erythrocytes in 19 vitamin-E deficient patients. A moderate but statistically significant decrease in the mean (51)Cr erythrocyte half-life value was found in this group. Measurement of erythrocyte survival before and after supplementation of 6 patients with vitamin E demonstrated that the shortened erythrocyte lifespan could be corrected to normal with this treatment. Other hematologic indices in deficient subjects, however, were normal and did not change upon supplementation with vitamin E. It is concluded that CF is invariably associated with vitamin E deficiency, provided that the patient in question has pancreatic achylia and is not taking supplementary doses of tocopherol. Concomitant hematologic effects consistent with mild hemolysis, but not anemia, occur and may be reversed with vitamin E therapy. Patients with CF should be given daily doses of a water-miscible form of vitamin E to correct the deficiency.

Pathogenesis and physiopathology of cystic fibrosis of the pancreas. Fibrocystic disease of the pancreas (Mucoviscidosis).

CYSTIC fibrosis of the pancreas is the most recently recognized of the major chronic diseases of man. Reported for the first time by Fanconi1 in Switzerland in 1936, fibrocystic disease of the panc...

Glucose Intolerance in Cystic Fibrosis

Abstract Moderate to severe oral glucose intolerance was observed in 42 per cent of 31 patients with cystic fibrosis of the pancreas. Serum insulin concentrations after glucose were low in all patients regardless of glucose tolerance. When glucagon or tolbutamide was infused at the height of the reduced insulin response to oral glucose, serum insulin levels promptly increased 100 per cent or more in all cases. Since family histories, characteristic complications and post-mortem signs of diabetes mellitus were absent and the decrease in the number of beta cells was only modest, the glucose intolerance in cystic fibrosis is probably not due to coexistent diabetes mellitus or to beta-cell loss but, rather, to the anatomic disorganization of the islands of Langerhans produced by fibrosis of the pancreas.

Sweat electrolyte disturbances associated with childhood pancreatic disease.

Abstract The abdominal sweat content of chloride, sodium and potassium was found to be markedly-increased in fifty patients with fibrocystic disease of the pancreas as compared with sixty control cases representing a variety of other diseases. The rate of sweating was not significantly different in the two groups. The abnormal increase in sweat electrolyte levels in patients with cystic fibrosis of the pancreas was shown not to be secondary to pancreatic deficiency or to chronic pulmonary disease. Renal and adrenal function in respect to sodium chloride was found to be normal in fibrocystic patients studied under rigidly controlled metabolic conditions. The defect must therefore be in the sweat glands themselves. In hot weather the abnormally high electrolyte levels in the sweat lead at times to massive salt depletion followed by peripheral vascular collapse, hyperpyrexia, coma and death. This sequence of events can be avoided by timely intravenous administration of physiologic saline solution. Several family members of known patients with cystic fibrosis of the pancreas were found to have sweat electrolyte abnormalities similar to those described in the patients. At times these were associated with generalized obstructive emphysema, without demonstrable pancreatic involvement. This leads to speculation as to the existence of incomplete forms of the disease and their relation to certain types of chronic pulmonary disease. While the pancreatic lesions were the first to attract attention to cystic fibrosis of the pancreas, this disorder is in reality a generalized disease in which many and perhaps all exocrine glands are affected.

Emotional adjustment of adolescents and young adults with cystic fibrosis

Twenty-seven adolescents and young adults with cystic fibrosis were studied to evaluate the phychological impact of this chronic illness. At first glance, most patients appeared to function adequately on a daily basis. However, four sources of psychological stress, leading to emotional disturbance, were identified: altered physical appearance causing distorted body images and denial of sexuality, strained interpersonal relationships resulting in isolation and mental strain, conflicts in upbringing, and increased awareness of the future and of death. Guidelines for the physician treating these young adults and their families include: (1) encouragement for greater involvement by the patients father; (2) assisting the mother to find outside interests and to allow more independence to the patient; (3) stressing communication about cystic fibrosis within the home; (4) emphasizing outside activity for each patient; (5) repeated discussions of the patients concerns while emphasizing his strengths; (6) anticipation of problems, specific to cystic fibrosis, such as sterility in males; and (7) encouragement of interpatient communication.

Low sweat electrolytes in a patient with cystic fibrosis

A patient with the clinical syndrome of cystic fibrosis characterized by chronic pulmonary disease, infection with mucoid Pseudomonas aeruginosa, sinusitis, nasal polyposis, abnormal pancreatic bicarbonate response to secretin stimulation, but normal levels of trypsin and chymotrypsin in the duodenal drainage, and a sibling with autopsy-documented cystic fibrosis, is described. Sweat chloride ranged from 20 to 44 meq/liter and sweat sodium from 36 to 55 meq/liter. Immunoglobulin deficiency, alpha 1-antitrypsin deficiency, tuberculosis and abnormalities of ciliary ultrastructure were excluded. Review of sweat electrolytes in 213 patients with cystic fibrosis revealed that patients with normal pancreatic enzyme release have significantly lower sweat sodium and chloride concentrations (p < 0.0005) than do patients with pancreatic insufficiency. Chronic pulmonary disease, pancreatic insufficiency and elevated levels of sweat electrolytes comprise the classic diagnostic triad for cystic fibrosis. The expression of these features may be variable, but the sweat test remains the cardinal laboratory confirmation of the diagnosis. Over 98 percent of patients with cystic fibrosis have sweat chloride values greater than 60 meq/liter, 1 to 2 percent between 50 and 60 meq/liter, and only about one in 1,000, like our patient, less than 50 meq/liter. Patients with cystic fibrosis with borderline sweat chloride values frequently have chronic pulmonary disease but intact pancreatic enzyme release. In such patients, family history, ancillary clinical features and systemic exclusion of other syndromes assume special diagnostic importance.

Cystic fibrosis of the pancreas

In Andersen’s (1938) early account of cystic fibrosis of the pancreas the majority of patients died in the first year of life and the disease carried a hopeless prognosis, but since the introduction of antibiotic therapy for respiratory infections the outlook has steadily improved. In the cases studied at Boston (Schwachman and Kulczycki, 1958) the average age at death prior to 1948 was one year, but rose to 5 years for the period 1951 to 1956; and in 1956–57 almost 40% of 105 cases were more than 10 years old. Nearly 14% of the total series of 400 cases in New York (Andersen, 1958) were over the age of 10, some of them living normal adult lives and most of the older patients showing little or no progression of pulmonary changes.

Studies of salt excretion in sweat. Relationships between rate, conductivity, and electrolyte composition of sweat from patients with cystic fibrosis and from control subjects.

A device is described with which it is possible to measure the rate of sweating and the conductivity of sweat simultaneously. Interestingly, it was found that the sweat glands in patients with cystic fibrosis of the pancreas behave like those in normal individuals in that the concentration of electrolytes (as measured by the conductivity) is greater at rapid rates of sweating than at slow rates. However, the range of values in fibrocystic patients is so much higher than in controls as to not affect the diagnostic value of the sweat test. As interpreted, the data indicate that the precursor solution in patients with cystic fibrosis has a higher concentration of electrolytes than that in normal individuals. The rate of tubular salt absorption is approximately the same in patients with cystic fibrosis and in normal individuals.