Management of Pseudomonas Aeruginosa Lung Infection in Danish Cystic Fibrosis Patients

ABSTRACT. The annual mortality rate of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection at the Danish CF-centre ranged from 10 to 20% in the years 1970–1975. In this period the patients received antipseudomonal chemotherapy only during acute exacerbations of infection. From 1976 99 patients acquired chronic P. aeruginosa infection and were given regular and intensive antipseudomonal treatment 3–4 times per year. The patients were followed for 612 patient-years; 7 died and the 10-year survival rate after onset of P. aeruginosa infection was 90%±4%. The annual mortality rate is now 1–2%. Although precipitating antibodies against P. aeruginosa increased significantly, pulmonary function did not deteriorate with duration of infection. Cross-infection between patients caused an increased incidence of chronic P. aeruginosa infection which was reduced by hygienic measures.     

Evaluation of the PEP Mask in Cystic Fibrosis

ABSTRACT. Twenty-eight patients suffering from cystic fibrosis, with an age range of 8-21 years entered a randomised cross-over trial to study the efficacy of the Positive Expiratory Pressure (PEP) mask as a method of chest physiotherapy, both on its own and in conjunction with other physiotherapy techniques. Twenty-four of these patients completed the trial consisting of 4 treatment programmes each lasting one month and with no wash-out period between them. Five of these patients went on to a fifth programme of Forced Expiratory Technique (FET) alone. At the end of the trial, no significant difference was found between the programmes as regards growth, Shwachman score, Chrispin—Norman score or pulmonary function tests. Twenty-three patients chose to continue using the PEP mask in conjunction with FET long-term as their chest physiotherapy programme as they felt it was an effective treatment allowing increased independence, with postural drainage being kept to a minimum.     

Bile Acid Metabolism in Children with Cystic Fibrosis

ABSTRACT. Recycling of bile acids through the enterohepatic cycle is very efficacious. Bile acids contribute to bile formation and, by forming micelles, participate in lipid solubilization and absorption. The small fraction which escapes in the feces, is synthesized daily by the liver to compensate for losses. In CF, bile acid malabsorption has been documented; these large losses are accompanied by an interruption in the enterohepatic circulation with concomitant reduction in bile acid pool and disturbances in biliary composition. The various intraluminal factors implicated in bile acid malabsorption include: unhydrolysed triglycerides and phospholipids, precipitation of bile acids in acidic duodenal content, adsorption to residues and modification of colonic microflora. A defect in bile acid ileal uptake has also been advocated. These disturbances in bile acid metabolism associated with CF might lead to aggravation of diarrhea and steatorrhea, cholelithiasis and perhaps liver disease.     

Scanning Electron Microscopic Study of the Airways in Normal Children and in Patients with Cystic Fibrosis and Other Lung Diseases

Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to examine pulmonary tissue from 9 patients with cystic fibrosis (CF), 12 patients with diseases other than CF, and from two surgically resected specimens with no known airways disease. A region of the human airways, the transition zone, was observed between the end of the terminal bronchiole and the type II alveolar cell lining of the respiratory bronchioles. This region was lined predominantly by nonciliated bronchiolar (NCB) cells. Patients with CF exhibited indistinct transition zones, epidermoid metaplasia, large dilated bronchial gland, copious surface mucus, alveolar destruction, and unusual microvilli; no single lesion specific for cystic fibrosis was identified.     

Lethal Respiratory Failure in Preterm Infants due to Cystic Fibrosis

ABSTRACT. We present the first report of two preterm infants who died from respiratory failure secondary to cystic fibrosis which presented in the early neonatal period.     

Screening for Cystic Fibrosis

ABSTRACT. A neonatal screening program for CF by determination of albumin in meconium was performed in the north eastern part of the Netherlands from 1973 to 1979. In this period 94043 newborns were screened and 116953 were not. A follow-up study of CF patients in the above cohorts was started in 1980. The purposes of this study were to evaluate the effects of early diagnosis and treatment in CF patients by comparing the outcome in the two groups of patients. Although the results indicate that very early diagnosis and treatment have a beneficial effect on outcome, more studies are needed before a definite answer can be given as to whether or not mass neonatal screening should be started.     

Congenital Hypothyroidism and Cystic Fibrosis

ABSTRACT. We report a case of dysgenetic congenital hypothyroidism associated with cystic fibrosis. Impaired exocrine pancreatic secretion and/or transit abnormalities secondary to the treatment of meconium ileus resulted in decreased absorption of l -thyroxine and difficulties in management of hypothyroidism.     

Cystic Fibrosis in Denmark 1945 to 1985

ABSTRACT. The entire population of cystic fibrosis (CF) patients in Denmark diagnosed in the period January 1, 1945, to June 30,1985, comprised 514 persons of whom 62 were diagnosed at autopsy. Of the remaining 452 patients, 372 were probands and 80 were secondary cases. The effect of a centralized treatment on the prognosis was evaluated using a Cox's regression model. Furthermore an incidence analysis was performed using probands including autopsies. Centrab'zed treatment had a significantly beneficial effect on the prognosis ( p =0.02), the death intensity (hazard rate) being decreased by a factor of 0.60. It was calculated that at present 1 out of 4760 newborn Danes may be diagnosed as suffering from CF before the age of 15 years, and 3% of the Danish population are heterozygotes for CF.     

Pulmonary Resection for Localized Bronchiectasis in Cystic Fibrosis

ABSTRACT. Three children with cystic fibrosis and localized bronchiectasis were treated by surgical removal of the affected lobe, after attempts to clear the obstructed bronchus by medical therapy and bronchoscopy with suction and lavage had been unsuccessful. Three to six years after surgery, the results are excellent. Pulmonary disease is mild in all patients, shown by chest radiographs and pulmonary function tests. A review of 102 cases reported in the literature demonstrates that pulmonary surgery is effective and can be performed safely in selected patients.     

Decreased Renal Clearance of Sodium in Cystic Fibrosis

ABSTRACT. In 10 patients with cystic fibrosis (CF) and 10 controls of similar age quantitative segmental handling of sodium was estimated by lithium clearance. In the CF group, there was tendency for an increased glomerular filtration rate (GFR) and increased absolute proximal sodium reabsorption. The fractional distal sodium reabsorption was significantly ( p =0.015) increased and sodium clearance was significantly ( p ≤0.01) decreased in CF.     

Long-term Effects of Physical Exercise on Working Capacity and Pulmonary Function in Cystic Fibrosis

ABSTRACT. Seven patients with cystic fibrosis aged 6 to 20 were enrolled for 30 months in a daily exercise program. After 12 months conventional chest physiotherapy was withdrawn. Patients with low initial Shwachman scores improved as regards maximal working capacity. Spirometric data and volume of trapped gas indicated opening of closed airways. We suggest that physical exercise in general should be the basis of pulmonary therapy in cystic fibrosis. Other forms of physiotherapy are advisable when hard physical exercise is not feasible.     

Acylcarnitine is Low in Cord Blood in Cystic Fibrosis

ABSTRACT. Carnitine metabolites (total, free, short and long chain) were analyzed in cord blood of cystic fibrosis (n=5), non-CF siblings (n=7), and controls (n=8). Total acylcarnitine (short and long chain combined) was significantly lower (<0.001) in CF compared to both control groups. Total and free carnitine showed no significant differences between the three groups. These findings are compatible with disturbed fatty acid metabolism in utero and may be related to the increased energy expenditure characteristic of CF infants.     

Deterioration in Lung Function after General Anaesthesia in Patients with Cystic Fibrosis

ABSTRACT. 48 hours after oesophagoscopy and injection sclerotherapy of oesophageal varices under general anaesthesia, 11 studies of 6 children ith cystic fibrosis and portal hypertension showed a significant deterioration in 4 tests of lung function. The largest falls were seen in Forced Expiration Volume in one second ( p <0.01) and Forced Expiratory Flow between 25 % and 75 % of Vital Capacity ( p <0.02). In 14 studies of 10 children with portal hypertension from other causes a significant fall occurred only in Peak Expiratory Flow Rate ( p <0.01). The slight falls in Forced Expiratory Volume in one second and Forced Expiratory Flow between 25 % and 75 % of vital capacity were significantly smaller than those observed in the patients with cystic fibrosis ( p <0.05; p <0.01).     

Pancreatic Enzyme Supplementation as Acid-Resistant Microspheres versus Enteric-Coated Granules in Cystic Fibrosis

ABSTRACT. In order to compare the efficacy of pancreatic enzyme supplementation as pH-sensitive enteric-coated microspheres Pancrease® to that of conventional supplementation with enteric-coated Pancreatin® in cystic fibrosis, a double blind cross-over study was conducted. Eleven patients under 12 years of age received each of the enzyme preparations for four weeks. Treatment efficacy was evaluated by means of a symptom score card recording stool frequency, consistency, colour, odour, abdominal cramps and appetite as well as a 3 days fat absorption test. Weight increments were recorded 3 months before the study when patients were on Pancreatin, and 3 months after the study when patients were on Pancrease. In eight of the patients fat absorption was improved on Pancrease, but the difference did not reach statistical significance. However, the patients experienced significantly less dyspeptic symptoms, decreased stool frequency, better appetite and increments in weight were significantly higher on Pancrease compared to Pancreatin.     

Abnormal Pancreatic Electrolyte Secretion in Cystic Fibrosis

ABSTRACT. We performed pancreatic function tests on sixty-five cystic fibrosis (CF), and eleven control children. The technique used continuous IV infusion of cholecystokinin and secretin, with duodenal juice collection over a 90 min period, and was made quantitative by continuous duodenal infusion and distal collection of an unabsorbable marker (bromosulphthalein). Some CF patients had near normal pancreatic enzyme outputs, some had impaired but measurable levels, but most (79 %) had almost absent trypsin secretion. CF children with better pancreatic function, were younger and more likely to be male. All controls showed a large increase in bicarbonate concentration and secretion rate per kilogram body weight during the test, but most children with CF (96.5 %) did not. Because two of our CF patients had water and bicarbonate secretion within the control range, this finding does not exclude the diagnosis of CF. Sodium, potassium and chloride ion secretion in CF patients was lower than controls but overlap occurred. We found a linear correlation between acinar and tubular secretion in CF patients which indicates that there is probably not a primary genetic defect in pancreatic bicarbonate secretion in CF.     

Giant Pancreatic Retention Cyst in Cystic Fibrosis: A Case Report

This is the fourth reported large pancreatic retention cyst in a patient with cystic fibrosis. The cyst recurred 7 months after partial cystectomy and produced extrinsic obstructive jaundice. It is presumed that the retention cyst developed in the ventral pancreas as a consequence of ductal obstruction by inspissated mucus with secondary fibrosis.     

Determinants of Serum Vitamin D Levels in Preadolescent Cystic Fibrosis Children

ABSTRACT. The effects of liver disease, fat malabsorption and sunlight exposure on serum vitamin D levels were determined in 21 optimally treated preadolescent cystic fibrosis (CF) children over a 12-month period. Manifest liver disease and fat malabsorption appeared not to affect the vitamin D level. However, the level fell significantly in winter, although not below the normal range, suggesting that sunlight exposure is a more important determinant of vitamin D levels in preadolescent CF children than liver disease and fat malabsorption.     

Estimated Risk of Cross-Infection with Pseudomonas aeruginosa in Danish Cystic Fibrosis Patients

ABSTRACT. During the period 1970–1987 the number of cystic fibrosis (CF) patients treated at the Danish CF Centre increased from 54 to 226. The prevalence of patients with chronic P. aeruginosa infection (CF + P) increased from 35% to 59%, whereafter it decreased to 54%. The yearly incidence of new CF + P patients averaged 8.4% in 1970–1975, 17% in 1976–80, 6.5% in 1981–85, and 3% in 1986–87. These changes correlated to the increased "contact density" between CF + P and non-infected CF patients (CF-P) due to intensified treatment starting in 1976, and the reduced "contact density" due to separation of the two groups starting in 1981. The same trends were observed during an epidemic spread of a multiply resistant P. aeruginosa in the CF + P group, which was also interrupted by separation of two groups of patients, with and without the multiply resistant strain. The observed prevalences of CF + P in different age groups of patients are in accordance with a 20% incidence/year in patients older than three years. The highest probability of aquiring chronic P. aeruginosa infection was calculated to be 2%/day and the lowest 0.09%/day spent in the Centre. By employing a simple mathematical model of the spread of infectious diseases it can be shown, that the highest incidence of CF + P is present when the prevalence of CF + P is 20–80%, and that an increase in the total number of patients also increases the incidence of CF + P unless the patients are divided into smaller groups. The observations in the Danish CF Centre are in accordance with this model.     

Aldosterone in Cystic Fibrosis: Measurement in Saliva and Correlation with Disease Severity

ABSTRACT. Aldosterone was measured in the saliva of 20 patients with cystic fibrosis and a group of 20 normal children matched for age and sex. Mean levels were higher in the patient group but overall differences were small and statistically not significant. For the first time a link between aldosterone level and disease severity in patients with cystic fibrosis was established using a simple scoring system to assess disease activity. Urinary and salivary electrolytes were similar in the two groups. The results do not support the proposed hypothesis that the salivary glands of patients with cystic fibrosis are insensitive to aldosterone.     

Tissue Culture of Epithelial Cells from Urine II. Application to Patients with Cystic Fibrosis

The urine from patients with cystic fibrosis (CF) was screened for the presence of epithelial cells that could be serially propagated in vitro. The urine from two newborn infants with meconium ileus was an excellent source of epithelial cells, and over 400 cultures were initiated in each case. The urine of older CF patients hospitalized for pulmonary complications also yielded cells but in fewer numbers. No cells were obtained from older CF patients without pulmonary complications or from healthy volunteers. Hypoxia may be the factor stimulating cell exfoliation in the urine of sick CF patients and in a larger percentage of newborn infants.