G. Steinkamp

Energy supplements rich in linoleic acid improve body weight and essential fatty acid status of cystic fibrosis patients.

Background Patients with cystic fibrosis who have steatorrhea frequently are underweight and have essential fatty acid (EFA) depletion, which is associated with a poor clinical course. It has been stated that poor EFA status is difficult to correct in patients with cystic fibrosis, and an impaired EFA metabolism with reduced synthesis of long-chain polyunsaturated fatty acids has been proposed. In this study, the effects of an oral energy supplement rich in linoleic acid were investigated in patients with cystic fibrosis who had a body weight below 95% of normal for height. Methods Thirty-six patients (16 girls) more than 4 years of age were randomized either to a control group (n = 20, age 13.3 ± 3.8 years, mean ± SD) receiving intensive dietary counseling only, or an intervention group (n = 16, age, 10.4 ± 4.3 years) treated for 3 months with dietary counseling plus 628 ± 254 mL (=kcal) per day of an energy supplement rich in fat (31% of energy) and linoleic acid (16% of energy). Results In contrast to the control group, the patients with supplemented diets achieved significant increases of energy intake (2189 ± 731 kcal/day vs. 2733 ± 762 kcal/day), weight for height (82.8% ± 8.6% vs. 84.8% ± 9.6% of normal), and body fat (5.1 ± 1.7 kg vs. 5.8 ± 2.2 kg) as well as the initially low values of plasma phospholipid linoleic acid (11.8% ± 1.1% vs. 17.6% ± 1.6% of total phospholipid fatty acids) and its main metabolite arachidonic acid (4.4% ± 0.4% vs. 5.9% ± 0.3%). Conclusions Patients with cystic fibrosis with low body weight and poor EFA status benefit from EFA-rich energy supplements and can synthesize arachidonic acid from the precursor linoleic acid.

Treatment of pseudomonas aeruginosa colonisation in cystic fibrosis.

To test whether early treatment could postpone the chronic colonisation of the respiratory tract with mucoid strains of Pseudomonas aeruginosa in patients with cystic fibrosis, we performed a pilot study in 28 patients aged 2 to 18 years. A two week course of azlocillin (150 mg/kg/day) and tobramycin (10 to 15 mg/kg/day) was given after a mean duration of P aeruginosa colonisation of five months (range one to 11 months). Weight for height increased significantly by 3.5% (SEM 0.7%) of the predicted normal after chemotherapy. The eradication of P aeruginosa that was achieved in 18 children directly after hospital treatment was only temporary. Samples from only 10 and five patients remained negative three and six months after treatment, respectively. Five children remained free from P aeruginosa for a prolonged period of 14 to 32 months. We conclude that, apart from the clinical improvement in all patients, some children might benefit from early antipseudomonas treatment with respect to the bacteriological outcome. Most children, however, experience only a temporary reduction in colonisation. Further investigations in form of controlled clinical trials seem justified.

Long-Term Tobramycin Aerosol Therapy of Chronic Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis

Fourteen cystic fibrosis patients (aged 9 to 20 years), chronically infected with Pseudomonas aeruginosa (PA), inhaled 80 mg (2 ml) tobramycin twice daily, because a significant clinical deterioration had occurred. Mean duration of aerosol therapy was 20.3 months (range, 11 to 38 months). There were no toxic side effects and no significant systemic absorption, 50 of 70 tobramycin serum levels being below the minimal detectable value of 0.1 mg/l. After 12 months of therapy there was an improvement of lung function, Po2, and weight. The frequency of intravenous therapy was reduced. Tobramycin resistance occurred in 5.8% of all PA strains after 10 to 29 months and did not represent a clinical problem. In a few patients PA was eradicated from sputum.

Generation and Metabolism of Leukotrienes in Granulocytes of Patients with Cystic Fibrosis

We studied the generation and metabolism of lipoxygenase products in peripheral granulocytes from children suffering from cystic fibrosis (CF). Peripheral granulocytes were stimulated at different times (days) before and during anti-infectious treatment with the Ca ionophore (7.5 microM, 5 and 20 min), opsonized zymosan (2 mg) and arachidonic acid (50 microM); the amount of lipoxygenase products in the cell supernatants was determined by high performance liquid chromatography. Granulocytes from patients with CF, compared to an age-matched control group, showed an increased omega-oxidation of the synthesized leukotriene (LTB4) into 20-OH- and 20-COOH-LTB4 after stimulation with the Ca ionophore (ratio of LTB4 versus omega-oxidated products in patients with CF: 0.77 +/- 0.07, mean +/- SEM, n = 11; control group: 1.07 +/- 0.1, n = 11, p less than 0.01) whereas the combined amounts of LTB4 and its omega-oxidated products did not differ significantly. A comparable profile was observed with opsonized zymosan. Stimulation of the cells with the Ca ionophore combined with arachidonic acid led to a significantly increased formation of lipoxygenase products in the patient group, whereas only a slight enhancement was observed in the control group. During the 14-day anti-infectious treatment a normalization of the altered pattern was observed. 12-Hydroxyeicosatetraenoic acid (12-HETE) production from platelets within the granulocyte fraction was significantly depressed in the CF group compared to the controls (38.5 +/- 12.5 versus 339 +/- 93 ng/5 +/- 10(6) cells, p less than 0.005). Within the CF group a strong correlation between the release of LTB4 and its metabolites, the production of 12-HETE and clinical (e.g. pO2, FEV1) and laboratory findings (e.g. IgE and IgG levels, C-reactive protein) was established. Our data suggest that the inflammatory process in patients with CF is associated with an alteration of the lipoxygenase pathway of granulocytes which correlates with the clinical signs of inflammation.

Mild course of cystic fibrosis associated with heterozygosity for infrequent mutations in the first nucleotide-binding fold of CFTR

The mild clinical course of a patient with cystic fibrosis is presented who inherited the two mutations Gly551→Asp and Arg553→Stop in the cystic fibrosis transmembrane conductance regulator gene. The missense mutation Arg 553→Stop discovered in American Blacks is also present on cystic fibrosis chromosomes of Caucasian ancestry.

Cystic fibrosis: the impact of analytical technology for genotype-phenotype studies

The generalized exocrinopathy cystic fibrosis (CF) is the most common severe genetic disease in Caucasian populations. A panel of more than 700 chromosomes from German and Turkish CF patients was screened for disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene by chemical cleavage of mismatch, single strand conformation polymorphism, restriction analysis and direct sequencing of genomic DNA amplified by polymerase chain reaction. Besides the major 3-bp deletion, delta F508 that was found on 73% of German CF chromosomes, more than 50 other missense, nonsense, frame-shift, and splice-site mutations have already been identified. In general, a CFTR mutation is linked with a single 10-marker haplotype which indicates that in most cases a particular mutation spread from a common ancestor. The comparison of mutation genotypes with the disease phenotype emphasized the causative role of the type and localization of the CFTR mutation for clinical course and prognosis. Pancreatic status and the risk of colonization of airways with opportunistic pathogens are genetically determined. Most patients who are harbouring mutations in the nucleotide binding folds were suffering from severe CF disease. Mild or even aberrant forms of CF were observed for many missense mutations located in the putative transmembrane domains or for mutations that are expected to result in a truncated protein of half of wild-type CFTR.

Wertigkeit der abdominellen Sonographie bei cystischer Fibrose

Die Cystische Fibrose (CF) ist die haufigste angeborene Stoffwechselerkrankung, die bereits im Kindesalter zum Tode fuhren kann. Dank der Fortschritte in Diagnostik und Therapie werden heute Lebensalter uber 20 und 30 Jahre erreicht. Dies fuhrt dazu, das bei besserer Therapierbarkeit der pulmonalen Manifestation der Erkrankung nicht-pulmonale Manifestationen eine grosere Bedeutung erlangen oder gar den limitierenden Faktor bei einer geplanten Herz- Lungentransplantation bilden. Ziel der Untersuchung war die Erfassung von sonographisch erkennbaren abdominalen Veranderungen bei Patienten mit CF, die von der Kinderklinik der Medizinischen Hochschule betreut werden.

PERCUTANEOUS ENDOSCOPIC CONTROLLED GASTROSTOMY (PEG) FOR ALIMENTATION OF CHILDREN WITH CYSTIC FIBROSIS

The benefit of a hyperalimentation in patients with cystic fibrosis is well known. Oral hyperalimentation is difficult to perform and gastric tubes are not well accepted by the patients. In a prospective study we investigated whether PEG might be an alternative in the application of hypercaloric diet. So far PEG was performed in 9 children aged from 7,2 to 17,9 years. In 8 patients we have a follow-up of at least 3 months. Those patients entered the study where there was 1. a percentage ideal weight for height (IWH) below 80% 2. and/or no improvement of the IWH above 3% despite optimal conventional nutrition in a 6 month period. PEG was performed under general anaesthesia according to the method of Keymling°. Except of two dislocations of the PEG-tube, which were easily corrected, we saw no complications. PEG was well accepted by the patients and their parents. In addition to normal nutrition the children received 1000 kcal bulkage-free diet over night. After 3 months there was a mean increase of IWH of 9% (3-12%), of triceps skin fold thickness of 2,91 mm (-0,3-6,9 mm) and of upper arm circumference of 1,88 cm (0,9-2,9 cm). From these data we conclude that PEG is a very effective and save procedure in the nutritional therapy in patients with cystic fibrosis.°Keymling M, Schlee P, Wörner W. Die perkutane endoskopisch kontrollierte Gastrostomie. DMW 112:182(1987)