Prospective study of fatty acid supplementation over 3 years in patients with cystic fibrosis

Intravenous fatty acid supplementation (10% Intralipid, 10 ml/kg body weight) was given to 10 patients with cystic fibrosis (CF), in intervals for 3 years. One year of intensive treatment with supplementation every fortnight was followed by 1 year of intermission and then 1 year of the same treatment given for 2 days every 2 months. Compared with matched CF patients, the clinical course, evaluated by Shwachmann scoring, showed less deterioration in the treated group, especially during the year of intensive treatment. Single parameters, such as pulmonary function tests, pulmonary X-ray films, clinical infections, bacterial growth of sputa, and sweat electrolyte concentration, showed no differences. It is concluded that if there is any benefit of this kind of treatment in CF, it has to be very intensive. At present, the psychological stress involved in repeated parenteral administrations over long periods prevents its use in clinical routine.     

Nutritional rehabilitation in cystic fibrosis: a 5 year follow-up study.

Previously, we reported catch-up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard therapy. To evaluate long-term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV1 and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV1, p less than 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short- and long-term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study.     

Disposition of tobramycin in patients with cystic fibrosis: a prospective controlled study

The pharmacokinetics of tobramycin in adolescents or young adults with cystic fibrosis and in age-matched controls were prospectively compared. Patients with CF had a higher tobramycin total body clearance (121.2 +/- 14.2 ml/min/1.73 m2) than did controls (102.2 +/- 18.9 ml/min/1.73 m2, P less than 0.05). This was not associated with a higher glomerular filtration rate (iothalamate total body clearance 147.5 +/- 29.2 ml/min/1.73 m2 in patients vs 142.9 +/- 33.3 ml/min/1.73 m2 in controls) or a lower binding of gentamicin to serum proteins (14.3% +/- 2.6% in patients vs 17.4% +/- 3.8% in controls). Tobramycin renal clearance was not significantly different in the two groups (89.5 +/- 17.9 ml/min/1.73 m2 in patients vs 81.0 +/- 15.8 ml/min/1.73 m2 in controls). In the control group, tobramycin total body and renal clearances were highly correlated with iothalamate total body clearance (r = +0.95 and +0.88, P less than 0.01). In patients with cystic fibrosis, the correlation was not significant (r = +0.56, P greater than 0.05 for total body clearance, and r = 0.32, P greater than 0.1 for renal clearance). There was no significant difference in volume of distribution normalized to body surface area or in half-life of elimination. The higher tobramycin total body clearance without an increase in renal clearance, and the lower correlation with glomerular filtration rate indicate that an extrarenal clearance pathway might play a significant role in the elimination of tobramycin from the serum of patients with cystic fibrosis.     

Cough plate versus cough swab in patients with cystic fibrosis; a pilot study.

BACKGROUND: Accurate identification of lower respiratory tract pathogens is important in the management of cystic fibrosis patients. AIM: To evaluate the cough plate as an alternative method of obtaining respiratory samples for microbiological culture. METHODS AND RESULTS: Using sputum culture as the "gold standard", the cough plate method identified significantly more positive cases than either dry or moistened cough swabs. Of 20 patients who had a positive sputum culture, 16 had a positive culture on cough plate compared to seven positive cultures each on moistened swab and on dry swab respectively. CONCLUSIONS: In this study cough plates were more sensitive than cough swabs in isolating respiratory pathogens in sputum producers. As patients prefer it, the cough plate merits further evaluation, particularly in non-sputum producers.     

Modified oral rehydration therapy in a case with cystic fibrosis

Infants with cystic fibrosis can develop episodes of hyponatremic, hypochloremic dehydration with metabolic alkalosis, and management is difficult. In this paper, we present a nine-month-old case with cystic fibrosis with pseudo-Bartter syndrome, who was rehydrated with two types of modified oral rehydration solution. Intravenous rehydration was impossible due to inaccessibility of route. With this oral rehydration treatment, her purging rate decreased, and serum sodium levels improved and remained stable. In cases with impossible intravenous route, one of these modified rehydration solutions could be given.     

Benefits of breastfeeding in cystic fibrosis: a single-centre follow-up survey

AIM: To study the effect of breastfeeding (BF) on growth, lung function and number of infections during the first 3 years of life in children with cystic fibrosis (CF). MATERIAL AND METHODS: One hundred forty-six CF patients, 5-18 years old, were recruited at their annual care visit. Information about infant feeding, psychosocial and socioeconomic conditions and smoking exposure was obtained by interviews. Anthropometric parameters at 1 year of age and the number of infections and hospitalisations during the first 3 years of life were obtained from clinical charts. Anthropometrics and pulmonary function parameters were obtained at enrollment. RESULTS: In CF patients, particularly those with pancreatic insufficiency, the prevalence of BF was lower than the general Italian population. After multivariate analysis patients with prolonged BF showed higher values of CED expiratory volume in 1 sec (FEV-1) (p = 0.001) and a lower number of infections during the first 3 years of life (p = 0.098). CONCLUSION: Prolonged BF is beneficial in children with CF and may protect them against decline of pulmonary function. Particular attention should be paid to promote BF in infants with CF.     

Bone mineral density and bone acquisition in children and young adults with cystic fibrosis: a follow-up study

OBJECTIVE: To investigate bone mineral density and bone homeostasis in cystic fibrosis (CF) and to assess changes in a 2-year period. METHODS: Thirty-eight patients with clinically stable CF (11 children, 16 adolescents, 11 young adults) were enrolled. No patient was treated with corticosteroids before or during the study. Weight and height Z scores and bone mineral density (BMD) Z-score at the femoral neck and the lumbar spine were recorded at the beginning of the study and after 2 years. Osteocalcin and cross-link excretion, both measurements of bone turnover were also measured. Correlations between BMD, bone turnover parameters, disease severity, pubertal stage, and nutritional state were calculated. The maternal BMD was also determined and related to that of the child. RESULTS: Height and weight Z scores were normal in children and below normal in adolescents. Puberty was delayed in most patients. Bone age was lower than chronological age in adolescents. Lumbar spine and femoral neck BMD Z scores were below normal in each age group. Disease severity determined by Schwachman score correlated with lumbar BMD (r = 0.45, P < 0.02). BMD Z scores did not change during 2 year follow-up. Maternal and patient lumbar and femoral BMD correlated significantly (r = 0.51, P < 0.01, and r = 0.54, P < 0.01, respectively). CONCLUSIONS: Bone deficit is present in patients with CF who have never received steroid treatment. Delay of puberty, chronic inflammation, or genetic susceptibility might be responsible for this phenomenon which was found in patients who had never received steroids and who were in relatively good clinical state.     

Negative effects of oral fatty acid supplementation on sweat chloride in cystic fibrosis.

Essential fatty acid supplementation with oral safflower oil (1 gm/kg/day) to 11 cystic fibrosis patients (aged 6 months to 14 years) for one year produced no significant change in sweat chloride concentration (mEq/liter) or sweat rate (gm/min/m2), Addition of vitamin E (10 mg/kg/day) to the safflower oil had no effect on sweat chloride concentration or rate compared to placebo. No clinical improvement could be detected compared to a control group. These results do not support previous reports of the effects of fatty acid supplementation on sweat electrolyte concentrations in cystic fibrosis.     

Myocardial fibrosis — a rare complication in patients with cystic fibrosis

We report a 10-month-old male infant who was admitted to our hospital with a history of failure to thrive and bulky stools. On examination, he was dystrophic and had a protruding abdomen, but he was well oxygenated and his lungs were clear on auscultation. A tachycardia of 145 beats per min and radiological evidence of cardiomegaly indicated involvement of the heart, but an ECG failed to show signs of myocarditis or cardiac hypertrophy. An elevated sweat chloride concentration of 141 mEq/l confirmed the diagnosis of cystic fibrosis (CF). Molecular analysis revealed heterozygosity for the common mutation delta F₅₀₈. He died unexpectedly of a sudden cardiac arrest 2 days later. Autopsy revealed scattered myocardial necrosis and fibrosis. Some 50 documented cases of myocardial fibrosis in infants with CF have been reported. Suggested causes such as malnourishment and hypovitaminosis remain speculative as systematic studies have yet to be done.     

Intravenous linoleic acid supplementation in children with cystic fibrosis.

Ten children with CF in matched pairs were infused with either Intralipid or with 10% glucose on a double blind basis every other week for one year. Although statistically there was significantly greater gain in height and weight in the study year compared to the previous year only for the test group, both groups improved more than expected. Cumulative data analysis showed greater improvement for the Intralipid group (23 of a possible 45 points) compared to the glucose group (-2 points; P less than .02). This study indicates the need to better define the role of nutrition in the pathophysiology of CF. Meanwhile, it is recommended that all children with CF have plasma linoleic acid levels measured at least once yearly, and if levels are low, appropriate supplements should be given.     

Chest radiographs in cystic fibrosis. A follow-up study with application of a quantitative scoring system

A modified Chrispin-Norman score was used to investigate at what age typical X-ray signs of cystic fibrosis (CF) appear and for the follow-up of patients with CF. Scores of patients with chronic obstructive lung disease (COLD) and with innocent heart murmurs were used for comparison. The findings were: 1. Hyperinflation and line shadows are early but not specific symptoms of CF. 2. Mottled and ring shadows can be considered as specific for CF. In most patients they only appear after the age of 3. They are never present in COLD. 3. The mean annual increase between the ages of 3–8 is 2 points. No difference existed between boys and girls in total scores and annual increase up to the age of puberty. 4. CF patients with portal hypertension have the same scores as CF patients without portal hypertension.     

Factors affecting diabetes mellitus onset in cystic fibrosis: evidence from a 10-year follow-up study

This study reports the results of genotype characterization and of a 10-y prospective evaluation of clinical status, glucose tolerance and insulin secretion in 28 originally normoglycaemic patients with cystic fibrosis (CF). The aim of the study was to assess whether any genetic, clinical or metabolic parameters could identify in advance those patients at risk of developing diabetes mellitus over time. During the follow-up 42.8% of patients became diabetic. Neither gender, age nor clinical parameters were significantly different at entry in the patients who eventually developed diabetes compared with those who did not. Insulin secretion during oral glucose tolerance tests (OGTT) deteriorated over time in both groups, whereas a progressive deterioration of glucose tolerance was only evident in the patients who developed diabetes and increased baseline glucose areas were the only predictive parameter of diabetes onset. Genotype analysis revealed significant differences between patients with and without diabetes: ΔF508 homozygosis was more frequent in the first group and N1303K mutation in the second group. In conclusion, in CF: (i) increased glucose areas during OGTT and deterioration of glucose tolerance over time can predict the evolution towards diabetes; and (ii) ΔF508 homozygosis may predispose to the risk of diabetes, whilst N1303K mutation seems to play a protective role.     

Dopamine-beta-hydroxylase in patients with cystic fibrosis

The enzymatic activity of plasma dopamine-beta-hydroxylase (DBH) was determined in 92 children/adolescents with cystic fibrosis, in 25 parents (heterozygotes) of these patients and in 68 healthy controls. Statistically significant (P<0.01) lower DBH levels were found in cystic fibrosis patients (17.9±1.4 mol/min per 1, SEM) compared to the controls (25.5±2.1 mol/min per 1). In 37 patients plasma norepinephrine and dopamine levels were compared to the enzymatic activity, no significant correlation between these variables being shown (r=-0.134 for norepinephrine; r=0.159 for dopamine). However, due to the large variability of DBH within the groups and due to the lack of relationship of this enzymatic activity to plasma catecholamines, it is concluded that these differences may neither account for the observed elevation of plasma dopamine in cystic fibrosis patients (0.94–6.73 nmol/l vs. 0.01–0.986 nmol/l for controls) nor for their putative autonomic dysfunction.Abbreviations DBH dopamine-beta-hydroxylase - CF cystic fibrosis - NE norepinephrine - DA dopamine - HZ heterozygote - COMT catechol-O-methyltransferase