Randomized, double-blind, placebo-controlled pilot trial of megestrol acetate in malnourished children with cystic fibrosis

BACKGROUND: Undernutrition is common in patients with cystic fibrosis (CF). Nutritional rehabilitation has been shown to improve linear growth, pulmonary function, well-being, and resistance to infection in this population. The purpose of this study was to determine whether the administration of megestrol acetate (MA) induces weight gain in malnourished patients with CF, and to assess the composition of weight gain. METHODS: In a randomized, placebo-controlled, double-blind, crossover study, 12 children with CF received MA (10 mg/kg/d) or placebo for 12 weeks, followed by a 12-week washout period, then the alternative treatment. Anthropometrics, caloric intake, and clinical assessment were obtained every 6 weeks; pulmonary function tests, biochemistry, hematology, cortisol, growth hormone, insulin, C-peptide, insulin-like growth factor-1, insulin-like growth factor binding protein-3, and dual-energy x-ray absorptiometry scans were obtained every 12 weeks. RESULTS: Six children did not complete the study, three for reasons unrelated to the study, two because they developed diabetes while receiving MA, and one who had glucose intolerance while receiving the placebo. Average weight gain was 3.05 kg in the MA group and 0.3 kg in the placebo group. The change in weight z score was +0.76 in the MA group and -0.05 in the placebo group. The change in height z score was -0.06 in the MA group and +0.06 in the placebo group. Lean body mass and body fat increased by 1507 g and 1192 g respectively in the MA group. Pulmonary function tests improved in the MA group; serum cortisol levels decreased. Side effects included glucosuria, insomnia, hyperactivity, and irritability. CONCLUSIONS: Weight, body fat, and lean body mass increased and pulmonary function improved in the children with CF given MA. Adrenal suppression, glucose intolerance, and diabetes are side effects.     

Longitudinal relationship among growth, nutritional status, and pulmonary function in children with cystic fibrosis: analysis of the Cystic Fibrosis Foundation National CF Patient Registry

OBJECTIVE: To determine prospectively the relationship among growth, nutritional status, and pulmonary function over a 4-year period in a large cohort of children with cystic fibrosis (CF). STUDY DESIGN: CF Foundation National CF Patient Registry data collected from 1991 to 1995 for 968 children (507 male) aged 5 to 8 years with pancreatic insufficiency and forced expiratory volume in 1 second within 60% to 140% of predicted values (FEV(1)%) were analyzed longitudinally. Variables hypothesized to affect FEV(1)% included age, sex, z scores for height, weight, percent of height-appropriate body weight, and annual number of days hospitalized. RESULTS: The significant decline in FEV(1)% was curvilinear and dependent on baseline FEV(1)%; children with initial FEV(1)% > or = 90 declined 2.6 U/y more than those with initial FEV(1)% <90. Boys gained but girls declined in z scores for height. Girls decreased in z scores for weight at a greater rate than boys. The z scores for weight and percent of height-appropriate body weight were significantly associated with longitudinal changes in FEV(1)%, after adjustment was done for hospitalizations. CONCLUSIONS: Growth, nutritional status, and pulmonary function are not stable in prepubertal children with CF and pancreatic insufficiency. Important sex-related differences in growth occur before puberty. Growth and nutritional status are associated with changes in FEV(1)%, suggesting that nutritional intervention may slow the decline in pulmonary function in children with CF.     

Megestrol acetate treatment of growth failure in children infected with human immunodeficiency virus

OBJECTIVE: To evaluate the effect of megestrol acetate on weight gain and linear growth in human immunodeficiency virus-infected children with growth failure. METHODS: All human immunodeficiency virus-infected children with growth failure treated with megestrol acetate at our institution were evaluated retrospectively. Weight, height, and weight:height ratio were documented from 6 months before initiation of megestrol acetate until 6 months after treatment was discontinued. Measurements were corrected for age and sex by conversion to z-scores. Incremental growth was determined before, during, and after treatment. The potential effects of CD4+ T-lymphocyte count and percentage, antiretroviral therapy, and intercurrent illnesses on growth were evaluated. RESULTS: Nineteen patients were treated with a total of 27 courses of megestrol acetate. The median duration of therapy was 7 months (range, 3 to 11 months), and the median megestrol acetate dose was 7.91 mg/kg/day (range, 4.06 to 8.56 mg/kg/day). From 6 months and 3 months before treatment to the onset of therapy, median changes in weight z-scores were -.27 and -.15, respectively. During megestrol acetate treatment, median changes in weight z-scores were +.29 after 1 month of therapy, +.40 after 3 months, and +.57 after 6 months. After megestrol acetate therapy was discontinued, poor weight gain and weight loss resumed. Median 6-month growth velocities for weight were less than the 10th percentile before megestrol acetate, greater than the 97th percentile during treatment, and less than the 3rd percentile after treatment was discontinued. Megestrol acetate therapy was not associated with changes in linear growth. Antiretroviral therapy, CD4+ T-lymphocyte count or percentage, or intercurrent illnesses were not associated with statistically significant differences in response to megestrol acetate therapy. CONCLUSIONS: Megestrol acetate treatment of growth failure in pediatric human immunodeficiency virus disease is associated with weight gain, without affecting linear growth.     

Effect of exocrine pancreatic function on resting energy expenditure in cystic fibrosis

AIM: To prove the hypothesis that exocrine pancreatic function determines resting energy expenditure (REE) in cystic fibrosis (CF). METHOD: Thirty-eight CF individuals, 9-34 (19.98 +/- 1.0) years, were divided into three groups: Six pancreatic sufficient patients (PS; group A), 21 pancreatic insufficient patients (PI), whose pulmonary function was comparable to that of group A (group B1) and 11 PI patients, whose pulmonary function was significantly worse than that of group A (group B2). REE was estimated by indirect calorimetry. Predicted REE was based on Schofield equations. Measured REE was expressed as % of the predicted. BMI, BMI z-scores, serum albumin, cholesterol and triglycerides levels were related to REE. Results were expressed as mean +/- standard error. RESULTS: Groups B1 and B2 had significantly higher REE% (111.7 +/- 2.75% and 119.94 +/- 3.8, respectively) as opposed to group A (98.9 +/- 3.81%; p = 0.022 and 0.035, respectively) whose REE% was similar to that predicted. REE% between group B1 and B2 was not statistically significant. In groups A, B1 and B, mean FEV1% was 86.33 +/- 10.1%, 90.24 +/- 4.39%, 44.54 +/- 3.47%, respectively, mean BMI was 25.6 +/- 2.06, 19.48 +/- 0.64 and 20.09 +/- 8.8, respectively, BMI z-scores were 0.75 +/- 0.51, -0.52 +/- 0.24 and -1.07 +/- 0.37, respectively. Significant correlation was demonstrated between REE%, BMI z-scores and cholesterol levels in group A. CONCLUSION: Clinically stable CF patients, who had comparable pulmonary function, exhibited increased REE% only in the presence of exocrine pancreatic insufficiency. REE% strongly correlated with BMI z-scores in pancreatic sufficiency. These findings support the hypothesis that pancreatic rather than pulmonary function may determine nutritional status as well as REE in CF.     

Differences in resting energy expenditure between male and female children with cystic fibrosis

OBJECTIVES: To evaluate which factors might contribute to raised resting energy expenditure (REE) in patients with cystic fibrosis (CF). STUDY DESIGN: REE and anthropometry were measured in 134 (males = 68) children with CF and 100 (males = 51) controls (range, 3-18.7 years) in an outpatient setting. Bacterial colonization, liver disease, inhaled steroid use, pancreatic and pulmonary function, sex, and genotype were determined and regression analysis was used to determine the predictors of REE in the group with CF. RESULTS: REE for children with CF was increased on average by 7.2% compared with controls. This increase was greater for females than for males. REE in males was positively associated with fat-free mass (FFM), pancreatic insufficiency (PI), and liver disease, and negatively associated with pulmonary function, whereas in females, REE was positively associated with FFM and PI. REE (adjusted for FFM) was higher in children with a severe mutation (5495 +/- 47 kJ) compared with a mild mutation (5,176 +/- 124 kJ, P <.02). CONCLUSIONS: PI, severe mutations, and female sex are the main contributing factors to elevated REE in patients with CF with near normal pulmonary function.     

Association between serum oncofetal antigens CA 19-9 and CA 125 and clinical status in patients with cystic fibrosis

In cystic fibrosis (CF), mucus plugging in the airways and in the gastrointestinal tract leads to severe morbidity and mortality. The mucin-associated antigens CA 19-9 and CA 125 are markers of gastrointestinal malignancy, and CA 19-9 has also been reported in association with pulmonary function in CF. Aim: To test whether these antigens might serve as markers for the severity of pulmonary and gastrointestinal disease in CF. Methods: In 99 patients, aged 1 to 48 y, serum levels of CA 19-9 and CA 125 were measured by RIA and ELISA and related to clinical data. Results: Patients with severe mutations had significantly increased serum levels of CA 125, indicating an association with a more severe CF phenotype. This was further supported by the association with lung function, chronic pulmonary colonization of Pseudomonas aeruginosa and pancreatic insufficiency. CA 19-9 was also shown to be associated with lung function and Ps. aeruginosa colonization. No gastrointestinal malignancy was found in our patients despite very high values of CA19-9 in some patients. During a 5-y follow-up, the very high serum levels of CA 19-9 decreased along with improved general condition of the patients.

Conclusion: Increased serum levels of CA 125 in CF patients were associated with severe cystic fibrosis transmembrane conductance regulator mutations and a severe phenotype. Both antigens were associated with pseudomonas colonization and lung function and CA 125 also with pancreatic insufficiency. The estimates of CA 19-9 are hampered by the influence of the Lewis histo-blood group system on the synthesis of CA 19-9.     

Edetate sodium aerosol in Pseudomonas lung infection in cystic fibrosis

In vitro and animal experimental data suggest the combination of edetate sodium (EDTA) by aerosol plus oral antimicrobials might be effective in the treatment of chronic Pseudomonas infection in patients with cystic fibrosis (CF). For six months we studied the effects of edetate sodium administered by ultrasonic nebulizer to ten children with CF and chronic Pseudomonas aeruginosa infection in a double-blind, placebo-controlled, crossover study. The children had evidence of mild to moderate disease at entry in the study, with a mean (+/- SD) forced expiratory volume in the first second of 85% (+/- 18%) of the predicted value and a mean (+/- SD) Shwachman-Kulczycki score of 83 (+/- 7)/100. Each child was on a three-month regimen of aerosolized edetate sodium plus oral tetracycline twice daily followed by three months of placebo aerosol plus tetracycline or vice versa. Progress was assessed by measurement of pulmonary function, physical examination, and sputum cultures at four weekly intervals, plus chest roentgenograms on entry and after each of the three-month treatment periods. Daily symptoms were assessed using a diary card system. Two patients could not complete the study, one because of severe respiratory relapse, the other because of antibiotic side effects. Of the remaining eight patients, none showed any improvement in pulmonary function, weight gain, or growth acceleration, and none was rendered free of Pseudomonas lung infection. Daily symptom scores and chest roentgenograms were unaltered by edetate sodium. We conclude that the combination of aerosol edetate sodium plus oral tetracycline over a three-month period does not modify the clinical course nor the pulmonary flora in patients with CF with chronic Pseudomonas lung infection.     

Prospective randomised treatment with recombinant human growth hormone in cystic fibrosis.

AIM: To evaluate the efficacy and safety of treatment with recombinant growth hormone (rGH) in patients with cystic fibrosis (CF). METHODS: Twenty patients with CF (aged 10-23 years) were randomised to age and sex matched treatment and control groups. The treatment group received daily subcutaneous injections of 1 IU/kg/wk rGH for 12 months. Pulmonary function (forced expiratory volume in one second (FEV1) and airway resistance), exercise capacity measured with a bicycle ergometer, body composition (dual energy x ray absorptiometry), and weight were assessed at the beginning of the study and after 6 and 12 months. RESULTS: rGH treatment did not improve weight and pulmonary function, but lean body mass increased significantly in the treatment group. Exercise capacity increased in the treatment group from 143 (16) W (mean (SD)) to 164 (19) W after 12 months of rGH treatment. CONCLUSION: Treatment of CF patients with rGH for one year improved the exercise capacity significantly but not pulmonary function. The improved exercise capacity needs confirmation in a larger population before such an expensive treatment is justified.     

Controlled trial of oral N-acetylcysteine in cystic fibrosis

ABSTRACT. To assess the efficacy of oral N-acetylcysteine (NAC) 200mg given thrice daily in cystic fibrosis (CF) we conducted a double blind placebo controlled cross over trial on 20 patients with mild to moderate pulmonary disease. No significant difference between the 3 month treatment periods with NAC and placebo were detected on daily peak expiratory flow rates (PEFR), subjective sputum viscosity, and cough frequency scores. Neither was there any statistically significant difference in weight gain, antibiotic usage or chest radiograph (CXR) scores.     

Prospective randomised treatment with recombinant human growth hormone in cystic fibrosis

Aim: To evaluate the efficacy and safety of treatment with recombinant growth hormone (rGH) in patients with cystic fibrosis (CF). Methods: Twenty patients with CF (aged 10–23 years) were randomised to age and sex matched treatment and control groups. The treatment group received daily subcutaneous injections of 1 IU/kg/wk rGH for 12 months. Pulmonary function (forced expiratory volume in one second (FEV₁) and airway resistance), exercise capacity measured with a bicycle ergometer, body composition (dual energy x ray absorptiometry), and weight were assessed at the beginning of the study and after 6 and 12 months. Results: rGH treatment did not improve weight and pulmonary function, but lean body mass increased significantly in the treatment group. Exercise capacity increased in the treatment group from 143 (16) W (mean (SD)) to 164 (19) W after 12 months of rGH treatment. Conclusion: Treatment of CF patients with rGH for one year improved the exercise capacity significantly but not pulmonary function. The improved exercise capacity needs confirmation in a larger population before such an expensive treatment is justified.     

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.     

Clinical and genetic risk factors for cystic fibrosis-related liver disease

OBJECTIVE: The aim of this study was to define the role of possible risk factors for the development of cystic fibrosis (CF)-related liver disease and to analyze the association between liver disease and the different genotypes present in the Israeli CF patient population. PATIENTS AND METHODS: All patients followed at the seven CF centers in Israel were included in this study. Liver disease was determined by persistently elevated serum liver enzymes and/or bilirubin, and/or significant ultrasonographic changes suggestive of chronic liver disease. The following clinical parameters were evaluated: ethnic origin, age at assessment of liver function, sex, history of meconium ileus, pancreatic function, history of distal intestinal obstruction syndrome, pulmonary function, and cystic fibrosis transmembrane conductance regulator mutation analysis. RESULTS: Of the 288 patients screened, 80 (28%) had liver disease. Of the 256 patients with pancreatic insufficiency, 80 (31%) had liver disease compared with none of the 32 patients with pancreatic sufficiency. Genotype-phenotype correlation was performed on 207 patients carrying identified mutations that were previously classified according to phenotype severity. Liver disease was found in 56 (32%) of 173 patients carrying mutations associated with a severe phenotype and in 6 (38%) of 16 patients carrying at least one mutation associated with a variable genotype (G85E and/or 5T allele). None of the 18 patients carrying the 3849+10kb C->T mutation had liver disease. Prevalence of liver disease increased with age. No correlation was found between liver disease and severity of lung disease, nutritional status, history of meconium ileus, or distal intestinal obstruction syndrome. CONCLUSION: CF patients who have pancreatic insufficiency and carry mutations associated with a severe or a variable genotype are at increased risk to develop liver disease.     

Long-term comparative trial of positive expiratory pressure versus oscillating positive expiratory pressure (flutter) physiotherapy in the treatment of cystic fibrosis

OBJECTIVE: The objective was to evaluate the long-term effects of physiotherapy with an oscillating positive pressure device ("flutter") compared with physiotherapy with the use of a positive expiratory pressure (PEP) mask in patients with cystic fibrosis (CF).Study design: Forty children with CF were randomly assigned to performing physiotherapy with the PEP mask or the flutter device for 1 year. Clinical status, pulmonary function, and compliance were measured at regular intervals throughout the study. RESULTS: The flutter group demonstrated a greater mean annual rate of decline in forced vital capacity compared with the PEP group (-8.62 +/- 15.5 vs 0.06 +/- 7.9; P =.05) with a similar trend in forced expiratory volume in 1 second (-10.95 +/- 19.96 vs -1.24 +/- 9.9; P =.08). There was a significant decline in Huang scores (P =.05), increased hospitalizations (18 vs 5; P =.03), and antibiotic use in the flutter group. CONCLUSION: Flutter was not as effective in maintaining pulmonary function in this group of patients with CF compared with PEP and was more costly because of the increased number of hospitalizations and antibiotic use.     

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.     

Effects of Bifidobacterium lactis Bb12 supplementation on body weight, fecal pH, acetate, lactate, calprotectin, and IgA in preterm infants

Preterm infants are prone to abnormal bacterial colonization of the intestine with ensuing adverse health effects. To examine whether the oral application of Bifidobacterium lactis Bb12 (probiotic) may improve selected indicators of health status in preterm infants, a double blind, placebo controlled randomized clinical study was performed on 69 preterm infants (<37 gestation wk). Weight gain was defined as the primary outcome measure. In antibiotic-treated infants, probiotic supplementation resulted in a higher body weight compared with placebo (p < 0.001). In the probiotic group, the fecal pH was significantly lower than in the placebo group. The fecal concentrations of acetate and lactate were 42 and 38% higher, respectively, in the probiotic group than in the placebo group. Fecal calprotectin was lower in the probiotic group (p = 0.041), while fecal IgA was higher in this group compared with the placebo group (p = 0.021).     

Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations

BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes.     

Age-related alterations of immunoreactive pancreatic cationic trypsinogen in sera from cystic fibrosis patients with and without pancreatic insufficiency

Serum immunoreactive cationic trypsinogen levels were determined in 99 control subjects and 381 cystic fibrosis (CF) patients. To evaluate the status of the exocrine pancreas all CF patients had previously undergone fecal fat balance studies and/or pancreatic stimulation tests. Three hundred fourteen CF patients had fat malabsorption and/or had inadequate pancreatic enzyme secretion (pancreatic insufficiency) requiring oral pancreatic enzyme supplements with meals. Sixty-seven CF patients did not have fat malabsorption and/or had adequate enzyme secretion (pancreatic sufficiency) and were not receiving pancreatic enzyme supplements with meals. Mean serum trypsinogen in 99 control subjects was 31.4 +/- 14.8 micrograms/liter (+/- 2 SD) and levels did not vary with age or sex. In CF infants (less than 2 yr) with pancreatic insufficiency, mean serum trypsinogen was significantly above the non-CF values (p less than 0.001). Ninety-one percent of the CF infants had elevated levels. Serum trypsinogen values in the pancreatic insufficient group declined steeply up to 5 years, reaching subnormal values by age 6. An equation was developed which described these age-related changes very accurately. Only six CF patients with pancreatic insufficiency had serum trypsinogen levels above the 95% confidence limits of this equation. In contrast, there was no age related decline in serum trypsinogen among the CF group with pancreatic sufficiency. Under 7 yr, serum trypsinogen failed to distinguish the two groups. In those over 7 yr of age, however, serum trypsinogen was significantly higher than the CF group with pancreatic insufficiency (p less than 0.001), and 93% had values within or above the control range.(ABSTRACT TRUNCATED AT 250 WORDS)     

A two-year randomized, placebo-controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities.

OBJECTIVE: Our objective was to determine whether long-term treatment of young patients with cystic fibrosis (CF) with dornase alfa maintains lung function and reduces respiratory tract exacerbations. STUDY DESIGN: This was a 96-week, randomized, double-blind, placebo-controlled trial involving 49 CF centers. Inclusion criteria were age 6 to 10 years and forced vital capacity > or = 85% predicted. Patients were excluded for hospitalization for complications of CF within 2 months and use of dornase alfa within 6 months. Patients were treated with dornase alfa 2.5 mg or placebo once daily with a jet nebulizer and a compressor. RESULTS: Patients were randomized, 239 to dornase alfa and 235 to placebo. At baseline the mean age was 8.4 years, the mean forced expiratory volume in 1 second 95% predicted, the mean forced expiratory flow, midexpiratory phase 85% predicted, and the mean forced vital capacity 102% predicted. At 96 weeks the treatment benefit for dornase alfa compared with placebo in percent predicted (mean +/- SE) was 3.2 +/- 1.2 for forced expiratory volume in 1 second (P =.006), 7.9 +/- 2.3 for forced expiratory flow between 25% and 75% of vital capacity (P =.0008), and 0.7 +/- 1.0 for forced vital capacity (P =.51). The risk of respiratory tract exacerbation was reduced by 34% in patients who received dornase alfa (relative risk 0.66, P =.048). There was no statistically significant difference between the groups in changes in weight-for-age percentile. Adverse event profiles for the treatment groups were similar. CONCLUSIONS: Treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period.     

A randomized controlled trial of a 3-year home exercise program in cystic fibrosis

OBJECTIVES: To evaluate the effects of a 3-year home exercise program on pulmonary function and exercise tolerance in mildly to moderately impaired patients with cystic fibrosis (CF) and to assess whether regular aerobic exercise is a realistic treatment option. STUDY DESIGN: Seventy-two patients with CF (7-19 years) were randomly assigned to an exercise group (a minimum of 20 minutes of aerobic exercise, at a heart rate of approximately 150 beats/min, 3 times weekly) or a control group (usual physical activity participation). Pulmonary function, exercise tolerance, clinical status, hospitalizations, and compliance with therapy were monitored during scheduled visits to the hospital's CF clinic. RESULTS: Sixty-five patients were included in the analyses. The control group demonstrated a greater annual decline in percent of predicted forced vital capacity compared with the exercise group (mean slope +/- SD, -2.42 +/- 4.15 vs -0.25 +/- 2.81; P =.02), with a similar trend for forced expiratory volume in 1 second (-3.47 +/- 4.93 vs -1.46 +/- 3. 55; P =.07). Patients remained compliant with the exercise program over the study period. An improved sense of well-being was reported with exercise. CONCLUSIONS: Pulmonary function declined more slowly in the exercise group than in the control group, suggesting a benefit for patients with CF participating in regular aerobic exercise. Consistent compliance with the home exercise program and a self-reported positive attitude toward exercise provide further evidence of the feasibility and value of including an aerobic exercise program in the conventional treatment regimen of patients with CF.     

Profile and factors determining outcome in a cohort of cystic fibrosis patients seen at the Aga Khan University Hospital, Karachi, Pakistan

Cystic fibrosis is the most common potentially lethal autosomal recessive, genetic disease associated with pulmonary and pancreatic insufficiency. It is caused by variations in the CFTR (cystic fibrosis transmembrane regulator) gene. The most common mutation in the CFTR gene designated DeltaF508, is found in only 33 per cent of CF patients in Pakistan. The variability in presentation and clinical severity of disease may be a function of genotypic-phenotypic factors. Our aim was to attempt to define the disease in this region and to lay the ground work for future mutational analysis. This study was a retrospective chart review was conducted to identify cystic fibrosis patients seen at the Aga Khan University Hospital over a 10-year period. Our study identified 56 patients diagnosed by a pilocarpine iontophoresis sweat test. A chart review was then done to look at the various clinical profiles. 58.3 per cent of our patients presented in the first 6 months of life supporting the hypothesis that CF may be a severe disease in Asians with an earlier age of presentation. Most of the patients (80.6 per cent) presented with pulmonary problems while 83.9 per cent had failure to thrive. The most frequently isolated pathogen was Pseudomonas aeruginosa in 87.5 per cent of the patients tested. 70 per cent of the patients died in the first year of life. The clinical parameters studied suggest a severe form of CF in Pakistani patients and provides a foundation for future studies to define genotype/phenotype correlations of the specific mutations involved in Pakistani CF patients.