Psychosocial functioning of young adults with cystic fibrosis and their families

BACKGROUND: The psychosocial functioning of adolescents and young adults with cystic fibrosis still living in the parental home was investigated. With its proven genetic aetiology cystic fibrosis is an ideal model with which to assess the impact of a chronic and life threatening disorder on family and individual psychological and social functioning. METHODS: Twenty nine patients with cystic fibrosis and their families were compared with those of 27 patients with anorexia nervosa and 31 well controls. Assessments were made using self reporting, interview, and observational methods. RESULTS: Most patients with cystic fibrosis were in robust psychological health and only differed from their healthy peers in that they were much less likely to be in employment. Mothers of patients with cystic fibrosis or anorexia nervosa were more likely than the mothers of the well group to be emotionally distressed, although this was not so for fathers. Young people in both illness groups were more likely to have parents with high levels of expressed emotion. Most families of patients with cystic fibrosis had good problem solving abilities. CONCLUSIONS: In spite of the burden of illness in cystic fibrosis psychological functioning in many respects matches that of well young people.     

The difficulties of treating infection in adults with cystic fibrosis

OBJECTIVE: Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy. DESIGN: Prospective study. PATIENTS: A series of 68 patients with chronic hepatitis C completed a therapeutic trial of interferon alpha 2b (IFN), randomized for dose adaptation, lasting for 24 weeks. MEASUREMENTS: TSH and autoantibodies against thyroid were looked for at (-2) weeks and 24 weeks in all patients. Blood samples obtained at (-2), 12, and 24 weeks were stored for additional hormonal studies in patients who developed thyroid dysfunction. Such patients with thyroid dysfunction were followed up for at least one year. RESULTS: Only one out of 68 patients had abnormal TSH levels, and two had thyroid autoantibodies prior to interferon therapy. Eight patients (12%) developed thyroid dysfunction (five hypothyroidism and three hyperthyroidism) during treatment. In four patients (all of them with thyroid dysfunction, P < 0.001) antimicrosomal, antithyroglobulin, and/or anti-TSH receptor antibodies appeared during interferon therapy. All patients recovered normal thyroid function within 1.5 years after interferon withdrawal. No pretreatment risk factor was identified. The patients with thyroid dysfunction did not significantly differ from the others as regards the dose of interferon they received or the rate of normalization of transaminases. CONCLUSION: (i) A 12% incidence of thyroid dysfunction was observed under interferon therapy; (ii) secondary appearance under interferon therapy of elevated thyroid autoantibodies was a risk factor; (iii) the thyroid disorders induced by interferon were reversible.     

Lipid levels in adults with cystic fibrosis

The systemic treatment of soft tissue sarcomas is difficult due to the limited availability of active cytotoxic drugs. Combinations of cytotoxic drugs at standard doses do increase toxicity but do not improve response rates or survival. All combinations are limited by myelosuppression, mainly leukocytopenia. For at least two of the four active drugs (doxorubicin and ifosfamide) studies have shown a clear dose-response relationship. Recent studies have focused on increasing dose-intensity by increasing dosages or shortening treatment intervals, which is only possible by the use of hematological growth factors. This review will focus on the latter concept.     

Hypertrophic osteoarthropathy in adults with cystic fibrosis

Three adult patients with cystic fibrosis presented with arthralgia, and investigation for the usual causes of arthritis proved negative. Radiographs of long bones revealed periostitis and new bone fromation characteristic of hypertrophic osteoarthropathy. Symptomatic improvement occurred after analgesic and anti-inflammatory therapy. In patients with cystic fibrosis and bone or joint pain, the diagnosis of hypertrophic osteoarthropathy should be considered and long bone radiographs obtained.     

Quality of life in adults with cystic fibrosis

BACKGROUND: Cystic fibrosis is an inherited condition with a high mortality and morbidity. The aims of this study were to assess quality of life in a population of adults with cystic fibrosis, to compare quality of life with published scores from a healthy population and other patient groups, and to examine the relation between quality of life and other measured clinical variables. METHODS: Patients over 16 years of age attending an adult cystic fibrosis outpatient clinic were surveyed at a time when they were clinically stable. A self-complete questionnaire was administered which comprised the Nottingham Health Profile (NHP) together with six additional questions related to cystic fibrosis. RESULTS: Completed questionnaires were obtained from 240 subjects (100 women) of median age 26 years (range 16-56). Mean (SD) forced expiratory volume in one second (FEV1) was 49 (26)% predicted, forced vital capacity (FVC) was 68 (26)% predicted, and the FEV1:FVC ratio was 59 (16)%. In this cross sectional study different patterns of perceived quality of life were seen in men and women. In part 1 of the NHP there was an age related trend compared with norms in men, with more distress/disability in the dimensions of emotion, sleep, and social isolation in the older age groups. In women there was no age related trend in the degree of distress/disability compared with norms. The mean score was different from norms in the dimensions of pain, emotion and sleep. For the patients with cystic fibrosis as a whole the scores in part 1 were comparable with published scores of patients with minor non-acute conditions. Scores in part 2 of the NHP for men were different from norms in six of the seven areas of daily living (all except home life). For women the scores were different from norms in the areas of looking after the home, social life, hobbies, and holidays. There were correlations between several of the quality of life dimensions and other measured variables such as FEV1, breathlessness score, and the time spent on home treatment. CONCLUSIONS: Men and women with cystic fibrosis have different patterns of perceived quality of life, and there is an age related trend of perceived quality of life in men in some dimensions. Quality of life scores in this group, as assessed by the NHP, are similar to those reported in subjects with minor non-acute conditions.     

Functional iron deficiency in adults with cystic fibrosis

Functional iron deficiency (transferrin saturation < 16%) was found in 44 (62%) of 71 adult cystic fibrosis (CF) patients. Haemoglobin concentration and mean cell volume were lower in iron-deficient patients, in whom there was a non-significant trend for lower serum ferritin. Ten iron-deficient patients and two patients with transferrin saturation > = 16% (normal iron) were anaemic. There were no significant differences between iron-deficient and normal-iron patients in intake of calories, protein, iron and vitamin C as determined by 4-day records of dietary intake. Dietary iron deficiency is not an important factor in functional iron deficiency in adult CF patients. Impairment of absorption by exogenous pancreatic enzyme supplements is unlikely to be significant as enzyme intake was the same in the two groups. Iron-deficient patients had lower Shwachman-Kulczycki scores and lower percent predicted forced expiratory volume in 1 s (FEV1% predicted) and forced vital capacity (FVC% predicted). There was a non-significant trend for higher values of white cell count and plasma viscosity in the iron-deficient group. Chronic inflammation is likely to be the primary cause of functional iron deficiency in adult CF patients. Fifteen patients completed 3-month courses of oral iron replacement with no deterioration in pulmonary function, but with no effect on haemoglobin concentration.     

Severe Clostridium difficile-associated colitis in young patients with cystic fibrosis

We report four patients with cystic fibrosis and fulminant Clostridium difficile-associated colitis: two died, and one required hemicolectomy. Three of four patients carried the N1303K mutation. Severe and fatal C. difficile colitis can occur in cystic fibrosis patients, possibly with a genotype-specific predilection (i.e., N1303K/other). Because cystic fibrosis patients may have a wide spectrum of gastrointestinal symptoms, disease caused by C. difficile must be considered when these patients have acute abdominal pain, diarrhea, or severe leukocytosis.     

Long-term change in exercise capacity, body mass, and pulmonary function in adults with cystic fibrosis

STUDY OBJECTIVES: Cross-sectional studies in patients with cystic fibrosis (CF) have shown that exercise capacity is correlated with pulmonary function and body mass. We have examined whether the same relationships are seen longitudinally in adults with CF. DESIGN: Subjects who first performed progressive maximal cycle ergometry between 1986 and 1989 were retested using an identical protocol a mean of 6.3 years later. PARTICIPANTS AND SETTING: Adults with CF attending a regional center. MEASUREMENTS AND RESULTS: The principal exercise measures were peak oxygen uptake (VO2peak), ventilation (VEpeak), oxygen saturation, and heart rate. Spirometry, weight, and height were also recorded at each time point. At baseline, subjects had a mean age of 19.8 years, body mass index (BMI) of 19.0, FEV1 of 69% predicted, VO2peak of 1.56 L/min, and VEpeak of 48.9 L/min. At repeated testing after a mean interval of 6.3 years, the FEV1 had fallen significantly to 54% predicted (p < 0.001) and the BMI had risen significantly to a mean of 20.9 (p < 0.001). There were no significant differences in VO2peak or VEpeak, although VEpeak was a significantly higher proportion (72% vs 61%) of predicted maximal voluntary ventilation. CONCLUSIONS: Adults with mild to moderate pulmonary dysfunction were able to increase body mass and maintain VO2peak despite a declining FEV1. VO2peak was not reduced by the decrease in FEV1 because VEpeak was unaffected. Improved nutrition may have contributed to maintaining fitness.     

Relationships between nasal potential difference and respiratory function in adults with cystic fibrosis

This study investigated the relations between nasal transepithelial electric potential difference (PD) and the phenotype and genotype of cystic fibrosis (CF) adult patients. Basal nasal PD was measured in 95 adult CF patients who were classified into three groups of nasal PD (expressed as absolute values) according to the 10th and the 90th percentiles (28.3 and 49.2 mV, respectively), which defined group 1 (nasal PD < or =28.3 mV), group 2 (nasal PD 28.3-49.2 mV) and group 3 (nasal PD > or =49.2 mV). Patients from group 1 had a higher forced vital capacity (FVC) than patients from groups 2 and 3 (76.5+/-22.4 versus 57.4+/-21.2 and 55.7+/-21.1% predicted, respectively, p<0.05) and a higher forced expiratory volume in one second (FEV1) (69.3+/-24.0 versus 42.5+/-22.4 and 42.2+/-21.4% pred, respectively, p<0.01). Among patients with severe mutations (deltaF508 homozygotes, or one deltaF508 mutation plus another "severe" mutation, or two "severe" mutations), patients from group 1 had a higher FVC, FEV1 and arterial oxygen tension than patients from groups 2 and 3 (p<0.05 for each comparison). The results show that in adult cystic fibrosis patients a normal basal nasal potential difference is related to milder respiratory disease, irrespective of the severity of the genotype.     

Lower respiratory illness in infants and young children with cystic fibrosis: evaluation of treatment with intravenous hydrocortisone

The enzyme-linked immunosorbent assay (ELISA) using HLA class I molecules purified from pooled platelets has the potential to detect HLA antibodies with increased efficiency without sacrificing sensitivity or specificity. This test, which was originally developed in our institution, has been independently validated by recent studies and is now commercially available. We now present evidence of its usefulness as a routine HLA antibody screening test for renal transplant patients. A total of 515 patients were tested monthly by ELISA (13.9 tests/patient) and by antiglobulin-enhanced panel reactivity (6.3 tests/patient). In patients found to be unsensitized, the incidence of false-positive results was less for ELISA than for the panel studies. In patients who were highly sensitized, both tests performed equally well, whereas discordant results were registered mainly in cases of mild sensitization. Because 66% of our patients were not sensitized, the ELISA was effective in reducing the number of more involved tests aimed at characterizing the antibodies. These results provide a foundation to use the pooled platelet HLA ELISA on a routine basis for HLA antibody screening.     

Effects of non-REM sleep on ventilation and respiratory mechanics in adults with cystic fibrosis

A polysaccharide containing 2-acetamido-2-deoxy-D-glucose (GlcNAc), 2-acetamido-2-deoxy-L-fucose (FucNAc), and 2-acetamido-2-deoxy-D-galacturonic acid (GalNAcA) was isolated from an aqueous phenol extract of lipid-free, isolated cell walls of the reference strain for Acinetobacter baumannii serogroup O5, by mild acid hydrolysis of the extract and chromatography of the water-soluble products on Sephadex G-50. By means of NMR studies, methylation analysis, carboxyl reduction and chemical degradations, the repeating unit of the polymer was identified as a branched tetrasaccharide of the structure shown. The serologically active polymer is believed to correspond to the side chain of the O5 lipopolysaccharide: [table: see text]     

Drug management of noninfective complications of cystic fibrosis

Cystic fibrosis (CF) is the commonest lethal hereditary disease in Caucasians. The disease involves a gene mutation located at the long arm of chromosome 7, and more than 300 mutations have been identified. CF is a systemic illness affecting the upper respiratory tract and airways, sweat and salivary glands, pancreas, gastrointestinal tract, liver and male reproductive system. The course is highly variable depending on the specific molecular abnormalities in the mutant gene. The current approach to therapy now involves the use of: (i) chest physiotherapy; (ii) bronchodilators when there is evidence of airways hyperreactivity; (iii) oral and intravenous antibiotics for acute pulmonary exacerbations and aerosolised antibiotics for prevention; (iv) recombinant human deoxyribonuclease I (dornase alfa) to promote airways clearance; (v) amiloride to improve sputum viscosity; (vi) pancreatic enzyme replacement therapy along with nutritional support and supplements; (vi) vitamins; and (vii) ursodeoxycholic acid in selected patients. The use of antiprotease and anti-inflammatory agents has been shown to be useful in preventing the damage secondary to chronic lung infection. In patients with severely impaired lung function, lung transplantations have been performed with good results. Finally, it seems probable that lung disease in CF patients will be ameliorated or prevented in the future with early gene therapy, using vectors such as recombinant adenoviruses, adeno-associated virus, lipofection or retrovirus. However, this require extensive basic and clinical research.     

Meconium ileus equivalent in adults with cystic fibrosis of pancreas: a report of six cases

Eleven episodes of "meconium ileus equivalent" have been seen in six adults with cystic fibrosis of the pancreas. Three patients were initially treated surgically; one died and the other two developed serious postoperative chest infections. Six episodes were successfully treated medically with acetylcysteine orally and by enema, nasogastric suction, and intravenous fluids. Operation should be avoided if possible, and maintenance treatment with acetylcysteine may be necessary to prevent relapse.     

The Irish cystic fibrosis database

We have found records of 1014 Irish cystic fibrosis patients alive by December 1994, belonging to 883 families. Prevalence in the population is 1/3475 and incidence at birth 1/1461, with a gene frequency of 2.6%. Twenty percent of the patients are aged over 20 years, but at present survival rate falls rapidly after that age. We have identified 85% of the mutations on the CFTR gene in a sample of 29% of the families (506 CF chromosomes). Mutation delta F508 is found in 72% of Irish CF chromosomes, G551D in 6.9%, and R117H in 2%. These are the highest frequencies reported for the latter two mutations world wide. Another seven mutations are found in an additional 4% of CF families. We present new microsatellite haplotype data that could be useful for genetic counselling of CF families bearing some of the 15% of CF mutations still unidentified, and comment on possible uses of our database.     

Essential fatty acid deficiency in well nourished young cystic fibrosis patients

Essential fatty acid deficiency is well known in cystic fibrosis patients, but its pathogenesis remains unclear. It might be related to protein-energy malnutrition which is a common feature of cystic fibrosis or to some specific defects in fatty acid metabolism. To avoid the deleterious effects of protein-energy malnutrition, this study assesses the plasma phospholipid fatty acid pattern in well nourished young cystic fibrosis subjects. Sixteen cystic fibrosis subjects aged 6.6-20.0 years were studied and compared to 16 healthy controls matched for gender, age and nutritional status. Plasma phospholipids were separated by thin layer chromatography and phospholipid fatty acid pattern was determined by gas liquid chromatography. Anthropometry and dual-energy X-ray absorptiometry showed that lean body mass, fat-free mass and fat mass were similar in the two groups. Nutritional inquiry showed higher ingestion of macronutrients by cystic fibrosis subjects than by controls. Plasma phospholipid palmitoleic acid and eicosatrienoic acid were higher, and by contrast linoleic acid and docosahexaenoic acid were lower in cystic fibrosis subjects than in controls. The ratio linoleic acid/arachidonic acid was lower and the ratio eicosatrienoic acid/arachidonic acid was higher in cystic fibrosis subjects than in controls. CONCLUSION: Essential fatty acid deficiency is present in young cystic fibrosis subjects in the absence of protein-energy malnutrition. It means that this deficiency is probably related to specific defects in fatty acid metabolism.     

Comprehensive analysis of risk factors for acquisition of Pseudomonas aeruginosa in young children with cystic fibrosis

Racial differences in insulin secretion and insulin sensitivity in healthy children were studied by administering a 2-hour hyperglycemic clamp (225 mg/dL) to 14 black and 16 white healthy adolescents (Tanner II-V), and 12 black and 11 white prepubertal children, matched for age, body mass index, and Tanner I pubertal development. In prepubertal children, fasting and first-phase insulin concentrations were higher in blacks compared with whites (14.7+/-1.3 vs 10.4+/-1.2, P=0.02, and 76.9+/-6.8 vs 52.1+/-6.4 microu/mL, P=0.016). There were no differences in second-phase insulin levels and insulin sensitivity index. In pubertal adolescents, first-phase and second-phase insulin concentrations were higher in blacks compared with whites (first-phase: 157.3+/-18.3 vs 77.0+/-8.7 microu/mL, P=0.0003; second-phase: 175.0+/-24.3 vs 108.7+/-8.8 microu/mL, P=0.012). Insulin sensitivity index was 35% lower in black adolescents compared with whites (P=0.02). These findings indicate that significant differences in insulin secretion and sensitivity are detectable early in childhood in healthy African-American vs American whites. However, genetic (race) vs environmental factors (physical activity/fitness, energy balance) should be carefully scrutinized as potential factors responsible for such differences.     

Osteoporosis in patients with cystic fibrosis

Decreased bone density and increased risk of fractures are seen in patients with cystic fibrosis. Suboptimal vitamin D levels, nutrition problems, hypogonadism, inactivity, corticosteroid use, and cytokines may contribute to the low bone mass seen in these patients. Treatment recommendations must be individualized and may include nutrition, vitamin D, estrogen or testosterone, and exercise. In high-risk patients calcitonin or growth hormone could be considered.     

The cystic fibrosis transmembrane conductance regulator and ATP

The purpose of this study was to monitor changes in preoperative routines following recommendations given in 1989 by the Swedish Council on Technology Assessment and by the Swedish Consensus Conference on Preoperative Routines, both suggesting a more individualized utilization of preoperative testing. This was a multicenter, prospective, repetitive study conducted at seven Swedish hospitals providing surgical care. The subjects included all patients presenting at the operating theaters for surgical interventions requiring general or regional anesthesia. The main outcome measures were the frequency of reports of performed preoperative ECG, chest x-ray, and analysis of serum concentration of potassium. Before general recommendations were issued in 1989, 47% of the patients had had a preoperative ECG, 26% had had a chest x-ray, and in 61% serum potassium concentration had been measured. In 1991 these frequencies had been reduced by 5, 6, and 9 percentage points, respectively (all figures given standardized for age and sex). Large differences were found between individual hospitals. Although recommendations suggesting a more restrictive and individualized utilization of preoperative testing have sparked important revisions in Swedish hospitals, there seems to be substantial potential remaining for further reduction of perfunctory use of preoperative screening.     

The pancreas in cystic fibrosis: chemical composition and comparative morphology

Sections of pancreas from 16 individuals who died with cystic fibrosis (CF) were classified by morphometric criteria into four categories in increasing order of pancreatic involvement. The concentration of acini, islets, main ducts, lobular ducts, connective tissue, and fat was compared with control levels. The results show that in the least involved pancreases, from neonates who died under 5 months of age, acini were reduced to 33% of control levels and the following were increased: islets, to 410%, lobular ducts, to 250%; and main ducts, to 1700% of controls. With increasing severity of the pancreatic disease the acini were further reduced to 5% and lobular ducts to 37% of control levels, respectively. Main ducts increased by 19-fold, and fatty infiltration accounted for more than 25% of the fresh weight of the pancreas in 9 of the 16 specimens. Comparative biochemical studies of 35 fibrocystic pancreases were quantitatively related to the severity of the pancreatic involvement as follows. Water and volatile matter, normally accounting for 80 +/-% of the weight of the fresh pancreas, was reduced to less than 30% in the most affected organs. The concentration of zinc diminished from near normal mean levels of 193 mugZn/g dry pancreas to 10% of this amount in the severely involved pancreas. Elevated concentrations of calcium, amounting to over 10 times control level, were found in obstructed ductal structures. Calcium was depleted from pancreatic sections adjacent to the obstructions. The following biochemical indicators were significantly different in their mean levels in the 35 fibrocystic pancreases when compared with the 17 controls: (P less than or equal to 0.001) fat, water, zinc, calcium, copper, magnesium, potassium, and sodium (P less than or equal to 0.01).