Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study.

AIMS/HYPOTHESIS: Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis-related glucose intolerance. METHODS: We enrolled 898 cystic fibrosis patients from Sweden, Norway and Denmark. Vitamin D intake was assessed using a seven-day food record. Serum 25-hydroxyvitamin D (s25OHD) and HbA(1c) were measured, and an OGTT was carried out. Multiple linear and logistic regressions were used for HbA(1c) and cystic fibrosis-related diabetes/OGTT result as outcome variables, respectively. Each model was controlled for country, and for known cystic fibrosis-related diabetes risk factors: age, sex, genotype, liver dysfunction, long-term corticosteroid treatment, and lung and pancreatic function. RESULTS: Degree of vitamin D insufficiency (OR 1.36; p = 0.032) and s25OHD < 30 nmol/l (OR 1.79; p = 0.042) were significant risk factors for cystic fibrosis-related diabetes. Accordingly, HbA(1c) value was positively associated with s25OHD < 30 nmol/l and < 50 nmol/l, as well as with degree of vitamin D insufficiency (adjusted R (2) = 20.5% and p < 0.05 in all). In subgroup analyses, s25OHD < 30 nmol/l determined the HbA(1c) value in paediatric patients (adjusted R (2) = 20.2%; p = 0.017), but not in adults. CONCLUSIONS/INTERPRETATION: Vitamin D status is associated with HbA(1c) and diabetes in cystic fibrosis, particularly in children. The study justifies prospective studies on the proposed role of vitamin D deficiency in the pathophysiology of diabetes mellitus.

Inverse relation between vitamin D and serum total immunoglobulin G in the Scandinavian Cystic Fibrosis Nutritional Study.

BACKGROUND/OBJECTIVES: The hallmark of cystic fibrosis (CF) is chronic lung inflammation. The severity of lung disease is closely correlated with immunoglobulin G (IgG) levels. Beyond its contribution to the bone health, the importance of vitamin D has not been fully recognized owing to the lack of human studies providing evidence of its benefit. In the context of the recently described immunomodulatory functions of vitamin D, we aimed to assess the relationship between vitamin D and IgG levels. SUBJECTS/METHODS: Eight hundred and ninety-six CF patients were included (0.53-65.9 years) from seven centers in Denmark, Norway and Sweden. Serum 25-hydroxyvitamin D (25OHD) and total IgG were measured, spirometry was carried out and vitamin D intake data were gathered using a 7-day dietary food record. Multiple linear regression analyses were performed for IgG and forced expiratory volume in 1λs (FEV1) as dependent variables, and serum 25OHD, daily food and supplemented vitamin D sources of intake as independent variables. The model was controlled for age, gender, genotype, CF-related diabetes, season, infection/colonization status, long-term oral corticosteroid treatment, long-term treatment with macrolide antibiotics, pancreatic insufficient phenotype and body mass index z-score. RESULTS: Serum total IgG levels were negatively associated with serum 25OHD (adjusted R (2) = 0.376; beta = -0.02; P<0.001), supplemented vitamin D intake per kg bodyweight (adjusted R (2) = 0.375; beta = -0.82; P < 0.001) and total vitamin D intake per kg bodyweight (adjusted R (2) = 0.398; beta = -0.60; P = 0.002). Serum 25OHD was positively associated with FEV1 (adjusted R (2) = 0.308; beta = 0.0007; P = 0.025). CONCLUSIONS: Increasing vitamin D intake may positively modulate inflammation in CF. This study supports the proposed role of vitamin D in the immune system during infection and substantiates prospective studies.

Prevalence trends of obesity and overweight among 10-year-old children in western Sweden and relationship with parental body mass index.

AIM: To determine the regional prevalence, secular and family-related trends of obesity and overweight among 10-y-old children. METHODS: A cross-sectional study of 10-y-old children, born in 1990, was performed during September 2000 to June 2001 at school health centres in three communities in the western part of Sweden. Evaluation was performed in 6311 children, or 81% of the target population. Data from a cohort of children, born in 1974, who form the national growth charts, were available for comparison. RESULTS: The mean body mass index was 17.9 kg/m2 in 10-y-old children born in 1990 and 17.0 kg/m2 for 10-y-olds born in 1974 (p < 0.0001). Of the 10-y-old children in 2000-2001, born in 1990, 18% were overweight and 2.9 % obese, which corresponds to a twofold increase in presence of overweight and a fourfold increase in presence of obesity among 10-y-old children from 1984 to 2000. There was a significant correlation between parental and child body mass index. The prevalence of obesity and being overweight appeared to be higher in children whose parents did not participate in the study. CONCLUSION: During a 16-y period, from 1984 to 2000, a twofold increase in being overweight and a fourfold increase in obesity were seen among 10-y-old children in the western part of Sweden. Parental ponderosity or reluctance to participate in the study was related to a higher prevalence of being overweight or obese in the children. There is a need for the healthcare system to recognize the threats to the health of the population of this new "epidemic" and initiate preventive measures and treatment programmes.

Passive smoking in cystic fibrosis.

The families of 32 children with cystic fibrosis (CF) were interviewed about both their tobacco consumption and their childrens physical activities. Hospital records informed about treatment frequency, lung function and clinical score. Cystic fibrosis families smoked far more than the Swedish average and the passive smokers among our patients seemed to fare less well in all parameters. The children of smoking mothers required significantly longer periods of intravenous antibiotic treatment (P greater than 0.05). Frequent physical exercise seemed to compensate for the potential harmful effects of passive smoking and children with high physical activity living in families who smoked needed significantly less frequent antibiotic treatment than the inactive children (P greater than 0.02). Although this series is small, the results indicate that a smoke-free environment may be important for CF patients. General information is insufficient and extensive psychological support to the families is probably necessary.

Antistaphylococcal antibodies in cystic fibrosis.

Chronic colonization with Staphylococcus aureus is found in 40-50% of the sputum producing patients with cystic fibrosis treated at Stockholm's Cystic Fibrosis Center, Huddinge University Hospital. 30-40% of these patients had increased ELISA IgG antibody titres against teichoic acid and against alpha-toxin. About half of the number of patients showed increased antibody titres to either antigen during infection. Increased antibody titres against staphylococcal antigens were only found in less than or equal to 10% of patients not chronically colonized with S. aureus (no different from the normal population). The serum titres of antistaphylococcal antibodies were significantly higher in the chronically colonized patients (p less than 0.001). Patients who were also chronically harbouring Pseudomonas aeruginosa had the highest titres of both antibodies. The titres increased with clinical signs of infection and were normalized by antimicrobial chemotherapy. To conclude, the use of ELISA IgG antibodies may prove suitable for routine evaluation of the need for, and control of the efficacy of antistaphylococcal chemotherapy in cystic fibrosis.

Prospective study of serum antibodies to Pseudomonas aeruginosa exoproteins in cystic fibrosis.

Serum immunoglobulin G to four purified antigens from Pseudomonas aeruginosa, phospholipase C, alkaline protease, exotoxin A, and elastase, were determined in 62 patients with cystic fibrosis by enzyme-linked immunosorbent assay. The patients were followed for 12 to 24 months in a prospective study. Increased titers, i.e., titers more than 2 standard deviations above those of normal controls, were exclusively found in patients chronically colonized with P. aeruginosa and not in patients harboring only Staphylococcus aureus. The frequencies of elevated titers of antibody to the different antigens varied from 100% (phospholipase C) to 58% (alkaline protease and exotoxin A) to 15% (elastase) in the chronically colonized patients. Mean serum titer levels, expressed as multiples of the age-correlated upper normal limit (=1), were significantly higher to phospholipase C in patients with dual colonization with P. aeruginosa and S. aureus than in those colonized only with P. aeruginosa (P less than 0.001). Conversely, the other three antigens showed significantly higher serum antibody titer levels in patients harboring only P. aeruginosa (P less than 0.001). In five patients who became colonized with P. aeruginosa during the study period, serum antibodies to phospholipase C and exotoxin A increased first. Exceptions to the general pattern of antibody responses were found in three patients chronically colonized with Escherichia coli. They showed a delayed enhancement of anti-phospholipase C titers after the chronic P. aeruginosa colonization. Serum titers were not influenced by exacerbations of pulmonary infection or by antimicrobial therapy. The determination of titers of serum antibody to phospholipase C seems to be a valuable indicator of a chronic colonization with P. aeruginosa. The results further suggest that bacterial metabolism and interactions may influence the antibody response.

Prospective study of serum staphylococcal antibodies in cystic fibrosis.

Serum IgG antibodies to teichoic acid and alpha toxin from Staphylococcus aureus were measured in 62 patients with cystic fibrosis by enzyme linked immunosorbent assays. The patients were followed up for 12-24 months in a prospective study. Raised titres were found exclusively in patients chronically colonised with S aureus. Patients colonised with both S aureus and Pseudomonas aeruginosa had significantly higher titres against teichoic acid than those carrying S aureus alone. Titres were significantly higher when there were clinical signs of low grade infection in the patients chronically colonised with S aureus alone, and in those with both S aureus and P aeruginosa. Significant reduction in titres occurred after antimicrobial treatment given either orally or intravenously in patients with normal erythrocyte sedimentation rates and white cell counts. Measurement of staphylococcal antibody titres may be valuable in monitoring pulmonary infection and antimicrobial treatment in patients with cystic fibrosis.

Granulocyte elastase-alpha 1-antiproteinase complex in cystic fibrosis: sensitive plasma assay for monitoring pulmonary infections.

Elastase in plasma was determined as a complex of granulocyte elastase and alpha 1-antiproteinase (GEC) by an enzyme-linked immunosorbent assay in 67 patients with cystic fibrosis. The patients were observed for 1 years, when clinically infected and noninfected. Although noninfected patients had GEC levels within the normal range, the mean value was significantly higher than the mean values in patients in an optimal noninfectious state (P less than 0.01) and in healthy controls (P less than 0.001). Clinical signs of (in most cases) low-grade infection were paralleled by significant increases in GEC levels (P less than 0.001). There was no correlation with different types of bacteria or age of patients. No cross reaction to Pseudomonas elastase could be found in vitro or in vivo. Significant decreases of GEC values were seen after intravenously administered antimicrobial therapy (P less than 0.001), and although the white blood cell count and erythrocyte sedimentation rate were rarely increased above the normal range, they decreased congruently (P less than 0.001), and lung function improved (P less than 0.001). The sensitivity of GEC was significantly higher than that for erythrocyte sedimentation rate (P less than 0.01) and white blood cell count (P less than 0.05). Determination of GEC values seems to be a simple and sensitive measurement for monitoring treatment in cystic fibrosis, especially of low-grade infections in patients with normal standard blood tests.