Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis.

OBJECTIVES: Despite improved nutrition and intensive treatment, subjects with cystic fibrosis have difficulty in maintaining anabolism during intercurrent infections, which can result in reduced body mass index and impaired skeletal growth. Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP3 are sensitive to changes in nutritional status. The aim of this study was to determine the relation between circulating concentrations of these peptides, body mass index, and clinical status in cystic fibrosis. METHODS: Serum concentrations of IGF-I and IGFBP3 were measured in 197 subjects (108 males, 89 females; mean age 9.69 years, range 0.41-17.9 years) and these data were analysed with respect to body mass index, pubertal stage, and clinical status as assessed by Shwachman score and forced expiratory volume in one second (FEV1). RESULTS: The mean height SD score of the children studied was -0.2 (SD 1.14) and the body mass index SD score -0.26 (1.4). The body mass index SD score declined with increasing age (r = -0.18) and paralleled changes in IGF-I concentrations, which also declined. The IGF-I SD score (calculated from control data) correlated with age (r = -0.53). The abnormalities were most obvious during late puberty, when IGF-I and IGFBP3 concentrations were significantly reduced compared with those in control subjects matched for pubertal stage. The IGF-I SD score correlated with height SD score (r = 0.14) and the decline in IGF-I concentrations with the fall in body mass index SD score (r = 0.42). IGF-I SD scores also correlated with the Shwachman score (r = 0.33) and FEV1 (r = 0.17). CONCLUSIONS: The close relation between declining IGF-I and IGFBP3 concentrations and body mass index in patients with cystic fibrosis may simply reflect poor nutritional status and insulin hyposecretion. Nevertheless, IGF-I deficiency could also contribute towards the catabolism observed in these patients, and IGF-I SD scores correlated with other measures of clinical status such as the Shwachman score and FEV1.

Nocturnal cortisol secretion in healthy adults before and after inhalation of budesonide.

We have previously demonstrated dose-dependent nocturnal cortisol suppression by inhaled beclomethasone and budesonide in asthmatic children. This has now been confirmed in a controlled study. Eighteen healthy adults inhaled either a single evening dose of 400 micrograms budesonide or placebo or 400 micrograms budesonide twice daily for 2 wk. Overnight blood samplings for cortisol and adrenocorticotropic hormone were taken at the beginning of the trial, at the end of the treatment period, and after stopping the medications. Compared with placebo, the nocturnal cortisol production was significantly reduced by 40% after a single dose of budesonide (p = 0.020) and by 37% after 2 wk of budesonide (p = 0.045). These data indicate that there is a single-dose rather than a cumulative suppressive effect of inhaled corticosteroids using the specific dose and regimen studied in this protocol. The effect is not related to the underlying problem, namely asthma. The clinical relevance of these findings can only be elucidated in long-term follow-up studies. We believe that our findings explain the recent identification of abnormalities in bone turnover on inhaled corticosteroids in the absence of other systemic effects. The findings emphasize the need for a cautious step-wise approach to asthma therapy.

Rise in total IgE as an indicator of allergic bronchopulmonary aspergillosis in cystic fibrosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis is a serious complication of cystic fibrosis and may be difficult to diagnose. The aim of this study was to define the usefulness of measuring total IgE compared with other major criteria in the diagnosis of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. METHODS: A retrospective analysis was carried out of the case records of 160 children attending a tertiary referral paediatric cystic fibrosis clinic. RESULTS: Sixteen children had a total IgE level above 500 IU/ml. Eleven children had six or more other major criteria and were considered to have allergic bronchopulmonary aspergillosis. These 11 children had a fourfold rise in IgE in association with clinical deterioration. A further child had a fourfold rise in IgE to 341 IU/l, and was also thought to have allergic bronchopulmonary aspergillosis. Eleven had a fall in IgE with successful treatment; one patient died with uncontrolled disease. Only one of these 12 children had negative precipitins to Aspergillus fumigatus. The five children with a raised IgE not thought to have bronchopulmonary aspergillosis had four or fewer major criteria and were not treated; none had positive precipitins. CONCLUSIONS: A fourfold rise in total IgE, particularly to above 500 IU/ml, is strongly suggestive of the diagnosis of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. The measurement of total IgE has the merit of being simple to perform and objective. Positive aspergillus precipitins provide useful confirmatory evidence. These two criteria, taken in conjunction with clinical deterioration and new radiological shadowing, allow simplification of the diagnosis of allergic bronchopulmonary aspergillosis in cystic fibrosis.

Endocrine and lung function in asthmatic children on inhaled corticosteroids.

The safety of inhaled corticosteroids in the treatment of chronic asthma has been questioned. In a prospective crossover study asthmatic children not controlled on other medications were commenced on beclomethasone dipropionate (BDP) or budesonide (BUD), both administered at the dose of 200 micrograms twice per day for 2 wk each in randomized order. Recordings at home included twice daily symptom scores, peak expiratory flow readings, and the use of additional antiasthma medications. Before and after each treatment period the patients were admitted for overnight blood sampling for cortisol, ACTH, and growth hormone, 24-h urine collections for cortisol, and detailed lung function tests. A total of 12 children completed the study. The nocturnal serum cortisol production was significantly reduced by 27 and 35% after 2 and 4 wk of treatment (p = 0.005, p = 0.004; Wilcoxon test), and the urinary free cortisol showed a similar reduction of 33 and 48% (p = 0.023, p = 0.005). Such suppression could be shown on both drugs, BDP and BUD, and there was no significant difference between them. The ACTH and growth hormone values were not significantly changed on any treatment. Lung function tests showed an impressive improvement in FVC, FEV1, FEF50, and FEF25 after 2 wk of treatment regardless of the medication. Differences in lung function improvements between the two drugs were very small and not of clinical relevance. The observations indicate that even low-dose inhaled corticosteroids in the form of BDP or BUD have a systemic effect, which emphasizes the importance of using the minimum dose compatible with good control of asthma.

Allergen avoidance in the homes of atopic asthmatic children: the effect of Allersearch DMS.

Allersearch DMS (an alcohol based purified benzyltannate complex) is an acaricide with allergen denaturing properties. The living rooms in the homes of 16 atopic asthmatic children were thoroughly cleaned and treated with Allersearch DMS and the effect on allergen concentrations in carpet and soft-furnishing dusts was determined. The skin-test reactivity of the children to their own dust, collected before and after treatment, was compared. In 13 of the 16 homes the concentration of major house dust mite allergen Der p I was reduced in the carpet dust after treatment (P < 0.001) and in 11 homes major cat allergen Fel d I was reduced (P = 0.03). Changes in allergen concentrations in soft-furnishing dusts were not significant. Control homes, which were cleaned but not treated, showed no significant difference in allergen concentrations. There were highly significant reductions in skin-test reactivity to both types of dust after treatment (P < 0.004, P < 0.008) suggesting an effect of the compound on allergens other than those individually monitored. The change in skin-test response to soft-furnishing correlated significantly (P < 0.05) with the number of individual sensitivities detected in each child. Controlled clinical trials of the effect of Allersearch DMS as part of an allergen avoidance study are now necessary.

Double blind trial of ionisers in children with asthma sensitive to the house dust mite.

BACKGROUND: Manufacturers of ionisers claim many benefits from the use of their devices, including the relief of asthma. Particles removed from the air are likely to include airborne allergens, so ionisers may achieve an effect by reducing the allergen load. METHODS: The effect of ionisers on airborne concentrations of house dust mite allergen Der p I was investigated in a double blind, crossover, placebo controlled trial in the homes of 20 children with allergic asthma. Subjects recorded their peak expiratory flow rate (PEFR) twice daily and completed a daily symptom score and treatment schedule on a diary card for two six week periods, one with an active ioniser and the other with a placed ioniser (randomly allocated) used in the living room and the bedroom. RESULTS: Airborne Der p I concentrations fell significantly during the active period compared with the placebo period, but there was no significant change in PEFR, symptom scores, or treatment usage. There was an increase in night time cough which almost reached significance during the active period. CONCLUSIONS: This study indicates that the use of ionisers cannot be recommended in the homes of asthmatic subjects to improve their symptoms. The significant reduction of airborne allergen concentrations may be of use as part of a multidevice allergen avoidance regimen, but the increase in night time cough requires further study.

Energy and nutrient intakes in cystic fibrosis.

The diets of 20 children with cystic fibrosis were analysed for energy and nutrient content with simultaneous measurement of energy losses in stools. Median energy intakes were in excess of the WHO estimated daily requirements (118.2%) when expressed as MJ/kg/24 hours, the excess almost accounted for by energy losses in the stools. When expressed as MJ/24 hours, however, median energy intakes were 98.7% of that estimated for normal children of median weight for age. Compared with recently published data for normal school children the fat content of the diet was reduced (30.0%) as were intakes of iron and zinc. Children whose whole milk intakes were high had the greatest amount of fat and energy in their diets and were able to absorb energy in excess of that recommended. We conclude that many children with cystic fibrosis are still on low fat diets and whole milk is the single most useful food for the provision of extra dietary fat and energy.

Increased resting energy expenditure in cystic fibrosis.

To explore the hypothesis that there is an increased metabolic rate in cystic fibrosis, resting energy expenditure was measured by indirect calorimetry in 23 subjects with cystic fibrosis in a stable clinical state and in 42 normal control subjects. Resting energy expenditure was found to be elevated by an average of 0.45 MJ/24 h [95% confidence interval (CI) = 0.26-0.64, t = 4.91, P less than 0.001] (108 kcal/24 h), or 9.2% above expected values derived from the regression relating resting energy expenditure to whole body weight and sex in control subjects. When related to lean body mass, values were still elevated by 0.36 MJ/24 h (95% CI = 0.18-0.53, t = 4.15, P less than 0.001) (86 kcal/24 h), or 7.2%. The increased values were found to be independent of age, sex, or body size. There were significant correlations between increased values and poor pulmonary function as measured by the ratio of the forced expiratory volume in 1 s to forced vital capacity (r = -0.44, P less than 0.05) and subclinical infection as indicated by the blood leukocyte count (r = 0.40, P less than 0.05). However, the correlations were low, suggesting that other factors may contribute to the increased resting energy expenditure, possibly including the putative metabolic defect in cystic fibrosis.

Nocturnal adrenal suppression in asthmatic children taking inhaled beclomethasone dipropionate.

Plasma cortisol was measured every 20 min and sleep was monitored in nineteen asthmatic children, twelve of whom were receiving various doses of inhaled beclomethasone dipropionate (BDP). Children receiving inhaled BDP had lower cortisol secretion during the night than those who were not taking inhaled BDP, a delayed rise from the nocturnal nadir, and low early morning levels. Inhaled BDP produces a dose-dependent adrenal suppression.