Demographics of glucose metabolism in cystic fibrosis.

We investigated the prevalence of cystic fibrosis-related diabetes (CFRD) and its association with various demographic and clinical conditions in a Dutch child and adult cystic fibrosis (CF) population. Patients were classified as having either normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or CFRD. Associations with the following parameters were studied: age, gender, BMI, mutations, pulmonary function, infection status, and hospitalization. In our patient population the prevalence of IGT and CFRD was 16% and 31% respectively. After excluding pancreatic sufficient patients, the prevalence of CFRD was 40% and in patients over 40 years 52%. Compared with patients with NGT, CFRD patients were older, had more in-hospital days and had worse pulmonary function. Women developed CFRD at a significantly younger age than men. CFRD is a frequently occurring co-morbidity in patients with CF. The prevalence of CFRD is increasing in ageing CF populations and deserves rising attention in CF management.

Recombinant human deoxyribonuclease for the treatment of acute asthma in children.

BACKGROUND: Airway obstruction in acute asthma is the result of airway smooth muscle contraction, inflammation and mucus plugging. Case reports suggest that mucolytic therapy might be beneficial in acute asthma. The aim of this study was to determine the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase) in addition to standard treatment at the emergency department in children with an asthma exacerbation. METHODS: In a multicentre randomised double-blind controlled clinical trial, 121 children brought to the emergency room for a moderate to severe asthma exacerbation were randomly assigned to receive either a single dose of 5 mg nebulised rhDNase or placebo following the second dose of bronchodilators. An asthma score (scale 5-15) was assessed at baseline and at 1, 2, 6, 12 and 24 h. The primary outcome variable was the asthma score 1 h after the study medication. RESULTS: One hour after the study medication the asthma score in the rhDNase group showed an adjusted mean decrease from baseline of 1.0 (95% CI 0.5 to 1.6) points compared with 0.7 (95% CI 0.3 to 1.2) points in the placebo group (mean difference 0.4 (95% CI -0.2 to 1.0) points; p = 0.23). The asthma score over the study period of 24 h also did not differ significantly between the rhDNase and placebo group (mean difference 0.2 (95% CI -0.3 to 0.7) points, p = 0.40). The duration of oxygen supplementation and number of bronchodilator treatments in the first 24 h were similar in both groups. CONCLUSION: Adding a single dose of nebulised rhDNase to standard treatment in the emergency room has no beneficial effects in children with moderate to severe acute asthma.

[Facial paresis in children; consider Lyme disease]. / Facialisparese bij kinderen; denk aan Lyme-ziekte.

Three girls, aged 3, 7 and 13 years, developed acute peripheral facial palsy. The first patient was initially diagnosed as having Bell's palsy. The third patient had negative serology at first assessment, on the basis of which the diagnosis of Lyme disease was temporarily rejected. Ultimately, all three appeared to have neuroborreliosis. They were treated with intravenous ceftriaxone and recovered well. Facial palsy in childhood is frequently caused by Lyme borreliosis and infection with Borrelia burgdorferi should therefore be investigated, even if there are no signs of a tick bite or erythema migrans. Diagnosis is made by serology, followed by immunoblotting to confirm a positive result. In case of strong suspicion based on the patient's history or physical examination or a positive serology, lumbar puncture should be carried out. Antibiotic treatment facilitates recovery and prevents complications.

Efficacy, safety and tolerability of 3 day azithromycin versus 10 day co-amoxiclav in the treatment of children with acute lower respiratory tract infections.

To compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were included in a multicentre randomized double-blind, double-dummy study. The diagnosis of LRTI was based on the presence of respiratory signs and symptoms in combination with consolidation on a chest radiograph or clinical evidence of LRTI. Patients received oral azithromycin suspension (10 mg/kg/24 h) or placebo in one dose for 3 days and co-amoxiclav (45/11.25 mg/kg/24 h) or placebo in three doses for 10 days. Of 110 eligible patients, 56 and 54 patients, respectively, were treated with azithromycin or co-amoxiclav. The percentage of patients cured or clinically improved at days 10-13 (primary endpoint) was 91% for azithromycin and 87% for co-amoxiclav. This difference of 4% (90% confidence interval: -6%, +14%) was not statistically significant (P= 0.55). Significantly (P = 0.01) more related adverse events were found in the co-amoxiclav group. This was largely due to a higher percentage (43% versus 19%) of gastrointestinal complaints. A 3 day course of azithromycin (three doses) is as effective in the treatment of LRTI in children as a 10 day course of co-amoxiclav (30 doses). The azithromycin group had fewer adverse events. We conclude that azithromycin is an effective, safe and well-tolerated drug in the treatment of children with LRTI. An additional advantage is the easy administration and short duration of therapy.

Hospital admissions and readmissions for asthma in the age group 0-4 years.

SUMMARY. Childhood rates for admission and readmission for asthma are highest under the age of 5 years. From a registration study in 0-4-year-olds, 100 patients (68 male) were admitted to hospital for asthma and followed for 1 year, yielding a total of 136 admissions. To examine factors that may play a role in admissions and readmissions, histories and laboratory tests for atopic status at initial presentation, and clinical data on admission were evaluated. Age groups 0-1 year (n = 54) and 2-4 years (n = 46) were analyzed separately, of whom 20 (37%) and 9 (20%) patients, respectively, had at least one readmission. In the age group 2-4 years, patients with antibodies against inhalant allergens, determined by radioallergosorbent test (RAST), had a significantly higher risk of readmission (RR = 1.54; 95% CI, 1.22-1.95). In the age group 0-1, year prevalence of sensitization to inhalant allergens was low (20% vs. 72% in age group 2-4 years) and constituted only a slight risk (P = 0.097) for readmission. A history of eczema showed a negative association in the age group 0-1 year. Treatment of the first admission did not differ between children only admitted once and those requiring readmission. In both age groups, clinical features at admission did not differ significantly between first and subsequent admissions, and neither did length of stay. Number of readmissions were higher in the age group 0-1 year than in the age group 2-4 years (27/81 (33%) vs. 9/55 (16%), P = 0.028), with no indication of a lower threshold for admission. In the age group 0-1 year, 60% of the readmissions occurred within 2 months of first hospitalization. Moreover, in the age group 0-1 year a trend was observed that inhaled steroids were prescribed less frequently on discharge following first admission in those children who were readmitted than in the children who had a first admission only (4/20 (20%) vs. 15/34 (44%), P = 0.073). More "aggressive" therapy with anti-inflammatory drugs and close medical follow-up after discharge seem to be indicated.

Nasal peak inspiratory flow through Turbuhaler in children with symptomatic rhinitis and in healthy children.

Topical treatment of allergic or vasomotor rhinitis is possible by means of pressurized metered dose inhalers, aqueous spray, or dry powder inhalers. In children, little is known about nasal drug delivery by dry powder inhalation. The airflow through the device is critical for the drug release and a sufficient nasal inspiratory flow is needed for intranasal drug delivery from a dry powder inhaler. In order to investigate from what age children with allergic or vasomotor rhinitis can reliably use such a device, device-dependent nasal peak inspiratory flow (DnPIF) was measured. The maximal DnPIF was measured in children aged 4-13 years making use of a dry powder inhaler (Turbuhaler) connected to a spirometer (Vitalograph). In the clinically relevant context, instructions from the doctor and one week's use of a Turbuhaler at home were found to be sufficient to obtain a good inhalation technique and were shown to improve DnPIF at least as effectively as visual feedback training at the clinic. Children with rhinitis, as well as healthy children from the age of 6 years, were able to generate a DnPIF sufficient to obtain a reliable nasal delivery of a dry powder drug dose. DnPIF values correlated with age. Consequently, a recommendation to use a nasal Turbuhaler from the age of 6 for topical drug delivery in the treatment of allergic or vasomotor rhinitis seems reasonable.

Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma.

When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment.

Risk factors for exacerbations and hospital admissions in asthma of early childhood.

Hospital admissions and readmissions for asthma in early childhood remain causes for concern. The purpose of this study was to identify predisposing risk factors related to asthma exacerbations and precursors of hospital admissions in young children. Subjects were patients with doctor-diagnosed asthma from a clinical registration study, aged 0-4 years, and followed up for 2 years. Data from histories and laboratory tests for atopic status at initial presentation, and the patient's condition at visits over the 2-year follow-up period were evaluated. Exacerbation was defined as increases in cough and/or wheeze and/or breathlessness, increase in beta(2)-agonist use, and a clinical need for a short course of oral corticosteroids. Age groups 0-1 year and 2-4 years, based on age at initial presentation, were analyzed separately. In the age group 0-1 year, 71/113 (63%) patients had at least one exacerbation, and 20 experienced recurrent exacerbations (>/=3). Predisposing risk factors for exacerbation were damp housing (odds ratio (OR) 7.6 (2. 0-28.6)) and colds (OR 3.6 (1.4-9.6)), and for recurrent exacerbations sensitization to inhalant allergens (Phadiatop(R)) (OR 8.1 (1.6-40.5)) and damp housing (OR 3.8 (1.1-12.8)). Hospital admissions were significantly associated with number of exacerbations. In the age group 2-4 years, 58/144 (40%) patients had at least one exacerbation, and 21 experienced recurrent exacerbations (>/=2). Predisposing risk factors for exacerbation were mean age at initial presentation (OR 0.92 (0.88-0.97)) and level of total IgE (OR 2.3 (1.4-3.9)), whereas for recurrent exacerbations no predictor variables were found. Hospital admissions were significantly associated with damp housing. Results from this study may facilitate recognition of young asthmatic patients at risk of (recurrent) exacerbations, and help to identify those in whom early intervention with anti-inflammatory therapy may be necessary. We also emphasize the importance of preventive measures in decreasing damp housing.

Prognostic characteristics of asthma diagnosis in early childhood in clinical practice.

A registration study from clinical practice was set up to assess the prognostic value of symptoms and laboratory data at first visit for doctor-diagnosed 'asthma' in early childhood. A total of 419 children aged 0-4 y, who were newly referred to the outpatient department of the Juliana Children's Hospital with possible asthma were enrolled over a 2-y period. Data from history taking, physical examination, laboratory tests for atopic status at first visit and data from follow-up visits were recorded. Two years after the first visit all medical records were reviewed for diagnostic label. The age groups 0-1 y and 2-4 y were analysed separately, because respiratory symptoms are often transient and sensitization to inhalant allergens is uncommon before the age of 2 y. The clinical diagnosis 'asthma' was made in 113 of 231 (49%) children aged 0-1 y and in 144 of 188 (77%) children aged 24 y. Characteristics from history taking indicated shortness of breath was the most prognostic symptom in both age groups. Eczema, wheeze and non-allergic provoking factors (weather conditions) were further predisposing factors in the 0-1 y group, as were allergic provoking factors (inhalant allergens) and absence of ear-nose-throat-history in the 2-4 y group. Adding laboratory data to history total serum IgE had prognostic value, but specific serum IgE against inhalant allergens (Phadiatop) was a strong predisposing factor, especially in the 2-4 y group. These prognostic characteristics may enhance early recognition of asthma in infants and improve asthma care in clinical practice.

[Acute respiratory insufficiency in children]. / Acute respiratoire benauwdheid bij kinderen.

Acute respiratory distress in children is often a consequence of asthma. Other causes are subglottic laryngitis, epiglottitis, aspiration of a foreign body, acute bacterial pneumonia or pneumothorax. History and physical examination should differentiate between the various diseases. Asthma is characterized by recurrent symptoms and signs, while this is not the case with the other causes of acute breathlessness described. An asthma exacerbation is often preceded by one or more prodromes. In case of aspiration of a foreign body, like a peanut, immediate action is needed to prevent irreversible damage to the airways. Subglottic laryngitis and epiglottitis are both characterized by an inspiratory stridor; in case of epiglottitis immediate action is needed, while in case of subglottic laryngitis observation time is available in most cases. Pneumothorax as a cause of acute breathlessness is rare in childhood; it should be considered in male smoking leptosomic asthmatic adolescents.

Occurrence of a late response to exercise in asthmatic children: multiple regression approach using time-matched baseline and histamine control days.

At the present time, there is still controversy concerning the presence of a late asthmatic response (LAR) to exercise challenge in asthma. We have, therefore, investigated the occurrence of a LAR after exercise in asthmatic children visiting an out-patient clinic, using time-matched baseline and histamine control days, and a statistical analysis according to recently published recommendations. After a screening exercise day, 17 children (aged 7-14 yrs) randomly performed, on three subsequent study days, either: a second standardized exercise challenge; or a histamine challenge whilst matching the bronchoconstriction after exercise; or measurement of baseline lung function without any challenge. Measurements of forced expiratory volume in one second (FEV1) were made repeatedly during 8 h. Analysis was performed using multiple regression analysis for each patient, with FEV1 as the dependent, and test day (exercise or control) and clock time as independent variables during the period 2-8 h after exercise. A significant interaction (p < 0.05) between test day and clock time was considered to be indicative of a LAR. Fifteen children completed the study. All children showed an early asthmatic reaction to exercise (range 14-62% fall in FEV1). In two children, a significant interaction (p < 0.05) was found between test day and clock time. However, the difference in FEV1 between exercise and control days for each clock time did not exceed the 99.6% confidence limits of normal diurnal variation in any of the children. We conclude that, in children with mild-to-moderate asthma, a LAR to exercise does not occur. This suggests that exercise is only a symptomatic trigger of asthma. Whether exercise is capable of inducing inflammation needs to be further investigated.

Prolonged recovery from exercise-induced asthma with increasing age in childhood.

It has been suggested that children with asthma recover more quickly from exercise-induced bronchoconstriction than adults. On the basis of clinical observation we hypothesized that recovery rate from exercise-induced asthma (EIA) in childhood also decreases with age. In 14 children (aged 7-12 years) with a history of EIA, we measured spontaneous recovery from bronchoconstriction induced by two different stimuli: exercise and histamine. The children visited the laboratory three times. After a screening exercise test on the first visit, standardized bronchoprovocation tests with either exercise or histamine were performed on the following two visits in random order. The degree of bronchoconstriction induced by histamine was matched for that observed after exercise. During recovery, forced expiratory volume in 1 second (FEV1) was measured repeatedly up to 2 hours postchallenge. The recovery rate (% increase in FEV1/min) was calculated from the linear slope of the time-response curve. Differences in recovery rate between the two stimuli were analyzed by paired t-test, and age-related differences were analyzed using multiple regression analysis. For the group as a whole, recovery rate was not different between the two stimuli (mean +/- SD: 1.22 +/- 0.91 for exercise, and 1.46 +/- 0.65, for histamine, P = 0.31). However, the recovery rate for exercise-induced bronchoconstriction decreased significantly with age (r = -0.74, P = 0.003), in contrast to the recovery rate for histamine (r = -0.15, P = 0.60). Consequently, in the oldest age group (11-12 years, n = 5) recovery rate from exercise challenge was significantly slower than in the younger age group (7-10 years, n = 9), i.e., 0.54 +/- 0.17 and 1.60 +/- 0.93, respectively, P = 0.009, and slower than the recovery rate from histamine challenge: 0.54 +/- 0.17 and 1.33 +/- 0.54, respectively, P = 0.03. In the younger age group the recovery rates from exercise and histamine were not different (1.60 +/- 0.93 and 1.54 +/- 0.73, respectively, P = 0.83). We conclude that recovery from EIA in childhood decreases with increasing age. These data suggest that the mechanism of exercise-induced asthma in childhood changes with age. This might be due to changes in mediator production or response to mediator release.

Large lungs after childhood asthma. A case-control study.

Several studies have suggested that the TLC after childhood asthma is increased compared wtih that in healthy subjects. The aim of this study was to assess whether TLC is increased after childhood asthma and whether this is associated with an increased growth of the lung during adolescence. During a mean period of 29 months we studied 53 patients and 106 healthy control subjects who were matched for sex, age, and standing height. The patients had had asthma for a mean period of 10 yr. We found that in asthmatics TLC was increased in both sexes by about 7% predicted compared with that in the matched control subjects. The growth of TLC in ml/yr during adolescence was less in patients; this can be accounted for by a delay in pubertal development. When corrected for the delay in growth of stature, growth of TLC in ml/cm in asthmatics was similar to that found in control subjects. These findings support the hypothesis of a developmental change of enhanced lung growth during childhood asthma; they do not support a mechanism with progressive loss of elastic recoil of the lung.

[Trends in consultations and prescriptions for children with COPD]. / Trends in consulten en prescripties wegens CARA bij kinderen.

National data were provided on consultations (first, repeat) and prescriptions in patients having ambulatory care for asthma and COPD combined, by age group (0-4, 5-11, and 12-19 yr) and doctor's category (GP, specialist) over the period 1981-1990. Prescriptions were subdivided into (1) beta 2-agonists, anticholinergics, ketotifen, methylxanthines, cromoglycate, inhaled steroids, oral steroids, (2) antibiotics, (3) other drugs. Age specific rates/1000 persons/year were calculated. Rates for first consultations remained steady, pointing to a stable incidence. Rates for repeat consultations increased in the 0-4 yr age group (GP and specialist) and the 5-11 yr age group (specialist). Prescription rates for the pulmonary medication group also rose in particular in these two age groups. For the GP, however, they were counterbalanced by decreasing trends in prescriptions of the 'other drugs', pointing to a shift towards more rational treatment. The increased ratios of prescription rate to consultation rate, not only for the anti-inflammatory drugs but for the bronchodilators as well, especially in the specialist category, suggest an increased morbidity (severity) from obstructive airways disease in childhood.

An analysis of the costs of a hospital-wide Picture Archiving and Communication System with the software package CAPACITY.

Within the scope of the Dutch PACS project, the costs of a hospital wide PACS in the Utrecht University Hospital were estimated, with the help of the software package CAPACITY. The cost analysis was based on the most recent specifications of the costs of the equipment, on extrapolations, and on the experience acquired with a PACS prototype in the Utrecht University Hospital. Savings due to a possible reduction in the length of stay, or due to logistic improvements were not taken into account. The results indicate that the extra costs of a hospital wide PACS would amount to 3.2% of the total hospital budget. By taking into account the expected price movements, it is predicted that a hospital wide PACS may allow enough savings to pay itself back, when installed near the turn of the century. The result of this cost analysis depends on a large number of assumptions. Therefore two sensitivity analyses are carried out, i.e., concerning the number of workstations required and concerning the organizational impact of PACS.