Bacille-Calmette-Guerin vaccination and the development of allergic disease in children: a randomized, prospective, single-blind study.

BACKGROUND: The increase in the prevalence of allergic diseases in countries with a so-called western lifestyle may be due to a decrease in exposure to infectious agents in early life. OBJECTIVE: To establish the effect of Bacille-Calmette-Guerin (BCG) vaccination in 6-week-old high-risk infants in a prospective single-blind, randomized, placebo-controlled trial on the prevalence of allergic disease at the age of 4 and 18 months. METHODS: Subjects were 121 predominantly Caucasian high-risk newborns, having either a mother, or both a father and at least one sibling with past or present allergic disease. BCG or placebo was administered at the age of 6 weeks, and repeated once when both a post-vaccination scar and a positive TB skin test were absent at the age of 4 months. RESULTS: At the age of 18 months, the prevalence of allergic disease was not significantly different between the two groups. A trend towards less eczema (P=0.07) and significantly less use of medication for eczema was shown in the BCG group compared with the placebo group (P=0.04). CONCLUSION: A single (or once repeated) BCG vaccination in 6-week-old high-risk Caucasian infants was not associated with a 50% reduction in the prevalence of allergic disease. However, there could be a smaller beneficial effect of BCG, especially because a trend towards less eczema and significantly less use of medication for eczema was shown. For definite proof, a larger study should be carried out.

Radiological and functional changes over 3 years in young children with cystic fibrosis.

The aim of the present study was to evaluate airway disease progression assessed by chest radiology, expiratory interrupter resistance (Rint,exp) and spirometry in young children with cystic fibrosis (CF) over a 3-yr period. Two chest radiographs combined with two R(int,exp) measurements were performed with a 3-yr interval in 21 preschool children (age (mean+/-sd) 3.2+/-0.9 yrs) and 30 schoolchildren with CF (age 7.2+/-1.9 yrs). Chest radiographs were scored using five different CF scoring systems and Rint,exp measurements were expressed as height-adjusted Z-scores. Spirometry was assessed in schoolchildren and the results were expressed as a percentage of predicted values. Chest radiograph scores worsened significantly over the 3-yr period and a tendency towards more pronounced changes was observed, especially for the Wisconsin score, in preschool children. Most preschool and schoolchildren had Rint,exp Z-scores within the normal range at start and follow-up, and the annual change in Rint,exp Z-score was not significant. In schoolchildren, only the forced expiratory volume in one second as a percentage of forced vital capacity declined significantly during the study period. In summary, in young children with cystic fibrosis, chest radiograph scores worsen significantly over time even while lung function remains stable.

Moyamoya and extracranial vascular involvement: fibromuscular dysplasia? A report of two children.

We present two patients with moyamoya syndrome and the unusual involvement of extracranial vessels. The first case illustrates the rare association between moyamoya and primary pulmonary hypertension. In the second patient, moyamoya was complicated by stenoses of vertebral, renal, and mesenteric arteries. In both cases, a systemic intima-proliferative disease, such as fibromuscular dysplasia (FMD), was suspected to be the cause of both intracranial and extracranial arterial disease.

Spirometry in young children: should computer-animation programs be used during testing?

Currently, computer-animation programs are frequently used to instruct and stimulate young children in performing maximal expiratory flow/volume (MEFV) curves. The reproducibility and maximal performance of MEFV manoeuvres with and without the use of two computer-animation programs (the "candles" and the "balloon" programs) were evaluated. Eighty-eight children, aged 4-8 yrs, were randomly assigned to one of the two animation programs. All children performed two series of at least three technically acceptable curves, one series with the incentive and one without, in random order. With the use of computer-animation programs, a lower proportion of children were able to fulfil international criteria for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) reproducibility. The use of incentives improved reproducibility and performance of peak expiratory flow (PEF). Performance of FVC decreased significantly in 6-8-yr-old children using the animation programs. Training with a program for a short period of time before the formal lung-function test may be valuable. According to the results, however, the use of these programs during tests under the guidance of an experienced lung-function technician cannot be routinely recommended because of possible deteriorating effects on reproducibility and performance of forced expiratory manoeuvres.

Treatment of children with cystic fibrosis: central, local or both?

UNLABELLED: Owing to a lack of longitudinal studies, the effect of centralization of care on pulmonary function and survival remains unclear. Three different levels of involvement of centralized care in the treatment of paediatric cystic fibrosis patients were compared with regard to longitudinal pulmonary function and nutritional and microbiological status in a 3-y period, and the literature was reviewed on the possible advantages and disadvantages of centralized care. The study included 105 paediatric patients attending the Cystic Fibrosis Centre between January 1997 and January 2001. Twenty-three patients were treated by local paediatricians according to the protocol of the Centre and were seen only once a year at the Centre, for an annual check-up (local care). Forty-one patients were treated at the Centre only (centralized care). The remaining 41 patients were treated in close cooperation between the Centre and local hospitals, with patients visiting the doctors alternately (shared care). The mean annual changes in pulmonary function and body mass index from all patients, as well as a microbiological survey, were reviewed. No significant differences were found between the three groups for annual changes in FEV1, FVC and body mass index, nor did the review of microbial colonization show any significant differences between the groups. Because the groups in this study were relatively small, the results might have been influenced by lack of power. CONCLUSION: In this relatively small group, no differences in pulmonary function, nutritional status or microbiological colonization between the three levels of involvement of centralized care could be found. This could signify that local paediatricians have a special role in the care for patients with cystic fibrosis, in close cooperation with the specialists at the Centre.

[Diagnostic image (39). Leiomyosarcoma of the lungs]. / Diagnose in beeld (39). Leiomyosarcoom van de long.

A 12-year-old girl was unsuccessfully treated for a suspected empyema of the thorax. Afterwards a CT scan, colour doppler flow ultrasonography and a biopsy led to leiomyosarcoma of the lung being diagnosed.

Insulin-like growth factors and leucine kinetics during exercise training in children with cystic fibrosis.

BACKGROUND: Little is known about the metabolic effects of exercise training in children with cystic fibrosis. The hypothesis for the current study was that in patients with declining clinical status, exercise increases circulating insulin-like growth factors (IGFs) and improves protein kinetics. METHODS: This was a prospective intervention study in 10 children with cystic fibrosis who participated in a structured isoenergetic exercise (cycling) training program for 3 months. Measurements of IGFs, protein kinetics (using intravenous [13C]-1-leucine tracer infusions) and nutritional balance studies were conducted at baseline and after 3 months. RESULTS: Standard deviation scores of plasma IGF-I, IGF-II, and IGF binding protein (BP)-3 were all decreased at baseline (mean +/- SE: -2.0+/-0.2, -2.0+/-0.2. -0.6+/-0.2, respectively). IGF-I and IGF-II concentrations were significantly higher after exercise training (standard deviation scores -1.4+/-0.3 and -1.3 +/-0. 1, respectively; compared with baseline: one-tailed t-test P = 0.03 and 0.002). The standard deviation score of the IGF-I/IGF BP-3 ratio, an indicator of free IGF-I in the circulation, normalized during exercise training (0.0+/-0.6 vs. -1.3+/-0.2 SD units at baseline, one-tailed t-test P = 0.04). There was no significant difference in protein intake and fasting protein breakdown, oxidation, and protein synthesis or in energy balance and fat absorption. CONCLUSIONS: These results show that isoenergetic exercise training can be safely recommended to patients with cystic fibrosis. It provides a positive anabolic stimulus to IGF status but is not sufficient to adequately augment protein accretion in patients with diminished nutritional status.

Attitudes towards reproductive issues and carrier testing among adult patients and parents of children with cystic fibrosis (CF).

Assessing the reproductive choices of parents of children with cystic fibrosis (CF) is important in getting a greater insight into the possible needs for counselling of carrier couples in the reproductive decision-making process. Also, parents' reproductive attitudes might indicate critical issues for discussion with regard to introducing general population screening programmes. Data were available from two groups of subjects: 287 adult patients with CF (mean age 27.5 years) and 288 parents of a child with CF (mean age of child 7.7 years) who participated in a Dutch national survey. Attitudes towards reproductive issues and carrier screening and parents' reproductive behaviour were analysed in terms of responses to questionnaires. To avoid having another child with CF, most parents decided against further pregnancies or used other reproductive options. Prenatal diagnosis was used by 72% of parents, whereas 76% of parents planning more children intended using this option. Intention to use prenatal diagnosis was associated with the strength of religious conviction, and was not associated with perceived severity of CF, health of the child, or future therapeutic possibilities. Respondents demonstrated difficulties in deciding to abort for CF. A majority of parents and adult patients supported carrier couple identification within CF families. The results suggest that those most closely involved with CF will accept the reproductive choices of carrier couples identified in population screening programmes.

[Diagnostic image (18). Pulmonary tuberculosis]. / Diagnose in beeld (18). Tuberculose van de long.

In an 8-year-old Somali girl who had been in the Netherlands for 3 years and who was suffering from cough for 2 months, tuberculosis of the lung was diagnosed.

Peripheral muscle weakness and exercise capacity in children with cystic fibrosis.

Exercise intolerance in cystic fibrosis (CF) is attributed to diminished nutritional and pulmonary function. We studied the pathophysiology of such intolerance in relation to muscle force and fat-free mass (FFM), in 15 children with moderately severe symptoms of CF (FEV1 < 80% predicted and/or weight for age < -1 SD of reference median), 13 children with mild symptoms of CF (FEV1 and weight above these thresholds), and 13 healthy controls. Cycle maximal workload (Wmax) and V O2max were assessed. Maximal peripheral muscle force was measured, and FFM was calculated from skinfolds. Patients with mild CF, as compared with matched controls, had lower values of Wmax per kilogram of FFM (3.9 +/- 0.5 versus 4.6 +/- 0.3 W/kg [mean +/- SD], respectively; difference = 0.7 [95% CI = 0.4 to 1.1]), and diminished maximal muscle force (2.7 +/- 0.4 kN versus 3.1 +/- 0.7 kN; difference = 0.44 [95% CI = 0.03 to 0.87]), but similar V O2max. Patients with moderate CF had lower FFM, muscle force, and exercise tolerance than did the other groups. Oxygen cost of work was elevated in both groups of CF patients. Muscle force showed a strong positive correlation with Wmax in patients and controls, with disproportionately lower regression slopes in the CF patients. In children with CF, muscle force is decreased and associated with diminished maximal work load, even in the absence of diminished pulmonary or nutritional status.

Tidal breathing analysis as a measure of airway obstruction in children three years of age and older.

This study was designed to evaluate the value and applicability of tidal breathing pattern analysis to assess airflow obstruction in young children. The time needed to reach maximal tidal expiratory flow (TME) divided by total expiratory time (TE) was measured in 228 healthy children 3 to 11 yr of age, 64 patients with asthma, and 12 children with cystic fibrosis. In 70 patients both TME/TE and forced maximal expiratory flow volume (MEFV) parameters were measured. The mean TME/TE in healthy subjects was 43.0 +/- 7.6%. The within-subject reproducibility was high (repeatability index, 5.3%). In the asthmatic patients the mean TME/TE was significantly lower (30.0 +/- 8.2%, p < 0.001), and it increased to 36.5 +/- 7.9% after bronchodilation (n = 44, p < 0.001). The TME/TE level of the subgroup of patients with asthma and FEV1/FVC > or = 0.80 was lower when compared with age-matched normal subjects (30.9 +/- 8.5, p < 0.0001), but it was in a higher range when compared with asthmatics with FEV1/FVC < 0.80 (25.9 +/- 7.9, p < 0.001). In the cystic fibrosis group the mean TME/TE was 27.4 +/- 10.7% without a significant change after bronchodilation. TME/TE correlated significantly with MEFV parameters. Tidal breathing analysis proved easy to perform in children older than 3 yr of age. The TME/TE ratio may be a reliable and simple indicator for airway obstruction.

Efficiency of oxidative work performance of skeletal muscle in patients with cystic fibrosis.

BACKGROUND: Exercise intolerance in patients with cystic fibrosis is commonly attributed to reduced pulmonary and nutritional status. The possible role of diminished efficiency of mitochondrial oxidative phosphorylation in relation to skeletal muscle performance was investigated in patients with cystic fibrosis. METHODS: In vivo synthesis of ATP in skeletal muscle during submaximal exercise was studied in eight patients with cystic fibrosis aged 12-17 years, and in 19 healthy control subjects aged 8-36 years. The intracellular pH and concentrations of phosphate compounds were calculated at four steady states from phosphorus-31 labelled nuclear magnetic resonance spectroscopy measurements in the forearm muscle during bulb squeezing in an exercise protocol. Normalised power output, expressed as percentage maximal voluntary contraction (Y, in %MVC), was related to the energy force of ATP hydrolysis (X = ln [ATP]/[ADP][Pi]). This relationship provides an in vivo measure of efficiency of oxidative work performance of skeletal muscle. RESULTS: During all workloads (but not at rest) intracellular pH was higher in the patients with cystic fibrosis than in the controls. The linear least square fit for Y = a-bX showed high correlations in both groups; the slope b was 19% lower in the patients than in the controls (11.8% v 14.5% MVC/ln M; 95% confidence interval for difference 0.3 to 5.0). CONCLUSIONS: In patients with cystic fibrosis oxidative work performance of skeletal muscle is reduced. This may be related to secondary pathophysiological changes in skeletal muscle in cystic fibrosis.

Pulmonary hemosiderosis and immune complex glomerulonephritis.

Two children with a syndrome of pulmonary hemorrhage and immune complex nephritis are reported. Clinical history suggests that pulmonary lesions precede renal abnormalities. Necrotizing glomerulonephritis with granular immune deposits along the glomerular basement membrane was found. Although the etiology of this disease complex is still unknown, the clinical and pathological findings in these patients suggest that immune complex glomerulonephritis is an unusual complication of idiopathic pulmonary hemosiderosis.

Risk of cross-colonization and infection by Pseudomonas aeruginosa in a holiday camp for cystic fibrosis patients.

The risk of cross-colonization and subsequent infection by Pseudomonas aeruginosa in holiday camps for cystic fibrosis patients was studied in 91 children by culturing sputum at their arrival, at their departure, 2 months later, and at regular intervals thereafter. The isolated strains were subjected to serotyping, phage typing, pyocin typing, and genotyping by random amplified polymorphic DNA fingerprinting-PCR. It was concluded from random amplified polymorphic DNA fingerprinting-PCR typing that the Pseudomonas flora was not constant in most children. Some children harbored one genotype, whereas some harbored two or more different genotypes simultaneously. Most culture-positive children easily acquired a strain of another genotype which replaced the former one or coexisted with the original one. The incidence of sputum conversion was 7.7% in previously negative children; the incidence of permanent colonization and infection was 1.9%. This risk was comparable with that observed in the community. We conclude that the risk of cross-infection is trivial compared with the obvious joy and social benefit derived from a holiday camp.

Cystic fibrosis and outpatient treatment with parenteral antibiotics in children.

Despite recent key insights into the pathogenesis of cystic fibrosis, the treatment of patients suffering from this disease remains largely symptomatic. Control of respiratory infections is a vital part of patient management, involving daily physiotherapy and administration of mucolytics, bronchodilators and oral or intravenous antibiotics as necessary. For those patients requiring frequent courses of intravenous antibiotics, home treatment appears preferable to repeated hospital admissions. A home care programme for cystic fibrosis has been running at the Wilhelmina Children's Hospital in Utrecht since 1991, with the aid of two specialist nurses to provide support and instruction for children and their parents. While parents of younger children were often reluctant to accept the increased responsibility for their child's care, children who had received a period of home treatment were enthusiastic about its use and eager for the programme to continue. However, anxiety of patients and parents and medical instability may be of such importance in certain circumstances that treatment is not always given at home, even after former successful periods of home care.