Wim M. C. van Aalderen

Follow−up of asthma from childhood to adulthood: Influence of potential childhood risk factors on the outcome of pulmonary function and bronchial responsiveness in adulthood

The outcome of asthma in 406 children, aged 8 to 12 years, was studied. Follow-up in adulthood was 86%, with a mean age of 24.7 years and a mean interval of follow-up of 14.8 years. The predictive value of gender and various childhood variables on the adult level of pulmonary function (forced expiratory volume in 1 second [FEV1]) and bronchial responsiveness in adulthood was assessed. An increase in mean percent predicted FEV1 from childhood to adulthood was found, both in subjects with (76%) and without (24%) current respiratory symptoms. The only childhood variable predictive of adult level of FEV1 was the level of percent predicted FEV1 (p < 0.01). The proportion of subjects with a histamine provocative concentration causing a 10% decrease in FEV1 less than or equal to 16 mg/ml decreased significantly in adulthood. The degree of bronchial responsiveness had increased slightly in adults with symptoms (p = 0.87), whereas it had decreased significantly in subjects without symptoms (p < 0.01). Female subjects were significantly more responsive in adulthood than male subjects (p = 0.047). The childhood degree of bronchial responsiveness significantly predicted the presence of bronchial responsiveness in adulthood (p = 0.02). We conclude that childhood percent predicted FEV1 is relevant to predict the outcome of the adult pulmonary function level, whereas female gender and the childhood degree of bronchial responsiveness are important for the prediction of adult degree of bronchial responsiveness among children with asthma.

Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens.

BACKGROUND Exposure to cat and dog allergens is very common in the Western World and is a serious cause of asthma in sensitized subjects. OBJECTIVE We sought to study the clinical effects of air cleaners in living rooms and bedrooms of asthmatic children sensitized to cat or dog allergens. METHODS Twenty asthmatic children sensitized to pet allergens (cat/dog) and with an animal at home participated in a double-blind, placebo-controlled, cross-over study in which the effects of air cleaners placed in the living room and bedroom for 3 months were compared with the effects of sham air cleaners. Before and after each study period, lung function, airway hyperresponsiveness (adenosine monophosphate), and peak flow variation were recorded. Cat and dog allergen levels were assessed in the filters of the air cleaners. RESULTS After a 3-month intervention with active air cleaners, airway hyperresponsiveness decreased significantly, showing a 1.2 doubling dose increase of PC(20 )adenosine (P =.003). Peak flow amplitude also decreased (P =. 045). Substantial amounts of airborne cat and dog allergen were captured by the air cleaners in living rooms and bedrooms as well. Allergen levels in floor dust were not changed. CONCLUSION In young asthmatic patients sensitized and exposed to pets in the home, application of air cleaners in living rooms and bedrooms was accompanied by a significant improvement in airway hyperresponsiveness and a decrease in peak flow amplitude.

Local Interferon‐γ Levels during Respiratory Syncytial Virus Lower Respiratory Tract Infection Are Associated with Disease Severity

To investigate the role of cell-mediated immunity during respiratory syncytial virus (RSV) infection, interferon (IFN)-gamma and interleukin (IL)-10 levels in nasopharyngeal secretions were measured in infants with lower respiratory tract infection (LRTI) caused by RSV. A novel technique was used to measure in vivo cytokine levels in nasopharyngeal aspirates (NPAs). Cytokine levels in the NPAs of 17 mechanically ventilated infants and 43 nonventilated hospitalized infants were compared. As expected, mechanically ventilated infants were significantly younger than nonventilated infants (7 vs. 14 weeks). IFN-gamma levels were above the limit of detection in the NPAs of 3 (18%) mechanically ventilated infants and in the NPAs of 26 (60%) nonventilated infants. IL-10 levels in the NPAs of mechanically ventilated and nonventilated infants were comparable. It is hypothesized that maturation-related mechanisms have a key role in the development of RSV LRTI that results in mechanical ventilation.

Positive Pressure Ventilation with the Open Lung Concept Optimizes Gas Exchange and Reduces Ventilator-Induced Lung Injury in Newborn Piglets

Previous studies demonstrated that high-frequency oscillatory ventilation using the open lung concept (OLC) resulted in superior gas exchange and a reduction in ventilator-induced lung injury (VILI). We hypothesized that these beneficial effects could also be achieved by applying the OLC during positive pressure ventilation. After repeated whole-lung-lavage, newborn piglets were assigned to either OLC positive pressure ventilation (PPVOLC), OLC high-frequency oscillatory ventilation (HFOVOLC), or conventional positive pressure ventilation (PPVCON) and ventilated for 5 h. In both OLC groups, collapsed alveoli were actively recruited and thereafter stabilized using the lowest possible airway pressures. In the PPVCON group, ventilator settings were adjusted to prevent critical hypoxia. Airway pressure, blood gas analysis, pressure-volume curve, and alveolar protein infiltration was recorded. A lung injury score was used for histologic comparison. Mean airway pressures were comparable in the three ventilation groups over time (1.2-1.5 kPa). Arterial oxygenation increased to mean values above 60 kPa in both OLC groups compared with 10 kPa in the PPVCON group (p < 0.001). Maximal lung compliance was superior in both OLC groups (PPVOLC: 91 ± 23; HFOVOLC: 90 ± 31 mL/kPa/kg, p < 0.01) compared with the PPVCON group (39 ± 14 mL/kPa/kg). Alveolar protein infiltration was significantly reduced in the PPVOLC group (0.33 ± 0.10 mg/mL, p < 0.01) and the HFOVOLC group (0.40 ± 0.13 mg/mL, p < 0.01) compared with the PPVCON group (0.70 ± 0.15 mg/mL). Lung injury scores were significantly higher in the PPVCON group (33.5 ± 9.5, p < 0.01) compared with both OLC groups (PPVOLC: 10.5 ± 2.6; HFOVOLC: 11 ± 2.2). There were no differences between the two OLC groups. We conclude that, in surfactant-depleted newborn piglets, application of the OLC during PPV is feasible and results in superior gas exchange and a reduction in VILI compared with conventional PPV. These beneficial effects are comparable to HFOV.

Delayed initiation of breast development in girls with higher prenatal dioxin exposure; a longitudinal cohort study

OBJECTIVES While many studies have assessed the health impacts of PCDD/Fs and PCBs on animals and humans, long-term consequences for especially adolescents, have not (yet) been well documented. This is certainly also true for the effects of PBDE exposure. As part of a longitudinal cohort study, now well into its second decade, effects of perinatal and current PCDD/F exposure, as well as current dl-PCB and PBDE exposures, on puberty, were assessed. STUDY DESIGN Prenatal, lactational and current PCDD/F, dl-PCB and PBDE concentrations were determined using GC-MS. Pubertal development and growth were assessed by means of physical examination and the Tanner scale. 33 Children (born between 1986 and 1991) consented to the current follow-up study. Outcomes were evaluated using linear regression or the non parametric Spearmans correlation coefficient. RESULTS A delay in initiation of breast development was found in girls (n = 18) with higher prenatal (p = 0.023) and lactational PCDD/F exposure (p = 0.048). The males revealed a negative trend with age at first ejaculation. For other endpoints on puberty and growth (pubic hair, axillary hair, genital stage, length, BMI, testicular volume, menarche) no significant relation was found with any of the measured compounds. DISCUSSION AND CONCLUSION A relation between prenatal PCDD/F exposure and later initiation of breast development was seen. A Belgian study found a delay in breast development with higher current serum concentrations of dioxin-like compounds. The initiation of puberty is a complex process and it is yet not clear how dioxin-like compounds precisely affect this process prenatally. Further follow-up into adulthood is warranted, in order to detect the possibility of developing malignancies and fertility problems.

Thyroid hormone metabolism and environmental chemical exposure

BackgroundPolychlorinated dioxins and –furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism.Influences of brominated flame retardants, PCDD/F’s and dioxin like-PCBs (dl-PCB’s) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3’, 5,5’tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3’,5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort.MethodsVena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB and PBDE levels.ResultsThe current levels of T3 were positively correlated to BDE-99. A positive trend with FT4 and BDE-99 was also seen, while a positive correlation with T3 and dl-PCB was also seen. No correlation with TBG was seen for any of the contaminants. Neither the prenatal nor the current PCDD/F levels showed a relationship with the thyroid parameters in this relatively small group.ConclusionOnce again the thyroid hormone metabolism (an increase in T3) seems to have been influenced by current background levels of common environmental contaminants: dl-PCBs and BDE-99. T3 is a product of target organs and abnormalities might indicate effects on hormone transporters and could cause pathology. While the influence on T3 levels may have been compensated, because the adolescents functioned normal at the time of the study period, it is questionable if this compensation is enough for all organs depending on thyroid hormones.

Probiotics and prebiotics in atopic dermatitis: review of the theoretical background and clinical evidence

van der Aa LB, Heymans HSA, van Aalderen WMC, Sprikkelman AB. Probiotics and prebiotics in atopic dermatitis: review of the theoretical background and clinical evidence.
Pediatr Allergy Immunol 2010: 21: e355–e367.
© 2009 John Wiley & Sons A/S

Impact of Wheezing After Respiratory Syncytial Virus Infection on Health-Related Quality of Life

Background: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is often followed by recurrent wheezing episodes during childhood. The effect of postbronchiolitis wheezing on the well-being of the child is not known. This study aimed to determine the impact of RSV LRTI hospitalization before age 13 months on health-related quality of life (HRQoL) at age 3 years. Methods: HRQoL was measured in a previously described cohort of children with a history of RSV infection and compared with control term children from the open population. HRQoL was determined during the winter season in index and control children. We used a validated questionnaire, which measures the health status of children in 13 domains weighted by the impact of the health status problems on well-being. The lung domain was the focus of this study. In addition daily respiratory symptoms of the index children were recorded prospectively up to age 3 years and correlated with HRQoL scores. Results: HRQoL was lower in index children (n = 128) than in control children (n = 340) for the lung, gastrointestinal tract and sleeping domains. HRQoL scores for social and developmental domains were similar for index and control children. As anticipated the largest difference between index and control children was found in the lung domain (77.6 ± 2.2 vs. 93.9 ± 0.8, P < 0.01). HRQoL in the lung domain was lower during the winter than during the summer season (77.6 ± 2.2 vs. 85.6 ± 1.9, P < 0.01), which was explained by increased airway morbidity during the winter season. We found a high correlation between lung HRQoL scores and total number of wheezing days during follow-up. Conclusions: Postbronchiolitis wheezing has broad implications for long-term well-being of children. Decreased HRQoL was attributed to postbronchiolitis wheezing, but not to preexistent risk factors, such as premature birth. This study underscores the importance of developing new strategies to prevent and treat long term airway morbidity after RSV LRTI.

The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts

U-BIOPRED aims to characterise paediatric and adult severe asthma using conventional and innovative systems biology approaches. A total of 99 school-age children with severe asthma and 81 preschoolers with severe wheeze were compared with 49 school-age children with mild/moderate asthma and 53 preschoolers with mild/moderate wheeze in a cross-sectional study. Despite high-dose treatment, the severe cohorts had more severe exacerbations compared with the mild/moderate ones (annual medians: school-aged 3.0 versus 1.1, preschool 3.9 versus 1.8; p<0.001). Exhaled tobacco exposure was common in the severe wheeze cohort. Almost all participants in each cohort were atopic and had a normal body mass index. Asthma-related quality of life, as assessed by the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Paediatric Asthma Caregivers Quality of Life Questionnaire (PACQLQ), was worse in the severe cohorts (mean±se school-age PAQLQ: 4.77±0.15 versus 5.80±0.19; preschool PACQLQ: 4.27±0.18 versus 6.04±0.18; both p≤0.001); however, mild/moderate cohorts also had significant morbidity. Impaired quality of life was associated with poor control and airway obstruction. Otherwise, the severe and mild/moderate cohorts were clinically very similar. Children with severe preschool wheeze or severe asthma are usually atopic and have impaired quality of life that is associated with poor control and airflow limitation: a very different phenotype from adult severe asthma. In-depth phenotyping of these children, integrating clinical data with high-dimensional biomarkers, may help to improve and tailor their clinical management. Children with severe preschool wheeze or severe asthma are usually atopic and have impaired quality of life http://ow.ly/RrrGE

Inpatient Treatment of Children and Adolescents With Severe Obesity in the Netherlands: A Randomized Clinical Trial

IMPORTANCE Severe childhood obesity has become a major health problem, and effective, evidence-based interventions are needed. The relative effectiveness of inpatient compared with ambulatory treatment remains unknown. OBJECTIVE To determine whether an inpatient treatment program is more effective than an ambulatory treatment program at achieving a sustained weight loss in children and adolescents with severe obesity. DESIGN, SETTING, AND PARTICIPANTS We conducted a randomized clinical trial with a 2-year follow-up at a tertiary referral center for pediatric obesity in the Netherlands. We recruited 90 children and adolescents aged 8 to 18 years with severe obesity (body mass index [BMI] z score, ≥3.0 or >2.3 with obesity-related health problems). INTERVENTIONS Patients were randomly assigned to an inpatient (6 months of hospitalization on working days) or an ambulatory (12 days of hospital visits at increasing intervals during a 6-month period) treatment program. Both treatment programs involved an intensive, family-based, lifestyle intervention, including exercise, nutritional education, and behavior modification for the patients and their caregiver(s). MAIN OUTCOMES AND MEASURES Change in BMI z score. Secondary outcomes included fasting insulin, fasting plasma glucose, 2-hour plasma glucose, and lipid levels, insulin sensitivity, liver function test results, waist circumference, blood pressure, body composition, and aerobic fitness (peak oxygen consumption, Vo₂). Outcomes were analyzed by intention to treat. RESULTS Immediately after treatment, reductions in the BMI z score were significantly larger for the inpatient than the ambulatory groups (mean [SE] difference, -0.26 [0.12; 95% CI, -0.59 to -0.01]; P = .04). Change from baseline for the BMI z score in the inpatient group was -18.0% (P = .001) immediately after treatment, -8.5% (P = .008) at 18 months, and -6.3% (P = .38) at 30 months; in the ambulatory group, changes from baseline were -10.5% (P = .001), -6.2% (P = .39), and -1.5% (P > .99), respectively. The favorable outcomes of the inpatient group could not be sustained at 12 and 24 months after treatment. In addition, significant differences in favor of the inpatient group immediately after treatment were found for levels of fasting insulin (-6.37 IU/L; P = .02), total cholesterol (-19.51 mg/dL; P = .01), low-density lipoprotein cholesterol (-13.48 mg/dL; P = .03), and triglycerides (-25.39 mg/dL; P = .01), and insulin sensitivity (-1.37; P = .02), fat mass (-3.31%; P = .03), and peak Vo₂ (378.2 mL/min; P = .01). CONCLUSIONS AND RELEVANCE In severely obese children and adolescents, inpatient treatment was superior to ambulatory treatment immediately after treatment, but effects were not sustained at long-term follow-up. These findings stress the need to further study maintenance strategies for sustainable weight loss. TRIAL REGISTRATION trialregister.nl Identifier: NTR1172.