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Abstract: The striking difference between men and women in headache prevalence is suggested to develop in adolescence. Although headaches are common and affect quality of life and daily functioning, the evidence needed to develop effective counselling and preventive approaches is still limited. Using data collected at age 11, 14, 17, and 20 years in the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study (n = 3064 with ≥ 1 questionnaire), we assessed headache prevalence and incidence in girls and boys and explored associations with early life, environmental, lifestyle, health, and psychosocial factors. Associations were analysed longitudinally with generalized linear mixed models and discrete time hazard models. From age 11 to 20 years, the prevalence of headache increased from 9.4% to 19.8% in girls and hardly changed in boys (7.6%-6.1%). Headache commonly co-occurred with other unfavorable health and psychosocial conditions. Eighty-eight percent of the girls and 76% of boys with headache also reported at least one of the following at age 17: sleeping problems, asthma, hay fever, musculoskeletal complaints, fatigue, low mental health, or worrying. Results suggest higher headache prevalence in adolescents following lower educational tracks, in those who skip breakfast ≥2 days per week, and in boys exposed to tobacco smoke in infancy. In girls, sleeping problems and musculoskeletal complaints were associated with higher odds of incident headache and residential greenness with lower odds of incident headache. The high prevalence and strong female predominance of headache, already in adolescence and often with comorbidities, deserve recognition by professionals in (preventive) health care settings and schools., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Objectives: This study aimed to evaluate the effectiveness of systematic assessment of asthma-like symptoms and environmental tobacco smoke (ETS) exposure during regular preventive well-child visits between age 1 and 4 years by well-child professionals., Methods: Sixteen well-child centres in Rotterdam, the Netherlands, were randomised into 8 centres where the brief assessment form regarding asthma-like symptoms and ETS exposure was used and 8 centres that applied usual care. 3596 and 4179 children (born between April 2002 and January 2006) and their parents visited the intervention and control centres, respectively. At child's age 6 years, physician-diagnosed asthma ever, wheezing, fractional exhaled nitric oxide (FeNO), airway resistance (Rint), health-related quality of life (HRQOL) and ETS exposure at home ever were measured. Linear mixed models were applied., Results: No differences in asthma, wheezing, FeNO, Rint or HRQOL measurements between intervention and control group were found using multilevel regression in an intention-to-treat analysis (p>0.05). Children of whom the parents were interviewed by using the brief assessment form at the intervention well-child centres had a decreased risk on ETS exposure at home ever, compared to children who visited the control well-child centres, in an explorative per-protocol analysis (aOR = 0.71, 95% CI:0.59-0.87)., Conclusions: Systematic assessment and counselling of asthma-like symptoms and ETS exposure in early childhood by well-child care professionals using a brief assessment form was not effective in reducing the prevalence of physician-diagnosed asthma ever and wheezing, and did not improve FeNO, Rint or HRQOL at age 6 years. Our results hold some promise for interviewing parents and using information leaflets at well-child centres to reduce ETS exposure at home in preschool children., Trial Registration: Controlled-Trials.com ISRCTN15790308.

Purpose: This study compares HRQOL among subgroups of infants with asthma-like symptoms to a subgroup without such symptoms and examines independent associations between asthma-like symptoms during the first year of life and HRQOL at age 12 months., Methods: Our study sample included 5,000 infants participating in the Generation R study. Their parents completed structured questionnaires to obtain information on asthma-like symptoms, HRQOL, infants', and maternal characteristics. Asthma-like symptoms were defined according to the number of positive answers to 12 items on lower respiratory symptoms. HRQOL was measured using the ITQOL. Higher scores indicated better HRQOL., Results: Infants with asthma-like symptoms had significantly lower HRQOL scores for all ITQOL scales. Among the subgroup with severe symptoms (4% of the infants), relevant deficits in HRQOL were observed for most ITQOL scales, particularly for General Health, Bodily Pain, and Family Activities (effect sizes ≥ 0.8). In multivariate linear models, asthma-like symptoms were independently associated with 6 ITQOL scales. The population attributable risks were especially high for Family Activities, General Health, Parental Emotional, and Parental Time., Conclusions: Asthma-like symptoms during the first year of life are associated with impaired quality of life at age 12 months. At population level, asthma-like symptoms were associated with lower HRQOL, regardless of symptom severity.

Background: Assessing prescription patterns of asthma medication for children is helpful to optimize prescribing by general practitioners (GPs). The aim was to explore prescription patterns in children with physician-diagnosed asthma and its determinants in general practice., Methods: We used the Second Dutch National Survey of General Practice (DNSGP-2) with children aged 0-17 years registered in 87 general practices. All children with at least one asthma prescription were included (n = 2993). Prescription rates and prescription of continuous (≥3 prescriptions/year) versus intermittent asthma medication were calculated. Data, including several GP characteristics, were analysed using multivariate logistic regression accounting for clustering within practices., Results: During one year, 16% of the children with physician-diagnosed asthma (n = 3562) received no asthma medication. Of the 2993 children with asthma receiving asthma medication (on average 2.9 prescriptions/year), 61% received one or two prescriptions, 39% received three or more. Continuous medication with a bronchodilator and/or a corticosteroid was prescribed in 22% of these children. One out of 5 children receiving continuous medication was prescribed a bronchodilator only. In 7.5% of the prescriptions, asthma medications other than bronchodilators or corticosteroids were prescribed. Prescribing asthma medication varied widely between practices, but none of the children and GP determinants had an independent effect on prescribing continuous versus intermittent medication., Conclusion: In general practice, the annual number of asthma prescriptions per child with asthma is relatively low. One in 20 children is prescribed bronchodilators only continuously, indicating room for improvement. Child and GP characteristics cannot be used for targeting educational efforts.

Background: Prevention of childhood asthma is an important public health objective. This study evaluates the effectiveness of early detection of preschool children with asthma symptoms, followed by a counselling intervention at preventive child health centres. Early detection and counselling is expected to reduce the prevalence of asthma symptoms and improve health-related quality of life at age 6 years., Methods/design: This cluster randomised controlled trial was embedded within the Rotterdam population-based prospective cohort study Generation R in which 7893 children (born between April 2002 and January 2006) participated in the postnatal phase. Sixteen child health centres are involved, randomised into 8 intervention and 8 control centres. Since June 2005, an early detection tool has been applied at age 14, 24, 36 and 45 months at the intervention centres. Children who met the intervention criteria received counselling intervention (personal advice to parents to prevent smoke exposure of the child, and/or referral to the general practitioner or asthma nurse). The primary outcome was asthma diagnosis at age 6 years. Secondary outcomes included frequency and severity of asthma symptoms, health-related quality of life, fractional exhaled nitric oxide and airway resistance at age 6 years. Analysis was according to the intention-to-treat principle. Data collection will be completed end 2011., Discussion: This study among preschool children provides insight into the effectiveness of early detection of asthma symptoms followed by a counselling intervention at preventive child health centres., Trial Registration: Current Controlled Trials ISRCTN15790308.

Purpose: The prevalence of asthma symptoms among preschool children is difficult to determine with accuracy because no gold standard is available for diagnosis. The aim of this study was to compare parent-reported wheezing or shortness of breath among infants as assessed by questionnaire and physician-interview., Methods: We studied 1,202 children participating in the Generation R study. Their parents completed a written questionnaire at home when the infant was 12 months old, including items on wheezing or shortness of breath. During the regular free-of-charge youth healthcare visit at age 14 months, the physician interviewed the parents to assess the presence of wheezing or shortness of breath., Results: The prevalence of wheezing or shortness of breath estimated from questionnaire was significantly higher than from physician-interview (36% vs. 20%; P < 0.001): observed agreement 73% (kappa 0.36). Only 41% of questionnaire-reported symptoms were assessed through the physician-interview, while 73% of physician-interviewed symptoms were reported in the questionnaire. Compared with infants in the subgroup with agreement on the presence of wheezing or shortness of breath, the infants in the subgroups without agreement significantly less often received anti-asthma medication and significantly less often had abnormal respiratory sounds or bronchiolitis or croup, and their mothers were significantly less often working. The proportion of infants receiving anti-asthma medication was higher in interview-data compared with questionnaire-data (22.7% vs. 3.9%; P < 0.001)., Conclusions: Questionnaire yielded higher prevalence rates for wheezing or shortness of breath than physician-interview. Physician-reported symptoms are associated with a higher proportion of infants receiving anti-asthma medication. Parent-reported asthma symptoms should be confirmed by pediatricians whenever possible.

Background: Sodium cromoglycate has been recommended as maintenance treatment for childhood asthma for many years. Its use has decreased since 1990, when inhaled corticosteroids became popular, but it is still used in many countries., Objectives: To determine the efficacy of sodium cromoglycate compared to placebo in the prophylactic treatment of children with asthma., Search Strategy: We searched the Cochrane Airways Group Trials Register (October 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), MEDLINE (January 1966 to November 2007), EMBASE (January 1985 to November 2007) and reference lists of articles. We also contacted the pharmaceutical company manufacturing sodium cromoglycate. In 2007 we updated the review., Selection Criteria: All double-blind, placebo-controlled randomised trials, which addressed the effectiveness of inhaled sodium cromoglycate as maintenance therapy, studying children aged 0 up to 18 years with asthma., Data Collection and Analysis: Two authors independently assessed trial quality and extracted data. We pooled study results., Main Results: Of 3500 titles retrieved from the literature, 24 papers reporting on 23 studies could be included in the review. The studies were published between 1970 and 1997 and together included 1026 participants. Most were cross-over studies. Few studies provided sufficient information to judge the concealment of allocation. Four studies provided results for the percentage of symptom-free days. Pooling the results did not reveal a statistically significant difference between sodium cromoglycate and placebo. For the other pooled outcomes, most of the symptom-related outcomes and bronchodilator use showed statistically significant results, but treatment effects were small. Considering the confidence intervals of the outcome measures, a clinically relevant effect of sodium cromoglycate cannot be excluded. The funnel plot showed an under-representation of small studies with negative results, suggesting publication bias., Authors' Conclusions: There is insufficient evidence to be sure about the efficacy of sodium cromoglycate over placebo. Publication bias is likely to have overestimated the beneficial effects of sodium cromoglycate as maintenance therapy in childhood asthma.

Background: In pre-school children a diagnosis of asthma is not easily made and only a minority of wheezing children will develop persistent atopic asthma. According to the general consensus a diagnosis of asthma becomes more certain with increasing age. Therefore the congruence between asthma medication use and doctor-diagnosed asthma is expected to increase with age. The aim of this study is to evaluate the relationship between prescribing of asthma medication and doctor-diagnosed asthma in children age 0-17., Methods: We studied all 74,580 children below 18 years of age, belonging to 95 GP practices within the second Dutch national survey of general practice (DNSGP-2), in which GPs registered all physician-patient contacts during the year 2001. Status on prescribing of asthma medication (at least one prescription for beta2-agonists, inhaled corticosteroids, cromones or montelukast) and doctor-diagnosed asthma (coded according to the International Classification of Primary Care) was determined., Results: In total 7.5% of children received asthma medication and 4.1% had a diagnosis of asthma. Only 49% of all children receiving asthma medication was diagnosed as an asthmatic. Subgroup analyses on age, gender and therapy groups showed that the Positive Predictive Value (PPV) differs significantly between therapy groups only. The likelihood of having doctor-diagnosed asthma increased when a child received combination therapy of short acting beta2-agonists and inhaled corticosteroids (PPV = 0.64) and with the number of prescriptions (3 prescriptions or more, PPV = 0.66). Both prescribing of asthma medication and doctor-diagnosed asthma declined with age but the congruence between the two measures did not increase with age., Conclusion: In this study, less than half of all children receiving asthma medication had a registered diagnosis of asthma. Detailed subgroup analyses show that a diagnosis of asthma was present in at most 66%, even in groups of children treated intensively with asthma medication. Although age strongly influences the chance of being treated, remarkably, the congruence between prescribing of asthma medication and doctor-diagnosed asthma does not increase with age.

It is estimated that viruses play a role in 30% to 80% of asthma exacerbations. Thus, virus vaccination in patients with asthma could play an important role in preventing asthma exacerbations and other complications. Influenza is the only agent for which a routine vaccine is currently available. This article discusses whether influenza vaccination in patients with asthma, based on the available evidence, is justified. Cost-effectiveness of (influenza) vaccination for patients with asthma is questionable. For the other major viruses involved, the present state of affairs is described. Although progress is being made, a vaccine may be available in the near future only for respiratory syncytial virus (RSV). Meanwhile, clinicians and patients should aim for an optimal treatment with the currently available asthma medication.

Background: The risks of influenza vaccination in asthmatic children are still being discussed. Especially, the risk that influenza vaccination may exacerbate asthma is an issue in this debate., Methods: We conducted a randomised double-blind placebo-controlled trial in 696 children 6-18 years of age with asthma recruited in general practice during two influenza seasons, 1999-2000 and 2000-2001. Children participated for only one season. During the first week after vaccination, participants recorded local, influenza like and asthma symptoms as well as use of medication, health care use and absenteeism., Results: Except for cough during the day in the first season, favouring placebo, there were no differences indicating that vaccination exacerbates asthma., Conclusions: Influenza vaccination does not seem to exacerbate asthma.

There is little evidence that influenza vaccination reduces asthma exacerbations. We determined whether influenza vaccination is more effective than placebo in 6-18-year-old children with asthma. We performed a randomized, double-blind, placebo-controlled trial. Parenteral vaccination with inactivated influenza vaccine or placebo took place approximately November 1, and children were followed until April 1 of the next year. Airway symptoms were reported in a diary. When symptom scores reached a predefined level, a pharyngeal swab was taken. Primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Three hundred forty-nine children were assigned placebo, and 347 were assigned vaccine. Pharyngeal swabs positive for influenza were related to 42 asthma exacerbations, 24 in the vaccine group and 18 in the placebo group, a difference of 33% favoring placebo (31% after adjustment for confounders; 95% confidence interval, -34% to 161%). Influenza-related asthma exacerbations were of similar severity in both groups; they lasted 3.1 days shorter in the vaccine group (95% confidence interval, -6.2 to 0.002 days, p = 0.06). We conclude that influenza vaccination did not result in a significant reduction of the number, severity, or duration of asthma exacerbations caused by influenza. Additional studies are warranted to justify routine influenza vaccination of children with asthma.

Background: Allergic rhinitis (AR) and asthma are both inflammatory diseases and are often associated. Relationships between fractional exhaled nitric oxide (FeNO) and asthma, atopy, and quality of life have been shown. Aims: This study aimed to determine whether FeNO in children with AR (n=158) or combined AR and asthma (n=93) was associated with clinical symptoms, house dust mite (HDM)-specific lgE, and rhinitis-specific quality of life, both cross-sectionally and longitudinally. Methods: Children with AR aged 6-18 years (n=251) in primary care were assessed for FeNO, nasal symptom scores, asthma symptom scores, quality of life, and HDM-specific IgE at baseline and 2 years later. Results: We found similarly elevated FeNO in children with only AR and in those with combined AR and asthma. No correlations were found between FeNO and nasal or asthma symptoms and rhinitis-related quality of life. Longitudinal correlations were strongest for HDM-specific IgE (r=0.91, p<0.0001). Conclusions: FeNO was similar in a selected group of children with AR with and without asthma in primary care and was unrelated to symptoms or quality of life in both groups. FeNO is unlikely to be a useful biomarker of the clinical severity of upper or lower airway disease in primary care. [ABSTRACT FROM AUTHOR]

Background: Prevention of childhood asthma is an important public health objective. This study evaluates the effectiveness of early detection of preschool children with asthma symptoms, followed by a counselling intervention at preventive child health centres. Early detection and counselling is expected to reduce the prevalence of asthma symptoms and improve health-related quality of life at age 6 years. Methods/design: This cluster randomised controlled trial was embedded within the Rotterdam population-based prospective cohort study Generation R in which 7893 children (born between April 2002 and January 2006) participated in the postnatal phase. Sixteen child health centres are involved, randomised into 8 intervention and 8 control centres. Since June 2005, an early detection tool has been applied at age 14, 24, 36 and 45 months at the intervention centres. Children who met the intervention criteria received counselling intervention (personal advice to parents to prevent smoke exposure of the child, and/or referral to the general practitioner or asthma nurse). The primary outcome was asthma diagnosis at age 6 years. Secondary outcomes included frequency and severity of asthma symptoms, health-related quality of life, fractional exhaled nitric oxide and airway resistance at age 6 years. Analysis was according to the intention-to-treat principle. Data collection will be completed end 2011. Discussion: This study among preschool children provides insight into the effectiveness of early detection of asthma symptoms followed by a counselling intervention at preventive child health centres. [ABSTRACT FROM AUTHOR]

Vaccinations have been incriminated in the increase of atopic disorders. Especially the measles-mumps-rubella (MMR) vaccination is often refused by people having a notion that these infectious diseases are beneficial for a healthy development of a child’s immune system. This practice endangers herd immunity and is the cause of repeated outbreaks. As the clinical course of infections and also its possible impact on the development of atopy may be different in vaccinated and unvaccinated individuals, we explored in vaccinated and unvaccinated children associations of MMR infection with atopic disorders. Using data from a previously conducted study on the relationship between the diphtheria-tetanus-pertussis-(inactivated) poliomyelitis vaccination in the first year of life and atopic disorders, the study population of 1872 8–12-yr-old was divided as children MMR-unvaccinated and children MMR-vaccinated in the first year of life. Within each group the association between MMR infections and atopic disorders (both as reported by the parents) was assessed. We found a statistically significant positive association between measles infection and ‘any atopic disorder’ [adjusted odds ratio, OR (95% confidence interval, CI): 1.77 (1.20–2.61)] in the MMR-vaccinated group, mainly because of the relationship with eczema. For rubella there was a negative association with eczema and food allergy in the unvaccinated group: adjusted OR (95% CI): 0.57 (0.38–0.85) and 0.23 (0.07–0.76), respectively. All other associations were not statistically significant. We found a positive relationship between measles infection and any atopy in a group of MMR-vaccinated children and a negative association between rubella infection and eczema and food allergy in unvaccinated children. However, we cannot conclude that these relationships are causal. The negative association with rubella may be an artefact. This study shows no evidence for any protective effects from MMR diseases for the development of atopy and therefore supports conclusions found elsewhere that childhood vaccinations do not cause atopy. [ABSTRACT FROM AUTHOR]

Pertussis infection has been suspected to be a potential causal factor in the development of atopic disease because of the effect of pertussis immunization on specific IgE antibodies. Although several studies found a positive association between pertussis infection and atopic disorders, this relationship has not yet been studied in a population stratified by vaccination status. To assess the association between pertussis infection and atopic disorders in pertussis-unvaccinated children and in pertussis-vaccinated children. Using data from a previously conducted study on the relationship between the diphtheria-tetanus-pertussis-(inactivated) poliomyelitis vaccination in the first year of life and atopic disorders, the study population of 1872 8–12 yr old was divided into children pertussis-unvaccinated and children pertussis-vaccinated in the first year of life. Within each group, the association between pertussis infection and atopic disorders (both as reported by the parents) was assessed. In the unvaccinated group, there were no significant associations between pertussis infection and atopic disorders. In the vaccinated group, all associations between pertussis infection and atopic disorders were positive, the associations with asthma [odds ratio (OR) = 2.24, 95% confidence interval (CI95%): 1.36–3.70], hay fever (OR = 2.35, CI95%: 1.46–3.77) and food allergy (OR = 2.68, CI95%: 1.48–4.85) being significant. There was a positive association between pertussis infection and atopic disorders in the pertussis vaccinated group only. From the present study, it cannot be concluded whether this association is causal or due to reverse causation. [ABSTRACT FROM AUTHOR]

Bernsen RMD, de Jongste JC, van der Wouden JC. Birth order and sibship size as independent risk factors for asthma, allergy, and eczema. Pediatr Allergy Immunol 2003: 14: 464–469. © 2003 Blackwell Munksgaard This study was carried out to disentangle the independent relations of birth order and sibship size with the presence of asthma, allergy and eczema. In a retrospective study, 700 families in the Netherlands were selected with index children born in 1988–90. Data were extracted from reports of health examinations at the age of 6 years of these children and their siblings. Birth order, and not sibship size, appeared to be a strong risk factor for allergy (excluding eczema). Children with higher birth order had a lower risk of allergy compared with first-borns (adjusted odds ratios: 0.43, 0.26 and 0.05 for second-, third- and fourth- or higher borns, respectively; p < 0.0001). Allergy including eczema also had a significant relation with birth order (p = 0.01). For asthma there appeared no clear relation with birth order. For asthma a non-significant relationship with sibship size (adjusted for birth order) was found (p = 0.06): first-born children in small sibships were more at risk than those in larger sibships. For allergy and eczema no such trend was observed. In conclusion, birth order is inversely related to the risk of allergy, independent of the size of the sibship. [ABSTRACT FROM AUTHOR]

Background: Asthma and other chronic airway diseases can be effectively treated by inhaler therapy. This study evaluates the knowledge among Dutch children and their parents regarding asthma inhaler therapy and appropriateness of its use. Findings: Five general practices selected all children aged 0 to 12 years on asthma inhalation medication. Children demonstrated inhaler use and were interviewed with their parents. Conclusion: Dutch children make essential mistakes related to inhaler use that are easy to avoid. We recommend a better explanation and demonstration of the technique, and recommend involvement of the parents during instruction. [ABSTRACT FROM AUTHOR]