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Abstract: Objectives: To study topical corticosteroid use in Dutch asthmatic children using pharmacy dispensing data and to assess whether Dutch physicians prescribe topical corticosteroids in this population according to clinical guidelines. Methods: Medication histories of children using asthma medication were extracted from the pharmacy dispensing system in 100 Dutch community pharmacies. The incidence rate and the potency of topical corticosteroid prescriptions per age were assessed. The topical corticosteroid incidence rates of the different age groups were compared using the Pearson chi‐square test. Generalized linear models were used to study the prescription behavior of general practitioners and atopic dermatitis‐related specialists regarding different classes of topical corticosteroids. Results: Thirty percent of the infants received a topical corticosteroid prescription, compared with 15%‐18% of the children aged 4 and older. Similarly, the mean number of topical corticosteroid prescriptions in infants was 2.2 per year, compared with 1.6‐1.9 in children aged 4 and older. In concordance with the clinical guidelines, we observed that atopic dermatitis‐related specialists more often prescribed first prescriptions of potent and very potent topical corticosteroids than general practitioners (relative risk = 2.55, 95% confidence interval = 1.79‐3.63). Statistically significant differences (P < .01) were found between potencies of prescribed topical corticosteroids. Conclusion: Younger children receive more topical corticosteroid prescriptions than children aged 4 and older, and there is a statistically significantly higher prescription rate of topical corticosteroid for infants. Sometimes general practitioners do not follow guidelines and prescribe more‐potent topical corticosteroids without a prior prescription of the same potency by a specialist. [ABSTRACT FROM AUTHOR]

Objective: Severe asthma exacerbations are often treated with short courses of oral corticosteroids (OCS). This study assessed the incidence of OCS being prescribed in asthmatic children of various age groups and calculated their chances of receiving subsequent OCS prescriptions.Methods: Longitudinal Dutch community pharmacy data of 2272 children who were regular users of asthma medication was analyzed retrospectively. Incidence rates for first, second and third prescriptions of OCS were calculated, stratified by age and sex. Probabilities of receiving first, second or third OCS prescriptions were assessed with Kaplan–Meier analysis.Results: Incidence rates for first OCS prescriptions were 4.5 for the 1styear of life per 100 person-years (100PY); 3.9 for the 2nd; 4.6 for the 3rd; 4.2 for the 4th, and 4.7 for the 5thyear of life per 100PY. This was relatively high compared to incidence rates for children between the ages of 6 and 11 (ranging between 2.2 per 100PY (age 9) and 3.7(age 11)). Incidence rates for second and third OCS prescriptions were very high: 78.2(95%CI: 45.0–123.7) and 241.2(95%CI: 81.2–583.4) per 100PY for infants, respectively. The chances of receiving a first OCS prescription was higher in males (Pvalue < 0.01).Conclusions: In the Netherlands, the incidence of OCS being prescribed to children being treated with asthma medication in early childhood is relatively high for first OCS prescriptions and extremely high for second and third OCS prescriptions compared to other ages. Furthermore, there is a high probability of receiving a further OCS prescription shortly after an OCS prescription. [ABSTRACT FROM PUBLISHER]

Background: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children with certain combinations of co-morbid allergic conditions.Methods: For this cross-sectional study, 703 children (ages 4 to 12 years) from the PACMAN cohort study were selected. All of the children were regular users of asthma medication. The study population was divided into nine subgroups according to parental-reported allergies of the child (hay fever, eczema, food allergy or combinations of these). In order to assess whether these subgroups differed clinically, the groups were compared for child characteristics (age, gender, family history of asthma), asthma exacerbations in the past year (oral corticosteroids (OCS) use; asthma-related emergency department (ED) visits), asthma control, fractional exhaled nitric oxide level (FeNO), and antihistaminic usage.Results: In our study, 79.0% of the parents reported that their child suffered from at least one atopic condition (hay fever, food allergy and eczema), and one quarter of the parents (25.6%) reported that their child suffered from all three atopic conditions. Having more than one atopic condition was associated with an increased risk of OCS use (OR = 3.3, 95% CI = 1.6 - 6.6), ED visits (OR = 2.3, 95% CI = 1.2 - 4.6) in the past year and inadequate short term asthma control (OR = 1.9, 95% CI = 1.3 - 2.8).Conclusions: Children who use asthma medication often also have other allergic conditions. Parental reported allergies were associated with a higher risk of more severe asthma (more asthma complaints and more asthma exacerbations). [ABSTRACT FROM AUTHOR]

Background: The diagnosis of childhood asthma covers a broad spectrum of pathological mechanisms that can lead to similarly presenting clinical symptoms, but may nonetheless require different treatment approaches. Distinct underlying inflammatory patterns are thought to influence responsiveness to standard asthma medication. Methods/design: The purpose of the PACMAN2 study is to identify inflammatory phenotypes that can discriminate uncontrolled childhood asthma from controlled childhood asthma by measures in peripheral blood and exhaled air. PACMAN2 is a nested, case-control follow-up study to the ongoing pharmacy-based "Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects" (PACMAN) study. The original PACMAN cohort consists of children aged 4-12 years with reported use of asthma medication. The PACMAN2 study will be conducted within the larger PACMAN cohort, and will focus on detailed phenotyping of a subset of the PACMAN children. The selected participants will be invited to a follow-up visit in a clinical setting at least six months after their baseline visit based on their adherence to usage of inhaled corticosteroids, their asthma symptoms in the past year, and their age (= 8 years). During the follow-up visit, current and long-term asthma symptoms, medication use, environmental factors, medication adherence and levels of exhaled nitric oxide will be reassessed. The following measures will also be examined: pulmonary function, exhaled volatile organic compounds, as well as inflammatory markers in peripheral blood and blood plasma. Comparative analysis and cluster-analyses will be used to identify markers that differentiate children with uncontrolled asthma despite their use of inhaled corticosteroids (ICS) (cases) from children whose asthma is controlled by the use of ICS (controls). Discussion: Asthmatic children with distinct inflammatory phenotypes may respond differently to antiinflammatory therapy. Therefore, by identifying inflammatory phenotypes in children with the PACMAN2 study, we may greatly impact future personalised treatment strategies, uncover new leads for therapeutic targets and improve the design of future clinical studies in the assessment of the efficacy of novel therapeutics. [ABSTRACT FROM AUTHOR]

Data on baseline characteristics of children with asthma to predict individual treatment responses are lacking. We aimed to set up a data-collection system which can easily fill this gap in clinical practice. A web-based application was developed, named 'Portal for children with respiratory and allergic symptoms', hereafter called Electronic Portal (EP). It contains health- and disease-related questionnaires on respiratory- and allergic diseases. All patients, 1-18 years of age, with respiratory- and/or allergic complaints are invited to enter the EP before their first visit. By using the EP large amounts of data, gathered during routine patient care can be used for research purposes. This may help to further investigate the different treatment related asthma phenotypes and will be helpful to monitor risk factors for other atopic diseases and respiratory infections. [ABSTRACT FROM AUTHOR]

To cite this article: Vijverberg SJH, Koster ES, Koenderman L, Arets HGM, van der Ent CK, Postma DS, Koppelman GH, Raaijmakers JAM, Maitland-van der Zee A-H. Exhaled NO is a poor marker of asthma control in children with a reported use of asthma medication: a pharmacy-based study. Pediatr Allergy Immunol 2012: 23: 529-536. Abstract Background: A high fraction of nitric oxide in exhaled breath (FeNO) has been suggested to be a marker of ongoing airway inflammation and poorly controlled disease in asthma. The usefulness of FeNO to monitor asthma control is still debated today. Aim: To assess the validity of FeNO as a marker of asthma control in children with reported use of asthma medication. Methods: Fraction of nitric oxide in exhaled breath was measured in 601 children (aged 4-12 yr) with reported use of asthma medication in the past 6 months and in 63 healthy non-asthmatic children (aged 5-12). Asthma control was assessed by the Asthma Control Questionnaire (ACQ). A receiver-operator characteristics (ROC) curve was generated to assess the accuracy of FeNO as a marker for asthma control. Logistic regression analysis was used to study whether clinical, healthcare, medication, and environmental factors are associated with high FeNO levels (>25 ppb). Results: Fraction of nitric oxide in exhaled breath had a poor accuracy to discriminate well-controlled from not well-controlled asthma [area under the ROC curve: 0.56 (95% CI: 0.52-0.61, p = 0.008)]. In addition, high FeNO (>25 ppb) was associated with lower medication adherence rates (OR: 0.4; 95% CI 0.3-0.6), fewer antibiotic courses in the past year (OR: 0.6; 95% CI: 0.4-0.9), fewer leukotriene antagonists use in the past year (OR: 0.4; 95% CI: 0.2-0.9), and fewer visits to a (pulmonary) pediatrician (OR: 0.6; 95% CI: 0.4-0.9). Children living in a non-urban environment had more often high FeNO levels (OR: 1.7; 95% CI: 1.1-2.6). Conclusion: High FeNO is a poor marker of asthma control in children with reported use of asthma medication. Various other factors, including medication adherence and medication use, are associated with increased FeNO levels. [ABSTRACT FROM AUTHOR]

To cite this article: Koster ES, Raaijmakers JAM, Vijverberg SJH, Koenderman L, Postma DS, Koppelman GH, van der Ent CK, Maitland-van der Zee A-H. Limited agreement between current and long-term asthma control in children: the PACMAN cohort study. Pediatr Allergy Immunol 2011: 22: 776-783 Abstract Background: Several studies have shown that predictors of asthma treatment outcomes differ depending on the definition of the outcome chosen. This provides evidence that different outcomes studied may reflect distinct aspects of asthma control. To assess predictors of asthma control, we need firm outcome phenotypes. The aim of this study was to investigate the association between measurements of current and long-term asthma control. Methods: We included 527 children using inhaled corticosteroids participating in the Pharmacogenetics of Asthma medication in Children: Medication with ANti-inflammatory effects cohort. Current asthma control (previous week) was defined using the Asthma Control Questionnaire. Long-term asthma control was based on Global Initiative for Asthma guidelines. Not well-controlled asthma in a season was defined as ≥3 of the following items present in a season: (i) day-time or (ii) night-time symptoms, (iii) limitations in activities, and (iv) rescue medication use. Asthma control during (i) the previous season and (ii) the year preceding the pharmacy visit was used as long-term asthma control definitions. Current and long-term asthma control were compared to investigate agreement. Results: Long-term uncontrolled asthma rates were highest in autumn and winter (50%) and lowest in summer (32%) (p < 0.05). Overall agreement between current and long-term asthma control was limited (66% for previous season and 68% for previous year). Conclusion: Congruence between current and long-term asthma control was limited. Furthermore, we showed significant seasonal differences. It is therefore important to calculate asthma control over a longer period of time, instead of using current asthma control as indicator. [ABSTRACT FROM AUTHOR]

Introduction. Seasonal variation in asthma has been widely recognized. The aim of this study was to describe seasonal patterns of asthma symptoms and asthma medication use in a cohort of pediatric asthma medication users and to study determinants of seasonal childhood asthma. Methods. For this study, 602 children participating in the Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects) cohort were included. Parents were asked about their child's respiratory symptoms and quick-reliever medication use over the past year. Logistic regression analysis was used to study determinants of seasonality in asthma control (the level of disease control based on symptoms, limitations in activities, and rescue medication use). Results. There was a decline in asthma symptoms and asthma medication use during the summer period and a peak occurred from autumn to spring. The prevalence of wheeze ranged from 32% in summer to 56% in autumn. The prevalence of respiratory symptoms and medication use was significantly lower during summer (p < .0001). Oral steroids and antibiotics use and strong parental necessity beliefs were associated with uncontrolled asthma, regardless of seasonality. Allergic rhinitis was associated with an increased risk of uncontrolled asthma during spring [odds ratio (OR): 1.9; 95% confidence interval (CI): 1.3-2.8] and summer (OR: 1.9; 95% CI: 1.2-3.0). Eczema was associated with a higher risk of uncontrolled asthma during autumn (OR: 1.5; 95% CI: 1.0-2.2) and winter (OR: 1.3; 95% CI: 1.0-1.9). Conclusion. We showed seasonal patterns in asthma symptoms and medication use. Associations were shown between allergic rhinitis and asthma control during spring/summer and eczema was associated with uncontrolled asthma during autumn/winter. Seasonality in asthma morbidity and health-care use is most likely associated with atopic constitution and viral infections, which are common during fall, winter, and spring. [ABSTRACT FROM AUTHOR]

Background. Little is known about factors that determine prescribing of asthma therapy in infancy.Objective. To describe factors related to the initiation and refill of asthma therapy in infancy.Methods. This study included 1202 infants who participated in a prospective birth cohort study: the ‘Wheezing Illnesses Study Leidsche Rijn (WHISTLER)’. Outcomes, asthma therapy initiation and refill, were assessed using prescription data. Logistic regression analysis was used to study determinants of therapy initiation in two groups: total population and infants with a respiratory system symptom diagnosis. In addition, determinants of refilling prescriptions were studied in infants who started therapy in their first year of life.Results. Fifteen per cent of all infants started asthma therapy in their first year of life. Respiratory symptoms were an important driver of both initiation and refill of prescriptions. In the total population, therapy initiation was associated with male gender [odds ratio (OR): 1.6, 95% confidence interval (CI): 1.1–2.6], day-care attendance (OR: 1.6, 95% CI: 1.0–2.5) and breastfeeding (OR: 0.6, 95% CI: 0.3–1.0). For infants with a respiratory system symptom diagnosis, day-care attendance was associated with an increased chance of therapy initiation (OR: 5.3, 95% CI: 1.8–16.2) and breastfeeding was associated with a lower chance of starting therapy (OR: 0.4, 95% CI: 0.1–1.1). Dutch children had a higher chance of refilling prescriptions in infancy (OR: 5.3, 95% CI: 1.1–26.8).Conclusions. Apart from other factors involved, the principal reason for initiation and refill of asthma therapy in infancy was the presence of respiratory symptoms. This appeared the only reason to prescribe medication and physicians are not distracted by other factors. [ABSTRACT FROM AUTHOR]

This study describes the impact of undiagnosed and diagnosed asthma on quality of life in schoolchildren aged 7-10 years and their caregivers in a cross-sectional community-based study. Diagnosed asthma was defined as the parents' confirmation of a physician's diagnosis of asthma. Undiagnosed asthma was defined by asthma symptoms combined with airway reversibility or bronchial hyperresponsiveness. Quality of life was evaluated in all children with asthma and a sample of healthy controls by the Pediatric Asthma Quality of Life Questionnaire, and by the Paediatric Asthma Caregiver's Quality of Life Questionnaire. We studied the impact of breathing problems on school absence. Compared with healthy controls, quality of life scores among children and their caregivers were lower if the child had asthma (P < 0.05), with lowest scores in diagnosed asthma (P < 0.05 compared with undiagnosed asthma). Children with asthma reported more school absence (P < 0.05), with highest absence rate in those with diagnosed asthma. In conclusion, both undiagnosed and diagnosed asthma have a significant impact on the quality of life of both children and their caregivers. [ABSTRACT FROM AUTHOR]

Background: Asthma and excessive body weight frequently coexist, whereas the exact relationship between the 2 diseases is unknown. Objective: To study whether asthma combined with excessive body weight has a greater effect on quality of life in children than the separate effects of asthma or excessive body weight alone. Methods: In a cross-sectional design, 1758 school children (age 7-10 years) participated: 4 study groups were composed of children with asthma and with/without excessive body weight, and healthy controls with/without excessive body weight. Diagnosis of asthma was defined by either a doctor''s diagnosis or by core questions of the International Study of Asthma and Allergies in Childhood questionnaire in combination with either reversible airway obstruction or bronchial hyperresponsiveness. Excessive body weight was defined by using international cutoff points for body mass index. Quality of life was evaluated by the Pediatric Asthma Quality of Life Questionnaire. Results: For all domains of quality of life, children with both asthma and excessive body weight had lower scores than children with either asthma alone or excessive body weight alone. Compared with healthy controls, the score was 25% lower in children with asthma and excessive body weight, 14% lower in children with asthma and normal weight, and only 1% lower in overweight controls. Conclusion: Excessive body weight is associated with an additional decrease in quality of life in children with asthma. Clinical implications: Clinicians should be aware of the interaction between asthma and excessive body weight and the effect on quality of life and should give extra attention to children with both conditions. [Copyright &y& Elsevier]