Long-term adherence to inhaled corticosteroids in children with asthma: Observational study.

INTRODUCTION: Non-adherence to daily controller medication in childhood asthma is strongly dependent on potentially modifiable factors such as parental illness perceptions and medication beliefs. The extent to which adherence in children can be improved by addressing modifiable determinants of non-adherence has not been studied to date, however. We assessed long-term adherence and its determinants in children with asthma enrolled in a comprehensive asthma care program employing shared decision making with parents. METHODS: Observational study in 135 children 2-12 years of age with asthma attending a hospital-based outpatient clinic. One-year adherence to inhaled corticosteroids was measured by electronic devices. Parental illness perceptions and medication beliefs, and asthma control were assessed by validated questionnaires. RESULTS: Median (interquartile range) adherence was 84% (70-92%). 55 children (41%) did not achieve the pre-defined level of good adherence (≥80%) and this was associated with poorer asthma control. Parental perceived medication necessity was high, with a median (interquartile range) BMQ necessity score of 17 (16-20). Parents' replies to the five key questions on the core issues of the program showed high concordance of their illness perceptions and medication beliefs with the medical model of asthma and its treatment. Differences in these perceptions between adherent and non-adherent families were small and non-significant. CONCLUSIONS: Poor adherence may persist in children despite a high level of concordance between medical team and parents on illness perceptions and medication beliefs, even in the absence of socio-economic barriers to good adherence. Achieving good adherence in all children is a complex task, requiring interventions not covered in current guidelines of managing asthma in children.

RSV infection among children born moderately preterm in a community-based cohort.

UNLABELLED: We aimed to determine the rates of proven respiratory syncytial virus (RSV) hospitalization and disease severity among children born moderately preterm (MP, gestational age [GA] 32-36 weeks, n = 964), children born full-term (FT, GA 38-42 weeks, n = 572), and children born early preterm (EP, GA <32 weeks, n = 524). Our second aim was to identify risk factors for RSV hospitalization among MP. We extracted data from parental questionnaires and medical records, retrieved from a community-based cohort of children aged 43-49 months. The RSV hospitalization rates of MP were higher than FT (3.9 vs. 1.2 %, relative rate 3.2; 95 % confidence interval (CI) 1.4-7.1) and equal to EP (3.9 vs. 3.2 %, relative rate 1.2; 95 % CI 0.7-2.1). MP were hospitalized at an earlier age than EP. Disease severity (based on the type of treatment and hospitalization length) was equal in all groups. Risk factors for RSV hospitalization in MP were younger age and lower birth weight. In multivariable analyses, shorter GA and passive smoking independently increased the likelihood of RSV hospitalization in MP. CONCLUSION: The rates of hospitalization due to proven RSV infection are higher in MP than FT and not different between MP and EP. No difference in disease severity was observed. Among MP, the rates of RSV hospitalization are higher for lower GA and when exposed to passive smoking.

Health-related quality of life in food-allergic adults from eight European countries.

BACKGROUND: Food allergy can impair health-related quality of life (HRQL). Food Allergy Quality of Life Questionnaires (FAQLQs) have been developed and validated, including an adult form (FAQLQ-AF). HRQL has not, to date, been measured across different European countries using a uniform methodology. OBJECTIVE: To translate and validate the FAQLQ-AF for use in 8 European countries (Iceland, The Netherlands, Poland, France, Spain, Italy, Greece, and Sweden). METHODS: The English FAQLQ-AF was translated, back-translated, and compared for use in the 8 relevant European languages. Adults with a perceived food allergy were recruited from outpatient departments and through a community survey. Participants completed the FAQLQ-AF, the Food Allergy Independent Measure, and questions concerning participants' characteristics. Validity of the FAQLQ-AF was analyzed for use in the 8 countries. RESULTS: The FAQLQ-AF had strong construct validity (r > 0.59) and an excellent internal consistency (Cronbach α > 0.95) in all countries. Total FAQLQ-AF scores (range 3.2-5.0) were significantly different across participating countries. CONCLUSION: The FAQLQ-AF is a suitable and valid instrument for measuring HRQL in food-allergic adults in Iceland, The Netherlands, Poland, France, Spain, Italy, Greece, and Sweden. The impact of food allergy on HRQL seems to differ among adults from the 8 participating European countries.

Effects of dietary induced weight loss on exercise-induced bronchoconstriction in overweight and obese children.

RATIONALE: Previous studies showed that obesity in asthmatic children is associated with more severe exercise-induced bronchoconstriction (EIB), compared with non-obese asthmatic children. This study investigates the effect of weight loss on EIB in overweight and obese asthmatic children. METHODS: In this intervention study, children aged 8-18 years with EIB and moderate to severe overweight, followed a diet based on healthy daily intake for 6 weeks. Before and after the diet period they underwent an exercise challenge test in cold air. Primary outcome was change in exercise-induced fall in FEV1 and relation between weight loss and EIB. Secondary outcomes were changes in recovery of FEV1 ("area under the curve"; AUC), fraction of exhaled nitric oxide (FeNO) and scores of the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and Asthma Control Questionnaire (ACQ). RESULTS: Twenty children completed the study. After the diet period, weight, and body mass index (BMI) were significantly reduced (changes respectively -2.6% and -1.5 kg/m(2), P < 0.01). There was a significant improvement of the percentage exercise-induced fall in FEV1 (30.6% vs. 21.8%, P < 0.01), AUC and PAQLQ score. The reduction in BMI z-score was significantly related to the reduction in the percentage exercise-induced fall in FEV1 in children that lost weight (r = 0.53, P = 0.03). There were no changes in FeNO and ACQ. CONCLUSIONS: Dietary induced weight loss in overweight and obese asthmatic children leads to significant reduction in severity of EIB and improvement of the quality of life. The reduction in BMI z-score is significantly related to the improvement of EIB.

It's the adherence, stupid (that determines asthma control in preschool children)!

Although guideline-based asthma care and adherence to inhaled corticosteroids are predictors of asthma control, the role of adherence in maintaining long-term asthma control is largely unknown. This study was designed to explore the relationship between adherence to inhaled corticosteroids and long-term asthma control in young children with asthma. In this observational study, 81 2-6-year-old asthmatic children, using inhaled corticosteroids, closely followed-up in a programme with extensive self-management training, were enrolled. Adherence was measured daily for 12 months using Smartinhaler (Nexus6 Ltd, Auckland, New Zealand) devices. Long-term asthma control was assessed by parents and physicians and included clinical assessment, an asthma control questionnaire and lung function measurement. We examined the association of adherence to asthma control, adjusting for seasonal influences and clinical characteristics. Median (interquartile range) adherence was 87% (70-94%), and 64 (79%) children had well-controlled asthma throughout follow-up. Adherence >80% was associated with better asthma control, and we found no important confounders of this association. Children with persistent mild symptoms had lower adherence rates (p=0.028). Guideline-based asthma care was associated with good asthma control in most children. Adherence to inhaled corticosteroids was an independent strong predictor of long-term asthma control, with highest levels of asthma control found in children with adherence >80% of doses prescribed.

Food allergy knowledge of parents - is ignorance bliss?

BACKGROUND: Food allergic children are at least partially dependent on their parents to care for their food allergy. In addition, parents are often responsible for the education of others regarding food allergy, including the family, school, neighbors, and friends. The aim of this study was to investigate food allergy knowledge, attitudes, and beliefs of parents with food allergic children in the Netherlands. In addition, a cross-cultural comparison was made between parents from the USA and parents from the Netherlands. METHODS: The original Chicago Food Allergy Research Survey for Parents of Children with Food Allergy (CFARS-PRNT) was translated into Dutch. Parents of children with at least one doctor-diagnosed food allergy were included. Knowledge scores and attitude/beliefs scores were determined and compared with the data from 2945 parents from the USA. Predictors of overall knowledge scores were investigated. RESULTS: Dutch parents of children completed the translated CFARS-PRNT (n = 299). The mean overall knowledge score in the Netherlands was 9.9 after adjusting for guessing, compared with 12.7 in the USA (p < 0.001). Attitudes and beliefs regarding food allergy among parents from the Netherlands were generally more optimistic. The overall knowledge scores could be predicted by country of origin, educational degree, being member of a patient organization, visiting an allergist, and a history of anaphylaxis. CONCLUSIONS: Food allergy knowledge among parents of food allergic children from the Netherlands is suboptimal when compared with their counterparts from the USA, although these parents tend to be more optimistic toward food allergy than parents from the USA.

Long-term follow-up after two years of asthma treatment guided by airway responsiveness in children.

INTRODUCTION: Children with persistent asthma may have diminished lung function in early adulthood. In our previous study ('CATO') we showed preservation of lung function in asthmatic children, during 2 years of treatment that was guided by airway hyperresponsiveness (AHR). The aim of the present prospective follow up study was to investigate whether the positive effect of the AHR strategy on lung function had persisted beyond the duration of the intervention study, after several years of usual care by paediatrician and general practitioner. METHODS: With a mean interval of 4.4 y after the last visit, 137 subjects (67% of the original CATO population) participated in this follow-up study. Evaluation consisted of spirometry (n = 137), a methacholine challenge test (n = 83), data on inhaled steroid treatment and asthma exacerbations (n = 137), and an asthma symptom diary during 6 weeks (n = 90). RESULTS: At follow-up, lung function, % symptom-free days and exacerbation rates of both treatment strategy groups was similar. The mean dose of inhaled corticosteroids had diminished from 550 µg/day at the end of CATO to 235 µg/day at follow-up. The decrease in AHR measured at the end of CATO was maintained at follow-up for both treatment strategy groups. CONCLUSION: The beneficial effect on lung function of 2 years treatment guided by AHR was lost after 3-7 years of usual care. This suggests that an AHR-guided treatment strategy may need to be sustained in order to preserve lung function.

General practitioners' prescribing behaviour as a determinant of poor persistence with inhaled corticosteroids in children with respiratory symptoms: mixed methods study.

OBJECTIVES: To evaluate general practitioners' (GPs') prescribing behaviour as a determinant of persistence with and adherence to inhaled corticosteroids (ICS) in children. DESIGN: Prospective observational study of persistence with and adherence to ICS followed by a focus group study of the GPs prescribing this treatment. SETTING: 7 primary care practices in the area of Zwolle, the Netherlands. PARTICIPANTS: 134 children aged 2-12 years had been prescribed ICS in the year before the study started by their 19 GPs. MAIN OUTCOME MEASURES: Patterns and motives of GPs' prescribing behaviour and the relationship with persistence with and adherence to ICS. RESULTS: GPs' prescribing behaviour was characterised by prescribing short courses of ICS to children with various respiratory symptoms without follow-up for making a diagnosis of asthma. This was driven by the GPs' pragmatic approach to deal with the large number of children with respiratory symptoms, and by beliefs about ICS which differed from currently available evidence. This prescribing behaviour was the main reason why 68 (51%) children did not persist with the use of ICS. In children with persistent use of ICS and a GP's advice to use ICS on a daily basis, the median (IQR) adherence was 70% (41-84%), and was similar for patients with persistent asthma and children lacking a diagnosis or symptoms of asthma. CONCLUSIONS: Inappropriate prescription of ICS to children by GPs is common and drives the lack of persistence with ICS therapy in primary care. This finding should be taken into account when interpreting data from large prescription database studies. Improving primary healthcare providers' knowledge and competence in diagnosing and managing asthma in children is needed.

Moderately preterm children have more respiratory problems during their first 5 years of life than children born full term.

RATIONALE: Pulmonary outcomes of moderate-preterm children (MP) are unknown. OBJECTIVES: To investigate the prevalence of respiratory symptoms during infancy and at preschool age of MP compared with full-term (FT) and early preterm children (EP) and to determine factors associated with respiratory symptoms of MP at school age. METHODS: Prospective cohort study. OUTCOME VARIABLES: number of rehospitalizations caused by respiratory problems, prevalence of respiratory symptoms determined by ISAAC Questionnaires, and factors associated with respiratory symptoms determined by univariate and multivariate analyzes. MEASUREMENTS AND MAIN RESULTS: A total of 988 MP, 551 EP, and 573 FT children were included. The number of hospitalizations caused by respiratory problems during the first year of life was doubled in MP compared with FT (6% vs. 3%; P < 0.001). At preschool age, compared with FT, MP reported more cough or wheeze during a cold (63% vs. 50%; P < 0.001); cough or wheeze without a cold (23% vs. 15%; P = 0.001); nocturnal cough (33% vs. 26%; P = 0.005); dyspnea (8% vs. 4%; P = 0.011); and use of medication (inhaled steroids, 9% vs. 6%; P = 0.042) (antibiotics, 12% vs. 7%; P = 0.002). Factors associated with respiratory symptoms at 5 years among MP were respiratory problems, eczema, rehospitalization in infancy, passive smoking in infancy, family history of asthma, and higher social class. Multivariate analyzes showed the same results except for rehospitalization in infancy. CONCLUSIONS: MP have more respiratory symptoms than FT during early childhood. Factors associated with respiratory symptoms at school age are early respiratory problems, family history of asthma, higher social class, and passive smoking.

The prospective association between behavioural problems and asthma outcome in young asthma patients.

AIM: The aim of this prospective study was to examine the association between behavioural problems and medical and psychological outcomes in clinically treated children and adolescents with asthma. METHODS: Patients (n = 134) were recruited from two high-altitude asthma clinics in Switzerland and one asthma clinic in the Netherlands. Outcome measures were Asthma Control Test (ACT), Paediatric Asthma Quality of Life Questionnaire (PAQLQ(S)), forced expiratory volume in 1 sec (FEV1 ) and fractional concentration of exhaled nitric oxide (FeNO). Parents completed the Child Behaviour Checklist (CBCL) (predictor variable). Data were collected at the start and end of treatment. Multiple regression analysis was used while adjusting for demographic variables, clinic and length of stay. RESULTS: More severe internalizing behavioural problems were associated with less improvement of total quality of life (t = -2.26, p = 0.03) and the domains symptoms (t = -2.04, p = 0.04) and emotions (t = -2.3, p = 0.02) after clinical treatment. Behavioural problems were not associated with a change of lung function measurements (FEV1 and FeNO) and asthma control (ACT) during treatment. CONCLUSION: A focus of healthcare professionals on the treatment of internalizing behavioural problems may optimize the quality of life in clinically treated youth with asthma.

Urinary eosinophil protein X in childhood asthma: relation with changes in disease control and eosinophilic airway inflammation.

The aim of this study was to assess cross-sectional and longitudinal correlations between uEPX and other markers of asthma control and eosinophilic airway inflammation. Methods. We measured uEPX at baseline, after 1 year and after 2 years in 205 atopic asthmatic children using inhaled fluticasone. At the same time points, we assessed symptom scores (2 weeks diary card), lung function (forced expiratory volume in one second (FEV(1))), airway hyperresponsiveness (AHR), and percentage eosinophils in induced sputum (% eos). Results. We found negative correlations between uEPX and FEV(1) at baseline (r = -0.18, P = 0.01), after 1 year (r = -0.25, P < 0.01) and after 2 years (r = -0.21, P = 0.02). Within-patient changes of uEPX showed a negative association with FEV(1) changes (at 1 year: r = -0.24, P = 0.01; at 2 years: r = -0.21, P = 0.03). Within-patient changes from baseline of uEPX correlated with changes in % eos. No relations were found between uEPX and symptoms. Conclusion. In this population of children with atopic asthma, uEPX correlated with FEV(1) and % eos, and within-subjects changes in uEPX correlated with changes in FEV(1) and % eos. As the associations were weak and the scatter of uEPX wide, it seems unlikely that uEPX will be useful as a biomarker for monitoring asthma control in the individual child.

Dysfunctional breathing in children with asthma: a rare but relevant comorbidity.

Hyperventilation and other clinical manifestations of dysfunctional breathing have been reported in childhood, but the prevalence is unknown. In adults, dysfunctional breathing may be a relevant comorbidity in asthma. We aimed to determine the prevalence of dysfunctional breathing in children with asthma and its impact on asthma control. We performed a cross-sectional survey in 203 asthmatic children (aged 5-18 years), using the Nijmegen Questionnaire and the paediatric Asthma Control Questionnaire. Dysfunctional breathing was found in 11 (5.3%) children; more females (eight (12.9%) out of 62) than males (three (2.1%) out 144, p=0.002). There was a dose-dependent relationship between increasing Nijmegen Questionnaire scores (increased risk of dysfunctional breathing) and poorer asthma control. Poor asthma control was more common in patients with dysfunctional breathing (10 (90.9%) out of 11 children) than in children without (65 (32.3%) out of 192 children; OR 19.3, 95% CI 3.14-430.70; p<0.0001). The median Asthma Control Questionnaire in children with dysfunctional breathing was higher (median (range) 2.00 (1.50-3.17)) than in children without (0.50 (0.17-1.17); p<0.001). The prevalence of dysfunctional breathing in children and adolescents referred to a hospital-based paediatric asthma clinic for severe or difficult-to-control asthma is 5%. The association between dysfunctional breathing and asthma control suggests that this may be a clinically relevant comorbidity in paediatric asthma.

Preschool children with high adherence to inhaled corticosteroids for asthma do not show behavioural problems.

AIM: To assess prevalence of behavioural problems in preschool children with asthma with electronically verified exposure to inhaled corticosteroids (ICS). METHODS: Cross-sectional study of 81 children 2-5 years of age using daily ICS for persistent asthma. During 3 months' follow-up, adherence to ICS treatment was recorded by an electronical logging device (Smartinhaler(®)). Parents completed the Child Behavior Checklist 1.5-5 years (CBCL 1.5-5) to assess behavioural problems; results were compared to a published reference group of healthy children. RESULTS: The median (interquartile range) adherence to ICS was 92 (78-97) %. There was no difference in total CBCL score between children with asthma on ICS (mean, [SD] 32.10 [1.99]) and the reference group (33.30 [1.87], 95% CI for difference -6.62 to 4.22). Children with asthma were more likely to have somatic complaints (95% CI for difference 0.64 to 1.96) and less likely to have anxious/depressive symptoms (95% CI for difference -1.57 to -0.25) than the reference group. CBCL scores were not significantly related to the electronically measured adherence rates. CONCLUSIONS: Maintenance treatment with ICS, taken daily as prescribed, is not associated with an increased risk of behavioural problems in preschool children.

[Inhaled corticosteroids and behavioural changes in children]. / Inhalatieglucocorticoïden en gedragsveranderingen bij kinderen.

Behavioural changes, such as hyperactivity, aggression, mood swings and agitation may occur during the use of inhaled corticosteroids. Children are particularly vulnerable to this possible adverse drug reaction. As this side effect is reversible, timely recognition is important in order to prevent unnecessary diagnostic investigations and problems at home or at school. In this article we present two patients, a seven-year-old boy and a nine-year-old girl, who illustrate the importance of awareness of this unwanted effect of inhaled corticosteroids.

Food allergy-related quality of life after double-blind, placebo-controlled food challenges in adults, adolescents, and children.

BACKGROUND: Currently, the longitudinal validity (validity over time) and responsiveness (ability to measure change over time) of the Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF), the Food Allergy Quality of Life Questionnaire-Teenager Form (FAQLQ-TF), and the Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF) are unknown. Additionally, the self-reported impact of a double-blind, placebo-controlled food challenge (DBPCFC) on health-related quality of life (HRQL) in adults (≥18 years of age), adolescents (13-17 years of age), and children (8-12 years of age) is unknown. OBJECTIVE: The aims of this study were to assess the longitudinal validity and responsiveness of the FAQLQ-AF, FAQLQ-TF, and FAQLQ-CF and to assess the impact of a DBPCFC on HRQL. METHODS: Two hundred twenty-one participants suspected of food allergy were included from Dutch allergy centers. Participants undergoing a DBPCFC (experimental group) completed the FAQLQ and Food Allergy Independent Measure (FAIM) 1 month before (baseline) and 6 months after (follow-up) a DBPCFC. Participants not undergoing a DBPCFC (control group) completed the questionnaire package twice with a 7-month interval. RESULTS: HRQL scores improved after a DBPCFC, with greater improvements in HRQL scores after a negative outcome (food allergy ruled out) than a positive outcome (food allergy confirmed), demonstrating responsiveness of the FAQLQs. Significant correlations were shown between the change (follow-up minus baseline) in FAQLQ and FAIM scores supporting longitudinal validity of these questionnaires: FAQLQ-AF (Pearson correlation coefficient = 0.71, P < .001), FAQLQ-TF (Pearson correlation coefficient = 0.35, P = .018), and FAQLQ-CF (Pearson correlation coefficient = 0.51, P < .001). CONCLUSIONS: Our findings demonstrate the longitudinal validity and responsiveness of the FAQLQs. Greater improvements in HRQL scores were shown after a negative outcome than after a positive outcome.

High inhaled corticosteroids adherence in childhood asthma: the role of medication beliefs.

Our aim was to study determinants of adherence in young asthmatic children over a 3-month period, including the role of parental illness and medication perceptions as determinants of adherence. Consecutive 2-6-yr-old children with asthma, using inhaled corticosteroids (ICS), followed-up at our paediatric asthma clinic (where patients are being extensively trained in self-management, and are followed-up closely) were enrolled. Adherence was measured electronically using a Smartinhaler® and calculated as a percentage of the prescribed dose. We examined the association of adherence to a range of putative determinants, including clinical characteristics and parental perceptions about illness and medication. Median (interquartile range) adherence, measured over 3 months in 93 children, was 92 (76-97)%, and most children had well controlled asthma. 94% of parents expressed the view that giving ICS to their child would protect him/her from becoming worse. Adherence was significantly associated with asthma control and with parental perceptions about medication. The high adherence rate observed in our study was associated with parental perceptions about ICS need. The high perceived need of ICS may probably be ascribed to the organisation of asthma care (with repeated tailored education and close follow-up).

Allergic rhinitis is associated with poor asthma control in children with asthma.

BACKGROUND: Asthma and allergic rhinitis are the two most common chronic disorders in childhood and adolescence. To date, no study has examined the impact of comorbid allergic rhinitis on asthma control in children. OBJECTIVE: To examine the prevalence of allergic rhinitis in children with asthma, and the impact of the disease and its treatment on asthma control. METHODS: A cross-sectional survey in 203 children with asthma (5-18 years) using validated questionnaires on rhinitis symptoms (stuffy or runny nose outside a cold) and its treatment, and the paediatric Asthma Control Questionnaire (ACQ). Fraction of nitric oxide in exhaled air (FeNO) was measured with a Niox Mino analyser; total and specific IgE levels were assessed by the Immunocap system. RESULTS: 157 children (76.2%) had symptoms of allergic rhinitis but only 88 of these (56.1%) had been diagnosed with the condition by a physician. ACQ scores were worse in children with allergic rhinitis than in those without the condition (p=0.012). An ACQ score ≥ 1.0 (incomplete asthma control) was significantly more likely in children with allergic rhinitis than in those without (OR 2.74, 95% CI 1.28 to 5.91, p=0.0081), also after adjustment for FeNO levels and total serum IgE. After adjustment for nasal corticosteroid therapy, allergic rhinitis was no longer associated with incomplete asthma control (OR 0.72, 95% CI 0.47 to 1.12, p=0.150). CONCLUSION: Allergic rhinitis is common in children with asthma, and has a major impact on asthma control. The authors hypothesise that recognition and treatment of this condition with nasal corticosteroids may improve asthma control in children, but randomised clinical trials are needed to test this hypothesis.

Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children.

RATIONALE: Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. METHODS: This was a double-blind, randomized, placebo-controlled, parallel group study. Subjects aged 12-17 years, with mild-to-moderate asthma, intermittent allergic rhinitis and ≥ 10% fall in FEV(1) at a screening exercise challenge were randomized to 22 ± 3 days treatment with intranasal fluticasone furoate or placebo. The primary outcome was change in exercise induced fall in FEV(1) . Secondary outcomes were changes in the area under the curve (AUC), asthma control questionnaire (ACQ), pediatric asthma quality of life questionnaire (PAQLQ), and exhaled nitric oxide (FeNO). RESULTS: Twenty-five children completed the study. Mean exercise induced fall in FEV(1) (± SD) decreased significantly (95% CI: 0.7-18.2%, P = 0.04) in the fluticasone furoate group from 28.4 ± 15.8% to 19.0 ± 13.8%, compared to the placebo group (27.4 ± 16.0% to 27.4 ± 19.2%). The change in AUC was not significantly different between treatment groups. However, within the fluticasone furoate group the AUC decreased significantly (P = 0.01). Although total PAQLQ score did not improve, the activity limitation domain score improved significantly within the fluticasone furoate group (P = 0.03). No significant changes were observed in FeNO and ACQ. CONCLUSION: Treatment of allergic rhinitis in asthmatic children with an intranasal corticosteroid reduces EIB and tends to improve quality of life.

Protocadherin-1 polymorphisms are associated with eczema in two Dutch birth cohorts.

BACKGROUND: Eczema and asthma share a common genetic background and show linkage to chromosome 5q31-33. Protocadherin-1 (PCDH1) is located in this region and was identified as a susceptibility gene for bronchial hyper-responsiveness (BHR), a hallmark of asthma. PCDH1 encodes an adhesion molecule, expressed in airway and skin epithelium. We determined whether PCDH1 polymorphisms, previously associated with asthma or BHR, also associated with questionnaire and UK Working Party (UKWP) defined eczema. METHODS: Four PCDH1 polymorphisms were genotyped in two Dutch birth cohorts, PIAMA (n = 967) and KOALA Birth Cohort Study (n = 1560). Association with eczema was determined by chi-square tests and generalized estimating equations (GEE). RESULTS: Insertion deletion IVS3-116 was associated with development of UKWP eczema in PIAMA [age 4, OR = 1.90 (1.14-3.18)] and borderline with questionnaire-reported eczema in PIAMA [GEE, OR = 1.33 (0.98-1.81)]. Furthermore, IVS3-116 was associated with questionnaire-reported eczema in KOALA [age 1, OR = 1.44 (1.00-2.07)]. Pooled analysis of questionnaire-reported eczema of both cohorts resulted in a significant association of IVS3-116 with eczema [OR = 1.26 (1.01-1.58)]. Rs3822357 (A-allele) associated with protection for eczema in PIAMA only [questionnaires, OR = 0.19 (0.06-0.63)]. CONCLUSION: PCDH1 gene variant IVS3-116 associates with eczema in two independent birth cohorts. Combined with previous observations, this indicates a shared genetic susceptibility to BHR, asthma and eczema.

The effect of stepping down combination therapy on airway hyperresponsiveness to mannitol.

RATIONALE: Controversy exists about the safety of long acting beta2-agonist (LABA) treatment, in particular in children. Combination therapy with a LABA and an inhaled corticosteroid (ICS) is prescribed to children with moderate asthma and can be stepped down by withdrawal of the LABA when asthma is well controlled. OBJECTIVE: To analyze the effect of stepping down from LABA/ICS combination therapy to monotherapy with the same dose of ICS on the airway response to mannitol in asthmatic children. METHODS: 17 children, aged 12-17 years, with clinically stable asthma, receiving combination therapy, were analyzed in this observational prospective open-label study. Children performed a mannitol challenge at baseline and 30±4 days after their medication was stepped down to ICS monotherapy. The changes in the provoking dose of mannitol to cause a 15% fall in FEV(1) (PD(15)), response-dose ratio and recovery time following a short acting beta2-agonist to ≥95% of baseline FEV(1) were assessed. RESULTS: Mannitol PD(15) and response-dose ratio did not significantly change after stepping down. The recovery time following a short acting beta2-agonist to ≥95% of baseline FEV(1) was significantly shorter (p=0.01) after the withdrawal of the LABA. CONCLUSIONS: In short-term follow-up, stepping down clinically stable asthmatic children from combination therapy to monotherapy with an ICS does not change airway hyperresponsiveness (AHR) to mannitol but does shorten recovery time to baseline lung function following a rescue short acting beta2-agonist.