Genetic variation in uncontrolled childhood asthma despite ICS treatment.

Genetic variation may partly explain asthma treatment response heterogeneity. We aimed to identify common and rare genetic variants associated with asthma that was not well controlled despite inhaled corticosteroid (ICS) treatment. Data of 110 children was collected in the Children Asthma Therapy Optimal trial. Associations of genetic variation with measures of lung function (FEV1%pred), airway hyperresponsiveness (AHR) to methacholine (Mch PD20) and treatment response outcomes were analyzed using the exome chip. The 17q12-21 locus (containing ORMDL3 and GSMDB) previously associated with childhood asthma was investigated separately. Single-nucleotide polymorphisms (SNPs) in the 17q12-21 locus were found nominally associated with the outcomes. The strongest association in this region was found for rs72821893 in KRT25 with FEV1%pred (P=3.75*10(-5)), Mch PD20 (P=0.00095) and Mch PD20-based treatment outcome (P=0.006). No novel single SNPs or burden tests were significantly associated with the outcomes. The 17q12-21 region was associated with FEV1%pred and AHR, and additionally with ICS treatment response.

Predictors of health-related quality of life of European food-allergic patients.

BACKGROUND: Although food allergy has universally been found to impair HRQL, studies have found significant differences in HRQL between countries, even when corrected for differences in perceived disease severity. However, little is known about factors other than disease severity which may contribute to HRQL in food-allergic patients. Therefore, the aim of this study was to identify factors which may predict HRQL of food-allergic patients and also to investigate the specific impact of having experienced anaphylaxis and being prescribed an EAI on HRQL. METHODS: A total of 648 European food-allergic patients (404 adults, 244 children) completed an age-specific questionnaire package including descriptive questions. Multivariable regression analyses were performed to develop models for predicting HRQL of these patients. RESULTS: For adults, the prediction model accounted for 62% of the variance in HRQL and included perceived disease severity, type of symptoms, having a fish or milk allergy, and gender. For children, the prediction model accounted for 28% of the variance in HRQL and included perceived disease severity, having a peanut or soy allergy, and country of origin. For both adults and children, neither experiencing anaphylaxis nor being prescribed an epinephrine auto-injector (EAI) contributed to impairment of HRQL. CONCLUSIONS: In this study, food allergy-related HRQL may be predicted to a greater extent in adults than in children. Allergy to certain foods may cause greater HRQL impairment than others. Country of origin may affect HRQL, at least in children. Experiencing anaphylaxis or being prescribed an EAI has no impact on HRQL in either adults or children.

Online version of the food allergy quality of life questionnaire-adult form: validity, feasibility and cross-cultural comparison.

BACKGROUND: Food-allergic reactions occur in 3-4% of the adult population in Western countries. It has been shown that food allergy may 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). These questionnaires may be particularly useful for cross-cultural comparisons. OBJECTIVES: The aims of this study were to translate the FAQLQ-AF from Dutch into English and validate an online version in the United States. Additionally, HRQL of American and Dutch food-allergic adults was compared. METHODS: The Dutch FAQLQ-AF was translated into English as set out by the World Health Organization and converted to an electronic online format. Participants (food allergic American adults) were recruited through the 'Food Allergy and Anaphylaxis Network' website and completed the questionnaire online. Construct validity, internal consistency, discriminative ability and feasibility were analysed. A cross-cultural comparison was made using the Dutch FAQLQ-AF scores. RESULTS: Data from 180 American participants were analysed. The online FAQLQ-AF had a good construct validity (correlation with FAIM: ρ=0.72; P<0.001), internal consistency (Cronbach's α=0.95) and was discriminative for 'anaphylaxis' vs. 'no anaphylaxis' and 'number of food allergies'. The most striking finding was a significantly greater impairment in HRQL in the American participants, as compared with their Dutch counterparts (the total FAQLQ-AF scores were 4.3 vs. 3.5, respectively; P<0.001, where 1 signifies no impairment and 7 signifies extreme impairment in HRQL). CONCLUSIONS AND CLINICAL RELEVANCE: The online American FAQLQ-AF is a valid instrument to measure HRQL in food-allergic patients in the United States. Additionally, HRQL of American food-allergic adults may be more impaired than Dutch food-allergic adults. The FAQLQ-AF can now be used to determine the HRQL in American food-allergic adults and can assist clinicians in optimizing management strategies for food-allergic patients.

Parents report better health-related quality of life for their food-allergic children than children themselves.

BACKGROUND: Food allergy affects 5-6% of children and impairs health-related quality of life (HRQL). Children and parents may differ in their views concerning the child's HRQL. In food allergy, child- and parent-proxy-reported HRQL have never been compared using valid disease-specific instruments. OBJECTIVE: The aim of this study was to compare child- and parent-proxy reports on HRQL in food-allergic children (8-12 years). METHODS: The Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF), and -Parent Form (FAQLQ-PF) and the Food Allergy Independent Measure-Child Form and -Parent Form (FAIM-CF and -PF) were completed by Dutch food-allergic child-parent pairs. Child- and parent-proxy reports were correlated and tested for significant differences. Construct validity (Spearman's correlation coefficient between the FAQLQs and FAIMs) and internal consistency (Cronbach's α) were assessed and compared. RESULTS: Seventy-four child-parent pairs were included. The FAQLQ-CF score was significantly higher than the FAQLQ-PF score (3.74 vs. 2.68, P<0.001, where 1 indicates no impairment and 7 indicates extreme impairment). FAIM-CF and -PF scores were almost identical (3.29 vs. 3.33, P=0.594). There was moderate agreement between the FAQLQ-CF and -PF scores (ICC=0.57 [P<0.001]) and good agreement between the FAIM-CF and -PF scores (ICC=0.80 [P<0.001]). Construct validity was confirmed for the FAQLQ-CF (ρ=0.60, P<0.001) and -PF (ρ=0.58, P<0.001). Internal consistency was excellent for the FAQLQ-CF (α=0.95) and -PF (α=0.95). CONCLUSIONS AND CLINICAL RELEVANCE: Parents reported significantly less impact of food allergy on the child's HRQL than children themselves, while reported perceptions of disease severity were nearly identical. This may reflect real differences in perspectives between children and parents and may indicate that parents tend to underestimate their child's HRQL impairment. It is important for clinicians to include both the child's and their parent's perceptions in order to perform a complete assessment of the impact of food allergy on the child's HRQL and to identify areas of disagreement that need special attention in clinical practice.

Adolescent-parent disagreement on health-related quality of life of food-allergic adolescents: who makes the difference?

BACKGROUND: Food-allergic adolescents are at highest risk for food allergy fatalities, which may be partly due to compromised self-management behavior. Such behavior may be negatively influenced by conflictual situations caused by adolescent-parent disagreement on the adolescent's health-related quality of life (HRQL). Comparisons of adolescent-self-reported and parent-proxy-reported HRQL of food-allergic adolescents have never extensively been studied. The aims of this study were to investigate disagreement in adolescent-self-reports and parent-proxy-reports on the HRQL of food-allergic adolescents and to investigate the factors influencing adolescent-parent disagreement. METHODS: Teenager Form (TF) and Parent Form (PFA) of the Food Allergy Quality of Life Questionnaire (FAQLQ), Food Allergy Independent Measure (FAIM), and Brief-Illness Perception Questionnaire (Brief-IPQ) were sent to food-allergic Dutch adolescents (13-17 years) and their parents. ICCs, t-tests, and Bland-Altman plots were used to investigate adolescent-parent disagreement. Participant characteristics, illness expectations, and illness perceptions influencing adolescent-parent disagreement were studied using regression analysis. RESULTS: Seventy adolescent-parent pairs were included. There were a moderate correlation (ICC = 0.61, P < 0.001) and no significant difference (3.78 vs 3.56, P = 0.103) between adolescent-self-reported and parent-proxy-reported HRQL at group level. However, Bland-Altman plots showed relevant differences (exceeding the minimal important difference) for 63% of all adolescent-parent pairs. Adolescent's age (> 15 years), poorer adolescent-reported illness comprehension (Brief-IPQ-TF, coherence), and higher adolescent-reported perceived disease severity (Food Allergy Independent Measure-Teenager Form & -Parent Form) were associated with adolescent-parent disagreement. CONCLUSIONS: Adolescent-parent disagreement on the adolescent's HRQL was mainly associated with adolescents' rather than parents' perceptions and characteristics. Illness comprehension of the adolescent may be an important target for intervention aimed at reducing adolescent-parent disagreement.

Comorbidities of asthma during childhood: possibly important, yet poorly studied.

Asthma in adults is associated with comorbidities such as obesity, gastro-oesophageal reflux, dysfunctional breathing and mental disorders. Herein, we provide an overview of the current state of evidence on these comorbidities in childhood asthma. The prevalence, known mechanisms and possible treatment options for each comorbid condition will be discussed. Obesity is an increasing health problem in children, but its relationship with asthma remains unclear. Allergic rhinitis is a very common comorbidity in asthma, both in children and in adults, but its effect on childhood asthma severity has not been studied. The prevalence and treatment options of dysfunctional breathing, a known comorbidity in adult asthma, have not yet been studied in paediatric asthma. Food allergies appear to cause more severe reactions in patients with asthma. Depressive disorders are more prevalent in childhood asthma than in healthy children, but seem to be poorly recognised and treated in children. Although gastro-oesophageal reflux is commonly thought to be a comorbid disease complicating asthma, it remains uncertain whether treatment improves asthma control. In conclusion, knowledge of asthma comorbidities in childhood is sparse. Further studies are urgently needed to identify the prevalence, and, more importantly, the effects of these comorbidities and their treatment on the degree of asthma control in children.

Health-related quality of life of food allergic patients: comparison with the general population and other diseases.

BACKGROUND: To date no studies have compared generic health-related quality of life (HRQL) of food allergic patients from childhood to adulthood with that of the general population or patients with other chronic diseases. The aim of this study was to compare generic HRQL of food allergic patients with the general population and other diseases. METHODS: Generic HRQL questionnaires (CHQ-CF87 and RAND-36) were completed by 79 children, 74 adolescents and 72 adults with food allergy. The generic HRQL scores were compared with scores from published studies on the general population and patients with asthma, irritable bowel syndrome (IBS), diabetes mellitus (DM) and rheumatoid arthritis (RA). RESULTS: Food allergic children and adolescents reported fewer limitations in school work due to behavioural problems (P < or = 0.013), but food allergic adolescents and adults reported more pain (P = 0.020), poorer overall health (P < 0.001), more limitations in social activities (P < 0.001) and less vitality (P = 0.002) than individuals from the general population. Food allergic patients reported poorer generic HRQL than patients with DM, but better generic HRQL than patients with RA, asthma and IBS. CONCLUSION: HRQL is impaired in food allergic adolescents and adults, compared to the general population, and it is intermediate in magnitude between DM and RA, asthma and IBS. Children show the least impact on generic HRQL from food allergy.

Health-related quality of life of food allergic patients measured with generic and disease-specific questionnaires.

BACKGROUND: Health-related quality of life (HRQL) has never been measured with both generic and disease-specific questionnaires in the same group of food allergic patients. The aim of this study was to compare HRQL of food allergic patients as measured with generic and disease-specific questionnaires. METHODS: Generic questionnaires (CHQ-CF87 and RAND-36) and disease-specific HRQL questionnaires (FAQLQ-CF, -TF and -AF) were completed by 79 children, 74 adolescents and 72 adults with food allergy. Floor and ceiling effects, percentage of agreement and multivariate stepwise regression analysis were used to compare the generic and disease-specific measurements. RESULTS: The Food Allergy Quality of Life Questionnaires (FAQLQs) showed minimal floor or ceiling effects. The CHQ-CF87 and RAND-36 showed minimal floor effects, but remarkable ceiling effects (> 73%) were found for the scales role functioning-emotional (RE), role functioning-behaviour (RB), role functioning-physical (RP) in children and adolescents and the scale RE (> 79%) in adults. Additionally, we found low percentages of agreement between the generic and disease-specific questionnaires to identify the same food allergic patients with the best or worst HRQL. Only patients with the best disease-specific HRQL also tended to have the best generic HRQL. Finally, the explained variance in HRQL by patient characteristics was higher in the disease-specific questionnaires (30.7-62.8%) than in the generic scales (6.7-31.7%). CONCLUSION: Disease-specific HRQL questionnaires may be more suitable to measure clinically important impairments in HRQL or HRQL differences over time in food allergic patients. However, generic HRQL questionnaires are indispensable for the comparison between different diseases and are thus complementary.

Development, validity and reliability of the food allergy independent measure (FAIM).

BACKGROUND: The Food Allergy Quality of Life Questionnaire-Child Form, -Teenager Form and -Adult Form (FAQLQ-CF, -TF and -AF) have recently been developed. To measure construct validity in the FAQLQs, a suitable independent measure was needed with which FAQLQ scores could be correlated. However, in food allergy, no appropriate independent measure existed, which could be used for this purpose. AIMS OF THE STUDY: The aim of this study was to describe the development of a Food Allergy Independent Measure Child-Form, -Teenager Form and -Adult Form (FAIM-CF, -TF and -AF) and to assess their validity and reliability. METHODS: The FAIMs were developed using previously established methodology to capture the patients' expectation of outcome (EO). Face validity was determined by expert opinion. FAIM questions showing no correlation to any potential items in the FAQLQs were considered irrelevant and eliminated. To measure test-retest reliability, one-hundred and one patients were included and completed the FAIM twice with a 10-14 day interval. The intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC) and Bland-Altman plots were used to assess test-retest reliability. RESULTS: Six FAIM questions were developed and considered relevant for the FAIM-CF and -AF, and five questions were relevant for the FAIM-TF. The FAIMs showed good reliability with ICCs and CCCs above 0.70 and with mean differences all close to zero. CONCLUSIONS: Food allergy independent measures were developed for children, adolescents and adults and were shown to be valid, relevant and reliable. This supports the suitability of the FAIMs for evaluating construct validity.

Airway obstruction at time of symptoms prompting use of reliever therapy in children with asthma.

BACKGROUND: In asthma treatment, doses of inhaled corticosteroids are often adapted to symptoms and need for bronchodilators. However, in cross-sectional studies in emergency room settings, lung function and respiratory symptoms are not always concordant. Available longitudinal data are based on written peak flow diaries, which are unreliable. Using home spirometry, we studied prospectively whether mild respiratory symptoms, prompting reliever therapy are accompanied by a clinically relevant drop in lung function in children with asthma. METHODS: For 8 weeks, children with asthma scored symptoms and measured peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV(1)) on a home spirometer twice daily. Additional measurements were recorded when respiratory symptoms prompted them to use bronchodilators. RESULTS: The mean difference between symptom free days and at times of symptoms was 6.6% of personal best for PEF (95% CI: 3.2-10.0; p = 0.0004) and 6.0% of predicted for FEV(1) (95% CI: 3.0-9.0; p = 0.0004). There was complete overlap in PEF and FEV(1) distributions between symptom free days and at times of symptoms. CONCLUSIONS: Although statistically significant, the degree of airway narrowing at times of respiratory symptoms, prompting the use of reliever therapy, is highly variable between patients, limiting the usefulness of home spirometry to monitor childhood asthma.

Development and validation of a self-administered Food Allergy Quality of Life Questionnaire for children.

BACKGROUND: Having a food allergy may affect health-related quality of life (HRQL). Currently, no validated, self-administered, disease-specific HRQL questionnaire exists for children with food allergy. OBJECTIVE: The aim of this study was to develop and validate the Food Allergy Quality of Life Questionnaire--Child Form (FAQLQ-CF) in the Dutch language. METHODS: Interviews with food-allergic children (n=13, 8-12 years) generated 139 HRQL items. The most important items were identified by 51 food-allergic children using the clinical impact method. This resulted in the FAQLQ-CF containing 24 items (total score range 1 'not troubled' to 7 'extremely troubled'). The FAQLQ-CF, the Food Allergy Independent Measure (FAIM) and a generic HRQL questionnaire (CHQ-CF87) were sent to 115 food-allergic children for cross-sectional validation of the FAQLQ-CF. RESULTS: Construct validity was demonstrated by the correlation between the FAQLQ-CF and the FAIM (rho=0.60, P<0.001). The FAQLQ-CF had an excellent internal consistency (Cronbach's alpha=0.94) and discriminated between children who differed in number of food allergies (>2 food allergies vs. < or =2 food allergies; total FAQLQ-CF score, 4.3 vs. 3.6; P=0.036), but did not discriminate between reported anaphylaxis or not. The total FAQLQ-CF score correlated with 8 of the 11 CHQ-CF87 sub-scales which demonstrated convergent/discriminant validity. CONCLUSION: The FAQLQ-CF is the first self-administered disease-specific HRQL questionnaire for food-allergic children. This questionnaire has a strong internal consistency and cross-sectional validity. It discriminates between children who differ in number of food allergies, and it was short and easy to use in the population studied. Therefore, the FAQLQ-CF may be a useful tool in clinical research.

Development and validation of the Food Allergy Quality of Life Questionnaire - Adult Form.

BACKGROUND: Health-related quality of life (HRQL) may be affected by food allergy. Presently, no disease-specific HRQL questionnaire exists for food allergic adults. Therefore, we developed and validated the Food Allergy Quality of Life Questionnaire - Adult Form (FAQLQ-AF) in the Dutch language. METHODS: Twenty-two food allergic patients (> or =18 years) were interviewed and generated 180 HRQL items. The most important items were identified by 54 food allergic patients using the clinical impact method resulting in the FAQLQ-AF containing 29 items (score range 1 'not troubled' to 7 'extremely troubled'). The FAQLQ-AF, the Food Allergy Independent Measure (FAIM) and a generic HRQL questionnaire (RAND-36) were sent to 100 other food allergic adults for cross-sectional validation of the FAQLQ-AF. RESULTS: Cross-sectional validity was assessed by the correlation between FAQLQ-AF and FAIM (rho = 0.76, P < 0.001). The FAQLQ-AF had excellent internal consistency (Cronbach's alpha = 0.97). The FAQLQ-AF discriminated between patients who differ in severity of symptoms (anaphylaxis vs no anaphylaxis, total FAQLQ-AF score 4.9 vs 4.1; P = 0.041) and number of food allergies (>3 food allergies vs< or =3 food allergies, total FAQLQ-AF score 5.2 vs 4.2; P = 0.008). The total FAQLQ-AF score was correlated with one RAND-36 scale (convergent/discriminant validity). CONCLUSIONS: The FAQLQ-AF is the first disease-specific HRQL questionnaire for food allergic adults and reflects the most important issues that food allergic patients have to face. The questionnaire is valid, reliable and discriminates between patients with different disease characteristics. The FAQLQ-AF is short and easy to use and may therefore be a useful tool in clinical research.

Reference values for peak flow and FEV1 variation in healthy schoolchildren using home spirometry.

Current reference values for diurnal peak flow variation in healthy children (median 8.2%; 95th percentile 31%) are so high that considerable overlap exists with those of asthmatic children. These values have been obtained using written peak flow diaries, which are unreliable. The aim of the present study was to obtain reliable reference values for the variation in peak flow and forced expiratory volume in one second (FEV(1)) in healthy schoolchildren using home spirometry with electronic data storage. Healthy schoolchildren (n = 204; 100 males) aged 6-16 yrs measured their peak flow and FEV(1) twice daily for 2 weeks using an electronic home spirometer. The variation in peak flow and FEV(1) were calculated as a diurnal amplitude as a percentage of the day's mean. The mean peak flow variation was 6.2% (95th percentile 12.3%) and the mean FEV(1) variation was 5.7% (95th percentile 11.8%). Using home spirometry with electronic data storage, healthy schoolchildren show considerably less peak flow and forced expiratory volume in one second variation than previously reported on the basis of written peak flow diaries. Being the 95th percentiles of the distributions in healthy children, a peak flow variation of 12.3% and an forced expiratory volume in one second variation of 11.8% are suggested as cut-off values for disease when using home spirometry.

Happiness to be gained in paediatric asthma care.

The aim of the present study was to establish the efficacy in terms of morbidity and health-related quality of life (HRQoL) of a group asthma education-exercise programme to children with low (below 10th percentile value) quality-of-life scores. A controlled, randomised, open, clinical trial was conducted. In total, 36 out of 53 unhappy children, among 204 (68%) respondents, treated in four paediatric practices, enrolled (mean age 10 yrs; range: 8-12 yrs), after random allocation in control and intervention groups (child, parent, teacher). Measurements were taken at baseline (T0) and after 3, 6 (T6) and 9 months (T9; intervention group only at 9 months). All but four controls completed the study. From T0-T6, changes (Delta) in HRQoL were clinically important and significantly greater in the intervention group than in the control group, both for generic HRQoL (effect size (ES) 0.95; Delta 16%+/-12% versus -1+/-4%) and for asthma-specific HRQoL (ES 0.58; Delta 15%+/-17% versus 1.5+/-14%). T9 measurements were consistent with T6 findings. Changes in sick days (ES 0.78), oral prednisone courses (ES 0.71) and doctor visits (ES 0.74) over a 6-month period were greater in the intervention group than in the control group. Changes could not be ascribed to change in lung function or medication. In unhappy children, quality of life and morbidity may improve with a low intensity asthma education-exercise programme, even without gains in pulmonary function or exercise tolerance.

Should children with a history of anaphylaxis to foods undergo challenge testing?

BACKGROUND: Data on the frequency of resolution of anaphylaxis to foods are not available, but such resolution is generally assumed to be rare. OBJECTIVE: To determine whether the frequency of negative challenge tests in children with a history of anaphylaxis to foods is frequent enough to warrant challenge testing to re-evaluate the diagnosis of anaphylaxis, and to document the safety of this procedure. METHODS: All children (n=441) who underwent a double-blind, placebo-controlled food challenge (DBPCFC) between January 2003 and March 2007 were screened for symptoms of anaphylaxis to food by history. Anaphylaxis was defined as symptoms and signs of cardiovascular instability, occurring within 2 h after ingestion of the suspected food. RESULTS: Twenty-one children were enrolled (median age 6.1 years, range 0.8-14.4). The median time interval between the most recent anaphylactic reaction and the DBPCFC was 4.25 years, range 0.3-12.8. Twenty-one DBPCFCs were performed in 21 children. Eighteen of 21 children were sensitized to the food in question. Six DBPCFCs were negative (29%): three for cows milk, one for egg, one for peanut, and one for wheat. In the positive DBPCFCs, no severe reactions occurred, and epinephrine administration was not required. CONCLUSIONS: This is the first study using DBPCFCs in a consecutive series of children with a history of anaphylaxis to foods, and no indications in dietary history that the food allergy had been resolved. Our study shows that in such children having specific IgE levels below established cut-off levels reported in other studies predicting positive challenge outcomes, re-evaluation of clinical reactivity to food by DBPCFC should be considered, even when there are no indications in history that anaphylaxis has resolved. DBPCFCs can be performed safely in these children, although there is a potential risk for severe reactions.

Ready-to-use introduction schedules for first exposure to allergenic foods in children at home.

BACKGROUND: The vast majority of children will undergo their first exposure to common allergenic foods at home. However, the first exposure may lead to clinical reactions. It has been proposed to introduce allergenic foods gradually into the diets of children at risk for food allergy, but no practical dietary advice has been devised. OBJECTIVE: The aim of this study was to devise safe introduction schedules for common allergenic foods for use at home, based on the challenge doses as administered in double-blind, placebo-controlled food challenge (DBPCFCs) in children who were never exposed previously to these foods. METHODS: Seventy-two DBPCFCs were performed in 63 children as a first known exposure. The incrementing challenge doses were converted into equivalent portions of these foods in their usual household form and incorporated in introduction schedules. The feasibility of the introduction scales was tested in parents of the children attending our clinic. RESULTS: Based on the results of the positive challenges (37) in which severe reactions did not occur, detailed introduction schedules and a reference photograph of the required increasing amounts of food were devised for use at home. Feasibility testing showed that, when using these introduction schedules, parents portioned the initial doses significantly lower than without detailed instructions. CONCLUSIONS: The introduction schedules and reference photograph provide information for parents to introduce the required amounts of allergenic foods in initial low doses at home. This is expected to improve the safety of this procedure.

Respiratory health in prematurely born preschool children with and without bronchopulmonary dysplasia.

OBJECTIVE: To investigate the respiratory health of preterm infants with bronchopulmonary dysplasia (BPD) at preschool age and to determine whether lung function (measured by forced oscillation technique (FOT) and interruption technique (Rint) is affected by BPD in preterm infants compared with preterm infants without BPD. PARTICIPANTS: 3 to 5 years of age born preterm with BPD (N = 40, mean gestational age 28 weeks, mean birth weight 1051 g), and without BPD (N = 36, mean gestational age 29 weeks, mean birth weight 1179 g). OUTCOME VARIABLES: prevalence of symptoms determined by European Community Respiratory Health Survey and lung function measured by FOT and Rint. RESULTS: A large percentage of infants in both preterm groups reported respiratory symptoms during the last 12 months. Lung function measurements showed higher resonant frequency (Hz) in BPD compared with non-BPD (mean 26.8 vs 22.7, P < .001) and lower mean reactance X(4-24) (hPa.s/l)(-3.0 vs -1.9, P = .005). No differences were found in respiratory resistance between the groups, although the mean values of both groups were increased compared with reference values. CONCLUSION: Preterm birth affects respiratory health at 3 to 5 years of age. Children with BPD could be distinguished from children without BPD based on a higher resonant frequency and a lower mean reactance.

Hypertrichosis as a side effect of inhaled steroids in children.

Three spontaneous reports of patients in whom a relationship between hypertrichosis and inhaled corticosteroids (ICS) was suspected, were reported to Lareb, The Netherlands Pharmacovigilance Center. We sought evidence for and against a causal relationship between hypertrichosis and ICS in children. The relationship between hypertrichosis and ICS was studied mathematically by assessing the Reporting Odds Ratio (ROR) and by determining the Naranjo Score (NS). We also studied the reports sent to the Pharmacovigilance Database of the Uppsala Monitoring Centre (UMC) of the WHO and reviewed the literature. In the Dutch children, the ROR between hypertrichosis and ICS was 14.6 (95%CI 3.6-59.5), the NS was 4. In the database of the UMC 20 more reports on hypertrichosis and ICS were found, contributing to the results of the Dutch database. Taken together, 11 boys and 12 girls were involved with a mean age of 7 years (range 1-17). The time between the start of ICS and the occurrence of hypertrichosis varied between 1 month and 3 years. Besides the hypertrichosis, growth retardation was found in 5 children and adrenal suppression in 12. In 12 children the outcome after cessation was reported: in 6 children the hypertrichosis improved, whilst in 6 it did not. We found sufficient evidence to support the suspicion that hypertrichosis might be a true adverse effect of ICS. We found no simple dose-effect relationship but obviously there is an individual susceptibility. After cessation of ICS the exaggerated hair growth will not disappear in all children. Hypertrichosis may be a useful clinical pointer to exogenous steroid excess.

Urinary eosinophil protein X in children with atopic asthma.

UNLABELLED: The aim of this study was to investigate the relationship between urinary eosinophil protein X (uEPX) and asthma symptoms, lung function, and other markers of eosinophilic airway inflammation in asthmatic school children. METHODS: A cross-sectional study was performed in 180 steroid dependent atopic children with stable moderately severe asthma, who were stable on 200 or 500 microg of fluticasone per day. uEPX was measured in a single sample of urine and was normalized for creatinine concentration (uEPX/c). Symptom scores were kept on a diary card. FEV1 and PD20 methacholine were measured. Sputum induction was performed in 49 and FE(NO) levels measured in 24 children. RESULTS: We found an inverse correlation between uEPX/c and FEV1 (r = -.20, P = .01) and a borderline significant correlation between uEPX/c and PD20 methacholine (r = -.15, P = .06). Symptom score, %eosinophils and ECP in induced sputum and FE(NO) levels did not correlate with uEPX/c. CONCLUSION: uEPX/c levels did not correlate with established markers of asthma severity and eosinophilic airway inflammation in atopic asthmatic children.

[Bronchopulmonary dysplasia in ex-prematures approaching adulthood]. / Bronchopulmonale dysplasie bij ex-prematuren die volwassen worden.

Many patients born prematurely who developed bronchopulmonary dysplasia (BPD) as neonates are now approaching adulthood. Adults with BPD are at increased risk for respiratory difficulties including respiratory and lung function disorders. Respiratory symptoms include wheezing, cough and dyspnoea. In adult BPD patients lung function is impaired, notably by bronchus obstruction, hyperreactivity and reduced diffusion capacity; exercise capacity is also diminished. The pathophysiology of BPD is not identical to that of asthma and standard treatment for asthma is therefore not effective. Premature infants are currently treated with surfactant therapy that results in less intensive artificial respiration and oxygen being required. The classical BPD clinical picture that results from tissue damage and scarring is therefore becoming less common but another new BPD picture is emerging. This is characterised by large irregularly formed sacculi and alveoli with septation only just beginning and poor vascularization. Patients with chronic respiratory symptoms who were born prematurely should therefore undergo comprehensive testing, including detailed lung function tests and exhaled nitric oxide levels.