Episodic viral wheeze and multiple-trigger wheeze in preschool children are neither distinct nor constant patterns. A prospective multicenter cohort study in secondary care.

OBJECTIVES: To evaluate whether episodic viral wheeze (EVW) and multiple-trigger wheeze (MTW) are clinically distinguishable and stable preschool wheezing phenotypes. METHODS: Children of age 1 to 4 year with recurrent, pediatrician-confirmed wheeze were recruited from secondary care; 189 were included. Respiratory and viral upper respiratory tract infection (URTI) symptoms were recorded weekly by parents in an electronic diary during 12 months. Every 3 months, diary-based symptoms were classified as EVW or MTW and compared to phenotypes assigned by pediatricians based on clinical history. We collected nasal samples for respiratory virus PCR during URTI, respiratory symptoms and in absence of symptoms. RESULTS: Of 660 3-month periods, the diary-based phenotype was EVW in 11%, MTW in 54% and 35% were free from respiratory episodes. Pediatrician-based classification showed 59% EVW and 26% MTW. The Kappa measure of agreement between diary-based and pediatrician-assigned phenotypes was very low (0.12, 95%CI, 0.07-0.17). Phenotypic instability was observed in 32% of cases. PCR was positive in 71% during URTI symptoms, 66% during respiratory symptoms and 38% in the absence of symptoms. CONCLUSION: This study shows that EVW and MTW are variable over time within patients. Pediatrician classification of these phenotypes based on clinical history does not correspond to prospectively recorded symptom patterns. The applicability of these phenotypes as a basis for therapeutic decisions and prognosis should be questioned.

Asthma medication in children who are overweight/obese: justified treatment?

BACKGROUND: The prevalence of asthma and obesity have increased over the last decades. A possible association between these two chronic illnesses has been suggested, since the prevalence of asthmatic symptoms rises with increasing Body Mass Index (BMI). However, asthma is only one of several possible causes of shortness of breath in obese children. The aim of this study is to evaluate the prevalence of overtreatment with asthma medication in a cohort overweight/obese children with respiratory symptoms visiting a pediatric outpatient clinic. METHODS: Children referred to a pediatric outpatient clinic aged ≥4- ≤ 18 years with overweight/obesity (defined as BMI-sds > 1.1) and asthmatic symptoms were included. The diagnosis asthma was evaluated and classified in no, unlikely, probable and confirmed asthma, based on clinical parameters and/or spirometry results. Overtreatment was defined as asthma medication prescribed in participants classified as no or unlikely asthma. And undertreatment as probable or confirmed asthma without asthma medication prescribed . RESULTS: Three hundred thirty-eight participants were included, of which 92.6% (313/338) had a prescription for asthma medication. Overtreatment was observed in 27.2% (92/338) participants. Nine participants were undertreated. CONCLUSION: More than 25% overtreatment with asthma medication was observed in a cohort overweight/obese children with asthmatic symptoms. This finding emphasizes that the diagnosis of asthma must be confirmed before commencement of medication. The diagnosis of asthma should be based on standard questionnaires evaluating asthmatic symptoms, lung functions test and regular reassessments. Further studies concerning overtreatment with asthma medication in normal weight pediatric populations are warranted, to evaluate whether overtreatment is specific for overweight/obese children.

Screening children for pulmonary arteriovenous malformations: Evaluation of 18 years of experience.

BACKGROUND: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease with multi-systemic vascular dysplasia. Early diagnosis through screening is important to prevent serious complications. How best to screen children of affected parents for pulmonary arteriovenous malformations (PAVMs) is often subject to debate. Transthoracic contrast echocardiogram (TTCE) is considered optimal in screening for PAVMs in adults. Guidelines for the screening of children are not specific, reflecting the lack of scientific evidence on the best method to use. OBJECTIVE: Aims of this study are (i) to evaluate our current screening method, consisting of history, physical examination, pulse oximetry, and chest radiography and (ii) to assess whether postponing more invasive screening for PAVMs until adulthood is safe. METHODS: This is a prospective observational cohort study using a patient database. RESULTS: Over a period of 18 years (mean follow-up 9.21 years, SD 4.72 years), 436 children from HHT families were screened consecutively. A total of 175/436 (40%) children had a diagnosis of HHT. PAVMs were detected in 39/175 (22%) children, 33/39 requiring treatment by embolotherapy. None of the screened children suffered any PAVM-associated complications with this screening method. CONCLUSION: This study shows that a conservative screening method during childhood is sufficient to detect large PAVMs and protect children with HHT for PAVM-related complications. Postponing TTCE and subsequent chest CT scanning until adulthood to detect any smaller PAVMs does not appear to be associated with major risk.

Sensitization predicts asthma development among wheezing toddlers in secondary healthcare.

INTRODUCTION: Some wheezing toddlers develop asthma later in childhood. Sensitization is known to predict asthma in birth cohorts. However, its predictive value in secondary healthcare is uncertain. AIM: This study examines the predictive value of sensitization to inhalant allergens among wheezing toddlers in secondary healthcare for the development of asthma at school age (≥6 years). METHODS: Preschool children (1-3 years) who presented with wheezing in secondary healthcare were screened on asthma at school age with the International Study of Asthma and Allergies in Childhood questionnaire. The positive and negative predictive value (PPV and NPV) of specific IgE to inhalant allergens (cut-off concentration 0.35 kU/L) and several non-invasive variables from a child's history (such as hospitalization, eczema, and parental atopy) were calculated. The additional predictive value of sensitization when combined with non-invasive predictors was examined in multivariate analysis and by ROC curves. RESULTS: Of 116 included children, 63% developed asthma at school age. Sensitization to inhalant allergens was a strong asthma predictor. The odds ratio (OR), PPV and NPV were 7.4%, 86%, and 55%, respectively. Eczema (OR 3.4) and hospital admission (OR 2.6) were significant non-invasive determinants. Adding sensitization to these non-invasive predictors in multivariate analysis resulted in a significantly better asthma prediction. The area under the ROC curve increased from 0.70 with only non-invasive predictors to 0.79 after adding sensitization. CONCLUSION: Sensitization to inhalant allergens is a strong predictor of school age asthma in secondary healthcare and has added predictive value when combined with non-invasive determinants. Pediatr Pulmonol. 2017;52:729-736. © 2017 Wiley Periodicals, Inc.

Respiratory tract infections and asthma control in children.

INTRODUCTION: Asthma control is considered the major goal of asthma management, while many determinants of control are difficult to modify. We studied the association between respiratory infection episodes (RTIs) of various types and asthma control. METHODS: Cross-sectional data were used from children aged 4-18 years with physician-diagnosed asthma who participated in a web-based electronic portal for children with asthma, allergies or infections. Asthma control was measured using the Childhood Asthma Control Test (C-ACT) or the Asthma Control Test (ACT). Linear regression was used to analyse the association between categories of numbers of various types of RTIs sustained in the preceding 12 months (categorized) and asthma control, adjusted for potential confounders. RESULTS: Asthma control was assessed in 654 children, and 68.5% were clinically well controlled (ACT ≥ 20). Higher total numbers of RTIs in the last 12 months were strongly associated with a lower level of asthma control (p(trend) < 0.001). Similarly strong statistically significant associations were found for subtypes of RTI: ≥4 vs. 0 otitis episodes: coefficient -1.7 (95% CI -3.3 to -0.2); ≥5 vs.0 colds: coefficient -2.3 (95% CI -3.0 to -1.6); ≥3 vs. 0 bronchitis episodes: coefficient -3.1 (95% CI -4.0 to -2.3), each with p(trend) < 0.05. CONCLUSION: Higher numbers of reported respiratory tract infections are associated with lower level of asthma control. The different type of respiratory tract infections contribute equally to less controlled asthma.

Diagnostic properties of C-reactive protein for detecting pneumonia in children.

BACKGROUND: The diagnostic value of C-reactive protein (CRP) level for pneumonia in children is unknown. As a first step in the assessment of the value of CRP, a diagnostic study was performed in children at an emergency department (ED). METHODS: In this cross-sectional study, data were retrospectively collected from children presenting with suspected pneumonia at the ED of Antonius Hospital Nieuwegein in The Netherlands between January 2007 and January 2012. Diagnostic outcome was pneumonia yes/no according to independent radiologist. (Un)adjusted association between CRP level and pneumonia and diagnostic value of CRP were calculated. RESULTS: Of 687 presenting children, 286 underwent both CRP measurement and chest radiography. 148 had pneumonia (52%). The proportion of pneumonia increased with CRP level. Negative predictive values declined, but positive predictive values increased with higher CRP thresholds. Univariable odds ratio for the association between CRP level and pneumonia was 1.2 (95% CI 1.11-1.21) per 10 mg/L increase. After adjustment for baseline characteristics CRP level remained associated with pneumonia. CONCLUSIONS: CRP level has independent diagnostic value for pneumonia in children presenting at the ED with suspected pneumonia, but low levels do not exclude pneumonia in this setting. These results prompt evaluation of CRP in primary care children with LRTI.

The expert network and electronic portal for children with respiratory and allergic symptoms: rationale and design.

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.

[Diagnosis of fetal alcohol spectrum disorders]. / Diagnostiek van foetale alcoholspectrumstoornissen.

Prenatal alcohol exposure may cause decreased growth of the child, congenital abnormalities, specific facial characteristics, and, most importantly, mental retardation and behavioural disorders, all known as fetal alcohol spectrum disorders (FASD). A significant number of pregnant women in the Netherlands drink alcohol, but the prevalence of FASD in our country is unknown. Repeated and high peak blood alcohol concentrations, for example in the case of binge drinking by the mother, result in more severe abnormalities; a safe limit for alcohol consumption in pregnancy cannot be defined. In 2007 and 2008, Dutch paediatricians reported a total of 56 diagnosed cases of FASD, mostly adopted and foster children. Possibly the condition has not always been diagnosed. Use of international guidelines for diagnosis by the medical profession may improve detection. The guidelines of the Canadian Public Health Agency provide a useful and generally accepted classification, with strict cut-off points to avoid overdiagnosis; attention should always be paid to the broad differential diagnosis.

Atopic disease and exhaled nitric oxide in an unselected population of young adults.

BACKGROUND: Several studies have reported elevated levels of fractional exhaled nitric oxide (FeNO) in atopic patients, particularly in asthmatic patients, suggesting that FeNO is a marker of bronchial inflammation. However, the independent influence of different atopic entities (eczema, allergic rhinitis, and asthma) on FeNO has never been studied in the general population. OBJECTIVE: To study the influence of a questionnaire-based diagnosis of atopic diseases and IgE and lung function measurements on FeNO levels. METHODS: This study was part of a follow-up on otitis media of a birth cohort of 1,328 children born in Nijmegen, the Netherlands, between September 1, 1982, and August 31, 1983. Within the birth cohort, the incidence of asthma, allergic rhinitis, and eczema was determined, and off-line FeNO, spirometry, and IgE measurements were performed at the age of 21 years. RESULTS: FeNO measurements were successfully performed in 361 participants. Median FeNO levels were significantly higher in those with vs without eczema (23.6 vs 18.0 ppb; P < .0001), those with vs without allergic rhinitis (20.7 vs 17.8 ppb; P = .0001), and those with vs without atopic asthma (23.3 vs 18.1 ppb; P = .02) but not in those with vs without asthma (20.8 vs 18.3 ppb; P = .24). Eczema, allergic rhinitis, smoking, sex, and atopic sensitization appeared to be independently associated with log FeNO in this population sample, whereas (atopic) asthma was not. No effect on FeNO levels was observed for lung function parameters. CONCLUSION: Eczema, allergic rhinitis, and atopic status were all independently associated with elevated FeNO levels, whereas (atopic) asthma was not. This finding implies that future studies into the role of FeNO in asthma should consider the influence of atopic disease outside the lungs.

Prediction of asthma in young adults using childhood characteristics: Development of a prediction rule.

OBJECTIVE: To develop an easily applicable prediction rule for asthma in young adulthood using childhood characteristics. METHODS: A total of 1,055 out of 1,328 members of a Dutch birth cohort were followed from 2 to 21 years of age. Univariate and multivariate logistic regression analyses were used to evaluate the predictive value of childhood characteristics on asthma at 21 years of age. A prognostic function was developed, and the area under the receiving operating characteristic (ROC) curve was used to estimate the predictive ability of the prognostic models. RESULTS: Of the 693 responding subjects, 86 (12%) were diagnosed with asthma. Independent prognostic factors at ages 2 and 4 years were female gender (odds ratios (OR) 1.9 and 2.1; 95% confidence intervals (CI) 1.2-3.2 and 1.3-2.5), smoking mother (OR 1.6 and 1.6; CI 1.0-2.7 and 1.0-2.6), lower respiratory tract illness (OR 1.9 and 2.4; CI 1.0-3.6 and 1.4-4.0), and atopic parents (OR 2.1 and 1.9; CI 1.3-3.4 and 1.2-3.1). The predictive power of both models was poor; area under ROC curve was 0.66 and 0.68, respectively. CONCLUSION: Asthma in young adulthood could not be predicted satisfactorily based on childhood characteristics. Nevertheless, we propose that this method is further tested as a tool to predict development of asthma.

Persistence of upper respiratory tract infections in a cohort followed from childhood to adulthood.

OBJECTIVE: To assess (1) prevalences of recurrent URTIs (rURTIs) and relapsing/persistent rURTIs and associated medical consumption between 0 and 21 years of age and (2) whether rURTIs experienced in early life predispose to upper airway disease later in life. METHODS: A cohort of all children born in Nijmegen, The Netherlands, between September 1982 and September 1983, was assessed repeatedly from 2 to 21 years of age with questionnaires regarding infections of the upper respiratory tract (URTIs), use of antibiotics, ENT operations and known risk factors for URTIs. RESULTS: One hundred and sixty-one of the 693 cohort member (23%) suffered from relapsing rURTIs between 0 and 21 years of age, whereas only 7 (1%) suffered from persistent rURTIs throughout this period. Two hundred and six (30%) had used antibiotics more than once; and 220 (32%) had undergone at least one ENT operation. Of the 166 participants with rURTI between 8 and 21 years, 140 (84%) had had rURTI before. CONCLUSIONS: rURTIs are highly prevalent throughout early life and associated medical consumption is substantial. The challenge therefore is to develop therapeutic/preventive strategies that will prevent rURTIs in the first years of life.