Long-term predictors of loss of asthma control in school-aged well-controlled children with mild to moderate asthma: A 5-year follow-up.

BACKGROUND: Long-term follow-up studies establishing risk factors for loss of asthma control in well-controlled children with mild to moderate disease are lacking and are of importance for improving patient quality of life and utilization of health-care resources. METHODS: Loss of asthma control was assessed in 146 school-aged children with well-controlled mild to moderate asthma from a Danish pediatric asthma outpatient clinic based on hospital admissions, emergency department (ED), or outpatient management of exacerbations, oral corticosteroid (OCS) use, or step-up of regular asthma treatment according to Global Initiative for Asthma (GINA) guidelines through a 5-year follow-up period. Risk factors included sex, ethnicity, age, body mass index (BMI), atopic comorbidity and predisposition, lung function, fractional exhaled nitric oxide (FeNO) level, exercise challenge test results, regular physical activity, GINA treatment step at baseline, and adherence to controller therapy. RESULTS: A total of 27 (18%) children experienced 56 acute events defined by hospital admission, ED, or outpatient management. Risk of experiencing any acute event was increased with female sex (adjusted odds ratio, aOR = 2.4 (1.0-5.9), p = 0.047) and higher baseline GINA treatment step (aOR = 1.6 (1.1-2.5), p = 0.03). Furthermore, female sex (aOR = 6.1 (1.4-42.2), p = 0.01) and higher FeNO (aOR = 1.8 (1.0-3.2), p = 0.04) were associated with OCS prescriptions, whereas no risk factors were identified for GINA treatment step-up during the 5-year follow-up. CONCLUSIONS: Female sex, higher FeNO, and higher baseline GINA treatment step increase the risk of long-term loss of control including acute events and OCS use in well-controlled children with mild to moderate asthma. These findings are important for primary physicians and clinicians in asthma outpatient clinics to identify seemingly well-controlled children at risk to plan more frequent follow-ups.

Objective confirmation of asthma diagnosis, treatment adherence and patient outcomes in children and adolescents.

AIM: The aim of this study was to investigate the diagnostic workup in children with asthma hypothesising that objective confirmation of the diagnosis is associated with improved treatment adherence and patient outcomes. METHODS: We reviewed medical records of children aged 5-18 years diagnosed with asthma at the Department of Paediatric and Adolescent Medicine, Herlev-Gentofte Hospital, Denmark, in 2018. Objective confirmation of the diagnosis was based on either (1) lung function, (2) bronchodilator response, (3) bronchial hyperresponsiveness and/or (4) elevated FeNO and was associated with treatment adherence (proportion of days covered, PDC), lung function development and exacerbations during a two-year follow-up period. RESULTS: A total of 88 children were included. Asthma was objectively confirmed in 67 (76%). Children with objective confirmation of the diagnosis were more likely to redeem short-acting beta-2-agonist prescriptions: at least once, aOR = 1.3 (95% CI, 1.1-13.1), p = 0.036, and were more adherent to inhaled corticosteroid treatment: PDC>80%, aOR = 10.4 (1.8-201.1), p = 0.033. Further, objective confirmation was associated with improved lung function and reduced bronchodilator response, but not with exacerbations. CONCLUSION: Objective confirmation of the asthma diagnosis in children is associated with an increased treatment adherence and improved lung function, which underlines the importance of conducting objective tests in the diagnostic workup in paediatric asthma management.

Allergic Comorbidity Is a Risk Factor for Not Attending Scheduled Outpatient Visits in Children with Asthma.

Asthma is one of the most common chronic diseases in children globally. Previous studies have shown that not attending asthma primary care consultations is associated with poorer treatment adherence and increased risk of loss of asthma control on a short-term basis. Here, we investigated long-term patterns and predictors of not attending scheduled asthma outpatient visits during 5-years of follow-up in 146 children with asthma. Of the 146 children, 67 (46%) did not attend at least one scheduled appointment, amounting to a total of 122 (10.8%) missed of 1133 scheduled appointments. In a multivariate analysis adjusting for total scheduled visits in the 5-year period any allergic sensitization was a significant risk factor for not attending ≥1 scheduled appointment (aOR = 6.6 (95% CI, 1.3-39.7), p = 0.03), which was not the case for asthma treatment step or lung function. Furthermore, atopic predisposition decreased the risk of non-attendance (aOR = 0.36 (0.13-0.92), p = 0.04). We found no association between non-attendance, treatment adherence or loss of asthma control. This study highlights that allergic comorbidity, but not degree of asthma severity, identifies a group of children with asthma who are prone to not attend scheduled outpatient appointments.

[Primary prevention of food allergy in childhood].

Delayed introduction of allergenic foods has failed to prevent the development of food allergy in children. This observation has led to randomised controlled trials of early introduction of allergenic foods. These trials are presented in this review. Early introduction of peanut in the LEAP and EAT trials and the introduction of cooked egg in PETIT and EAT was safe and significantly reduced challenge-proven peanut and egg allergy. Further studies are needed to explore the optimal age for introduction to different allergenic foods to reduce the prevalence of food allergy.

Assessment of adherence to asthma controllers in children and adolescents.

BACKGROUND: Low adherence to asthma controllers is known to increase the risk of uncontrolled disease and poor health outcomes. We aimed to study risk factors of long-term adherence to preventive medications in children and adolescents with asthma. METHODS: Adherence was assessed during a two-year period in 155 children with asthma followed in a tertiary pediatric asthma outpatient clinic using percentage of days covered (PDC) based on physician prescriptions and pharmacy claims data. The risk factor analysis included age, sex, ethnicity, BMI, atopic comorbidity, spirometry incentives, and fractional exhaled nitric oxide (FeNO). RESULTS: Ninety-five children, 50 (53%) males, mean age of 16.3 years (SD, 2.36), received at least one prescription for asthma controllers in the study period. Fifty-two (54%) children were classified as non-adherent with a PDC cutoff at 80%. Adherence was negatively associated with age: adherence ratio (AR) 0.84 (95% CI, 0.73-0.95), P = .008; forced expiratory volume in 1 second (FEV1): AR per L 0.6 (0.91-1.0), P = .03; unfilled inhaled beta-2-agonist prescription: AR 0.45 (0.23-0.89), P = .02; and FeNO level: AR per ppb 0.98 (0.97-0.99), P = .03, where age and FeNO retained significance in multivariate analysis. Type and number of asthma controllers were not associated with adherence. CONCLUSIONS: This study shows low adherence to preventive medication among half of the children with asthma, which is associated with increasing age and FeNO level. Therefore, an extra effort should be directed toward teenagers transitioning from pediatric to adult medicine and toward inhaled corticosteroid-treated patients with elevated FeNO to increase their adherence to asthma controllers.

Envenomation by the common European adder (Vipera berus): a case series of 219 patients.

OBJECTIVES: Every year, several patients are bitten by the common European adder (Vipera berus). The aim of this study is to present a large consecutive case series of patients bitten by V. berus, and to identify signs and symptoms indicative of complicated illness. PATIENTS AND METHODS: This is a retrospective case series from the Hospital of South West Jutland, Denmark. All 219 patients bitten by V. berus (diagnosed by history or clinical findings) from 1994 to 2012 were identified through hospital databases. A severity grading from 1 to 5 was applied, and epidemiology, symptoms and signs, complications, treatment and laboratory data were extracted from the hospital databases. RESULTS: The most common complaints on admission were pain, nausea, abdominal pain, diarrhoea and dizziness, with discoloration and oedema being the most common symptoms. Few patients experienced syncope, palpitations or respiratory distress. Fifteen percent of all patients were transferred to the ICU and 2% (all children) were suspected of having compartment syndrome. Leucocytosis, gastrointestinal symptoms and hypotension were risk factors for complicated disease. CONCLUSION: Most patients only showed symptoms of no or mild envenomation. Fifteen percent were transferred to the ICU and five patients (all children) required fasciotomy because of suspected compartment syndrome. Only 10 patients received antivenom.

Decrease by 50% of plasma IgA tissue transglutaminase antibody concentrations within 2 months after start of gluten-free diet in children with celiac disease used as a confirming diagnostic test.

BACKGROUND: Histological examination of small bowel biopsies is normally the gold standard for the diagnosis of celiac disease (CD). The objective of this study was to investigate whether the rate of decreases in elevated plasma IgA tissue transglutaminase antibody (IgA-tTG) and/or IgG deamidated gliadin peptides antibody (IgG - DGP) concentrations could be used as a confirming test for CD in children on a gluten-free diet (GFD) when biopsy was omitted in the diagnostic process. METHODS: In this retrospective study we compared children (≤18 years old) with a CD-confirming biopsy (n = 16) to children without a biopsy (n = 18). After initiation of GFD the antibody half-life (the time (T½) when the antibody concentration is 50% decreased) was determined in all children. RESULTS: Children with a biopsy (IgA-tTG, T½ = 1.9 months; IgG - DGP, T½ = 2.2 months) and children without a biopsy (IgA-tTG, T½ = 1.6 months; IgG - DGP, T½ = 2.7 months) had comparable T½ (mean) results (p < 0.05) supporting that all children had the CD diagnosis. CONCLUSIONS: When biopsy was omitted a rapid rate of decrease in CD antibody concentrations confirmed the CD diagnosis in children on GFD. The half-lives (T½) of IgA-tTG were less than 2 months in CD children.

Mapping of HLA- DQ haplotypes in a group of Danish patients with celiac disease.

BACKGROUND: A cost-effective identification of HLA- DQ risk haplotypes using the single nucleotide polymorphism (SNP) technique has recently been applied in the diagnosis of celiac disease (CD) in four European populations. The objective of the study was to map risk HLA- DQ haplotypes in a group of Danish CD patients using the SNP technique. METHODS: Cohort A: Among 65 patients with gastrointestinal symptoms we compared the HLA- DQ2 and HLA- DQ8 risk haplotypes obtained by the SNP technique (method 1) with results based on a sequence specific primer amplification technique (method 2) and a technique used in an assay from BioDiagene (method 3). Cohort B: 128 patients with histologically verified CD were tested for CD risk haplotypes (method 1). Patients with negative results were further tested for sub-haplotypes of HLA- DQ2 (methods 2 and 3). RESULTS: Cohort A: The three applied methods provided the same HLA- DQ2 and HLA- DQ8 results among 61 patients. Four patients were negative for the HLA- DQ2 and HLA- DQ8 haplotypes (method 1) but were positive for the HLA- DQ2.5-trans and HLA- DQ2.2 haplotypes (methods 2 and 3). Cohort B: A total of 120 patients were positive for the HLA- DQ2.5-cis and HLA- DQ8 haplotypes (method 1). The remaining seven patients were positive for HLA- DQ2.5-trans or HLA- DQ2.2 haplotypes (methods 2 and 3). One patient was negative with all three HLA methods. CONCLUSIONS: The HLA- DQ risk haplotypes were detected in 93.8% of the CD patients using the SNP technique (method 1). The sensitivity increased to 99.2% by combining methods 1 - 3.

Exhaled nitric oxide predicts exercise-induced bronchoconstriction in asthmatic school children.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is of particular importance in children with asthma. It is an important measure of asthma control and should be monitored by exercise testing. However, exercise testing puts a large demand on health-care resources and is therefore not widely used in routine monitoring of pediatric asthma control. The fractional concentration of exhaled nitric oxide (FeNO) also reflects uncontrolled asthma. We hypothesized that FeNO may be used for prescreening of asthmatic children to exclude those with good asthma control unlikely to have EIB, thereby reducing the need for exercise testing. OBJECTIVE: The aim of this study was to estimate the value of FeNO as a predictor of EIB in asthmatic children. METHODS: Stable outpatient asthmatic school children performed standard exercise challenge tests and measurement of FeNO. RESULTS: FeNO and response to a standardized submaximal exercise test on the treadmill were measured in 111 school children with asthma. EIB could be excluded with a probability of 90% in asthmatic children with FeNO levels < 20 parts per billion (ppb) without current inhaled corticosteroid treatment, and < 12 ppb in children with current inhaled corticosteroid treatment. CONCLUSION: Measurement of FeNO is a simple, and time- and resource-efficient tool that may be used to screen for EIB testing and therefore optimizes the resources for exercise testing in pediatric asthma monitoring.