Loss of control in preschoolers with asthma is a risk factor for disease persistency.

AIM: To describe the relationship between loss of control events in preschoolers with asthma and persistence of disease. METHODS: We reviewed medical records of children <6 years diagnosed with asthma in 2018 to assess loss of control events during three years of follow-up. Asthma persistency was defined by redeem of short-acting ß2-agonist or asthma controllers within one year after the end of follow-up. Logistic regression models were applied to analyse the association between loss of control events and persistence of asthma. RESULTS: We included 172 patients (median age 1.8 years), whereof 126 (73.3%) experienced a loss of control event and 87 (50.6%) had asthma one year after the end of follow-up. Any loss of control event was associated with persistence of asthma adjusted for controller treatment at inclusion, prior exacerbations, atopic comorbidity and caesarean section: aOR, 10.9 (95% CI, 3.9-34.6), p < 0.001. This was also significant restricted to events in the first year of follow-up: 3.52 (1.50-8.67), p < 0.01 and among children only experiencing one event: 6.4 (1.7-27.3), p = 0.01. CONCLUSION: Loss of control events during a 3-year period among preschoolers with asthma are closely related to disease persistency, which may aid clinicians to assess risk of persistent asthma in young children.

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.

Risk Factors for Non-Adherence to Inhaled Corticosteroids in Preschool Children with Asthma.

Non-adherence to asthma controllers increases morbidity among school-aged children. This study aimed to determine non-adherence risk factors in preschool children with asthma. We investigated 172 children <6 years diagnosed with asthma in 2018 and analyzed baseline characteristics and loss of control events extracted from the medical records for four years following diagnosis. At end of follow-up, 79 children had a prescription of inhaled corticosteroids (ICS) and were included in the analyses. Adherence was assessed in a two-year period through pharmacy claims using percentage of days covered (PDC) analyzed dichotomously with non-adherence defined as PDC < 80% and using adherence ratio (AR) defined as days with medical supply divided by days without. Of the 79 children, 59 (74.7%) were classified as non-adherent. In analyses adjusted for sex, age and exacerbations prior to inclusion, adherence was positively associated with having had a loss of control event requiring a step-up in asthma controller (aAR:2.34 [1.10;4.98], p = 0.03), oral corticosteroids (aAR:2.45 [1.13;5.34], p = 0.026) or redeeming a short-acting b2-agonist prescription (aAR:2.91 [1.26;6.74], p = 0.015). Further, atopic comorbidity was associated with increased adherence (aAR:1.18 [1.01;1.37], p = 0.039), whereas having a first degree relative with asthma was associated with worse adherence (aAR:0.44 [0.23;0.84], p = 0.015). This study found poor adherence to ICS among three quarters of preschool children with asthma. Increasing adherence was associated with atopic comorbidity and loss of control events, whereas lower adherence was associated with atopic predisposition. These findings should be considered to improve adherence in preschool children with asthma.

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.

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.

[Hereditary hypokaliaemic periodic paralysis in a 13-year-old boy].

Hypokaliaemic periodic paralysis is a rare hereditary neuro-muscular disease caused by an error in the ion-canals in muscle cells resulting in decreased excitabiliy. It presents itself in the late childhood or teenage years with a periodic paralysis without involving respiratory and heart muscles. Our patient was a 13-year-old boy, who woke up with decreased strength in arms and legs after excessive physical activity and a high carbo-hydrate intake. Tests showed a low P-potassium level. The patient had full remission of his symptoms within 24 hours.

Low incidence of children with acute epiglottis after introduction of vaccination.

INTRODUCTION: The aim of this retrospective case series is to describe the epidemiology, symptoms and findings of acute epiglottitis in hospitalized patients after the introduction of the Haemophilus influenzae type B (HIB) vaccine and to identify any symptoms or findings predictive of a prolonged hospital stay. MATERIAL AND METHODS: Medical records on all patients discharged with the International Classification of Diseases 10 diagnostic code DJ051, acute epiglottitis, from January 1997 to December 2012 were reviewed. A total of 41 patients were identified. RESULTS: In all, 37 patients were included, only one of whom was a child. The dominating symptom was a sore throat (97.2%). A hoarse voice was found in 20 patients (58.8%), and 14 patients (40.0%) were drooling. Thirteen patients (36.1%) had trouble breathing. Nine patients (24.3%) were diagnosed with abscess. Two adults tested positive for HIB. The average length of hospitalization was 6.1 days. The average stay in the intensive care unit was 1.2 days for patients who were not intubated and 4.0 days for patients who were intubated or tracheotomised. Six patients (16.2%) were intubated. One patient (2.7%) was directly tracheotomised. CONCLUSION: Our study shows that the incidence of adult acute epiglottis seems to remain unchanged compared with a previous investigation from the same geographical region. The disease is potentially life-threatening, and intubation or tracheostomy was required in 18.9% patients in this study. Respiratory distress had the largest impact on the length of hospitalization. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[Late debut of neonatal pneumonia caused by Chlamydia trachomatis]. / Sen debut af neonatal pneumoni forårsaget af Chlamydia trachomatis.

A newborn colonized with Chlamydia trachomatis will often show symptoms of conjunctivitis and/or pneumonia. We report a case of interstitial pneumonia caused by C. trachomatis in a 2-month-old boy admitted with RSV. We point to the importance of C. trachomatis in the differential diagnostics of an infant with respiratory symptoms even in the presence of additional infectious agents.

[Malignant ovarian tumour as cause of virilisation in a 12 year-old girl]. / Malign ovarietumor som årsag til virilisering af en 12-årig pige.

Virilisation in girls includes androgen dependent growth of terminal hair, acne, deepening of the voice and increased muscle mass. Sudden onset of symptoms, rapid progression, short duration and hyperandrogenaemia are ominous signs and the patient must be referred to a specialist as soon as possible to rule out cancer and avoid worsening of the irreversible virilisation. We describe a girl with severe virilisation as the sole symptom of an androgen producing Sertoli-Leydig cell tumour. Ovarian tumours are rare in children and malignant ovarian tumours account for less than 1% of childhood cancer.

Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study.

OBJECTIVE: To study the association between wheezy symptoms in young children and the presence of bacteria in the airways. DESIGN: Birth cohort study. SETTING: Clinical research unit in Copenhagen. PARTICIPANTS: Children of asthmatic mothers, from age 4 weeks to 3 years, with planned visits and acute admissions to the research clinic. MAIN OUTCOME MEASURE: Frequency of bacteria and virus carriage in airway aspirates during wheezy episodes and at planned visits without respiratory symptoms. RESULTS: 984 samples (361 children) were analysed for bacteria, 844 (299 children) for viruses, and 696 (277 children) for both viruses and bacteria. Wheezy episodes were associated with both bacterial infection (odds ratio 2.9, 95% confidence interval 1.9 to 4.3; P<0.001) and virus infection (2.8, 1.7 to 4.4; P<0.001). The associations of bacteria and viruses were independent of each other. CONCLUSION: Acute wheezy episodes in young children were significantly associated with bacterial infections similar to but independent of the association with virus infections.

Elevated exhaled nitric oxide in high-risk neonates precedes transient early but not persistent wheeze.

RATIONALE: Elevated fractional exhaled nitric oxide (Fe(NO)) concentration has been suggested to predict early childhood wheeze and sensitization. OBJECTIVES: To investigate the association between Fe(NO) in asymptomatic neonates and the development of wheeze patterns and atopic intermediary phenotypes in the first 6 years of life. METHODS: We measured Fe(NO) in 253 healthy 1-month-old neonates from the Copenhagen Prospective Study on Asthma in Childhood birth cohort and monitored prospectively wheezy episodes by daily diary cards during the first 6 years of life. Total IgE, specific IgE, and blood eosinophil count were assessed at age 6 months, 4 years, and 6 years. Associations were studied by Cox regression, logistic regression, and generalized linear models. MEASUREMENTS AND MAIN RESULTS: Increased neonatal Fe(NO) level was significantly associated with the development of recurrent wheeze in the first year of life (hazard ratio, 2.63; 95% confidence interval, 1.1 to 6.2; P = 0.026) but not thereafter. The association was unaffected by environmental tobacco smoke exposure. Fe(NO) was not associated with elevated levels of total IgE, specific IgE, or blood eosinophil count at any age point and was unrelated to neonatal lung function. CONCLUSIONS: An elevated Fe(NO) level in asymptomatic neonates born to mothers with asthma preceded the development of transient early wheezing, but not persistent wheezing during preschool age, and was unrelated to atopy. This suggests an early disease process other than small airway caliber contributing to the transient wheezing phenotype.

Childhood asthma after bacterial colonization of the airway in neonates.

BACKGROUND: Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life. METHODS: The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-month-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age. RESULTS: Hypopharyngeal samples were cultured from 321 neonates at 1 month of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly associated with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after beta2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, respectively). CONCLUSIONS: Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.

Acute relief of exercise-induced bronchoconstriction by inhaled formoterol in children with persistent asthma.

STUDY OBJECTIVE: To compare the acute bronchodilatory effect of the long-acting beta2-agonist formoterol against the short-acting beta2-agonist (SABA) terbutaline during exercise-induced bronchoconstriction (EIB) in children with asthma. DESIGN: A randomized, double-blind, placebo-controlled, crossover study of the immediate effect of formoterol, 9 microg, vs terbutaline, 0.5 mg, and placebo administered as dry powder at different study days. Exercise challenge test was used as a model of acute bronchoconstriction. PATIENTS: Twenty-four 7- to 15-year-old children with persistent asthma. INTERVENTIONS: The children performed standardized treadmill exercise tests, breathing dry air, with a submaximal workload. Study medication was administered 5 min after exercise if FEV1 dropped > or = 15% within 5 min after exercise. FEV1 and forced expiratory flows were measured repeatedly until 60 min after dose. RESULTS: Formoterol and terbutaline offered a significant acute bronchodilatory effect from 3 min after dose compared with placebo (p < 0.001). There was no difference between formoterol and terbutaline in FEV1 5 min after dose (p = 0.15), with a mean increase from each predrug baseline of 62% of the maximum increase for both. Median times to recovery within 5% of baseline FEV1 were 5.0 min and 7.4 min for formoterol and terbutaline, respectively (p = 0.33). CONCLUSION: Single-dose formoterol, 9 microg, via dry powder inhaler provided an acute bronchodilatory effect similar to terbutaline during EIB in schoolchildren with persistent asthma. Formoterol is at least as effective as SABA and may be considered an alternative in the treatment of acute bronchoconstriction in school children.

Intermittent inhaled corticosteroids in infants with episodic wheezing.

BACKGROUND: We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing. METHODS: We assigned one-month-old infants to treatment with two-week courses of inhaled budesonide (400 mug per day) or placebo, initiated after a three-day episode of wheezing, in this single-center, randomized, double-blind, prospective study of three years' duration. The primary outcome was the number of symptom-free days; key secondary outcomes were the time to discontinuation due to persistent wheezing and safety, as evaluated by height and bone mineral density at the end of the study. RESULTS: We enrolled 411 infants and randomly assigned 294 to receive budesonide at a first episode of wheezing. The proportion of symptom-free days was 83 percent in the budesonide group and 82 percent in the placebo group (absolute difference, 1 percent; 95 percent confidence interval, -4.8 to 6.9 percent). Twenty-four percent of children in the budesonide group had persistent wheezing, as compared with 21 percent in the placebo group (hazard ratio, 1.22; 95 percent confidence interval, 0.71 to 2.13)--a finding that was unaffected by the presence or absence of atopic dermatitis. The mean duration of the acute episodes was 10 days in both groups and was independent of respiratory viral status. Height and bone mineral density were not affected by treatment. CONCLUSIONS: Intermittent inhaled corticosteroid therapy had no effect on the progression from episodic to persistent wheezing and no short-term benefit during episodes of wheezing in the first three years of life. (ClinicalTrials.gov number, NCT00234390.).