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.

Adverse reactions after oral provocation with aluminium in children with vaccination granulomas and aluminium contact allergy.

BACKGROUND: According to their parents, some children with aluminium contact allergy and vaccination granulomas may react to aluminium-containing foods by developing dermatitis, granuloma itch and subjective symptoms. OBJECTIVES: The objective of this study is to determine whether oral intake of aluminium-containing pancakes can cause adverse events and/or systemic contact dermatitis (SCD) in children with vaccination granulomas and aluminium contact allergy. PATIENTS/METHODS: A total of 15 children aged 3-9 years (mean age, 5 years) with vaccination granulomas and positive patch-test results to aluminium chloride hexahydrate 2%/10% pet. completed a 3-week blinded randomized controlled crossover oral aluminium/placebo provocation study with pancakes. Granuloma itch and other subjective symptoms were evaluated daily on a visual analogue scale (VAS). Dermatitis was evaluated by the primary investigator, and sleep patterns were tracked with an electronic device. Aluminium bioavailability was assessed by measuring aluminium excretion in the urine. The children served as their own controls with the placebo provocations. RESULTS: All 15 children completed the study. The mean VAS scores were slightly higher during aluminium provocations compared with placebo for granuloma itch (mean VAS, 1.5 vs. 1.4, p = 0.6) but identical for other subjective symptoms (0.6 vs. 0.6, p = 1). There were no differences in sleep patterns and no significant correlation between urinary aluminium excretion and symptom severity. Three children developed a symmetrical rash on the face or buttocks on day 4 of the aluminium provocations, but not during placebo provocations. CONCLUSIONS: No difference was found between oral aluminium intake and the occurrence of subjective symptoms and granuloma itch, but on a case-basis oral aluminium may be associated with the development of systemic contact dermatitis.

Patterns of Clinical Reactivity in a Danish Cohort of Tree Nut Allergic Children, Adolescents, and Young Adults.

Background: Tree nut allergy is associated with severe reactions and poly-sensitization to other nuts and peanuts often occurs. There are regional differences in sensitization profiles that result in differences in clinical presentation. Denmark is located in a birch pollen endemic area, which could influence the allergy patterns due to pollen cross-sensitization. Objective: This study aimed to investigate patterns of sensitization and clinical reactivity to tree nuts and peanuts and threshold levels for oral food challenges (OFCs) in a Danish cohort of tree nut allergic children, adolescents, and young adults. Methods: Forty tree nut allergic subjects were assessed for clinical reactivity to six nuts, i.e., hazelnut, walnut, pistachio, cashew, almond, and peanut, by OFCs or convincing medical history of an immediate allergic reaction or tolerance. Clinical presentation and allergen-specific immunoglobulin E (sIgE) levels together with eliciting dose and rescue medication in OFCs were furthermore assessed. Results: Allergy to two or more tree nuts was observed in most cases. Hazelnut-walnut dual allergy was common but not exclusively observed as concomitant allergies. Allergy to cashew was coincided in all but one of the assessed subjects with pistachio allergy. Half of all assessed subjects were allergic to peanuts. Oral symptoms followed by a skin reaction were the most common symptomatology that lead to OFC cessation and subjects often presented with symptoms from two or more organ systems. OFC threshold levels were within the same range, but cashew was distinguished from other nuts by causing allergic symptoms at the lowest dose. Clinical reactivity and the allergy patterns were to some extent reflected by sIgE levels and by correlations in sIgE between the nuts. Conclusions: In this Northern European cohort, subjects with clinically relevant tree nut allergy were generally allergic to two or more tree nuts and close to half of them also to peanuts. There were two distinct and independent allergic phenotypes; the majority of hazelnut allergic subjects were also allergic to walnut, and all but one subject with cashew allergy were dual allergic to pistachio. These findings are consistent with a strong sIgE correlation between hazelnut and walnut and a close to total sIgE correlation between cashew and pistachio.

Ethylene glycol toxicosis in milk-fed dairy calves.

BACKGROUND: Ethylene glycol (EG) (antifreeze) toxicosis has mostly been reported in dogs and cats, while reports on EG toxicosis in cattle are sparse. We report EG toxicosis in 25 milk-fed calves associated with a leak in the cooling pipes in a milk taxi. The milk taxi was connected to a geothermal heating system in which EG was used as antifreeze. CASE PRESENTATION: Although the assistant responsible for feeding milk to the calves observed a few blue-colored droplets of liquid on the surface of the milk in the milk taxi and suspected EG contamination, the milk was fed to the calves. Within hours, the calves became depressed and some died within the next 2 days. Necropsy and histopathology revealed widespread severe acute renal tubular necrosis with numerous birefringent crystals in the tubular lumen. Biochemical analysis of serum showed severe damage to the kidneys (marked azotemia) and hypochloremia, hyponatremia and hyperkalemia; findings consisting with metabolic acidosis. After feeding the calves, the assistant inspected the milk taxi and found a leaking cooling pipe. CONCLUSIONS: The suspected EG toxicosis was confirmed by the observation of renal tubular necrosis, numerous intratubular crystals, and metabolic acidosis. EG toxicosis due to leaking pipes connected to a geothermal heating system has not been reported previously. Alternative antifreeze products that are less toxic than EG are recommended for use if there is a risk of contamination of human and animal foodstuffs in case of a leak in the system.

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.

Does aluminium in sunscreens cause dermatitis in children with aluminium contact allergy: A repeated open application test study.

BACKGROUND: Parents report that children with aluminium contact allergy and vaccination granulomas may react to aluminium-containing sunscreen following application. OBJECTIVES: To evaluate whether contact dermatitis develops following repeated application of aluminium-containing sunscreens in children with aluminium sensitization and vaccination granulomas. METHODS: Sixteen children aged 2-9 years (mean age 5 years) with vaccination granulomas and a positive patch test reaction to aluminium chloride hexahydrate 2%/10% petrolatum completed a blinded repeated open application test (ROAT) with two daily applications of two sunscreens for 14 days. One cream contained aluminium and the other did not. The children served as their own controls. RESULTS: Sixteen children completed the study. Only one child (6%) had a positive skin reaction during ROAT on day 2 to the sunscreen with aluminium. None reacted to the sunscreen without aluminium. CONCLUSIONS: Use of aluminium-containing sunscreens may on a case basis lead to allergic contact dermatitis in aluminium allergic 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.

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.

Biologicals in childhood severe asthma: the European PERMEABLE survey on the status quo.

INTRODUCTION: Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe. METHODS: Structured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data. RESULTS: We interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals. CONCLUSION: Substantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.

[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.

Maternal life and work stressors during pregnancy and asthma in offspring.

BACKGROUND: Maternal stressors during pregnancy are potential risk factors for asthma in offspring. However, previous studies have been limited by the use of self-reported data focusing on stressors either in private life or at work. This study examined the association between maternal stressors both in private life and at work during pregnancy and asthma in offspring. METHODS: In the Danish National Birth Cohort, 75 156 live-born singletons born during 1996-2002 were identified. Maternal information on job title were available around weeks 12-16 of gestation. Data on maternal bereavement, life-threatening illness, suicide attempt and alcohol or drug abuse of a close relative and offspring childhood asthma (3-10 years of age) were obtained from Danish nationwide registers. Maternal psychosocial work stressors (job control, psychological job demands, emotional job demands, work-related violence and threats of work-related violence) were estimated by the use of job-exposure matrices. The association between maternal stress and childhood asthma was analysed in Cox models adjusted for maternal age, comorbidity and parity. RESULTS: Neither private-life nor work stressors were related to onset of asthma in offspring. Separate analyses by parental atopy or onset of asthma in offspring supported the main findings. CONCLUSIONS: This study does not support an elevated risk of childhood asthma related to exposure to stress during pregnancy.

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.

Sharing our story individualized and triadic nurse meetings support couples adjustment to living with deep brain stimulation for Parkinson's disease.

Treatment with deep brain stimulation for Parkinson's disease, leads to a rapid improvement in mobility, which may challenge patients and spouses when adjusting to everyday life. An intervention, developed to support the adjustment to everyday life with DBS, demonstrated that individualized meetings with a specialized nurse was experienced as important and fruitful by both patient and spouses. Purpose: The aim was to gain a deeper understanding of how the meetings contributed to the adjustment process. Method: 38 audio-recorded meetings and six written summaries from eight couples participating in the intervention, were analyzed in a hermeneutic process. Results: The analysis revealed four themes: A relational triad of co-creating personal knowing. Sharing and listening in an atmosphere of trust and openness. Unveiling the couple's everyday life, coping strategies and expectations. Supporting adjustment through knowing their personal story. Conclusion: The triadic dynamics in the meetings were quite particular. The main focus was the patients' and spouses' stories, individually and as a couple. The DBS nurse pursues solutions based on professional and specialized knowledge of Parkinson's disease and the couple's everyday life. Thus, the intervention meetings offered tailored, individualized and specialized care in supporting adjustment to DBS for PD both individually and as couples.

Children with vaccination granulomas and aluminum contact allergy: Evaluation of predispositions, avoidance behavior, and quality of life.

BACKGROUND: Aluminum contact allergy is mostly seen in children with vaccination granulomas, following immunization with aluminum-adsorbed childhood vaccines. OBJECTIVES: To characterize a cohort of children with vaccination granulomas and aluminum allergy concerning early life conditions, exacerbating factors, avoidance behavior, treatments, and potential impact on quality of life. METHODS: A questionnaire study was conducted among 177 children aged 0 to 15 years with vaccination granulomas and aluminum allergy, and a reference group of 61 children aged 3 to 14 years with various types of dermatitis undergoing patch testing. RESULTS: All children in the granuloma group were reportedly affected by itch. Infection exacerbated the itch in 59%. Other worsening factors were eating tin-foiled/canned food (31%) and use of aluminum-containing sunscreen (46%). Many parents took precautions to avoid aluminum exposure. Children with granulomas were more likely to be nonadherent to the National Vaccination Program than the reference group (27% vs 2%, P < .001). Parents in the granuloma group reported a decreased life quality for both parents and children compared with the reference group. CONCLUSIONS: Itching vaccination granulomas and aluminum allergy have a considerable negative impact on affected children and their families, causing avoidance behavior, reduced adherence to vaccination programs, and a negative effect on the overall life quality.

Immunoglobulin G structure and rheumatoid factor epitopes.

Antibodies are important for immunity and exist in several classes (IgM, IgD, IgA, IgG, IgE). They are composed of symmetric dimeric molecules with two antigen binding regions (Fab) and a constant part (Fc), usually depicted as Y-shaped molecules. Rheumatoid factors found in patients with rheumatoid arthritis are autoantibodies binding to IgG and paradoxically appear to circulate in blood alongside with their antigen (IgG) without reacting with it. Here, it is shown that rheumatoid factors do not react with native IgG in solution, and that their epitopes only become accessible upon certain physico-chemical treatments (e.g. heat treatment at 57 °C), by physical adsorption on a hydrophobic surface or by antigen binding. Moreover, chemical cross-linking in combination with mass spectrometry showed that the native state of IgG is a compact (closed) form and that the Fab parts of IgG shield the Fc region and thereby control access of rheumatoid factors and presumably also some effector functions. It can be inferred that antibody binding to pathogen surfaces induces a conformational change, which exposes the Fc part with its effector sites and rheumatoid factor epitopes. This has strong implications for understanding antibody structure and physiology and necessitates a conceptual reformulation of IgG models.

[Biological drugs for treatment of children and adolescents with severe asthma].

Prerequisites for successful treatment of severe asthma in children and adolescents with biological drugs are: 1) systematic assessment, excluding and treating other causes of lack of asthma control, 2) immunological phenotyping of the patient, and 3) choice of biological drug targeting the specific disease mechanism. Anti-immunoglobulin (Ig) E and anti-interleukin (IL)-5 have a clinically relevant effect reducing exacerbation rate, but there is still a need for studies in children and adolescents being treated with anti-IgE and anti-IL-5 as well as newer biological drugs, which affect lung function, asthma control and quality of life.

[Fibrous dysplasia in a 12-year-old boy with severe house dust mite allergy].

In this case report, a two-year-old boy debuted with irritative and obstructive nasal symptoms and a positive house dust mite allergy test. Antihistamines and nasal steroids were prescribed, but he had persistent nasal symptoms. An initial ear-nose-throat examination was without pathology. At the age of 12 he presented with fever, headache and nasal obstruction, and an MRI scan showed a 4 × 3 × 3 cm tumour in the right ethmoid sinus. Eventually, he was diagnosed with fibrous dysplasia. Persistent nasal obstruction despite medical treatment in children with allergic rhinitis should always lead to an ear-nose-throat examination and possibly MRI scan to rule out nose and sinus tumours.

Risk of childhood asthma following prenatal exposure to negative life events and job stressors: A nationwide register-based study in Denmark.

Objectives This study aimed to examine the association between negative life events, job stressors (low job control or high psychosocial job demands) and offspring asthma phenotypes (early-onset transient, early-onset persistent and late-onset asthma). Methods In a population-based cohort study comprising 547 533 liveborn singletons, we determined negative life events and offspring asthma at age six years using data from Danish nationwide registers. We assessed job demands and job control from gender-specific job exposure matrices. Prevalence ratios (PR) of each asthma phenotype were estimated using log-binomial regression. Results Maternal exposure to negative life events prenatally was not significantly associated with offspring asthma. Among mothers with low job demands, low job control was associated with increased risk for early-onset transient asthma [PR=1.14, 95% confidence interval (CI) 1.09-1.19], early-onset persistent asthma (PR=1.17, 95% CI 1.11-1.23), and late-onset asthma (PR=1.06, 95% CI 1.00-1.14). Among mothers with high job demands, low job control was not associated with offspring asthma apart from a reduced risk of early-onset persistent asthma (PR=0.94, 95% CI 0.90-0.97). These associations were independent of child sex and parental atopic history. Conclusions Maternal stressors in private life do not seem to influence offspring asthma significantly. Low job control is associated with offspring asthma, which is modified by maternal psychosocial job demands. Our findings warrant further exploration.