Referral Pathways for Children with Atopic Diseases in Denmark.

Atopic diseases such as atopic dermatitis, food allergy, allergic rhinoconjunctivitis, and/or asthma are common. In Denmark, however, there are multiple referral pathways for these diseases in the healthcare system and they are poorly understood. To describe how children with atopic diseases navigate their way through the Danish healthcare system, a questionnaire was distributed to children aged ≤ 17 years, who were being treated for atopic diseases between August 2020 and June 2021, either by a practising specialist or a hospital department, in the Capital Region of Denmark. A total of 279 children completed the questionnaire and most were referred to a specialist or to a hospital by their general practitioner. No "common track" to hospital existed for patients with ≥ 3 atopic diseases. These patients were more often referred to a hospital compared with children with 2 atopic diseases or fewer (odds ratio [OR] 3.79; 95% CI 2.07-7.24). The primary determinants for hospital treatment were food allergy (OR 4.69; 95% CI 2.07-10.61) and asthma (OR 2.58; 95% CI 1.18-5.63). In conclusion, children with multiple atopic diseases were more likely to be referred to hospital departments than to practising specialists, mainly due to food allergies.

Parents of children with atopic diseases - experiences with care and the interaction with healthcare professionals over time.

OBJECTIVE: To explore how the parents of children with atopic dermatitis and allergic diseases such as food allergy, allergic rhinoconjunctivitis, and asthma experience interactions with the Danish healthcare system over time. DESIGN AND METHODS: A qualitative design with individual in-depth interviews. The analysis was inspired by Systematic Text Condensation. SUBJECTS: Eleven parents of children with atopic dermatitis and allergic diseases who received treatment at hospitals in the Capital Region of Denmark. The families had experiences of cross-sectoral patient care. RESULTS: Despite having the same diseases, the children's care pathways were very different. Mapping demonstrated the intricacy of care pathways for this group of children. We identified three aspects that impacted interaction with healthcare: responsibility, tasks, and roles. The families experienced care when the distribution of tasks and responsibilities associated with treatment and system navigation were consistent with both their expectations and their actual experiences. At the same time, families frequently experienced limited collaboration between healthcare professionals resulting in perceived fragmented care and an extended role for parents as care coordinators. Families felt cared for when healthcare professionals knew both their biomedical and biographical circumstances, and adjusted the level of support and care in accordance with the families' particular needs, expectations, and evolving competences. CONCLUSION: We suggest that a possible pathway to improve care may be through a partnership approach as part of family-centered care, with general practitioners having a key role in helping to articulate the individual needs and expectations of each family.

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.

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.

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.

[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.

Component-resolved in vitro diagnosis of hazelnut allergy in Europe.

BACKGROUND: Food allergy to hazelnut occurs both with and without concomitant pollen allergy. OBJECTIVE: We sought to evaluate a panel of hazelnut allergens for diagnosis of hazelnut allergy in Spain, Switzerland, and Denmark. METHODS: Fifty-two patients with a positive double-blind, placebo-controlled food challenge result with hazelnuts; 5 patients with a history of anaphylaxis; 62 patients with pollen allergy but hazelnut tolerance; and 63 nonatopic control subjects were included. Serum IgE levels to hazelnut extract, recombinant hazelnut allergens (rCor a 1.04, rCor a 2, rCor a 8, rCor a 11), and native allergens (nCor a 9, nCor a Bd8K, nCor a Bd11K) were analyzed by means of ImmunoCAP. RESULTS: Among patients with hazelnut allergy, 91% (Switzerland/Spain, 100%; Denmark, 75%) had IgE to hazelnut extract, 75% to rCor a 1.04, 42% to rCor a 2, 28% to rCor a 8, and 2% to rCor a 11. The highest rate of sensitization to Cor a 1.04 was found in the northern regions (Switzerland/Denmark, 100%; Spain, 18%), whereas IgE to the lipid transfer protein rCor a 8 prevailed in Spain (Spain, 71%; Switzerland, 15%; Denmark, 5%). IgE to profilin rCor a 2 was equally distributed (40% to 45%). Among control subjects with pollen allergy, 61% had IgE to hazelnut extract, 69% to rCor a 1.04, 34% to rCor a 2, 10% to rCor a 8, and 6% to rCor a 11. CONCLUSION: Component-resolved in vitro analyses revealed substantial differences in IgE profiles of hazelnut allergic and hazelnut tolerant patients across Europe.

[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.

[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.

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.

Intranasal corticosteroids compared with oral antihistamines in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: Intranasal corticosteroids (INS) (corticosteroid nasal sprays) and oral antihistamines (OA) are two of the most common treatments for patients with allergic rhinitis (AR). To our knowledge, there are no systematic reviews on this topic including trials published after 2007. OBJECTIVE: To compare INS with nonsedating OAs as treatments for AR. METHODS: The systematic review and meta-analysis were based on the Grades of Recommendation, Assessment, Development, and Evaluation principles and the Patient, Intervention, Comparison, and Outcome approach. Primary literature was searched up to January 22, 2015. Criteria for eligibility were randomized controlled trials that compared the efficacy and/or adverse effects of INS and OA in patients with AR. Continuous outcome data were analyzed by using standardized mean differences (SMD) for multiple outcome measures, and mean differences in the case of a single study or outcome. Pooled estimates of effects, 95% confidence interval (CI), were calculated by using random-effects models. RESULTS: The meta-analysis included five randomized controlled trials with a total of 990 patients. INS were superior to OAs in improving total nasal symptoms score (SMD -0.70 [95% CI, -0.93 to -0.47]) and in relieving the following: nasal obstruction (SMD -0.56 [95% CI, -0.82 to -0.29]), rhinorrhea (SMD -0.47 [95% CI, -1.00 to 0.05]), nasal itching (SMD -0.42 [95% CI, -0.65 to -0.18]), sneezing (SMD -0.52 [95% CI, -0.73 to -0.32]), and quality of life mean difference -0.90 [95% CI, -1.18 to -0.62]). There was no difference in relief of ocular symptoms (SMD -0.08 [95% CI, -0.23 to 0.08]). In addition, four randomized controlled trials were included in a narrative analysis. The results in the narrative analysis were comparable with those found in the meta-analysis. CONCLUSION: INS were superior to OAs in improving nasal symptoms and quality of life in patients with AR.

[Anaphylaxis]. / Anafylaksi.

Anaphylaxis is a potentially life-threatening systemic allergic reaction involving several organ systems. Recognition of the reaction leading to prompt treatment is essential for a good outcome. The lifesaving treatment is intramuscular injection of adrenaline (0.3-0.5 mg for adults and children > 40 kg, 0.3 mg for children 20-40 kg and 0.15 mg for infants < 20 kg). The patient must be placed on the back with elevated lower extremities to improve cerebral and cardiac circulation. High dose oxygen and crystalloid fluid load are needed to improve oxygenation and cardiac output.

Food allergy to apple and specific immunotherapy with birch pollen.

Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty patients were included in the final evaluation of the effect of SIT. The challenges were positive in 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after treatment compared to 10, 4, and 10 patients, respectively, before SIT. The symptom scores to apple during challenges decreased in all groups, but only significantly in the placebo group (p = 0.03). As evaluated by the questionnaire, the severity of food allergy in general did not change and there were no differences between the groups. In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity, SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo. Therefore, oral allergy syndrome (OAS) to apple should not be considered as a main criterion for selecting patients for birch pollen immunotherapy at present.

[Anaphylaxis].

Anaphylaxis is a potentially life-threatening systemic allergic reaction involving several organ systems. Recognition of the reaction leading to prompt treatment is essential for a good outcome. The lifesaving treatment is intramuscular injection of adrenaline (0.3-0.5 mg for adults and children > 40 kg, 0.3 mg for children 20-40 kg and 0.15 mg for infants < 20 kg). The patient must be placed on the back with elevated lower extremities to improve cerebral and cardiac circulation. High dose oxygen and crystalloid fluid load are needed to improve oxygenation and cardiac output.

Occupational exposure during pregnancy and the risk of hay fever in 7-year-old children.

OBJECTIVES: The prevalence of allergic diseases including hay fever has increased in the last decades, especially in Westernised countries. The aim of this study was to analyse whether occupational exposure during pregnancy is associated with development of hay fever in 7-year-old Danish children. METHODS: A total of 42,696 women and their children from the Danish National Birth Cohort were categorised according to maternal occupational exposure. Exposure information was obtained by combining job title in pregnancy with a commonly used asthma Job Exposure Matrix. Information on hay fever in the child was obtained by an internet questionnaire at follow-up at 7 years of age. RESULTS: Adjusted logistic regression analyses showed no significant association between maternal occupational exposure during pregnancy and hay fever among the 7-year-old children. Stratifying for atopic status in the children did not change the results. The prevalence of hay fever was 10.0% in the atopic children compared with 3.6% in the non-atopic children. Maternal atopic disposition increased the risk of hay fever in the offspring, odds ratio (OR) 2.49 [95% confidence interval (CI) 2.26; 2.74]. Rural residence during pregnancy decreased the risk for hay fever [OR 0.74 (95% CI 0.59; 0.92)] as did parity, OR 0.72 (95% CI 0.66; 0.80) and 0.70 (95% CI 0.48; 1.00) for 2nd and 3rd child, respectively, compared with the firstborn child. CONCLUSION: The results suggest that occupational exposure among pregnant women in Denmark is not a risk factor for hay fever among young children.

Maternal occupational exposure to asthmogens during pregnancy and risk of asthma in 7-year-old children: a cohort study.

OBJECTIVES: The objective of this study was to examine whether maternal exposure to asthmogens during pregnancy is associated with the development of asthma in 7-year-old Danish children, taking atopic status and sex into consideration. DESIGN: The study is a prospective follow-up of a birth cohort. SETTING AND PARTICIPANTS: A total of 41 724 women and their children from The Danish National Birth Cohort were categorised according to maternal occupational exposure. Exposure information was obtained by combining job title in pregnancy and 18 months after pregnancy with a commonly used asthma Job Exposure Matrix. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was parent-reported asthma among their 7-year-old children in an internet-based questionnaire. Secondary outcome was asthma among the same children with or without atopic dermatitis and among boys and girls, respectively. RESULTS: Prenatal exposure to low molecular weight (LMW) agents was borderline associated with asthma in children with OR 1.17 (0.95 to 1.44) for children with atopic dermatitis and 1.10 (0.98 to 1.22) for children without. Maternal postnatal exposure was associated with asthma (OR 1.15 (1.04 to 1.28). After mutual adjustment,postnatal exposure (OR 1.13 (0.99 to 1.29) and the combined effects of prenatal and postnatal exposure (OR 1.34 (1.19 to 1.51)) seem to increase the risk of asthma in children. No significant associations were observed for other prenatal or postnatal exposures. The gender of the child did not modify the aforementioned associations. CONCLUSIONS: Maternal occupational exposures during pregnancy do not seem to be a substantial risk factor for the development of asthma in 7-year-old children. Maternal prenatal and postnatal exposures to LMW agents may predispose the propensity of the children to develop asthma. Future studies should prioritise the characterisation of the timing of exposure in relation to the birth.

[Indication for adrenalin autoinjector after anaphylaxis]. / Indikation for adrenalinautoinjektor efter anafylaksi.

Anaphylaxis is a potentially fatal hypersensitivity reaction, which should be treated with adrenaline. Patients at risk of recurrent anaphylaxis after the initial episode should be prescribed an adrenalin autoinjector. The patients include persons, who are allergic to insect venom, before they reach the maintenance dose of allergen-specific immunotherapy, persons with food allergy who are at risk of accidental intakes, persons with anaphylaxis induced by low-intensity physical activity, and idiopathic anaphylaxis. The recommended dose of adrenaline is 0.15 mg for children up to 20 kg and 0.30 mg for larger children and adults.

[Allergology in Denmark 2006]. / Allergologi i Danmark 2006.

Allergic diseases are prominent, possibly life threatening, and a cause of worldwide concern. Evidence-based education of doctors in the specialty of allergology is a prerequisite for correct diagnosis and treatment of patients with allergic diseases. Recently, the specialty of allergology has been abolished in Denmark, without any upgrading of the education of doctors in related specialties. As a consequence, one could fear that allergy expertise will be disappearing. We propose collaboration among experts from related specialties with joint mediation of knowledge through a centre of allergology, common educational programs for doctors in training and physician specialists, and collaboration in regional centres of allergology.