Risks for comorbidity in children with atopic disorders: an observational study in Dutch general practices.

OBJECTIVE: This study aimed to investigate both atopic and non-atopic comorbid symptoms and diseases in children with physician-diagnosed atopic disorders (atopic eczema, asthma and allergic rhinitis). METHODS: All children aged 0-18 years listed in a nationwide primary care database (the Netherlands Institute for Health Services Research-Primary Care Database) with routinely collected healthcare data in 2014 were selected. Children with atopic disorders were matched on age and gender with non-atopic controls within the same general practice. A total of 404 International Classification of Primary Care codes were examined. Logistic regression analyses were performed to examine the associations between the presence of atopic disorders and (non-)atopic symptoms and diseases by calculating ORs. RESULTS: Having one of the atopic disorders significantly increased the risk of having other atopic-related symptoms, even if the child was not registered as having the related atopic disorder. Regarding non-atopic comorbidity, children with atopic eczema (n=15 530) were at significantly increased risk for (infectious) skin diseases (OR: 1.2-3.4). Airway symptoms or (infectious) diseases (OR: 2.1-10.3) were observed significantly more frequently in children with asthma (n=7887). Children with allergic rhinitis (n=6835) had a significantly distinctive risk of ear-nose-throat-related symptoms and diseases (OR: 1.5-3.9). Neither age nor gender explained these increased risks. CONCLUSION: General practitioners are not always fully aware of relevant atopic and non-atopic comorbidity. In children known to have at least one atopic disorder, specific attention is required to avoid possible insufficient treatment and unnecessary loss of quality of life.

Atopic children and use of prescribed medication: A comprehensive study in general practice.

PURPOSE: A comprehensive and representative nationwide general practice database was explored to study associations between atopic disorders and prescribed medication in children. METHOD: All children aged 0-18 years listed in the NIVEL Primary Care Database in 2014 were selected. Atopic children with atopic eczema, asthma and allergic rhinitis (AR) were matched with controls (not diagnosed with any of these disorders) within the same general practice on age and gender. Logistic regression analyses were performed to study the differences in prescribed medication between both groups by calculating odds ratios (OR); 93 different medication groups were studied. RESULTS: A total of 45,964 children with at least one atopic disorder were identified and matched with controls. Disorder-specific prescriptions seem to reflect evidence-based medicine guidelines for atopic eczema, asthma and AR. However, these disorder-specific prescriptions were also prescribed for children who were not registered as having that specific disorder. For eczema-related medication, about 3.7-8.4% of the children with non-eczematous atopic morbidity received these prescriptions, compared to 1.4-3.5% of the non-atopic children. The same pattern was observed for anti-asthmatics (having non-asthmatic atopic morbidity: 0.8-6.2% vs. controls: 0.3-2.1%) and AR-related medication (having non-AR atopic morbidity: 4.7-12.5% vs. controls: 2.8-3.1%). Also, non-atopic related medication, such as laxatives and antibiotics were more frequently prescribed for atopic children. CONCLUSIONS: The present study shows that atopic children received more prescriptions, compared to non-atopic children. Non-atopic controls frequently received specific prescriptions for atopic disorders. This indicates that children with atopic disorders need better monitoring by their GP.

Reliably estimating prevalences of atopic children: an epidemiological study in an extensive and representative primary care database.

Electronic health records stored in primary care databases might be a valuable source to study the epidemiology of atopic disorders and their impact on health-care systems and costs. However, the prevalence of atopic disorders in such databases varies considerably and needs to be addressed. For this study, all children aged 0-18 years listed in a representative primary care database in the period 2002-2014, with sufficient data quality, were selected. The effects of four different strategies on the prevalences of atopic disorders were examined: (1) the first strategy examined the diagnosis as recorded in the electronic health records, whereas the (2) second used additional requirements (i.e., the patient had at least two relevant consultations and at least two relevant prescriptions). Strategies (3) and (4) assumed the atopic disorders to be chronic based on strategy 1 and 2, respectively. When interested in cases with a higher probability of a clinically relevant disorder, strategy 2 yields a realistic estimation of the prevalence of atopic disorders derived from primary care data. Using this strategy, of the 478,076 included children, 28,946 (6.1%) had eczema, 29,182 (6.1%) had asthma, and 28,064 (5.9%) had allergic rhinitis; only 1251 (0.3%) children had all three atopic disorders. Prevalence rates are highly dependent on the clinical atopic definitions used. The strategy using cases with a higher probability of clinically relevant cases, yields realistic prevalences to establish the impact of atopic disorders on health-care systems. However, studies are needed to solve the problem of identifying atopic disorders that are missed or misclassified. ATOPIC DISORDERS: CLINICAL INFORMATION IMPROVES PREVALENCE ESTIMATES: The prevalence of atopic disorders in children can be more reliably calculated by incorporating clinical information with diagnosis data. Researchers in the Netherlands, led by David Pols from the Erasmus University Medical Center Rotterdam, examined the electronic health records of more than 660,000 children, aged 0 to 18, from a Dutch primary care database to determine the number of cases of atopic eczema, asthma, and allergic rhinitis. They looked for diagnosed children who also had at least two relevant clinical consultations and at least two relevant prescriptions. This strategy helps correct for the problem of overestimation, because it doesnot assume that a child, once diagnosed, will have an atopic disorder for life. However, other methods are still needed to identify cases that are missed or misclassified in the health database.

Development and Validation of Search Filters to Identify Articles on Family Medicine in Online Medical Databases.

Physicians and researchers in the field of family medicine often need to find relevant articles in online medical databases for a variety of reasons. Because a search filter may help improve the efficiency and quality of such searches, we aimed to develop and validate search filters to identify research studies of relevance to family medicine. Using a new and objective method for search filter development, we developed and validated 2 search filters for family medicine. The sensitive filter had a sensitivity of 96.8% and a specificity of 74.9%. The specific filter had a specificity of 97.4% and a sensitivity of 90.3%. Our new filters should aid literature searches in the family medicine field. The sensitive filter may help researchers conducting systematic reviews, whereas the specific filter may help family physicians find answers to clinical questions at the point of care when time is limited.

Interrelationships between Atopic Disorders in Children: A Meta-Analysis Based on ISAAC Questionnaires.

PURPOSE: To study the prevalence and interrelationship between asthma, allergic rhinitis and eczema using data obtained from ISAAC questionnaires. METHOD: The Medline, Pubmed Publisher, EMBASE, Google Scholar and the Cochrane Controlled Clinical Trials Register databases were systematically reviewed to evaluate epidemiological data of children with atopic disorders. To study these interrelationships, a new approach was used. Risk ratios were calculated, describing the risk of having two different atopic disorders when the child is known with one disorder. RESULTS: Included were 31 studies, covering a large number of surveyed children (n=1,430,329) in 102 countries. The calculated worldwide prevalence for asthma, eczema and allergic rhinitis is 12.00% (95% CI: 11.99-12.00), 7.88% (95% CI: 7.88-7.89) and 12.66% (95% CI: 12.65-12.67), respectively. The observed prevalence [1.17% (95% CI: 1.17-1.17)] of having all three diseases is 9.8 times higher than could be expected by chance. For children with asthma the calculated risk ratio of having the other two disorders is 5.41 (95% CI: 4.76-6.16), for children with eczema 4.24 (95% CI: 3.75-4.79), and for children with allergic rhinitis 6.20 (95% CI: 5.30-7.27). No studied confounders had a significant influence on these risk ratios. CONCLUSIONS: Only a minority of children suffers from all three atopic disorders, however this co-occurrence is significantly higher than could be expected by chance and supports a close relationship of these disorders in children. The data of this meta-analysis supports the hypothesis that there could be a fourth distinct group of children with all three disorders. Researchers and clinicians might need to consider these children as a separate group with distinct characteristics regarding severity, causes, treatment or prognosis.

Sensitisation patterns and association with age, gender, and clinical symptoms in children with allergic rhinitis in primary care: a cross-sectional study.

BACKGROUND: Polysensitisation is a frequent phenomenon in patients with allergic rhinitis. However, few studies have investigated the characteristics of polysensitised children, especially in primary care. OBJECTIVES: This analysis describes the patterns of sensitisation to common allergens and the association with age, gender, and clinical symptoms in children in primary care diagnosed with allergic rhinitis. METHODS: Cross-sectional data from two randomised double-blind placebo-controlled studies were used to select children aged 6-18 years (n=784) with a doctor's diagnosis of allergic rhinitis or use of relevant medication for allergic rhinitis in primary care. They were assessed for age, gender, specific IgE (type and number of sensitisations), nasal and eye symptom scores. RESULTS: In 699 of the 784 children (89%) with a doctor's diagnosis or relevant medication use, a positive IgE test for one or more allergens was found. Polysensitisation (>2 sensitisations) was found in 69% of all children. Sensitisation was more common in children aged 9-13 than in younger children aged 5-8 years (p=0.03). Monosensitisation and polysensitisation were not significantly different in girls and boys. The severity of clinical symptoms did not differ between polysensitised and monosensitised children, but symptoms were significantly lower in non-sensitised children. CONCLUSIONS: Polysensitisation to multiple allergens occurs frequently in children with allergic rhinitis in general practice. Overall, clinical symptoms are equally severe in polysensitised and monosensitised children. Treatment decisions for allergic rhinitis should be made on the basis of a clinical history and allergy testing.

Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells.

Increasing evidence suggests that neuropeptides play a role in the regulatory mechanisms between the neuroendocrine and immune systems. A differential expression of the five known somatostatin (SS) receptors (sst1-5) has been demonstrated in human immune cells and tissues. However, little is known concerning regulation and expression of sst1-5 and the peptide SS. Therefore, we investigated the expression and the time-dependent regulation of sst1-5, SS, and cortistatin (CST), a novel SS-like peptide, in human monocytes (MO), monocyte-derived macrophages (MP), and dendritic cells (DC) in the basal and lipopolysaccharide (LPS)-activated state. MO, MP, and DC selectively expressed sst2 mRNA. SS mRNA was not detectable, whereas all samples expressed CST mRNA. Expression levels of sst2 and CST mRNA showed marked differences and were in the rank order of MP>>DC>>>MO. LPS stimulation did not induce expression of SS or sst1,3,4,5. However, sst2 mRNA expression was upregulated significantly by stimulation with LPS. CST mRNA was upregulated as well. During differentiation of MO in MP or DC, time-dependent, significantly increasing sst2 and CST mRNA levels were found. By confocal microscopy, the presence of sst2 receptors was demonstrated on MP, but not on DC. This study demonstrates for the first time a selective and inducible expression of the recently discovered CST, as well as sst2, in human monocyte-derived cells, suggesting a role for a CST-sst2 system rather than a SS-sst2 system in these immune cell types.