Asthma and allergy trajectories in children based on combined parental report and register data.

BACKGROUND: Trajectories of asthma and allergy in children are heterogeneous and commonly derived from parental report of disease or clinical records. This study combined parental-reported and register-based dispensed medication data to characterize childhood trajectories of co-existing asthma, allergic rhinitis, and eczema. METHODS: From a Swedish population-based birth cohort (N = 5654), survey responses collected at the age of 1, 4.5, 8, and 12 years were linked to dispensed medication register data for the period of 2-13 years. Trajectories were identified with latent class analysis. Statistical metrics and clinical interpretability guided the model selection. RESULTS: Nine distinct trajectories were identified: three asthma-dominated (early-onset remitting [n = 189, 3.3%], late-onset [n = 117, 2.1%], and persistent [n = 149, 2.6%]), two eczema-dominated (persistent [n = 190, 3.4%] and remitting [n = 432, 7.6%]), one allergic rhinitis-dominated (late-onset [n = 259, 4.6%]), two multimorbidity (mid-childhood asthma and late-onset allergic rhinitis [n = 144, 2.5%], and persistent eczema and late-onset allergic rhinitis [n = 90, 1.6%]), and one low-disease burden trajectory (n = 4084, 72.2%). Differences were seen across the trajectories in the proportion of parental report of disease and dispensed medication as well as by class and quantity of medication dispensed. CONCLUSION: Combined parental-reported and dispensed medication data enriches characterization of longitudinal trajectories of asthma and allergy in children by merging subjective experience of disease with healthcare utilization. The identified trajectories were characterized by distinct disease development and prescription patterns suggesting clinically differential morbidity burden.

Exogenous female sex steroid hormones and new-onset asthma in women: a matched case-control study.

BACKGROUND: Evidence on the role of exogenous female sex steroid hormones in asthma development in women remains conflicting. We sought to quantify the potential causal role of hormonal contraceptives and menopausal hormone therapy (MHT) in the development of asthma in women. METHODS: We conducted a matched case-control study based on the West Sweden Asthma Study, nested in a representative cohort of 15,003 women aged 16-75 years, with 8-year follow-up (2008-2016). Data were analyzed using Frequentist and Bayesian conditional logistic regression models. RESULTS: We included 114 cases and 717 controls. In Frequentist analysis, the odds ratio (OR) for new-onset asthma with ever use of hormonal contraceptives was 2.13 (95% confidence interval [CI] 1.03-4.38). Subgroup analyses showed that the OR increased consistently with older baseline age. The OR for new-onset asthma with ever MHT use among menopausal women was 1.17 (95% CI 0.49-2.82). In Bayesian analysis, the ORs for ever use of hormonal contraceptives and MHT were, respectively, 1.11 (95% posterior interval [PI] 0.79-1.55) and 1.18 (95% PI 0.92-1.52). The respective probability of each OR being larger than 1 was 72.3% and 90.6%. CONCLUSIONS: Although use of hormonal contraceptives was associated with an increased risk of asthma, this may be explained by selection of women by baseline asthma status, given the upward trend in the effect estimate with older age. This indicates that use of hormonal contraceptives may in fact decrease asthma risk in women. Use of MHT may increase asthma risk in menopausal women.

Sensitization to molecular dog allergens in an adult population: Results from the West Sweden Asthma Study.

BACKGROUND: As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population. METHODS: Data were derived from the West Sweden Asthma Study, a population-based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5 and Can f 6 using ImmunoCAP™. Polysensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin or prostatic kallikrein). RESULTS: Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without. CONCLUSION: Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization.

Comparison of clinician diagnosis of COVID-19 with real time polymerase chain reaction in an adult-representative population in Sweden.

BACKGROUND: Due to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population. METHODS: COVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19. RESULTS: Of 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77-80%) and 93% (95%CI 93-93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53-55%), while negative predictive value (NPV) was 98% (95%CI 98-98%) and Youden's index 71% (95%CI 70-72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden's index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74-90%]) than those without (78% [95%CI 77-79%]) COPD. CONCLUSIONS: The accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR.

Low agreement between Swedish national registers and parental questionnaires on allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) has been well documented using questionnaire-based studies. Here, we examine the agreement between parental-reported data during childhood with the emphasis on 12-year-olds and data from two national Swedish registers to determine whether register data on AR can supplement or replace questionnaire data. METHODS: Data were collected from a prospective, longitudinal cohort study of children born in western Sweden in 2003. Parental questionnaires were filled out at 6 months and one, four, eight, and 12 years of age. A total of 3634 children were linked to the Swedish Prescribed Drug Register (SPDR) and the National Patient Register (NPR) using personal identity numbers. The agreement between the register and questionnaire data was estimated using Cohen's kappa with 95% confidence intervals. RESULTS: According to the SPDR, 9.9% (n = 360/3634) of the children were dispensed specific AR medication at 11-13 years of age compared with the 12 years questionnaire where 23% reported AR medication use during the last 12 months. The overall agreement between questionnaire and SPDR data on AR medication was slight (kappa 0.05). At 11-12 years, 1.8% (n = 65/3634) of the children received an outpatient AR diagnosis in the NPR, while 10% reported doctor-diagnosed AR in the questionnaire. The overall agreement between questionnaire and NPR data on AR diagnosis was slight (kappa 0.16). CONCLUSIONS: There was poor agreement between questionnaire and register data regarding AR and dispensed medication. Explanations could include over-the-counter drugs and diagnosis in primary care, which are not included in the registers.

Siblings and risk of allergic rhinitis: A systematic review and meta-analysis.

Following the "hygiene hypothesis" and the increase in the prevalence of atopic diseases such as allergic rhinitis, a plethora of studies have investigated the role of sibship composition as a protective factor, but findings are conflicting. The aim of this study was to synthesize the global literature linking birth order and sibship size (number of siblings) to the risk of allergic rhinitis. Fifteen databases were systematically searched, with no restrictions on publication date or language. Observational studies with defined sibship composition (birth order or sibship size) as exposure and allergic rhinitis or allergic rhinoconjunctivitis (self-reported or clinically diagnosed) as outcome were eligible. Study selection, data extraction, and quality assessment were performed independently in pairs. Relevant data were summarized in tables. Comparable numerical data were analyzed using meta-analysis with robust variance estimation (RVE). Seventy-six reports with >2 million subjects were identified. Being second- or later-born child was associated with protection against both current (pooled risk ratio [RR] 0.79, 95% CI 0.73-0.86) and ever (RR 0.77, 95% CI 0.68-0.88) allergic rhinitis. Having siblings, regardless of birth order, was associated with a decreased risk of current allergic rhinitis (RR 0.89, 95% CI 0.83-0.95) and allergic rhinoconjunctivitis (RR 0.92, 95% CI 0.86-0.98). These effects were unchanged across age, time period, and geographical regions. Our findings thus indicate that primarily, a higher birth order, and to a lesser extent the number of siblings, is associated with a lower risk of developing allergic rhinitis.

Infants were introduced to complementary feeding earlier in 2018 compared with 2003.

AIM: Until 2001, the Swedish advice was to postpone the introduction of eggs, fish and peanuts until the age of 1 year. One reason was to reduce the risk of food allergy. The earlier introduction of complementary feeding is now advised. Our aim was to study adherence to current recommendations and whether the time of introduction changed between 2003 and 2018. METHODS: Data were obtained from two prospective, longitudinal, population-based cohort studies of children born in 2003 (n = 4987) and in 2018 (n = 3936). Parents answered comparable questionnaires when the children were 6 and 12 months old. RESULTS: At 6 months, in the 2018 cohort, eggs were introduced to 67.2% of the infants, fish to 78.9%, gluten to 89.1%, cow's milk to 76.6% and peanuts to 46.2%. In adjusted Cox regression analyses, introduction of complementary feeding with gluten, fish and eggs was made significantly earlier in the 2018 cohort compared with the 2003 cohort, adjusted for heredity, own allergic disease and parental educational level (p < 0.01). CONCLUSION: Complementary feeding with eggs, fish and gluten was introduced earlier in infants born in 2018 compared with 2003, possibly reducing the risk of developing allergic disease. Current recommendations from child welfare centres are being followed.

Level of education and asthma control in adult-onset asthma.

OBJECTIVE: Education in itself and as a proxy for socioeconomic status, may influence asthma control, but remains poorly studied in adult-onset asthma. Our aim was to study the association between the level of education and asthma control in adult-onset asthma. METHODS: Subjects with current asthma with onset >15 years were examined within the Obstructive Lung Disease in Northern Sweden study (OLIN, n = 593), Seinäjoki Adult Asthma Study (SAAS, n = 200), and West Sweden Asthma Study (WSAS, n = 301) in 2009-2014 in a cross-sectional setting. Educational level was classified as primary, secondary and tertiary. Uncontrolled asthma was defined as Asthma Control Test (ACT) score ≤19. Altogether, 896 subjects with complete data on ACT and education were included (OLIN n = 511, SAAS n = 200 and WSAS n = 185). RESULTS: In each cohort and in pooled data of all cohorts, median ACT score was lower among those with primary education than in those with secondary and tertiary education. Uncontrolled asthma was most common among those with primary education, especially among daily ICS users (42.6% primary, 28.6% secondary and 24.2% tertiary; p = 0.001). In adjusted analysis, primary education was associated with uncontrolled asthma in daily ICS users (OR 1.92, 95% CI 1.15-3.20). When stratified by atopy, the association between primary education and uncontrolled asthma was seen in non-atopic (OR 3.42, 95% CI 1.30-8.96) but not in atopic subjects. CONCLUSIONS: In high-income Nordic countries, lower educational level was a risk factor for uncontrolled asthma in subjects with adult-onset asthma. Educational level should be considered in the management of adult-onset asthma.

Swedish survey of infant sleep practices showed increased bed-sharing and positive associations with breastfeeding.

AIM: Many countries lack monitoring of infant sleep practices, despite associations with sudden infant death. We studied sleep positions, bed-sharing and breastfeeding in a new birth cohort. METHODS: Data were obtained from a prospective, population-based cohort study of children born in western Sweden in 2018. The parents of 9,465 six-month-old infants, via postal questionnaires, were asked about their infants' sleeping positions at three and six months, including where they slept and any bed-sharing arrangements. The data were compared with our earlier 2003-2004 birth cohort. RESULTS: Questionnaires were completed by the parents of 3,590 (38%) infants. At three months, 54% of the infants slept in a separate cot in their parents' room. A further 43% slept in their parents' bed: 42% in baby nests and 42% in close contact with their parents. At six months, 33% bed-shared, compared with 20% in 2003-2004 (p < 0.001). Bed-sharing was positively associated with breastfeeding (odds ratio at three months: 1.5-2.8, 95% confidence interval: 1.1-4.5). CONCLUSION: Most infants slept in separate cots during the first three months. However, bed-sharing showed an increasing trend and baby nests were popular. Bed-sharing was positively associated with breastfeeding, but the association may not be causal.

Late introduction of solids into infants' diets may increase the risk of food allergy development.

BACKGROUND: This study investigated risk factors associated with food allergy or food intolerance among school children in two Swedish towns. METHODS: Questionnaires were used to collect data on self-reported food allergy or intolerance (SRFA) in children aged 7-8 years from Mölndal in southwestern Sweden and Kiruna in northern Sweden. It included questions about specific food allergy or intolerance to cows' milk, hens' eggs, fish, peanuts, tree nuts, and cereals and also age of onset, type of symptoms and age of cessation. Information was also gathered on family allergy history, dietary habits, and certain lifestyle aspects. RESULTS: Of 1838 questionnaires distributed, 1029 were returned: 717/1354 (53%) from Mölndal and 312/484 (64%) from Kiruna. The cumulative incidence of SRFA was 19.6% with a significantly higher cumulative incidence in Kiruna (28.5%) than in Mölndal (15.7%), P < .001. Solids were introduced at a later age in Kiruna. Introduction of solids into a child's diet from the age of 7 months or later, and maternal history of allergic disease, were both risk factors associated with a higher risk of food allergy or intolerance. CONCLUSION: Late introduction of solids into an infant's diet may be one risk factor for developing food allergy or intolerance. Later introduction of solids in Kiruna may be one explanation for the higher cumulative incidence of SRFA in that region.

Higher parental education was associated with better asthma control.

AIM: Inhaled corticosteroids have resulted in the improved control of asthma and a reduced need for hospitalisation. This study aimed to examine the prevalence of uncontrolled asthma and factors that affect asthma control. METHODS: The data came from a longitudinal cohort study of children. The parents answered questionnaires from age 6 months to 12 years. The response rate at age 12 years was 76% (3637/4777) and doctor-diagnosed asthma was reported in 6.4% (n = 233). Asthma control was examined with the Asthma Control Test (ACT), where scores below 20 denote uncontrolled asthma. RESULTS: Of the children with asthma at age 12 years, 15% had an ACT value below 20, that is uncontrolled asthma. Independent risk factors for uncontrolled asthma were wheeze triggered by exercise (adjusted OR, aOR 5.6; 1.9-16.6), cat at home (aOR 3.5; 1.2-10.0) and current doctor-diagnosed rhinitis (aOR 2.8; 95% CI 1.1-7.0). A higher education in the parents reduced the risk of uncontrolled asthma (aOR 0.3; 95% CI 0.1-0.8). Only six children (i.e. 2.6%) reported hospitalisation due to asthma during the last year. CONCLUSION: Of the children with asthma, 15% had uncontrolled asthma. Higher education in the parents was associated with better asthma control in the children.

Randomised study of children with obesity showed that whole body vibration reduced sclerostin.

AIM: New strategies are required to increase physical activity and improve metabolic profiles in children with obesity. We studied the effect of whole body vibration (WBV) on children with obesity on biochemical markers of energy and bone metabolism, anthropometric measurements, muscle parameters and calcaneal bone mineral density (BMD). METHODS: This was a randomised, prospective, controlled study of 30 children with a median age of 13 years (range 7-17) at Queen Silvia Children's Hospital, Gothenburg, Sweden, from 2013 to 2015. The target for the intervention group was to perform WBV three times a week for 12 weeks, and the study parameters were assessed at baseline and 12 weeks. RESULTS: The 16 in the WBV group achieved 51% of the planned activity, mainly at home, and were compared with 14 controls. Sclerostin, bone-specific alkaline phosphatase and carboxy-terminal collagen cross-links decreased in the WBV group (p < 0.05) and balance improved (p < 0.006), but osteocalcin and insulin remained unchanged. Anthropometric data, muscle strength and calcaneal BMD did not differ between the groups. CONCLUSION: WBV did not affect most of the clinical parameters in children with obesity, but the reduction in sclerostin implies that it had direct effects on osteocytes, which are key players in bone mechanotransduction.

NKG2D gene variation and susceptibility to viral bronchiolitis in childhood.

BACKGROUND: Genetic factors associated with bronchiolitis are inadequately characterized. We therefore inspected a selected subpopulation of our previous genome-wide association study (GWAS) of bronchiolitis for overlap with known quantitative trait loci (QTLs) to identify susceptibility loci that potentially affect mRNA and protein levels. METHODS: GWAS included a Finnish-Swedish case-control population (n = 187), matched for age and site. We integrated GWAS variants (p < 10-4) with QTL data. We subsequently verified allele-specific expression of identified QTLs by flow cytometry. Association of the resulting candidate loci with bronchiolitis was tested in three additional cohorts from Finland and Denmark (n = 1201). RESULTS: Bronchiolitis-susceptibility variant rs10772271 resided within QTLs previously associated with NKG2D (NK group 2, member D) mRNA and protein levels. Flow cytometric analysis confirmed the association with protein level in NK cells. The GWAS susceptibility allele (A) of rs10772271 (odds ratio [OR] = 2.34) corresponded with decreased NKG2D expression. The allele was nominally associated with bronchiolitis in one Finnish replicate (OR = 1.50), and the other showed directional consistency (OR = 1.43). No association was detected in Danish population CONCLUSIONS: The bronchiolitis GWAS susceptibility allele was linked to decreased NKG2D expression in the QTL data and in our expression analysis. We propose that reduced NKG2D expression predisposes infants to severe bronchiolitis.

Eating fish and farm life reduce allergic rhinitis at the age of twelve.

BACKGROUND: The prevalence of allergic rhinitis has increased, but the cause of this rise is partly unknown. Our aim was to analyse the prevalence, risk factors, and protective factors for allergic rhinitis in 12-year-old Swedish children. METHODS: Data were collected from a prospective, longitudinal cohort study of children born in western Sweden in 2003. The parents answered questionnaires when the children were 6 months to 12 years. The response rate at 12 years was 76% (3637/4777) of the questionnaires distributed. RESULTS: At the age of 12, 22% of children had allergic rhinitis and 57% were boys. Mean age at onset was 7.8 years, and 55% reported their first symptoms after 8 years. The most common trigger factors were pollen (85%), furry animals (34%), and house dust mites (17%). A multivariate analysis showed that the adjusted odds ratios and 95% confidence intervals for the independent risk factors for allergic rhinitis at 12 were as follows: parental allergic rhinitis (2.32, 1.94-2.77), doctor-diagnosed food allergy in the first year (1.75, 1.21-2.52), eczema in the first year (1.61, 1.31-1.97), and male gender (1.25, 1.06-1.47). Eating fish once a month or more at age of 12 months reduced the risk of allergic rhinitis at 12 years of age (0.70, 0.50-0.98) as did living on a farm with farm animals at 4 years (0.51, 0.32-0.84). Continuous farm living from age 4 to 12 seemed to drive the association. CONCLUSIONS: Allergic rhinitis affected > 20% of 12-year-olds, but was lower in children who ate fish at 12 months or grew up on a farm with farm animals.

Antibiotics in the first week of life were associated with atopic asthma at 12 years of age.

AIM: This study explored the prevalence of atopic and nonatopic asthma in 12-year-old children and whether they were associated with different risk factors. In particular, we wanted to analyse whether receiving antibiotics during the first week of life was associated with asthma at that age. METHODS: Data were obtained from a longitudinal cohort study of 5654 Swedish children born in 2003. The parents answered questionnaires from the age of six months until 12 years. The response rate at 12 years was 3637/4777 (76%). RESULTS: At 12 years, 6.4% reported current doctor-diagnosed asthma. Treatment with antibiotics during the first week of life was associated with an increased risk of atopic asthma, with an adjusted odds ratio of 2.2 and 95% confidence interval of 1.2-4.2. Being born small for gestational age was associated with an increased risk of nonatopic asthma, with an adjusted odds ratio of 3.8 and 95% confidence interval of 1.1-13.7. Asthma that only occurred with colds was reported by 28%. CONCLUSION: Antibiotic treatment during the first week of life was associated with an increased risk of atopic asthma at 12 years, suggesting an immune-mediated effect. Being born small for gestational age increased the risk of nonatopic asthma.

Area-based study shows most parents follow advice to reduce risk of sudden infant death syndrome.

AIM: Guidance on reducing the risk of sudden infant death syndrome (SIDS) was successfully introduced to a number of countries in the early 1990s. The most important recommendations were supine sleeping for infants and non-smoking for mothers. This 2012-2014 study examined adherence to the national Swedish SIDS advice. METHODS: We asked 1000 parents with infants registered at child healthcare centres in western Sweden to complete a questionnaire on infant care from birth to 12 months of age. RESULTS: We analysed 710 responses and found that, in the first three months, 1.3% of the infants were placed in the prone sleeping position and 14.3% were placed on their side. By three to five months, this had risen to 5.6% and 23.6%. In the first three months, 83.1% were breastfed, 84.1% used a pacifier and 44.2% shared their parents' bed, while 5.8% slept in another room. Bed sharing was more likely if infants were breastfed and less likely if they used pacifiers. During pregnancy, 2.8% of the mothers smoked and the mothers who had smoked during pregnancy were less likely to bed share. CONCLUSION: Overall adherence to the SIDS advice was good, but both prone and side sleeping practices should be targeted.

Allergic rhinoconjunctivitis continued to increase in Swedish children up to 2007, but asthma and eczema levelled off from 1991.

AIM: This study investigated whether allergies among schoolchildren increased in Sweden between 1979 and 2007 and whether the geographical differences observed in previous studies remained. METHODS: We collected questionnaire data on asthma, allergic rhinoconjunctivitis (ARC) and eczema in children aged seven to eight years from Mölndal, Gothenburg, in south-western Sweden and Kiruna in northern Sweden in 1979 (n = 4682), 1991 (n = 2481) and 2007 (n = 1029). The same regions and questions were used in all three studies, and extra questions on food allergy or intolerance were added in 2007. RESULTS: In 1979, 1991 and 2007, the total prevalence of asthma was 2.5%, 5.7% and 7.1%, ARC was 5.5%, 8.1% and 11.1% and eczema was 7.1%, 18.3% and 19.7%, respectively. Asthma prevalence remained higher in Kiruna, but no significant regional differences were seen for ARC and eczema. Almost 20% reported a history of food allergy or intolerance, with a higher prevalence in Kiruna. The allergy risk was reduced if both parents were born outside Sweden. CONCLUSION: The prevalence of ARC continued to increase between 1991 and 2007, but increases in asthma and eczema started to level off in 1991. Some geographical differences remained, but total allergy rates were similar in Kiruna and Mölndal in 2007.