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.

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.

Parental questionnaires provided reliable data on childhood asthma compared with national registers.

BACKGROUND: Much of our knowledge of childhood asthma comes from questionnaire-based studies. Our main aim was to assess the agreement between parental-reported data at 12 years of age and data from two national Swedish registers. METHODS: Data were obtained from the prospective, longitudinal, population-based Children of Western Sweden cohort, which focused on children born in 2003. The parents answered questionnaires at six months and one, four, eight and 12 years of age. Personal identity numbers linked 3634 children to the Swedish Prescribed Drug Register (SPDR) and the National Patient Register (NPR). RESULTS: At 12 years of age, there was substantial overall agreement between the asthma medication reported by the parents in the questionnaire and the SPDR for any asthma medication (94.8%, kappa 0.71) and maintenance treatment (95.3%, kappa 0.68). In contrast, the agreement between the outpatient asthma diagnoses in the NPR and the questionnaire-based asthma was 30.5% and it was 32.8% between the NPR and the dispensed asthma medication in the SPDR. Hospitalization was rare for obstructive diseases after early childhood, and 38.2% of the 12-year-old children only received a short-acting beta agonist, with no maintenance treatment. CONCLUSION: There was good agreement between the questionnaire-based data on asthma medication and the national drug register, but the National Patient Register provided incomplete information on asthma diagnoses, probably because it did not include primary care diagnoses. The results show that well-constructed parental questionnaires can provide reliable data on childhood 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.

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.

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.

The allergic march comprises the coexistence of related patterns of allergic disease not just the progressive development of one disease.

AIM: This study explored the development and comorbidity of allergic diseases by analysing the relationship between allergic manifestations in infancy and at the age of 8. METHODS: We included 5654 children born in Sweden in 2003 in a longitudinal study. Parents answered postal questionnaires when the children were six months and one, four-and-a-half and eight years of age. RESULTS: The response rate at eight years was 4051 (71.6%), and we analysed 3382 children with complete data. The number of manifestations in infancy increased the risk of allergic disease at eight years of age: 72% of children with one early manifestation were symptom free at 8, compared to 45% with two or more manifestations. Similar manifestations occurred in infancy and at the age of 8, for example recurrent wheeze increased the risk of doctor-diagnosed asthma by an adjusted odds ratio of 6.5. Eczema and food allergy independently increased the risk of all four allergic manifestations at eight years. CONCLUSION: Allergic disease at the age of 8 was related to the number of allergic manifestations in infancy. Manifestations were similar at both ages, suggesting an allergic march with the coexistence of disease patterns rather than the progressive development of one disease.

A persistently high body mass index increases the risk of atopic asthma at school age.

AIM: Being overweight has been associated with the risk of developing childhood asthma, but studies have produced conflicting results, for example with regard to possible links to allergic diseases. This study aimed to explore the relationship between body mass index (BMI) and school-age asthma. METHODS: Data were obtained from a prospective, longitudinal study of 5044 children born in western Sweden. The parents answered questionnaires at six months and one, four-and-a-half and eight years of age. The response rate to the final questionnaire at the age of eight was just over 80%. BMI was adjusted for age and gender, and a high BMI was defined as the 85th percentile and above. RESULTS: A multivariate analysis showed an independently increased risk of doctor-diagnosed asthma among children with a persistently high BMI, both in infancy and at school age, with an adjusted odds ratio (aOR) of 2.9 and a 95% confidence interval (CI) of 1.3-6.4. In addition, persistently high BMI was associated with an increased risk of atopic asthma (aOR 4.7, 95% CI 2.0-11.0). CONCLUSION: A persistently high BMI during childhood increased the risk of doctor-diagnosed asthma at school age. The increased risk of atopic asthma suggests an effect mediated via the immune system.

Antibiotics in the first week of life is a risk factor for allergic rhinitis at school age.

BACKGROUND: Heredity as well as external factors influences the development of allergic rhinitis. The aim of this study was to analyse early risk factors and protective factors for allergic rhinitis at school age. METHODS: This is a prospective, longitudinal study of children born in western Sweden in 2003 where 50% of the birth cohort was randomly selected. The parents answered questionnaires at 6 months, 12 months, 4.5 yr and 8 yr. At 8 yr, 5044 questionnaires were distributed. Of these, 4051 responded, that is, 80.3%. Current allergic rhinitis was defined as symptoms and use of medication during the past 12 months. RESULTS: Current allergic rhinitis at 8 yr was reported by 10.9%. Mean onset age was 5.7 yr, and 61.9% were boys. In a multivariate analysis, antibiotics in the first week of life increased the risk of allergic rhinitis (adjusted odds ratio 1.75, 95% confidence interval (1.03, 2.97)). Increased risk was also seen with parental allergic rhinitis (aOR 2.73 (2.12, 3.52)), food allergy first year (aOR 2.45 (1.61, 3.73)), eczema first year (aOR 1.97 (1.50, 2.59)) and male gender (aOR 1.35 (1.05, 1.74)). Living on a farm at 4.5 yr reduced the risk (aOR 0.31 (0.13, 0.78)). CONCLUSION: Antibiotics in the first week of life increased the risk of allergic rhinitis at school age, while living on a farm at preschool age reduced the risk. Both findings are compatible with the hygiene hypothesis.

Early fish introduction and neonatal antibiotics affect the risk of asthma into school age.

BACKGROUND: The early introduction of fish has been reported to reduce the risk of wheezing disorder in early childhood, while broad-spectrum antibiotics in the first week have been associated with an increased risk. However, it is uncertain whether the effects remain into school age. The aim was to explore these risk factors for doctor-diagnosed asthma at 8 years. METHODS: Data were obtained from a prospective, longitudinal study of a cohort of children born in western Sweden. The parents answered questionnaires at 6 months and 1, 4.5 and 8 years of age. The response rate at 8 years was 80% of the questionnaires distributed (4051/5044), that is, 71% of the families entering the study (4051/5654). RESULTS: At 8 years, 5.7% reported current doctor-diagnosed asthma. Of these, 65% had atopic asthma and 35% non-atopic asthma. In the multivariate analysis, atopic heredity, male gender and own allergic disease during infancy were risk factors for doctor-diagnosed asthma at 8 years. In addition, the introduction of fish before the age of 9 months independently reduced the risk (adjusted OR 0.6; 95% CI 0.4-0.96), while broad-spectrum antibiotics in the first week independently increased the risk of current asthma at school age (aOR 2.3; 1.2-4.2). Regarding types of asthma, the effects were significant in atopic asthma but not in non-atopic asthma. CONCLUSION: The early introduction of fish and neonatal antibiotic treatment influence the risk of asthma into school age. The significant effect on atopic asthma is of particular importance, as this phenotype is of major clinical significance.

Birth order, sibship size, and risk of atopic dermatitis, food allergy, and atopy: A systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis and food allergy are two frequently concomitant manifestations of the presence of atopy. A substantial number of studies have been published on the association of birth order and sibship size (number of siblings) with atopic dermatitis, food allergy, and atopy. The present work is the first systematic synthesis of the existing literature on this topic. METHODS: Fifteen databases were searched. Screening, data extraction, and quality assessment were performed by independent pairs. Comparable numerical data were statistically synthesized using random-effects robust variance estimation. RESULTS: In total, 114 studies were included out of 8819 papers obtained from database searches. Birth order ≥2 versus 1 was associated with lower risk of ever atopic dermatitis (pooled risk ratio [RR] 0.91, 95% CI 0.84-0.98), current food allergy (RR 0.77, 95% CI 0.66-0.90), and positive skin prick test (SPT) to common aeroallergens (RR 0.86, 95% CI 0.77-0.97). Sibship size ≥2 versus 1 was associated with decreased risk of current atopic dermatitis (RR 0.90, 95% CI 0.83-0.98), ever atopic dermatitis (RR 0.92, 95% CI 0.86-0.97), and positive SPT to common aeroallergens (RR 0.88, 95% CI 0.83-0.92). No putative associations were seen regarding atopy assessed through allergen-specific immunoglobulin E with common allergens. CONCLUSION: The presence of siblings and being second-born or later may decrease the lifetime risk of atopic dermatitis and food allergy, albeit marginally. Similar association was seen with SPT sensitization. However, significant protection was not found for IgE sensitization.

Is sibship composition a risk factor for childhood asthma? Systematic review and meta-analysis.

BACKGROUND: Following the "hygiene hypothesis", the role of sibship composition in asthma and wheezing has been extensively studied, but the findings are inconsistent. For the first time, this systematic review and meta-analysis synthesized evidences from studies investigating the association of sibship size and birth order with risk of asthma and wheezing. METHODS: Fifteen databases were searched to identify eligible studies. Study selection and data extraction were performed independently by pairs of reviewers. Meta-analysis with robust variance estimation (RVE) was used to produce pooled risk ratio (RR) effect estimates from comparable numerical data. RESULTS: From 17,466 identified records, 158 reports of 134 studies (> 3 million subjects) were included. Any wheezing in the last ≤ 1.5 years occurred more frequently in infants with ≥ 1 sibling [pooled RR 1.10, 95% confidence interval (CI) 1.02-1.19] and ≥ 1 older sibling (pooled RR 1.16, 95% CI 1.04-1.29). The pooled effect sizes for asthma were overall statistically nonsignificant, although having ≥ 1 older sibling was marginally protective for subjects aged ≥ 6 years (pooled RR 0.93, 95% CI 0.88-0.99). The effect estimates weakened in studies published after 2000 compared with earlier studies. CONCLUSIONS: Being second-born or later and having at least one sibling is associated with a slightly increased risk of temporary wheezing in infancy. In contrast, being second-born or later is associated with marginal protection against asthma. These associations appear to have weakened since the turn of the millennium, possibly due to lifestyle changes and socioeconomic development. Video Abstract.