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.

Level of education, but not occupation, is differentially associated with asthma phenotypes in adults.

CONCLUSION: Education, but not occupation, was differentially associated with adult asthma phenotypes in the general population. Further research into socioeconomic status variation in various asthma phenotypes is warranted.

Machine learning-derived phenotypic trajectories of asthma and allergy in children and adolescents: protocol for a systematic review.

INTRODUCTION: Development of asthma and allergies in childhood/adolescence commonly follows a sequential progression termed the 'atopic march'. Recent reports indicate, however, that these diseases are composed of multiple distinct phenotypes, with possibly differential trajectories. We aim to synthesise the current literature in the field of machine learning-based trajectory studies of asthma/allergies in children and adolescents, summarising the frequency, characteristics and associated risk factors and outcomes of identified trajectories and indicating potential directions for subsequent research in replicability, pathophysiology, risk stratification and personalised management. Furthermore, methodological approaches and quality will be critically appraised, highlighting trends, limitations and future perspectives. METHODS AND ANALYSES: 10 databases (CAB Direct, CINAHL, Embase, Google Scholar, PsycInfo, PubMed, Scopus, Web of Science, WHO Global Index Medicus and WorldCat Dissertations and Theses) will be searched for observational studies (including conference abstracts and grey literature) from the last 10 years (2013-2023) without restriction by language. Screening, data extraction and assessment of quality and risk of bias (using a custom-developed tool) will be performed independently in pairs. The characteristics of the derived trajectories will be narratively synthesised, tabulated and visualised in figures. Risk factors and outcomes associated with the trajectories will be summarised and pooled estimates from comparable numerical data produced through random-effects meta-analysis. Methodological approaches will be narratively synthesised and presented in tabulated form and figure to visualise trends. ETHICS AND DISSEMINATION: Ethical approval is not warranted as no patient-level data will be used. The findings will be published in an international peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023441691.

Socioeconomic status and different forms of rhinitis in Swedish adults.

BACKGROUND: Rhinitis encompasses diverse forms. Each form has distinct pathophysiology and clinical manifestations and may be influenced by differential risk factors. The association between socioeconomic status (SES) and different forms of rhinitis remains poorly understood. Our aim was to examine SES variations in allergic rhinitis, chronic rhinitis, and chronic rhinosinusitis in adults. METHODS: Based on a 2016 postal questionnaire survey within the West Sweden Asthma Study, we analyzed data from 36,213 subjects aged 16-75 years. The measures of SES were levels of education and occupation. Adjusted logistic regression was used to examine associations between SES and the rhinitis outcomes. RESULTS: Attaining a secondary school and tertiary education, compared to a primary school, were associated with increased risk of allergic rhinitis (secondary OR 1.33, 95% CI 1.22-1.45; tertiary 1.54, 1.41-1.69) and chronic rhinitis (secondary 1.18, 1.08-1.29; tertiary 1.17, 1.06-1.28). The influence of occupation was consistent with respect to allergic rhinitis. For instance, compared to the lowest occupational skill level, the highest level (OR 1.24, 95% CI 1.04-1.48) and the lower high occupation levels (1.24, 1.04-1.49) were associated with an increased risk of allergic rhinitis. No significant link was found between education and chronic rhinosinusitis or between occupation levels and risk of either chronic rhinitis or chronic rhinosinusitis. CONCLUSION: Individuals with higher education and those at higher occupational levels may be at higher risk of having different forms of rhinitis than those at lower education and occupation levels. Assessment of rhinitis burden via SES can be one strategy to develop preventive strategies.

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.

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 patterns to cat molecular allergens in subjects with allergic sensitization to cat dander.

BACKGROUND: The use of molecular allergology has increasingly become common in the diagnosis and management of allergic diseases. However, there is still a lack of data on cat molecular allergens in adults. Therefore, we aimed to uncover the sensitization patterns to cat molecular allergens. METHODS: Participants were recruited from the West Asthma Sweden Study, a population-based study enriched with asthma subjects aged 16-75 years. Of 1872, 361 individuals were positive for cat dander immunoglobulin E and were further analysed for cat molecular allergens (Fel d 1/2/4/7). Sensitization patterns were classified as monosensitization, polysensitization, and concomitant sensitization, and were related to demographic and clinical measurements. RESULTS: Among cat-sensitized subjects, 84.2% were sensitized to secretoglobin, while 42.4% were sensitized to lipocalins. Nearly half of the subjects were monosensitized to Fel d 1. Polysensitization was observed in 20.2%, and concomitant sensitization to protein families was seen in 7.2%. Asthma prevalence, cat exposure, and rural living were associated with poly- and concomitant sensitization to protein families. Concomitant sensitization to single allergens was more common in those with asthma than in those without, while concomitant sensitization to both Fel d 1 and Fel d 4 was the most common pattern in individuals with asthma. Sensitization patterns also differed according to cat ownership and the degree of urbanization. CONCLUSION: Sensitization to molecular allergens was observed in 90.9% of cat-sensitized subjects and showed variations across participants' background characteristics and the presence of asthma. Identification of sensitization patterns to cat allergens might provide better characterization of cat-allergic subjects.

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.

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.

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.

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.

Interaction of smoking and social status on the risk of respiratory outcomes in a Swedish adult population: A Nordic Epilung study.

BACKGROUND: Evidence abounds on the independent roles of social class and smoking in relation to obstructive airway diseases, but data are sparse on the impact of their interaction. We evaluated whether and to what extent social class and smoking interact in relation to risk of respiratory diseases in adults. METHODS: Data from the population-based studies, West Sweden Asthma Study (WSAS, n = 23,753) and Obstructive Lung Disease in Northern Sweden studies (OLIN, n = 6519), were used, constituting randomly selected adults aged 20-75 years. Bayesian network analysis was used to estimate the probability for the interaction between smoking and socioeconomic status in relation to respiratory outcomes. RESULTS: Occupational and educational SES modified the association between smoking and the probability of allergic and non-allergic asthma. Former smokers who were at intermediate non manual employees and manual workers in service had higher probability of allergic asthma compared to professionals and executives. Furthermore, former smokers with primary education had higher probability of non-allergic asthma than those with secondary and tertiary education. Similarly, former smokers among professionals and executives had higher probability of non-allergic asthma than manual and home workers and primary educated. Likewise, allergic asthma due to former smoking was higher among highly educated compared to low educated. CONCLUSIONS: Beyond their independent roles, socioeconomic status and smoking interact in defining the risk of respiratory diseases. Clearer understanding of this interaction can help to identify population subgroups at most need of public health interventions.

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.

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.

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.

Sibship size, birth order and risk of asthma and allergy: protocol for a systematic review and meta-analysis.

INTRODUCTION: The hygiene hypothesis suggests that reduced exposure to microbes might have contributed to the increase in prevalence and incidence of asthma and allergy observed during the second half of the last century. Following this proposal, several studies have investigated the role of sibship size and birth order in the development of asthma and allergic diseases, but the underlying evidence is conflicting. The objective of the present systematic review will be to identify, critically appraise and synthesise previous primary studies investigating the association of sibship size and birth order with the risk of asthma and allergic diseases. METHODS AND ANALYSIS: The following databases will be searched: AMED, CABI, CINAHL, Embase, Google Scholar, OAIster, Open Access Theses and Dissertations, Open Grey, ProQuest Dissertations & Theses Global, PsycINFO, PubMed, SciELO, Scopus, Web of Science and WHO Global Index Medicus. Studies published up until 31 December 2020 will be eligible. There will be no restrictions by language and geographical location. Risk of bias in the included studies will be assessed using the Effective Public Health Practice Project quality assessment tool. The produced evidence will be synthesised narratively, and studies that present comparable numerical data will be included in meta-analyses using random effects model. ETHICS AND DISSEMINATION: Only data from the published literature will be included in this systematic review. Therefore, no ethical approval is required. The final review paper will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020207905.