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Highlights:

• Severe obesity strongly associates to blood neutrophils in adult-onset asthma.
• B-neutrophils may partly mediate associations between obesity and asthma control.
• Clinical evaluation of adult-onset asthma should include assessing B-neutrophils.

Objective: Adult-onset asthma is a recognized but heterogeneous phenotype and has been described to associate with poor asthma control. Knowledge about associations between clinical characteristics including comorbidities and control of adult-onset asthma is limited, especially in older populations. We aimed to study how clinical biomarkers and comorbidities are associated with uncontrolled asthma among middle-aged and older individuals with adult-onset asthma.

Methods: Clinical examinations including structured interview, asthma control test (ACT), spirometry, skin prick test (SPT), blood sampling, and measurement of exhaled fractional nitric oxide (FeNO) was performed in a population-based adult-onset asthma cohort in 2019–2020 (n = 227, 66.5% female). Analyses were performed among all included, and separately in middle-aged (37–64 years, n = 120) and older (≥65 years, n = 107) participants.

Results: In bivariate analysis, uncontrolled asthma (ACT ≤ 19) was significantly associated with a blood neutrophil count ≥5/µl, BMI ≥30, and several comorbidities. In multivariable regression analysis, uncontrolled asthma was associated with neutrophils ≥5/µl (OR 2.35; 95% CI 1.11–4.99). In age-stratified analysis, BMI ≥30 (OR 3.04; 1.24–7.50), eosinophils ≥0.3/µl (OR 3.17; 1.20–8.37), neutrophils ≥5/µl (OR 4.39; 1.53–12.62) and allergic rhinitis (OR 5.10; 1.59–16.30) were associated with uncontrolled asthma among the middle-aged. Among the older adults, uncontrolled asthma was only associated with comorbidities: chronic rhinitis (OR 4.08; 1.62–10.31), ischemic heart disease (OR 3.59; 1.17–10.98), malignancy (OR 3.10; 1.10–8.73), and depression/anxiety (OR 16.31; 1.82–146.05).

Conclusions: In adult-onset asthma, comorbidities were strongly associated with uncontrolled asthma among older adults, while clinical biomarkers including eosinophils and neutrophils in blood were associated with uncontrolled asthma among middle-aged.

Objective: To study asthma exacerbations, healthcare utilization and health status among subjects with asthma with different treatment regimens and levels of asthma control.

Methods: In 2012-2014, n = 1425 adults from a population-based asthma cohort within the OLIN studies (Obstructive Lung disease in Northern Sweden) were invited to a follow-up including spirometry and a structured interview, n = 1006 participated. Asthma Control Test (ACT) was used to detect uncontrolled asthma, and physical and mental dimensions of health were measured with SF-8. Pharmacological treatment use was classified by Global Initiative for Asthma treatment steps. Out of n = 830 with current asthma, n = 714 answered ACT (57% women, 32-92 years) and were included in the study.

Results: Uncontrolled asthma increased per treatment step (no treatment 9.9%, treatment step 1-3 24.1%, and treatment steps 4-5 39.9%, p < 0.001). A higher proportion of subjects with uncontrolled asthma reported exacerbations, healthcare utilization, and worse health status than those with controlled asthma. The proportion of subjects reporting exacerbations, healthcare visits, emergency room visits and regular follow-up visits increased per treatment step. Worse health was associated with uncontrolled asthma, but not with the level of treatment. A higher proportion of women than men reported exacerbations, any healthcare visits, and lower health. Regular follow-up visits to a physician were uncommon (women 21.2% vs. men 14.6%, p = 0.022).

Conclusions: Uncontrolled asthma is common in all treatment steps, and is associated with worse health status. However, health status did not differ by treatment steps. Identifying subjects with uncontrolled asthma regardless of treatment regimens should be a priority, thus follow-up visits are important.

BACKGROUND: Longitudinal population-based studies about the natural history of allergic sensitization are rare. The aim was to study incidence and persistence of airborne allergen sensitization up to young adulthood and risk factors for early and late onset of sensitization.

METHODS: All children aged 7-8 years in two municipalities in Northern Sweden were invited to a parental questionnaire and skin prick tests (SPTs) to ten airborne allergens, and 2148 (88%) participated. The protocol was repeated at age 11-12 and 19 years, and 1516 participated in all three examinations.

RESULTS: Prevalence of any positive SPT increased from 20.6% at age 7-8 years to 30.6% at 11-12 years, and 42.1% at 19 years. Animals were the primary sensitizers at age 7-8 years, 16.3%, followed by pollen, 12.4%. Mite and mold sensitization was low. Mean annual incidence of any positive SPT varied between 2.8 and 3.4/100 per year, decreased by age for animal, and was stable for pollen. Sensitization before age 7-8 years was independently associated with family history of allergy, OR 2.1 (95% CI 1.6-2.8), urban living, OR 1.9 (95% CI 1.2-2.9), and male sex, OR 1.3 (95% CI 1.0-1.7), and negatively associated with birth order, OR 0.8 (95% CI 0.7-1.0), and furry animals at home, OR 0.7 (95% CI 0.7-0.9). Incidence after age 11-12 years was associated only with family history of allergy. Multisensitization at age 19 years was significantly associated with early age at sensitization. Remission of sensitization was uncommon.

CONCLUSION: The increasing prevalence of allergic sensitization by age was explained by high incidence and persistence. After age 11-12 years, the factors urban living, number of siblings, and male sex lost their importance.

BACKGROUND: Epidemiologic data describing the association between allergic sensitization and asthma and allergic rhinitis in adults are scarce.

OBJECTIVE: To determine the prevalence and impact of specific sensitization to airborne allergens on asthma and allergic rhinitis among adults in relation to age.

METHODS: A random population sample (age 21-86 years) was examined with structured interview and analysis of specific IgE to 9 common airborne allergens. Of those invited, 692 (68%) subjects participated in blood sampling. IgE level of 0.35 U/mL or more to the specific allergen was defined as a positive test result.

RESULTS: Allergic sensitization decreased with increasing age, both in the population sample and among subjects with asthma and allergic rhinitis. In a multivariate model, sensitization to animal was significantly positively associated with asthma (odds ratio [OR], 4.80; 95% CI, 2.68-8.60), whereas sensitization to both animal (OR, 3.90; 95% CI, 2.31-6.58) and pollen (OR, 4.25; 95% CI, 2.55-7.06) was significantly associated with allergic rhinitis. The association between allergic sensitization and rhinitis was consistently strongest among the youngest age group, whereas this pattern was not found for asthma. The prevalence of allergic sensitization among patients with asthma decreased by increasing age of asthma onset, 86% with asthma onset at age 6 y or less, 56% at age 7 to 19 years, and 26% with asthma onset at age 20 years or more.

CONCLUSIONS: Sensitization to animal was associated with asthma across all age groups; allergic rhinitis was associated with sensitization to both pollen and animal and consistently stronger among younger than among older adults. Early onset of asthma was associated with allergic sensitization among adults with asthma.

Background: Allergic sensitization is the most important risk factor for asthma and rhinitis among children, adolescents and young adults. Less is known about the incidence and remission of allergic sensitization, particularly in older adults. Furthermore, it is not clear if the earlier documented increase in prevalence of allergic sensitization continues. This thesis is focused on prevalence, incidence and remission of allergic sensitization to airborne allergens among adolescents and adults as well as on time trends in prevalence among adults. Furthermore, associated risk factors and the relation of allergic sensitization to asthma and rhinitis were assessed.

Methods: In the study of children and adolescents, incidence, remission and prevalence of allergic sensitization were assessed in a cohort study of schoolchildren, aged 7-8 years (y) at baseline. In the studies of adults, incidence and remission of allergic sensitization were assessed in a randomly selected adult population sample in 1994 (n=664) aged 20-69 y, which was followed up in 2004 (n=555). Trends in prevalence of allergic sensitization were assessed by comparing two cross-sectional studies; the cohort from 1994 and another randomly selsected population sample examined in 2009 (n=737). The relation of allergic sensitization to asthma and rhinitis was determined in the adult cohort in 2009. Allergic sensitization was assessed by skin prick test (SPT) with ten common airborne allergens at ages 7-8, 11-12 and 19 y in the cohort of children and in the participants ≤ 60 y in the adult cohorts. Specific IgE to nine airborne allergens was analyzed in the adult cohorts in 2004 and 2009. Risk factors for allergic sensitization and variables defining respiratory disease and symptoms were assessed by questionnaires in the cohort of children and by structured interviews in the adult cohorts.

Results: The 10-year cumulative incidence of allergic sensitization among the adults from 1994 to 2004 was 5%, while remission was 32%. In both adult cohorts, the prevalence of allergic sensitization was highest among young adults, aged 20-29 y, 55% and 61% and decreased significantly with increasing age. Among children and adolescents, both incidence and persistence of allergic sensitization were high, and the prevalence of allergic sensitization increased by age from 21% at age 7-8 y to 42% at age 19 y. Multisensitization at age 19 y was strongly associated with early onset of sensitization. The prevalence of sensitization to the major specific allergens birch, timothy, cat and dog as well as multisensitization (from 40% in 1994 to 56% in 2009, p=0.002) increased significantly from 1994 to 2009 among the adults. Sensitization to any allergen increased from 35% to 39%, however not significantly (p=0.13). A family history of allergic rhinitis was strongly and consistently associated with allergic sensitization in all ages. Male sex and urban living were significantly positively and birth order and furry animals at home in childhood were negatively associated with onset of sensitization before the age of 7-8 y, but not with onset of sensitization from 11-12y to 19 y. Young adult age and urban living were significant factors associated with allergic sensitization in adult age. Sensitization to any animal was significantly positively associated with current asthma (OR4.80 (95% CI 2.68-8.60)), whereas both sensitization to any pollen (OR 4.25 (2.55-7.06)) and any animal (OR 3.90 (95% CI 2.31-6.58)) were associated with current allergic rhinitis. The association between allergic sensitization and allergic rhinitis was strongest in young adult age and decreased with increasing age, while asthma was similarly associated with sensitization to any animal across all adult ages. Among asthmatics, the prevalence of allergic sensitization decreased with increasing age of asthma onset.

Conclusion: Both incidence and persistence of allergic sensitization were high among children and adolescents explaining the increase in prevalence by increasing age. An inverse pattern with low incidence and high remission of allergic sensitization was seen among adults. The decrease in prevalence of allergic sensitization by increasing adult age might at least partly be explained by normal ageing and not only by an effect of year of birth (cohort effect). The significant increase in prevalence of sensitization to the specific allergens explained the significant increase in multisensitization over 15 years. A family history of allergy was the strongest and the only consistent risk factor for allergic sensitization in all ages. The prevalence of allergic sensitization decreased with increasing age of asthma onset among adult asthmatics.

BACKGROUND: Studies on time trends of allergic sensitization among adults are rare. The aim of the study was to compare the prevalence of allergic sensitization to common airborne allergens among adults 15 years apart and to identify risk factors for allergic sensitization.

METHODS: Clinical examinations including skin prick test (SPT) and structured interviews were performed in two random population samples in 1994 and 2009. Furthermore, specific IgE was analyzed in 2009. SPT data were available for 483 subjects in 1994 and for 463 subjects in 2009 in ages 20--60 years. Specific IgE was analyzed in 692 subjects in ages 20--79 years.

RESULTS: Sensitization to cat (16% to 26%, p < 0.001), dog (13% to 25%, p < 0.001), birch (13% to 18%, p = 0.031) and timothy (12% to 21%, p < 0.001), based on SPT, increased significantly from 1994 to 2009. Sensitization to any positive SPT increased from 35% to 39%, p = 0.13.The proportion of having >=3 positive SPT reactions increased from 40% to 56%, p = 0.002. The sensitization pattern yielded similar results based on specific IgE. Risk factors for allergic sensitization were having a family history of allergy (OR 3.1, 95% CI 2.0-4.8 for any positive SPT; OR 2.7, 95% CI 1.8-4.0 for any elevated IgE) and urban living (OR 1.7, 95% CI 1.0-2.7; OR 1.5, 95% CI 1.0-2.4).

CONCLUSIONS: The prevalence of allergic sensitization to major airborne allergens as well as multi-sensitization increased significantly between the study years. Young age, a family history of allergy and urban living were significant risk factors for allergic sensitization.

BACKGROUND: Prospective studies on the incidence and remission of allergic sensitization among adults are rare.

OBJECTIVE: We sought to assess the incidence, remission, risk factors, and prevalence of allergic sensitization in relation to aging over a 10-year period.

METHODS: In 1994, a sample of 664 adults (68% of invited) participated in clinical examinations, including a structured interview and skin prick tests (SPTs). The sample was randomly selected from a large questionnaire survey in Northern Sweden. In 2004, 555 subjects (93% of invited) were re-examined by using the same methods as in 1994. IgE levels were also measured in 2004.

RESULTS: In 1994, the prevalence of any positive SPT response was significantly related to age, with the highest prevalence (55%) in subjects aged 20 to 29 years and the lowest prevalence (26%) in subjects aged 50 to 60 years. A similar age-related prevalence was found in 2004, and sensitization to pollen and pets was most common in both years. The results of the SPTs were verified by means of specific IgE measurement. The incidence of any positive SPT response was low. Only 9 subjects had any positive SPT response (ie, a cumulative incidence of 5% over 10 years). Remission was greater (ie, 32% over 10 years). The main risk factors for allergic sensitization were young age and a family history of allergy. Having had furred animals at home during childhood was negatively related to specific IgE levels.

CONCLUSION: The low incidence and high remission in adulthood explain the decreasing prevalence of allergic sensitization by age. Thus the low prevalence of allergic sensitization among the elderly found in cross-sectional studies is an effect of normal aging and not primarily a birth cohort effect.