Treatable traits and exacerbation risk in patients with uncontrolled asthma prescribed GINA step 1-3 treatment: A nationwide asthma cohort study.

BACKGROUND AND OBJECTIVE: Uncontrolled asthma in patients treated for mild/moderate disease could be caused by non-pulmonary treatable traits (TTs) that affect asthma control negatively. We aimed to identify demographic characteristics, behavioural (smoking) and extrapulmonary (obesity, comorbidities) TTs and the risk for future exacerbations among patients with uncontrolled asthma prescribed step 1-3 treatment according to the Global Initiative for Asthma (GINA). METHODS: Twenty-eight thousand five hundred eighty-four asthma patients (≥18 y) with a registration in the Swedish National Airway Register between 2017 and 2019 were included (index-date). The database was linked to other national registers to obtain information on prescribed drugs 2-years pre-index and exacerbations 1-year post-index. Asthma treatment was classified into step 1-3 or 4-5, and uncontrolled asthma was defined based on symptom control, exacerbations and lung function. RESULTS: GINA step 1-3 included 17,318 patients, of which 9586 (55%) were uncontrolled (UCA 1-3). In adjusted analyses, UCA 1-3 was associated with female sex (OR 1.34, 95% CI 1.27-1.41), older age (1.00, 1.00-1.00), primary education (1.30, 1.20-1.40) and secondary education (1.19, 1.12-1.26), and TTs such as smoking (1.25, 1.15-1.36), obesity (1.23, 1.15-1.32), cardiovascular disease (1.12, 1.06-1.20) and depression/anxiety (1.13, 1.06-1.21). Furthermore, UCA 1-3 was associated with future exacerbations; oral corticosteroids (1.90, 1.74-2.09) and asthma hospitalization (2.55, 2.17-3.00), respectively, also when adjusted for treatment step 4-5. CONCLUSION: Over 50% of patients treated for mild/moderate asthma had an uncontrolled disease. Assessing and managing of TTs such as smoking, obesity and comorbidities should be conducted in a holistic manner, as these patients have an increased risk for future exacerbations.

Exploring proteomic plasma biomarkers in eosinophilic and neutrophilic asthma.

BACKGROUND: Few biomarkers identify eosinophilic and neutrophilic asthma beyond cell concentrations in blood or sputum. Finding novel biomarkers for asthma endotypes could give insight about disease mechanisms and guide tailored treatment. Our aim was to investigate clinical characteristics and inflammation-related plasma proteins in relation to blood eosinophil and neutrophil concentrations in subjects with and without asthma. METHODS: We included 24-26-year-old subjects (n = 2063) from the Swedish population-based cohort BAMSE. Subjects with asthma (n = 239) and without asthma (n = 1824) were subdivided based on blood eosinophil and neutrophil concentrations (cut-offs 0.3 × 109 /L and 5.0 × 109 /L, respectively). We measured the levels of 92 plasma proteins using Olink Proseek Multiplex Inflammation Panel Assay. Group statistics tests were used to analyse the data, as well as adjusted multiple logistic regression models. RESULTS: Among subjects with asthma, 21.8% had eosinophilic asthma and 20.5% neutrophilic asthma. Eosinophilic asthma, but not neutrophilic asthma, was associated with a distinct clinical phenotype with, for example, higher proportions of eczema and sensitization. Most plasma proteins that associated with high eosinophil and/or neutrophil blood concentrations in subjects with asthma showed similar associations in subjects without asthma. However, out of these proteins, MMP10 levels were associated with eosinophilic asthma and were significantly higher as compared to controls with high eosinophilic concentration, while CCL4 levels associated with high neutrophil concentration only in subjects with asthma. CONCLUSIONS: Eosinophilic asthma was associated with a clear clinical phenotype. With our definitions, we identified MMP10 as a possible plasma biomarker for eosinophilic asthma and CCL4 was linked to neutrophilic asthma. These proteins should be evaluated further in clinical settings and using sputum granulocytes to define the asthma endotypes.

Health-related quality of life decreases in young people with asthma during the transition from adolescence to young adulthood: a birth cohort study.

BACKGROUND: During the transition from paediatric to adult healthcare there is a gap between asthma guidelines and actual management with decreased healthcare consultations and dispensations of asthma medications after the transition to adult healthcare among young people with asthma. How health-related quality of life (HRQoL) develops during the transition from adolescence to young adulthood is unclear. Our aim was therefore to investigate HRQoL among young people with asthma during the transition to adulthood. Further, to assess if level of asthma control and physical activity influence any potential association between asthma and HRQoL. METHODS: The study population consisted of 2268 participants from the ongoing Swedish population-based prospective birth cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology). HRQoL was measured using the instrument EQ-5D-3 L and three general questions. The EQ-5D-3 L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3 L instrument and questions on general health, symptoms and treatment of asthma, and lifestyle factors were based on data from follow-ups at 16 and 24 years. Cross-sectional analyses were made. RESULTS: At the 24-year follow-up, the adjusted median values of EQ VAS were lower compared with at the 16-year follow-up; among both participants with asthma (80 vs. 85, p < 0.01) and those without asthma (80 vs. 87, p < 0.01). At the 24-year follow-up, participants with uncontrolled asthma had a lower adjusted median EQ VAS score than peers with controlled/partly controlled asthma (75 vs. 80, p = 0.03). Further, young adults with asthma who did not fulfil the WHO recommendations on physical activity had lower EQ VAS scores than peers who did (70 vs. 80, p < 0.01). CONCLUSION: HRQoL is lower in young adulthood than in adolescence. Young adults with asthma having uncontrolled disease or who are physically inactive appear to be particularly vulnerable.

Non-adherence and sub-optimal treatment with asthma medications in young adults: a population-based cohort study.

OBJECTIVE: Pharmacological treatment plays a key role in the management of asthma, but medication adherence is generally low. Our aim was to assess factors associated with dispensing patterns of, and adherence to, asthma medication in young adults with asthma. METHODS: The study included young adults (age 22-24 years) from the Swedish population-based birth cohort BAMSE (n = 3,064) with linkage to register data on dispensed asthma medications and recorded diagnosis. Dispensing information was collected in January 2014-June 2019 (the study period) to cover the period of questionnaire data. Adherence to asthma medication was defined as refilling a prescription within 18 months. RESULTS: In total, 234 individuals (7.6%) had asthma (doctor's diagnosis of asthma in combination with respiratory symptoms) and had been dispensed at least one prescription of asthma medication during the study period. Among them, 77% were dispensed a controller medication. The mean number of prescriptions dispensed per individual was higher in males than females (11.0 vs. 7.2; p < 0.01). The proportion of asthmatics with only a short-acting ß2-agonist (SABA) dispensed was 22%, of which 33% were classified as having uncontrolled asthma. Adherence to controller medication was 60% and higher among those with an asthma diagnosis from specialized care than those diagnosed in primary care (RR 1.32 95% CI 1.03-1.69). Sex, socioeconomic status, and non-allergic comorbidity did not affect adherence. CONCLUSION: Young adults with asthma had few prescriptions of asthma medication dispensed, indicating sub-optimal treatment. A considerable proportion was dispensed only SABA. Furthermore, adherence to controller medication was relatively low.

Lost in the transition from pediatric to adult healthcare? Experiences of young adults with severe asthma.

Objective: Asthma is a multifaceted disease, and severe asthma is likely to be persistent. Patients with severe asthma have the greatest burden and require more healthcare resources than those with mild-to-moderate asthma. The majority with asthma can be managed in primary care, while some patients with severe asthma warrant referral for expert advice regarding management. In adolescence, this involves a transition from pediatric to adult healthcare. This study aimed to explore how young adults with severe asthma experienced the transition process.Methods: Young adults with severe asthma were recruited from an ongoing Swedish population-based cohort. Qualitative data were obtained through individual interviews (n = 16, mean age 23.4 years), and the transcribed data were analyzed with systematic text condensation.Results: Four categories emerged based on the young adults' experiences: "I have to take responsibility", "A need of being involved", "Feeling left out of the system", and "Lack of engagement". The young adults felt they had to take more responsibility, did not know where to turn, and experienced fewer follow-ups in adult healthcare. Further, they wanted healthcare providers to involve them in self-management during adolescence, and in general, they felt that their asthma received insufficient support from healthcare providers.Conclusions: Based on how the young adults with severe asthma experienced the transition from pediatric to adult healthcare, it is suggested that healthcare providers together with each patient prepare, plan, and communicate in the transition process for continued care in line with transition guidelines.

Does asthma affect school performance in adolescents? Results from the Swedish population-based birth cohort BAMSE.

BACKGROUND: Asthma is common among schoolchildren and may influence quality of life and school attendance. However, it is unclear if asthma affects school performance. The aim of this study was to examine whether different phenotypes of asthma affect school performance during adolescence. METHODS: The study population consisted of 1715 adolescents from a population-based birth cohort, followed up to age 16 with questionnaires and clinical examinations. Asthma was defined as at least 4 wheeze episodes or at least 1 wheeze episode in combination with inhaled steroids in the last 12 months. School grades were obtained from Statistics Sweden, and logistic regression analysis was performed to investigate the association between the final overall grade from secondary school and asthma phenotypes. RESULTS: Among the adolescents, 20.8% have had ever asthma; 24.2% early transient, 47.2% school-age onset, and 24.2% persistent asthma. At 16 years, 7.8% had asthma; 71.7% multimorbidity and 73.9% allergic asthma. A statistically significant association for performing less well was seen for ever asthma (ORadj  = 1.43, 95% CI = 1.09-1.88). In analyses of asthma onset, an association was seen for school-age onset (ORadj  = 1.49, CI = 1.02-2.16) and a tendency for persistent asthma (ORadj  = 1.61, CI = 0.98-2.66), although with overlapping confidence intervals. Further, adolescents with uncontrolled asthma tended to perform less well (ORadj  = 2.60, CI = 0.87-7.80) compared to adolescents with partly controlled (ORadj  = 1.12, CI = 0.68-1.83) and fully controlled (ORadj  = 1.29, CI = 0.55-3.01) asthma. CONCLUSIONS: Our results indicate that asthma impairs school performance in adolescence. Moreover, some evidence suggests the adolescents with asthma during school age and with poorer asthma control to be more likely to perform less well.

Adherence to inhaled corticosteroid therapy and treatment escalation in the Swedish adult asthma population.

BACKGROUND: Patients with uncontrolled asthma should be evaluated for medication adherence. This study aimed to identify characteristics associated with poor adherence to inhaled corticosteroids (ICS) and to explore adherence prior to treatment escalation. METHODS: This nationwide longitudinal cohort study included adult asthma patients (n = 30880) with a healthcare visit including Asthma Control Test (ACT) and registered in the Swedish National Airway Register between 1 July 2017 and 28 February 2019 (index date). Patient data was crosslinked to other national registers. Treatment steps two years pre- and one year post-index, were identified by prescribed drugs. Poor adherence was defined as Medication Possession Ratio <80 %. RESULTS: Poor adherence was identified in 73 % of patients in treatment steps 2-5, where of 35 % had uncontrolled asthma (ACT≤19). In adjusted models, poor adherence was associated with better disease control; ACT≤19 (OR 0.78, 95 % CI 0.71-0.84), short-acting ß2-agonist (SABA) overuse (0.69, 0.61-0.79) and exacerbations (0.79, 0.70-0.89) in steps 2-3. Among patients with uncontrolled asthma, poor adherence was associated with SABA overuse (1.71, 1.50-1.95), exacerbations (1.29, 1.15-1.46), current smoking (1.38, 1.21-1.57) and inversely associated with asthma management education (0.85, 0.78-0.93. Similar results were observed in steps 4-5. When investigating post-index treatment, 53 % remained stationary, 30 % stepped down and 17 % escalated treatment. Prior to escalation, 49 % had poor adherence. CONCLUSIONS: Poor ICS adherence was associated with better asthma control. Among uncontrolled patients, poor adherence was associated with SABA overuse and exacerbations. Our result highlights the importance of asthma management education to improve adherence in uncontrolled patients.

Uncontrolled asthma in school-aged children-a nationwide specialist care study.

Background: Uncontrolled asthma (UCA) is different from severe asthma and can be identified in children across all ranges of prescribed treatment. Objective: Our aim was to characterize uncontrolled childhood asthma in pediatric specialist care. Methods: We performed a nationwide cross-sectional study of 5497 children (aged 6-17 years) with asthma who were treated by pediatricians at outpatient clinics during 2019 and registered in the Swedish National Airway Register. UCA was defined as an Asthma Control Test score of 19 or lower and/or 2 or more exacerbations in the past year and/or an FEV1 value less than 80% predicted. Treatment was categorized from step 1 to step 5 according to the Global Initiative for Asthma. Results: UCA was identified in 1690 children (31%), of whom 64% had an Asthma Control Test score of 19 or lower, 20% had recurrent exacerbations, and 31% had an FEV1 value less than 80% predicted. UCA was associated with female sex (odds ratio [OR] = 1.29 [95% CI = 1.15-1.45]), older age (OR = 1.02 [95% CI = 1.00-1.04]), obesity (OR = 1.43 [95% CI = 1.12-1.83]), and more treatment using steps 1 and 2 as a reference (step 3, OR = 1.28 [95% CI = 1.12-1.46]); steps 4-5, OR = 1.32 [95% CI = 1.10-1.57]). UCA in children prescribed treatment steps 1 and 2 (group UCA1-2) occurred in 28% of all children at this treatment step (n = 887). Children in group UCA1-2 had exacerbations more frequently than did those children with UCA who were prescribed steps 4 and 5 treatment (24% vs 15% [P = .001]). Conclusion: UCA was common and associated with female sex, increasing age, obesity, and higher Global Initiative for Asthma treatment step. Surprisingly, UCA was also common in children prescribed less than the maximum treatment, and those children could be considered undertreated patients.

COVID-19 vaccine uptake among young adults: Influence of asthma and sociodemographic factors.

Background: Asthma was initially described as a risk factor for severe coronavirus disease 2019 (COVID-19), but the uptake of COVID-19 vaccine among young adults with asthma is not well studied. Objective: The aims were to assess COVID-19 vaccine uptake among young adults in general and to explore potential determinants including sociodemographic factors and asthma. Methods: Participants from the population-based birth cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) were included: 4,064 in the study population, 3,064 in a follow-up at age 24 years, and 2,049 in a COVID-19 follow-up (mean age, 26.5 years). Asthma and asthma-associated characteristics were assessed through questionnaires and clinical data. Data on all COVID-19 vaccines registered between January 1, 2021, and February 15, 2023, were extracted from the National Vaccination Register. Results: In the study population (n = 4,064), 53.9% had ≥3 COVID-19 vaccine doses registered. In the 24-year follow-up population (n = 3,064), vaccine uptake differed in relation to education (P < .001). Among the participants with university/college education, 65.7% had an uptake of ≥3 doses of vaccine, compared to 54.1% among the participants with elementary school/high school education. Participants with asthma had decreased odds of receiving ≥3 doses (adjusted odds ratio = 0.62; 95% confidence interval, 0.41-0.92) and ≥2 compared to peers without asthma. Those with uncontrolled disease also had decreased odds of receiving ≥3 doses (adjusted odds ratio = 0.30; 95% confidence interval, 0.13-0.66) and ≥2 compared to participants with controlled asthma. Conclusions: COVID-19 vaccine uptake among young adults is lower in individuals from households with lower socioeconomic status and among those with asthma, including uncontrolled asthma.

Characterization of Asthma Trajectories from Infancy to Young Adulthood.

BACKGROUND: Development of asthma is complicated by the multidimensional nature of the disease. OBJECTIVE: To identify and characterize trajectories of asthma from infancy to young adulthood, and their associations with lung function and inflammatory and respiratory markers in adolescence and young adulthood. METHODS: A latent class analysis was performed in a population-based cohort (N = 4089). Parental and self-reported symptoms of asthma were used to investigate asthma development. We characterized background factors, allergic comorbidity, and IgE sensitization and investigated associations with asthma markers. RESULTS: A 4-class solution of asthma trajectories was identified: never/infrequent (n = 3291 [80.4%]), early-onset transient (n = 307 [7.5%]), adolescent-onset (n = 261 [6.4%]), and persistent asthma (n = 230 [5.6%]). Uncontrolled asthma was equally prevalent in the adolescent-onset and persistent asthma trajectory groups, at both age 16 (41.7% vs 42.4%; P = .90) and 24 years (53.7% vs 52.4%; P = .81). The persistent asthma trajectory group had a higher proportion of eosinophil counts greater than or equal to 0.3 (109 cells/L) at age 24 years compared with the adolescent-onset trajectory group (31.0% vs 18.5%; P < .01). CONCLUSIONS: The adolescent-onset and persistent asthma trajectory groups had equal burdens of asthma control in adolescence and young adulthood. However, the persistent asthma trajectory group showed more signs of type 2 inflammation than the adolescent-onset trajectory group. This unbiased approach highlights the need of identifying patients with adolescent asthma to optimize care, because they suffer the same lack of asthma control as those with persistent asthma.

A Gap Between Asthma Guidelines and Management for Adolescents and Young Adults.

BACKGROUND: For adolescents, asthma management can be challenging during the transition to adulthood, and changes in health care and pharmacological treatment may occur. OBJECTIVE: To investigate asthma-related health care consumption and pharmacological dispensation during the transition process. METHODS: In a Swedish birth cohort study, questionnaire and clinical data from the 16- and 24-year follow-ups were linked to national and regional registries for asthma-related health care consumption and dispensed medications during an 8-year period: 4 years before and after age 18 y, respectively. RESULTS: In the study population (n = 1808), 14% fulfilled the study definition of current asthma at the 16- and 24-year follow-up and 8% (n = 147) had persistent asthma. Among them, register data showed that in the 4-year period before their 18th birthday, 39% (58 of 147) had at least 1 consultation, similar to 37% (55 of 147) in the following 4-year period. The mean number of consultations before age 18 years was 1.6, compared with 1.0 after age 18 years (P = .02). At least 1 dispensation of any inhaled corticosteroid before age 18 years was found for 73% (107 of 147), compared with 50% (74 of 147) after age 18 years. The mean number of dispensed any inhaled corticosteroid was 3.1 before 18 years and 2.1 after 18 years (P < .01). Only 3% (5 of 147) had a regular dispensation of any inhaled corticosteroid once a year during the 8-year period. CONCLUSIONS: Health care consultations were fewer than recommended in guidelines and decreased after the transition to adult health care. Almost no one had dispensed regular asthma medications during the 8-year period.