Healthcare Resource Utilisation of Severe Uncontrolled T2low and Non-T2low Asthma in Finland During 2018-2021.

Purpose: Patients with asthma and low levels of type 2 inflammatory biomarkers (T2 low) have limited effective treatment options. Such biomarkers include eg blood eosinophils (b-eos) and fractional exhaled nitric oxide (FeNO). The healthcare resource utilisation (HCRU) of severe uncontrolled T2 low asthma remains unexplored. Thus, this study aimed to estimate the HCRU of T2 low and non-T2 low severe uncontrolled asthma patients using real-world data in Finland. Patients and Methods: Adult patients with an asthma diagnosis during baseline (2012-2017) at the pulmonary department of Turku University Hospital were included and followed during 2018-2021, or until death. Total HCRU costs and respiratory-related HCRU costs were evaluated. The main drivers for the HCRU and costs were assessed with gamma and negative binomial regression models. Results: Of the severe uncontrolled asthma patients with T2 status available, 40% (N=66) were identified with T2 low and 60% (N=103) with non-T2 low asthma. The average cumulative cost per patient was similar in patients with T2 low compared with non-T2 low, with all-cause costs cumulating in four years of follow-up to 37,524€ (95% CI: 27,160, 47,888) in T2 low compared to 34,712€ (25,484, 43,940) in non-T2 low. The corresponding average cumulative respiratory-related costs were 5178€ (3150, 7205) in T2 low compared to 5209€ (4104, 6313) in non-T2 low. Regression modelling identified no differences between the T2-status groups when assessing all-cause healthcare costs per patient-year (PPY). On the other hand, the regression modelling predicted more inpatient days PPY for severe uncontrolled patients with T2 low status compared to the patients with non-T2 low status. Conclusion: Patients with uncontrolled severe T2 low asthma use equal healthcare resources as corresponding non-T2 low patients. This study brought new insights into the HCRU of severe uncontrolled asthma patients per T2 status, which has not previously been investigated.

Relation of changes in peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) during bronchoconstriction.

Diagnosis of asthma can be confirmed based on variability in peak expiratory flow (PEF) or changes in forced expiratory volume in 1 s (FEV1) measured with spirometry. Our aim was to use methacholine challenge as a model of induced airway obstruction to assess how well relative changes in PEF reflect airway obstruction in comparison to relative changes in FEV1. We retrospectively studied 878 patients who completed a methacholine challenge test. To assess congruency along with differences between relative changes in FEV1 and PEF during airway obstruction, a regression analysis was performed, and a Bland & Altman plot was constructed. ROC analysis, sensitivity, specificity, positive and negative predictive values and κ-coefficient were used to analyze how decrease in PEF predicts decrease of 10% or 15% in FEV1. The relative change in PEF was on average less than the relative change in FEV1. In the ROC analysis areas under the curve were 0.844 and 0.893 for PEF decrease to predict a 10% and 15% decrease in FEV1, respectively. The agreement between changes in PEF and FEV1 varied from fair to moderate. Airway obstruction detected by change in PEF was false in about 40% of cases when compared to change in FEV1. Change in PEF is not a very accurate measure of airway obstruction when compared to change in FEV1. Replacing peak flow metre with a handheld spirometer might improve diagnostic accuracy of home monitoring in asthma.

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

Salbutamol Easyhaler provides non-inferior relief of methacholine induced bronchoconstriction in comparison to Ventoline Evohaler with spacer: A randomized trial.

BACKGROUND: Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs) offer an alternative, but concerns exist whether DPIs provide an effective relief during an obstructive event. OBJECTIVE: We aimed to show non-inferiority of Salbutamol Easyhaler DPI compared to pMDI with spacer in treating methacholine-induced bronchoconstriction. Applicability of Budesonide-formoterol Easyhaler DPI as a reliever was also assessed. METHODS: This was a randomized, parallel-group trial in subjects sent to methacholine challenge (MC) test for asthma diagnostics. Participants with at least 20 % decrease in forced expiratory volume in 1 s (FEV1) were randomized to receive Salbutamol Easyhaler (2 × 200 µg), Ventoline Evohaler with spacer (4 × 100 µg) or Budesonide-formoterol Easyhaler (2 × 160/4.5 µg) as a reliever. The treatment was repeated if FEV1 did not recover to at least -10 % of baseline. RESULTS: 180 participants (69 % females, mean age 46 yrs [range 18-80], FEV1%pred 89.5 [62-142] %) completed the trial. Salbutamol Easyhaler was non-inferior to pMDI with spacer in acute relief of bronchoconstriction showing a -0.083 (95 % LCL -0.146) L FEV1 difference after the first dose and -0.032 (-0.071) L after the last dose. The differences in FEV1 between Budesonide-formoterol Easyhaler and Salbutamol pMDI with spacer were -0.163 (-0.225) L after the first and -0.092 (-0.131) L after the last dose. CONCLUSION: The study confirms non-inferiority of Salbutamol Easyhaler to Ventoline Evohaler with spacer in relieving acute bronchoconstriction, making Easyhaler a sustainable and safe reliever for MC test and supports its use during asthma attacks.

Exploring Definitions and Predictors of Severe Asthma Clinical Remission Post-Biologic in Adults.

RATIONALE: There is no consensus on criteria to include in an asthma remission definition in real-life. Factors associated with achieving remission post-biologic-initiation remain poorly understood. OBJECTIVES: To quantify the proportion of adults with severe asthma achieving multi-domain-defined remission post-biologic-initiation and identify pre-biologic characteristics associated with achieving remission which may be used to predict it. METHODS: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1-year pre- and post-biologic-initiation. A priori-defined remission cut-offs were: 0 exacerbations/year, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted forced expiratory volume in one second ≥80%. Remission was defined using 2 (exacerbations + LTOCS), 3 (+control or +lung function) and 4 of these domains. The association between pre-biologic characteristics and post-biologic remission was assessed by multivariable analysis. MEASUREMENTS AND MAIN RESULTS: 50.2%, 33.5%, 25.8% and 20.3% of patients met criteria for 2, 3 (+control), 3 (+lung function) and 4-domain-remission, respectively. The odds of achieving 4-domain remission decreased by 15% for every additional 10-years asthma duration (odds ratio: 0.85; 95% CI: 0.73, 1.00). The odds of remission increased in those with fewer exacerbations/year, lower LTOCS daily dose, better control and better lung function pre-biologic-initiation. CONCLUSIONS: One in 5 patients achieved 4-domain remission within 1-year of biologic-initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission post-biologic, indicating that biologic treatment should not be delayed if remission is the goal. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Multi-Disciplinary Expert Perspective on the Management of Type 2 Inflammation-Driven Severe CRSwNP: A Brief Overview of Pathophysiology and Recent Clinical Insights.

Severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disabling airway disease that significantly impacts patients' lives through the severity of symptoms, the need for long-term medical treatment and the high risk of recurrence post-surgery. Biological agents targeting type 2 immune responses underlying the pathogenesis of CRSwNP have shown effectiveness in reducing polyp size and eosinophilic infiltrate, and in decreasing the need for additional sinus surgeries. However, despite recent progress in understanding and treating the disease, type 2 inflammation-driven severe CRSwNP continues to pose challenges to clinical management due to several factors such as persistent inflammation, polyp recurrence, heterogeneity of disease, and comorbidities. This article presents the findings of a scientific discussion involving a panel of ear, nose and throat (ENT) specialists and pulmonologists across Sweden and Finland. The discussion aimed to explore current management practices for type 2 inflammation-driven severe CRSwNP in the Nordic region. The main topics examined encompassed screening and referral, measurements of disease control, treatment goals, and future perspectives. The experts emphasized the importance of a collaborative approach in the management of this challenging patient population. The discussion also revealed a need to broaden treatment options for patients with type 2 inflammation-driven CRSwNP and comorbid conditions with shared type 2 pathophysiology. In light of the supporting evidence, a shift in the disease model from the presence of polyps to that of type 2 inflammation may be warranted. Overall, this discussion provides valuable insights for the scientific community and can potentially guide the future management of CRSwNP.

Association of temperature and absolute humidity with incidence of exercise-induced bronchoconstriction in children.

AIM: Exercise test outdoors is widely used to diagnose asthma in children, but it is unclear how much outdoor air factors affect the results. METHODS: We analysed 321 outdoor exercise challenge tests with spirometry in children 6-16 years conducted due to suspicion of asthma or for assessing the effect of medication on asthma. We studied the association of FEV1 decrease and incidence of exercise-induced bronchoconstriction (EIB) with temperature, relative humidity (RH) and absolute humidity (AH). RESULTS: Asthma was diagnosed in 57% of the subjects. AH ≥5 g/m3, but not RH or temperature, was associated with the EIB incidence (p = 0.035). In multivariable logistic regression, AH ≥5 g/m3 was negatively associated (OR = 0.51, 95% CI [0.28─0.92], p = 0.026) while obstruction before exercise (OR = 2.11, 95% CI [1.16─3.86], p = 0.015) and IgE-mediated sensitisation were positively associated with EIB (OR = 2.24, 95% CI [1.11─4.51], p = 0.025). AH (r = -0.12, p = 0.028) and temperature (r = -0.13, p = 0.023) correlated with decrease in FEV1. In multivariable linear regression, only AH was associated with FEV1 decrease (coefficient = -0.044, 95% CI [-0.085 to -0.004], p = 0.033). CONCLUSION: AH of outdoor air associates with occurrence and severity of EIB in outdoor exercise tests in children. Care should be taken when interpreting negative outdoor exercise test results if AH of air is high.

Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

Agreement between self-reported and registered age at asthma diagnosis in Finland.

INTRODUCTION: In epidemiological studies, the age at asthma onset is often defined by patients' self-reported age at diagnosis. The reliability of this report might be questioned. Our objective was to evaluate the agreement between self-reported and registered age at asthma diagnosis and assess features contributing to the agreement. METHODS: As part of the FinEsS respiratory survey in 2016, randomly selected population samples of 13,435 from Helsinki and 8000 from Western Finland were studied. Self-reported age at asthma diagnosis was compared to age at asthma diagnosis registered in the Finnish register on special reimbursement for asthma medication. The reimbursement right is based on lung function criteria according to GINA and Finnish guidelines. If the difference was less than 5 years, self-reported diagnosis was considered reliable. Features associated with the difference between self-reported and registered age at asthma diagnosis were evaluated. RESULTS: Altogether 197 subjects from Helsinki and 144 from Western Finland were included. Of these, 61.9% and 77.8%, respectively, reported age at diagnosis reliably. Median difference between self-reported and registered age at diagnoses was - 2.0 years (IQR - 9.0 to 0) in Helsinki and - 1.0 (IQR - 4.3 to 0) in Western Finland indicating earlier self-reported age at diagnosis. More reliable self-report was associated with non-allergic subjects and subjects who reported having asthma diagnosis more recently. CONCLUSIONS: Agreement between self-reported and registered age at asthma diagnosis was good especially with adult-onset asthma patients. Poor agreement in early-onset asthma could be related to delay in registration due to reimbursement criteria.

Diagnoses and prescription patterns among users of medications for obstructive airway diseases in Finland.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common diseases mostly treated in primary care. However, the usage patterns of drugs for obstructive airway diseases (R03 drugs) at the national level are not known. OBJECTIVE: The aims of this study were to describe (1) for which diagnoses each class of R03 drugs were used, (2) the usage pattern of different drug classes for asthma and COPD, and (3) how often these medications were used without a diagnosis of asthma or COPD in Finland. METHODS: We sent questionnaires that included questions on physician-diagnosed asthma and COPD to a random sample of 2000 Finnish subjects who had been dispensed R03 medications in the previous year. Details of R03 medications dispensed were retrieved from national registries. RESULTS: Altogether, 803 subjects (40.6%) responded. Of these, 61.6% had asthma, 5.7% had both asthma and COPD, 5.1% had COPD, and 27.5% had neither asthma nor COPD. Among subjects with asthma or asthma and COPD, inhaled corticosteroids (ICS) were the most frequently dispensed class of drugs (93.7% and 97.8%, respectively). Even among subjects with COPD, ICS were dispensed as frequently (68.3%) as long-acting bronchodilators (70.7%). Antileukotrienes were dispensed mainly to asthmatic individuals only (18.4%) but far less frequently than ICS. The use of theophylline and roflumilast was rare. CONCLUSIONS: R03 medications are dispensed far more frequently for asthma than for COPD and often also for subjects without asthma or COPD. In line with guidelines, asthma is treated mainly with ICS, but there seems to be overuse of ICS for COPD.

Relation of changes in PEF and FEV1 in exercise challenge in children.

Decrease in forced expiratory volume in one second (FEV1 ) of 10% or 15% in exercise challenge test is considered diagnostic for asthma, but a decrease of 15% in peak expiratory flow (PEF) is recommended as an alternative. Our aim was to assess the accuracy of different PEF cut-off points in comparison to FEV1 . We retrospectively studied 326 free running exercise challenge tests with spirometry in children 6-16 years old. FEV1 and PEF were measured before and 2, 5, 10 and 15 min after exercise. Receiver operating characteristics (ROC) analysis, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and Ï°-coefficient were used to analyse how decrease in PEF predicts decrease of 10% or 15% in FEV1 . In the ROC analysis, areas under the curve were 0.851 (p < 0.001) and 0.921 (p < 0.001) for PEF decrease to predict a 10% and 15% decrease in FEV1 , respectively. The agreement between changes in PEF and FEV1 varied from slight to substantial (Ï° values of 0.199-0.680) depending on the cut-points. Lower cut-off for decrease in PEF had higher sensitivity and NPV, while higher cut-off values had better specificity and PPV. Decrease of 20% and 25% in PEF seemed to be the best cut-offs for detecting 10% and 15% decrease in FEV1 , respectively. Still, a fifth of the positive findings based on PEF were false. Change in PEF is not a precise predictor of change in FEV1 in exercise test. The currently recommended cut-point of 15% decrease in PEF seems to be too low and leads to high false positive rate.

Comorbidity Burden in Severe and Nonsevere Asthma: A Nationwide Observational Study (FINASTHMA).

BACKGROUND: Asthma, affecting more than 330 million people worldwide, is associated with a high level of morbidity, mortality, and socioeconomic costs. OBJECTIVE: In this cross-sectional study, we analyzed the comorbidity burden in patients with severe asthma compared with nonsevere asthma and investigated the role of corticosteroid use on the risk of comorbidities. METHODS: All adults (≥18 y) with a diagnosis of asthma (International Classification of Diseases-10th revision code J45.x) between 2014 and 2017 were identified and data were collected until 2018 from Finnish nationwide registers. Asthma was defined as continuously or transiently severe or nonsevere based on annual dispensed inhaled corticosteroids (ICS), oral corticosteroids (OCS), and hospitalizations. RESULTS: Of 193,730 adult identified patients diagnosed with asthma, 86.3% had nonsevere, 8.1% transiently severe, and 5.6% continuously severe asthma. Excess prevalence of pneumonia was observed in continuously (22%) and transiently severe (14%) compared with nonsevere patients after adjusting for age and sex. Cataract, osteoporosis, obesity, heart failure, and atrial fibrillation were also more frequent in severe asthma patients. The ICS and/or OCS use contributed to the risk of several comorbidities in a dose-dependent manner, particularly pneumonia, osteoporosis, obesity, heart failure, and atrial fibrillation. High OCS use and the presence of comorbidities were associated with increased health care resource use. CONCLUSIONS: Patients with severe asthma have a high burden of comorbidities, especially pneumonia. Many of the comorbidities have a strong dose-dependent association with ICS and OCS treatment, suggesting that corticosteroid doses should be carefully evaluated in clinical practice.

Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma.

BACKGROUND: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. OBJECTIVE: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. METHODS: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). RESULTS: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti-IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. CONCLUSION: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. TRIAL REGISTRATION: The ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).

Adult Severe Asthma Registries: A Global and Growing Inventory.

Aim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests. Methods: Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR's Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised. Results: Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting >90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases. Conclusion: Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations.

Age at asthma diagnosis and onset of symptoms among adults with allergic and non-allergic asthma.

Background: Childhood-onset allergic asthma is the best-known phenotype of asthma. Adult-onset asthma, also an important entity, is instead often shown to be more non-allergic. There is still a lack of studies concerning the association of allergies and age at asthma onset from childhood to late adulthood. The aim of the study was to assess the age at onset of asthma symptoms and age at asthma diagnosis among adults with allergic and non-allergic asthma. Methods: Questionnaires were sent to 2000 randomly selected Finnish adults aged 18-80 years who were dispensed medication for obstructive airway diseases during the previous year. The corrected sample size was 1978 subjects after exclusion of non-analysable data. The response rate was 40.6%. Self-reported doctor-diagnosed asthma was considered allergic if a concomitant self-reported doctor-diagnosed pollen and/or animal allergy was reported with asthma symptoms upon allergen exposure. Results: Of the 496 participants with asthma, 42.7% were considered to have allergic asthma. The median ages at asthma diagnosis and onset of asthma symptoms were 31 (IQR 17-46) and 20 (9.25-40) years in participants with allergic asthma and 49 (37.75-58) and 40.5 (30-50) years in participants with non-allergic asthma (p < 0.001), respectively. Of the participants with asthma diagnosed at ≥30 years of age, 18% of allergic and 7% of non-allergic participants reported having had asthma symptoms under 20 years of age. Conclusions: Both the onset of symptoms and diagnosis occurred at a younger age among adults with allergic asthma than among those with non-allergic asthma. Only a minority of adults with non-allergic asthma had already had symptoms in younghood.

Severe asthma trajectories in adults: findings from the NORDSTAR cohort.

BACKGROUND: There is limited evidence on the pathways leading to severe asthma and we are presently unable to effectively predict the progression of the disease. We aimed to describe the longitudinal trajectories leading to severe asthma and to describe clinical events preceding disease progression in a nationwide population of patients with severe asthma. METHODS: We conducted an observational study based on Swedish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. We identified adult patients with severe asthma in 2018 according to the European Respiratory Society/American Thoracic Society definition and used latent class analysis to identify trajectories of asthma severity over a 10-year retrospective period from 2018. RESULTS: Among 169 128 asthma patients, we identified 4543 severe asthma patients. We identified four trajectories of severe asthma that were labelled as: trajectory 1 "consistently severe asthma" (n=389 (8.6%)), trajectory 2 "gradual onset severe asthma" (n=942 (20.7%)), trajectory 3 "intermittent severe asthma" (n=1685 (37.1%)) and trajectory 4 "sudden onset severe asthma" (n=1527 (33.6%)). "Consistently severe asthma" had a higher daily inhaled corticosteroid dose and more prevalent osteoporosis compared with the other trajectories. Patients with "gradual onset severe asthma" and "sudden onset severe asthma" developed type 2-related comorbidities concomitantly with development of severe asthma. In the latter group, this primarily occurred within 1-3 years preceding onset of severe asthma. CONCLUSIONS: Four distinct trajectories of severe asthma were identified illustrating different patterns of progression of asthma severity. This may eventually enable the development of better preventive management strategies in severe asthma.