Exploring definitions and predictors of response to biologics for severe asthma.

BACKGROUND: Biologic effectiveness is often assessed as 'response', a term which 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 4 asthma outcome domains were assessed in the 1-year period pre- and post-biologic-initiation in patients with predefined level of pre-biologic impairment. Responder cut-offs were: ≥50% reduction in exacerbation rate, ≥50% reduction in long-term oral corticosteroid [LTOCS] daily dose, ≥1 category improvement in asthma control, and ≥100mL improvement in FEV1. Responders were defined using single- and multiple-domains. The association between pre-biologic characteristics and post-biologic-initiation response were examined by multivariable analysis. RESULTS: 2,210 patients were included. Responder rate ranged from 80.7% (n=566/701) for exacerbation-response to 10.6% (n=9/85) for 4-domain-response. Many responders still exhibited significant impairment post-biologic-initiation: 46.7% (n=206/441) of asthma control-responders with uncontrolled asthma pre-biologic still had incompletely-controlled disease post-biologic-initiation. Predictors of response were outcome-dependent. Lung function-responders were more likely to have higher pre-biologic FeNO (OR:1.20 for every 25ppb increase), and shorter asthma duration (OR:0.81, for every 10-year increase in duration). Higher BEC and presence of T2-related comorbidities were positively associated with higher odds of meeting LTOCS-, control- and lung function-responder criteria. CONCLUSION: Our findings underscore the multi-modal nature of 'response', show that many responders experience residual symptoms post-biologic-initiation, and that predictors of response vary according to outcome assessed.

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 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.

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.

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.

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.

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).

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.

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.

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.

Type 2 Low Biomarker Stability and Exacerbations in Severe Uncontrolled Asthma.

We investigated the stability of T2 low status, based on low levels of T2 biomarkers, and exacerbation rates in T2 low and non-T2 low asthma from clinical retrospective data of severe uncontrolled asthma patients. Knowledge of the T2 low biomarker profile is sparse and biomarker stability is uncharted. Secondary care patients with severe uncontrolled asthma and at least two blood eosinophil counts (BEC) and fractional exhaled nitric oxide (FeNO) measured for determination of type 2 inflammation status were evaluated from a follow-up period of 4 years. Patients were stratified into four groups: T2 low150 (n = 31; BEC < 150 cells/µL and FeNO < 25 ppb), non-T2 low150 (n = 138; BEC > 150 cells/µL and/or FeNO > 25 ppb), T2 low300 (n = 66; BEC < 300 cells/µL and FeNO < 25 ppb), and non-T2 low300 (n = 103; BEC > 300 cells/µL and/or FeNO > 25 ppb). Exacerbation rates requiring hospital care, stability of biomarker status, and cumulative OCS and ICS doses were assessed during follow-up. Among patients with severe uncontrolled asthma, 18% (n = 31) were identified as T2 low150, and 39% (n = 66) as T2 low300. In these groups, the low biomarker profile was stable in 55% (n = 11) and 72% (n = 33) of patients with follow-up measures. Exacerbation rates were different between the T2 low and non-T2 low groups: 19.7 [95% CI: 4.3-45.6] in T2 low150 vs. 8.4 [4.7-13.0] in non-T2 low150 per 100 patient-years. BEC and FeNO are useful biomarkers in identifying T2 low severe uncontrolled asthma, showing a stable follow-up biomarker profile in up to 72% of patients. Repeated monitoring of these biomarkers is essential in identifying and treating patients with T2 low asthma.

Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry.

BACKGROUND: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone. OBJECTIVE: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS. METHODS: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models. RESULTS: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48]). CONCLUSIONS: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization.

Acute respiratory infections hamper training and competition in cross-country skiers, especially in those with asthma.

Acute respiratory infections (ARinf) are one of the leading causes that prevent athletes from training and competing. The aim of this study was to investigate the burden of ARinfs during one season among cross-country skiers. All Finnish cross-country skiers enrolled in the largest national competitions in winter 2019 (n = 1282) were sent a postal questionnaire. A higher proportion of skiers with than without asthma had to refrain from competitions because of ARinf (76.9% vs. 62.2%, p = 0.011) but there was no significant difference in refraining from training (91.2% vs. 83.8%, p = 0.084). In skiers with asthma, the median duration of a single ARinf episode was longer (5.0 days, IQR 3.8-6.8 vs. 4.0 days, IQR 3.0-6.7, p = 0.017), and they had more days of absence because of ARinf throughout the season (median 15 days (IQR 8-28) vs. 10 days (IQR 6-18), p = 0.006) in comparison to non-asthmatics. However, many of the skiers either trained (54.4%) or competed (22.5%) during an ARinf.

Cross-country skiers often experience respiratory symptoms during and after exercise but have a low prevalence of prolonged cough.

Background: Cross-country skiers train and compete during the winter for long periods of time in subfreezing conditions, which strains the airways and provokes respiratory symptoms. This study aimed to compare the prevalence of exercise-related symptoms and prolonged cough in competitive cross-country skiers versus the general population and to investigate the association between these symptoms and asthma. Methods: A questionnaire was sent to Finnish cross-country skiers (n=1282) and a random sample of the general population (n=1754), with response rates of 26.9% and 19.0%, respectively. Results: Both groups were mostly asymptomatic at rest, but symptoms were increased in both groups during and after exercise. Cough was more prevalent after exercise in skiers and phlegm production was more common during and after exercise in skiers. Asthma did not provoke specific symptoms, but symptom prevalence was higher in asthmatic individuals. Skiers had a higher prevalence of cough after exercise (60.6% vs 22.8%, p<0.001) compared with controls, but controls had a higher prevalence of prolonged cough (4.1% vs 9.6%, p=0.004). In participants without asthma, cold air triggered symptoms more often in skiers than controls, while strong odours triggered symptoms more often in asthmatic controls than skiers. Chronic cough lasting more than 8 weeks was rare, reported by 4.8% of controls and 2.0% of skiers. Conclusion: Cross-country skiers, especially those with asthma, experience a higher burden of exercise-related respiratory symptoms compared with controls. However, repeated exposure to cold air does not appear to result in long-term hypersensitivity of the cough reflex arc.

Palliation of Dyspnea With Mouthpiece Ventilation in Patients With Chronic Obstructive Pulmonary Disease: A Pilot Feasibility Study.

Background: Mouthpiece ventilation (MPV) reduces hypoventilation, but its efficacy in relieving dyspnea in patients with acute chronic obstructive pulmonary disease exacerbation (AECOPD) is unclear. Objective: To assess the feasibility of MPV in relieving dyspnea among patients with AECOPD. Methods: In this prospective single-arm pilot study, the change in dyspnea on numeric rating scale (NRS) after using MPV and side effects of the treatment were studied in 18 patients with AECOPD. Results: The median decrease in dyspnea was 1.5 (95% confidence interval = 0.0-2.5, p = 0.006) on NRS after the intervention lasting a median of 16.9 minutes. Of the patients, 61% found MPV beneficial. The use of MPV did not increase the sense of anxiety or pain. Conclusions: MPV is feasible and may relieve dyspnea in patients with AECOPD, but the intervention needs further evaluation. clinicaltrials.gov study number: NCT03025425.

Specialist Palliative Care Consultation for Patients with Nonmalignant Pulmonary Diseases: A Retrospective Study.

Background: Few patients with chronic nonmalignant pulmonary diseases receive specialist palliative care consultation, despite their high symptom burden in end of life. Objectives: To study palliative care decision making, survival, and hospital resource usage in patients with nonmalignant pulmonary diseases with or without a specialist palliative care consultation. Methods: A retrospective chart review of all patients with a chronic nonmalignant pulmonary disease and a palliative care decision (palliative goal of therapy), who were treated in Tampere University Hospital, Finland, between January 1, 2018 and December 31, 2020. Results: A total of 107 patients were included in the study, 62 (58%) had chronic obstructive pulmonary disease (COPD), and 43 (40%) interstitial lung disease (ILD). Median survival after palliative care decision was shorter in patients with ILD than in patients with COPD (59 vs. 213 days, p = 0.004). Involvement of a palliative care specialist in the decision making was not associated with the survival. Patients with COPD who received palliative care consultation visited less often emergency room (73% vs. 100%, p = 0.019) and spent fewer days in the hospital (7 vs. 18 days, p = 0.007) during the last year of life. When a palliative care specialist attended the decision making, the presence and opinions of the patients were recorded more often, and the patients were more frequently referred to a palliative care pathway. Conclusions: Specialist palliative care consultation seems to enable better end-of-life care and supports shared decision making for patients with nonmalignant pulmonary diseases. Therefore, palliative care consultations should be utilized in nonmalignant pulmonary diseases preferably before the last days of life.