Diffusing capacity for carbon monoxide (DLCO) is a measure of gas exchange in the lungs. Reduced DLCO with normal spirometry is a common finding that is incompletely understood. To assess determinants of isolated, reduced DLCO in an unselected population. The Swedish CArdioPulmonary bioImage Study (SCAPIS) is a multicentre population-based study of adults aged 50–64 years. The 5th percentile of DLCO in healthy never smokers was used as the lower limit of normal (LLN). Using multivariable analysis, we studied factors associated with DLCO < LLN in 24 261 subjects with normal spirometry, defined as FEV1, FVC and FEV1/FVC > LLN. Emphysema and interstitial lung abnormalities (ILA) were assessed through computed tomography, physical activity through accelerometry and other factors through questionnaires. Isolated DLCO < LLN (n = 1 472) was independently associated with emphysema (odds ratio and 95

BACKGROUND:The 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report classifies individuals with chronic obstructive pulmonary disease (COPD) who have experienced ≥2 moderate (outpatient) or ≥1 severe (emergency department or hospitalization) exacerbations within the last year as being at high risk of future exacerbation (category E). OBJECTIVES:This study aimed to investigate the risk of exacerbation and death associated with the individual components of the GOLD E category. METHODS:We conducted a retrospective cohort study using health administrative data from Ontario, Canada (2007-2018). Individuals ≥65 years of age with physician-diagnosed COPD were followed for up to 5 exacerbations, until their death, or the study period ended. After each exacerbation, individuals were assigned to 1 of 3 GOLD subgroups: E moderate (≥2 moderate), E severe (≥1 severe), and AB (≤1 moderate). Under a landmark analysis framework, Fine-Gray subdistribution hazards (sdHR) competing risk models were created for each event, and the risk of exacerbation and death was estimated. RESULTS:There were 279 798 individuals included. Individuals in the GOLD E moderate subgroup were at a higher risk of future exacerbation (COPD, chronic obstructive pulmonary disease exacerbations 3-5 = 1.16-1.23) and a lower risk of death (sdHR exacerbations 3-5 = 0.75-0.82) than GOLD AB individuals. In comparison, patients in the GOLD E severe subgroup were at lower risk of future exacerbation (sdHR exacerbations 2-5 = 0.89-0.95), but higher risk of death (sdHR exacerbations 2-5 = 1.56-1.59). CONCLUSIONS:These findings indicate that COPD patients in the GOLD E moderate subgroup have a different risk of future exacerbation and death than individuals in the GOLD E severe subgroup.

Introduction Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may cause stress-induced transient acute cardiac dysfunction through myocardial stunning, in the form of exacerbation-triggered Takotsubo syndrome (referred to as Takotsubo stunning). Although prior studies suggest an association between AECOPD and transient cardiac dysfunction, existing evidence is limited to retrospective cohorts, case reports and expert consensus. Therefore, the incidence and clinical impact of Takotsubo stunning with acute heart failure (AHF) during AECOPD remain unknown and may be overlooked due to overlapping clinical symptoms. Cardiac Assessment and Takotsubo-stunning among COPD-exacerbations in-Hospital (CATCH study) aims to determine the incidence of Takotsubo stunning during AECOPD and to evaluate its clinical implication.Methods and analysis CATCH is a prospective observational cohort study enrolling adults (≥18 years) admitted for AECOPD at Sahlgrenska University Hospital (Gothenburg, Sweden). Participants with chronic left ventricular systolic dysfunction (left ventricular ejection fraction <50%), pre-existing chronic regional wall motion abnormalities (RWMA) or prior type 1 myocardial infarction are excluded. Following informed consent, participants undergo echocardiographic screening for RWMA and/or systolic left ventricular dysfunction. Screening-positive patients have follow-up echocardiography at 24 hours (±6) and 30 days (±48 hours). Those with reversible dysfunction constitute the CATCH case group, while screening-negative participants serve as controls. Additional assessments include ECG, chest X-ray, N-terminal pro-B-type natriuretic peptide blood analysis and COPD severity. Primary outcomes include the incidence of reversible RWMA or left ventricular dysfunction (proxy for Takotsubo stunning) and in-hospital clinical signs of AHF (Killip class >1). A sample size of 150 patients is required for detecting AHF differences (α=0.05, 80% power).Ethics and dissemination The study received ethical approval from the Swedish Ethical Review Authority. All participants provided written informed consent. Results will be disseminated through peer-reviewed journals and scientific meetings.Registration details The CATCH study is registered at ClinicalTrials.gov (NCT06597331). The reference number for ethical approval is 2024-02071-01 (with addenda 2024-05448-02 and 2025-05861-02).

Background:Physician diagnosed COPD with normal spirometry (dnsCOPD) (sometimes labeled pre-COPD) and Preserved Ratio Impaired Spirometry (PRISm) has been studied in population-based cohorts, but not in physician diagnosed COPD (dCOPD) patients from routine clinical practice. The Swedish National Airway Register (SNAR) is a large nationwide register including data from dCOPD patients from over 1000 clinics across all regions of Sweden and is representative of the COPD care in Sweden. We aimed to identify and characterize patients with dnsCOPD, PRISm and spirometrically confirmed COPD (sCOPD) from dCOPD patients in SNAR, stratify them further according to symptoms and exacerbations risk using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) A/B/E classification, and assess differences in risk for exacerbations, cause-specific hospitalisations and mortality. Methods:We enrolled patients aged ≥30 years with dCOPD in the SNAR from 1 January 2014 to 30 June 2022 with complete spirometry i.e., postbronchodilator values for both forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (index date). Patients with concomitant asthma were excluded. Patients were stratified into dnsCOPD (FEV1/FVC ≥0.7 and FEV1 ≥80% predicted), PRISm (FEV1/FVC ≥0.7 and FEV1 <80% predicted) and sCOPD (FEV1/FVC <0.7). Further substratification was based on GOLD A/B/E (A: COPD assessment test (CAT) score <10 points and <2 moderate, 0 severe exacerbations within 1 year before the index date, B: CAT-score ≥10 points and <2 moderate, 0 severe exacerbations, E: ≥2 moderate or ≥1 severe exacerbation(s)). Patients were followed until 31 November 2022. Competing risk regression was used to calculate subdistribution hazard ratios (SHR)s with 95% confidence intervals (CIs) for exacerbation, hospitalisation and mortality. Findings:Of 45,653 patients with dCOPD, 5.4% had dnsCOPD, 11.4% had PRISm and 83.3% had sCOPD. Smoking history was similar between groups (ever smoker: dnsCOPD: 79% PRISm: 82% sCOPD: 86%) and inhalation therapy was common in all groups (any inhaler: 75%, 80% and 80%, triple combination: 22%, 28% and 35%). Patients with PRISm had a high prevalence of obesity (dnsCOPD: 30%, PRISm: 43%, COPD: 22%), cardiovascular disease (dnsCOPD: 39%, PRISm: 48%, COPD: 41%) and diabetes (dnsCOPD: 10%, PRISm: 17%, COPD: 9%). Baseline GOLD group B or E were highly prevalent in dnsCOPD (B: 54%, E: 11%), PRISm (B: 59%, E: 14%), as well as in COPD (B: 54%, E: 17%). DnsCOPD and PRISm patients had lower risk of exacerbations (SHR 0.69, 95%CI 0.64-0.74 and 0.85, 95%CI 0.81-0.89), respiratory hospitalisation (0.40, 95%CI 0.34-0.46 and 0.68, 95%CI 0.62-0.73), and respiratory mortality (0.22, 95%CI 0.13-0.37 and 0.60, 95%CI 0.48-0.75) compared to sCOPD. Cardiovascular mortality was lower in dnsCOPD (0.41, 95%CI 0.19-0.86), but similar in PRISm (0.73, 95%CI 0.49-1.08) compared to sCOPD. The A/B/E classification was predictive for all outcomes in dnsCOPD and PRISm. DnsCOPD and PRISm group E patients had higher risks for all outcomes than sCOPD group A or B. Interpretation:DnsCOPD and PRISm are prevalent in a real-life cohort of patients with a physician diagnosis of COPD. These patients are symptomatic, might suffer from exacerbations and are commonly treated with inhaled therapy, equally to sCOPD. Patients with PRISm had a high prevalence of obesity, diabetes and cardiovascular disease. DnsCOPD and PRISm had generally lower overall risks of exacerbation or respiratory events, although PRISm patients showed similar cardiovascular risk to sCOPD. The A/B/E classification predicted future events, even in dnsCOPD and PRISm patients. Funding:This study is performed with support from The Swedish Heart-Lung Foundation (20200150) and the Swedish government and country council ALF grant (ALFGBG-824371).

Background:Airway obstruction is a characteristic spirometric finding in asthma but the clinical significance of other abnormal spirometric patterns is less well described. We aimed to explore pre- and post-bronchodilator (BD) prevalences and clinical characteristics of preserved ratio impaired spirometry (PRISm), dysanapsis and airflow obstruction with low forced expiratory volume in 1 s (FEV1) in children diagnosed with asthma. Methods:We extracted specialist care data (clinical and spirometry) from the Swedish National Airway Register (n=3301, age 5-17 years). Normal spirometry was defined as FEV1≥ lower limit of normal (LLN) and FEV1/forced vital capacity (FVC)≥LLN. PRISm was defined as forced FEV1< LLN and FEV1/FVC≥LLN, dysanapsis as FEV1/FVC10% were considered positive (BDRpos). Groups were compared using parametric tests and associations were explored using logistic regression analysis. Results:Pre-/post-BD PRISm, dysanapsis and obstruction with low FEV1 were identified in 9%/7%, 10%/4% and 8%/2%, respectively. Compared with normal spirometry, all three groups were associated with older age and BDRpos in pre-BD analyses. Furthermore, dysanapsis was associated with overweight/obesity and obstruction with low FEV1 with uncontrolled asthma and more treatment. Interpretation:In this paediatric asthma cohort, PRISm and dysanapsis were associated with BDRpos and they were at least as common as airflow obstruction with reduced FEV1. These spirometric phenotypes should be addressed in the management of childhood asthma and testing of BDR should be considered also in children with PRISm and dysanapsis.

Spirometry aids in diagnosing and monitoring asthma by assessing airflow limitations and bronchodilator (BD) responses [1]. The American Thoracic Society and European Respiratory Society recently updated BD response criteria, now defining a positive response as a > 10% increase in FEV1 (post-BD) relative to the predicted value. Previously, it required a > 12% and ≥ 200 mL increase from pre-BD values [1]. This change aims to reduce biases related to age, sex, and height, but is based on adult data and unvalidated in children. Paediatric studies have indicated that the new BD response could lead to overdiagnosing asthma [2]. One study reported that children who tested positive, based on the new criteria, had a higher baseline FEV1, forced vital capacity (FVC), and FEV1/FVC [3]. We used data from a real-world paediatric, specialist care asthma cohort to explore the concordance between the old and new BD response criteria and the clinical characteristics of the children identified by them. The study complied with the Declaration of Helsinki and was approved by the Swedish Ethical Review Authority (2019-04915). Informed consent was waived. Data on asthma diagnoses were extracted from the Swedish National Airway Register [4]. Spirometry data were assessed using pre- and post-bronchodilator FEV1 and FEV1/FVC and are presented as percentages below the lower limit of normal (z-score < −1.645) using references from the Global Lung Initiative [5]. Old BD responses were calculated using the previous definition [1]: ((post-bronchodilatorFEV1 (L) − pre-bronchodilatorFEV1 (L))/pre-bronchodilatorFEV1 (L)) × 100. A change of > 12% and ≥ 200 mL was considered positive. New BD responses were calculated using the updated defintition [1]: ((post-bronchodilatorFEV1 (L) − pre-bronchodilatorFEV1 (L))/predicted value (L)) × 100. A change of > 10% was considered positive. Age was categorised as 5–11 and 12–17 years. The body mass index, calculated as weight (kilograms)/height2 (meters), was categorised as normal weight or overweight/obesity using age-dependent cut-offs. An asthma control test score of ≤ 19 denoted uncontrolled asthma. Treatment for asthma included bronchodilators, inhaled corticosteroids, leukotriene receptor antagonists, and biological treatments. Treatment was categorised as step 1–2 or step 3–5, as defined by the Global Initiative for Asthma. Statistical analyses were conducted using SPSS Statistics version 29 (IBM Corp, New York, USA). Chi-square tests were used for between-group comparisons, and statistical significance was p < 0.05. Cohen's kappa estimated the agreement between old and new BD responses. The study comprised 3301 children aged 5–17 years with complete pre- and post-bronchodilator spirometry data. Both old and new BD responses were negative in 2770 cases (84%) whereas the other 531 (16%) had a positive test result (Table 1). Using the new BD responses yielded more positive results than old BD responses. Almost a third of the children who were positive in one or both tests had discordant results. The kappa value for agreement between the old and new BD responses was 0.79. Positive old BD responses, but negative new BD responses, were found in 30 children (0.9%). These children were older and more likely to have had FEV1 < LLN and airway obstruction both pre- and post-bronchodilators, compared with the 137 children with negative old BD responses and positive new BD responses (Table 1). Old BD responses were positive in 8.5% with pre-bronchodilator FEV1 > LLN and new BD responses in 13.1% of that group. Two studies have evaluated the impact of the new BD responses on children. A population-based study [2] assessed the spirometry results of 2293 children, including 14.4% with current asthma. New BD responses were positive in 36% with asthma and 25% without, compared to 17% and 10% for the old BD responses. The effects of changing the BD responses were also evaluated using data from a pulmonary function laboratory on 1224 children referred for cough or asthma [3]. The new BD response was positive in 18% and the old BD response in 15%. Children with a positive new BD response had higher baseline FEV1, forced vital capacity (FVC) and FEV1/FVC than those with a positive old response. Our results extend previous findings. They show that children with positive old, but negative new, BD responses differed from children with negative old, but positive new, BD responses. They were older, prescribed more treatment, and had more impaired lung function. When the new BD response was used, children with less asthma morbidity were classified as having a positive bronchodilator response, and a few children with more morbidity were classified as having no bronchodilator response. However, the bronchodilator response is not the only factor used to evaluate troublesome asthma in clinical settings, and current treatment also impacts bronchodilator responses. Nevertheless, the findings underline that bronchodilator responses from adults cannot be extrapolated to children. Interestingly, both the old and new BD responses were positive in a significant proportion of children with pre-bronchodilator FEV1 above the lower limit of normal. This challenges clinical guidelines that only recommend bronchodilator responses in children with pre-bronchodilator airway obstruction. The study's strengths included the large cohort and before and after bronchodilator lung function measurements. All the children were diagnosed with asthma and the results are not necessarily generalisable to healthy children or those with suspected asthma. The limitations included no knowledge of adherence to prescribed medications or whether the data originated from new referrals or follow-up visits. Some data on body mass index, asthma control tests, and asthma treatment were also missing. In Sweden, spirometry is generally performed by specialised paediatric nurses and many have national licences to perform this. We can consider that the quality of spirometry was good, even though we did not have access to the original data. In conclusion, switching from the old to new BD responses meant that children with less asthma morbidity were classified as having a positive bronchodilator response. A few children with more morbidity were classified as having no bronchodilator response. This underlines that bronchodilator response results from adults cannot be extrapolated to children. Cut-off values balance sensitivity and specificity, and BD responses should be interpreted with other markers and clinical judgement. Caroline Stridsman: conceptualization, methodology, project administration, resources, writing – review and editing, funding acquisition. Helena Backman: conceptualization, methodology, writing – review and editing. Lowie E. G. W. Vanfleteren: conceptualization, methodology, writing – review and editing. Anna Asarnoj: writing – review and editing, methodology, conceptualization. Henrik Ljungberg: conceptualization, methodology, writing – review and editing. Anne Lindberg: conceptualization, methodology, writing – review and editing. Apostolos Bossios: conceptualization, methodology, writing – review and editing. Jon R. Konradsen: conceptualization, methodology, formal analysis, project administration, writing – original draft, funding acquisition, resources. The authors declare no conflicts of interest.

Background Airway obstruction is a characteristic spirometric finding in asthma but the clinical significance of other abnormal spirometric patterns is less well described. We aimed to explore pre- and post-bronchodilator (BD) prevalences and clinical characteristics of preserved ratio impaired spirometry (PRISm), dysanapsis and airflow obstruction with low FEV1 in children diagnosed with asthma. Methods We extracted specialist care data (clinical and spirometry) from the Swedish National Airway Register (n=3301, age 5–17 years). Normal spirometry was defined as FEV1≥ lower limit of normal (LLN) and FEV1/FVC≥LLN. PRISm was defined as forced FEV1< lower limit of normal (LLN) and FEV1/FVC≥LLN, dysanapsis as FEV1/FVC10% were considered positive (BDRpos). Groups were compared using parametric tests and associations explored using logistic regression analysis. Results Pre-/post-BD PRISm, dysanapsis, and obstruction with low FEV1 were identified in 9%/7%, 10%/4%, and 8%/2%, respectively. Compared to normal spirometry, all three groups were associated with older age and BDRpos in pre-BD analyses. Furthermore, dysanapsis was associated with overweight/obesity and obstruction with low FEV1 with uncontrolled asthma and more treatment. Interpretation In this pediatric asthma cohort, PRISm and dysanapsis were associated with a positive BDR and they were at least as common as airflow obstruction with reduced FEV1. These spirometric phenotypes should be addressed in the management of childhood asthma and testing of BDR should be considered also in children with PRISm and dysanapsis.

BACKGROUND:While anti-interleukin (IL) 5 therapy has been shown to be efficacious to reduce exacerbation rates (ERs) in patients with severe eosinophilic asthma and might also benefit patients with coexisting chronic obstructive pulmonary disease (COPD), it is unknown whether anti-IL5 therapy reduces all types of exacerbations in heterogeneous (smoking) real-life patients. METHODS:Adults initiating mepolizumab or benralizumab between 2017 and 2019 were identified in Belgian nationwide data. The ER in the year before anti-IL5 therapy initiation was compared to the year after. Exacerbations were classified as severe (hospitalised) exacerbations or moderate (outpatient) exacerbations treated with antibiotics, oral corticosteroids (OCS) or the combination. RESULTS:Among 807 patients initiating anti-IL5 therapy, severe ER was 40±4 exacerbations per 100 patient years pretreatment versus 17±3 post-treatment initiation (p<0.001, relative risk reduction (RRR) -56%, number needed to treat (NNT)=4) and significantly reduced both in patients without COPD (n=616, ERpre=15±2, ERpost=6±1, p<0.001, NNT=11) as with coexisting COPD (n=191, ERpre=119±12, ERpost=53±9, p<0.001, NNT=2). For moderate exacerbations, ERs were significantly reduced for all types of exacerbations in both patients with or without COPD, except for OCS only-treated exacerbations in patients with coexisting COPD (p=0.288). Current smoking reduced anti-IL5 effectiveness on OCS-treated exacerbations (NNT >1), although current smokers with coexisting COPD still had a great reduction in hospitalisations (ERpre=152±23, ER post=55±18, p<0.001, NNT=1, RRR=-64%). CONCLUSIONS:In this nationwide cohort study, treatment targeting eosinophilic inflammation was significantly associated with reduced moderate and severe exacerbations, with seemingly less impact on corticosteroid-treated exacerbations in (current smoking) patients with coexisting COPD, but still a large number of hospitalisations were prevented.

Comorbid obstructive sleep apnoea, together with impaired cardiac function, is prevalent in patients with COPD. Disease burden is elevated in this "triple trouble" phenotype, emphasising the need for its identification. https://bit.ly/40YK46z.

BackgroundBronchoscopic lung volume reduction using one-way endobronchial valves (BLVR-EBV) improves exercise capacity and quality of life in patients with severe emphysema. However, its effect on symptoms of fatigue, anxiety and depression is unclear. Furthermore, if the combination of pulmonary rehabilitation (PR) and BLVR-EBV yields additional impact on these symptoms remains unknown. We hypothesized that BLVR-EBV would reduce symptoms of fatigue, anxiety and depression and that the combination of BLVR-EBV with PR would lead to additional reduction when compared to BLVR-EBV alone.MethodsThe SoLVE study (NCT03474471) was a prospective multicentre randomised controlled trial to examine the impact and optimal timing of PR on exercise physiology and patient reported outcomes in patients receiving BLVR-EBV treatment. Subjects were randomised into three groups: PR before BLVR-EBV, PR after BLVR-EBV and BLVR-EBV alone.Fatigue severity was assessed using the Checklist Individual Strength fatigue subscale (CIS-fatigue). The Hospital Anxiety and Depression Scale evaluated symptoms of anxiety (HADS-A) and depression (HADS-D).ResultsNinety-seven participants were included. After 6-months follow-up the overall mean change after BLVR-EBV with or without PR was −8.2±10.6 points on CIS-fatigue score, −2.2±2.9 points on HADS-A and −2.3±3.0 points on HADS-D (p<0.001). No significant differences were observed between groups for changes in CIS-fatigue, HADS-A and HADS-D.ConclusionBLVR-EBV is an effective intervention to improve symptoms of fatigue, anxiety and depression. The combination of PR and BLVR-EBV did not result in additional improvement when compared to BLVR-EBV alone.

Rationale: Few studies have identified risk sets for perinatal factors and airflow obstruction into middle adulthood. Objectives: To investigate associations between gestational age (GA), GA-adjusted birthweight, and mode of delivery and persistent airflow obstruction among patients 7-49 years old with obstructive lung diseases. Methods: The study population encompassed 44,778 individuals with asthma or chronic obstructive pulmonary disease (COPD) and one or more registration of post-bronchodilator values of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) recorded in the Swedish National Airway Register in 2014-2022 and with both GA and birthweight data in the Medical Birth Register between 1973-2015. Persistent airflow obstruction was defined as a FEV1/FVC z-score below the lower limit of normal. Analyses were done separately for children, young adults, and middle-aged adults. Results: Subjects who were extremely, very, moderate, and late preterm-born all had increased odds ratios (ORs) of persistent airflow obstruction up to age 49 years compared with those term-born. Middle-aged adults born small for GA had increased OR of persistent airflow obstruction compared with those appropriate for GA (OR, 1.49; 95% confidence interval, 1.23-1.81). In the risk sets, GA was the most significant covariate for persistent airflow obstruction. GA-adjusted birthweight was an additional covariate for those born late preterm, term, or postterm. Mode of delivery did not contribute. Conclusions: GA was an independent covariate of persistent airflow obstruction and, in the risk sets, proved to be the most important covariate in patients of all ages with either asthma or COPD. GA-adjusted birthweight further improved the prediction.

BackgroundRemote patient monitoring (RPM) has been evaluated in COPD, but with varying results. We aimed to evaluate whether a tablet system that monitors disease-related parameters in patients with COPD could influence physical and mental health-related quality of life, compared with usual care (UC).Methods70 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D COPD (61% women, aged 71±8 years, forced expiratory volume in 1 s % predicted 41±13%, COPD Assessment Test (CAT) 19±7 points) were recruited at the COPD centre in Gothenburg, Sweden, and randomised to a tablet-based RPM system or UC for a 26-week period, after which they crossed over to the alternative management for another 26 weeks. The Short Form-12 (SF-12) (primary outcome), CAT, modified Medical Research Council (mMRC) Dyspnoea Scale, EuroQol-5 Dimensions (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) were evaluated at four visits. Exacerbations were continuously reported, as was adherence to RPM.Results59 patients completed the study: 28 patients randomised to start with UC and 31 randomised to start with RPM. The changes in the SF-12 Physical Component Summary (PCS) (UC: −1.17±6.90versusRPM: −1.06±8.15) and Mental Component Summary (MCS) (UC: 0.63±11.14versusRPM: −0.63±8.15), as well as in CAT, the mMRC scale, the EQ-5D, HADS anxiety, HADS depression and number of exacerbations, were similar in both intervention periods. Neither the 26-week UC period nor the intervention significantly affected the measured outcomes. There was a 95% adherence rate during RPM.ConclusionsA 26-week tablet-based RPM system that monitors CAT, oxygen saturation, blood pressure, pulse, weight and physical activity, connected to a case manager, is feasible and safe, but did not influence health-related quality of life in patients with COPD GOLD D.