Background Chronic obstructive pulmonary disease (COPD) in never-smokers may have other clinical characteristics than tobacco smoking-related COPD.Research question What are the risk factors, biomarkers, respiratory symptoms and health status in never-smoking individuals with COPD?Study design and methods We investigated never-smokers with COPD (n=154, mean age 60 years) from the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS), and compared them with four control groups: never-smokers with normal lung function (n=281), current smokers with normal lung function (n=97), ex-smokers with COPD (n=103) and current smokers with COPD (n=55). COPD was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) less than the lower limit of normal (LNN) after bronchodilation. We examined fractional exhaled nitric oxide (FeNO), blood biomarkers, respiratory symptoms, health status, medical history and living conditions.Results The never-smoker COPD group reported more respiratory symptoms and worse health status than never-smokers with normal lung function, but fewer symptoms, milder airflow limitation and better health status compared with ex-smokers and smokers with COPD. Never-smokers with COPD had more self-reported asthma. Moreover, never-smokers with COPD had higher Immunoglobulin E sensitisations to a mix of aeroallergens, higher geometrical mean FeNO levels and blood eosinophil counts than never-smokers with normal lung function. When participants with self-reported asthma were excluded, never-smokers with COPD still had more wheeze, cough and higher FeNO.Conclusion Never-smokers with COPD had more respiratory symptoms and elevated markers of type-2 inflammation, suggesting they might represent a distinct clinical phenotype which may differ from smoking-related COPD. They may therefore need to be treated and followed differently.Trial registration number NCT03049202.

RATIONALE:Long-term oxygen therapy (LTOT) given for at least 15 hours/day improves survival in patients with severe chronic hypoxemia. However, the recent REDOX trial showed that LTOT prescribed for 24 hours/day was not superior to 15 hours/day in terms of death, hospitalizations, or self-reported outcomes. OBJECTIVES:We aimed to examine the cost effectiveness of prescribing LTOT for 24 versus 15 hours/day. METHODS:A cost minimization analysis of the REDOX trial data on 241 patients with severe hypoxemic respiratory failure randomized 1:1 to either LTOT 24 hours/day (n = 117) or 15 hours/day (n = 124) and followed up to 12 months. Data on medical care consumption including prescribed medication costs, specialized outpatient care, and inpatient care were retrieved from national registries. Mean differences in healthcare consumption costs (United States dollars [$], 2024 prices) between groups were analyzed using generalized linear models. The cost analysis took a healthcare payer perspective and oxygen therapy costs are presented separately as out-of-pocket payments. RESULTS:During the 12 months of follow-up, patients prescribed LTOT for 24 hours/day had significantly lower mean costs for respiratory-specific medications (-$175 [95% CI, -$329 to -$29]) but higher oxygen therapy costs ($173 [95% CI, $80 to $268]), compared to patients prescribed LTOT 15 hours/day. There were no significant differences between the groups in mean specialized outpatient and inpatient care costs, total medication costs, or in overall total costs (-$4951 [95% CI, -$10 667 to $443]) but numerically favoring usage of LTOT 24 hours/day. A population-level projection shows substantial potential cumulative cost savings of $7.64 million if LTOT 24 hours/day is adopted. CONCLUSIONS:In addition to previously shown similar treatment efficacy, overall healthcare costs did not significantly differ between LTOT prescribed 15 hours/day and LTOT 24 hours/day. However, there is an observable numerical difference in favor of usage of LTOT 24 hours/day.

Elevated troponin I (TnI) has been reported in patients with chronic obstructive pulmonary disease (COPD) without cardiovascular disease (CVD), suggesting non-ischaemic mechanisms. We assessed this association in a population-based cohort of 22 526 individuals without known CVD or significant coronary artery calcification. TnI showed no association with COPD (adjusted OR 0.87, 95% CI 0.60 to 1.26; highest category vs below limit of detection) or with forced expiratory volume in 1 s/forced vital capacity (adjusted difference 0.002, 95% CI -0.001 to 0.004). Median TnI was 2.2 ng/L in both obstructive and non-obstructive groups. These findings do not support a pulmonary source of TnI elevation in mild to moderate, stable COPD and suggest that TnI elevations should prompt cardiovascular evaluation rather than being attributed to pulmonary disease alone.

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.

IntroductionFlexible bronchoscopy is regarded as a safe examination and is commonly used in the diagnostic work-up for lung diseases, but is also important in pulmonary research. We aimed to investigate participants’ experiences when undergoing bronchoscopy in a research setting.MethodsParticipants were recruited from the Swedish CArdioPulmonary bioImage Study (SCAPIS). A subset from this cohort (n = 45, mean age 60.5 years, 20 with normal lung function and 25 with chronic obstructive pulmonary disease, COPD) was selected for bronchoscopy. The procedure was explained both orally and in writing during a pre-procedure visit. The information included premedication, monitoring, local anesthesia, airway sampling [bronchoalveolar lavage (BAL), bronchial wash, and mucosal biopsies], and urine and blood samples. Questionnaires pre- and/or post-procedure were used to assess experiences and health impacts.ResultsIn general, participants found the bronchoscopy procedure acceptable and only a few (18%) found it unpleasant. A majority (80%) reported their experience to be much better or as expected. Almost all participants (93%) were very satisfied with the information provided. Topical anesthesia was seen as more unpleasant (20%) than airway sampling (11%). Notably, more women and participants with normal lung function reported BAL as unpleasant. After the procedure, chills, fever, and hemoptysis were reported, but no serious adverse events occurred. Increased cough and phlegm were noted.ConclusionThe present study, conducted by experienced bronchoscopists and healthcare teams, demonstrates that a bronchoscopy in a research setting in well-informed participants with normal lung function or COPD was well-tolerated.

Background:There is published evidence that a modest increase in blood eosinophils during stable COPD indicates future risk for exacerbations and a potential utility of inhaled corticosteroids. This has been perceived as an argument for targeting systemic eosinophil mobilization to prevent exacerbations in COPD, but there are no published data on systemic eosinophil mobilization during exacerbations in patients without allergy. Methods:We investigated long-term tobacco smokers (LTS: ≥10 pack-years) with COPD and chronic bronchitis (COPD-CB; GOLD stage 1-4; n = 47) but no allergy; LTS without COPD and CB (LTS; n = 10), and healthy never-smokers (HNS; n = 10) during stable disease for cross-sectional comparisons. For longitudinal comparisons, we followed the COPD-CB group for 15 months during stable disease and exacerbations, excluding samples affected by systemic corticosteroids. We quantified blood concentrations of eosinophils, the activity marker eosinophilic cationic protein (ECP) and the chemokine interleukin (IL)-4. Results:During stable disease, the concentrations of eosinophils were similar for the COPD-CB and the LTS group, although higher than in the HNS group. The concentrations of ECP and IL-4 were not markedly different in the COPD-CB and LTS groups either. During exacerbations, the concentrations of eosinophils, ECP and IL-4 were not further increased, and there was even a mathematical trend towards a decrease for these concentrations. Conclusion:The clinical evidence presented here suggests that, by average, there is no additional mobilization of eosinophils during exacerbations in patients with COPD and chronic bronchitis but no allergy. Thus, in this common phenotype, the immunological rationale for targeting systemic eosinophils during exacerbations remains unaccounted for, which motivates verification studies in large cohorts stratified for allergy and chronic bronchitis.

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.

Background Long-term oxygen supplementation for at least 15 hours per day prolongs survival among patients with severe hypoxemia. On the basis of a nonrandomized comparison, long-term oxygen therapy has been recommended to be used for 24 hours per day, a more burdensome regimen.Methods To test the hypothesis that long-term oxygen therapy used for 24 hours per day does not result in a lower risk of hospitalization or death at 1 year than therapy for 15 hours per day, we conducted a multicenter, registry-based, randomized, controlled trial involving patients who were starting oxygen therapy for chronic, severe hypoxemia at rest. The patients were randomly assigned to receive long-term oxygen therapy for 24 or 15 hours per day. The primary outcome, assessed in a time-to-event analysis, was a composite of hospitalization or death from any cause within 1 year. Secondary outcomes included the individual components of the primary outcome assessed at 3 and 12 months.Results Between May 18, 2018, and April 4, 2022, a total of 241 patients were randomly assigned to receive long-term oxygen therapy for 24 hours per day (117 patients) or 15 hours per day (124 patients). No patient was lost to follow-up. At 12 months, the median patient-reported daily duration of oxygen therapy was 24.0 hours (interquartile range, 21.0 to 24.0) in the 24-hour group and 15.0 hours (interquartile range, 15.0 to 16.0) in the 15-hour group. The risk of hospitalization or death within 1 year in the 24-hour group was not lower than that in the 15-hour group (mean rate, 124.7 and 124.5 events per 100 person-years, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.72 to 1.36; 90% CI, 0.76 to 1.29; P=0.007 for nonsuperiority). The groups did not differ substantially in the incidence of hospitalization for any cause, death from any cause, or adverse events.Conclusions Among patients with severe hypoxemia, long-term oxygen therapy used for 24 hours per day did not result in a lower risk of hospitalization or death within 1 year than therapy for 15 hours per day. (Funded by the Crafoord Foundation and others; REDOX ClinicalTrials.gov number, NCT03441204.) Oxygen therapy prolongs survival in patients with severe hypoxemia but is a burden. In this trial, therapy for 24 rather than 15 hours per day did not reduce the risk of hospitalization or death at 1 year.

Background Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population. Methods Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50–64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease. Results We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0–29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6–66.0%), stress (31.6–76.8%), respiratory disease (20.1–37.1%), depression (17.1–26.6%), cardiac disease (6.3–12.7%), anemia (0.8–3.3%), and peripheral arterial disease (0.3–0.8%). Stress was the main factor in women and current smokers. Conclusion Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting—supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Background:A substantial proportion of individuals with COPD have never smoked, and it is implied to be more common than previously anticipated but poorly studied. Aim:To describe the process of recruitment of never-smokers with COPD from a population-based cohort (n = 30 154). Methods:We recruited never-smokers with COPD, aged 50-75 years, from six University Hospitals, based on: 1) post broncho-dilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.70 and 2) FEV1 50-100% of predicted value and 3) being never-smokers (self-reported). In total 862 SCAPIS participants were identified, of which 652 were reachable and agreed to a first screening by telephone. Altogether 128 (20%) were excluded due to previous smoking or declined participation. We also applied a lower limit of normal (LLN) of FEV1/FVC (z-score<-1.64) according to the Global Lung Initiative to ensure a stricter definition of airflow obstruction. Results:Data on respiratory symptoms, health status, and medical history were collected from 492 individuals, since 32 were excluded at a second data review (declined or previous smoking), prior to the first visit. Due to not matching the required lung function criteria at a second spirometry, an additional 334 (68%) were excluded. These exclusions were by reason of: FEV1/FVC ≥0.7 (49%), FEV1 > 100% of predicted (26%) or z-score ≥ -1,64 (24%). Finally, 154 never-smokers with COPD were included: 56 (36%) women, (mean) age 60 years, FEV1 84% of predicted, FEV1/FVC: 0.6, z-score: -2.2, Oxygen saturation: 97% and BMI: 26.8 kg/m2. Conclusions:The challenges of a recruitment process of never-smokers with COPD were shown, including the importance of correct spirometry testing and strict inclusion criteria. Our findings highlight the importance of repeated spirometry assessments for improved accuracy in diagnosing COPD.

Rationale: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity of the lung for carbon monoxide (DlCO) are present, but characteristics and symptoms vary with smoking exposure. Objective: To study the prevalence of CAL, emphysema, and impaired DlCO in relation to smoking and respiratory symptoms in a middle-aged population. Methods: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DlCO testing, and high-resolution computed tomography and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) < 0.7. Results: The overall prevalence was 8.8% for CAL, 5.7% for impaired DlCO (DlCO < LLN), and 8.8% for emphysema, with a higher prevalence in current smokers than in ex-smokers and never-smokers. The proportion of never-smokers among those with CAL, emphysema, and impaired DlCO was 32%, 19%, and 31%, respectively. Regardless of smoking habits, the prevalence of respiratory symptoms was higher among people with CAL and impaired DlCO than those with normal lung function. Asthma prevalence in never-smokers with CAL was 14%. In this group, asthma was associated with lower FEV1 and more respiratory symptoms. Conclusions: In this large population-based study of middle-aged people, CAL and impaired DlCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD.

Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using preor postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group hadmore respiratory symptoms, emphysema (13.5% vs. 4.1%; P < 0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P < 0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant.

Background: Chronic rhinosinusitis (CRS) is a common disease of the upper airways causing nasal obstruction, loss of smell, facial pain and poor quality of life. Studies on CRS in COPD are scarce. Aims: To study the impact of CRS in COPD in terms of risk of exacerbations. Methods: We identified patients with COPD, aged ≥ 30 years, registered in the Swedish National Airway Register between January 2017 and August 2020. Patients were stratified for the absence or presence of CRS, defined as ≥2 prescriptions of nasal corticosteroids within one year before inclusion, and followed until January 2021 for moderate (prescription of oral corticosteroids) and severe (hospital admission for respiratory cause) exacerbations in national registries. A sensitivity analysis excluding patients with allergic rhinosinusitis (defined as additional prescription of antihistamins) was done. Results: Of the 45350 eligible COPD patients, 2539 (5.6%) had CRS. Patients with and without CRS respectively had similar age (71±9 vs 72±9 years), sex (male: 41% vs. 44%), BMI (28±13 vs. 27±13), CAT score (14±8 vs 13±7) and FEV1 % pred. (62±18 vs 60±18), while those with CRS were less often active smokers (28% vs 38%). Patients with CRS had an elevated hazard ratio (HR) for moderate exacerbations (HR 1.74; (95% CI:1.61-1.88), but not for severe exacerbations (HR 1.01, 95% CI: 0.95–1.08), adjusted for age, sex, smoking and FEV1. Most CRS patients (n=1622 (64%)) did not use antihistamins and those patients had similar results. Conclusion: In this nationwide cohort study, CRS was associated with a higher risk of moderate exacerbations in COPD and should be considered in the management of COPD.