To Örebro University

BACKGROUND: Comorbid conditions and breathlessness are associated with poor outcomes in chronic obstructive pulmonary disease (COPD). We evaluated the associations of comorbid heart disease and depression/anxiety with breathlessness in daily life among people with COPD.

METHODS: Cross-sectional analysis from the PRAXIS cohort in central Sweden. Data on patient characteristics and the modified Medical Research Council (mMRC) and Dyspnea-12 breathlessness instruments (D-12) were obtained from questionnaires in 2022. Lung function data were collected from record review. Outcome variables were clinically significant breathlessness defined as mMRC≥2 and D-12 total (>2.7), physical (>1.4) and affective (>1.2) scores above published minimal clinical important differences. Associations of heart disease and depression/anxiety with each outcome were analyzed using multivariable Poisson regression adjusted for relevant confounders.

RESULTS: In 522 included patients, mMRC >2 was present in 59% and increased D-12 total, physical and affective domain scores in 69%, 74%, and 50%, respectively. Heart disease was independently associated with mMRC (relative risk ratio [95% confidence interval] 1.34 [1.17-1.53]), D12 physical domain (1.12[1.02-1.24]) and D-12 affective domain (1.20[1.02-1.42]). Depression/anxiety was independently associated with increased D-12 affective domain (1.25[1.04-1.49]). In addition, previous exacerbations and GOLD stage 3-4 were associated with mMRC and D-12, respectively.

CONCLUSION: In COPD, comorbid heart disease is associated with both activity-related breathlessness and with physical and affective domains of breathlessness while depression/anxiety is associated with the affective domain of breathlessness. As the influence of different dimensions of breathlessness may differ according to comorbidity the D-12 instrument adds more information when assessing breathlessness in patients with COPD.

Breathlessness has relatively low variability in daily life, with a gradual decline throughout the day after a morning peak. People who were inactive, and those with more intense breathlessness limiting their exertion had higher levels of breathlessness.

BACKGROUND: Long-term oxygen therapy (LTOT) improves survival in patients with chronic severe resting hypoxaemia, but effects on hospitalisation are unknown. This study evaluated the potential impact of starting LTOT on acute exacerbation and hospital burden in patients with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and pulmonary hypertension (PH).

METHODS: Longitudinal analysis of consecutive patients in the population-based Swedish DISCOVERY cohort who started LTOT between 2000 and 2018 with a follow-up duration≥3 months. Total and hospitalised acute exacerbations of the underlying disease, all-cause hospitalisations, and all-cause outpatient visits were annualised and compared between the year before and after LTOT initiation for each disease cohort, and by hypercapnic status in patients with COPD.

RESULTS: Patients with COPD (n=10 134) had significant reduction in annualised rates of total and hospitalised acute exacerbations, as well as all-cause hospitalisations, following LTOT initiation, with increment in those with ILD (n=2507) and PH (n=850). All-cause outpatient visits increased across all cohorts following LTOT initiation. Similar findings were observed in patients with hypercapnic and non-hypercapnic COPD. Sensitivity analyses of patients with 12 months of follow-up showed reduced acute exacerbations and all-cause hospitalisations in the ILD and PH cohorts.

CONCLUSION: LTOT is associated with reduced rates of both total and hospitalised acute exacerbations and all-cause hospitalisations in patients with COPD, as well as patients with ILD and PH with 12 months of follow-up. There is increased all-cause outpatient visits in all disease groups following LTOT initiation.

PURPOSE: Myocardial infarctions (MIs) can occur in underlying obstructive coronary artery disease (MI-CAD) or in non-obstructive coronary arteries (MINOCA). The primary objectives of the study were to investigate the prevalence of MI-CAD and MINOCA in people with CAL, and to explore if CAL is an independent risk factor for MI-CAD and MINOCA. Secondary objectives were to explore these research questions stratified by sex and by smoking history.

PATIENTS AND METHODS: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) of people aged 50-64 years. CAL was defined as a post-bronchodilator ratio of forced expiratory volume in one second and forced vital capacity below 0.70. MI-CAD was defined as a self-reported MI with coronary computed tomography angiography findings of previous revascularization or at least one significant coronary stenosis (>50%), and MINOCA as self-reported MI with no previous revascularization and no significant coronary stenosis.

RESULTS: In total, 1735 (8.3%) of 20,882 included participants had CAL. MI-CAD was more common than MINOCA both in people with (2.8 vs 0.6%) and without CAL (1.2 vs 0.3%). Compared with those without CAL, people with CAL had an almost doubled independent risk of both MI-CAD ([adjusted OR] 1.72; [95% CI] 1.22-2.42) and MINOCA (1.99; 1.02-3.86). In men, CAL was associated with increased risk of MINOCA (2.63; 1.23-5.64), and in women with increased risk for MI-CAD (3.43; 1.68-1.26).

CONCLUSION: Middle-aged people with CAL have an almost doubled risk of both MI-CAD and MINOCA, compared with people without CAL. In contrast to people without CAL, the risk of MINOCA is increased in men and the risk of MI-CAD is increased in women. In a clinical context, both MI types should be considered in CAL.

Background: Chronic obstructive pulmonary disease (COPD) is associated with increased risk for cardiovascular disease (CVD). We aimed to explore temporal changes in CVD prevalence and cardiovascular (CV) mortality and associations with treatment in patients with COPD and long-term oxygen therapy (LTOT).

Methods: Population-based DISCOVERY cohort study using data from 1987 to 2022 from the Swedish National Registry for Respiratory Failure and the National Patient Registry. Annual prevalence of CVD (ischemic heart disease, heart failure, atrial fibrillation/flutter, cerebral infarctions/hemorrhages) at start of LTOT, and all cause- and CV mortality rates per year were calculated. Associations of beta-blockers, ACE/AII-inhibitors, statins and inhaled corticosteroids (ICS) with CV mortality and new acute CV events (myocardial infarctions or cerebral infarctions/hemorrhages) were analysed using Cox regression, adjusting for sex, age, PaO2 on air, body mass index, performance status, forced expiratory volume in one second, CVD and exacerbation frequency at LTOT start.

Results: During the study period, 18,733 patients (58% women, mean age+SD 74+8 years) started LTOT, and of these 17,066 died. The CVD prevalence at LTOT start changed from 32% in 1989 to 53% in 2022. Mortality rates decreased from 38 to 34 % (all-cause) and from 5.4% to 4.6% (CV). The proportion of CV deaths was unchanged at 14%. ICS treatment was independently associated with lower risk for CV mortality (HR [95%CI] 0.75 [0.66-0.86]) and for new acute CV events (0.78 [0.70-0.87]).

Conclusions: CVD prevalence but not CV mortality has increased in oxygen-dependent COPD. ICS may be of benefit to prevent CV events.

INTRODUCTION: The study aimed to compare prevalence of comorbid allergic manifestations and rhinitis, allergy testing and associations with patient-related outcomes in patients with asthma and COPD.

METHODS: Cross-sectional study of randomly selected Swedish patients with a doctor's diagnosis of asthma (n = 1291) or COPD (n = 1329). Self-completion questionnaires from 2014 provided data on demographics, rhinitis, allergic symptoms at exposure to pollen or furry pets, exacerbations, self-assessed severity of disease and scores from the Asthma Control Test (ACT) and the COPD Assessment Test (CAT), and records were reviewed for allergy tests.

RESULTS: Allergic manifestations were more common in asthma (75%) compared with COPD (38%). Rhinitis was reported in 70% of asthma and 58% of COPD patients. Allergy tests had been performed during the previous decade in 28% of patients with asthma and in 8% of patients with COPD. In patients with asthma; comorbid allergy and rhinitis were both independently associated with increased risk for poor asthma symptom control (ACT < 20) (OR [95% CI] 1.41 [1.05 to 1.87] and 2.13 [1.60 to 2.83]), exacerbations (1.58 [1.15 to 2.17] and 1.38 [1.02 to 1.86]), and self-assessed moderate/severe disease (1.64 [1.22 to 2.18] and 1.75 [1.33 to 2.30]). In patients with COPD, comorbid allergy and rhinitis were both independently associated with increased risk for low health status (CAT ≥ 10) (OR [95% CI] 1.46 [1.20 to 1.95] and 2.59 [1.97 to 3.41]) respectively, with exacerbations during the previous six months (1.91 [1.49 to 2.45] and 1.57 [1.23 to 2.01]), and with self-assessed moderate/severe disease (1.70 [1.31 to 2.22] and 2.13 [1.66 to 2.74]).

CONCLUSION: Allergic manifestations and rhinitis are more common in asthma than COPD but associated with worse outcomes in both diseases. This highlights the importance of examining and treating comorbid allergy and rhinitis, not only in asthma but also in COPD.

BACKGROUND: Studies on the survival of patients with home mechanical ventilation (HMV) are sparse. We aimed to analyse the impact of controlled hypercapnia on survival over 27 years among patients with HMV in Sweden.

STUDY DESIGN AND METHODS: Population-based cohort study of adult patients starting HMV in the Swedish Registry for Respiratory Failure (Swedevox) during 1996-2022 cross-linked with the National Cause of Death registry. Mortality risk factors were analysed using crude and multivariable Cox regression models, including adjustments for anthropometrics, comorbidities, the underlying diagnosis causing chronic hypercapnic respiratory failure (CRF) and the control of hypercapnia (P aCO2 ≤6.0 kPa) at follow-up.

RESULTS: We included 10 190 patients (50.1% women, age 62.9±14.5 years). Control of hypercapnia at follow-up after 1.3±0.9 years was associated with lower mortality, hazard ratio (HR) 0.74 (95% CI 0.68-0.80) and the association was strongest in those with pulmonary disease, restrictive thoracal disease (RTD), obesity hypoventilation syndrome (OHS) and amyotrophic lateral sclerosis (ALS). Predictors for increased mortality included age, Charlson Comorbidity Index, supplemental oxygen therapy and acute start of HMV therapy. Median survival varied between 0.8 years (95% CI 0.8-0.9 (n=1401)) for ALS and 7.6 years (95% CI 6.9-8.6 (n=1061)) for neuromuscular disease. Three-year survival decreased from 76% (95% CI 71-80) between 1996 and 1998 to 52% (95% CI 50-55) between 2017 and 2019. When adjusting for underlying diagnosis and age, the association between start year and decreased survival disappeared, HR 1.00 (95% CI 0.99-1.01).

CONCLUSION: Controlling P aCO2 is a key treatment goal for survival in HMV therapy. Survival differed markedly between diagnosis and age groups, and survival rates have declined as the patient group has aged.

Background: Home mechanical ventilation (HMV), noninvasive ventilation and invasive ventilation outside a hospital setting, is a key treatment to improve outcomes in chronic hypoventilation.

Research Question: What are the temporal trends observed over 27 years in Sweden regarding the incidence, prevalence, diagnostic spectrum, and patient characteristics associated with HMV?

Study Design and Methods: This was a national population-based longitudinal analysis of the Course of Disease in Patients Reported to the Swedish CPAP Oxygen and Ventilator Registry (DISCOVERY) study of patients initiating HMV between 1996 and 2022. Time trends stratified by the underlying diagnosis group (lung disease, predominantly COPD, restrictive thoracal diseases, obesity hypoventilation syndrome [OHS], neuromuscular diseases, amyotrophic lateral sclerosis, and other neurologic disorders) were analyzed using linear regression models. Results: We included 10,555 patients aged ≥ 16 years (mean age 63 [SD, 15] years; 50% women). Between 1996 and 1998 and 2020 and 2022, the HMV incidence increased threefold to 7 per 100,000 people, and the prevalence increased sixfold to 33 per 100,000 people. The most common indication for incident HMV shifted from restrictive thoracal diseases (35% in 1996-1998 to 3% in 2020-2022) to lung disease (14% to 31%), OHS (23% to 33%), and amyotrophic lateral sclerosis (4% to 14%) by 2020 to 2022 (P < .001). The proportion of women increased from 47% to 54% (P < .013) and the age at initiation of HMV increased from 58 [SD, 15] to 66 [SD, 14] years (P < .001). Lung function measured as vital capacity at treatment start increased significantly in all diagnosis groups except for OHS, where both vital capacity and FEV1 decreased. In the registry's first and last 3-year periods, the proportion of patients ventilated invasively decreased from 10% to 2% (P < .001).

Interpretation: In the 27 years until 2022, the incidence and prevalence of HMV in Sweden have increased markedly, patient demographics have changed, and use of invasive ventilation has decreased. The average age of patients initiated on HMV has increased, but treatment is started earlier in the disease trajectory.

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: Long-term oxygen therapy (LTOT) improves survival in severe hypoxemia and is recommended 24h/day based on non-randomized data. However, LTOT 24h/day is burdensome and recent observational data indicate no difference in patient-related outcomes for 24 versus 15h/day. We tested the hypothesis that LTOT prescribed 24 versus 15h/day would not reduce risk of hospitalization or death at one year.

Methods: In this multicenter, registry-based, randomized, clinical trial using the Swedish Registry for Respiratory Failure, patients starting LTOT were randomized (in a 1:1 ratio) to LTOT 24 or 15h/day. Primary outcome was time to all-cause hospitalization or mortality at one year. Secondary outcomes were hospitalizations and mortality (all-causes, respiratory, or cardiac disease) at three and twelve months, in all patients and stratified according to severity of baseline hypoxemia and underlying condition (chronic obstructive pulmonary disease or other).

Results: Between May 2018 and April 2022, 241 patients were randomized to LTOT 24h/day (n=117) or 15h/day (n=124). No patient was lost to follow-up. Compared to LTOT 15h/day, LTOT 24h/day did not improve the primary outcome of hospitalization or death up to one year (hazard ratio, 0.99; 90% confidence interval, 0.76–1.29; non-superiority p=0.007), or any secondary outcomes overall or in any sub-group. Self-reported adherence to the randomized treatment was high (for 24h/day: median 24.0 [interquartile range, 21.0–24.0]; for 15h/day: median 15.0 [15.0–16.0] h/day) at twelve months.

Conclusion: LTOT prescribed for 24h/day compared with 15h/day did not decrease the risk of hospitalization or death up to one year.