Risk Factors Associated with Asthma Control and Quality of Life in Patients with Mild Asthma Without Preventer Treatment, a Cross-Sectional Study.

Purpose: To study risk factors for uncontrolled asthma and insufficient quality of life (QoL) in patients with mild asthma, ie those without preventer treatment. Patients and Methods: Patients aged 18-75 years with a doctor's diagnosis of asthma randomly selected from primary and secondary care in Sweden. Mild asthma was defined as self-reported current asthma and no preventer treatment. Data were collected from self-completed questionnaires in 2012 and 2015. Well-controlled asthma was defined as Asthma Control Test (ACT) ≥20 points and no exacerbation and uncontrolled asthma as ACT<20 points and/or at least one exacerbation in the previous six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ), where a total mean score of ≥ 6 indicated sufficient and < 6 insufficient QoL. Multivariate logistic regression analyses were performed using asthma control and Mini-AQLQ as dependent variables. Asthma control was dichotomized as controlled and uncontrolled asthma and the Mini-AQLQ as sufficient QoL (mean score ≥6) and insufficient QoL (mean score <6). Results: Among 298 patients, 26% had uncontrolled asthma, 40% insufficient QoL and 20% both uncontrolled asthma and insufficient QoL. Age ≥60 years, obesity, daily smoking, rhinitis and inadequate knowledge of asthma self-management were independently associated with poor asthma control. Factors independently associated with insufficient QoL were age ≥60 years, overweight, obesity, rhinitis, sinusitis and inadequate knowledge of asthma self-management. Age ≥60 years, obesity, rhinitis and inadequate knowledge of asthma self-management were independently associated with both uncontrolled asthma and insufficient QoL. Conclusion: Among asthma patients without preventer medication, 26% had uncontrolled asthma and 40% had insufficient asthma-related QoL. Older age, obesity, and rhinitis were risk factors for both poor asthma control and a reduced QoL, but having good knowledge of asthma self-management reduced this risk. Our findings suggest that this group of patients requires further attention and follow-up.

Many patients with little symptoms of asthma do not take asthma-preventer medication as their asthma is recognized as mild. Still, it is well-known that in this group there are patients with frequent and severe symptoms and acute attacks of asthma, defined as uncontrolled asthma. Quality of life (QoL) is less studied in these patients. Our aim was to study patient characteristics and factors with a higher risk for uncontrolled asthma and insufficient QoL in patients with mild asthma. We studied patients with asthma diagnosis 18­75 of age in Sweden who reported asthma and no asthma preventer medication. They answered questionnaires about characteristics, knowledge of asthma, asthma symptoms, acute asthma attacks and QoL. A test for asthma symptom control, the Asthma Control Test (ACT), was answered, where 20 points or more meant good asthma symptom control. Patients were regarded as having uncontrolled asthma if they had less than 20 points and/or at least one acute asthma attack the last six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire. A mean score of 6 or more meant sufficient and less than 6 insufficient QoL. Of the 298 patients, 26% had uncontrolled asthma, 40% had insufficient QoL and 20% had both. Patients with risk for both uncontrolled asthma and insufficient QoL were 60 years and over, with obesity, rhinitis and those who reported insufficient knowledge of how to handle asthma. Our results suggest that patients with mild asthma need more attention, better management and follow-ups.

Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.

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.

Occupational Dust Exposure as a Risk Factor for Developing Lung Function Impairment.

OBJECTIVE: Dust exposure is high in several industries. We investigated associations of exposure in paper mills, wood pellet plants, and iron foundries with lung function impairment. METHODS: Respirable silica, inhalable paper dust, or inhalable wood dust were collected as personal samples and spirometry was performed. Multiple linear regression analyzed associations with FEV 1 %pred and FVC%pred. RESULTS: Wood pellet workers with high exposure to inhalable dust had lower FEV 1 %pred (95% CI) (-9.4 [-16 to -2.6]) and FVC%pred (-9.8 [-15 to -4.0]) compared with lowest exposure level. Workers at paper mills and foundries had no dose-dependent association but lower FEV 1 %pred and FVC%pred than in workers at wood pellets plants. CONCLUSIONS: Increased exposure to inhalable wood dust is associated with decreased lung function. Foundry and paper mill workers have generally lower lung function than wood pellet workers. Spirometry should be considered in workers in industries with airborne particulate matter pollution.

Pharmacological treatment of asthma in Sweden from 2005 to 2015.

OBJECTIVE: Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting ß2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment. METHODS: Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 (n = 1182) and 2015 (n = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi2-test. Odds ratios (ORs) were calculated using logistic regression. RESULTS: Maintenance treatment with ICS together with long-acting ß2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% (p = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, p < 0.001), while SABA use decreased (46.4- 41.8%, p = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, p = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use. CONCLUSIONS: The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.

Machine learning slice-wise whole-lung CT emphysema score correlates with airway obstruction.

OBJECTIVES: Quantitative CT imaging is an important emphysema biomarker, especially in smoking cohorts, but does not always correlate to radiologists' visual CT assessments. The objectives were to develop and validate a neural network-based slice-wise whole-lung emphysema score (SWES) for chest CT, to validate SWES on unseen CT data, and to compare SWES with a conventional quantitative CT method. MATERIALS AND METHODS: Separate cohorts were used for algorithm development and validation. For validation, thin-slice CT stacks from 474 participants in the prospective cross-sectional Swedish CArdioPulmonary bioImage Study (SCAPIS) were included, 395 randomly selected and 79 from an emphysema cohort. Spirometry (FEV1/FVC) and radiologists' visual emphysema scores (sum-visual) obtained at inclusion in SCAPIS were used as reference tests. SWES was compared with a commercially available quantitative emphysema scoring method (LAV950) using Pearson's correlation coefficients and receiver operating characteristics (ROC) analysis. RESULTS: SWES correlated more strongly with the visual scores than LAV950 (r = 0.78 vs. r = 0.41, p < 0.001). The area under the ROC curve for the prediction of airway obstruction was larger for SWES than for LAV950 (0.76 vs. 0.61, p = 0.007). SWES correlated more strongly with FEV1/FVC than either LAV950 or sum-visual in the full cohort (r = - 0.69 vs. r = - 0.49/r = - 0.64, p < 0.001/p = 0.007), in the emphysema cohort (r = - 0.77 vs. r = - 0.69/r = - 0.65, p = 0.03/p = 0.002), and in the random sample (r = - 0.39 vs. r = - 0.26/r = - 0.25, p = 0.001/p = 0.007). CONCLUSION: The slice-wise whole-lung emphysema score (SWES) correlates better than LAV950 with radiologists' visual emphysema scores and correlates better with airway obstruction than do LAV950 and radiologists' visual scores. CLINICAL RELEVANCE STATEMENT: The slice-wise whole-lung emphysema score provides quantitative emphysema information for CT imaging that avoids the disadvantages of threshold-based scores and is correlated more strongly with reference tests than LAV950 and reader visual scores. KEY POINTS: • A slice-wise whole-lung emphysema score (SWES) was developed to quantify emphysema in chest CT images. • SWES identified visual emphysema and spirometric airflow limitation significantly better than threshold-based score (LAV950). • SWES improved emphysema quantification in CT images, which is especially useful in large-scale research.

Risk and outcomes of COVID-19 in patients with oxygen-dependent chronic respiratory failure- a national cohort study.

BACKGROUND: We aimed to evaluate cumulative occurrence and impact of COVID-19 in patients with chronic respiratory failure (CRF) treated with long-term oxygen therapy (LTOT). MATERIAL AND METHODS: Data were obtained from the SCIFI-PEARL study on the entire Swedish population and on patients with oxygen-dependent CRF and no COVID-19 diagnosis before start of LTOT. Analyses were performed for three time periods; pre-alpha (Jan-Dec 2020), alpha (Jan-Mar 2021) and delta/omicron (Apr 2021-May 2022). Cumulative incidence of laboratory-verified COVID-19 was compared between patients with CRF and the general population. Risk factors for severe (hospitalised) to critical (intensive care, or death ≤30 days after infection) COVID-19, and the impact of COVID-19 on one-year mortality, were analysed using multivariable Cox regression. RESULTS: Cumulative incidence of COVID-19 was higher in patients with CRF than in the general population during the pre-alpha period (6.4%/4.9%, p = 0.002), but less common during the alpha and delta/omicron periods (2.9%/3.8% and 7.8%/15.5%, p < 0.0001 for both). The risk of severe/critical COVID-19 was much higher in CRF patients during all periods (4.9%/0.5%, 3.8%/0.2% and 15.5%/0.5%, p < 0.0001 for all). Risk factors for COVID-19 infection in people with CRF were higher age, cardiovascular and renal disease, and COVID-19 was associated with increased one-year mortality following infection in the pre-alpha (HR 1.79; [95% CI] 1.27-2.53) and alpha periods (1.43; 1.03-1.99). CONCLUSION: Patients with CRF had higher risk of severe/critical COVID-19 than the general population. COVID-19 infection was associated with excess one-year mortality.

How can we identify subglottic stenosis in patients with suspected obstructive disease?

PURPOSE: Subglottic stenosis, a rare condition of the upper airway, is frequently misdiagnosed as obstructive lung disease. The aim of this study was to investigate whether subglottic stenosis could be identified and distinguished from asthma and chronic obstructive pulmonary disease (COPD) using spirometry or the dyspnea index (DI). METHODS: The study population included 43 patients with asthma, 31 patients with COPD and 50 patients with subglottic stenosis planned to undergo endoscopic intervention. All patients completed the DI and underwent dynamic spirometry registering both inspiratory and expiratory volumes and flows, including the expiratory disproportion index (EDI), the ratio of forced expiratory volume in 1 s to peak expiratory flow. One-way analysis of variance assessed the discrepancy of the variables among the study groups, and receiver operating curve (ROC) analysis determined the measurement with the best discriminatory power providing a cutoff value, maximizing both sensitivity and specificity. RESULTS: The only statistically significant variables differing between all three groups were the EDI and the DI. The EDI showed an excellent area under the ROC curve (0.99, p < 0.001) with a cutoff value of 0.39 (98% sensitivity, 96% specificity), followed by DI (0.87, p < 0.001) with a cutoff score of > 25 (83% sensitivity and 78% specificity). CONCLUSION: In patients with dyspnea of unknown cause, an increase in EDI should arouse a suspicion of extrathoracic airway obstruction, advocating for further evaluation with laryngotracheoscopy.

Symptom Duration, Recurrence, and Long-Term Effects of Swimming-Induced Pulmonary Edema: A 30-Month Follow-Up Study.

BACKGROUND: Swimming-induced pulmonary edema (SIPE) has been reported to subside within 24 to 48 h, but comprehensive follow-up studies on symptom duration and long-term effects are missing. RESEARCH QUESTION: What are the symptom duration, recurrence, and long-term effects of SIPE? STUDY DESIGN AND METHODS: A follow-up study was conducted, based on 165 cases of SIPE from Sweden's largest open-water swimming event with 26,125 individuals participating during 2017-2019. Data on patient characteristics, clinical findings, and symptoms were collected at admission. Telephone interviews at 10 days and 30 months were performed to explore symptom duration, recurrence of SIPE symptoms, need for medical evaluation, and long-term effects of self-assessed general health and physical activity level. RESULTS: Follow-up at 10 days was performed for 132 cases and at 30 months for 152 cases. Most of the patients were women, and their mean age was 48 years. At the 10-day follow-up, symptom duration > 2 days after the swimming race was reported by 38%. The most common symptoms were dyspnea and cough. In patients at 30-month follow-up, recurrence of respiratory symptoms during open-water swimming was reported by 28%. In multivariable logistic regression, asthma was independently associated with both symptom duration > 2 days and recurrence of SIPE symptoms (P = .045 and P = .022, respectively). Most participants reported equal or improved general health (93%) and physical activity level (85%) after experiencing SIPE, but 58% had not swum in open water since the event. INTERPRETATION: The present large cohort study challenges the established hallmark of SIPE symptom duration < 48 h, whereas SIPE recurrence was in the previously reported range. At 30 months, most patients reported unchanged self-assessed general health and physical activity level. These findings add to our understanding of the course of SIPE and can provide evidence-based information to swimmers and health care professionals.

Diagnostic spirometry in COPD is increasing, a comparison of two Swedish cohorts.

Spirometry should be used to confirm a diagnosis of chronic obstructive pulmonary disease (COPD). This test is not always performed, leading to possible misdiagnosis. We investigated whether the proportion of patients with diagnostic spirometry has increased over time as well as factors associated with omitted or incorrectly interpreted spirometry. Data from medical reviews and a questionnaire from primary and secondary care patients with a doctors' diagnosis of COPD between 2004 and 2010 were collected. Data were compared with a COPD cohort diagnosed between 2000 and 2003. Among 703 patients with a first diagnosis of COPD between 2004 and 2010, 88% had a diagnostic spirometry, compared with 59% (p < 0.001) in the previous cohort. Factors associated with not having diagnostic spirometry were current smoking (OR 2.21; 95% CI 1.36-3.60), low educational level (OR 1.81; 1.09-3.02) and management in primary care (OR 2.28; 1.02-5.14). The correct interpretation of spirometry results increased (75% vs 82%; p = 0.010). Among patients with a repeated spirometry, 94% had a persistent FEV1/FVC or FEV1/VC ratio <0.70.

Breathlessness and exercise performance to predict mortality in long-term oxygen therapy - The population-based DISCOVERY study.

BACKGROUND: Patients with chronic respiratory failure treated with long-term oxygen therapy (LTOT) often have severe breathlessness, impaired exercise performance, and high but variable mortality that is difficult to predict. We aimed to evaluate breathlessness and exercise performance upon starting LTOT as predictors of overall and short-term mortality. METHODS: This was a longitudinal, population-based study of patients who initiated LTOT between 2015 and 2018 in Sweden. Breathlessness was measured using the Dyspnea Exertion Scale, and exercise performance using the 30s-Sit-To-Stand test. Associations with overall and three-month mortality were analyzed using Cox-regression. Subgroup analyses were performed for patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) respectively. The predictive capacity of models was assessed using a C-statistic. RESULTS: A total of 441 patients (57.6% female, aged 75.4 ± 8.3 years) were analyzed, of whom 141 (32%) died during a median follow-up of 260 (IQR 75-460) days. Both breathlessness and exercise performance were independently associated with overall mortality in the crude models, but only exercise performance remained independently associated with overall mortality when models were adjusted for other predictors, when short-term mortality was analyzed, or when breathlessness and exercise capacity were analyzed concurrently. The multivariable model including exercise performance but not breathlessness provided a relatively high predictive capacity for overall mortality, C-statistic 0.756 (95% CI 0.702-0.810). Similar results were seen in the COPD and ILD subgroups. CONCLUSION: Exercise performance as measured by the 30s-STS may be useful to identify patients with higher mortality on LTOT for optimized management and follow-up.

Factors Associated with the Non-Exacerbator Phenotype of Chronic Obstructive Pulmonary Disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) and no exacerbations may need less maintenance treatment and follow-up. The aim was to identify factors associated with a non-exacerbator COPD phenotype. Methods: Cross-sectional analysis of 1354 patients from primary and secondary care, with a doctor's diagnosis of COPD. In 2014, data on demographics, exacerbation frequency and symptoms using COPD Assessment Test (CAT) were collected using questionnaires and on spirometry and comorbid conditions by record review. The non-exacerbator phenotype was defined as having reported no exacerbations the previous six months. Multivariable logistic regression with the non-exacerbator phenotype as dependent variable was performed, including stratification and interaction analyses by sex. Results: The non-exacerbator phenotype was found in 891 (66%) patients and was independently associated with COPD stage 1 (OR [95% CI] 5.72 [3.30-9.92]), stage 2 (3.42 [2.13-5.51]) and stage 3 (2.38 [1.46-3.88]) compared with stage 4, and with CAT score <10 (3.35 [2.34-4.80]). Chronic bronchitis and underweight were inversely associated with the non-exacerbator phenotype (0.47 [0.28-0.79]) and (0.68 [0.48-0.97]), respectively. The proportion of non-exacerbators was higher among patients with no maintenance treatment or a single bronchodilator. The association of COPD stage 1 compared with stage 4 with the non-exacerbator phenotype was stronger in men (p for interaction 0.048). In women, underweight and obesity were both inversely associated with the non-exacerbator phenotype (p for interaction 0.033 and 0.046 respectively), and in men heart failure was inversely associated with the non-exacerbator phenotype (p for interaction 0.030). Conclusion: The non-exacerbator phenotype is common, especially in patients with no maintenance treatment or a single bronchodilator, and is characterized by preserved lung function, low symptom burden, and by absence of chronic bronchitis, underweight and obesity and heart failure. We suggest these patients may need less treatment and follow-up, but that management of comorbid conditions is important to avoid exacerbations.

Association between obstructive sleep apnoea and cancer: a cross-sectional, population-based study of the DISCOVERY cohort.

OBJECTIVES: Nocturnal hypoxia in obstructive sleep apnoea (OSA) is a potential risk factor for cancer. We aimed to investigate the association between OSA measures and cancer prevalence in a large national patient cohort. DESIGN: Cross-sectional study. SETTINGS: 44 sleep centres in Sweden. PARTICIPANTS: 62 811 patients from the Swedish registry for positive airway pressure (PAP) treatment in OSA, linked to the national cancer registry and national socioeconomic data (the course of DIsease in patients reported to Swedish CPAP, Oxygen and VEntilator RegistrY cohort). OUTCOME MEASURES: After propensity score matching for relevant confounders (anthropometric data, comorbidities, socioeconomic status, smoking prevalence), sleep apnoea severity, measured as Apnoea-Hypopnoea Index (AHI) or Oxygen Desaturation Index (ODI), were compared between those with and without cancer diagnosis up to 5 years prior to PAP initiation. Subgroup analysis for cancer subtype was performed. RESULTS: OSA patients with cancer (n=2093) (29.8% females, age 65.3 (SD 10.1) years, body mass index 30 (IQR 27-34) kg/m2) had higher median AHI (n/hour) (32 (IQR 20-50) vs 30 (IQR 19-45), n/hour, p=0.002) and median ODI (n/hour) (28 (IQR 17-46) vs 26 (IQR 16-41), p<0.001) when compared with matched OSA patients without cancer. In subgroup analysis, ODI was significantly higher in OSA patients with lung cancer (N=57; 38 (21-61) vs 27 (16-43), p=0.012)), prostate cancer (N=617; 28 (17-46) vs 24, (16-39)p=0.005) and malignant melanoma (N=170; 32 (17-46) vs 25 (14-41),p=0.015). CONCLUSIONS: OSA mediated intermittent hypoxia was independently associated with cancer prevalence in this large, national cohort. Future longitudinal studies are warranted to study the potential protective influence of OSA treatment on cancer incidence.

Balloon dilatation is superior to CO2 laser excision in the treatment of subglottic stenosis.

INTRODUCTION: Endoscopic treatment of subglottic stenosis (SGS) is regarded as a safe procedure with rare complications and less morbidity than open surgery yet related with a high risk of recurrence. The abundance of techniques and adjuvant therapies complicates a comparison of the different surgical approaches. The primary aim of this study was to investigate disease recurrence after CO2 laser excisions and balloon dilatation in patients with SGS and to identify potential confounding factors. MATERIALS AND METHODS: In a tertiary referral center, two cohorts of previously undiagnosed patients treated for SGS were retrospectively reviewed and followed for 3 years. The CO2 laser cohort (CLC) was recruited between 2006 and 2011, and the balloon dilatation cohort (BDC) between 2014 and 2019. Kaplan‒Meier and multivariable Cox regression analyzed time to repeated surgery and estimated hazard ratios (HRs) for different variables. RESULTS: Nineteen patients were included in the CLC, and 31 in the BDC. The 1-year cumulative recurrence risk was 63.2% for the CLC compared with 12.9% for the BDC (HR 33.0, 95% CI 6.57-166, p < 0.001), and the 3-year recurrence risk was 73.7% for the CLC compared with 51.6% for the BDC (HR 8.02, 95% CI 2.39-26.9, p < 0.001). Recurrence was independently associated with overweight (HR 3.45, 95% CI 1.16-10.19, p = 0.025), obesity (HR 7.11, 95% CI 2.19-23.04, p = 0.001), and younger age at diagnosis (HR 8.18, 95% CI 1.43-46.82, p = 0.018). CONCLUSION: CO2 laser treatment is associated with an elevated risk for recurrence of SGS compared with balloon dilatation. Other risk factors include overweight, obesity, and a younger age at diagnosis.

Comorbid conditions as predictors of mortality in severe COPD - an eight-year follow-up cohort study.

Purpose: Co-morbidities are common in chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. The aim of the present study was to explore the prevalence of several comorbid conditions in severe COPD, and to investigate and compare their associations with long-term mortality. Methods: In May 2011 to March 2012, 241 patients with COPD stage 3 or 4 were included in the study. Information was collected on sex, age, smoking history, weight and height, current pharmacological treatment, number of exacerbations the recent year and comorbid conditions. At December 31st, 2019, mortality data (all-cause and cause specific) were collected from the National Cause of Death Register. Data were analyzed using Cox-regression analysis with gender, age, previously established predictors of mortality and comorbid conditions as independent variables, and all-cause mortality and cardiac and respiratory mortality, respectively, as dependent variables. Results: Out of 241 patients, 155 (64%) were deceased at the end of the study period; 103 patients (66%) died of respiratory disease and 25 (16%) of cardiovascular disease. Impaired kidney function was the only comorbid condition independently associated with increased all-cause mortality (HR (95% CI) 3.41 (1.47-7.93) p=0.004) and respiratory mortality (HR (95%CI) 4.63 (1.61 to 13.4), p = 0.005). In addition, age ≥70, BMI <22 and lower FEV1 expressed as %predicted were significantly associated with increased all-cause and respiratory mortality. Conclusion: In addition to the risk factors high age, low BMI and poor lung function; impaired kidney function appears to be an important risk factor for mortality in the long term, which should be taken into account in the medical care of patients with severe COPD.

Risk factors for impaired respiratory function post COVID-19: A prospective cohort study of nonhospitalized and hospitalized patients.

BACKGROUND: Severe COVID-19 increases the risk for long-term respiratory impairment, but data after mild COVID-19 are scarce. Our aims were to determine risk factors for reduced respiratory function 3-6 months after COVID-19 infection and to investigate if reduced respiratory function would relate to impairment of exercise performance and breathlessness. METHODS: Patients with COVID-19 were enrolled at the University Hospitals of Umeå and Örebro, and Karlstad Central Hospital, Sweden. Disease severity was defined as mild (nonhospitalized), moderate (hospitalized with or without oxygen treatment), and severe (intensive care). Spirometry, including diffusion capacity (DLCO ), was performed 3-6 months after hospital discharge or study enrollment (for nonhospitalized patients). Breathlessness (defined as ≥1 according to the modified Medical Research Council scale) and functional exercise capacity (1-min sit-to-stand test; 1-MSTST) were assessed. RESULTS: Between April 2020 and May 2021, 337 patients were enrolled in the study. Forced vital capacity and DLCO were significantly lower in patients with severe COVID-19. Among hospitalized patients, 20% had reduced DLCO , versus 4% in nonhospitalized. Breathlessness was found in 40.6% of the participants and was associated with impaired DLCO . A pathological desaturation or heart rate response was observed in 17% of participants during the 1-MSTST. However, this response was not associated with reduced DLCO . CONCLUSION: Reduced DLCO was the major respiratory impairment 3-6 months following COVID-19, with hospitalization as the most important risk factor. The lack of association between impaired DLCO and pathological physiological responses to exertion suggests that these physiological responses are not primarily related to decreased lung function.

High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19.

Background: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae. Methods: This was a prospective, multicenter, cohort study including 434 patients. At 6 months, physical exercise capacity was assessed by a 1-minute sit-to-stand test (1MSTST) and persistent symptoms were reported and HRQoL was evaluated through the EuroQol 5-level 5-dimension (EQ-5D-5L) questionnaire. Patients with both persistent symptoms and reduced HRQoL were classified into a new definition of post-acute COVID syndrome, PACS+. Risk factors for developing persistent symptoms, reduced HRQoL and PACS+ were identified by multivariable Poisson regression. Results: Persistent symptoms were experienced by 79% of hospitalized, and 59% of non-hospitalized patients at 6 months. Hospitalized patients had a higher prevalence of self-assessed reduced overall health (28 vs. 12%) and PACS+ (31 vs. 11%). PACS+ was associated with reduced exercise capacity but not with abnormal pulse/desaturation during 1MSTST. Hospitalization was the most important independent risk factor for developing persistent symptoms, reduced overall health and PACS+. Conclusion: Persistent symptoms and reduced HRQoL are common among COVID-19 survivors, but abnormal pulse and peripheral saturation during exercise could not distinguish patients with PACS+. Patients with severe infection requiring hospitalization were more likely to develop PACS+, hence these patients should be prioritized for clinical follow-up after COVID-19.

Comorbid Heart Disease in Patients with COPD is Associated with Increased Hospitalization and Mortality - A 15-Year Follow-Up.

Purpose: The aim of this study was to examine the association of comorbid heart disease, defined as chronic heart failure or ischemic heart disease, on all-cause and cause-specific hospitalization and mortality in patients with COPD over a period of nearly 15 years. Materials and Methods: The cohort study included patients with COPD from primary and secondary care in 2005 with data from questionnaires and medical record reviews. The Swedish Board of Health and Welfare provided hospitalization and mortality data from 2005 through 2019. Cox regression analyses, adjusted for sex, age, educational level, smoking status, BMI, exacerbations, dyspnea score and comorbid diabetes or hypertension, assessed the association of comorbid heart disease with all-cause and cause-specific time to first hospitalization and death. Linear regression analyses, adjusted for the same variables, assessed this association with hospitalization days per year for those patients that had been hospitalized. Results: Of the 1071 patients, 262 (25%) had heart disease at baseline. Cox regression analysis showed a higher risk of hospitalization for patients with heart disease for all-cause (HR (95% CI) 1.55; 1.32-1.82), cardiovascular (2.14; 1.70-2.70) and other causes (1.27; 1.06-1.52). Patients with heart disease also had an increased risk of all-cause (1.77; 1.48-2.12), cardiovascular (3.40; 2.41-4.78) and other (1.50; 1.09-2.06) mortality. Heart disease was significantly associated with more hospitalization days per year of all-cause (regression coefficient 0.37; 95% CI 0.15-0.59), cardiovascular (0.57; 0.27-0.86) and other (0.37; 0.12-0.62) causes. No significant associations were found between heart disease and respiratory causes of hospitalization and death. Conclusion: Comorbid heart disease in patients with COPD is associated with an increased risk for all-cause hospitalization and mortality, mainly due to an increase of hospitalization and death of cardiovascular and other causes, but not because of respiratory disease. This finding advocates the need of a strong clinical focus on primary and secondary prevention of cardiovascular disease in patients with COPD.

Does multimorbidity result in de-prioritisation of COPD in primary care?

The aim of this study was to describe factors associated with having COPD regularly reviewed in primary care by a nurse or physician and assess whether there was de-prioritisation for COPD in multimorbid patients. We defined de-prioritisation as not having at least one check-up by a physician during a two-year period. Among 713 COPD patients in the Swedish PRAXIS study, 473 (66%) had at least one check-up during the study period (ending in 2014). Patients with check-ups were more likely to have three or more comorbid conditions (31.9% vs. 24.6%) and exacerbations (35.1% vs. 21.7%) than those without. Compared with those without comorbidity, those with three or more diagnoses had increased relative risk ratios (and 95% CI) for consultations discussing COPD with only a physician (5.63 (2.68-11.79)), COPD-nurse only (1.67 (0.83-3.37)) or both (2.11 (1.09-4.06)). COPD patients received more frequent check-ups considering COPD if they had comorbidity or a history of exacerbations. We found no evidence of de-prioritisation for COPD in multimorbid patients.

Adherence to CPAP therapy in Down syndrome: the population-based DISCOVERY study.

STUDY OBJECTIVES: Persons with Down syndrome (DS) have an increased risk of obstructive sleep apnea (OSA) needing continuous positive airway pressure (CPAP), but data on the therapy and outcomes in this population are scarce. We aimed to compare patient characteristics and outcomes of CPAP treatment for patients with OSA with and without DS. METHODS: This was a population-based, longitudinal study on patients initiating CPAP therapy between July 2010 and March 2018 in Sweden and a population-based sex- and age-matched control group (control:case ratio 5:1), with linked data from the Swedish National Patient Registry and the Prescribed Drug Registry (DISCOVERY study cohort). RESULTS: Patients with DS (n = 64) had a higher apnea-hypopnea index (51.7 ± 30.3 vs 36.8 ± 29.1 events/h, P < .001), Epworth Sleepiness Scale score (13.7 ± 5.9 vs 11.0 ± 4.9, P = .001), rate of previous surgery of tonsils and/or adenoids (21.9% vs 8.2%, P = .001), and more thyroid replacement hormone therapy (45.3% vs 7.8%, P < .001), but lower use of cardiovascular drugs (7.8% vs 22.3%, P = .003) compared with controls. At follow-up after 1.3 ± 0.9 years, there were no differences in nocturnal CPAP usage time (5.6 ± 2.4 vs 5.5 ± 2.0 hours, P = .77), CPAP adherence ≥ 4 hours/night (62% vs 65%, P = .93), or improvement in Epworth Sleepiness Scale score (-5.4 ± 6.8 vs -5.0 ± 2.0, P = .84) between DS and non-DS patients. CONCLUSIONS: OSA severity was substantially higher in patients with DS despite an increased rate of tonsil surgery. Treatment outcomes in terms of adherence and improved daytime sleepiness were comparable between groups, underlining the importance of both OSA diagnosis and treatment in patients with DS. CITATION: Svensson M, Ekström M, Sundh J, Ljunggren M, Grote L, Palm A. Adherence to CPAP therapy in Down syndrome: the population-based DISCOVERY study. J Clin Sleep Med. 2023;19(3):453-458.

Six-Minute Walking Test and 30 Seconds Chair-Stand-Test as Predictors of Mortality in COPD - A Cohort Study.

Background: Physical inactivity is strongly associated with worse prognosis in Chronic Obstructive Pulmonary Disease (COPD), and assessment of physical function is very important. The six minute walking test (6MWT) is an established test known to predict mortality in COPD, and 30 seconds chair stand test (30sCST) is a potential alternative test. The study aimed to investigate and compare the associations of 6MWT and 30sCSTs with mortality. Methods: Data on patient demographics, established mortality predictors and results from 6MWT and 30sCST were collected from 2016 to 2019 from 97 consecutively included patients with COPD. In August 2021, mortality data were retrieved from patient records. Correlation analysis of 6MWT and 30sCST was performed. The predictive abilities of 6MWT and 30sCST, respectively, were analyzed using Kaplan Meyer-curves and Cox regression with adjustment for sex, age, body mass index below 22 and comorbid cardiovascular disease. Results: A positive correlation between 6MWT and 30sCST was shown (r = 0.61, p < 0.0001). Independent associations with mortality were found for 6MWD 250-349 (HR (95% CI) 3.19 (1.12 to 9.10), p = 0.030) and 6MWD <250 (4.27 (1.69 to10.8), p = 0.002) compared with 6MWD ≥350 meters, and for 30sCST <4 (3.31 (1.03 to 10.6), p = 0.045) compared with 30sCST≥11 risings. When both 6MWT and 30sCST were included in the multivariable model, 6MWD 250-349 (3.09 (1.02 to 9.37), p = 0.046) and 6MWD <250 (3.57 (1.26 to 10.1), p = 0.016) compared with 6MWD ≥350 meters predicted mortality. Conclusion: 30sCST and 6MWT correlates moderately and are independently associated with mortality in patients with COPD. Although 6MWT is the best predictor of mortality, 30sCST may be used as an alternative to identify patients at risk.