Pulmonary volumes and signs of chronic airflow limitation in quantitative computed tomography.

BACKGROUND: Computed tomography (CT) offers pulmonary volumetric quantification but is not commonly used in healthy individuals due to radiation concerns. Chronic airflow limitation (CAL) is one of the diagnostic criteria for chronic obstructive pulmonary disease (COPD), where early diagnosis is important. Our aim was to present reference values for chest CT volumetric and radiodensity measurements and explore their potential in detecting early signs of CAL. METHODS: From the population-based Swedish CArdioPulmonarybioImage Study (SCAPIS), 294 participants aged 50-64, were categorized into non-CAL (n = 258) and CAL (n = 36) groups based on spirometry. From inspiratory and expiratory CT images we compared lung volumes, mean lung density (MLD), percentage of low attenuation volume (LAV%) and LAV cluster volume between groups, and against reference values from static pulmonary function test (PFT). RESULTS: The CAL group exhibited larger lung volumes, higher LAV%, increased LAV cluster volume and lower MLD compared to the non-CAL group. Lung volumes significantly deviated from PFT values. Expiratory measurements yielded more reliable results for identifying CAL compared to inspiratory. Using a cut-off value of 0.6 for expiratory LAV%, we achieved sensitivity, specificity and positive/negative predictive values of 72%, 85% and 40%/96%, respectively. CONCLUSION: We present volumetric reference values from inspiratory and expiratory chest CT images for a middle-aged healthy cohort. These results are not directly comparable to those from PFTs. Measures of MLD and LAV can be valuable in the evaluation of suspected CAL. Further validation and refinement are necessary to demonstrate its potential as a decision support tool for early detection of COPD.

Residual radiological opacities correlate with disease outcomes in ICU-treated COVID-19.

Background: Few studies consider both radiological and functional outcomes in COVID-19 survivors treated in the intensive care unit (ICU). We investigated clinical findings and pulmonary abnormalities on chest computed tomography (CT) and compared outcomes of severe versus mild-moderate acute respiratory distress syndrome (ARDS) on long-term follow-up. Methods: This longitudinal cohort study included 118 COVID-19 patients (median age, 58 years; 79% men). Thoracic CT scans were performed 4, 10, and 22 months after hospital discharge. Two independent blinded radiologists analyzed the 10 months scans and scored the radiology findings semi-quantitatively, as no/minor versus widespread opacities [low-radiology opacity grade (ROG) versus high-ROG]. ARDS severity was based on the PaO2/FiO2 ratio. The 6 min walk test (6MWT) was performed after 3 and 9 months, and lung diffusion capacity for carbon monoxide (DLCO) and lung volume measurement after 9 and 15 months. Dynamic spirometry was done at all time points. Residual symptoms and health-related quality-of-life (HRQL) were evaluated using validated questionnaires. Results: At 10 months, most patients (81/118; 69%) were classified as high-ROG, of which 70% had severe ARDS during hospitalisation; 69% of those with mild-moderate ARDS also had high-ROG. Patients with high-ROG had longer ICU stay and lower PaO2/FiO2 during hospitalisation (p < 0.01). At 9 months follow-up, patients with high-ROG had smaller lung volumes as % of predicted values [mean (±CI): 80 (77-84) vs. 93 (88-98) (p < 0.001)], lower DLCO as % of predicted values [74 (70-78) vs. 87 (82-92) (p < 0.001)], lower oxygen saturation during 6MWT (p = 0.02), and a tendency to more severe dyspnoea (p = 0.07), but no difference was found in HRQL compared with no/minor ROG (p = 0.92). A higher opacity score was related to lower DLCO at follow-up (r = -0.48, p < 0.001, Spearman rank test). Severe ARDS patients had slightly more severe fatigue at 9 months compared to mild-moderate, but no differences in dyspnoea or lung function at follow-up. Fibrotic-like changes were found in 93% of patients examined with CT scans at 2 years (55/118; 47%). Severe ARDS could predict widespread opacities (ROG > 25%) in most patients at follow-up at 10 months (AUC 0.74). Conclusion: Residual radiological abnormalities in ICU-treated COVID-19 patients, evaluated for up to 2 years, relate to persisting symptoms and impaired lung function, demanding careful follow-up regardless of ARDS severity at hospitalisation.

Factors most strongly associated with breathlessness in a population aged 50-64 years.

Background: Breathlessness is a troublesome and prevalent symptom in the population, but knowledge of related factors is scarce. The aim of this study was to identify the factors most strongly associated with breathlessness in the general population and to describe the shapes of the associations between the main factors and breathlessness. Methods: A cross-sectional analysis was carried out of the multicentre population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) of adults aged 50 to 64 years. Breathlessness was defined as a modified Medical Research Council breathlessness rating ≥2. The machine learning algorithm extreme gradient boosting (XGBoost) was used to classify participants as either breathless or nonbreathless using 449 factors, including physiological measurements, blood samples, computed tomography cardiac and lung measurements, lifestyle, health conditions and socioeconomics. The strength of the associations between the factors and breathlessness were measured by SHapley Additive exPlanations (SHAP), with higher scores reflecting stronger associations. Results: A total of 28 730 participants (52% women) were included in the study. The strongest associated factors for breathlessness were (in order of magnitude): body mass index ( SHAP score 0.39), forced expiratory volume in 1 s (0.32), physical activity measured by accelerometery (0.27), sleep apnoea (0.22), diffusing lung capacity for carbon monoxide (0.21), self-reported physical activity (0.17), chest pain when hurrying (0.17), high-sensitivity C-reactive protein (0.17), recent weight change (0.14) and cough (0.13). Conclusion: This large population-based study of men and women aged 50-64 years identified the main factors related to breathlessness that may be prevented or amenable to public health interventions.

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.

Large airway T cells in adults with former bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary Dysplasia (BPD) in infants born prematurely is a risk factor for chronic airway obstruction later in life. The distribution of T cell subtypes in the large airways is largely unknown. OBJECTIVE: To characterize cellular and T cell profiles in the large airways of young adults with a history of BPD. METHODS: Forty-three young adults born prematurely (preterm (n = 20), BPD (n = 23)) and 45 full-term-born (asthma (n = 23), healthy (n = 22)) underwent lung function measurements, and bronchoscopy with large airway bronchial wash (BW). T-cells subsets in BW were analyzed by immunocytochemistry. RESULTS: The proportions of both lymphocytes and CD8 + T cells in BW were significantly higher in BPD (median, 6.6%, and 78.0%) when compared with asthma (3.4% and 67.8%, p = 0.002 and p = 0.040) and healthy (3.8% and 40%, p < 0.001 and p < 0.001). In all adults born prematurely (preterm and BPD), lymphocyte proportion correlated negatively with forced vital capacity (r= -0.324, p = 0.036) and CD8 + T cells correlated with forced expiratory volume in one second, FEV1 (r=-0.448, p = 0.048). Correlation-based network analysis revealed that lung function cluster and BPD-birth cluster were associated with lymphocytes and/or CD4 + and CD8 + T cells. Multivariate regression analysis showed that lymphocyte proportions and BPD severity qualified as independent factors associated with FEV1. CONCLUSIONS: The increased cytotoxic T cells in the large airways in young adults with former BPD, suggest a similar T-cell subset pattern as in the small airways, resembling features of COPD. Our findings strengthen the hypothesis that mechanisms involving adaptive and innate immune responses are involved in the development of airway disease due to preterm birth.

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.

Factors important for health-related quality of life in men and women: The population based SCAPIS study.

INTRODUCTION: Health-related quality of life (HRQoL) is essential for human wellbeing, influenced by a complex interplay of factors, and is reported lower in women than men. We aimed to evaluate which factors were the most important for HRQoL in a middle-aged general population. METHODS: This was a cross-sectional, multi-centre study of 29,212 men (48%) and women (52%) aged 50-64 in the general population in Sweden. Physical and mental HRQoL (0-100) was assessed using the Short Form 12 questionnaire, and association was evaluated for 356 variables including demographics, lifestyle, symptoms, physiological measurements, and health conditions. Using machine learning, each variable´s importance for HRQoL was measured by an importance score, comparable to effect size, and summarised in 54 factors, in men and women separately. RESULTS: Men and women had similar mean and standard deviation (SD) scores for physical HRQoL (53.4 [SD 8.1] vs 51.4 [9.7]) and mental HRQoL (37.1 [5.0] vs 37.3 [5.4]). The most important factors for physical HRQoL were (importance score) physical activity (40), employment (36), pain (33), sleep (33), and sense of control (26). The most important factors for mental HRQoL were sense of control (18), physical activity (12), depression (12), pain (6), and employment (5). CONCLUSIONS: The factors important for HRQoL identified by this study are likely to be amenable to interventions, and our findings can support prioritising interventions. The identified factors need to be a target even before middle-age to lay the foundation for long and happy lives.

Mucins 3A and 3B Are Expressed in the Epithelium of Human Large Airway.

Aberrant mucus secretion is a hallmark of chronic obstructive pulmonary disease (COPD). Expression of the membrane-tethered mucins 3A and 3B (MUC3A, MUC3B) in human lung is largely unknown. In this observational cross-sectional study, we recruited subjects 45-65 years old from the general population of Stockholm, Sweden, during the years 2007-2011. Bronchial mucosal biopsies, bronchial brushings, and bronchoalveolar lavage fluid (BALF) were retrieved from COPD patients (n = 38), healthy never-smokers (n = 40), and smokers with normal lung function (n = 40). Protein expression of MUC3A and MUC3B in bronchial mucosal biopsies was assessed by immunohistochemical staining. In a subgroup of subjects (n = 28), MUC3A and MUC3B mRNAs were quantified in bronchial brushings using microarray. Non-parametric tests were used to perform correlation and group comparison analyses. A value of p < 0.05 was considered statistically significant. MUC3A and MUC3B immunohistochemical expression was localized to ciliated cells. MUC3B was also expressed in basal cells. MUC3A and MUC3B immunohistochemical expression was equal in all study groups but subjects with emphysema had higher MUC3A expression, compared to those without emphysema. Smokers had higher mRNA levels of MUC3A and MUC3B than non-smokers. MUC3A and MUC3B mRNA were higher in male subjects and correlated negatively with expiratory air flows. MUC3B mRNA correlated positively with total cell concentration and macrophage percentage, and negatively with CD4/CD8 T cell ratio in BALF. We concluded that MUC3A and MUC3B in large airways may be a marker of disease or may play a role in the pathophysiology of airway obstruction.

Presence of anti-modified protein antibodies in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Studies of autoimmunity and anti-citrullinated protein antibodies (ACPA) in idiopathic pulmonary fibrosis (IPF) have been confined to investigations of anti-cyclic citrullinated peptide (anti-CCP) antibodies which utilize synthetic peptides as surrogate markers for in vivo citrullinated antigens. We studied immune activation by analysing the prevalence of in vivo anti-modified protein antibodies (AMPA) in IPF. METHODS: We included patients with incident and prevalent IPF (N = 120), sex and smoking-matched healthy controls (HC) (N = 120) and patients with RA (N = 104). Serum (median time: 11 months [Q1-Q3: 1-28 months] from diagnosis) was analysed for presence of antibodies towards native and posttranslational modified (citrullinated [Cit, N = 25]; acetylated [Acet, N = 4] and homocitrullinated [Carb, N = 1]) peptides derived from tenascin (TNC, N = 9), fibrinogen (Fib, N = 11), filaggrin (Fil, N = 5), histone (N = 8), cathelicidin (LL37, N = 4) and vimentin (N = 5) using a custom-made peptide microarray. RESULTS: AMPA were more frequent and in increased levels in IPF than in HC (44% vs. 27%, p < 0.01), but less than in RA (44% vs. 79%, p < 0.01). We specifically observed AMPA in IPF towards certain citrullinated, acetylated and carbamylated peptides versus HC: tenascin (Cit(2033) -TNC2025-2040 ; Cit(2197) -TNC2177-2200 ; Cit(2198) -TNC2177-2200 ), fibrinogen (Cit(38,42) -Fibα36-50 ; Cit(72) -Fibß60-74 ) and filaggrin (Acet-Fil307-324 , Carb-Fil307-324 ). No differences in survival (p = 0.13) or disease progression (p = 0.19) between individuals with or without AMPA was observed in IPF. However, patients with incident IPF had better survival if AMPA were present (p = 0.009). CONCLUSION: A significant proportion of IPF patients present with specific AMPA in serum. Our results suggest autoimmunity as a possible characteristic for a subgroup of IPF that may affect disease outcome.

Rheumatoid Arthritis-Specific Autoimmunity in the Lung Before and at the Onset of Disease.

OBJECTIVE: The lung is implicated as a site for breach of tolerance prior to onset of seropositive rheumatoid arthritis (RA). To substantiate this, we investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from untreated early RA patients and anti-citrullinated protein antibody (ACPA)-positive individuals at risk for developing RA. METHODS: Single B cells (n = 7,680) were phenotyped and isolated from BAL samples from individuals at risk of RA (n = 3) and at RA diagnosis (n = 9). The immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n = 141). Monoclonal ACPAs were tested for reactivity patterns and binding to neutrophils. RESULTS: Using our single-cell approach, we found significantly increased proportions of B lymphocytes in ACPA+ compared to ACPA- individuals. Memory and double-negative B cells were prominent in all subgroups. Upon antibody re-expression, 7 highly mutated citrulline-autoreactive clones originating from different memory B cell subsets were identified, both in individuals at risk of RA and early RA patients. Lung IgG variable gene transcripts from ACPA+ individuals carried frequent mutation-induced N-linked Fab glycosylation sites (P < 0.001), often in the framework 3 of the variable region. Two of the lung ACPAs bound to activated neutrophils, 1 from an individual at risk of RA and 1 from an early RA patient. CONCLUSION: T cell-driven B cell differentiation resulting in local class switching and somatic hypermutation are evident in lungs before as well as in early stages of ACPA+ RA. Our findings add to the notion of lung mucosa being a site for initiation of citrulline autoimmunity preceding seropositive RA.

[Myositis-related interstitial lung disease - a systemic autoimmune desease often overlooked]. / Interstitiell lungsjukdom med myositantikroppar ofta förbisedd.

Interstitial lung disease can be the first sign of systemic autoimmune disease. If associated with myositis, interstitial lung disease may be the only symptom, with no presence of muscular weakness or other extramuscular manifestations. ANA-testing performed with indirect immune fluorescence may be negative. Testing for myositis antibodies should be considered as a step in the diagnostic process when strong clinical suspicion of interstitial lung disease of unknown origin is present. If interstitial lung disease is suspected, the patients should be referred to a specialist clinic for further investigation and, if possible, for discussion within a multidisciplinary team. Early suspicion of systemic inflammatory disease, rapid diagnosis and early start of treatment are crucial for future prognosis, quality of life and survival.

[Exercise training can improve dyspnea among persons with COPD and IPF]. / Fysisk aktivitet kan reducera dyspné vid KOL och lungfibros.

This article presents updated data regarding exercise training among persons with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Persons with stable COPD and IPF can improve quality of life, physical capacity and dyspnea after a period of exercise training. Persons with COPD exacerbation can improve quality of life and physical capacity, and decrease hospital re-admissions, if they start physical activity directly after the exacerbation. Persons with stable COPD and IPF should be recommended aerobic and muscle strengthening  training. For those with balance impairments balance training is also recommended. Persons with COPD exacerbation should be recommended activities of daily living (ADL) followed by muscle strengthening training and then aerobic training in the early recovery phase. Diagnosis-specific advice includes individually tailored exercise training, physical activity recommendations, breathing techniques, and that oxygen saturation during exercise should be ≥88 percent in COPD and ≥85 percent in IPF.

Lung perfusion disturbances in nonhospitalized post-COVID with dyspnea-A magnetic resonance imaging feasibility study.

BACKGROUND: Dyspnea is common after COVID-19. Though the underlying mechanisms are largely unknown, lung perfusion abnormalities could contribute to lingering dyspnea. OBJECTIVES: To detect pulmonary perfusion disturbances in nonhospitalized individuals with the post-COVID condition and persistent dyspnea 4-13 months after the disease onset. METHODS: Individuals with dyspnea and matched healthy controls were recruited for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), a 6-min walk test, and an assessment of dyspnea. The DCE-MRI was quantified using two parametric values: mean time to peak (TTP) and TTP ratio, reflecting the total lung perfusion resistance and the fraction of lung with delayed perfusion, respectively. RESULTS: Twenty-eight persons with persistent dyspnea (mean age 46.5 ± 8.0 years, 75% women) and 22 controls (mean age 44.1 ± 10.8 years, 73% women) were included. There was no systematic sex difference in dyspnea. The post-COVID group had no focal perfusion deficits but had higher mean pulmonary TTP (0.43 ± 0.04 vs. 0.41 ± 0.03, p = 0.011) and TTP ratio (0.096 ± 0.052 vs. 0.068 ± 0.027, p = 0.032). Post-COVID males had the highest mean TTP of 0.47 ± 0.02 and TTP ratio of 0.160 ± 0.039 compared to male controls and post-COVID females (p = 0.001 and p < 0.001, respectively). Correlations between dyspnea and perfusion parameters were demonstrated in males (r = 0.83, p < 0.001 for mean TTP; r = 0.76, p = 0.003 for TTP ratio), but not in females. CONCLUSIONS: DCE-MRI demonstrated late contrast bolus arrival in males with post-COVID dyspnea, suggestive of primary vascular lesions or secondary effects of hypoxic vasoconstriction. Since this effect was not regularly observed in female patients, our findings suggest sex differences in the mechanisms underlying post-COVID dyspnea, which warrants further investigation in dedicated trials.

[Lung complications in adults due to premature birth: an increasint patient population that needs to be followed up]. / Lungkomplikationer hos vuxna ibland kopplade till tidig födsel.

Infants born prematurely are susceptible for respiratory disease later in life. In particular, children born before 32 gestational weeks, treated with oxygen or respiratory support and diagnosed with bronchopulmonary dysplasia (BPD) have the highest risk.  Airways obstruction is the major lung function impairment, and it can be aggravated in adult life when age-related loss of lung function takes place. Events both in the neonatal period but also during childhood may, at least partly, explain the relatively large proportion of neversmokers with chronic obstructive pulmonary disease (COPD). Individuals born prematurely, specifically those with previous BPD, should have regular follow-ups in order to detect respiratory impairment.

Glucose Homeostasis in Relation to Neutrophil Mobilization in Smokers with COPD.

Purpose: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are common comorbidities in chronic obstructive pulmonary disease (COPD), but the underlying pathogenic mechanisms are poorly understood. Given that these morbidities all display increased neutrophil mobilization, the current study aimed to address whether glucose homeostasis relates to signs of neutrophil mobilization in COPD. Methods: The study population included healthy non-smokers (HNS) and long-term smokers without (LTS) and with COPD (LTS+COPD). No subject had T2DM or MetS. Serum cotinine was quantified to evaluate current smoking. Capillary blood glucose was measured after overnight fasting and during an oral glucose tolerance test (OGTT). Neutrophils were quantified in blood and bronchoalveolar lavage samples (BAL). The neutrophil-related cytokines IL-36α, -ß and -γ were quantified (ELISA) along with IL-6, IL-8, INF-γ and CXCL10 (U-Plex®) in plasma and cell-free BAL fluid (BALF). In addition, we quantified neutrophil elastase (ELISA) and net proteinase activity (substrate assay) in BALF. Results: The LTS+COPD group had lower fasting glucose, greater change in glucose during OGTT and higher neutrophil concentrations in BAL and blood compared with HNS. Fasting glucose correlated in a positive manner with blood neutrophil concentration, forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) and FEV1 (% of predicted) in LTS+COPD. In this group, the concentration of IL-36α in BALF correlated in a negative manner with fasting glucose, blood neutrophil concentration and FEV1, while the CXCL10 concentration in BALF correlated in a negative manner with glucose at the end of OGTT (120 min). We observed no corresponding correlations for neutrophil elastase, net proteinase or gelatinase activity. Conclusion: In smokers with COPD, altered glucose homeostasis is associated with local and systemic signs of increased neutrophil mobilization, but not with local proteinases. This suggests that other specific aspects of neutrophil mobilization constitute pathogenic factors that affect glucose homeostasis in COPD.

Accelerometer derived physical activity patterns in 27.890 middle-aged adults: The SCAPIS cohort study.

The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50-64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an "at-risk" behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.

Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease.

BACKGROUND: The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease. METHODS: Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure. RESULTS: In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramér's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramér's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes. CONCLUSION: In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.

Distal Lung Microenvironment Triggers Release of Mediators Recognized as Potential Systemic Biomarkers for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an unmet need of biomarkers that can aid in the diagnostic and prognostic assessment of the disease and response to treatment. In this two-part explorative proteomic study, we demonstrate how proteins associated with tissue remodeling, inflammation and chemotaxis such as MMP7, CXCL13 and CCL19 are released in response to aberrant extracellular matrix (ECM) in IPF lung. We used a novel ex vivo model where decellularized lung tissue from IPF patients and healthy donors were repopulated with healthy fibroblasts to monitor locally released mediators. Results were validated in longitudinally collected serum samples from 38 IPF patients and from 77 healthy controls. We demonstrate how proteins elevated in the ex vivo model (e.g., MMP7), and other serum proteins found elevated in IPF patients such as HGF, VEGFA, MCP-3, IL-6 and TNFRSF12A, are associated with disease severity and progression and their response to antifibrotic treatment. Our study supports the model's applicability in studying mechanisms involved in IPF and provides additional evidence for both established and potentially new biomarkers in IPF.