Biomarker Profiles Associated with COVID-19 Severity and Mortality.

INTRODUCTION: The aim of this study was to analyze biomarkers that might predict the severity and progression of the SARS-CoV-2 infection, both in the acute phase and after recovery. METHODS: Unvaccinated patients infected with the original strain of COVID-19 requiring ward (Group 1, n = 48) or ICU (Group 2, n = 41) admission were included. At the time of admission (visit 1), a clinical history was acquired, and blood samples were obtained. One and six months after discharge from the hospital (visits 2 and 3, respectively), a clinical history, lung function tests, and blood samples were carried out. At visit 2, patients also underwent a chest CT scan. Different cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, G-CSF, GM-CSF, IFN-É£, MCP-1, MIP-1ß, and TNF-α) and lung fibrosis biomarkers (YKL-40 and KL-6) were measured in blood samples obtained at visits 1, 2, and 3. RESULTS: At visit 1, IL-4, IL-5, and IL-6 levels were higher in Group 2 (p = 0.039, 0.011, and 0.045, respectively), and IL-17 and IL-8 levels were higher in Group 1 (p = 0.026 and 0.001, respectively). The number of patients in Groups 1 and 2 who died during hospitalization was 8 and 11, respectively. YKL-40 and KL-6 levels were higher in patients who died. Serum YKL-40 and KL-6 levels determined at visit 2 correlated negatively with FVC (p = 0.022 and p = 0.024, respectively) and FEV1 (p = 0.012 and p = 0.032, respectively) measured at visit 3. KL-6 levels also correlated negatively with the diffusing capacity of the lungs for carbon monoxide (DLCO, p = 0.001). CONCLUSIONS: Patients who required ICU admission had higher levels of Th2 cytokines, while patients admitted to the ward showed an innate immune response activation, with IL-8 release and Th1/Th17 lymphocyte contribution. Increased levels of YKL-40 and KL-6 were associated with mortality in COVID-19 patients.

Promotion of physical activity after hospitalization for COPD exacerbation: A randomized control trial.

BACKGROUND AND OBJECTIVE: Physical activity worsens during exacerbations of chronic obstructive pulmonary disease (COPD) and notably after hospitalizations. Pedometer-based interventions are useful to increase physical activity in stable patients with COPD. However, there is little information concerning the implementation of such programs following severe exacerbation. This study assessed the efficacy of a physical activity program after hospitalization for a COPD exacerbation. METHODS: We performed a prospective, 12-week, parallel group, assessor-blinded, randomized control trial in COPD patients hospitalized for an exacerbation. After discharge, physical activity and other secondary variables were assessed. Patients were allocated (1:1) to a physical activity promotion program (intervention group, IG) or usual care (control group, CG). Based on a motivational interview and accelerometer physical activity assessment, a patient-tailored, pedometer-based, progressive and target-driven program was designed. Linear mixed effect models were used to analyse between-group differences. RESULTS: Forty-six out of 61 patients recruited were randomized and 43 (IG = 20, CG = 23) completed the study. In-hospital and baseline characteristics were similar in both groups. After 12 weeks of intervention, the mean steps difference between groups was 2093 steps/day, p = 0.018, 95% CI 376-4012, favouring the IG. Only the IG significantly increased the number of steps/day compared to baseline (mean difference [95% CI] 2932 [1069-4795] steps; p = 0.004). There were no other between-group differences. CONCLUSION: After hospitalization for a COPD exacerbation, a patient-tailored physical activity program based on a motivational interview and the use of pedometers, with progressive and customized targets, improved the number of steps/day.

Demographic, exposure and clinical characteristics in a multinational registry of engineered stone workers with silicosis.

OBJECTIVES: To investigate differences in workplace exposure, demographic and clinical findings in engineered stone (ES) workers from a multinational consortium using the Engineered Stone Silicosis Investigators (ESSI) Global Silicosis Registry. METHODS: With ethics board approval in Israel, Spain, Australia and the USA, ES workers ages 18+ with a physician diagnosis of work-related silicosis were enrolled. Demographic, occupational, radiologic, pulmonary function and silica-related comorbidity data were compared cross-sectionally among countries using analysis of variance, Fisher's exact tests and logistic regression. RESULTS: Among 169 ES workers with silicosis, most were men, with mean age 51.7 (±11.4) years. Mean work tenure in stone fabrication or masonry was 19.9 (±9.8) years. Different methods of case ascertainment explained some inter-country differences, for example, workers in Queensland, Australia with a state-based surveillance program were likely to be identified earlier and with shorter work tenure. Overall, 32.5% of workers had progressive massive fibrosis, the most severe form of dust-related pneumoconiosis, of whom 18.5% reported ≤10 years of work tenure. Lung function impairment including restriction, reduced diffusion capacity and hypoxaemia was common, as was autoimmunity. CONCLUSIONS: Findings from a multinational registry represent a unique effort to compare demographic, exposure and clinical information from ES workers with silicosis, and suggest a substantial emerging population of workers worldwide with severe and irreversible silica-associated diseases. This younger worker population is at high risk for disease progression, multiple comorbidities and severe disability. The ESSI registry provides an ongoing framework for investigating epidemiological trends and developing prospective studies for prevention and treatment of these workers.

Predictors of respiratory complications in patients with C5-T5 spinal cord injuries.

STUDY DESIGN: Retrospective chart audit. OBJECTIVES: Describing the respiratory complications and their predictive factors in patients with acute traumatic spinal cord injuries at C5-T5 level during the initial hospitalization. SETTING: Hospital Vall d'Hebron, Barcelona. METHODS: Data from patients admitted in a reference unit with acute traumatic injuries involving levels C5-T5. Respiratory complications were defined as: acute respiratory failure, respiratory infection, atelectasis, non-hemothorax pleural effusion, pulmonary embolism or haemoptysis. Candidate predictors of these complications were demographic data, comorbidity, smoking, history of respiratory disease, the spinal cord injury characteristics (level and ASIA Impairment Scale) and thoracic trauma. A logistic regression model was created to determine associations between potential predictors and respiratory complications. RESULTS: We studied 174 patients with an age of 47.9 (19.7) years, mostly men (87%), with low comorbidity. Coexistent thoracic trauma was found in 24 (19%) patients with cervical and 35 (75%) with thoracic injuries (p < 0.001). Respiratory complications were frequent (53%) and were associated to longer hospital stay: 83.1 (61.3) and 45.3 (28.1) days in patients with and without respiratory complications (p < 0.001). The strongest predictors of respiratory complications were: previous respiratory disease (OR 5.4, 95% CI: 1.5-19.2), complete motor function impairment (AIS A-B) (OR 4.7, 95% CI: 2.4-9.5) and concurrent chest trauma (OR 3.73, 95% CI: 1.8-7.9). CONCLUSIONS: Respiratory complications are common in traumatic spinal cord injuries between C5-T5. We identified previous respiratory disease, complete motor function impairment and the coexistence of thoracic trauma as predictors of respiratory complications. Identification of patients at risk might help clinicians to implement preventive strategies.

The dyspnoea-inactivity vicious circle in COPD: development and external validation of a conceptual model.

The vicious circle of dyspnoea-inactivity has been proposed, but never validated empirically, to explain the clinical course of chronic obstructive pulmonary disease (COPD). We aimed to develop and validate externally a comprehensive vicious circle model.We utilised two methods. 1) Identification and validation of all published vicious circle models by a systematic literature search and fitting structural equation models to longitudinal data from the Spanish PAC-COPD (Phenotype and Course of COPD) cohort (n=210, mean age 68 years, mean forced expiratory volume in 1 s (FEV1) 54% predicted), testing both the hypothesised relationships between variables in the model ("paths") and model fit. 2) Development of a new model and external validation using longitudinal data from the Swiss and Dutch ICE COLD ERIC (International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts) cohort (n=226, mean age 66 years, mean FEV1 57% predicted).We identified nine vicious circle models for which structural equation models confirmed most hypothesised paths but showed inappropriate fit. In the new model, airflow limitation, hyperinflation, dyspnoea, physical activity, exercise capacity and COPD exacerbations remained related to other variables and model fit was appropriate. Fitting it to ICE COLD ERIC, all paths were replicated and model fit was appropriate.Previously published vicious circle models do not fully explain the vicious circle concept. We developed and externally validated a new comprehensive model that gives a more relevant role to exercise capacity and COPD exacerbations.

Intra-atrial re-entrant tachycardia in congenital heart disease: types and relation of isthmus to atrial voltage.

Background: Intra-atrial re-entrant tachycardia (IART) is a frequent and severe complication in patients with congenital heart disease (CHD). Cavotricuspid isthmus (CTI)-related IART is the most frequent mechanism. However, due to fibrosis and surgical scars, non-CTI-related IART is also frequent. Objective: The main objective of this study was to describe the types of IART and circuit locations and to define a cut-off value for unhealthy tissue in the atria. Methods and results: This observational study included all consecutive patients with CHD who underwent a first ablation procedure for IART from January 2009 to December 2015 (94 patients, 39.4% female, age: 36.55 ± 14.9 years, 40.4% with highly complex cardiac disease). During the study, 114 IARTs were ablated (1.21 ± 0.41 IARTs per patient). Cavotricuspid isthmus-related IART was the only arrhythmia in 51% (n = 48) of patients, non-CTI-related IART was the only mechanism in 27.7% (n = 26), and 21.3% of patients (n = 20) presented both types of IART. In cases of non-CTI-related IART, the most frequent location of IART isthmus was the lateral or posterolateral wall of the venous atria, and a voltage cut-off value for unhealthy tissue in the atria of 0.5 mV identified 95.4% of IART isthmus locations. Conclusion: In our population with a high proportion of complex CHD, CTI-related IART was the most frequent mechanism, although non-CTI-related IART was present in 49% of patients (alone or with concomitant CTI-related IART). A cut-off voltage of 0.5 mV could identify 95.4% of the substrates in non-CTI-related IART.

Intra-atrial re-entrant tachycardia in patients with congenital heart disease: factors associated with disease severity.

Aim: Intra-atrial re-entrant tachycardia (IART) is a common complication in patients with congenital heart disease (CHD) and is related to increased morbidity and mortality. Few reports have been published about factors associated to IART severity. The aim of this study is to analyse factors associated to severe clinical presentation of IART. Methods and Results: Observational study of all consecutive CHD patients who underwent a first IART ablation from January 2009 to December 2015 (94 patients, 39.4% female, and age: 36.55 ± 14.9 years). Severe clinical presentation was defined as heart failure, syncope, shock, electromechanical dissociation (EMD), or aborted sudden death. The majority of patients had moderately or highly complex cardiac defect (90.4%). Types of IART included cavotricuspid isthmus(CTI) dependent in 51% (48), non-CTI-related in 22.3% (20), and both types in 27.7% (26). In 38 patients (40.4%), a severe event occurred and in 16 (17%), the symptoms included shock, syncope, sudden death, or EMD. In 21 (22.3%), severe symptoms were the first manifestation of IART. In multivariate analysis, transposition of the great arteries (TGA) with right systemic ventricle (OR 5.32, 95% C.I. 1.6-7.02, P = 0.0005) and severe dilation of the venous atrium (VsA) (OR 4.17; 95% CI 1.4-8.12, P = 0.0009) were factors independently associated with severity. Conclusion: In our series of 94 CHD patients with a high proportion of moderately to highly complex cardiac defects, severe consequences of IART were frequent. Transposition of the great arteries with systemic right ventricle and severe dilation of VsA were independently associated to severity. Early invasive procedures should be considered for these high-risk patients.

Inspiratory capacity-to-total lung capacity ratio and dyspnoea predict exercise capacity decline in COPD.

BACKGROUND AND OBJECTIVE: Exercise capacity decline is a predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). Static pulmonary hyperinflation is a key determinant of exercise performance, but its effect on the longitudinal decline in exercise capacity remains unknown. We aimed to study the relationship between the inspiratory capacity-to-total lung capacity (IC/TLC) ratio and exercise capacity decline in COPD. METHODS: We measured IC/TLC and other relevant clinical and functional variables in 342 clinically stable patients with COPD. The 6-min walk distance (6MWD) was determined at recruitment and after a mean ± SD of 1.7 ± 0.3 years. The annual rate of change in 6MWD was calculated. Multiple imputation to account for losses during follow up was implemented, and multivariate regression was used to analyze predictive factors of 6MWD decline. RESULTS: Mean decline rate in the 6MWD was 21.9 ± 34.1 m/year. In the bivariate analysis, patients with lower levels of IC/TLC had greater 6MWD decline (-27.4 ± 42.5, -24.9 ± 36.5 and -13.4 ± 39.9 m/year in the first, second and third tertile of IC/TLC, respectively; P-for-trend = 0.018). From other potential risk factors considered, dyspnoea, health status, serum C-reactive protein and Borg dyspnoea score at the end of the exercise test were related to exercise capacity decline. In the multivariate regression model, only IC/TLC (ß = 0.7 m/year per each percentage unit of IC/TLC; P = 0.007) and dyspnoea (mMRC ≥ 2) (ß = -14.6 m/year; P = 0.013) were associated with the annual rate of 6MWD change. CONCLUSION: IC/TLC and dyspnoea in clinically stable patients with COPD predict their exercise capacity decline and may help to guide early therapeutic interventions.

Benefits of physical activity on COPD hospitalisation depend on intensity.

The present study aims to disentangle the independent effects of the quantity and the intensity of physical activity on the risk reduction of chronic obstructive pulmonary disease (COPD) hospitalisations.177 patients from the Phenotype Characterization and Course of COPD (PAC-COPD) cohort (mean±sd age 71±8 years, forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro 2 Armband accelerometer (BodyMedia, Pittsburgh, PA, USA) for eight consecutive days, providing data on quantity (steps per day, physically active days and daily active time) and intensity (average metabolic equivalent tasks) of physical activity. Information on COPD hospitalisations during follow-up (2.5±0.8 years) was obtained from validated centralised datasets. During follow-up 67 (38%) patients were hospitalised. There was an interaction between quantity and intensity of physical activity in their effects on COPD hospitalisation risk. After adjusting for potential confounders in the Cox regression model, the risk of COPD hospitalisation was reduced by 20% (hazard ratio (HR) 0.79, 95% CI 0.67-0.93; p=0.005) for every additional 1000 daily steps at low average intensity. A greater quantity of daily steps at high average intensity did not influence the risk of COPD hospitalisations (HR 1.01, p=0.919). Similar results were found for the other measures of quantity of physical activity. Greater quantity of low-intensity physical activity reduces the risk of COPD hospitalisation, but high-intensity physical activity does not produce any risk reduction.

Characterisation and prognosis of undiagnosed chronic obstructive pulmonary disease patients at their first hospitalisation.

BACKGROUND: Under-diagnosis of COPD is an important unmet medical need. We investigated the characteristics and prognosis of hospitalised patients with undiagnosed COPD. METHODS: The PAC-COPD cohort included 342 COPD patients hospitalised for the first time for an exacerbation of COPD (2004-2006). Patients were extensively characterised using sociodemographic, clinical and functional variables, and the cohort was followed-up through 2008. We defined "undiagnosed COPD" by the absence of any self-reported respiratory disease and regular use of any pharmacological respiratory treatment. RESULTS: Undiagnosed COPD was present in 34% of patients. They were younger (mean age 66 vs. 68 years, p = 0.03), reported fewer symptoms (mMRC dyspnoea score, 2.1 vs. 2.6, p < 0.01), and had a better health status (SGRQ total score, 29 vs. 40, p < 0.01), milder airflow limitation (FEV1% ref., 59% vs. 49%, p < 0.01), and fewer comorbidities (two or more, 40% vs. 56%, p < 0.01) when compared with patients with an established COPD diagnosis. Three months after hospital discharge, 16% of the undiagnosed COPD patients had stopped smoking (vs. 5%, p = 0.019). During follow-up, annual hospitalisation rates were lower in undiagnosed COPD patients (0.14 vs. 0.25, p < 0.01); however, this difference disappeared after adjustment for severity. Mortality was similar in both groups. CONCLUSIONS: Undiagnosed COPD patients have less severe disease and lower risk of re-hospitalisation when compared with hospitalised patients with known COPD.

Air pollution and biomarkers of systemic inflammation and tissue repair in COPD patients.

The origin(s) of systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated the impact of exposure to ambient air pollution on systemic biomarkers of inflammation (C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-6, IL-8 and fibrinogen) and tissue repair (hepatocyte growth factor (HGF)) in 242 clinically stable COPD patients (mean age 67.8 years and forced expiratory volume in 1 s 71.3% predicted) in Barcelona, Spain, in 2004-2006. A spatiotemporal exposure assessment framework was applied to predict ambient nitrogen dioxide (NO2) and levels of particles with a 50% cut-off aerodynamic diameter of 2.5 µm (PM2.5) at each participant's home address during 10 periods of 24 h (lags 1-10) and 1 year prior to the blood sampling date. We used linear regression models to estimate associations between biomarkers and exposure levels. An interquartile range (IQR) increase in NO2 exposure in lag 5 was associated with 51%, 10% and 9% increases in CRP, fibrinogen and HGF levels respectively. We also observed 12% and 8% increases in IL-8 associated with an IQR increase in NO2 exposure in lag 3 and over the year before sampling, respectively. These increases were larger in former smokers. The results for PM2.5 were not conclusive. These results show that exposure to ambient NO2 increases systemic inflammation in COPD patients, especially in former smokers.

Hospital admissions and exercise capacity decline in patients with COPD.

Exercise capacity declines with time and is an important determinant of health status and prognosis in patients with chronic obstructive pulmonary disease (COPD). We hypothesised that hospital admissions are associated with exercise capacity decline in these patients. Clinical and functional variables were collected for 342 clinically stable COPD patients. The 6-min walk distance (6MWD) was determined at baseline and after a mean±sd of 1.7±0.3 years. Information on hospitalisations during follow-up was obtained from centralised administrative databases. Linear regression was used to model changes in exercise capacity. Patients were mostly male (92%), with mean±sd age 67.9±8.6 years, post-bronchodilator forced expiratory volume in 1 s 54±17% predicted and baseline 6MWD 433±93 m. During follow-up, 6MWD decreased by 21.9±51.0 m·year(-1) and 153 (45%) patients were hospitalised at least once. Among patients admitted only for COPD-related causes (50% of those ever admitted), the proportion presenting a clinically significant loss of 6MWD was higher than in patients admitted for only nonrespiratory conditions (53% versus 29%, p=0.040). After adjusting for confounders, annual 6MWD decline was greater (26 m·year(-1), 95% CI 13-38 m·year(-1); p<0.001) in patients with more than one all-cause hospitalisation per year, as compared with those with no hospitalisations. Hospitalisations are related to a greater decline in exercise capacity in COPD.

Echocardiographic abnormalities in patients with COPD at their first hospital admission.

Cardiovascular disease accounts for significant morbidity and mortality in chronic obstructive pulmonary disease (COPD). Its prevalence and mechanisms of association have not been elucidated. The study aimed to assess the prevalence of echocardiographic abnormalities and potential risk factors in patients with COPD at their first exacerbation requiring hospital admission. Transthoracic echocardiography was prospectively performed in 342 patients (forced expiratory volume in 1 s 52 ± 16% predicted) 3 months after discharge. Significant cardiac alterations were present in 64% of patients; 27% left- and 48% right-heart disorders. The most common were right ventricle enlargement (30%) and pulmonary hypertension (19%). Left ventricle enlargement was present in 6%, left ventricle systolic dysfunction in 13%, left ventricle diastolic impairment in 12% and left atrial dilatation in 29%. Echocardiographic abnormalities were unrelated to COPD severity and were more frequent in patients with self-reported cardiac disease. They were also observed in 63% of patients with no known cardiac disease or cardiovascular risk factors other than smoking. We conclude that cardiac abnormalities are highly prevalent in COPD patients at the time of their first severe exacerbation, even in the absence of established cardiac disease or cardiovascular risk factors. Considering the prognostic and therapeutic implications of cardiac comorbidity, echocardiography should be considered in the assessment of patients with clinically significant COPD.

Poor sleep quality, COPD severity and survival according to CASIS and Pittsburgh questionnaires.

Poor sleep quality is frequent among COPD patients and it has been related to worse outcomes. The objective of this study was to compare the COPD and Asthma Sleep Impact Scale (CASIS) and the generic Pittsburgh Sleep Quality Index (PSQI) questionnaires as reliable tools for evaluating sleep quality and its relationship with COPD characteristics and survival. Stable COPD patients were prospectively evaluated. Anthropometric, sociodemographic, comorbidity, lung function and treatment data were collected. All patients completed CASIS and PSQI, mMRC dyspnea severity scale, COPD Assessment Test (CAT), sleep apnoea STOP-Bang and Hospital Anxiety and Depression Scale (HADS) questionnaires. Body mass index, airflow Obstruction, Dyspnea and Exacerbations (BODEx) index was calculated. Life status was determined after a mean follow-up of 3.7 (SD 1) years. We included 200 patients, 69.5% male, mean age 65.8 (9) years. Poor sleep was detected in 100 (50%) and 84 patients (42%) according to PSQI and CASIS questionnaires, respectively, with an agreement of 63%. Poor sleep was related to female gender, more severe dyspnea and worse BODEx, HADS and CAT scores according to both questionnaires. PSQI was associated to chronic pain or inferior urinary tract symptoms and CASIS to exacerbations, shorter walked distance in the 6-min walking test and treatment with oral corticosteroids or chronic oxygen. Thirty nine (19.5%) patients died during follow-up. Mortality was not associated to PSQI nor CASIS results. Unlike PSQI, CASIS is more related to COPD severity and its results are not influenced by comorbidities with known impact on sleep quality. In our sample, poor sleep quality was not associated with increased mortality.

Poor sleep is associated with deficits of attention in COPD patients.

BACKGROUND: Poor sleep and attention deficits are common in COPD. OBJECTIVES: To assess the relationship between self-reported poor sleep and attention deficits in COPD. We also studied the association between self-reported sleep and the attention tests with the objective characteristics of sleep. METHODS: Fifty-nine COPD patients were prospectively studied. Self-reported sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Objective characteristics of sleep were assessed by actigraphy and polysomnography. Attention was evaluated with the Oxford sleep resistance test (OSLER) and the Psychomotor vigilance test (PVT). RESULTS: 28 (47 %) patients referred poor sleep (PSQI >5). In the OSLER test they showed earlier sleep onset than patients with good sleep, median (Interquartil range): 31.2 min (25.4-40) vs 40 min (28.5-40), p: 0.048. They also spent more time making errors: 4.5 % (0.6-7.6) of total test time vs 0.7 % (0.2-5.3), p: 0.048. In PVT, patients with poor sleep presented a greater dispersion of the reaction time values with a higher value in the slowest 10 % of the reactions, 828 (609-1667) msec. vs 708 (601-993) msec, p: 0.028. No association was found between self-reported poor sleep and objective sleep variables. We found no correlation between OSLER and PVT results and polysomnographic variables except between sleep efficiency and PVT response speed (ß: 0.309, p: 0.018). CONCLUSION: Self-reported poor sleep in COPD is associated with attention deficits. Sleep quality should be included in future studies of this facet of cognition in COPD, as well as to assess its potential usefulness as a therapeutic target.

Cured meat consumption increases risk of readmission in COPD patients.

Recent studies have shown that a high dietary intake of cured meat increases the risk of chronic obstructive pulmonary disease (COPD) development. However, its potential effects on COPD evolution have not been tested. We aimed to assess the association between dietary intake of cured meat and risk of COPD readmission in COPD patients. 274 COPD patients were recruited during their first COPD admission between 2004 and 2006, provided information on dietary intake of cured meat during the previous 2 yrs, and were followed until December 31, 2007 (median follow-up 2.6 yrs). Associations between cured meat intake and COPD admissions were assessed using parametric regression survival-time models. Mean ± SD age was 68 ± 8 yrs, 93% of patients were male, 42% were current smokers, mean post-bronchodilator forced expiratory volume in 1 s (FEV(1)) was 53 ± 16% predicted, and median cured meat intake was 23 g · day(-1). After adjusting for age, FEV(1), and total caloric intake, high cured meat intake (more than median value) increased the risk of COPD readmission (adjusted HR 2.02, 95% CI 1.31-3.12; p=0.001). High cured meat consumption increases the risk of COPD readmission in COPD patients. The assessment of the effectiveness of healthy diet advice should be considered in the future.

Decreased Expression of EC-SOD and Fibulin-5 in Alveolar Walls of Lungs From COPD Patients.

INTRODUCTION: The aim of this study is to analyze the expression of the main oxidant scavenger superoxide dismutase (EC-SOD), its main binding protein Fibulin-5 and several oxidative and nitrosative-derived products in the lung of COPD patients and controls. MATERIALS AND METHODS: Lung tissue samples from 19 COPD patients and 20 control subjects were analyzed. The architecture of elastic fibres was assessed by light and electron microscope histochemical techniques, and levels of EC-SOD and fibulin-5 were analyzed by immunohistochemistry and RT-PCR. The impact of oxidative stress on the extracellular matrix was estimated by immunolocalization of 4-hydroxynonenal (4-HNE), malondialdehyde (MDA) and 3-nitrotyrosine (3-NYT) adducts. RESULTS: Alveolar walls of COPD patients exhibited abnormal accumulations of collapsing elastic fibres, showing a pierced pattern in the amorphous component. The semiquantitative analysis revealed that COPD patients have a significantly reduced expression of both EC-SOD and fibulin-5 (0.59±0.64 and 0.62±0.61, respectively) in alveolar, bronchiolar and arteriolar walls compared to control subjects (1.39±0.63 and 1.55±0.52, respectively, p<0.05). No significant changes in mRNA levels of these proteins were observed between groups. Among the oxidation markers, malondialdehyde was the best in distinguishing COPD patients. CONCLUSIONS: COPD patients show a reduced expression of EC-SOD and fibulin-5 in the lung interstitium. Paralleling the reduction of EC-SOD levels, the decrease of fibulin-5 expression in COPD lungs supports the hypothesis of an impaired pulmonary antioxidant response in COPD patients.

Impact of home CPAP-treated obstructive sleep apnea on COVID-19 outcomes in hospitalized patients.

STUDY OBJECTIVES: To investigate the association between moderate or severe obstructive sleep apnea treated with home continuous positive airway pressure (CPAP) and severe coronavirus disease 2019 (COVID-19). METHODS: Retrospective study of patients admitted for COVID-19. Patients with obstructive sleep apnea treated with home CPAP were identified and for each of them we selected 5 patients admitted consecutively in the following hours. The main outcome of the study was the development of severe COVID-19, defined as 1) death or 2) a composite outcome of death or the presence of severe hypoxemic respiratory failure at or during admission. The association between CPAP-treated obstructive sleep apnea and these outcomes was estimated by logistic regression analysis after applying inverse probability of treatment weighting using a propensity score-weighting approach. RESULTS: Of the 2,059 patients admitted, 81 (3.9%) were receiving treatment with home CPAP. Among the 486 patients included in the study, 19% died and 39% presented the composite outcome. The logistic regression analysis did not show an association of CPAP treatment either with death (odds ratio [OR]: 0.684; 95% confidence interval [CI]: 0.332-1.409; P = .303) or with the composite outcome (OR: 0.779; 95% CI: 0.418-1.452; P = .432). Death was associated with age (OR: 1.116; 95% CI: 1.08-1.152; P < .001) and number of comorbidities (OR: 1.318; 95% CI: 1.065-1.631; P = .012), and the composite outcome was associated with male sex (OR: 2.067; 95% CI: 1.19-3.589; P = .01) and number of comorbidities (OR: 1.241; 95% CI: 1.039-1.484; P = .018). CONCLUSIONS: In hospitalized patients with COVID-19, prior obstructive sleep apnea treated with home CPAP is not independently associated with worse outcomes. CITATION: Sampol J, Sáez M, Martí S, et al. Impact of home CPAP-treated obstructive sleep apnea on COVID-19 outcomes in hospitalized patients. J Clin Sleep Med. 2022;18(7):1857-1864.

Asbestos Exposure and Severity of COVID-19.

BACKGROUND: The aim of this study was to analyse the relationship between occupational exposure to asbestos and the severity of SARS-CoV-2 infection. METHODS: We evaluated patients who survived admission in our centre for COVID-19 pneumonia. Demographic, analytical, and clinical variables were collected during admission. After discharge, a previously validated occupational exposure to asbestos questionnaire was administered. Spirometry, CO diffusion test, the 6-min walk test, and high-resolution chest CT were performed. Patients who required respiratory support (oxygen, CPAP, or NIV) were considered severe. RESULTS: In total, 293 patients (mean age 54 + 13 years) were included. Occupational exposure to asbestos was detected in 67 (24%). Patients with occupational exposure to asbestos had a higher frequency of COVID-19 pneumonia requiring respiratory support (n = 52, 77.6%) than their unexposed peers (n = 139, 61.5%) (p = 0.015). Asbestos exposure was associated with COVID-19 severity in the univariate but not in the multivariate analysis. No differences were found regarding follow-up variables including spirometry and the DLCO diffusion, the 6-min walk test, and CT alterations. CONCLUSIONS: In hospitalised patients with COVID-19 pneumonia, those with occupational exposure to asbestos more frequently needed respiratory support. However, an independent association between asbestos exposure and COVID-19 severity could not be confirmed.

Cluster-derived obstructive sleep apnea phenotypes and outcomes at 5-year follow-up.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a heterogeneous, complex disease. We aimed to identify OSA phenotypes through cluster analysis and to perform a long-term follow-up to validate the phenotypes. METHODS: We applied a partitioning around medioids technique in a cohort of 1,217 participants recently diagnosed with OSA. We performed a 5-year follow-up analyzing the incidence of comorbidities, chronic medication, hospital admissions, mortality, and the influence of continuous positive airway pressure treatment on mortality risk. RESULTS: We identified three phenotypes: two predominantly male clusters, one composed of middle-aged participants with overweight, moderate OSA, and cardiovascular risk factors and the other consisting of older, obese participants with severe OSA, cardiovascular risk factors, ischemic heart disease (18.4%), and atrial fibrillation (9.7%). The third cluster was composed of 77% female participants with moderate OSA; cardiovascular risk factors; the highest prevalence of depression (15.7%); and high prescription of antidepressants (55.1%), anxiolytics (40.0%), hypnotics, sedatives (11.1%), nonsteroidal anti-inflammatory drugs (67.9%), and weak opioids (15.1%). The baseline characteristics of each cluster maintained the same trend over time regarding the incidence of new comorbidities, medication intake, hospitalization rates, and reasons for admission. The absence of continuous positive airway pressure treatment was associated with a significantly higher risk of all-cause mortality (hazard ratio 5.84, confidence interval 2.9-11.8), especially in the older men (hazard ratio 7.7, confidence interval 4.06-14.63) and predominantly female clusters (hazard ratio 2.79, confidence interval 1.34-5.79). CONCLUSIONS: We identified three phenotypes with relevant clinical and prognostic implications in order to improve personalized strategies in OSA management. CITATION: Silveira MG, Sampol G, Mota-Foix M, Ferrer J, Lloberes P. Cluster-derived obstructive sleep apnea phenotypes and outcomes at 5-year follow-up. J Clin Sleep Med. 2022;18(2):597-607.