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BACKGROUND: Acute exacerbations of COPD (AECOPDs) are increasingly recognized as episodes of heightened risk of cardiovascular events. It is not known whether exacerbation history is differentially associated with future myocardial infarction (MI) or pulmonary embolism (PE). RESEARCH QUESTION: Is the number and severity of AECOPDs associated with increased risk of MI or PE in a real-life cohort of patients with COPD? STUDY DESIGN AND METHODS: We identified a cohort of 66422 patients (≥30yr) with a primary diagnosis of COPD in the Swedish National Airway Register January 2014 to June 2022, with complete data on lung function. Patients were classified by moderate (prescription of oral corticosteroids) and severe (hospitalization) exacerbations the year before index date and were followed until Dec 2022 for hospitalization or death from MI or PE, corresponding to >265 000 patient-years, with a maximum follow-up time of 9 years. Competing-risk regression, according to Fine-Gray, was used to calculate subdistribution hazard ratios (SHRs) with 95% confidence intervals (CI). RESULTS: Compared with no AECOPDs in the baseline period, AECOPD number and severity was associated with increased long term risk of both MI and PE in a gradual fashion, ranging from a SHR of 1.10 (0.97-1.24) and 1.33 (1.11-1.60), respectively, for one moderate exacerbation, to 1.82 (1.36-2.44) and 2.62 (1.77-3.89), respectively, for two or more severe exacerbations. In a time-restricted follow-up sensitivity analysis, the associations were stronger during the first year of follow up and diminished over time. INTERPRETATION: The risk of MI and PE increases with the frequency and severity of AECOPD in this large real life cohort of patients with COPD.
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Lung hyperinflation (LH) is a common clinical feature in patients with chronic obstructive pulmonary disease (COPD). It results from a combination of reduced elastic lung recoil as a consequence of irreversible destruction of lung parenchyma and expiratory airflow limitation. LH is an important determinant of morbidity and mortality in COPD, partially independent of the degree of airflow limitation. Therefore, reducing LH has become a major target in the treatment of COPD over the last decades. Advances were made in the diagnostics of LH and several effective interventions became available. Moreover, there is increasing evidence suggesting that LH is not only an isolated feature in COPD but rather part of a distinct clinical phenotype that may require a more integrated management. This narrative review focuses on the pathophysiology and adverse consequences of LH, the assessment of LH with lung function measurements and imaging techniques and highlights LH as a treatable trait in COPD. Finally, several suggestions regarding future studies in this field are made.
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Pulmón , Fenotipo , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Pulmón/fisiopatología , Valor Predictivo de las Pruebas , Mediciones del Volumen Pulmonar , Resultado del TratamientoRESUMEN
Background: Alterations in body weight and composition are common in patients with chronic obstructive pulmonary disease (COPD) and are independent predictors for morbidity and mortality. Low vitamin D status is also more prevalent in patients with COPD compared to controls and has been related to lower lung function, muscle atrophy and impaired musculoskeletal function. This study aimed to evaluate the association between vitamin D levels and status with body composition (BC), as well as with its changes over time. Patients and Methods: Patients with COPD and controls without COPD, participating in the Individualized COPD Evaluation in relation to Ageing (ICE-Age) study, a prospective observational study, were included. Plasma 25-hydroxyvitamin D (25(OH)D) was measured at baseline and BC was measured by dual-energy X-ray absorptiometry scan, at baseline and after two years of follow-up. Multiple linear regression analyses were performed to assess the relationships between 25(OH)D (nmol/l) and longitudinal changes in BMI, fat-free mass index (FFMI), fat mas index (FMI) and bone mineral density (BMD). Results: A total of 192 patients with COPD (57% males, mean ± SD age, 62 ± 7, FEV1, 49 ± 16% predicted) and 199 controls (45% males, mean ± SD age 61 ± 7) were included in this study. Vitamin D levels were significantly lower in patients with COPD (64 ± 26 nmol/L, 95% CI 60-68 nmol/L versus 75 ± 25 nmol/L, 95% CI 72-79 nmol/L) compared to controls. Both patients and controls presented a significant decline in FFMI and T-score hip, but vitamin D level or status did not determine differences in BC or changes in BC over time in either COPD or controls. Conclusion: Vitamin D status was not associated with BC or longitudinal changes in BC. However, vitamin D insufficiency and low BMD were more prevalent in patients with COPD compared to controls.
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Absorciometría de Fotón , Biomarcadores , Composición Corporal , Densidad Ósea , Pulmón , Enfermedad Pulmonar Obstructiva Crónica , Deficiencia de Vitamina D , Vitamina D , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Vitamina D/sangre , Vitamina D/análogos & derivados , Anciano , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/fisiopatología , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/complicaciones , Factores de Tiempo , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Estudios de Casos y Controles , Biomarcadores/sangre , Estudios Longitudinales , Modelos Lineales , Factores de Riesgo , Volumen Espiratorio Forzado , Índice de Masa CorporalRESUMEN
Introduction: Assessing COVID-19 risk in asthma patients is challenging due to disease heterogeneity and complexity. We hypothesized that potential risk factors for COVID-19 may differ among asthma age groups, hindering important insights when studied together. Methods: We included a population-based cohort of asthma patients from the Swedish National Airway Register (SNAR) and linked to data from several national health registers. COVID-19 outcomes included infection, hospitalization, and death from Jan 2020 until Feb 2021. Asthma patients were grouped by ages 12-17, 18-39, 40-64, and ≥65 years. Characteristics of asthma patients with different COVID-19 outcomes were compared with those in their age-corresponding respective source population. Results: Among 201,140 asthma patients studied, 11.2% were aged 12-17 years, 26.4% 18-39, 37.6% 40-64, and 24.9% ≥65 years. We observed 18,048 (9.0%) COVID-19 infections, 2172 (1.1%) hospitalizations, and 336 (0.2%) COVID-19 deaths. Deaths occurred only among patients aged ≥40. When comparing COVID-19 cases to source asthma populations by age, large differences in potential risk factors emerged, mostly for COVID-19 hospitalizations and deaths. For ages 12-17, these included education, employment, autoimmune, psychiatric, and depressive conditions, and use of short-acting ß-agonists (SABA) and inhaled corticosteroids (ICS). In the 18-39 age group, largest differences were for age, marital status, respiratory failure, anxiety, and body mass index. Ages 40-64 displayed notable differences for sex, birth region, cancer, oral corticosteroids, antihistamines, and smoking. For those aged ≥65, largest differences were observed for cardiovascular comorbidities, type 1 diabetes, chronic obstructive pulmonary disease, allergic conditions, and specific asthma treatments (ICS-SABA, ICS-long-acting bronchodilators (LABA)). Asthma control and lung function were important across all age groups. Conclusion: We identify distinct differences in COVID-19-related risk factors among asthma patients of different ages. This information is essential for assessing COVID-19 risk in asthma patients and for tailoring patient care and public health strategies accordingly.
Why was the study done? Asthma patients may be more susceptible to COVID-19 outcomes. Asthma affects all ages, and COVID-19-related risk factors may vary with age. Investigating factors that contribute to COVID-19 infection, hospitalization, and mortality within distinct age groups of asthma patients can yield a more comprehensive understanding of the age-specific nuances of COVID-19 risk. What did the researchers do and find? We analyzed sociodemographic characteristics, comorbidities, prescribed medications, and clinical characteristics of asthma patients with COVID-19 in different age groups and compared them with their age-corresponding source asthma populations. Potential risk factors for COVID-19 and its outcomes differed by age group For ages 12-17, these included education, employment, autoimmune, psychiatric, and depressive conditions, and use of short-acting ß-agonists (SABA) and inhaled corticosteroids (ICS). In the 18-39 age group, largest differences were for age, marital status, respiratory failure, anxiety, and body mass index. Ages 40-64 displayed notable differences for sex, birth region, cancer, oral corticosteroids, antihistamines, and smoking. For those aged ≥65, largest differences were observed for cardiovascular comorbidities, type 1 diabetes, chronic obstructive pulmonary disease, allergic asthma, and specific asthma treatments (ICS-SABA, ICS-long-acting bronchodilators (LABA)). Asthma control and lung function were important across all age groups. What do these results mean? These results emphasize the importance of recognizing age-specific patterns contributing to COVID-19 risk for consideration in causal analyses. The findings also highlight the necessity for age-specific approaches in both clinical and public health interventions in managing COVID-19 in asthma patients.
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BACKGROUND AND OBJECTIVE: Both bronchoscopic lung volume reduction with endobronchial valves (BLVR-EBV) and pulmonary rehabilitation (PR) are effective treatments for improving exercise capacity and patient-reported outcomes in patients with severe Chronic Obstructive Pulmonary Disease (COPD). According to current recommendations, all BLVR-EBV patients should have undergone PR first. Our aim was to study the effects of PR both before and after BLVR-EBV compared to BLVR-EBV alone. METHODS: We included patients with severe COPD who were eligible for BLVR-EBV and PR. Participants were randomized into three groups: PR before BLVR-EBV, PR after BLVR-EBV or BLVR-EBV without PR. The primary outcome was change in constant work rate cycle test (CWRT) endurance time at 6-month follow-up of the PR groups compared to BLVR-EBV alone. Secondary endpoints included changes in 6-minute walking test, daily step count, dyspnoea and health-related quality of life. RESULTS: Ninety-seven participants were included. At 6-month follow-up, there was no difference in change in CWRT endurance time between the PR before BLVR-EBV and BLVR-EBV alone groups (median: 421 [IQR: 44; 1304] vs. 787 [123; 1024] seconds, p = 0.82) or in any of the secondary endpoints, but the PR after BLVR-EBV group exhibited a smaller improvement in CWRT endurance time (median: 107 [IQR: 2; 573], p = 0.04) and health-related quality of life compared to BLVR-EBV alone. CONCLUSION: The addition of PR to BLVR-EBV did not result in increased exercise capacity, daily step count or improved patient-reported outcomes compared to BLVR-EBV alone, neither when PR was administered before BLVR-EBV nor when PR was administered after BLVR-EBV.
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Broncoscopía , Tolerancia al Ejercicio , Neumonectomía , Enfisema Pulmonar , Calidad de Vida , Humanos , Masculino , Femenino , Broncoscopía/métodos , Neumonectomía/métodos , Anciano , Enfisema Pulmonar/cirugía , Enfisema Pulmonar/rehabilitación , Enfisema Pulmonar/fisiopatología , Persona de Mediana Edad , Resultado del Tratamiento , Prueba de Paso , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Prótesis e Implantes , Factores de Tiempo , Índice de Severidad de la EnfermedadRESUMEN
RATIONALE: According to GOLD, the ratio of FEV1/FVC is used to confirm airflow obstruction in COPD diagnosis, whereas FEV1% of predicted (FEV1%pred) is used for severity grading. STaging of Airflow obstruction by the FEV1/FVC Ratio (STAR) and its prediction of adverse outcomes has not been evaluated in general populations. OBJECTIVE: To compare the STAR (FEV1/FVC) versus GOLD (FEV1%pred) classification for the severity of airflow limitation in terms of exertional breathlessness and mortality in the general US population. METHODS: Severity stages according to STAR and GOLD were applied to the multi-ethnic National Health and Nutrition Examination Survey (NHANES) 2007-2012 survey including ages 18-80 years, using post-bronchodilatory FEV1/FVC<0.70 to define airflow obstruction in both staging systems. Prevalence of severity stages STAR 1-4 and GOLD 1-4 was calculated and associations with breathlessness and mortality were analyzed by multinomial logistic regression and Cox regression, respectively. RESULTS: STAR versus GOLD severity staging of airflow obstruction showed similar associations with breathlessness and all-cause mortality, regardless of ethnicity/race. In those with airflow obstruction, the correlation between the two classification systems was 0.461 (p<0.001). STAR reclassified 59% of GOLD stage 2 as having mild airflow obstruction (STAR 1). STAR 1 was more clearly differentiated from the non-obstructive compared to GOLD stage 1 in terms of both breathlessness and mortality. CONCLUSIONS: FEV1/FVC and FEV1%pred as measures of severity of airflow limitation show similar prediction of breathlessness and mortality in the adult US population across ethnicity groups. However, stage 1 differed more clearly from non-obstructive based on FEV1/FVC than FEV1%pred. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course. As a result, a range of lung-function trajectories exist in the population. Below average trajectories are associated with respiratory, cardiovascular, metabolic, and mental health comorbidities, as well as with premature death. This Review presents progressive research into lung-function trajectories and assists the implementation of this knowledge in clinical practice as an innovative approach to detect poor lung health early, monitor respiratory disease progression, and promote lung health. Specifically, we propose that, similar to paediatric height and weight charts used globally to monitor children's growth, lung-function charts could be used for both children and adults to monitor lung health status across the life course. To achieve this proposal, we introduce our free online Lung Function Tracker tool. Finally, we discuss challenges and opportunities for effective implementation of the trajectory concept at population level and outline an agenda for crucial research needed to support such implementation.
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Pulmón , Enfermedades Respiratorias , Adulto , Adolescente , Niño , Humanos , Salud Mental , Estado de SaludRESUMEN
BACKGROUND: Chronic airway obstruction (CAO) and restrictive spirometry pattern (RSP) are associated with mortality, but sex-specific patterns of all-cause and specific causes of death have hardly been evaluated. OBJECTIVES: To study the possible sex-dependent differences of all-cause mortality and patterns of cause-specific mortality among men and women with CAO and RSP, respectively, to that of normal lung function (NLF). DESIGN: Population-based prospective cohort study. METHODS: Individuals with CAO [FEV1/vital capacity (VC) < 0.70], RSP [FEV1/VC ⩾ 0.70 and forced vital capacity (FVC) < 80% predicted] and NLF (FEV1/VC ⩾ 0.70 and FVC ⩾ 80% predicted) were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-2004. Mortality data were collected through April 2016, totally covering 19,000 patient-years. Cox regression and Fine-Gray regression accounting for competing risks were utilized to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, body mass index, sex, smoking habits and pack-years. RESULTS: The adjusted hazard for all-cause mortality was higher in CAO and RSP than in NLF (HR, 95% CI; 1.69, 1.31-2.02 and 1.24, 1.06-1.71), and the higher hazards were driven by males. CAO had a higher hazard of respiratory and cardiovascular death than NLF (2.68, 1.05-6.82 and 1.40, 1.04-1.90). The hazard of respiratory death was significant in women (3.41, 1.05-11.07) while the hazard of cardiovascular death was significant in men (1.49, 1.01-2.22). In RSP, the higher hazard for respiratory death remained after adjustment (2.68, 1.05-6.82) but not for cardiovascular death (1.11, 0.74-1.66), with a similar pattern in both sexes. CONCLUSION: The higher hazard for all-cause mortality in CAO and RSP than in NLF was male driven. CAO was associated with respiratory death in women and cardiovascular death in men, while RSP is associated with respiratory death, similarly in both sexes.
All-cause and cause specific mortality in relation to different lung function patterns and sex; normal, obstructive and restricted lung functionChronic airway obstruction and restrictive spirometry pattern are associated with mortality, but sex specific patterns have hardly been evaluated.Aim: To study possible sex-dependent differences of all-cause and cause-specific mortality among men and women with chronic airway obstruction and restrictive spirometry pattern, respectively, compared to that of normal lung function.Methods: Individuals with chronic airway obstruction, restrictive spirometry pattern and normal lung function were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-04. Mortality data were collected through April 2016, totally covering 19,000 patient-years of observation time. We analyzed the Hazard Ratios for all-cause and cause-specific death comparing chronic airway obstruction and restrictive spirometry pattern to that of normal lung function, adjusting for age, body mass index, sex, smoking habits and pack-years. Similar analyses were conducted separately for men and women.Results: The hazard for all-cause mortality was higher in both chronic airway obstruction and restrictive spirometry pattern than in normal lung function and, the higher hazards were male-driven. In chronic airway obstruction the hazard of respiratory and cardiovascular deaths higher than in those with normal lung function. The increased hazard of respiratory death was significant in women while the increased hazard of cardiovascular death was significant in men. In restrictive spirometry pattern, the higher hazard for respiratory but not cardiovascular death persisted after adjustment, similarly in both sexes.Conclusions: The higher hazard for all-cause mortality in chronic airway obstruction and restrictive spirometry pattern than in normal lung function was male-driven. Chronic airway obstruction associated with respiratory death in women and cardiovascular death in men, while restrictive pattern associated with respiratory death, similarly in both sexes.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Masculino , Femenino , Causas de Muerte , Estudios de Cohortes , Estudios Prospectivos , Volumen Espiratorio Forzado , Pulmón , Espirometría , Capacidad VitalRESUMEN
INTRODUCTION: Patients with advanced emphysema eligible for bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBV) are characterized by severe static lung hyperinflation, which can be considered a treatable trait. Other treatable traits (TTs), which are assumed to be present in this highly selected patient group, have not been studied in detail nor how they may affect health-related quality of life (HRQL). AIMS: We aimed to evaluate a spectrum of TTs in COPD patients eligible for EBV treatment and their association with HRQL. METHODS: The SoLVE study (NCT03474471) was a prospective multicenter randomized controlled trial to examine the impact of pulmonary rehabilitation in COPD patients receiving EBV. The presence/absence of 16 TTs was based on pre-defined thresholds. HRQL was assessed with the St. George's Respiratory Questionnaire (SGRQ). Subjects were stratified into two groups, using the median split method, into higher or lower SGRQ total score. Logistic regression assessed the odds ratio (OR) of having a higher SGRQ total score per TT. RESULTS: Ninety-seven subjects were included, the mean number of TTs per patient was 8.1 ± 2.5. Low physical activity (95%), poor exercise capacity (94%) and severe fatigue (75%) were the most prevalent TTs. The sum of TTs present in a subject was associated with the SGRQ total score (r = 0.53; p < 0.001). Severe fatigue, depression, and anxiety were predictors of having a higher SGRQ total score. CONCLUSIONS: A high prevalence and co-occurrence of multiple TTs were identified in emphysema patients eligible for EBV. Patients with a higher number of TTs were more likely to have worse HRQL.
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Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Neumonectomía/métodos , Calidad de Vida , Estudios Prospectivos , Enfisema Pulmonar/epidemiología , Enfisema Pulmonar/cirugía , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Broncoscopía/métodos , Volumen Espiratorio Forzado , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: Bronchoscopic lung volume reduction (BLVR) is a novel and effective treatment for a specific phenotype of chronic obstructive pulmonary disease (COPD) characterized by advanced emphysema with static lung hyperinflation and severe breathlessness. This review aims to provide an overview of the recent advances made in BLVR. RECENT FINDINGS: For achieving optimal outcomes with BLVR, patient selection and target lobe identification is crucial. BLVR has recently also been established to improve pulmonary function, exercise capacity and quality of life in COPD patients falling outside the standard treatment criteria, including patients with moderate hyperinflation, chronic hypercapnic failure or with very low diffusion capacity. In a cluster analysis, target lobe characteristics like emphysema destruction, air trapping and perfusion were found to be important discriminators between responders and non-responders. A potential survival benefit has been demonstrated in BLVR-treated patients when compared to non-treated patients. Long-term outcomes showed sustained outcomes of BLVR; however, effects decline over time, probably due to disease progression. SUMMARY: BLVR using one-way endobronchial valves has become a guideline treatment offered in specialized intervention centres for a specific subgroup of COPD patients. Recent studies further characterize responders, describe extrapulmonary effects of BLVR and show positive long-term outcomes and a potential survival benefit.
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Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Neumonectomía/efectos adversos , Calidad de Vida , Broncoscopía/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Enfisema Pulmonar/cirugía , Enfisema Pulmonar/etiología , Enfisema/etiologíaRESUMEN
Background: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms. Methods: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64â years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing. Findings: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA. Interpretation: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.
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Most patients with chronic obstructive pulmonary disease (COPD) have at least one additional, clinically relevant chronic disease. Those with the most severe airflow obstruction will die from respiratory failure, but most patients with COPD die from non-respiratory disorders, particularly cardiovascular diseases and cancer. As many chronic diseases have shared risk factors (eg, ageing, smoking, pollution, inactivity, and poverty), we argue that a shift from the current paradigm in which COPD is considered as a single disease with comorbidities, to one in which COPD is considered as part of a multimorbid state-with co-occurring diseases potentially sharing pathobiological mechanisms-is needed to advance disease prevention, diagnosis, and management. The term syndemics is used to describe the co-occurrence of diseases with shared mechanisms and risk factors, a novel concept that we propose helps to explain the clustering of certain morbidities in patients diagnosed with COPD. A syndemics approach to understanding COPD could have important clinical implications, in which the complex disease presentations in these patients are addressed through proactive diagnosis, assessment of severity, and integrated management of the COPD multimorbid state, with a patient-centred rather than a single-disease approach.
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Multimorbilidad , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Sindémico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Comorbilidad , PulmónRESUMEN
Purpose: Several studies report decreased hospital admissions for acute exacerbations of COPD (AECOPD) during the COVID-19 pandemic. However, there are no studies that compare AECOPD admissions with admissions for respiratory infections, including COVID-19. This study aimed to examine hospital admission rates for AECOPD, pneumonia, influenza, and COVID-19 among COPD patients, before and during the COVID-19 pandemic. Patients and Methods: We obtained anonymized data on hospital admissions of patients with COPD and a primary diagnosis code for AECOPD, pneumonia, influenza, or COVID-19, from the hospital patient admission register at a large Swedish hospital. The study compared the pandemic period (February 2020-March 2022) to a period before the pandemic (June 2017-January 2020). Sequential phases of the pandemic were evaluated separately. Monthly admission rates were compared using Poisson regression, controlling for admission month. Results: Comparing monthly admission rates during the pandemic with the prepandemic period, incidence rate ratios were 0.72 for AECOPD (95% CI 0.67-0.77; p<0.001), 0.56 for pneumonia (95% CI 0.49-0.62; p<0.001), 0.18 for influenza during the winter period (95% CI 0.10-0.30; p<0.001) and 0.79 for total COPD admissions, including COVID-19 (95% CI 0.75-0.84; p<0.001). The study showed significantly lower rate ratios for AECOPD, pneumonia, and total COPD admissions during the first, second, third, and fifth (Omicron) waves. No significant effect on admissions was seen after the withdrawal of restriction measures. Conclusion: There was a significant reduction in the overall rate of hospital admissions among COPD patients for AECOPD, pneumonia, and respiratory viral infections during the pandemic despite the rise in COVID-19 admissions. However, prepandemic admission levels returned in the post-restriction period.
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COVID-19 , Gripe Humana , Enfermedad Pulmonar Obstructiva Crónica , Humanos , COVID-19/epidemiología , Pandemias , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Gripe Humana/terapia , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Pacientes Internos , HospitalesRESUMEN
Purpose: Population-based studies provide conflicting evidence about how inhaled corticosteroids (ICS) impact COVID-19 outcomes among COPD patients. We investigated whether regular ICS exposure affects risk, severity, or survival in SARS-CoV-2 infection, using a nationwide linked Swedish population register database. Patients and Methods: During January-December 2020, we studied two defined Swedish adult populations - Whole population [≥40 years] (N = 5243479), and COPD subpopulation [≥40 years] (N = 133372), in three study cohorts, respectively: 1. Overall cohort (index date 1 Jan 2020), 2. COVID-19 diagnosed sub-cohort (index date = diagnosis date), and 3. COVID-19 hospitalized sub-cohort (index date = admission date). Regular exposure was defined as ≥3 ICS prescriptions in the year before index. Hazard ratios (HRs) for outcomes (COVID-19 onset, hospitalization, ICU admission, or death) related to ICS exposure were estimated using Cox regression. Confounding was controlled by propensity score methods applying Average Treatment effect in the Treated (ATT) weighting. Results: Regular ICS use was associated with only very slightly increased onset of COVID-19, hospitalization, ICU admission, and death in the overall whole population cohort and in the overall COPD subpopulation cohort, except for ICU admission (marginally non-significant HRs, up to 1.13); and no clear increase in the diagnosed sub-cohorts. However, in the COVID-19 hospitalized COPD sub-cohort, ICS therapy showed reduced risks against progression to ICU admission and death, significant for death (HR 0.82 95% CI [0.67-0.99]). Conclusion: For COPD patients, ICS therapy offers some protection against progression to ICU admission and death among COVID-19 hospitalized patients. Our findings alleviate concerns about increased risks of COVID-19 by ICS treatment and provide evidence supporting the continuation of ICS therapy for COPD patients.
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COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Humanos , COVID-19/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Administración por Inhalación , SARS-CoV-2 , CorticoesteroidesRESUMEN
BACKGROUND: Several studies have shown the importance of the complement and coagulation systems in the pathogenesis of asthma. OBJECTIVES: We explored whether we could detect differentially abundant complement and coagulation proteins in the samples obtained from the small airway lining fluid by collection of exhaled particles in patients with asthma and whether these proteins are associated with small airway dysfunction and asthma control. METHOD: Exhaled particles were obtained from 20 subjects with asthma and 10 healthy controls (HC) with the PExA method and analysed with the SOMAscan proteomics platform. Lung function was assessed by nitrogen multiple breath washout test and spirometry. RESULTS: 53 proteins associated with the complement and coagulation systems were included in the analysis. Nine of those proteins were differentially abundant in subjects with asthma as compared to HC, and C3 was significantly higher in inadequately controlled asthma as compared to well-controlled asthma. Several proteins were associated with physiological tests assessing small airways. CONCLUSIONS: The study highlights the role of the local activation of the complement and coagulation systems in the small airway lining fluid in asthma and their association with both asthma control and small airway dysfunction. The findings highlight the potential of complement factors as biomarkers to identify different sub-groups among patients with asthma that could potentially benefit from a therapeutic approach targeting the complement system.
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Asma , Coagulación Sanguínea , Bronquiolos , Activación de Complemento , Alveolos Pulmonares , Asma/sangre , Asma/inmunología , Asma/fisiopatología , Humanos , Masculino , Femenino , Persona de Mediana Edad , Alveolos Pulmonares/inmunología , Alveolos Pulmonares/fisiopatología , Bronquiolos/inmunología , Bronquiolos/fisiopatologíaRESUMEN
Rationale: Evidence on risk factors for Coronavirus disease 2019 (COVID-19) outcomes among patients with COPD in relation to COVID-19 vaccination remains limited. The objectives of the present study were to characterise determinants of COVID-19 infection, hospitalisation, intensive care unit (ICU) admission and death in COPD patients in their unvaccinated state compared to when vaccinated. Methods: We included all COPD patients in the Swedish National Airway Register (SNAR). Events of COVID-19 infection (test and/or healthcare encounter), hospitalisation, ICU admission and death were identified from 1 January 2020 to 30 November 2021. Using adjusted Cox regression, associations between baseline sociodemographics, comorbidities, treatments, clinical measurements and COVID-19 outcomes, during unvaccinated and vaccinated follow-up time, were analysed. Results: The population-based COPD cohort included 87 472 patients, among whom 6771 (7.7%) COVID-19 infections, 2897 (3.3%) hospitalisations, 233 (0.3%) ICU admissions and 882 (1.0%) COVID-19 deaths occurred. During unvaccinated follow-up, risk of COVID-19 hospitalisation and death increased with age, male sex, lower education, non-married status and being foreign-born. Comorbidities increased risk of several outcomes, e.g. respiratory failure for infection and hospitalisation (adjusted hazard ratios (HR) 1.78, 95% CI 1.58-2.02 and 2.51, 2.16-2.91, respectively), obesity for ICU admission (3.52, 2.29-5.40) and cardiovascular disease for mortality (2.80, 2.16-3.64). Inhaled COPD therapy was associated with infection, hospitalisation and death. COPD severity was also associated with COVID-19, especially hospitalisation and death. Although the risk factor panorama was similar, COVID-19 vaccination attenuated HRs for some risk factors. Conclusion: This study provides population-based evidence on predictive risk factors for COVID-19 outcomes and highlights the positive implications of COVID-19 vaccination for COPD patients.
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Purpose: Long-acting bronchodilators (LABD), in general, reduce respiratory symptoms, improve exercise endurance time and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, there might be heterogeneity in improvement for several outcomes on an individual level. Therefore, we aimed to profile the multidimensional response in patients receiving tiotropium/olodaterol (T/O) using self-organizing maps (SOM). Materials and Methods: This is a secondary analysis of the TORRACTO study: a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effects of T/O (2.5/5 and 5/5 µg) compared with placebo after 6 and 12 weeks of treatment in patients with COPD. In the current study, we used endurance time, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), inspiratory capacity (IC) at rest and IC at isotime (ICiso) to identify clusters by means of SOM in patients treated with T/O. Results: Six clusters with distinct response profiles were generated at week 12 in COPD patients receiving T/O (n = 268). Patients in cluster 1 improved significantly on all outcomes, whilst cluster 5 showed strong improvement in endurance time (357s); contrarily, FEV1, FVC, ICrest and ICiso decreased when compared to baseline. Conclusion: Individual responses on endurance time and pulmonary function after 12 weeks of T/O are heterogeneous. This study identified clusters in COPD patients with markedly different multidimensional response on LABD.
Asunto(s)
Broncodilatadores , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Broncodilatadores/administración & dosificación , Análisis por Conglomerados , Estudios Multicéntricos como Asunto , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Relación Dosis-Respuesta a DrogaRESUMEN
Chronic obstructive pulmonary disease (COPD) is a disease of the airways and lungs due to an enhanced inflammatory response, commonly caused by cigarette smoking. Patients with COPD are often multimorbid, as they commonly suffer from multiple chronic (inflammatory) conditions. This intensifies the burden of individual diseases, negatively affects quality of life, and complicates disease management. COPD and comorbidities share genetic and lifestyle-related risk factors and pathobiological mechanisms, including chronic inflammation and oxidative stress. The receptor for advanced glycation end products (RAGE) is an important driver of chronic inflammation. Advanced glycation end products (AGEs) are RAGE ligands that accumulate due to aging, inflammation, oxidative stress, and carbohydrate metabolism. AGEs cause further inflammation and oxidative stress through RAGE, but also through RAGE-independent mechanisms. This review describes the complexity of RAGE signaling and the causes of AGE accumulation, followed by a comprehensive overview of alterations reported on AGEs and RAGE in COPD and in important co-morbidities. Furthermore, it describes the mechanisms by which AGEs and RAGE contribute to the pathophysiology of individual disease conditions and how they execute crosstalk between organ systems. A section on therapeutic strategies that target AGEs and RAGE and could alleviate patients from multimorbid conditions using single therapeutics concludes this review.
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Rationale: Risk stratification of patients according to chronic obstructive pulmonary disease severity is clinically important and forms the basis of therapeutic recommendations. No studies have examined the association for Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and group B patients with (A1 and B1, respectively) and without (A0 and B0, respectively) an exacerbation in the past year with future exacerbations, hospitalizations, and mortality in perspective with the new GOLD ABE classification. Objectives: The aim was to examine the association between GOLD A0, A1, B0, B1, and E patients and future exacerbations, respiratory and cardiovascular hospitalizations, and mortality. Methods: In this nationwide cohort study, we identified patients with a diagnosis of chronic obstructive pulmonary disease, aged ⩾30 years, and registered in the Swedish National Airway Register between January 2017 and August 2020. Patients were stratified in GOLD groups A0, A1, B0, B1, and E and were followed until January 2021 for exacerbations, hospitalizations, and mortality in national registries. Measurements and Main Results: The 45,350 eligible patients included 25% A0, 4% A1, 44% B0, 10% B1, and 17% E. Moderate exacerbations, all-cause and respiratory hospitalizations, and all-cause and respiratory mortality increased by GOLD group A0-A1-B0-B1-E, except for moderate exacerbations, which were higher in A1 than in B0. Group B1 had a substantially higher hazard ratio for future exacerbation (2.56; 95% confidence interval [95% CI] 2.40-2.74), all-cause hospitalization (1.28; 1.21-1.35), and respiratory hospitalization (1.44; 1.27-1.62), but not all-cause (1.04; 0.91-1.18) or respiratory (1.13; 0.79-1.64) mortality than group B0. The exacerbation rate for group B1 was 0.6 events per patient-year versus 0.2 for group B0 (rate ratio, 2.55; 95% CI, 2.36-2.76). Results were similar for group A1 versus group A0. Conclusions: Stratification of GOLD A and B patients with one or no exacerbation in the past year provides valuable information on future risk, which should influence treatment recommendations for preventive strategies.