Application of the Lancet Commission COPD classification to COPD Cohort Population in South Korea.

The Lancet Commissions on COPD recommended a new classification based on five main risk factors. Patients with COPD were prospectively enrolled in a Korean COPD subgroup study cohort between April 2012 and June 2022. Patients were classified according to the etiologies (Type 1: Genetically determined (COPD-G), Type 2: Abnormal lung development (COPD-D), Type 3: Infections (COPD-I), Type 4: Cigarette smoking (COPD-C), Type 5: Biomass and pollution (COPD-P)). The database enrolled 3476 patients. Among 3392 patients, 52 (2 %), 1339 (39 %), 2930 (86 %), and 2221 (65 %) were compatible with type 2 (COPD-D), 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Most patients (71 %, 2405) had multiple risk factors contributing to their COPD. However, 93, 712, and 182 patients had only type 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Type 3 (COPD-I) only patients were significantly younger, more often female, and had lower lung function. Both the rate and frequency of severe exacerbations were significantly higher in type 3 (COPD-I) only patients (p = 0.038 and p = 0.048, respectively). Compared with type 5 (COPD-P) only, type 3 (COPD-I) only was significantly associated with the risk of severe exacerbation (Odds ratio, 5.7 [95 % CI, 1.0-32.4]; P = 0.049, incident rate ratio, 8.7 [95 % CI, 1.7-44.0]; P = 0.009). Many patients were affected by multiple factors. Therefore, it is important to consider not only smoking history, but also other potential risk factors when evaluating patients with COPD. Further research is needed to explore the implications of this new COPD classification system for clinical practice and treatment strategies.

Subgroup analysis reveals higher reliability of the new comprehensive evaluation of Global Initiative for Chronic Obstructive Lung Disease 2019.

To estimate the severity of the disease in outpatients with chronic obstructive pulmonary disease (COPD) in Hunan Province, China and use the subgroup analysis to evaluate the reliability of the new comprehensive evaluation of Global Initiative for Chronic Obstructive Lung Disease (GOLD). COPD outpatients from 12 medical centers in Hunan Province, China were stratified into groups A-D, and group D patients were further stratified into subgroups D1-D3 according to the GOLD 2016 and 2019 comprehensive assessment. Demography, clinical characteristics and medications were compared among groups. In 1017 COPD outpatients, the distribution from group A to D and subgroup D1 to D3 was 41 (4.0%), 249 (24.5%), 17 (1.7%), 710 (69.8%) and 214 (30.2%), 204 (28.7%), 292 (41.1%), according to GOLD 2016. In terms of demographic and clinical characteristics related to A-D groups, there was a significant difference in COPD assessment test (CAT), modified Medical British Research Council (mMRC), the clinical COPD questionnaire(CCQ), age, BMI, education level, smoking history, comorbidities, the course of chronic bronchitis/emphysema, number of exacerbations/hospitalisations in the previous year, treatment protocols, forced expiratory volume in one second (FEV1) % predicted, and FEV1/forced vital capacity (FVC) (p < 0.01). Furthermore, some patients in groups C-D regrouped to groups A-B were all C1 and D1 subgroups according to GOLD 2019. Comparing subgroup D1 with group B, subgroup D2 and subgroup D3, it was found that the demography, clinical characteristics and medications of subgroup D1 were the closest to group B, according to GOLD 2016 (p < 0.01). The disease severity of outpatients with COPD in Hunan Province was more pronounced in group B and D and patients in groups A-D had different demography, clinical characteristics and medications. Subgroup analysis can explain to a certain extent that GOLD2019's new comprehensive assessment is more reliable than GOLD 2016.

Discriminative Accuracy of Chronic Obstructive Pulmonary Disease Screening Instruments in 3 Low- and Middle-Income Country Settings.

Importance: Most of the global morbidity and mortality in chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs), with significant economic effects. Objective: To assess the discriminative accuracy of 3 instruments using questionnaires and peak expiratory flow (PEF) to screen for COPD in 3 LMIC settings. Design, Setting, and Participants: A cross-sectional analysis of discriminative accuracy, conducted between January 2018 and March 2020 in semiurban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda, using a random age- and sex-stratified sample of the population 40 years or older. Exposures: Three screening tools, the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE; range, 0-6; high risk indicated by a score of 5 or more or score 2-5 with low PEF [<250 L/min for females and <350 L/min for males]), the COPD in LMICs Assessment questionnaire (COLA-6; range, 0-5; high risk indicated by a score of 4 or more), and the Lung Function Questionnaire (LFQ; range, 0-25; high risk indicated by a score of 18 or less) were assessed against a reference standard diagnosis of COPD using quality-assured postbronchodilator spirometry. CAPTURE and COLA-6 include a measure of PEF. Main Outcomes and Measures: The primary outcome was discriminative accuracy of the tools in identifying COPD as measured by area under receiver operating characteristic curves (AUCs) with 95% CIs. Secondary outcomes included sensitivity, specificity, positive predictive value, and negative predictive value. Results: Among 10 709 adults who consented to participate in the study (mean age, 56.3 years (SD, 11.7); 50% female), 35% had ever smoked, and 30% were currently exposed to biomass smoke. The unweighted prevalence of COPD at the 3 sites was 18.2% (642/3534 participants) in Nepal, 2.7% (97/3550) in Peru, and 7.4% (264/3580) in Uganda. Among 1000 COPD cases, 49.3% had clinically important disease (Global Initiative for Chronic Obstructive Lung Disease classification B-D), 16.4% had severe or very severe airflow obstruction (forced expiratory volume in 1 second <50% predicted), and 95.3% of cases were previously undiagnosed. The AUC for the screening instruments ranged from 0.717 (95% CI, 0.677-0.774) for LFQ in Peru to 0.791 (95% CI, 0.770-0.809) for COLA-6 in Nepal. The sensitivity ranged from 34.8% (95% CI, 25.3%-45.2%) for COLA-6 in Nepal to 64.2% (95% CI, 60.3%-67.9%) for CAPTURE in Nepal. The mean time to administer the instruments was 7.6 minutes (SD 1.11), and data completeness was 99.5%. Conclusions and Relevance: This study demonstrated that screening instruments for COPD were feasible to administer in 3 low- and middle-income settings. Further research is needed to assess instrument performance in other low- and middle-income settings and to determine whether implementation is associated with improved clinical outcomes.

Fenotipos clínicos de la enfermedad pulmonar obstructiva crónica en los pacientes atendidos en el Hospital neumológico de La Habana / Clinical phenotypes of chronic obstructive pulmonary disease in patients treated at the Hospital Neumológico de La Habana

Introducción: La identificación de los fenotipos clínicos son claves en la modulación de la expresión clínica, para un tratamiento integrado de la EPOC. Objetivos: Caracterizar los fenotipos clínicos de la EPOC en los pacientes atendidos en el Hospital Neumológico Benéfico Jurídico. Métodos:Se realizó un estudio observacional descriptivo retrospectivo, en 172 pacientes con diagnóstico de EPOC, en el Hospital Neumológico Benéfico Jurídico durante el año 2017.Resultados: El 38,4 % de los pacientes tenían edad entre 70-79 años. Del total de pacientes, el 54,6 % eran del sexo masculino. El 52,9 % eran fumadores activos y el 41,3 % exfumadores. Aunque las diferencias no fueron significativas, la edad avanzada y el sexo masculino fueron más frecuentes en el fenotipo enfisematoso agudizador y agudizador bronquítico crónico. El tabaquismo activo fue más frecuente en el fenotipo enfisematoso agudizador. Todos los pacientes con el fenotipo agudizador bronquítico crónico tuvieron dos o más exacerbaciones, mientras que el enfisematoso agudizador se relacionó con una severidad grave de la EPOC (46,7 %). Conclusiones: El sexo masculino y la edad avanzada muestran una tendencia a relacionarse con el fenotipo enfisematoso agudizador y agudizador bronquítico crónico, mientras que el tabaquismo activo es más frecuente en el fenotipo enfisematoso agudizador. El fenotipo agudizador bronquítico crónico se relaciona con mayores exacerbaciones y el enfisematoso agudizador con una mayor severidad de la EPOC.

Introduction: The identification of clinical phenotypes are key in the modulation of clinical expression, for an integrated treatment of COPD. Objectives: To characterize the clinical phenotypes of COPD in patients treated at the Hospital Neumológico Benéfico Jurídico. Methods: A retrospective descriptive observational study was carried out in 172 patients with a diagnosis of COPD at the Hospital Neumológico Benéfico Jurídico in 2017. Results: 38.4 % of the patients were between 70-79 years of age. Of the total number of patients, 54.6 % were male. 52.9 % were active smokers and 41.3 % ex-smokers. Although the differences were not significant, advanced age and male sex were more frequent in the exacerbator emphysematous and chronic bronchial exacerbator phenotype. Active smoking was more frequent in the exacerbating emphysematous phenotype. All patients with the chronic bronchial exacerbator phenotype had two or more exacerbations, while exacerbation emphysematous was associated with severe severity of COPD (46.7 %). Conclusions: Male sex and advanced age show a tendency to be related to the exacerbating emphysematous phenotype and chronic bronchitis exacerbator, while active smoking is more frequent in the exacerbating emphysematous phenotype. The chronic bronchitis exacerbator phenotype is related to greater exacerbations and exacerbation emphysematous with a greater severity of COPD

Metabolomic profiling of anaerobic and aerobic energy metabolic pathways in chronic obstructive pulmonary disease.

While there is no cure for chronic obstructive pulmonary disease (COPD), its progressive nature and the formidable challenge to manage its symptoms warrant a more extensive study of the pathogenesis and related mechanisms. A new emphasis on COPD study is the change of energy metabolism. For the first time, this study investigated the anaerobic and aerobic energy metabolic pathways in COPD using the metabolomic approach. Metabolomic analysis was used to investigate energy metabolites in 140 COPD patients. The significance of energy metabolism in COPD was comprehensively explored by the Global Initiative for Chronic Obstructive Lung Disease-GOLD grading, acute exacerbation vs. stable phase (either clinical stability or four-week stable phase), age group, smoking index, lung function, and COPD Assessment Test (CAT) score. Through comprehensive evaluation, we found that COPD patients have a significant imbalance in the aerobic and anaerobic energy metabolisms in resting state, and a high tendency of anaerobic energy supply mechanism that correlates positively with disease progression. This study highlighted the significance of anaerobic and low-efficiency energy supply pathways in lung injury and linked it to the energy-inflammation-lung ventilatory function and the motion limitation mechanism in COPD patients, which implies a novel therapeutic direction for this devastating disease.

Coding of COPD Exacerbations and the Implications on Clinical Practice, Audit and Research.

International Classification of Disease 10 (ICD-10) codes record hospital admissions. We aimed to measure the accuracy of COPD exacerbation (ECOPD) codes and examine coding practices for COPD exacerbation.Prospective screening and ICD-10 codes were used to identify potential ECOPD within the DECAF internal validation cohort. Two coding searches were performed. The first search identified patients with an ECOPD discharge code, and a second, broad search was developed to identify all clinically confirmed ECOPD.717 of 1,122 (64%) patients with an ECOPD code had confirmed ECOPD. Common reasons for misclassification in the 405 patients who did not have an ECOPD included: lack of obstructive spirometry to diagnose COPD; and hospital admission due to progressive malignancy, asthma or cardiovascular disease. The broad search identified an additional 297 patients with ECOPD missed by the ECOPD codes. The vast majority of this group had pneumonia complicating ECOPD.ECOPD codes are insufficiently reliable to identify patients with clinically confirmed ECOPD for the purposes of audit or research. Search strategies should include pneumonia codes, specialist review of medical notes and spirometry confirmation of COPD.

Causes of hospitalization and characteristics of Algerian chronic obstructive pulmonary disease patients in Tizi-Ouzou: a retrospective study.

Chronic obstructive pulmonary disease (COPD) is a progressive chronic inflammatory disease and the third cause of death worldwide in 2016. COPD epidemiology is well documented in high-income countries where the disease is well managed. However, the disease is neglected in low-income countries and there is lack of data. Our study aims to identify COPD patients' characteristics and hospital admission causes, and to determine disease etiologies and associated factors. A retrospective study was conducted in COPD Algerian patients using medical record data collected from January 2007 to May 2017 at the pulmonology department of the Belloua Hospital of Tizi-Ouzou city. Out of 133 hospital admissions for COPD during the study period, only 120 records were found and analyzed. Most of the admitted patients were men (96%) and the mean age was 74.29±9.56 years. Among them, 78.7% were in the GOLD stage III or IV and 9 deaths (7.5%) were recorded during the study period. Interestingly, disease severity is associated with increasing age of the patients and mortality (p=0.01 and p=0.02, respectively). Risk factors include cigarette smoking (93%), history of medical conditions (36.66%) with the most prevalent conditions being emphysema (38.63%) and asthma (27.27%), the cold season (47%), and occupational exposures (58%). Most of the admissions (64.16%) were due to acute dyspnea and 21.66 % to respiratory infections, however, 34.16 % of patients were readmitted at least one time. Comorbidities were observed in 57.5% of the patients, including cardiovascular diseases (63.76%) and diabetes (18.84%). These results show that COPD severity is associated with age and mortality. Better understanding of the COPD etiologies and the causes of hospital admission will lead to more effective management of the disease.

Uric acid and uric acid to creatinine ratio in the assessment of chronic obstructive pulmonary disease: Potential biomarkers in multicomponent models comprising IL-1beta.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, with oxidative stress and inflammation implicated in its development. Uric acid (UA) could exert anti-oxidative, pro-oxidative or pro-inflammatory effects, depending on the specific context. It was recently shown that soluble UA, and not just its crystals, could activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to interleukin (IL)-1ß secretion. We aimed to assess the differences in blood levels of UA and its ratio with creatinine (UCR) between COPD patients and healthy subjects, as well as their association with disease severity, smoking status, common COPD comorbidities and therapy regimes. The diagnostic characteristics of UA and UCR were also explored. This study included 109 stable COPD patients and 95 controls and measured white blood cells (WBC), C-reactive protein (CRP), fibrinogen (Fbg), IL-1ß, creatinine (CREAT) and UA. All of the parameters were increased in COPD patients, except for CREAT. UA and UCR were positively associated with WBC, CRP and IL-1ß. COPD smokers had lower UA and UCR values. Common COPD therapy did not affect UA or UCR, while patients with cardiovascular diseases (CVD) had higher UA, but not UCR, levels. Patients with higher UCR values showed worse disease-related outcomes (lung function, symptoms, quality of life, history of exacerbations, BODCAT and BODEx). Also, UCR differentiated patients with different severity of airflow limitation as well as symptoms and exacerbations. The great individual predictive potential of UCR and IL-1ß was observed with their odds ratios (OR) being 2.09 and 5.53, respectively. Multiparameter models of UA and UCR that included IL-1ß were able to correctly classify 86% and 90% of cases, respectively. We suggest that UA might be a useful biomarker when combined with IL-1ß, while UCR might be even more informative and useful in overall COPD assessments.

Initiation of triple therapy maintenance treatment among patients with COPD.

OBJECTIVES: Triple therapy is indicated for patients with very severe chronic obstructive pulmonary disease (COPD). Use of this treatment in the appropriate patient population is important to ensure optimal outcomes. This study quantified the use of triple therapy and assessed concordance with 2013-2016 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations within a national health plan. STUDY DESIGN: Retrospective cohort study using data from a large national health plan. METHODS: To estimate the prevalence of triple therapy using claims data, patients in the first of 2 cohorts were indexed on their first diagnosis of COPD between January 1, 2012, and December 31, 2014, and required to have 24 months postindex continuous enrollment. To assess concordance with GOLD recommendations, a second cohort was created and indexed on the date of triple therapy initiation between January 1, 2013, and November 30, 2016, and required to have 12 months preindex and 1 month postindex continuous enrollment. For both cohorts, patients were aged 40 years or older, with no International Classification of Diseases code for asthma, cystic fibrosis, or lung cancer during the study period. RESULTS: In the first cohort of 92,248 patients with COPD receiving any COPD maintenance medication, 17% were prescribed triple therapy. In the second cohort (n = 19,645), the majority (60%) of patients on triple therapy were classified as GOLD group A or B (ie, no evidence of any exacerbation or only 1 exacerbation not resulting in hospitalization at baseline). CONCLUSIONS: Results showed that triple therapy was often prescribed among patients classified as GOLD group A or B. Additional research is required, however, to further assess whether these patients may have had an exacerbation that was not evident in claims data. Treatment of COPD should be individualized to optimize outcomes and reduce adverse events.

Molecular Profiling of Vascular Remodeling in Chronic Pulmonary Disease.

Pulmonary hypertension and pulmonary vascular remodeling (PVR) are common in many lung diseases leading to right ventricular dysfunction and death. Differences in PVR result in significant prognostic divergences in both the pulmonary arterial and venous compartments, as in pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease (PVOD), respectively. Our goal was to identify compartment-specific molecular hallmarks of PVR, considering the risk of life-threatening pulmonary edema in PVOD, if treated by conventional pulmonary hypertension therapy. Formalin-fixed and paraffin-embedded tissues from fresh explanted human lungs of patients with PVOD (n = 19), PAH (n = 20), idiopathic pulmonary fibrosis (n = 13), and chronic obstructive pulmonary disease (n = 15), were analyzed for inflammation and kinome-related gene regulation. The generated neuronal network differentiated PVOD from PAH samples with a sensitivity of 100% and a specificity of 92% in a randomly chosen validation set, a level far superior to established diagnostic algorithms. Further, various alterations were identified regarding the gene expression of explanted lungs with PVR, compared with controls. Specifically, the dysregulation of microtubule-associated serine/threonine kinase 2 and protein-o-mannose kinase SGK196 in all disease groups suggests a key role in pulmonary vasculopathy for the first time. Our findings promise to help develop novel target-specific interventions and innovative approaches to facilitate clinical diagnostics in an elusive group of diseases.

Subtyping COPD by Using Visual and Quantitative CT Imaging Features.

BACKGROUND: Multiple studies have identified COPD subtypes by using visual or quantitative evaluation of CT images. However, there has been no systematic assessment of a combined visual and quantitative CT imaging classification. We integrated visually defined patterns of emphysema with quantitative imaging features and spirometry data to produce a set of 10 nonoverlapping CT imaging subtypes, and we assessed differences between subtypes in demographic features, physiological characteristics, longitudinal disease progression, and mortality. METHODS: We evaluated 9,080 current and former smokers in the COPDGene study who had available volumetric inspiratory and expiratory CT images obtained using a standardized imaging protocol. We defined 10 discrete, nonoverlapping CT imaging subtypes: no CT imaging abnormality, paraseptal emphysema (PSE), bronchial disease, small airway disease, mild emphysema, upper lobe predominant centrilobular emphysema (CLE), lower lobe predominant CLE, diffuse CLE, visual without quantitative emphysema, and quantitative without visual emphysema. Baseline and 5-year longitudinal characteristics and mortality were compared across these CT imaging subtypes. RESULTS: The overall mortality differed significantly between groups (P < .01) and was highest in the 3 moderate to severe CLE groups. Subjects having quantitative but not visual emphysema and subjects with visual but not quantitative emphysema were unique groups with mild COPD, at risk for progression, and with likely different underlying mechanisms. Subjects with PSE and/or moderate to severe CLE had substantial progression of emphysema over 5 years compared with findings in subjects with no CT imaging abnormality (P < .01). CONCLUSIONS: The combination of visual and quantitative CT imaging features reflects different underlying pathological processes in the heterogeneous COPD syndrome and provides a useful approach to reclassify types of COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Association of Symptoms of Obstructive Lung Disease and All-Cause Mortality in Older Adult Smokers.

OBJECTIVES: This study aims to investigate the impact of respiratory symptoms in current and former smokers with and without obstructive lung disease (OLD) on all-cause mortality. DESIGN: Secondary analysis in a prospective cohort (the Health, Aging and Body Composition study). SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Black and white men and women with a history of current and former smoking (N = 596; 63% male and 37% female) aged 70-79 years followed for 13 years. Participants were categorized into 4 mutually exclusive groups based on symptom profile and forced expiratory volume in the 1st second to forced vital capacity ratio. The groups were Less Dyspnea-No OLD (N = 196), More Dyspnea-No OLD (N = 104), Less Dyspnea-With OLD (N = 162), and More Dyspnea-With OLD (N = 134). MEASUREMENTS: All-cause mortality. RESULTS: Overall, 53% in Less Dyspnea-No OLD, 63% in More Dyspnea-No OLD, 67% in Less Dyspnea-With OLD, and 84% in More Dyspnea-With OLD died within the 13- year follow up period (log-rank χ2 = 44.4, P < .0001). The hazard ratio was highest for participants with OLD, both with (HR =1.91, 95% CI 1.44 - 2.54; P < .0001) and without dyspnea (HR = 1.52, 95% CI 1.15 - 2.02; p = .004). Participants without OLD but with dyspnea had a similar risk of death to subjects who had OLD but fewer symptoms. CONCLUSIONS: OLD is associated with high risk of death with different risk profiles based on symptom group. Patients with symptoms of shortness of breath without OLD should be considered an at-risk group given their similar mortality to those with OLD with minimal symptoms. J Am Geriatr Soc 67:2116-2122, 2019.

Supervivencia en una cohorte de pacientes con enfermedad pulmonar obstructiva crónica acorde a la clasificación GOLD 2017 / Survival in a cohort of patients with chronic obstructive pulmonary disease according to GOLD 2017 classification

Hasta el momento, no existe información sobre la evolución de los pacientes con enfermedad pulmonar obstructiva crónica (EPOC) de acuerdo con la nueva clasificación GOLD 2017. El objetivo de este estudio fue determinar, en una cohorte de pacientes con EPOC seguidos por veinte años, la influencia del cambio a la nueva clasificación en resultados de supervivencia por grupos y su asociación con otras variables como comorbilidades. Se evaluaron enfermos con EPOC (definición GOLD 2017) con seguimiento desde enero de 1996 a diciembre de 2016. Se usaron estadísticas convencionales y análisis de supervivencia de Log- Rank (Mantel-Cox). Se analizaron 354 pacientes: edad 66.5 ± 8.4, 66.7% hombres; ex-tabaquistas: 74.2% (56 paquetes-año); índice de Charlson 4.1 ± 1.7. A los 20 años, estaban vivos 219 (62%) y fallecidos 135 (38%), con un seguimiento de 28 meses (12-54.7). En el análisis uni y multivariado, el sexo masculino y la edad se asociaron a mayor mortalidad. Teniendo en cuenta solo la espirometría, a peor grado de obstrucción al flujo aéreo, la supervivencia es menor. Con la clasificación ABCD 2017, la peor supervivencia se encuentra en el grupo D y solo en este grupo es independiente del nivel de deterioro del VEF1 (p = 0.005). La nueva clasificación ABCD es predictora de mortalidad solo si está asociada a la función pulmonar.

Until now, there is no information on the evolution of patients with chronic obstructive pulmonary disease (COPD) according to the new GOLD classification. The objective of this study was to determine, in a cohort of patients with COPD followed by twenty years, the impact of the change to the new classification: survival by groups and their association with other variables such as comorbidities. COPD patients (GOLD 2017 definition) were evaluated with follow-up since January 1996 to December 2016. Conventional statistics and Log-Rank survival analysis (Mantel-Cox) were used. We analyzed 354 patients: age 66.5 ± 8.4, 66.7% men. Former smokers 74.2% (56 pack-year). Charlson index 4.1 ± 1.7. At the end of study 219 (62%) were alive and 135 (38%) died. The follow-up was 28 months (12-54.7). In the univariate and multivariate analysis, male sex and age were associated with higher mortality. Considering only the spirometry, to a worse degree of airflow obstruction, corresponded a lower survival. With the ABCD 2017 classification, the worst survival was observed in group D. Only in this group, survival is independent of the level of deterioration of FEV1 (p = 0.005). The new ABCD classification is a mortality predictor, only if it is associated to pulmonary function.

Feasibility of deriving a novel imaging biomarker based on patient-specific lung elasticity for characterizing the degree of COPD in lung SBRT patients.

OBJECTIVE:: Lung tissue elasticity is an effective spatial representation for Chronic Obstructive Pulmonary Disease phenotypes and pathophysiology. We investigated a novel imaging biomarker based on the voxel-by-voxel distribution of lung tissue elasticity. Our approach combines imaging and biomechanical modeling to characterize tissue elasticity. METHODS:: We acquired 4DCT images for 13 lung cancer patients with known COPD diagnoses based on GOLD 2017 criteria. Deformation vector fields (DVFs) from the deformable registration of end-inhalation and end-exhalation breathing phases were taken to be the ground-truth. A linear elastic biomechanical model was assembled from end-exhalation datasets with a density-guided initial elasticity distribution. The elasticity estimation was formulated as an iterative process, where the elasticity was optimized based on its ability to reconstruct the ground-truth. An imaging biomarker (denoted YM1-3) derived from the optimized elasticity distribution, was compared with the current gold standard, RA950 using confusion matrix and area under the receiver operating characteristic (AUROC) curve analysis. RESULTS:: The estimated elasticity had 90 % accuracy when representing the ground-truth DVFs. The YM1-3 biomarker had higher diagnostic accuracy (86% vs 71 %), higher sensitivity (0.875 vs 0.5), and a higher AUROC curve (0.917 vs 0.875) as compared to RA950. Along with acting as an effective spatial indicator of lung pathophysiology, the YM1-3 biomarker also proved to be a better indicator for diagnostic purposes than RA950. CONCLUSIONS:: Overall, the results suggest that, as a biomarker, lung tissue elasticity will lead to new end points for clinical trials and new targeted treatment for COPD subgroups. ADVANCES IN KNOWLEDGE:: The derivation of elasticity information directly from 4DCT imaging data is a novel method for performing lung elastography. The work demonstrates the need for a mechanics-based biomarker for representing lung pathophysiology.

Estudio comparativo de la estadificación de pacientes con EPOC según GOLD 2007, 2011 y 2019 / Comparative study of the categorization of COPD patients based on GOLD 2007, 2011 and 2019

INTRODUCCIÓN: La Enfermedad Pulmonar Obstructiva Crónica afecta a 260 millones de personas a nivel mundial y representará la tercera causa de muerte para el año 2020. MATERIALES Y MÉTODOS: Se realizó un estudio observacional descriptivo transversal con la finalidad de comparar la estadificación de un grupo de pacientes venezolanos con EPOC según la Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2007, 2011 y 2019. RESULTADOS: La muestra estuvo constituida por ochenta y nueve (89) pacientes con una edad promedio de 66,7 ± 0,9 años, siendo el 60,7% de los pacientes del sexo masculino y 82% fumadores. El 14,6% de los pacientes presentaban EPOC leve, 36% EPOC moderado, 41,6% EPOC severo y 7,9% EPOC muy severo. El valor del test Kappa de Cohen entre las escalas mMRC y CAT (COPD Assessment Test) fue de 0,529 (GOLD 2011) y 0,555 (GOLD 2019). CONCLUSIONES: 1) la poca concordancia entre el VEF1, grado de disnea e historial de exacerbaciones impacta la clasificación de la severidad de la EPOC al utilizar GOLD 2011; 2) la concordancia moderada entre las escalas mMRC y CAT sugiere que el tipo de cuestionario utilizado afecta la categorización de la severidad de la enfermedad; 3) los pacientes del grupo B mostraron una importante afectación en el intercambio gaseoso dado por valores más bajos de DLCO y oximetría arterial y 4) una proporción significativa de pacientes fueron clasificados en los grupos de alto riesgo (B y D) en GOLD 2011 y 2019.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) affects 260 million people worldwide and it is thought to become the third leading cause of mortality by the year 2020. MATERIAL AND METHODS: A transversal descriptive observational study was conducted to compare the categorization of a group of Venezuelan COPD patients according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2007, 2011 and 2019. RESULTS: Eighty-nine (89) patients with a mean age of 66.7 ± 0.9 years were included, 60.7% were male and 82% smokers. 14.6% of the patients had mild COPD, 36% moderate COPD, 41.6% severe COPD and 7.9% very severe COPD. Cohen's Kappa coefficient value between mMRC and COPD Assessment test (CAT) was 0,529 (GOLD 2011) and 0,555 (GOLD 2019). CONCLUSIONS: 1) the lack of concordance between FEV1 values, degree of dyspnea and history of exacerbations impacts COPD severity classification when using GOLD 2011; 2) moderate agreement between mMRC and CAT scales suggests that the type of questionnaire used to evaluate perception of dyspnea can affect disease severity categorization; 3) group B patients showed a significant gas exchange impairment due to lower values of DLCO and arterial oxymetry and 4) a significant proportion of patients were categorized in the high-risk groups (B and D) both in GOLD 2011 and 2019. Optimization of the evaluation of COPD severity is important to allow a better standardization of care and pharmacological management of patients with this disease.

Typing of chronic obstructive pulmonary disease using high-resolution computed tomography and the association with smoking, airway inflammation, and common comorbidities

Background/aim: This study performed typing of chronic obstructive pulmonary disease (COPD) using high-resolution computed tomography (HRCT) to determine the association with smoking, matrix metalloproteinases, and common comorbidities. Materials and methods: The study enrolled 94 hospitalized patients. Participants were divided into a group of 69 current and former smokers (group A) and a group of 25 that had never smoked (group B). Patients were also divided into 3 categories according to the degree of emphysema and bronchial wall thickness using HRCT to determine the association with levels of matrix metalloproteinase 9 (MMP-9) and TIMP-1, as well as associated comorbidities. These three categories were: type A - no or mild emphysema, with or without bronchial wall thickening; type E - emphysema without bronchial wall thickening; and type M - both emphysema and bronchial wall thickening. Results: The low attenuation area (LAA) scores in group A patients were higher than those in group B (t = 2.86, P < 0.01); correlation analysis showed that smoking was associated with a decline of the forced expiratory volume in 1 s and forced vital capacity ratio (FEV1/ FVC%) and higher LAA scores in patients with COPD (F = 4.46, F = 8.20, P < 0.05). The levels of MMP-9 in group A were higher than those in group B (t = 3.65, P < 0.01). Among COPD patients with more than 3 comorbidities, there were statistically significant differences in both the smoking group and the nonsmoking group (chi-square = 12.08, P < 0.01). When compared to type A patients, who had coincident cardiovascular diseases in the smoking group, patients of type M and E showed statistically significant differences (F = 2.42 and 2.12, P < 0.05). Conclusion: Emphysema was more severe in smokers. Metalloproteinase levels in smokers were higher than those in nonsmokers. Moreover, comorbidities were more severe in smokers.

Heme scavenging reduces pulmonary endoplasmic reticulum stress, fibrosis, and emphysema.

Pulmonary fibrosis and emphysema are irreversible chronic events after inhalation injury. However, the mechanism(s) involved in their development remain poorly understood. Higher levels of plasma and lung heme have been recorded in acute lung injury associated with several insults. Here, we provide the molecular basis for heme-induced chronic lung injury. We found elevated plasma heme in chronic obstructive pulmonary disease (COPD) (GOLD stage 4) patients and also in a ferret model of COPD secondary to chronic cigarette smoke inhalation. Next, we developed a rodent model of chronic lung injury, where we exposed C57BL/6 mice to the halogen gas, bromine (Br2) (400 ppm, 30 minutes), and returned them to room air resulting in combined airway fibrosis and emphysematous phenotype, as indicated by high collagen deposition in the peribronchial spaces, increased lung hydroxyproline concentrations, and alveolar septal damage. These mice also had elevated pulmonary endoplasmic reticulum (ER) stress as seen in COPD patients; the pharmacological or genetic diminution of ER stress in mice attenuated Br2-induced lung changes. Finally, treating mice with the heme-scavenging protein, hemopexin, reduced plasma heme, ER stress, airway fibrosis, and emphysema. This is the first study to our knowledge to report elevated heme in COPD patients and establishes heme scavenging as a potential therapy after inhalation injury.

Comparison of the clinical characteristics and comprehensive assessments of the 2011 and 2017 GOLD classifications for patients with COPD in China.

OBJECTIVE: Compared with the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD), there have been significant changes in the 2017 GOLD classification. The purpose of this study was to analyze the changes in clinical characteristics of the new A-B-C-D system and to explore its role in comprehensive assessment of COPD. SUBJECTS AND METHODS: A total of 631 stable COPD patients were included in a cross-sectional survey. Data collected included baseline data and pulmonary function testing results, respiratory muscle strength, symptoms and quality of life, exercise capacity, nutritional status, and anxiety and depression as a comprehensive assessment. Based on the 2011 GOLD and 2017 GOLD classifications, patients were divided into Groups A1-D1 and Groups A2-D2, respectively. RESULTS: In the 2011 GOLD, 64 subjects in Group C1 were reclassified into Group A2 (41.6%), while 77 subjects in Group D1 were reclassified into Group B2 (27.1%). The old and new grading systems were somewhat consistent (Cohen's kappa=0.6963, P<0.001). Lung function was lower, while the body mass index, airflow obstruction, dyspnea, and exercise capacity index (BODE index) was higher in Group A2 than in Group A1 (P<0.001). In Group B2, lung function, 6-minute walking distance (6MWD), and respiratory muscle strength were significantly lower than in Group B1 (P<0.001), while the BODE index (P<0.001) was higher. In comprehensive assessment, subjects in Groups B2 and D2 had significantly lower lung function, 6MWD, respiratory muscle strength, quality of life, higher symptom scores, and BODE index than subjects in Group A2 (P<0.001). The differences between Group A2 and C2 were small. CONCLUSION: Compared with the 2011 GOLD, the 2017 GOLD reclassified more patients into Groups A and B, those with significantly worse lung function and higher BODE index. In the comprehensive assessment of the new classification, Groups B and D may have greater disease severity. However, the effectiveness of the new grading system in predicting patient prognosis, and its guidance on the use of drugs, remains to be explored in future studies.