Pub Date : 2024-04-03DOI: 10.15326/jcopdf.2023.0477
I. M. Hardang, V. Søyseth, N. Kononova, Tor-Arne Hagve, G. Einvik
Background The prevalence of iron deficiency in patients with COPD varies in previous studies. We aimed to assess its prevalence according to three well-known criteria for iron deficiency, its associations with clinical characteristics of COPD and mortality. Methods In a cohort study consisting of 84 COPD patients, of which 21 had chronic respiratory failure, and 59 non-COPD controls, ferritin, TSat and mortality across 6.5 years were assessed. Associations between clinical characteristics and iron deficiency were examined by logistic regression, while associations with mortality were assessed in mixed effects Cox regression analyses. Results The prevalence of iron deficiency in the study population was 10-43% according to diagnostic criteria, and was consistently higher in COPD, peaking at 71% in participants with chronic respiratory failure. Ferritin < cutoff was significantly associated with FEV1 (OR 0.33 per liter increase), smoking (OR 3.2) and cardiovascular disease (OR 4.7). TSat < 20% was associated with BMI (OR 1.1 per kg/m2 increase) and hemoglobin (OR 0.65 per g/dL increase). The combined criterion of low ferritin and TSat was only associated with FEV1 (OR 0.39 per liter increase). Mortality was not significantly associated with iron deficiency (HR 1.2-1.8) in adjusted analyses. Conclusion The prevalence of iron deficiency in the study population increased with increasing severity of COPD. Iron deficiency, defined by ferritin < cutoff, was associated with bronchial obstruction, current smoking and cardiovascular disease, while TSat < 20% was associated with reduced level of hemoglobin and increased BMI. Iron deficiency was not associated with increased mortality.
{"title":"COPD: Iron Deficiency and Clinical Characteristics in Patients With and Without Chronic Respiratory Failure.","authors":"I. M. Hardang, V. Søyseth, N. Kononova, Tor-Arne Hagve, G. Einvik","doi":"10.15326/jcopdf.2023.0477","DOIUrl":"https://doi.org/10.15326/jcopdf.2023.0477","url":null,"abstract":"Background\u0000The prevalence of iron deficiency in patients with COPD varies in previous studies. We aimed to assess its prevalence according to three well-known criteria for iron deficiency, its associations with clinical characteristics of COPD and mortality.\u0000\u0000\u0000Methods\u0000In a cohort study consisting of 84 COPD patients, of which 21 had chronic respiratory failure, and 59 non-COPD controls, ferritin, TSat and mortality across 6.5 years were assessed. Associations between clinical characteristics and iron deficiency were examined by logistic regression, while associations with mortality were assessed in mixed effects Cox regression analyses.\u0000\u0000\u0000Results\u0000The prevalence of iron deficiency in the study population was 10-43% according to diagnostic criteria, and was consistently higher in COPD, peaking at 71% in participants with chronic respiratory failure. Ferritin < cutoff was significantly associated with FEV1 (OR 0.33 per liter increase), smoking (OR 3.2) and cardiovascular disease (OR 4.7). TSat < 20% was associated with BMI (OR 1.1 per kg/m2 increase) and hemoglobin (OR 0.65 per g/dL increase). The combined criterion of low ferritin and TSat was only associated with FEV1 (OR 0.39 per liter increase). Mortality was not significantly associated with iron deficiency (HR 1.2-1.8) in adjusted analyses.\u0000\u0000\u0000Conclusion\u0000The prevalence of iron deficiency in the study population increased with increasing severity of COPD. Iron deficiency, defined by ferritin < cutoff, was associated with bronchial obstruction, current smoking and cardiovascular disease, while TSat < 20% was associated with reduced level of hemoglobin and increased BMI. Iron deficiency was not associated with increased mortality.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"138 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140750273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-03DOI: 10.15326/jcopdf.2023.0492
P. Kaenmuang, A. Navasakulpong, Sarayut L Geater, Sirikorn Densrisereekul, S. Juthong
Background The blood eosinophil count (BEC) is an effective biomarker for predicting inhaled corticosteroid responsiveness in patients with chronic obstructive pulmonary disease (COPD). Methods A 12-month prospective observational study was conducted in patients with COPD. BEC was measured at enrolment, and after 6 and 12 months. Patients were classified into three groups according to their baseline BEC: <100, 100 - 299, and ≥300 cells/µL. We aimed to describe the patterns of blood eosinophil stability in patients with stable COPD and compare the exacerbation rates and other clinical outcomes at 6 and 12 months. Results A total of 252 patients with COPD were included. The <100, 100 - 299, and ≥ 300 cells/μL groups consisted of 14.7, 38.9, and 46.4% of patients, respectively. BEC stability was highest (85%) in the ≥300 cells/μL group for both durations. The lowest stability was observed in the <100 cells/μL group at 57 and 46% after 6 and 12 months, respectively. The persistent ≥ 300 cells/μL group had a higher incidence of moderate-to-severe exacerbation (IRR 2.44, 95% confidence interval (CI): 1.13-5.27, p value 0.023, as well as severe exacerbation (IRR 2.19, 95%CI: 1.39-3.45, p value 0.001). Other patient-reported outcomes did not differ significantly between groups. Conclusion Blood eosinophil levels had good stability in patients with COPD with BEC ≥300 cells/µL and was associated with a high risk of exacerbation in the persistent ≥300 cells/μL group. The variability of BEC was higher in patients with COPD with BEC <300 cells/µL.
{"title":"Blood Eosinophil Count Stability and Clinical Outcomes in Patients With Chronic Obstructive Pulmonary Disease in a High Endemic Area of Parasitic Infection: A Prospective Study.","authors":"P. Kaenmuang, A. Navasakulpong, Sarayut L Geater, Sirikorn Densrisereekul, S. Juthong","doi":"10.15326/jcopdf.2023.0492","DOIUrl":"https://doi.org/10.15326/jcopdf.2023.0492","url":null,"abstract":"Background\u0000The blood eosinophil count (BEC) is an effective biomarker for predicting inhaled corticosteroid responsiveness in patients with chronic obstructive pulmonary disease (COPD).\u0000\u0000\u0000Methods\u0000A 12-month prospective observational study was conducted in patients with COPD. BEC was measured at enrolment, and after 6 and 12 months. Patients were classified into three groups according to their baseline BEC: <100, 100 - 299, and ≥300 cells/µL. We aimed to describe the patterns of blood eosinophil stability in patients with stable COPD and compare the exacerbation rates and other clinical outcomes at 6 and 12 months.\u0000\u0000\u0000Results\u0000A total of 252 patients with COPD were included. The <100, 100 - 299, and ≥ 300 cells/μL groups consisted of 14.7, 38.9, and 46.4% of patients, respectively. BEC stability was highest (85%) in the ≥300 cells/μL group for both durations. The lowest stability was observed in the <100 cells/μL group at 57 and 46% after 6 and 12 months, respectively. The persistent ≥ 300 cells/μL group had a higher incidence of moderate-to-severe exacerbation (IRR 2.44, 95% confidence interval (CI): 1.13-5.27, p value 0.023, as well as severe exacerbation (IRR 2.19, 95%CI: 1.39-3.45, p value 0.001). Other patient-reported outcomes did not differ significantly between groups.\u0000\u0000\u0000Conclusion\u0000Blood eosinophil levels had good stability in patients with COPD with BEC ≥300 cells/µL and was associated with a high risk of exacerbation in the persistent ≥300 cells/μL group. The variability of BEC was higher in patients with COPD with BEC <300 cells/µL.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"64 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140748083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-03DOI: 10.15326/jcopdf.2023.0467
Kevin P Ferriter, Mike C Parent, Maggie Britton
Smoking, a leading cause of chronic respiratory disorders, is elevated among sexual minority (i.e., lesbian, gay, and bisexual) individuals. Elevations in smoking among sexual minority individuals may contribute to increased rates of chronic respiratory disorders among older sexual minority individuals. Data from 161,741 individuals (3.6% sexual minorities) aged 45 and older from the 2020 Behavioral Risk Factor Surveillance System were used to examine disparities in chronic respiratory disorders among older sexual minority individuals. Mediation was used to analyze a model with smoking mediating the relationship between sexual minority identity and self-reported chronic respiratory disorder. The results indicated that smoking mediated the relationship between sexual minority identity and self-reported chronic respiratory disorder. Smoking was 1.2 times more common, and the prevalence of chronic respiratory disorders was 1.2 times higher, among sexual minority individuals compared to heterosexual individuals. The present study indicates that smoking disparities observed among sexual minority individuals are linked to increased risk for chronic respiratory disorders, and also indicate that sexual minorities have an excess burden of chronic respiratory disorders.
{"title":"Sexual Orientation Health Disparities in Chronic Respiratory Disorders.","authors":"Kevin P Ferriter, Mike C Parent, Maggie Britton","doi":"10.15326/jcopdf.2023.0467","DOIUrl":"https://doi.org/10.15326/jcopdf.2023.0467","url":null,"abstract":"Smoking, a leading cause of chronic respiratory disorders, is elevated among sexual minority (i.e., lesbian, gay, and bisexual) individuals. Elevations in smoking among sexual minority individuals may contribute to increased rates of chronic respiratory disorders among older sexual minority individuals. Data from 161,741 individuals (3.6% sexual minorities) aged 45 and older from the 2020 Behavioral Risk Factor Surveillance System were used to examine disparities in chronic respiratory disorders among older sexual minority individuals. Mediation was used to analyze a model with smoking mediating the relationship between sexual minority identity and self-reported chronic respiratory disorder. The results indicated that smoking mediated the relationship between sexual minority identity and self-reported chronic respiratory disorder. Smoking was 1.2 times more common, and the prevalence of chronic respiratory disorders was 1.2 times higher, among sexual minority individuals compared to heterosexual individuals. The present study indicates that smoking disparities observed among sexual minority individuals are linked to increased risk for chronic respiratory disorders, and also indicate that sexual minorities have an excess burden of chronic respiratory disorders.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"1062 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140749290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-16DOI: 10.15326/jcopdf.2022.0388
®. Foundation, DO Manuel Izquierdo, DO PhD Chad R. Marion, DO Frank Genese, MD John D. Newell, PhD Wanda K. O’Neal, PhD Xingnan Li, PhD Gregory A. Hawkins, MD PhD Igor Barjaktarevic, MD PhD R. Graham Barr, MD Stephanie Christenson, MD Christopher B. Cooper, PhD David Couper, MD Jeffrey Curtis, M. M. Meilan K. Han, M. M. Nadia N. Hansel, MD Richard E. Kanner, MD Fernando J. Martinez, Iii Robert Paine, MD Vickram Tejwani, M. M. Prescott G. Woodruff, MD PhD Joe G. Zein, PhD Eric A. Hoffman, MD PhD Stephen P. Peters, PhD Deborah A. Meyers, MD Eugene R. Bleecker, MD Victor E. Ortega
Rationale Bronchiectasis is common among those with heavy smoking histories, but risk factors for bronchiectasis, including α1-antitrypsin deficiency and its implications for COPD severity are uncharacterized in such individuals. Objectives To characterize the impact of bronchiectasis on COPD and explore α1-antitrypsin as a risk factor for bronchiectasis. Methods SPIROMICS participants (N=914; ages 40-80 years; ≥20 pack-years smoking) had HRCT scans interpreted visually for bronchiectasis, based on airway dilation without fibrosis or cicatrization. We performed regression-based models of bronchiectasis with clinical outcomes and quantitative CT measures. We deeply sequenced the gene encoding α1-antritrypsin, SERPINA1, in 835 participants to test for rare variants, focusing on PiZ (Glu366Lys, rs28929474). Measurements and Main Results We identified bronchiectasis in 365 (40%), more frequently in women (45% versus 36%, p=0.0045), older participants (mean age=66[SD=8.3] versus 64[SD=9.1] years, p=0.0083), and those with lower lung function (FEV1%predicted=66%[SD=27] versus 77%[SD=25], p<0.0001; FEV1/FVC=0.54[0.17] versus 0.63[SD=0.16], p<0.0001]. Participants with bronchiectasis had greater emphysema (%voxels ≤-950HFU, 11%[SD=12] versus 6.3%[SD=9], p<0.0001) and PRMfSAD (26[SD=15] versus 19[SD=15], p<0.0001). Bronchiectasis was more frequent in the combined PiZZ and PiMZ genotype groups compared to those without PiZ, PiS, or other rare pathogenic variants (N=21 of 40[52%] versus N=283 of 707[40%], OR=1.97; 95%CI=1.002, 3.90, p=0.049), an association attributed to whites (OR=1.98; 95%CI = 0.9956, 3.9; p=0.051). Conclusions Bronchiectasis was common in those with heavy smoking histories and was associated with detrimental clinical and radiographic outcomes. Our findings support α1-antitrypsin guideline recommendations to screen for α1-antitrypsin deficiency in an appropriate bronchiectasis subgroup with a significant smoking history.
{"title":"Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History.","authors":"®. Foundation, DO Manuel Izquierdo, DO PhD Chad R. Marion, DO Frank Genese, MD John D. Newell, PhD Wanda K. O’Neal, PhD Xingnan Li, PhD Gregory A. Hawkins, MD PhD Igor Barjaktarevic, MD PhD R. Graham Barr, MD Stephanie Christenson, MD Christopher B. Cooper, PhD David Couper, MD Jeffrey Curtis, M. M. Meilan K. Han, M. M. Nadia N. Hansel, MD Richard E. Kanner, MD Fernando J. Martinez, Iii Robert Paine, MD Vickram Tejwani, M. M. Prescott G. Woodruff, MD PhD Joe G. Zein, PhD Eric A. Hoffman, MD PhD Stephen P. Peters, PhD Deborah A. Meyers, MD Eugene R. Bleecker, MD Victor E. Ortega","doi":"10.15326/jcopdf.2022.0388","DOIUrl":"https://doi.org/10.15326/jcopdf.2022.0388","url":null,"abstract":"Rationale\u0000Bronchiectasis is common among those with heavy smoking histories, but risk factors for bronchiectasis, including α1-antitrypsin deficiency and its implications for COPD severity are uncharacterized in such individuals.\u0000\u0000\u0000Objectives\u0000To characterize the impact of bronchiectasis on COPD and explore α1-antitrypsin as a risk factor for bronchiectasis.\u0000\u0000\u0000Methods\u0000SPIROMICS participants (N=914; ages 40-80 years; ≥20 pack-years smoking) had HRCT scans interpreted visually for bronchiectasis, based on airway dilation without fibrosis or cicatrization. We performed regression-based models of bronchiectasis with clinical outcomes and quantitative CT measures. We deeply sequenced the gene encoding α1-antritrypsin, SERPINA1, in 835 participants to test for rare variants, focusing on PiZ (Glu366Lys, rs28929474).\u0000\u0000\u0000Measurements and Main Results\u0000We identified bronchiectasis in 365 (40%), more frequently in women (45% versus 36%, p=0.0045), older participants (mean age=66[SD=8.3] versus 64[SD=9.1] years, p=0.0083), and those with lower lung function (FEV1%predicted=66%[SD=27] versus 77%[SD=25], p<0.0001; FEV1/FVC=0.54[0.17] versus 0.63[SD=0.16], p<0.0001]. Participants with bronchiectasis had greater emphysema (%voxels ≤-950HFU, 11%[SD=12] versus 6.3%[SD=9], p<0.0001) and PRMfSAD (26[SD=15] versus 19[SD=15], p<0.0001). Bronchiectasis was more frequent in the combined PiZZ and PiMZ genotype groups compared to those without PiZ, PiS, or other rare pathogenic variants (N=21 of 40[52%] versus N=283 of 707[40%], OR=1.97; 95%CI=1.002, 3.90, p=0.049), an association attributed to whites (OR=1.98; 95%CI = 0.9956, 3.9; p=0.051).\u0000\u0000\u0000Conclusions\u0000Bronchiectasis was common in those with heavy smoking histories and was associated with detrimental clinical and radiographic outcomes. Our findings support α1-antitrypsin guideline recommendations to screen for α1-antitrypsin deficiency in an appropriate bronchiectasis subgroup with a significant smoking history.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77725325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Pappe, R. Hammerich, J. Saccomanno, T. Sgarbossa, A. Pohrt, B. Schmidt, C. Grah, S. Eisenmann, A. Holland, S. Eggeling, F. Stanzel, M. Witzenrath, R. Hübner
Introduction Patient with chronic obstructive lung disease (COPD) have an increased risk of severe Coronavirus disease (COVID-19), which is why self-isolation was recommended. However, long periods of social isolation accompanied with limited access to health care systems might influence the outcome of patients with severe COPD negatively. Methods Data from COPD and pneumonia patients at Charité-Universitätsmedizin, Berlin and the volume of endoscopic lung volume reduction (ELVR) from the German lung emphysema registry (Lungenemphysem Register e.V.) were analyzed from pre-pandemic (2012 to 2019) to pandemic (2020 and 2021) period. In addition, 52 patients with COPD GOLD IV status included in the lung emphysema registry received questionnaires during lockdowns from June 2020 to April 2021. Results Admissions and ventilation therapies administered to COPD patients significantly decreased during the COVID-19 pandemic. Likewise, there was a reduction of ELVR treatments and follow-ups registered in German emphysema centers. Mortality was slightly higher among patients hospitalized with COPD during pandemic. Increasing proportions of COPD patients with GOLD III and GOLD IV status reported behavioral changes and subjective feelings of increasing COPD symptoms the longer the lockdown lasted. However, COPD symptom questionnaires revealed stable COPD symptoms over the pandemic time-period. Summary This study reveals reduced COPD admissions and elective treatment procedures of COPD patients during pandemic, but a slight increase of mortality among patients hospitalized with COPD irrespective of COVID-19. Correspondingly, patients with severe COPD reported subjective deterioration of their health status probably caused by their very strict compliance to lockdown measures.
{"title":"Impact of COVID-19 on Hospital Admissions, Health Status, and Behavioral Changes of Patients with COPD.","authors":"E. Pappe, R. Hammerich, J. Saccomanno, T. Sgarbossa, A. Pohrt, B. Schmidt, C. Grah, S. Eisenmann, A. Holland, S. Eggeling, F. Stanzel, M. Witzenrath, R. Hübner","doi":"10.2139/ssrn.4262045","DOIUrl":"https://doi.org/10.2139/ssrn.4262045","url":null,"abstract":"Introduction Patient with chronic obstructive lung disease (COPD) have an increased risk of severe Coronavirus disease (COVID-19), which is why self-isolation was recommended. However, long periods of social isolation accompanied with limited access to health care systems might influence the outcome of patients with severe COPD negatively. Methods Data from COPD and pneumonia patients at Charité-Universitätsmedizin, Berlin and the volume of endoscopic lung volume reduction (ELVR) from the German lung emphysema registry (Lungenemphysem Register e.V.) were analyzed from pre-pandemic (2012 to 2019) to pandemic (2020 and 2021) period. In addition, 52 patients with COPD GOLD IV status included in the lung emphysema registry received questionnaires during lockdowns from June 2020 to April 2021. Results Admissions and ventilation therapies administered to COPD patients significantly decreased during the COVID-19 pandemic. Likewise, there was a reduction of ELVR treatments and follow-ups registered in German emphysema centers. Mortality was slightly higher among patients hospitalized with COPD during pandemic. Increasing proportions of COPD patients with GOLD III and GOLD IV status reported behavioral changes and subjective feelings of increasing COPD symptoms the longer the lockdown lasted. However, COPD symptom questionnaires revealed stable COPD symptoms over the pandemic time-period. Summary This study reveals reduced COPD admissions and elective treatment procedures of COPD patients during pandemic, but a slight increase of mortality among patients hospitalized with COPD irrespective of COVID-19. Correspondingly, patients with severe COPD reported subjective deterioration of their health status probably caused by their very strict compliance to lockdown measures.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84279019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-24DOI: 10.15326/jcopdf.2021.0321
G. Wiesemann, Regina A Oshins, Tammy O Flagg, M. Brantly
The SERPINA1 gene encodes the serine protease inhibitor alpha-1 antitrypsin (AAT) and is located on chromosome 14q31-32.3 in a cluster of homologous genes likely formed by exon duplication. AAT has a variety of anti-inflammatory properties. Its clinical relevance is best illustrated by the genetic disease alpha-1 antitrypsin deficiency (AATD) which is associated with an increased risk for COPD and cirrhosis. While two SNPs, S and Z, are responsible for more than 95% of all individuals with AATD, there are a number of rare variants associated with deficiency and dysfunction, as well as those associated with normal levels and function. Our laboratory has identified a number of novel AAT alleles that we report in this manuscript. We screened more than 500,000 individuals for AATD alleles through our testing program over the past 20 years. The characterization of these alleles was accomplished by DNA sequencing, measurement of alpha-1 antitrypsin plasma levels and isoelectric focusing at pH 4-5. We report 22 novel AAT alleles discovered through our screening programs, such as Zlittle rock and QOchillicothe, and review the current literature of known AAT genetic variants.
{"title":"Novel SERPINA1 Alleles Identified through a Large Alpha-1 Antitrypsin Deficiency Screening Program and Review of Known Variants.","authors":"G. Wiesemann, Regina A Oshins, Tammy O Flagg, M. Brantly","doi":"10.15326/jcopdf.2021.0321","DOIUrl":"https://doi.org/10.15326/jcopdf.2021.0321","url":null,"abstract":"The SERPINA1 gene encodes the serine protease inhibitor alpha-1 antitrypsin (AAT) and is located on chromosome 14q31-32.3 in a cluster of homologous genes likely formed by exon duplication. AAT has a variety of anti-inflammatory properties. Its clinical relevance is best illustrated by the genetic disease alpha-1 antitrypsin deficiency (AATD) which is associated with an increased risk for COPD and cirrhosis. While two SNPs, S and Z, are responsible for more than 95% of all individuals with AATD, there are a number of rare variants associated with deficiency and dysfunction, as well as those associated with normal levels and function. Our laboratory has identified a number of novel AAT alleles that we report in this manuscript. We screened more than 500,000 individuals for AATD alleles through our testing program over the past 20 years. The characterization of these alleles was accomplished by DNA sequencing, measurement of alpha-1 antitrypsin plasma levels and isoelectric focusing at pH 4-5. We report 22 novel AAT alleles discovered through our screening programs, such as Zlittle rock and QOchillicothe, and review the current literature of known AAT genetic variants.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78588043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-13DOI: 10.15326/jcopdf.2022.0289
Jelena Mustra Rakic, S. Zeng, L. Rohdin-Bibby, Erin L. Van Blarigan, Xingjian Liu, Shuren Ma, J. Kane, R. Redberg, G. Turino, Eveline Oestreicher Stock, M. Arjomandi
Background Prolonged past exposure to secondhand tobacco smoke (SHS) in never-smokers is associated with abnormal lung function and reduced diffusing capacity suggestive of an associated lung tissue injury and damage. The mechanisms by which past SHS exposure may contribute to lung tissue damage are unknown. Elastin is a major constituent of extracellular matrix in lung parenchyma. Objective To determine whether past exposure to SHS is associated with ongoing lung tissue damage as indicated by elevated elastin degradation products that are linked to lung function. Methods We measured the plasma levels of elastin degradation markers (EDM) from 193 never-smoking flight attendants with history of remote SHS exposure in aircraft cabin and 103 nonsmoking flight attendants or sea-level control participants without such history of cabin SHS exposure, and examined those levels versus their lung function with adjustment for covariates. The cabin SHS exposure was estimated based on airline employment history and years of smoking ban enactment. Results The median [interquartile range] plasma EDM level for all participants was 0.30 [0.24-0.36] ng/mL with a total range of 0.16-0.65 ng/mL. Plasma EDM levels were elevated in those with history of exposure to cabin SHS compared to those not exposed (0.33±0.08 vs. 0.26±0.06 ng/mL; age- and sex-adjusted P<0.001). In those with history of cabin SHS-exposure, higher EDM levels were associated with lower diffusing capacity (parameter estimate (PE) [95%CI]=4.2 [0.4-8.0] %predicted decrease per 0.1 ng/mL increase in EDM; P=0.030). Furthermore, EDM levels were inversely associated with FEV1, FEV1/FVC, and FEF25-75 (PE [95%CI]=5.8 [2.1-9.4], 4.0 [2.2-5.7], and 12.5 [5.8-19.2] %predicted decrease per 0.1 ng/mL increase in EDM, respectively; P<0.001). Plasma EDM mediated a substantial fraction of the association of SHS with FEV1, FVC, and FEF25-75 (P<0.05). Conclusions Long after past exposure to SHS, there is ongoing elastin degradation beyond what is expected from the aging process, which likely contributes to lower lung function and reduced pulmonary capillary bed as seen in COPD.
{"title":"Elastin Degradation and Lung Function Deterioration with Remote Secondhand Tobacco Smoke Exposure in Never-smokers.","authors":"Jelena Mustra Rakic, S. Zeng, L. Rohdin-Bibby, Erin L. Van Blarigan, Xingjian Liu, Shuren Ma, J. Kane, R. Redberg, G. Turino, Eveline Oestreicher Stock, M. Arjomandi","doi":"10.15326/jcopdf.2022.0289","DOIUrl":"https://doi.org/10.15326/jcopdf.2022.0289","url":null,"abstract":"Background\u0000Prolonged past exposure to secondhand tobacco smoke (SHS) in never-smokers is associated with abnormal lung function and reduced diffusing capacity suggestive of an associated lung tissue injury and damage. The mechanisms by which past SHS exposure may contribute to lung tissue damage are unknown. Elastin is a major constituent of extracellular matrix in lung parenchyma.\u0000\u0000\u0000Objective\u0000To determine whether past exposure to SHS is associated with ongoing lung tissue damage as indicated by elevated elastin degradation products that are linked to lung function.\u0000\u0000\u0000Methods\u0000We measured the plasma levels of elastin degradation markers (EDM) from 193 never-smoking flight attendants with history of remote SHS exposure in aircraft cabin and 103 nonsmoking flight attendants or sea-level control participants without such history of cabin SHS exposure, and examined those levels versus their lung function with adjustment for covariates. The cabin SHS exposure was estimated based on airline employment history and years of smoking ban enactment.\u0000\u0000\u0000Results\u0000The median [interquartile range] plasma EDM level for all participants was 0.30 [0.24-0.36] ng/mL with a total range of 0.16-0.65 ng/mL. Plasma EDM levels were elevated in those with history of exposure to cabin SHS compared to those not exposed (0.33±0.08 vs. 0.26±0.06 ng/mL; age- and sex-adjusted P<0.001). In those with history of cabin SHS-exposure, higher EDM levels were associated with lower diffusing capacity (parameter estimate (PE) [95%CI]=4.2 [0.4-8.0] %predicted decrease per 0.1 ng/mL increase in EDM; P=0.030). Furthermore, EDM levels were inversely associated with FEV1, FEV1/FVC, and FEF25-75 (PE [95%CI]=5.8 [2.1-9.4], 4.0 [2.2-5.7], and 12.5 [5.8-19.2] %predicted decrease per 0.1 ng/mL increase in EDM, respectively; P<0.001). Plasma EDM mediated a substantial fraction of the association of SHS with FEV1, FVC, and FEF25-75 (P<0.05).\u0000\u0000\u0000Conclusions\u0000Long after past exposure to SHS, there is ongoing elastin degradation beyond what is expected from the aging process, which likely contributes to lower lung function and reduced pulmonary capillary bed as seen in COPD.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84837027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-20DOI: 10.15326/jcopdf.2021.0275
A. Boueiz, Zhonghui Xu, Yale Chang, A. Masoomi, A. Gregory, S. Lutz, D. Qiao, J. Crapo, J. Dy, E. Silverman, P. Castaldi
Background The heterogeneous nature of COPD complicates the identification of the predictors of disease progression. We aimed to improve the prediction of disease progression in COPD by using machine learning and incorporating a rich dataset of phenotypic features. Methods We included 4,496 smokers with available data from their enrollment and 5-year follow-up visits in the Genetic Epidemiology of COPD (COPDGene) study. We constructed linear regression (LR) and supervised random forest (RF) models to predict 5-year progression in FEV1 from 46 baseline features. Using cross-validation, we randomly partitioned participants into training and testing samples. We also validated the results in the COPDGene 10-year follow-up visit. Results Predicting the change in FEV1 over time is more challenging than simply predicting the future absolute FEV1 level. For RF, R-squared was 0.15 and the area under the ROC curves for the prediction of subjects in the top quartile of observed progression was 0.71 (testing) and respectively, 0.10 and 0.70 (validation). RF provided slightly better performance than LR. The accuracy was best for GOLD1-2 subjects and it was harder to achieve accurate prediction in advanced stages of the disease. Predictive variables differed in their relative importance as well as for the predictions by GOLD. Conclusion RF along with deep phenotyping predicts FEV1 progression with reasonable accuracy. There is significant room for improvement in future models. This prediction model facilitates the identification of smokers at increased risk for rapid disease progression. Such findings may be useful in the selection of patient populations for targeted clinical trials.
{"title":"Machine Learning Prediction of Progression in Forced Expiratory Volume in 1 Second in the COPDGene® Study.","authors":"A. Boueiz, Zhonghui Xu, Yale Chang, A. Masoomi, A. Gregory, S. Lutz, D. Qiao, J. Crapo, J. Dy, E. Silverman, P. Castaldi","doi":"10.15326/jcopdf.2021.0275","DOIUrl":"https://doi.org/10.15326/jcopdf.2021.0275","url":null,"abstract":"Background\u0000The heterogeneous nature of COPD complicates the identification of the predictors of disease progression. We aimed to improve the prediction of disease progression in COPD by using machine learning and incorporating a rich dataset of phenotypic features.\u0000\u0000\u0000Methods\u0000We included 4,496 smokers with available data from their enrollment and 5-year follow-up visits in the Genetic Epidemiology of COPD (COPDGene) study. We constructed linear regression (LR) and supervised random forest (RF) models to predict 5-year progression in FEV1 from 46 baseline features. Using cross-validation, we randomly partitioned participants into training and testing samples. We also validated the results in the COPDGene 10-year follow-up visit.\u0000\u0000\u0000Results\u0000Predicting the change in FEV1 over time is more challenging than simply predicting the future absolute FEV1 level. For RF, R-squared was 0.15 and the area under the ROC curves for the prediction of subjects in the top quartile of observed progression was 0.71 (testing) and respectively, 0.10 and 0.70 (validation). RF provided slightly better performance than LR. The accuracy was best for GOLD1-2 subjects and it was harder to achieve accurate prediction in advanced stages of the disease. Predictive variables differed in their relative importance as well as for the predictions by GOLD.\u0000\u0000\u0000Conclusion\u0000RF along with deep phenotyping predicts FEV1 progression with reasonable accuracy. There is significant room for improvement in future models. This prediction model facilitates the identification of smokers at increased risk for rapid disease progression. Such findings may be useful in the selection of patient populations for targeted clinical trials.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87635048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-06DOI: 10.15326/jcopdf.2022.0283
A. Machado, S. Almeida, C. Burtin, A. Marques
Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a negative impact on health status and disease progression, but their clinical presentation is heterogenous. A comprehensive understanding of people's experience during AECOPD is needed to develop person-centred interventions, such as pulmonary rehabilitation (PR). This study aimed to explore people's experience during mild to moderate AECOPD, and their thoughts on PR during this period. Methods Short, semi-structured interviews were conducted with people with mild to moderate AECOPD treated in the community, within 48h of the diagnosis. Interviews were audio recorded, transcribed and analysed by deductive thematic analysis using the Web Qualitative Data Analysis software. Results Eleven people with AECOPD (9 male, 67±10 years, FEV1 41±16%predicted) participated. Four themes and seventeen subthemes were identified: impact of AECOPD (symptoms, physiological changes, limitations in activities of daily living, social constrains, psychological and emotional challenges, family disturbances); dealing with AECOPD ([not] depending on others, planning and compensation strategies); main needs during AECOPD (breath better, feel less tired, get rid of sputum, be able to walk); and (un)certainty about PR (lack of knowledge, get better, exercises, design and timing, trust in health professionals). Conclusion AECOPD, even when not requiring hospital admission, have a huge negative impact on people's lives. People's thoughts about PR reflect the need to raise awareness for this intervention during AECOPD. This study provides a foundation for the development of meaningful person-centred interventions during AECOPD.
{"title":"Giving Voice to People - Experiences During Mild to Moderate Acute Exacerbations of COPD.","authors":"A. Machado, S. Almeida, C. Burtin, A. Marques","doi":"10.15326/jcopdf.2022.0283","DOIUrl":"https://doi.org/10.15326/jcopdf.2022.0283","url":null,"abstract":"Background\u0000Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a negative impact on health status and disease progression, but their clinical presentation is heterogenous. A comprehensive understanding of people's experience during AECOPD is needed to develop person-centred interventions, such as pulmonary rehabilitation (PR). This study aimed to explore people's experience during mild to moderate AECOPD, and their thoughts on PR during this period.\u0000\u0000\u0000Methods\u0000Short, semi-structured interviews were conducted with people with mild to moderate AECOPD treated in the community, within 48h of the diagnosis. Interviews were audio recorded, transcribed and analysed by deductive thematic analysis using the Web Qualitative Data Analysis software.\u0000\u0000\u0000Results\u0000Eleven people with AECOPD (9 male, 67±10 years, FEV1 41±16%predicted) participated. Four themes and seventeen subthemes were identified: impact of AECOPD (symptoms, physiological changes, limitations in activities of daily living, social constrains, psychological and emotional challenges, family disturbances); dealing with AECOPD ([not] depending on others, planning and compensation strategies); main needs during AECOPD (breath better, feel less tired, get rid of sputum, be able to walk); and (un)certainty about PR (lack of knowledge, get better, exercises, design and timing, trust in health professionals).\u0000\u0000\u0000Conclusion\u0000AECOPD, even when not requiring hospital admission, have a huge negative impact on people's lives. People's thoughts about PR reflect the need to raise awareness for this intervention during AECOPD. This study provides a foundation for the development of meaningful person-centred interventions during AECOPD.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"46 6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89185366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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