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Daniel N. Pfeffer, PhD1 Rahul Dhakne, MS2 Omnya El Massad, MSc1 Pulkit Sehgal, BS2 Thomas Ardiles, MD3 Michael O. Calloway, PhD4 M. Chris Runken, PharmD4 Charlie Strange, MD5,6
Author Affiliations
- Data and Analytics, EVERSANA, Milwaukee, Wisconsin, United States
- Data and Analytics, EVERSANA, Pune, India
- Medical Affairs, Grifols Shared Services North America, Durham, North Carolina, United States
- Global Health Economics and Outcomes Research/Real-World Evidence, Grifols Shared Services North America, Durham, North Carolina, United States
- Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Medical University of South Carolina, Charleston, South Carolina, United States
- AlphaNet, Coral Gables, Florida, United States
Address correspondence to:
M. Chris Runken, PharmD
Grifols, Shared Services North America
79 T.W. Alexander Drive
Durham, NC 27709
Phone: (919) 316-6343
Email: chris.runken@grifols.com
Abstract
Background: Despite guideline recommendations, most patients with chronic obstructive pulmonary disease (COPD) do not undergo alpha-1 antitrypsin deficiency (AATD) testing and approximately 90% of people with AATD in the United States remain undiagnosed. This study sought to develop a predictive model using real-world data to improve detection of AATD-positive patients in the general COPD population.
Methods: A predictive model using extreme gradient boosting was developed using the EVERSANA database, including longitudinal, patient-level medical claims, prescription claims, AATD-specific testing data, and electronic health records (EHR). The model was trained and then validated to predict AATD-positive status. Patients were coded as AATD positive based on the presence of any of the following criteria: (1) ≥2 AATD diagnosis codes in claims; (2) an AATD diagnosis code in the EHR; (3) a positive laboratory test for AATD; or (4) use of AATD-related medication. Over 500 variables were used to train the predictive model and >20 models were run to optimize the predictive power.
Results: A total of 13,585 AATD-positive patients and 7796 AATD-negative patients were included in the model. The inclusion of non-AATD laboratory test results was critical for defining cohorts and optimizing model prediction (e.g., respiratory comorbidities, and calcium, glucose, hemoglobin, and bilirubin levels). The final model yielded high predictive power, with an area under the receiver operating characteristic curve of 0.9.
Conclusions: Predictive modeling using real-world data is a sound approach for assessing AATD risk and useful for identifying COPD patients who should be confirmed by genetic testing. External validation is warranted to further assess the generalizability of these results.
Citation
Citation: Pfeffer DN, Dhakne R, El Massad O, et al. Improving the likelihood of identifying alpha-1 antitrypsin deficiency among patients with COPD: a novel predictive model using real-world data. Chronic Obstr Pulm Dis. 2025; 12(1): 1-11. doi: http://dx.doi.org/10.15326/jcopdf.2023.0491
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Andrew J. Devine, BS1* Noah J. Smith, BS2* Rashika Joshi, MD3 Brandon Brooks-Patton4 Jenna Dunham, BS4 Ansley N. Varisco5 Emily M. Goodman, MD6 Qiang Fan, PhD3 Basilia Zingarelli, MD, PhD2,3 Brian M. Varisco, MD2,3,6,7
Author Affiliations
- Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, United States
- College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States
- Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States
- Northern Kentucky University, Highland Heights, Kentucky, United States
- University of Arkansas at Little Rock, Little Rock, Arkansas, United States
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
- Arkansas Children’s Research Institute, Little Rock, Arkansas, United States
*Authors contributed equally
Address correspondence to:
Brian M. Varisco, MD
Arkansas Children’s Research Institute
13 Children’s Way
Little Rock, Arkansas, USA 72202
Phone: (501) 364-7512
Email: bvarisco@uams.edu
Abstract
Background: Alpha-1 antitrypsin (AAT) deficiency is the most common genetic cause of emphysema. Chymotrypsin-like elastase 1 (CELA1) is a serine protease neutralized by AAT and is important in emphysema progression. Cela1-deficiency is protective in murine models of AAT-deficient emphysema. KF4 anti-CELA1 antibody prevented emphysema in porcine pancreatic elastase (PPE) and cigarette smoke models in wild-type mice.
Methods: We evaluated potential toxicities of KF4 and its ability to prevent emphysema in AAT deficiency. We found Cela1 protein expression in mouse lungs, pancreas, small intestine, spleen, and bone marrow. In toxicity studies, mice treated with KF4 25mg/kg weekly for 4 weeks showed an elevation in blood urea nitrogen and slower weight gain compared to lower doses or equivalent dose immunoglobin G (IgG). By histologic grading of tissue injury of the lung, kidney, liver, and heart, there was some evidence of liver injury with KF4 25mg/kg, but in all tissues, injury was less than in control mice subjected to cecal ligation and puncture. In efficacy studies, KF4 doses as low as 0.5mg/kg reduced the lung elastase activity of AAT-/- mice treated with 0.2 units of PPE.
Results: In this injury model, AAT-/- mice treated with KF4 1mg/kg weekly, human purified AAT 60mg/kg weekly, and combined KF4 and AAT treatment had less emphysema than mice treated with IgG 1mg/kg weekly. However, the efficacy of KF4, AAT, or KF4 and AAT was similar.
Conclusion: While KF4 might be an alternative to AAT replacement, combined KF4 and AAT replacement does not confer additional benefit.
Citation
Citation: Devine AJ, Smith NJ, Joshi R, et al. KF4 anti-chymotrypsin-like elastase 1 antibody and purified alpha-1 antitrypsin have similar but not additive efficacy in preventing emphysema in murine alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2025; 12(1): 12-22. doi: http://dx.doi.org/10.15326/jcopdf.2024.0535
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Toru Shirahata, MD1,2 Nicholas A. Enzer, BS1,3 Victor Castro, BS4 Joe Chiles, MD5 Merry-Lynn McDonald, PhD5,6,7 Bina Choi, MD1,3 Alejandro A. Diaz, MD, MPH1,3 George R. Washko, MD, MSc1,3 Raúl San José Estépar, PhD1,8 Samuel Y. Ash, MD, MPH9,10 Farbod N. Rahaghi, MD, PhD1,3
Author Affiliations
- Applied Chest Imaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States
- Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States
- Boston University School of Medicine, Boston, Massachusetts, United States
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
- Department of Genetics, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
- Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, United States
- Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States
- Department of Critical Care Medicine, South Shore Hospital, South Weymouth, Massachusetts, United States
- Tufts University School of Medicine, Boston, Massachusetts, United States
Address correspondence to:
Toru Shirahata, MD
Dept. of Respiratory Medicine
Saitama Medical University
38 Morohongo, Moroyama-machi, Iruma-gun
Saitama, 350-0495, Japan
Email: t_shira@saitama-med.ac.jp
Abstract
Background: Cigarette smoke contributes to skeletal muscle wasting. While exercise and nutritional therapies are effective in improving skeletal muscle quantity and quality, the effect of medications on longitudinal muscle loss is unclear. We investigated whether long-term use of common medications affects longitudinal skeletal muscle changes in current and former smokers.
Methods: Using quantitative computed tomography imaging, we measured the 5-year changes in pectoralis muscle area (delta-PMA) and pectoralis muscle density (delta-PMD) of 4191 participants in the COPD Genetic Epidemiology (COPDGene®) study. We tested whether specific medications were associated with delta-PMA and/or delta-PMD using regression analyses. Propensity score matching (PSM) analysis was performed to determine the effect of the medications on longitudinal changes on delta-PMA.
Results: Over the study period, the median delta-PMA for the entire population showed a decrease of 2.23cm2 (interquartile range: -6.52, 1.54). Regression analyses demonstrated statin use was associated with less loss of PMA, whereas, aspirin use was associated with a greater loss of PMA. Specifically, in the PSM-adjusted analysis, statin use was associated with attenuated loss of PMA (median; -1.5 versus -2.5cm2, p=0.017), while aspirin use was associated with increased loss of PMA (median; -2.5 versus -1.9cm2, p=0.040).
Conclusions: In current and former smokers, statin use was associated with reduced pectoralis muscle wasting, while aspirin use was associated with increased muscle loss. Additional research is needed to verify these findings. (Clinicaltrials.gov identifier NCT00608764)
Citation
Citation: Shirahata T, Enzer NA, Castro V, et al. Effect of common medications on longitudinal pectoralis muscle area in smokers. Chronic Obstr Pulm Dis. 2025; 12(1): 23-32. doi: http://dx.doi.org/10.15326/jcopdf.2024.0557
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Jing Gennie Wang, MD1 Sonali Bose, MD, MPH2,3 Janet T. Holbrook, PhD4 Lin Nan, MD, ScM4 Michelle N. Eakin, PhD3 Abebaw M. Yohannes, PhD, MSc5,6 Robert A. Wise, MD3 Nicola A. Hanania, MD, MS7 on behalf of the American Lung Association Airways Clinical Research Centers*
Author Affiliations
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States
- Department of Physical Therapy, School of Health Professions, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, Texas, United States
*A complete list of members for the American Lung Association Airway Clinical Research Centers may be found in the Acknowledgements section
Address correspondence to:
Jing Gennie Wang, MD
241 W. 11th Ave
Suite 5000, 5065B
Columbus, OH 43201
Phone: (646) 617-3656
Email: jing.wang2@osumc.edu
Abstract
Background: Most studies on mental health among individuals with chronic obstructive pulmonary disease (COPD) utilize screening questionnaires, which detect psychiatric symptoms, but cannot be used to diagnose depression/anxiety disorders. We utilized the Mini-International Neuropsychiatric Interview (MINI) to identify depression/anxiety disorders meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnostic criteria and described associated disease burden in people with COPD.
Methods: This is a cross-sectional, secondary analysis of a multicenter study designed to evaluate anxiety questionnaires in COPD patients. Research coordinators administered both the MINI and screening questionnaires to determine participants who met diagnostic criteria for depression/anxiety disorders and to capture symptom burden, respectively. Bivariate analyses were conducted to assess differences in COPD and patient-reported outcomes between those with and without depression/anxiety disorders.
Results: Of 220 participants, 18 (8%) met the MINI criteria for depression and 17 (8%) for anxiety. Depression was associated with more breathlessness (modified Medical Research Council Dyspnea Scale 4 versus 3, p=0.045), higher COPD disease burden (COPD Assessment Test [CAT] 27 versus 17, p<0.001), worse sleep quality (Pittsburgh Sleep Quality Index 11 versus 7, p=0.001) and health-related quality of life (5-Level EQ-5D 0.31 versus 0.59, p<0.001). Anxiety was associated with lower CAT scores and worse health-related quality of life and function. Most with depression/anxiety disorders were not using antidepressants/anxiolytics, or receiving mental health counseling.
Conclusion: Depression and anxiety disorders meeting diagnostic criteria are relatively common comorbidities that substantially impair quality of life and are undertreated, highlighting a need to prioritize mental health as an integral part of comprehensive COPD care.
Citation
Citation: Wang JG, Bose S, Holbrook JT, et al. Clinical characteristics of patients with COPD and comorbid depression and anxiety: data from a national multicenter cohort study. Chronic Obstr Pulm Dis. 2025; 12(1): 33-42. doi: http://dx.doi.org/10.15326/jcopdf.2024.0534
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Ana-Maria Diaz, PharmD1 Lindsey M. Smith, PharmD, BCACP, BCCP1 Amber N. Peterson, APRN1 Macie L. Kent, PharmD, CACP, CPh1 Namitha J. Vellian, PharmD1
Author Affiliations
- Lakeland Regional Health, Lakeland, Florida, United States
Address correspondence to:
Ana-Maria Diaz, PharmD
Lakeland Regional Health
1324 Lakeland Hills Blvd
Lakeland, Florida 33805
Phone: (813) 401-0064
Email: Ana-Maria.Diaz@myLRH.org
Abstract
Background: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is one of the 6 conditions in the Hospital Readmissions Reduction Program for which institutions are penalized for high 30-day readmission rates. This institution’s transitions of care (TOC) pharmacists have prescribing authority to optimize guideline-directed medical therapy (GDMT), defined as discharging on rescue plus triple therapy inhalers under an approved protocol. While several studies evaluate the impact of pharmacist-led interventions on COPD readmission rates, there is a lack of literature with respect to pharmacists prescribing inhalers under an approved protocol. This study aims to evaluate all-cause 30-day COPD readmission rates.
Methods: This was an institutional review board-approved, single-center, retrospective evaluation conducted between May 2021 and August 2023. Patients were included if they met criteria under the Centers for Medicare and Medicaid Services Hospital Readmissions Reduction Program COPD model. Patients in the pre-implementation group received usual care, with postdischarge nurse follow-up while patients in the postimplementation group received TOC pharmacy services. The primary outcome was all-cause 30-day readmission rates. Secondary outcomes included readmission reason and proportion of patients discharged on GDMT.
Results: A total of 279 patients were included, with 187 patients in the pre-implementation group and 92 patients in the postimplementation group. All-cause 30-day readmission rates in the pre- and postimplementation groups were 26% and 14%, respectively (p=0.02). The proportion of patients discharged on GDMT was 26% in the pre-implementation group and 100% in the postimplementation group (p<0.001).
Conclusion: Utilizing a TOC pharmacy service may be associated with a reduction in all-cause 30-day readmission rates for patients with COPD.
Citation
Citation: Diaz AM, Smith LM, Peterson AN, Kent ML, Vellian NJ. Impact of pharmacist inhaler prescribing at discharge for chronic obstructive pulmonary disease on readmission rates. Chronic Obstr Pulm Dis. 2025; 12(1): 43-51. doi: http://dx.doi.org/10.15326/jcopdf.2024.0553
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Wang Chun Kwok, MBBS1 Ting Fung Ma, PhD2 Chung Ki Tsui, MPH1 James Chung Man Ho, MD1 Terence Chi Chun Tam, MBBS1
Author Affiliations
- Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
- Department of Statistics, College of Arts and Sciences, University of South Carolina, Columbia, South Carolina, United States
Address correspondence to:
Terence Chi Chun Tam, MBBS
4/F, Professorial Block
Department of Medicine
The University of Hong Kong, Queen Mary Hospital
102 Pokfulam Road
Pokfulam, Hong Kong, China
Email: cctam@hotmail.com
Abstract
Background: Triple therapy with inhaled corticosteroids and dual bronchodilator therapy is recommended for chronic obstructive pulmonary disease (COPD) patients who have exacerbations and eosinophilia. It can be administered by single inhaler triple therapy (SITT) or by multiple inhaler triple therapy (MITT). There is a lack of evidence of the benefits of SITT over MITT in the Chinese population, especially on switching from existing MITT to SITT.
Methods: A total of 70 Chinese patients with COPD were recruited in this open-label, double-arm clinical trial to investigate the number of critical inhaler errors, the modified Medical Research Council (mMRC) dyspnea scale, the Medication Adherence Report Scale for Asthma (MARS-A) score, and a satisfaction score upon switching from MITT to SITT.
Results: The mean number of critical inhaler errors was 0.4±1.0 in the SITT group and 1.1±1.8 in the MITT group( p=0.038) at the first visit; and 0.2±0.6 in the SITT group and 0.8±1.1 in the MITT group (p=0.007) at the second visit. The mean change in MARS-A from baseline to first visit was +3.76±7.48 in the SITT group and -1.27±7.76 in the MITT group (p-value 0.008). A total of 22 (59.5%) and 8 (24.2%) of the patients in the SITT and the MITT group respectively, had an increase in MARS-A score from baseline to first visit, with an adjusted odds ratio of 6.23 (95% confidence interval=1.63–23.77, p=0.007), favoring SITT. There was no significant difference in the change in the mMRC dyspnea scale and the satisfaction score between the 2 groups.
Conclusion: Switching from MITT to SITT in Chinese COPD patients may have the benefits of having fewer critical inhaler errors and a higher MARS-A score.
Citation
Citation: Kwok WC, Ma TF, Tsui CK, Ho JCM, Tam TCC. Prospective randomized study on switching triple inhaler therapy in COPD from multiple inhaler devices to a single inhaler device in a Chinese population. Chronic Obstr Pulm Dis. 2025; 12(1): 52-60. doi: http://dx.doi.org/10.15326/jcopdf.2024.0519
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Yingying Zhang, MM1 Guangxi Chen2 Aixia Huang, MM2 Ying Hu2 Chengfeng Fu, MM2,3
Author Affiliations
- Department of Laboratory Medicine, Affiliated Wuxi Fifth Hospital of Jiangnan University, Wuxi, China
- Respiratory and Critical Care Medicine, the Second People’s Hospital of Banan District, Chongqing, China
- Department of Respiratory Medicine, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
Address correspondence to:
Chengfeng Fu, MM
Respiratory and Critical Care Medicine
Second People’s Hospital of Banan District
Chongqing, China
Phone: +86 15086717989
Email: chengfengfu@stu.cqmu.edu.cn
Abstract
Objective: Chronic obstructive pulmonary disease (COPD) is closely associated with arthritis. This study aims to evaluate the correlation between COPD and mortality among participants with arthritis.
Methods: The study included 11,298 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2018, who self-reported having arthritis. Cox proportional hazard models were used to assess the association between COPD and mortality among participants with arthritis. Kaplan-Meier survival curves were plotted to compare survival probabilities between groups. Subgroup and sensitivity analyses were conducted to assess the robustness of the results.
Results: During an average follow-up of 8.8 years, 3061 all-cause deaths were observed, including 1024 related to cardiovascular disease (CVD). After weighted multivariable adjustment, COPD was found to be significantly associated with both all-cause and CVD mortality among these arthritis participants. The hazard ratio (HR) for all-cause mortality among arthritis patients with COPD was 1.41 (95% confidence interval [CI]: 1.25–1.60, p < 0.001), and the HR for CVD mortality was 1.29 (95% CI: 1.08–1.53, p < 0.001). Kaplan-Meier survival curves attributed higher rates of both all-cause and CVD mortality among participants with COPD compared to those without (log-rank test, p < 0.001). Additionally, COPD increased the risk of both chronic lower respiratory disease (CLRD) mortality (HR 5.46, 95% CI: 3.48–8.56, p < 0.001) and non-CLRD mortality (HR 1.24, 95% CI: 1.07–1.44, p=0.004).
Conclusion: In the American population, arthritis patients with COPD have higher risks of all-cause and CVD mortality compared to those without COPD.
Citation
Citation: Zhang Y, Chen G, Huang A, Hu Y, Fu C. Association between chronic obstructive pulmonary disease and mortality in participants with arthritis: data from the National Health and Nutrition Examination Survey 1999–2018. Chronic Obstr Pulm Dis. 2025; 12(1): 61-71. doi: http://dx.doi.org/10.15326/jcopdf.2024.0573
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Yukiko Kunitomo, MD, MHS1 Nirupama Putcha, MD, MHS1 Ashraf Fawzy, MD, MPH1 Sarath Raju, MD, MPH1 Meredith C. McCormack, MD, MHS1 Robert A. Wise, MD1 Nadia N. Hansel, MD, MPH1 Aparna Balasubramanian, MD, MHS1
Author Affiliations
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
Address correspondence to:
Aparna Balasubramanian, MD, MHS
1830 East Monument Street, Floor 5
Division of Pulmonary and Critical Care Medicine
Johns Hopkins University School of Medicine
Baltimore, Maryland 21205
Email: abalasu2@jhmi.edu
Abstract
Background: The impact of iron deficiency on COPD morbidity independent of anemia status is unknown. Understanding the association between iron deficiency, anemia status, and risk of hospitalization in COPD may inform an approach to these comorbidities.
Study Design and Methods: Adults ≥40 years from the Johns Hopkins COPD Precision Medicine Center of Excellence data repository with an outpatient iron profile and 1 year of subsequent follow-up time were included in the study. Baseline characteristics were compared across iron status, defined by transferrin saturation (TSAT), using t-tests and Chi-squared tests. The association between continuous TSAT and all-cause hospitalization over the 1-year follow-up period was assessed by logistic regression. Models were adjusted by covariates with an interaction term for anemia and stratified by sex.
Results: There were 6532 individuals included with an average age of 65±12 years, 59% were female, and 56% White. Fifty-two percent of the cohort were iron deficient (TSAT≤20%), among whom 27% were non-anemic. Iron-deficient individuals had lower lung function and a higher prevalence of heart failure and diabetes. Iron deficiency was more prevalent among females (57%) compared to males (44%). In adjusted models, a decrease in TSAT by 10% was associated with 14.3% higher odds of all-cause hospitalization for females (95%CI:1.0−1.3), but not among males (OR:1.08, 95%CI:0.9−1.3). There was effect modification by anemia such that the association between TSAT and all-cause hospitalization was greater in non-anemic women (p-value interaction=0.08).
Interpretation: Iron deficiency may be associated with adverse outcomes in the absence of anemia, with non-anemic women being a COPD sub-population particularly sensitive to iron deficiency.
Citation
Citation: Kunitomo Y, Putcha N, Fawzy A, et al. Iron deficiency and all-cause hospitalization risk in a clinical cohort of COPD. Chronic Obstr Pulm Dis. 2025; 12(1): 72-81. doi: http://dx.doi.org/10.15326/jcopdf.2024.0550
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