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Ingrid Marie Hardang, MD1,2 Vidar Søyseth, MD, PhD2,3 Natalia Kononova, MD2,4 Tor-Arne Hagve, MD, PhD1,2 Gunnar Einvik, MD, PhD2,3
Author Affiliations
- Department of Multidisciplinary Laboratory Medicine and Medical Biochemistry, Akershus University Hospital, Lørenskog, Norway
- Institute for Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Pulmonary Medicine, Akershus University Hospital, Lørenskog, Norway
- Department of Pulmonary Medicine, Østfold Hospital, Kalnes, Norway
Address correspondence to:
Gunnar Einvik, MD, PhD
Department of Pulmonary Medicine
Akershus University Hospital
1470 Lørenskog
Norway
Phone: +4741104542
Email: Gunnar.Einvik@medisin.uio.no
Abstract
Background: The prevalence of iron deficiency in patients with chronic obstructive pulmonary disease (COPD) varies in previous studies. We aimed to assess its prevalence according to 3 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 were non-COPD controls, ferritin, transferrin saturation (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 individuals with COPD, peaking at 71% in participants with chronic respiratory failure. Ferritin < cutoff was significantly associated with forced expiratory volume in 1 second (FEV1) (odds ratio [OR] 0.33 per liter increase), smoking (OR 3.2), and cardiovascular disease (OR 4.7). TSat < 20% was associated with body mass index (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 (hazard ratio [HR] 1.2–1.8).
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 levels of hemoglobin and increased BMI. Iron deficiency was not associated with increased mortality.
Citation
Citation: Hardang IM, Søyseth V, Kononova N, Hagve T-A, Einvik G. COPD: iron deficiency and clinical characteristics in patients with and without chronic respiratory failure. Chronic Obstr Pulm Dis. 2024; 11(3): 261-269. doi: http://dx.doi.org/10.15326/jcopdf.2023.0477
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María C. Fernández-Sánchez, MD1 Francisco J. Ruiz-López, MD, PhD2 José A. Ros-Lucas, MD, PhD2 Rubén Andújar-Espinosa, MD, PhD2 Juan Del Coso, PhD3 Teresa García-Pastor, PhD4
Author Affiliations
- Pneumology Unit, Internal Medicine Service, Rafael Mendez Hospital, Lorca, Spain
- Pneumonology Service, Arrixaca University Hospital, Murcia, Spain
- Centre for Sports Studies, Rey Juan Carlos University, Fuenlabrada, Spain
- Exercise Physiology Laboratory, Camilo José Cela University, Madrid, Spain
Address correspondence to:
Francisco José Ruiz-López
Pneumology Service
Arrixaca University Hospital
Ctra. Madrid-Cartagena s/n. El Palmar
Murcia, Spain 30120
Phone: +34653557861
Email: fjose.ruiz1@um.es
Abstract
Background: Daily physical activity is part of the self-management of patients with chronic obstructive pulmonary disease (COPD), and didactic information sessions may be insufficient for the provision of these skills. Prior activation can determine sensitivity to these sessions.
We evaluated whether the activation in patients with COPD, as measured by the Patient Activation Measure (PAM)-13 questionnaire, determined their responses to an educational group session on physical activity (PA), which were measured with actigraphy by the number of steps/day.
Methods: We conducted an uncontrolled clinical trial in an outpatient clinic with 75 patients with nonexacerbating COPD (forced expiratory volume in 1 second 30%–80%) who were selected consecutively. Patients were provided with an actigraph that they used for 15 days and completed the PAM-13 questionnaire. On the eighth day, they attended a group educational session where they were given PA information. We compared the changes in activity after the session by pooled PAM levels and the correlation between the change in the number of steps/day and the PAM-13 questionnaire.
Results: A total of 26 patients had activation levels of 1–2, while 49 patients had levels of 3–4. After the session, patients in Levels 1–2 decreased their number of steps (-596±42), while those in Levels 3–4 increased them (680±253, p<0.01). The level of activation was positively correlated with change in the number of steps/day (p<0.05).
Conclusion: COPD patients with greater activation showed greater improvements in daily PA after a group educational session.
Citation
Citation: Fernández-Sánchez MC, Ruiz-López FJ, Ros-Lucas JA, Andújar-Espinosa R, Del Coso J. García-Pastor T. Persons with chronic obstructive pulmonary disease and high levels of activation improved their physical activity skills after an educational session. Chronic Obstr Pulm Dis. 2024; 11(3): 270-281. doi: http://dx.doi.org/10.15326/jcopdf.2023.0456
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Mark L. Brantly, MD1 Brooks T. Kuhn, MD, MAS2 Humam W. Farah, MD3 Ravi Mahadeva, MD, FRCP4 Alexandra Cole, MBChB, FRNZCGP, DHP5 Catherina L. Chang, MD, FRACP6 Cynthia D. Brown, MD7 Michael A. Campos, MD8 Jorge E. Lascano, MD1 Erin K. Babcock, BS9 Sharvari P. Bhagwat, PhD9 Teresa F. Boyea, PharmD9 Carson A. Veldstra, BS9 Vasily Andrianov, MD9 James L. Kalabus, PhD9 Brendan P. Eckelman, PhD9 Andrew G. Veale, FRACP10
Author Affiliations
- Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, United States
- Department of Internal Medicine, University of California- Davis School of Medicine, Sacramento, California, United States
- Department of Internal Medicine, Pulmonary and Critical Care, Hannibal Clinic, Hannibal, Missouri, United States
- Department of Respiratory Medicine, University of Cambridge, Cambridge, United Kingdom
- Medical Department, Christchurch Clinical Studies Trust, Christchurch, New Zealand
- Department of Respiratory Medicine, Waikato Hospital, Hamilton, New Zealand
- Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Department of Medicine, University of Miami School of Medicine, Miami, Florida, United States
- Inhibrx, Inc., La Jolla, California, United States
- New Zealand Respiratory and Sleep Institute, Greenlane East, Auckland, New Zealand
Address correspondence to:
Mark L. Brantly, MD
Department of Medicine
University of Florida College of Medicine<
Gainesville, FL, United States
Phone: (352) 294-5117
Email: mbrantly@ufl.edu
Abstract
Background: Alpha-1 antitrypsin deficiency (AATD) is characterized by low alpha-1 antitrypsin (AAT) levels, predisposing individuals to lung disease. The standard of care, plasma-derived AAT (pdAAT), is delivered as weekly infusions to maintain serum AAT concentrations ≥11µM (≈50% of those in healthy individuals). INBRX-101, a recombinant human AAT-Fc fusion protein, was designed to have a longer half-life and achieve higher AAT levels than pdAAT.
Methods: In this phase 1 dose-escalation study (N=31), adults with AATD received 1 dose (part 1) or 3 doses (part 2) of 10 (part 1), 40, 80, or 120mg/kg INBRX-101 every 3 weeks (Q3W) via intravenous infusion. The primary endpoint was safety and tolerability. Secondary endpoints were pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of INBRX-101.
Results: INBRX-101 was well tolerated. Most treatment-emergent adverse events were grade ≤2. In part 2 (n=18; each dose, n=6), dose-related increases in serum functional AAT (fAAT) were observed; mean fAAT levels remained above the 21µM target for up to 4 weeks after the final dose in the 120-mg/kg cohort. Antidrug antibodies had no meaningful impact on PK or PD. INBRX-101 was detected in pulmonary epithelial lining fluid (PELF) from all patients assessed (n=11), and PELF fAAT increased after dosing. PK/PD modeling projected steady-state serum fAAT ≥21µM at 120 mg/kg Q3W (average concentration ≈43µM; trough concentration ≈28µM) and Q4W (≈34µM; ≈21µM).
Conclusion: The favorable safety profile and ability to maintain serum fAAT levels >21µM with extended-interval dosing, support a phase 2 trial evaluating Q3W and Q4W dosing of INBRX-101.
Citation
Citation: Brantly ML, Kuhn BT, Farah HW, et al. Recombinant alpha-1 antitrypsin–fc fusion protein INBRX-101 in adults with alpha-1 antitrypsin deficiency: a phase 1 study. Chronic Obstr Pulm Dis. 2024; 11(3): 282-292. doi: http://dx.doi.org/10.15326/jcopdf.2023.0469
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Tyus A. Kemper, BS1 Han Woo, PhD2 Daniel Belz, MD, MPH2 Ashraf Fawzy, MD, MPH2 Wendy Lorizio, MD, MPH2 Michelle N. Eakin, PhD, MA2 Nirupama Putcha, MD, MHS2 Meredith C. McCormack, MD, MHS2 Emily P. Brigham, MD, MHS3 Corrine Hanson, PhD4 Abigail L. Koch, MD5 Nadia N. Hansel, MD, MPH2,6
Author Affiliations
- Department of Health, Human Performance, and Recreation, Baylor University, Waco, Texas, United States
- Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
- Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Medical Nutrition Education, College of Allied Health Professions, University of Nebraska Medical Center, Omaha, Nebraska, United States
- Section on Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Miami, Miami, Florida, United States
- Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States
Address correspondence to:
Nadia Hansel MD, MPH
Division of Pulmonary and Critical Care Medicine
Johns Hopkins University
5501 Hopkins Bayview Circle 4th Floor
Baltimore, MD, 21224
Email: nhansel1@jhmi.edu
Abstract
Background: Omega-3 polyunsaturated fatty acids (PUFAs) have been associated with systemic anti-inflammatory responses. Dietary intake of omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has also been associated with lower chronic obstructive pulmonary disease (COPD) morbidity using self-report food frequency questionnaires.
Objective: The objective of this study was to investigate the relationship between measured PUFA intake using plasma EPA+DHA levels and COPD morbidity.
Methods: Former smokers with moderate-to-severe COPD living in low-income communities were enrolled in a 6-month prospective cohort study. Participants completed standardized questionnaires, spirometry, and plasma samples at 3-month intervals. Total plasma PUFAs were analyzed using gas chromatography/mass spectrometry for DHA and EPA concentrations. Linear or logistic mixed model regression was used to evaluate EPA+DHA’s and COPD morbidity’s association, accounting for demographics, lung function, pack years, comorbidities, and neighborhood poverty.
Results: A total of 133 plasma EPA+DHA samples from 57 participants were available. Participants exhibited average plasma EPA and DHA levels of 14.7±7.3µg/mL and 40.2±17.2µg/mL, respectively, across the 3 clinic visits. Each standard deviation increase in EPA+DHA levels was associated with 2.7 points lower St George’s Respiratory Questionnaire score (95% confidence interval [CI] -5.2, -0.2) and lower odds of moderate exacerbation (odds ratio 0.4; 95% CI 0.2, 0.9), but lacked significant association with the COPD Assessment Test score (95% CI -2.4, 0.8), modified Medical Research Council dyspnea scale (95% CI -02, 0.2), or severe exacerbations (95% CI 0.3, 1.4).
Conclusion: Plasma EPA+DHA levels are associated with better respiratory-specific quality of life and lower odds of moderate exacerbations in patients with moderate-to-severe COPD. Further research is warranted to investigate the efficacy of an omega-3 dietary intervention in the management of COPD morbidities.
Citation
Citation: Kemper TA, Woo H, Belz D, et al. Higher plasma omega-3 levels are associated with improved exacerbation risk and respiratory-specific quality of life in COPD. Chronic Obstr Pulm Dis. 2024; 11(3): 293-302. doi: http://dx.doi.org/10.15326/jcopdf.2023.0468
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