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Bryan Garcia, MD1* Matthew Mullins, BSc2* Lindsay Lim, MD, DTMH3 German Henostroza, MD3 Camilla Margaroli, PhD4
Author Affiliations
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
- University of Alabama at Birmingham Hospital, Birmingham, Alabama, United States
- Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, United States
- Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States
* co-first authors
Address correspondence to:
Camilla Margaroli, PhD
Division of Molecular and Cellular Pathology
Department of Pathology
University of Alabama at Birmingham
901 19th St S, Birmingham, AL 35205
Phone: (205) 975-1077
Email: cmargaroli@uabmc.edu
Abstract
Background: The incidence of infections caused by nontuberculous mycobacteria (NTM) are steadily increasing worldwide, and the most common site of infection is the lung. Clinical characteristics of individuals with NTM pulmonary disease (NTM-PD) demonstrate pronounced geographical heterogeneity. In the United States, NTM-PD has an affinity for postmenopausal White females, many of whom are never-smokers, whereas in Asia, NTM-PD is more common in males with post-tuberculosis lung disease. While these geographical differences are known on the global scale, it remains unclear whether radiographic sex-associated differences in NTM-PD are present within the U.S. cohort.
Objective/Method: In this single center, cross-sectional retrospective study of our patient registry, we sought to assess this knowledge gap by comparing radiographic and clinical features of individuals with NTM-PD by sex.
Results: We observed a significant preponderance of cavitary disease in men, while women commonly presented with bilateral apical fibrosis, increased nodules and tree-in-bud patterns in the lower lobes, and an increased risk of refractory disease and concomitant co-infection.
Conclusion: Results from this study demonstrate several sex-associated differences in the radiographic phenotype of NTM-PD and may be the result of differences in pre-existing risk factors that contribute to the development of NTM-PD. Future studies will be required to better assess the broad applicability of these findings to centers from other geographic regions where the underlying etiology of disease may vary.
Citation
Citation: Garcia B, Mullins M, Lim L, Henostroza G, Margaroli C. Sex-associated radiographic and clinical differences in nontuberculous mycobacteria pulmonary disease. Chronic Obstr Pulm Dis. 2025; 12(6): 455-465. doi: http://dx.doi.org/10.15326/jcopdf.2025.0622
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Kunning Zhou, MD1* Fan Wu, MD, PhD1,2* Zhishan Deng, MD, PhD1 Qi Wan, MD1 Suyin Huang, MD1,2 Nanshan Zhong, MD, PhD1,2 Yumin Zhou, MD, PhD1,2 Pixin Ran, MD, PhD1,2 on behalf of the Tie-COPD study investigators.
Author Affiliations
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Guangzhou National Laboratory, Guangzhou, China
* Authors contributed equally
Address correspondence to:
Pixin Ran, MD, PhD and Yumin Zhou, MD, PhD
State Key Laboratory of Respiratory Disease
National Clinical Research Center for Respiratory Disease
National Center for Respiratory Medicine
Guangzhou Institute of Respiratory Health
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou National Laboratory
Guangzhou, China
Email: pxran@gzhmu.edu.cn
Email: zhouyumin410@126.com
Abstract
Background: Patients with airflow limitation according to the fixed ratio but not the lower limit of normal (FR+LLN-) have a poorer respiratory prognosis and higher mortality than the normal fixed ratio. However, whether tiotropium treatment improves respiratory health outcomes in patients with FR+LLN- remains unclear.
Methods: This was a secondary analysis of the 24-month Tiotropium in Early Chronic Obstructive Pulmonary Disease Patients in China (Tie-COPD) study, a multicenter, randomized, double-blind clinical trial comparing tiotropium with placebo for mild-to-moderate COPD. FR+LLN- was defined as a postbronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio of <0.70 but ≥ the lower limit of normal. The primary endpoint was the between-group difference in the change from baseline to 24 months in prebronchodilator FEV1. Key secondary endpoints included the between-group difference in the annual decline in prebronchodilator FEV1 and exacerbations.
Results: In the Tie-COPD study, 92 patients (12%) had FR+LLN-. Tiotropium resulted in a significantly higher prebronchodilator FEV1 at 24 months (adjusted difference 191mL; 95% confidence interval [CI] 99, 283), with a least-squares mean change from baseline of 47mL (95% CI -13, 108) versus -140mL (95% CI -215, -64) with placebo. The annual decline in the prebronchodilator FEV1 was 24mL/year with tiotropium and 89mL/year with placebo (adjusted difference 60mL/year; 95% CI 2, 118) from 30 days through 24 months. Tiotropium reduced total exacerbations compared with placebo (relative risk=0.50; 95% CI 0.27, 0.94).
Conclusions: This study demonstrated tiotropium treatment improved lung function, ameliorated lung function decline, and reduced exacerbations compared with placebo in patients with FR+LLN-, providing evidence-based medicine support for the treatment in this population.
Citation
Citation: Zhou K, Wu F, Deng Z, et al. Tiotropium in patients with airflow limitation according to the fixed ratio but not the lower limit of normal: a secondary analysis of the Tie-COPD study. Chronic Obstr Pulm Dis. 2025; 12(6): 466-476. doi: http://dx.doi.org/10.15326/jcopdf.2025.0629
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Anderson N. Soriano-Moreno, MD, MSc1,2 Andres G. Lescano, MHS, PhD1 Robert H. Gilman, MD, DTMH3 J. Jaime Miranda, MD, PhD4 Antonio Bernabe-Ortiz, MD, MPH, PhD4 Adolfo Rubinstein, MD, MSc, PhD5 Laura Gutierrez, MSc5 Vilma Irazola, MD MSc5 Robert A. Wise, MD6 William Checkley, MD, PhD2,6
Author Affiliations
- The School of Public Health and Administration, Universidad Peruana Cayetano Heredia, Lima, Peru
- Center for Global Non-Communicable Disease Research and Training, Johns Hopkins University, Baltimore, Maryland, United States
- Program in Global Disease Epidemiology and Control, Department of International Health, Johns Hopkins University, Baltimore, Maryland, United States
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru
- Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina.
- Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
Address correspondence to:
William Checkley, MD, PhD
Division of Pulmonary and Critical Care
School of Medicine
Johns Hopkins University
1830 E Monument St, Suite 555
Baltimore, MD, 21287
Email: wcheckl1@jhmi.edu
Abstract
Introduction: In South America, the rise in chronic respiratory diseases and weight-related issues due to the ongoing epidemiological transition has prompted research into their interrelationship.
Methods: We sought to assess the association between body mass index (BMI) and bronchodilator responsiveness (BDR) among adults in Peru, Chile, Uruguay, and Argentina, using population-based data from 2 cohort studies. We defined BDR as a ≥12% and ≥200mL increase in either forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) after administration of a short-acting bronchodilator. The analysis also distinguished between FEV1- and FVC-specific BDR. We used logistic regression adjusted for confounders to evaluate associations with BMI.
Results: Among 7160 participants (55.2% men, mean age 57.3 years), 23.7% had a BMI <25kg/m2 and 35.5% had a BMI ≥30 kg/m2. Overall, 9.5% met the criteria for BDR; with 7.8% showing FEV1-specific and 4.9% FVC-specific responses. Compared to a BMI of 20–24.9kg/m2, a BMI ≥30kg/m2 was associated with higher odds of FVC-specific BDR (adjusted odds ratio = 1.47, 95% confidence interval 1.08–2.03), whereas a BMI <20kg/m2 was associated with FEV1-specific BDR among participants with asthma (6.61, 1.23–35.6) and chronic bronchitis (4.71, 1.28–15.9), and with higher odds of any BDR in those with chronic bronchitis (3.90, 1.19–11.9).
Conclusion: There was a differential relationship between BMI and types of BDR: higher BMI was associated with FVC-specific responsiveness, whereas lower BMI was linked to FEV1-specific BDR in individuals with asthma and chronic bronchitis and to overall BDR in those with chronic bronchitis.
Citation
Citation: Soriano-Moreno AN, Lescano AG, Gilman RH, et al. Body mass index and bronchodilator responsiveness in adults: analysis of 2 population-based studies in 4 South American countries. Chronic Obstr Pulm Dis. 2025; 12(6): 477-489. doi: http://dx.doi.org/10.15326/jcopdf.2025.608
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Jacopo Saccomanno, MD1* Thomas Elgeti, MD, PhD2* Stephanie Spiegel1 Eva Pappe, MD1 Thomas Sgarbossa, MD1 Antonia Petersen, MD2 Konrad Neumann3 Marcus A. Mall, MD, PhD4,5,6 Martin Witzenrath, MD, PhD1,7 Ralf-Harto Hübner, MD, PhD1
Author Affiliations
- Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Department of Radiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Center for Lung Research, associated partner site Berlin, Berlin, Germany
- German Center for Child and Adolescent Health, partner site Berlin, Berlin, Germany
- Capnetz Foundation, Hannover, Germany
*Authors contributed equally
Address correspondence to:
Jacopo Saccomanno, MD
Department of Infectious Diseases, Respiratory Medicine and Critical Care
Charité – Universitätsmedizin Berlin
Hindenburgdamm 30
12204 Berlin, Germany
Email: Jacopo.saccomanno@charite.de
Abstract
Background: Chronic obstructive pulmonary disease (COPD) is classified by its clinical phenotypes—chronic bronchitis and emphysema. A computed tomography (CT)-based mucus plug score (MPS) was recently identified as a biomarker to a subgroup of COPD patients with increased airway mucus plugs. While not necessarily linked to more pronounced symptoms or structural lung changes, mucus plugs are associated with increased mortality. Interestingly, a higher MPS seems to be associated with a lower body mass index (BMI), likewise associated with increased mortality. This study aims to characterize patients with advanced emphysema presenting for lung volume reduction therapy with a special focus on mucus plug occurrence.
Material and Methods: This retrospective, monocentric study assessed MPS in advanced COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] stages 3 or 4) and emphysema patients evaluated for lung volume reduction therapy at Charité-Universitätsmedizin Berlin. CT scans were analyzed for mucus plugging, and clinical data were obtained from the emphysema registry.
Results: A total of 127 CT scans were assessed for MPS. About 50% had no mucus plugs (score = 0), 25% had an intermediate burden (score 1–2), and 25% had a high burden (score ≥3). A higher MPS correlated with a lower BMI, more pronounced emphysema, and worse lung function, including forced expiratory volume in 1 second, vital capacity, and diffusing capacity of carbon monoxide. Residual volume, partial pressure of carbon dioxide, the 6-minute walk test, and quality-of-life parameters were unaffected. Multivariate regression analysis found a strong association between mucus plugs and BMI, showing that a decrease in BMI was associated with a higher mucus burden (p<0.001; coefficient of -1.584).
Interpretation: This study supports an association between high MPS and BMI in a vulnerable subgroup of advanced COPD patients. Further research is needed to understand the pathophysiology and consequences of mucus plugs, aiming for individualized risk assessments and treatment strategies.
Citation
Citation: Saccomanno J, Elgeti T, Spiegel S, et al. Association of mucus plugging and body mass index in patients with advanced COPD GOLD stages 3 or 4 with emphysema. Chronic Obstr Pulm Dis. 2025; 12(6): 490-499. doi: http://dx.doi.org/10.15326/jcopdf.2025.0617
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Gerald S. Zavorsky, PhD, RRT1 Roberto W. Dal Negro, MD2 Ivo van der Lee, MD, PhD3 Alexandra M. Preisser, MD4
Author Affiliations
- Department of Physiology and Membrane Biology, University of California, Davis, Davis, California, United States
- CESFAR – National Center for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy
- Department of Pulmonology, Spaarne Gasthuis, Haarlem, The Netherlands
- Institute for Occupational and Maritime Medicine, University Medical Center Hamburg–Eppendorf, Hamburg, Germany
Address correspondence to:
Gerald S. Zavorsky, PhD, RRT
Department of Physiology and Membrane Biology
University of California, Davis
Davis, CA
Email: gszavorsky@health.ucdavis.edu
Abstract
Background: Pulmonary diffusing capacity for nitric oxide (DLNO) remains underutilized despite potential advantages over pulmonary diffusing capacity for carbon monoxide (DLCO). We evaluated whether DLNO better detects emphysema than DLCO, spirometry, or lung volumes in smokers.
Methods: We performed an individual participant data meta-analysis of adult smokers (14–43 pack years) with and without computed tomography-defined emphysema using a standardized 10 ± 2-second breath-hold time double diffusion protocol. Variables were converted to z-scores. Prespecified models contrasted DLCO- versus DLNO-based approaches. Model selection used the Bayesian information criterion (BIC) and leave-one-out information criterion; discrimination used area under the receiver operating characteristic (AUROC) curve and Matthews correlation coefficient (MCC) with repeated cross-validation.
Results: After harmonization and quality control, 408 participants (85 emphysema, 323 controls) were analyzed. The lowest BIC (164.6) occurred for the 3-predictor model with total lung capacity (TLC), forced expiratory volume in 1 second (FEV1), and DLNO z-scores, with an 88% probability of being superior to the next-lowest BIC model (168.5). Discrimination (AUROC 0.97, 95% confidence interval [CI] 0.95–0.98) and classification (MCC 0.80, 95% CI 0.69–0.89) were high. Hierarchical partitioning showed unique contributions from FEV1 z-scores (R2=0.35) > DLNO z-scores (R2=0.21) > TLC z-scores (R2=0.11), totaling McFadden’s R2=0.663. Adding DLCO z-scores increased the total R2 trivially (by 0.003) and contributed largely shared information with DLNO (variance inflation factors ≤ 4.5). Category-free reclassification and Youden-threshold analyses showed small but favorable gains; the case–control risk gap improved by up to ~5% when adding DLNO to a DLCO-based model.
Interpretation: When predicting the likelihood of emphysema in smokers, a parsimonious z-score model comprising TLC, FEV1, and DLNO z-scores provides excellent performance and stable rank superiority.
Citation
Citation: Zavorsky GS, Dal Negro RW, van der Lee I, Preisser AM. Emphysema detection in smokers: diffusing capacity for nitric oxide beats diffusing capacity of carbon monoxide-based models. Chronic Obstr Pulm Dis. 2025; 12(6): 500-511. doi: http://dx.doi.org/10.15326/jcopdf.2025.0645
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Guobing Jia, MD1,2 Tao Guo, MD1 Lei Liu, MD3 Chengshi He, MS2
Author Affiliations
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Respiratory and Critical Care Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Respiratory and Critical Care Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
Address correspondence to:
Chengshi He, MS
Department of Respiratory and Critical Care Medicine
Hospital of Chengdu University of Traditional Chinese Medicine
Chengdu, China
Email: 18408293045@163.com
Abstract
Background: Some studies suggest that statins could reduce the risk of chronic obstructive pulmonary disease (COPD), but it is unclear if this effect is related to their lipid-lowering properties. The causal link between serum lipid levels and COPD risk remains uncertain. This study aims to clarify this potential causal relationship and evaluate the impact of lipid-lowering drug target genes on COPD.
Methods: Mendelian randomization (MR) was used to investigate causal associations between lipid levels, lipid-lowering drug target genes, and COPD risk. Data were obtained from publicly available genome-wide association study databases. The inverse variance weighted method was the primary statistical approach for evaluating causal effects, complemented by various sensitivity analyses.
Results: MR analysis demonstrated a causal relationship between low-density lipoprotein cholesterol (LDL-C) and a reduced risk of COPD (odds ratio [OR]=0.90, 95% confidence interval [CI]=0.85–0.95, P=1.50×10⁻⁴). Causal relationships were also identified for 2 lipid-lowering drug target genes, HMGCR (OR=0.63, 95%CI=0.54–0.75, P=4.92×10⁻⁸) and PCSK9 (OR=0.87, 95%CI=0.80–0.95, P=0.001), with a reduced COPD risk. Although MR analysis indicated a potential causal relationship between LPL (OR=0.86, 95%CI=0.79–0.94, P=6.37×10⁻⁴) and reduced COPD risk, colocalization analysis did not support this finding. No associations were observed between other lipid traits, lipid-lowering drug target genes, and COPD.
Conclusion: This study genetically identified causal relationships between serum LDL-C levels, the 2 coding genes HMGCR and PCSK9, and a reduced risk of COPD. These findings suggest that the protective effect of statins on COPD may occur independently of their lipid-lowering function. Further clinical validation is needed to confirm this hypothesis.
Citation
Citation: Jia G, Guo T, Liu L, He C. Lipids, lipid-lowering drug target genes and COPD risk: a Mendelian randomization study. Chronic Obstr Pulm Dis. 2025; 12(6): 512-521. doi: http://dx.doi.org/10.15326/jcopdf.2025.0632
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