Progression of Emphysema and Small Airways Disease in Cigarette Smokers

Pompe, Esther; Moore, Camille M.; Hoesein, Firdaus A. A. Mohamed; Jong, Pim A. de; Charbonnier, Jean-Paul; Han, MeiLan K.; Humphries, S.M.; Hatt, Charles R.; Galbán, Craig J.; Silverman, E.K.; Crapo, James D.; Washko, George R.; Regan, E.A.; Make, Barry J.; Strand, Matthew; Lammers, Jan‐Willem J.; Rikxoort, Eva M. van; Lynch, David A.; Investigators, COPDGene

doi:10.15326/jcopdf.2020.0140

Cited by 13 publications

(13 citation statements)

References 29 publications

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“…CT scans could detect emphysema in patients who do not meet the spirometry standards of COPD in 20% of smokers. 2 , 32 Lung function combined with chest CT may be better for assessing the disease progression and identifying subjects at risk of progression. In our study, the correlation analysis revealed that CD19 and POU2AF1 were significantly associated with lung function and CT indexes of emphysema.…”

Section: Discussionmentioning

confidence: 99%

“…1 As an important pathological manifestation of COPD, emphysema is defined as “abnormal permanent enlargement of air spaces distal to terminal bronchioles, accompanied by destruction of their walls without obvious fibrosis”. 2 Emphysema has been recognized as one of the COPD phenotypes and may be present in other phenotypes, as well as in smokers without COPD. 3 Moreover, emphysema is associated with the severity and progression of COPD.…”

Section: Introductionmentioning

confidence: 99%

“… 3 Moreover, emphysema is associated with the severity and progression of COPD. 2 Patients with emphysema are more likely to experience acute exacerbations of COPD and have multiple complications than those without emphysema. 4 Therefore, a better understanding of the detailed mechanisms underlying emphysema is helpful for preventing COPD progression.…”

Section: Introductionmentioning

confidence: 99%

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CD19 and POU2AF1 are Potential Immune-Related Biomarkers Involved in the Emphysema of COPD: On Multiple Microarray Analysis

Zhang¹,

Ye²,

Sun³

et al. 2022

JIR

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Purpose Emphysema is the main cause of the progression of chronic obstructive pulmonary disease (COPD). This study aimed to identify the key genes involved in COPD-related emphysema. Patients and Methods GSE76925 was downloaded from Gene Expression Omnibus database. Protein–protein interaction networks of differentially expressed genes (DEGs) between control and COPD groups were constructed to identify hub genes using Cytoscape. Diagnostic performance of hub genes was evaluated using receiver operating characteristic analysis. Correlation analysis was performed to identify the key genes by analyzing the relationship between the hub genes and lung function and computed tomography (CT) indexes of emphysema. COPD patients were then divided into two groups based on the median expression of key genes and DEGs between these two groups were identified. Enrichment analysis of DEGs and correlation analysis between key genes and the infiltration of the immune cells were also analyzed. Finally, the role of key genes was evaluated in a lung tissues dataset (GSE47460) and a blood dataset (GSE76705). Additionally, the expression of key genes was validated by quantitative real-time polymerase chain reaction and immunohistochemistry. Results CD19 and POU2AF1 had diagnostic efficacy for COPD and were significantly correlated with lung function and CT indexes of emphysema. Enrichment and immune analyses revealed that CD19 and POU2AF1 were correlated with the B cells in COPD. These results were consistent in GSE47460. The expression of CD19 and POU2AF1 in blood was the opposite of that in lung tissues, and CD19 and POU2AF1 were both significantly upregulated in COPD lung tissues at both the mRNA and protein levels. Conclusion CD19 and POU2AF1 may serve as key regulators of emphysema and contribute to the progression of COPD by regulating the B-cell immunology. Targeting B cells may be a promising strategy for treating COPD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD19 and POU2AF1 are Potential Immune-Related Biomarkers Involved in the Emphysema of COPD: On Multiple Microarray Analysis

Zhang¹,

Ye²,

Sun³

et al. 2022

JIR

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“… 58 This PRM approach was also successfully used in smokers without COPD, where it showed that these metrics can identify unique patterns of progression, and that both PRM fSAD and PRM EMPH , ie, PRM-derived emphysema, can independently predict future development of emphysema. 59 , 60 Bronchiectasis was also found to be associated with increased emphysema in smokers and those with both bronchiectasis and emphysema had lower FEV 1 and 6MWD. 17 In current or former smokers, the low attenuation area on low-dose CT imaging ordered as part of routine lung cancer screening may be able to detect quantitative emphysema and diagnose subjects with early COPD, allowing clinicians to monitor patients closely and perhaps initiate appropriate treatment when needed.…”

Section: Commercial Platformsmentioning

confidence: 96%

CT-Based Commercial Software Applications: Improving Patient Care Through Accurate COPD Subtyping

Wang¹,

Ram²,

Labaki³

et al. 2022

COPD

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Chronic obstructive pulmonary disease (COPD) is heterogenous in its clinical manifestations and disease progression. Patients often have disease courses that are difficult to predict with readily available data, such as lung function testing. The ability to better classify COPD into well-defined groups will allow researchers and clinicians to tailor novel therapies, monitor their effects, and improve patient-centered outcomes. Different modalities of assessing these COPD phenotypes are actively being studied, and an area of great promise includes the use of quantitative computed tomography (QCT) techniques focused on key features such as airway anatomy, lung density, and vascular morphology. Over the last few decades, companies around the world have commercialized automated CT software packages that have proven immensely useful in these endeavors. This article reviews the key features of several commercial platforms, including the technologies they are based on, the metrics they can generate, and their clinical correlations and applications. While such tools are increasingly being used in research and clinical settings, they have yet to be consistently adopted for diagnostic work-up and treatment planning, and their full potential remains to be explored.

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“…Studies have shown that the small airways contribute significantly to airflow obstruction in both COPD [ 4 ] and asthma [ 5 ]. Characterised by inflammation, hypersecretion of mucus and airway remodelling [ 6 ], small airways obstruction (SAO) has been shown to precede both emphysematous changes and reduction in traditional spirometric parameters in COPD [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Spirometry parameters used to define small airways obstruction in population-based studies: systematic review

et al. 2022

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Background The assessment of small airways obstruction (SAO) using spirometry is practiced in population-based studies. However, it is not clear what are the most used parameters and cut-offs to define abnormal results. Methods We searched three databases (Medline, Web of Science, Google Scholar) for population-based studies, published by 1 May 2021, that used spirometry parameters to identify SAO and/or provided criteria for defining SAO. We systematically reviewed these studies and summarised evidence to determine the most widely used spirometry parameter and criteria for defining SAO. In addition, we extracted prevalence estimates and identified associated risk factors. To estimate a pooled prevalence of SAO, we conducted a meta-analysis and explored heterogeneity across studies using meta regression. Results Twenty-five studies used spirometry to identify SAO. The most widely utilised parameter (15 studies) was FEF25–75, either alone or in combination with other measurements. Ten studies provided criteria for the definition of SAO, of which percent predicted cut-offs were the most common (5 studies). However, there was no agreement on which cut-off value to use. Prevalence of SAO ranged from 7.5% to 45.9%. As a result of high heterogeneity across studies (I2 = 99.3%), explained by choice of spirometry parameter and WHO region, we do not present a pooled prevalence estimate. Conclusion There is a lack of consensus regarding the best spirometry parameter or defining criteria for identification of SAO. The value of continuing to measure SAO using spirometry is unclear without further research using large longitudinal data. PROSPERO registration number CRD42021250206

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Progression of Emphysema and Small Airways Disease in Cigarette Smokers

Abstract: For personal use only. Permission required for all other uses.

Cited by 13 publications

References 29 publications

CD19 and POU2AF1 are Potential Immune-Related Biomarkers Involved in the Emphysema of COPD: On Multiple Microarray Analysis

CD19 and POU2AF1 are Potential Immune-Related Biomarkers Involved in the Emphysema of COPD: On Multiple Microarray Analysis

CT-Based Commercial Software Applications: Improving Patient Care Through Accurate COPD Subtyping

Spirometry parameters used to define small airways obstruction in population-based studies: systematic review

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