Chronic Obstructive Pulmonary Disease Definition: Is It Time to Incorporate the Concept of Failure of Lung Regeneration?

Confalonieri, Marco; Braga, Luca; Salton, Francesco; Ruaro, Barbara; Confalonieri, Paola

doi:10.1164/rccm.202208-1508le

Cited by 27 publications

(16 citation statements)

References 6 publications

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“…Known contributing factors include protease/antiprotease balance, chronic oxidative injury, immune responses with chronic proinflammatory signaling, and cell loss due to apoptotic, necroptotic, or other pathways of cell death (2,8–11,30). A failure of regeneration in distal airways and parenchyma, a consequence of the exhaustion of stem cell pools, was suggested recently as one of the drivers of emphysema (3). The regenerative ability of stem cells provides a level of resistance against a variety of environmental challenges, including exposure to cigarette smoke (31).…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to cigarette smoke is a major risk factor for chronic obstructive pulmonary disease ( COPD ), which kills >400,000 Americans each year (1). Lung cells in these individuals lose their ability to repair smoke-induced damage, which results in sustained inflammation, cell death, and emphysema (2,3). The cells that are most affected are type 1 alveolar epithelial cells ( AEC1s ) (4).…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial ncRNA LDL-805 declines in alveolar epithelial type 2 cells of chronic obstructive pulmonary disease patients

Mathuram,

Su,

Bard

et al. 2024

Preprint

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Rationale: We showed that levels of a murine mitochondrial noncoding RNA, mito-ncR-LDL805, increase in alveolar epithelial type 2 cells exposed to extracts from cigarette smoke. The transcripts translocate to the nucleus, upregulating nucleus-encoded mitochondrial genes and mitochondrial bioenergetics. This response is lost after chronic exposure to smoke in a mouse model of chronic obstructive pulmonary disease. Objectives: To determine if mito-ncR-LDL805 plays a role in human disease, this study aimed to (i) identify the human homologue, (ii) test if the smoke-induced response occurs in human cells, (ii) determine causality between the subcellular localization of the transcript and increased mitochondrial bioenergetics, and (iii) analyze mito-ncR-LDL805 transcript levels in samples from patients with chronic obstructive pulmonary disease. Methods: Levels and subcellular localization of the human homologue identified from an RNA transcript library were assessed in human alveolar epithelial type 2 cells exposed to smoke extract. Lipid nanoparticles were used for nucleus-targeted delivery of mito-ncR-LDL805 transcripts. Analyses included in situ hybridization, quantitative PCR, cell growth, and Seahorse mitochondrial bioenergetics assays. Measurements and Main Results: The levels of human homologue transiently increased and the transcripts translocated to the nuclei in human cells exposed to smoke extract. Targeted nuclear delivery of transcripts increased mitochondrial bioenergetics. Alveolar cells from humans with chronic obstructive pulmonary disease had reduced levels of the mito-ncR-LDL805. Conclusions: mito-ncR-LDL805 mediates mitochondrial bioenergetics in murine and human alveolar epithelial type 2 cells in response to cigarette smoke exposure, but this response is likely lost in diseases associated with chronic smoking, such as chronic obstructive pulmonary disease, due to its diminished levels.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial ncRNA LDL-805 declines in alveolar epithelial type 2 cells of chronic obstructive pulmonary disease patients

Mathuram,

Su,

Bard

et al. 2024

Preprint

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“…Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease, which can cause extensive lung parenchymal cell damage, 1 and is characterized by chronic airflow restriction in the surrounding airway accompanied by a series of irreversible pathological changes in the lungs, which usually gradually worsens over time. 2 COPD is the third most commonly diagnosed disease with high morbidity and mortality in the world. 3 , 4 However, the pathogenesis of COPD is not entirely clear and reported intricate relationships among the various pathogenesis, making it difficult to achieve effective prevention and control of COPD.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppression by Inflammation-Stimulated Amplification of Myeloid-Derived Suppressor Cells and Changes in Expression of Immune Checkpoint HHLA2 in Chronic Obstructive Pulmonary Disease

Xu¹,

Li²,

Jiang³

et al. 2023

COPD

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Background The interaction between immune checkpoint and myeloid-derived suppressor cells (MDSCs) play a significant role in inflammatory diseases. But their correlation with chronic obstructive pulmonary disease (COPD) remains unclear. Methods The differentially expressed immune checkpoints and immunocytes in the airway tissues of COPD patients were identified by bioinformatics analysis, followed by correlation analysis and identification of immune-related differential genes for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. The results of bioinformatics analysis were verified by ELISA and Real-Time PCR and transcriptome sequencing of the peripheral blood of both COPD patients and healthy subjects. Results The results of the bioinformatics analysis showed that the level of MDSCs in airway tissue and peripheral blood of COPD patients was higher than that of healthy controls. The expression of CSF1 in airway tissue and peripheral blood of COPD patients increased, and CYBB was increased in airway tissue and decreased in peripheral blood of COPD patients. The expression of HHLA2 in the airway tissue decreased in COPD patients, and showed a negative correlation with MDSCs, with a correlation coefficient of −0.37. The peripheral blood flow cytometry results indicated that MDSCs and Treg cells of COPD patients were higher than those in the healthy control group. The results of peripheral blood ELISA and RT-PCR showed that the HHLA2 and CSF1 levels in COPD patients were higher than those in the healthy control group. Conclusion In COPD, the bone marrow is stimulated to produce MDSCs, and a large number of MDSCs migrate to airway tissue through peripheral blood and cooperate with HHLA2 to exert an immunosuppressive effect. Whether MDSCs play an immunosuppressive effect during migration needs to be further confirmed.

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“…Chronic obstructive pulmonary disease (COPD) is a common chronic progressive respiratory disease characterized by irreversible and continuously progressive airflow limitations and recurrent respiratory symptoms ( Vogelmeier et al, 2017 ; Celli et al, 2022 ; Confalonieri et al, 2023 ). According to large-scale global epidemiological evidence, the global prevalence of COPD is 11.7% and is increasing each year ( Adeloye et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Comparison of treatment persistence, adherence, and risk of exacerbation in patients with COPD treated with single-inhaler versus multiple-inhaler triple therapy: A prospective observational study in China

et al. 2023

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Aim: This study sought to compare treatment persistence, adherence, and risk of exacerbation among patients with COPD treated with single-inhaler triple therapy (SITT) and multiple-inhaler triple therapy (MITT) in the Chinese population.Methods: This was a multicenter, prospective observational study. Patients with COPD from ten hospitals in Hunan and Guangxi provinces in China were recruited from 1 January 2020 to 31 November 2021 for the study and were followed up for one year. Treatment persistence, adherence, and exacerbation rates during the 12-month follow-up were analyzed in COPD patients treated with SITT and MITT.Results: A total of 1,328 patients were enrolled for final analysis, including 535 (40.3%) patients treated with SITT and 793 (59.7%) treated with MITT. Of these patients, the mean age was 64.9 years and most patients were men. The mean CAT score was 15.2 ± 7.1, and the median (IQR) FEV1% was 54.4 (31.2). The SITT group had a higher mean CAT score, more patients with mMRC >1, and lower mean FEV1% and FEV1/FVC than the MITT patients. Moreover, the proportion of patients with ≥1 exacerbation in the previous year was higher in the SITT cohort. SITT patients had, compared to MITT patients, a higher proportion of adherence (proportion of days covered, PDC) ≥0.8 (86.5% vs. 79.8%; p = 0.006), higher treatment persistence [HR: 1.676 (1.356–2.071), p < 0.001], lower risk of moderate-to-severe exacerbation [HR: 0.729 (0.593–0.898), p = 0.003], and severe exacerbation [HR: 0.675 (0.515–0.875), p = 0.003], as well as reduced all-cause mortality risk [HR: 0.475 (0.237-0.952), p = 0.036] during the 12-month follow-up. Persistence was related to fewer future exacerbations and mortality than non-persistence in the SITT and MITT groups.Conclusion: Patients with COPD treated with SITT showed improved treatment persistence and adherence, as well as a reduction in the risk of moderate-to-severe exacerbation, severe exacerbation, and mortality compared to patients treated with MITT in the Chinese population.Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR-POC-17010431.

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Chronic Obstructive Pulmonary Disease Definition: Is It Time to Incorporate the Concept of Failure of Lung Regeneration?

Cited by 27 publications

References 6 publications

Mitochondrial ncRNA LDL-805 declines in alveolar epithelial type 2 cells of chronic obstructive pulmonary disease patients

Mitochondrial ncRNA LDL-805 declines in alveolar epithelial type 2 cells of chronic obstructive pulmonary disease patients

Immunosuppression by Inflammation-Stimulated Amplification of Myeloid-Derived Suppressor Cells and Changes in Expression of Immune Checkpoint HHLA2 in Chronic Obstructive Pulmonary Disease

Comparison of treatment persistence, adherence, and risk of exacerbation in patients with COPD treated with single-inhaler versus multiple-inhaler triple therapy: A prospective observational study in China

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