New drugs under development for COPD

Uwagboe, Isabel; Adcock, Ian M.; Bello, Federica Lo; Caramori, Gaetano; Mumby, Sharon

doi:10.23736/s0026-4806.22.08024-7

Cited by 22 publications

(6 citation statements)

References 197 publications

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“…COPD, as an inflammatory disease, has long been a focus of interest for exploring anti-inflammatory therapy ( 41 ). While current research has not conclusively shown the effective improvement of the disease process with anti-inflammatory drugs, inflammation remains a central focus of COPD pathogenesis research, and anti-inflammatory treatment retains significant research value ( 42 , 43 ). Currently, COPD treatment primarily involves pharmacotherapy and non-pharmacological interventions.…”

Section: Discussionmentioning

confidence: 99%

Association of dietary inflammatory indices with sarcopenia and all-cause mortality in COPD patients

Jiang,

Ma,

Sun

et al. 2024

Front. Nutr.

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BackgroundSarcopenia frequently occurs as a comorbidity in individuals with COPD. However, research on the impact of Appendicular Skeletal Muscle Mass (ASM) on survival in COPD patients is scarce. Moreover, there is a lack of research on the association between dietary pro-inflammatory capacity and sarcopenia in COPD.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) covering the years 1999 to 2006 and 2011 to 2018. We aimed to investigate the relationship between the Dietary Inflammatory Index (DII) and sarcopenia prevalence among adults diagnosed with COPD in the United States. Furthermore, we sought to explore the relationship between sarcopenia, ASMI, and all-cause mortality. The study included a total of 1,429 eligible adult participants, divided into four groups based on quartiles of DII, with adjustments for sample weights. Methodologically, we used multivariable logistic regression analyses and to examine the association between DII and sarcopenia. Additionally, we used restricted cubic spline (RCS) tests to evaluate potential non-linear relationships. To assess the effect of sarcopenia on overall all-cause mortality, we used Kaplan–Meier models and Cox proportional hazards models. Moreover, we used RCS analyses to investigate potential non-linear relationships between ASMI and all-cause mortality. Subgroup analyses were conducted to confirm the reliability of our study findings.ResultsIn our COPD participant cohort, individuals with higher DII scores were more likely to be female, unmarried, have lower educational attainment, and show lower ASMI. Using multivariable logistic regression models, we found a positive association between the highest quartile of DII levels and sarcopenia incidence [Odds Ratio (OR) 2.37; 95% Confidence Interval (CI) 1.26–4.48; p = 0.01]. However, analysis of RCS curves did not show a non-linear relationship between DII and sarcopenia. Throughout the entire follow-up period, a total of 367 deaths occurred among all COPD patients. Kaplan–Meier survival curves showed a significantly higher all-cause mortality rate among individuals with concurrent sarcopenia (p < 0.0001). Cox proportional hazards model analysis showed a 44% higher risk of all-cause mortality among COPD patients with sarcopenia compared to those without sarcopenia [Hazard Ratio (HR): 1.44; 95% CI 1.05–1.99; p < 0.05]. Additionally, our final RCS analyses revealed a significant non-linear association between ASMI levels and all-cause mortality among COPD patients, with a turning point identified at 8.32 kg/m2. Participants with ASMI levels above this inflection point had a 42% lower risk of all-cause mortality compared to those with ASMI levels below it (HR 0.58; 95% CI 0.48–0.7).ConclusionWe observed a significant association between concurrent sarcopenia and an increased risk of all-cause mortality in COPD patients within the United States. Moreover, ASMI demonstrated a non-linear association with all-cause mortality, with a critical threshold identified at 8.32 kg/m2. Our findings also revealed an association between DII and the presence of sarcopenia. Consequently, further investigations are warranted to explore the feasibility of dietary DII adjustments as a means to mitigate muscle wasting and enhance the prognosis of COPD.

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Section: Discussionmentioning

confidence: 99%

Association of dietary inflammatory indices with sarcopenia and all-cause mortality in COPD patients

Jiang,

Ma,

Sun

et al. 2024

Front. Nutr.

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“…It is proved that ghrelin can increase the level of p62 through the AMPK/mTOR pathway, further restraining the hepatic autophagy from treating NAFLD [20]. Chronic obstructive pulmonary disease (COPD) belongs to chronic inflammatory lung disease caused by dysregulated autophagy [99]. It is observed that ghrelin can suppress the inflammation and autophagy.…”

Section: Ghrelin and Autophagymentioning

confidence: 99%

Emerging Relevance of Ghrelin in Programmed Cell Death and Its Application in Diseases

Zhang,

Zeng,

Liu

et al. 2023

IJMS

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Ghrelin, comprising 28 amino acids, was initially discovered as a hormone that promotes growth hormones. The original focus was on the effects of ghrelin on controlling hunger and satiation. As the research further develops, the research scope of ghrelin has expanded to a wide range of systems and diseases. Nevertheless, the specific mechanisms remain incompletely understood. In recent years, substantial studies have demonstrated that ghrelin has anti-inflammatory, antioxidant, antiapoptotic, and other effects, which could affect the signaling pathways of various kinds of programmed cell death (PCD) in treating diseases. However, the regulatory mechanisms underlying the function of ghrelin in different kinds of PCD have not been thoroughly illuminated. This review describes the relationship between ghrelin and four kinds of PCD (apoptosis, necroptosis, autophagy, and pyroptosis) and then introduces the clinical applications based on the different features of ghrelin.

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“…Chronic obstructive pulmonary disease (COPD) is characterized by consistent airway inflammation and irreversible airflow obstruction, which is the third leading cause of mortality in the world [ 1 , 2 ]. COPD is mainly triggered by the inhalation of toxic particles, especially tobacco smoke and polluted air [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Nrf2/HO-1 signaling activation alleviates cigarette smoke-induced inflammation in chronic obstructive pulmonary disease by suppressing NLRP3-mediated pyroptosis

Zhang,

Wang,

Wang

et al. 2024

J Cardiothorac Surg

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Background This study examined the effect of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway on chronic obstructive pulmonary disease (COPD) and the potential molecular mechanism. Methods A COPD mouse model was established by cigarette smoke exposure and administered with either ML385 or dimethyl fumarate (DMF). Airway resistance of mice was detected. IL-1β and IL-6 levels in mice alveolar lavage fluid were examined by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining and immunohistochemical of lung tissues were utilized to detect lung injury and NLRP3 expression. DMF was used to treat COPD cell model constructed by exposing normal human bronchial epithelial (NHBE) cells to cigarette smoke extract. NHBE cells were transfected by NLRP3-expression vectors. Expression of proteins was detected by Western blot. Results COPD mice showed the enhanced airway resistance, the inactivated Nrf2/HO-1 pathway and the overexpressed NLRP3, Caspase-1 and GSDMD-N proteins in lung tissues, and the increased IL-1β and IL-6 levels in alveolar lavage fluid. ML385 treatment augmented these indicators and lung injury in COPD mice. However, DMF intervention attenuated these indicators and lung injury in COPD mice. Nrf2/HO-1 pathway inactivation and overexpression of NLRP3, Caspase-1 and GSDMD-N proteins were observed in COPD cells. DMF intervention activated Nrf2/HO-1 pathway and down-regulated NLRP3, Caspase-1 and GSDMD-N proteins in COPD cells. However, NLRP3 overexpression abolished the effect of DMF on COPD cells. Conclusion Nrf2/HO-1 pathway activation may alleviate inflammation in COPD by suppressing the NLRP3-related pyroptosis. Activating the Nrf2/HO-1 pathway may be an effective method to treat COPD.

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New drugs under development for COPD

Cited by 22 publications

References 197 publications

Association of dietary inflammatory indices with sarcopenia and all-cause mortality in COPD patients

Association of dietary inflammatory indices with sarcopenia and all-cause mortality in COPD patients

Emerging Relevance of Ghrelin in Programmed Cell Death and Its Application in Diseases

Nrf2/HO-1 signaling activation alleviates cigarette smoke-induced inflammation in chronic obstructive pulmonary disease by suppressing NLRP3-mediated pyroptosis

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