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Clinical Research in Cardiology :... Feb 2024Many patients seen by cardiologists suffer chronic obstructive pulmonary disease (COPD) in addition to their primary cardiovascular problem. Yet, quite often COPD has... (Review)
Review
Many patients seen by cardiologists suffer chronic obstructive pulmonary disease (COPD) in addition to their primary cardiovascular problem. Yet, quite often COPD has not been diagnosed and, consequently, patients have not been treated of their pulmonary disease. Recognizing and treating COPD in patients with CVDs is important because optimal treatment of the COPD carries important benefits on cardiovascular outcomes. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) publishes an annual report that serves as a clinical guideline for the diagnosis and management of COPD around the world and has very recently released the 2023 annual report. Here, we provide a summary of the GOLD 2023 recommendations that highlights those aspects of more interest for practicing cardiologists dealing with patients with CVD who may suffer COPD.
Topics: Humans; Cardiologists; Pulmonary Disease, Chronic Obstructive; Lung
PubMed: 37233751
DOI: 10.1007/s00392-023-02217-0 -
Medicina Clinica Apr 2024Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition caused by decreased plasma and tissue levels of alpha-1 antitrypsin (AAT) that can lead to serious... (Review)
Review
Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition caused by decreased plasma and tissue levels of alpha-1 antitrypsin (AAT) that can lead to serious lung and liver disease in children and adults. AATD patients face challenges such as under diagnosis, clinical variability, and limited treatment options for liver disease. Early detection and biomarkers for predicting outcomes are needed to improve patient outcome. Currently, the only approved pharmacological therapy is augmentation therapy, which can delay the progression of emphysema. However, alternative strategies such as gene therapy, induced pluripotent stem cells, and prevention of AAT polymerization inside hepatocytes are being investigated. This review aims to summarize and update current knowledge on AATD, identify areas of controversy, and formulate questions for further research.
Topics: Adult; Child; Humans; alpha 1-Antitrypsin Deficiency; Biomarkers; Lung; Pulmonary Disease, Chronic Obstructive
PubMed: 37993348
DOI: 10.1016/j.medcli.2023.10.014 -
Signal Transduction and Targeted Therapy Oct 2023Patients with chronic obstructive pulmonary disease (COPD) who exhibit elevated blood eosinophil levels often experience worsened lung function and more severe...
Patients with chronic obstructive pulmonary disease (COPD) who exhibit elevated blood eosinophil levels often experience worsened lung function and more severe emphysema. This implies the potential involvement of eosinophils in the development of emphysema. However, the precise mechanisms underlying the development of eosinophil-mediated emphysema remain unclear. In this study, we employed single-cell RNA sequencing to identify eosinophil subgroups in mouse models of asthma and emphysema, followed by functional analyses of these subgroups. Assessment of accumulated eosinophils unveiled distinct transcriptomes in the lungs of mice with elastase-induced emphysema and ovalbumin-induced asthma. Depletion of eosinophils through the use of anti-interleukin-5 antibodies ameliorated elastase-induced emphysema. A particularly noteworthy discovery is that eosinophil-derived cathepsin L contributed to the degradation of the extracellular matrix, thereby leading to emphysema in pulmonary tissue. Inhibition of cathepsin L resulted in a reduction of elastase-induced emphysema in a mouse model. Importantly, eosinophil levels correlated positively with serum cathepsin L levels, which were higher in emphysema patients than those without emphysema. Expression of cathepsin L in eosinophils demonstrated a direct association with lung emphysema in COPD patients. Collectively, these findings underscore the significant role of eosinophil-derived cathepsin L in extracellular matrix degradation and remodeling, and its relevance to emphysema in COPD patients. Consequently, targeting eosinophil-derived cathepsin L could potentially offer a therapeutic avenue for emphysema patients. Further investigations are warranted to explore therapeutic strategies targeting cathepsin L in emphysema patients.
Topics: Animals; Humans; Mice; Asthma; Cathepsin L; Emphysema; Eosinophils; Lung; Pancreatic Elastase; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema
PubMed: 37816708
DOI: 10.1038/s41392-023-01634-x -
Thorax Nov 2023Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised...
BACKGROUND
Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations.
METHODS
New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined.
RESULTS
The algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91-1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near , which is implicated in mucin hypersecretion (p=1.1 ×10). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome.
CONCLUSION
Large-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD.
Topics: Humans; Pulmonary Emphysema; Case-Control Studies; Unsupervised Machine Learning; Pulmonary Disease, Chronic Obstructive; Lung; Emphysema; Tomography, X-Ray Computed
PubMed: 37268414
DOI: 10.1136/thorax-2022-219158