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Introduction: Exacerbations of COPD (ECOPDs) are important events in the course of COPD, accelerating the rate of decline in lung function and increasing the mortality risk. A growing body of evidence suggests the significance of the "frequent exacerbator" phenotype. This phenotype seems to be associated with a more severe airflow limitation, symptoms, health-related quality of life impairment, and higher mortality. However, there is no described biomarker that would help to identify this group of patients., Patients and Methods: Patients with COPD in "D" GOLD category were monitored for 3 years according to events of ECOPD. Serum samples were collected from the patients. Circulating level of plasma soluble receptor for advanced glycation end-products (sRAGE) was measured using commercially available high sensitivity kits. The receiver operating characteristic (ROC) curve analysis was used to assess the usefulness of sRAGE to identify frequent exacerbator phenotype. Log-rank test was used in the analysis of time to the subsequent exacerbation. Pearson ( R ) or Spearman's rank ( R S ) correlation coefficients were used for correlation analysis., Results: Nineteen patients were enrolled. The area under the ROC curve (AUROC) for sRAGE for the identification of frequent exacerbator phenotype was 0.81. Analysis identified the cutoff point as 850.407 pg/mL, characterized by a sensitivity of 0.80 (95% CI: 0.28-1.0) and specificity of 0.93 (95% CI: 0.66-1.0). Additionally, in the group with sRAGE ≤850.407 pg/mL, we observed significantly shorter time to the subsequent exacerbation: median of 32 vs 105.5 days ( P =0.03). Correlation analysis revealed significant negative correlation between sRAGE and the number of exacerbations requiring hospitalization during the whole time of follow-up ( R S =-0.53; P =0.02) and significant positive correlation with FEV 1 expressed as the percentage of reference value ( R =0.6; P =0.006)., Conclusion: sRAGE seems to be useful in the identification of frequent exacerbator phenotype. This parameter may also be used in the prediction of time to ECOPD. Our findings should be confirmed in a sufficiently powered larger sample., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: COPD represents a major global health issue, which is often accompanied by cardiovascular diseases. A considerable body of evidence suggests that cardiovascular risk is elevated by the activation of blood platelets, which in turn is exacerbated by inflammation. As reactive oxygen species are believed to be an important factor in platelet metabolism and functioning, the aim of our study was to perform a complex assessment of mitochondrial function in platelets in chronic smoke exposed animals with COPD-like lung lesions., Materials and Methods: Eight-week-old, male Dunkin Hartley guinea pigs (the study group) were exposed to the cigarette smoke from commercial unfiltered cigarettes (0.9 mg/cig of nicotine content) or to the air without cigarette smoke (control group), using the Candela Constructions ® exposure system. The animals were exposed for 4 hours daily, 5 days a week, with 2×70 mL puff/minute, until signs of dyspnea were observed. The animals were bled, and isolated platelets were used to monitor blood platelet respiration. The mitochondrial respiratory parameters of the platelets were monitored in vitro based on continuous recording of oxygen consumption by high-resolution respirometry., Results: An elevated respiration trend was observed in the LEAK-state (adjusted for number of platelets) in the smoke-exposed animals: 6.75 (5.09) vs 2.53 (1.28) (pmol O 2 /[s ⋅ 110 8 platelets]); bootstrap-boosted P 1α =0.04. The study group also demonstrated lowered respiration in the ET-state (normalized for protein content): 12.31 (4.84) vs 16.48 (1.72) (pmol O 2 /[s ⋅ mg of protein]); bootstrap-boosted P 1α =0.049., Conclusion: Our results suggest increased proton and electron leak and decreased electron transfer system capacity in platelets from chronic smoke-exposed animals. These observations may also indicate that platelets play an important role in the pathobiology of COPD and its comorbidities and may serve as a background for possible therapeutic targeting. However, these preliminary outcomes should be further validated in studies based on larger samples., Competing Interests: Disclosure The costs of this study were defrayed from regular finances of the Department of Pneumology and Allergy, The animal house of the Pharmaceutical Faculty, Department of Hemostasis and Hemostatic Disorders, of Medical University of Lodz, Poland, and of the Department of General and Inorganic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec of Medical University of Silesia, and Institute of Occupational Medicine and Environmental Health in Sosnowiec. AB is also supported by the fund for the young investigators of the Medical University of Lodz (502-03/1-151-03/502-14-364-18). KS received the Etiuda scholarship funded by the NCN (2016/20/T/NZ3/00505). LK is supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number P50DA036105 and the Center for Tobacco Products of the U.S. Food and Drug Administration. The content is solely the responsibility of the authors and does not necessarily represent the views of the NIH or the FDA. LK works as an expert for the Polish National Committee for Standardization and for the European Committee for standardization of requirements and test methods for e-liquids and emissions. Additionally, JK is and LK was an employee of the Institute of Occupational Medicine and Environmental Health. One of the institute’s objectives is outsourcing for the industrial sector, including manufacturers of e-cigarettes. However, this has no influence on studies design. The other authors report no conflicts of interest in this work.

Introduction: Exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events in the course of the disease, negatively influencing health status and disease progression. Therefore, there is a strong need for deeper understanding of the pathology of ECOPD to elaborate new therapeutic approaches and ameliorate prognoses. Contributions of mitochondria to pathobiology of COPD are still under investigation, although growing evidence suggests their important role in this disease. The aim of our study was to assess the morphometric parameters of mitochondria in lymphocytes of patients with ECOPD., Patients and Methods: Lymphocytes were isolated from the peripheral blood of patients with COPD. Transmission electron microscopy was used to assess absolute number of mitochondria per cell, mitochondrial content, and morphometric parameters of individual mitochondria. We also counted indexes for elongation and interconnectivity., Results: Eighteen patients (9 with ECOPD and 9 in the stable period of the disease) were analyzed. We observed significantly lower length of mitochondrion ( P =0.03) and significant decrease both in elongation ( P =0.03) and interconnectivity indexes ( P =0.04) in ECOPD patients., Conclusions: The morphometric parameters of mitochondria in lymphocytes derived from patients during the early period of ECOPD requiring hospitalization are altered in comparison to patients in the stable period of the disease. This suggests their contribution to pathobiology of ECOPD. These preliminary outcomes should be further validated in larger size samples., Competing Interests: Disclosure The authors report no conflict of interests in this work.

Although current therapies in chronic obstructive pulmonary disease (COPD) improve the quality of life, they do not satisfactorily reduce disease progression or mortality. There are still many gaps in knowledge about the cellular, molecular, and genetic mechanisms contributing to pathobiology of this disease. However, increasing evidence suggests that accelerated aging, chronic systemic inflammation, and oxidative stress play major roles in pathogenesis in COPD, thus opening new opportunities in therapy. Therefore, the aim of our review was to describe and discuss some of the most widely used therapeutics that affect the root cause of aging and oxidative stress (metformin, melatonin, sirolimus, statins, vitamin D, and testosterone) in context of COPD therapy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

COPD is associated with different comorbid diseases, and their frequency increases with age. Comorbidities severely impact costs of health care, intensity of symptoms, quality of life and, most importantly, may contribute to life span shortening. Some comorbidities are well acknowledged and established in doctors' awareness. However, both everyday practice and literature searches provide evidence of other, less recognized diseases, which are frequently associated with COPD. We call them underrecognized comorbidities, and the reason why this is so may be related to their relatively low clinical significance, inefficient literature data, or data ambiguity. In this review, we describe rhinosinusitis, skin abnormalities, eye diseases, different endocrinological disorders, and gastroesophageal reflux disease. Possible links to COPD pathogenesis have been discussed, if the data were available.