ABSTRACT
Male and female patients are usually considered clinically equivalent from a diagnostic and treatment point of view, and no relevance is given to the differences in morphometry and physiology of the respiratory system between the two sexes. This is a major limitation in the understanding of the pathology and effective management of multiple respiratory ailments. The present review analyses the available literature on the major respiratory diseases from a gender-difference perspective. We performed our research using the PubMed Advanced Browser. The research for each clinical condition was conducted by using the key words "gender" OR "sex." For example, considering asthma, the search criteria were "asthma" AND "gender" OR "sex." All the respiratory diseases considered in this review are deeply influenced by the sex of the patient in diverse ways. For example, in women, estrogens could play a protective role in some conditions, like IPF, while in others they are associated with increased risk of disease development, as in some types of severe asthma. Psychological symptoms are more frequent in women with obstructive conditions such as OSAS, COPD, and asthma. Despite the available evidence, current therapeutic strategies largely ignore these differences, and data on gender-weighted interventions are still scarce. Sex differences are common in respiratory diseases. They have largely been ignored in clinical approaches towards these diseases. Evidence has been generated in the last few decades in favor of gender-based diagnostic and therapeutic strategies.
ABSTRACT
Pathophysiology of the coronavirus 2 (SARS-CoV-2) infection is still largely unknown. Data suggest that platelets may have the potential to contribute to the thrombo-inflammation in COVID-19. The ?Pro-thrombotic status in patients with SARS-Cov-2 infection? (ATTAC-Co) study is a prospective, single-center study recruiting patients admitted to hospital because of respiratory failure due to COVID-19. Fifty-four patients with respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were enrolled as cases. Eleven patients with the same clinical presentation, but negative for SARS-CoV-2 infection, were included as controls. Blood samples were collected at three different time points (inclusion [T1], after 7 days [T2] and 14 days [T3]). Platelet aggregation by light transmittance aggregometry and the circulating levels of soluble CD40 ligand (sCD40L) and P-selectin were measured. The study investigated the relationship between platelet activation, myocardial injury, and mortality in patients affected by COVID-19. The baseline clinical features were similar between cases and controls. Platelet biomarkers did not differ between cases and controls, except for sCD40L which was higher in COVID-19 patients (p = .003). PA values were stable overtime during hospitalization;on the contrary, P-selectin and sCD40L values significantly reduced (p = .044 and p = .039, respectively). The PA values did not differ between ICU vs non-ICU patients. On the contrary, P-selectin and sCD40L values were higher in ICU vs. non-ICU patients (p=.004 e p=.008 respectively). Myocardial injury was observed in 20 patients (37%). Of these, the 46% were ICU patients. The PA values, P-selectin and sCD40L, were higher in patients with myocardial injury. 16 patients (30%) died. The PA, P-selectin and sCD40L values were higher and with a different trend over time in patients who died. Mortality was significantly higher in patients with myocardial injury vs. others (60% vs 11.7%, p < .001). Myocardial injury emerged as an independent predictor of mortality (HR 6.28, 95%CI 1.65-23.92, p = .007). In COVID-19 patients admitted to hospital for respiratory failure, heightened platelet activation is associated with severity of illness, myocardial injury, and mortality.
ABSTRACT
Background: The vascular endothelium represents a barrier between blood and vascular tissues and plays a pivotal role in maintaining vascular homeostasis by modulating vascular tone, inflammatory response, permeability and haemostasis. Normally, the endothelium plays an antithrombotic role and is resistant to leukocytes binding;during COVID-19 infection the endothelium is activated and expresses prothrombotic and leukocyte recruitment mediators. The SARS-COV2 virus might be able to infect endothelial cells, causing direct damage and amplifying the cytokine storm. Although previous studies have found that endothelial dysfunction is associated to the severity and mortality of COVID-19, it is not known how endothelial dysfunction biomarkers change over time. We have investigated molecular features and the temporal progression of markers of endothelial dysfunction during COVID-19 and determined the relationship with the exitus. Methods: Plasma levels of a panel of endothelial dysfunction biomarkers such as endothelin-1, endoglin, sE-selectin, thrombomodulin, sVCAM-1 and von Willebr and (vWF) factor were quantified in 54 COVID-19 patients at three different time points (at inclusion [T1], after 7±2 days [T2] and 14±2 days [T3]) and compared with those of 11 patients with the same clinical presentation but negative for SARS-CoV-2 at T1. Results: Endoglin, thrombomodulin, and sVCAM-1 at baseline are associated with death in COVID-19 patients. Thrombomodulin, sVCAM-1 and vWF levels raised over time in the COVID-19 patients who did not survive but remained at similar levels in survivors (Fig.1), while endothelin-1 levels increased over time in survivors but not in nonsurvivors. On multivariate analysis sVCAM-1 was independently associated with death (HR: 2.80;95% CI 1.35-5.78;p=0.0056). Patients with high sVCAM-1 on admission (> 1088 ng/mL) had higher mortality rates than those with low sVCAM-1 (< 1088 ng/mL) (log rank p=0.0049). Conclusion: Plasma levels and time course of some biomarkers of endothelial dysfunction are specific of COVID-19 pneumonia and are strongly related to mortality.
ABSTRACT
BACKGROUND: How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro. METHODS: We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively. RESULTS: ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR. CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.