The COVID-19 outbreak has caused over three million deaths worldwide. Understanding the pathology of the disease and the factors that drive severe and fatal clinical outcomes is of special relevance. ...Studying the role of the respiratory microbiota in COVID-19 is especially important as the respiratory microbiota is known to interact with the host immune system, contributing to clinical outcomes in chronic and acute respiratory diseases. Here, we characterized the microbiota in the respiratory tract of patients with mild, severe, or fatal COVID-19, and compared it to healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure between the study groups and correlated the results with clinical data. We found differences in the microbial composition for COVID-19 patients, healthy controls, and non-COVID-19 pneumonia controls. In particular, we detected a high number of potentially opportunistic pathogens associated with severe and fatal levels of the disease. Also, we found higher levels of dysbiosis in the respiratory microbiota of patients with COVID-19 compared to the healthy controls. In addition, we detected differences in diversity structure between the microbiota of patients with mild, severe, and fatal COVID-19, as well as the presence of specific bacteria that correlated with clinical variables associated with increased risk of mortality. In summary, our results demonstrate that increased dysbiosis of the respiratory tract microbiota in patients with COVID-19 along with a continuous loss of microbial complexity structure found in mild to fatal COVID-19 cases may potentially alter clinical outcomes in patients. Taken together, our findings identify the respiratory microbiota as a factor potentially associated with the severity of COVID-19.
Several COPD phenotypes have been described; the COPD-asthma overlap is one of the most recognized. The aim of this study was to evaluate the prevalence of three subgroups (asthma, COPD, and ...COPD-asthma overlap) in the Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) study population, to describe their main characteristics, and to determine the association of the COPD-asthma overlap group with exacerbations, hospitalizations, limitations due to physical health, and perception of general health status (GHS).
The PLATINO study is a multicenter population-based survey carried out in five Latin American cities. Outcomes were self-reported exacerbations (defined by deterioration of breathing symptoms that affected usual daily activities or caused missed work), hospitalizations due to exacerbations, physical health limitations, and patients' perception of their GHS obtained by questionnaire. Subjects were classified in three specific groups: COPD--a postbronchodilator (post-BD) FEV₁/FVC ratio of < 0.70; asthma--presence of wheezing in the last year and a minimum post-BD increase in FEV₁ or FVC of 12% and 200 mL; and overlap COPD-asthma--the combination of the two.
Out of 5,044 subjects, 767 were classified as having COPD (12%), asthma (1.7%), and COPD-asthma overlap (1.8%). Subjects with COPD-asthma overlap had more respiratory symptoms, had worse lung function, used more respiratory medication, had more hospitalization and exacerbations, and had worse GHS. After adjusting for confounders, the COPD-asthma overlap was associated with higher risks for exacerbations (prevalence ratio PR, 2.11; 95% CI, 1.08-4.12), hospitalizations (PR, 4.11; 95% CI, 1.45-11.67), and worse GHS (PR, 1.47; 95% CI, 1.18-1.85) compared with those with COPD.
The coexisting COPD-asthma phenotype is possibly associated with increased disease severity.
Health care workers are at high risk of being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our aim is to evaluate the efficacy and safety of hydroxychloroquine ...(HCQ) for prophylaxis of coronavirus disease 19 (COVID-19) in health personnel exposed to patients infected by SARS-CoV-2.
Double-blind randomized, placebo-controlled single center clinical trial. Included subjects were health care workers caring for severe COVID-19 patients. Main outcome was time to symptomatic SARS-CoV-2 infection.
127 subjects with a confirmed baseline negative RT-PCR SARS-CoV2 test were included in the trial. 62 assigned to HCQ and 65 to placebo. One subject (1.6%) in the HCQ group and 6 (9.2%) subjects in the placebo group developed COVID-19 (Log-Rank test p = 0.07). No severe COVID-19 cases were observed. The study was suspended because of a refusal to participate and losses to follow up after several trials reported lack of effectiveness of hydroxychloroquine in hospitalized patients with COVID-19.
The effect size of hydroxychloroquine was higher than placebo for COVID-19 symptomatic infection in health personnel, although this was not statistically significant. The trial is underpowered due to the failure to complete the estimated sample size.
•Different breath-prints of COPD, Breast Cancer, Lung Cancer and Healthy subjects.•Chemoresistive sensors provide a specific breath fingerprint of NCDs and controls.•PCA and CDA showed a separation ...between COPD, BC, LC patients and healthy subjects.•91.35% correct classification and 100% correct prediction in the single-blind study.
Analysis of volatile organic compounds (VOCs) in exhaled breath has been proposed as a screening method that discriminates between disease and healthy subjects, few studies evaluate whether these chemical fingerprints are specific when compared between diseases. We evaluated global VOCs and their discrimination capacity in chronic obstructive pulmonary disease (COPD), lung cancer, breast cancer and healthy subjects by chemoresistive sensors and chemometric analysis.
A cross-sectional study was conducted with the participation of 30 patients with lung cancer, 50 with breast cancer, 50 with COPD and 50 control subjects. Each participant's exhaled breath was analyzed with the electronic nose. A multivariate analysis was carried: principal component analysis (PCA) and, canonical analysis of principal coordinates (CAP). Twenty single-blind samples from the 4 study groups were evaluated by CAP.
A separation between the groups of patients to the controls was achieved through PCA with explanations of >90% of the data and with a correct classification of 100%. In the CAP of the 4 study groups, discrimination between the diseases was obtained with 2 canonical axes with a correct general classification of 91.35%. This model was used for the prediction of the single-blind samples resulting in correct classification of 100%.
The application of chemoresistive gas sensors and chemometric analysis can be used as a useful tool for a screening test for lung cancer, breast cancer and COPD since this equipment detects the set of VOCs present in the exhaled breath to generate a characteristic chemical fingerprint of each disease.
High HHV-8 viral load (VL) in Kaposi Sarcoma (KS) has been associated with Severe Immune Reconstitution Inflammatory Syndrome (Severe-IRIS-KS), which can occur after initiating cART, and leads to ...high mortality, particularly in patients with pulmonary involvement. We investigate if valganciclovir (as an anti-HHV-8 agent) initiated before cART reduces the mortality associated with Severe-IRIS-KS and the incidence of Severe-IRIS-KS.
Open-label parallel-group randomized clinical trial in AIDS cART naïve patients with disseminated KS (DKS) as defined by at least two of the following: pulmonary, lymph-node, or gastrointestinal involvement, lymphedema, or ≥30 skin lesions. In the experimental group (EG), patients received valganciclovir 900 mg BID four weeks before cART and continued until week 48; in the control group (CG), cART was initiated on week 0. Non-severe-IRIS-KS was defined as: an increase in the number of lesions plus a decrease of ≥one log10 HIV-VL, or an increase of ≥50cells/mm3 or ≥2-fold in baseline CD4+cells. Severe-IRIS-KS was defined as abrupt clinical worsening of KS lesions and/or fever after ruling out another infection following cART initiation, and at least three of the following: thrombocytopenia, anemia, hyponatremia, or hypoalbuminemia.
40 patients were randomized and 37 completed the study. In the ITT analysis, at 48 weeks, total mortality was the same in both groups (3/20), severe-IRIS-KS attributable mortality was 0/20 in the EG, compared with 3/20 in the CG (p = 0.09), similar to the per-protocol analysis: 0/18 in the EG, and 3/19 in the control group (p = 0.09). The crude incidence rate of severe-IRIS-KS was four patients developed a total of 12 episodes of Severe-IRIS-KS in the CG and two patients developed one episode each in the EG. Mortality in patients with pulmonary KS was nil in the EG (0/5) compared with 3/4 in the CG (P = 0.048). No difference was found between groups in the number of non-S-IRIS-KS events. Among survivors at week 48, 82% achieved >80% remission.
Although mortality attributable to KS was lower in the EG the difference was not statistically significant.
Chronic exposure to indoor biomass smoke from the combustion of solid organic fuels is a major cause of disease burden worldwide. Almost 3 billion people use solid fuels such as wood, charcoal, and ...crop residues for indoor cooking and heating, accounting for approximately 50% of all households and 90% of rural households globally. Biomass smoke contains many hazardous pollutants, resulting in household air pollution (HAP) exposure that often exceeds international standards. Long-term biomass-smoke exposure is associated with Chronic Obstructive Pulmonary Disease (COPD) in adults, a leading cause of morbidity and mortality worldwide, chronic bronchitis, and other lung conditions. Biomass smoke-associated COPD differs from the best-known cigarette smoke-induced COPD in several aspects, such as a slower decline in lung function, greater airway involvement, and less emphysema, which suggests a different phenotype and pathophysiology. Despite the high burden of biomass-associated COPD, the molecular, genetic, and epigenetic mechanisms underlying its pathogenesis are poorly understood. This review describes the pathogenic mechanisms potentially involved in lung damage, the development of COPD associated with wood-derived smoke exposure, and the influence of genetic and epigenetic factors on the development of this disease.
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