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Rogelio Perez-Padilla,1 Maria Montes de Oca,2 Ireri Thirion-Romero,1 Fernando C Wehrmeister,3 Maria Victorina Lopez,4 Gonzalo Valdivia,5 Jose R Jardim,6 Adriana Muino,4 Ana Maria B Menezes3 On behalf of the PLATINO Group1National Institute of Respiratory Diseases, Mexico City, Mexico; 2Pulmonary Division, Hospital Universitario de Caracas, Universidad Central de Venezuela, and Centro Medico de Caracas, Caracas, Venezuela; 3Post-Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil; 4Universidad de la Republica. Hospital Maciel, Montevideo, Uruguay; 5Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; 6Paulista School of Medicine, Federal University of São Paulo, São Paulo, BrazilCorrespondence: Rogelio Perez-Padilla, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, Col. Sección XVI, 14080, CDMX, Mexico City, Mexico, Email perezpad@gmail.comBackground: Preserved ratio impaired spirometry (PRISm) has been associated with adverse outcomes and increased transition to other spirometric categories over time. We aimed to examine its prevalence, trajectories over time, and outcomes in a population-based sample from Latin America.Methods: Data were obtained from two population-based surveys of adults from three cities in Latin America (PLATINO study), conducted on the same individuals 5– 9 years after their baseline examination. We estimated the frequency of PRISm defined by FEV1/FVC≥ 0.70 with FEV1 < 80%, describing their clinical characteristics, longitudinal transition trajectories over time, factors associated with the transition.Results: At baseline, 2942 participants completed post-bronchodilator spirometry, and 2026 at both evaluations. The prevalence of normal spirometry was 78%, GOLD-stage 1 10.6%, GOLD 2– 4 6.5%, and PRISm was: 5.0% (95% CI 4.2– 5.8). PRISm was associated with less schooling, more reports of physician-diagnosis of COPD, wheezing, dyspnea, missing days at work, having ≥ 2 exacerbations in the previous year but without accelerated lung function decline. Mortality risk was significantly higher in PRISm (HR 1.97, 95% CI 1.2– 3.3) and COPD GOLD 1– 4 categories (HR 1.79, 95% CI 1.3– 2.4) compared with normal spirometry. PRISm at baseline most frequently transitioned to another category at follow-up (46.5%); 26.7% to normal spirometry and 19.8% to COPD. The best predictors of transition to COPD were closeness of FEV1/FVC to 0.70, older age, current smoking, and a longer FET in the second assessment.Conclusion: PRISm, is a heterogeneous and unstable condition prone to adverse outcomes that require adequate follow-up.Keywords: preserved ratio impaired spirometry PRISm, airflow obstruction, COPD, lung function decline

The small airway, present since the origins of humanity and described barely a century ago, has recently been discovered as the anatomical site where inflammation begins in some obstructive lung diseases, such as asthma and Chronic Obstructive Pulmonary Disease (COPD), per se. Small airway dysfuction was identified in up to 91% of asthmatic patients and in a large proportion of COPD patients. In subjects without pathology, small airway represent 98.8% (approximately 4500 ml) of the total lung volume, contributing only between 10-25% of the total lung resistance; however, in subjects with obstruction, it can represent up to 90% of the total resistance. Despite this, its morphological and functional characteristics allow its dysfunction to remain undetected by conventional diagnostic methods, such as spirometry. Hence the importance of this review, which offers an overview of the tools available to assess small airway dysfunction and the possible therapies that act in this silent zone., Competing Interests: Los autores declaran no tener ningún conflicto de intereses al publicar el presente artículo. Todos los autores tienen colaboración similar en la autoría de esta investigación.

The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations in severe COVID-19 cases. Until now, the importance of developing a neutralizing antibody response in the acute phase and its relationship with progression to severe disease or fatal outcome among hospitalized patients remains unclear. In this study, we aim to characterize and compare longitudinally the primary humoral immune host response in the early stages of the disease, looking for an association between neutralization, antibody titers, infective viral lineage, and the clinical outcome in hospitalized and non-hospitalized patients. A total of 111 patients admitted at INER from November 2021 to June 2022 were included. We found that patients with negative or low neutralization showed a significant reduction in survival probability compared to patients with medium or high neutralization. We observed a significant decrease in the median of neutralization in patients infected with viral variants with changes in RBD of the spike protein. Our results suggest that developing an early and robust neutralizing response against SARS-CoV-2 may increase survival probability in critical patients.

The reduction of air pollution during the #COVID19 lockdown in Mexico City possibly reduced the exacerbation rate in #COPD patients due to biomass and tobacco despite that the self-isolation was not as strict as expected. https://bit.ly/3Iyv98t., Competing Interests: Conflict of interest: F. Montiel-Lopez has nothing to disclose. Conflict of interest: D. Rodríguez-Ramírez has nothing to disclose. Conflict of interest: M. Cassou-Martínez has nothing to disclose. Conflict of interest: M.C. Miranda-Márquez has nothing to disclose. Conflict of interest: C. González-González has nothing to disclose. Conflict of interest: R.H. Sansores has nothing to disclose. Conflict of interest: M.E. Mayar-Maya has nothing to disclose. Conflict of interest: R. Pérez-Padilla has nothing to disclose. Conflict of interest: R.E. Robles-Hernández has nothing to disclose. Conflict of interest: I. Thirion-Romero has nothing to disclose. Conflict of interest: O. Pérez-Bautista has nothing to disclose. Conflict of interest: A. Ramírez-Venegas has nothing to disclose., (Copyright ©The authors 2022.)

Introduction: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors have declared that no competing interests exist.

Background: Point-of-care rapid tests to identify SARS-CoV-2 can have clinical benefits., Methods: A cross-sectional study in adults visiting emergency services or screening sites of referral hospitals for COVID-19 to validate the diagnostic performance of a rapid antigen test for SARS-CoV-2 (Abbott's Panbio) compared with reverse transcription-polymerase chain reaction (RT-PCR) testing. Tests were performed by health personnel in a routine situation during a COVID-19 outbreak., Results: A total of 1060 participants (mean age 47, 46% with a self-reported comorbidity) were recruited from 8 hospitals in Mexico. Participants provided 1060 valid Panbio rapid test-RT-PCR test pairs with 45% testing positive in the RT-PCR. Overall sensitivity of the Panbio test was 54.2% (95% CI 51%-57%), and 69.1% (95% CI 66%-73%) for patients during the first week of symptoms. Sensitivity depended on viral load (cycle threshold (Ct) of RT-PCR) and days of symptoms. With a Ct ≤25, sensitivity was 82% (95% CI, 76%-87%). Specificity of the Panbio test was >97.8% in all groups., Conclusions: The Panbio rapid antigen test for SARS-CoV-2 had good specificity but low sensitivity. A negative test requires confirmation with RT-PCR, especially for testing after the first week of symptoms., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The novel coronavirus pandemic (COVID-19) represents a major public health problem and it is key to find a treatment that reduces mortality. Our objective was to estimate whether treatment with 400 mg/day of Hydroxychloroquine for 10 days reduces in-hospital mortality in subjects with severe respiratory disease due to COVID-19 compared with placebo., Material and Methods: A double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of Hydroxychloroquine for the treatment of severe disease by COVID-19 through an intention-to-treat analysis. Eligible for the study were adults aged more than 18 years with COVID-19 confirmed by RT-PCR and lung injury requiring hospitalization with or without mechanical ventilation. Primary outcome was 30-day mortality. Secondary outcomes: days of mechanical ventilation, days of hospitalization and cumulative incidence of serious adverse events., Results: A total of 214 patients with COVID-19 were recruited, randomized and analyzed. They were hypoxemic with a mean SpO2 of 65% ± 20, tachycardic (pulse rate 108±17 min-1) and tachypneic (32 ±10 min-1); 162 were under mechanical ventilation at randomization. Thirty-day mortality was similar in both groups (38% in Hydroxychloroquine vs. 41% in placebo, hazard ratio [HR] 0.88, 95% Confidence Interval [95%CI] 0.51-1.53). In the surviving participants, no significant difference was found in secondary outcomes., Conclusion: No beneficial effect or significant harm could be demonstrated in our randomized controlled trial including 214 patients, using relatively low doses of Hydroxychloroquine compared with placebo in hospitalized patients with severe COVID-19., Competing Interests: CONACYT (National Council of Science and Technology of Mexico) and SANOFI participated. SANOFI provided the tested drug and identical placebo. Commercial funding does not alter our adherence to PLOS ONE editorial policies.

Supplemental oxygen (SO) increases survival in hypoxemic patients. In hypoxia, mammals respond by modulating O 2 -sensitive transducers that stabilize the transcription factor hypoxia-inducible factor-1-alpha (HIF-1α), which transactivates the genes that govern angiogenesis and metabolic pathways. Residing at high altitudes exposes millions of people to hypoxemia with potential adverse consequences on their health. We aimed to identify markers of hypoxemia that can be used in the evaluation of patients in addition to pulse oximetry and arterial blood gases, especially those that could respond after 1 month of oxygen use. We performed a prospective pilot study at 2240 m above sea level, with repeated measurements before and after (b/a) 1-month home oxygen therapy in 70 patients with lung diseases, of which 24/20 have COPD, 41/39 obstructive sleep apnea (OSA), and 5/2 with interstitial lung diseases (ILD), all of them having chronic hypoxemia, as well as 70 healthy subjects as controls. Proteins evaluated included HIF-1α, vascular endothelial growth factor (VEGF), and erythropoietin (EPO). Among the main results, we found that hypoxemic patients had normal levels of HIF-1α but increased EPO compared with healthy controls. VEGF levels were heterogeneous in the sample studied, similar to the control group in COPD, slightly increased in OSA, and decreased in fibrosis. With oxygen treatment, the HIF-1α and EPO decreased in COPD and OSA but not in fibrosis, and VEGF remained constant over time. In conclusion, erythropoietin and HIF-1α identified hypoxemia initially and responded to oxygen. In pulmonary fibrosis, HIF-1α, EPO, and VEGF increased with oxygen therapy, which is likely linked to the disease's pathogenesis and clinical course rather than hypoxemia.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Background: A 6 s spirometry with an inexpensive pocket spirometer efficiently selects individuals for a diagnostic-quality spirometry for airflow limitation, but could also be useful to identify individuals with a restrictive pattern., Objectives: We evaluated an inexpensive simplified spirometer (chronic obstructive pulmonary disease [COPD]-6) as a screening tool to identify spirometric abnormalities., Methods: A population-based survey in Mexico City, with 742 participants performing pre- and post-BD spirometry and a three-maneuver 6 s spirometry (pre-BD) with a COPD-6. We evaluated forced expiratory volume in 1 s (FEV1), FEV6, and FEV1/FEV6 from the COPD-6, crude and expressed as the percentage of predicted (%P), to discriminate post-bronchodilator airflow obstruction (FEV1/forced vital capacity [FVC] < 5th percentile) or restriction (FVC or FEV1 <5th percentile with normal FEV1/FVC) through receiver operating characteristics and their area under the curve (AUC)., Results: FEV1%P was the best predictor to identify pre- and post-BD ventilatory abnormalities (best cutoff point 87%P, AUC 92% for restrictive pattern, 89% for obstructive pattern, and 91% for any spirometric abnormality). Deriving to clinical spirometry only those with < 87%P (26% of the sample) missed only 12% of spirometric abnormalities most of the latter mild., Conclusions: An FEV1 < 87%P from a pre-BD 6 s spirometry correctly identified individuals with spirometric ventilatory defects, either obstructive or restrictive.