Publications by authors named "Rogelio Pérez-Padilla"

173 Publications

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Nat Commun 2021 04 15;12(1):2349. Epub 2021 Apr 15.

Infectious and Tropical Diseases Department, Angers University Hospital, Angers, France.

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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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 We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed,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 We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients).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.
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http://dx.doi.org/10.1038/s41467-021-22446-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050319PMC
April 2021

Application of chemoresistive gas sensors and chemometric analysis to differentiate the fingerprints of global volatile organic compounds from diseases. Preliminary results of COPD, lung cancer and breast cancer.

Clin Chim Acta 2021 Mar 22;518:83-92. Epub 2021 Mar 22.

CONACYT Research Fellow, Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí. Avenida Sierra Leona No. 550, CP 78210, Colonia Lomas Segunda Sección, San Luis Potosí, SLP, Mexico. Electronic address:

Background: 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.

Methods: 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.

Results: 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%.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.cca.2021.03.016DOI Listing
March 2021

Screening Tool for Restrictive and Obstructive Ventilatory Abnormalities in a Population-Based Survey.

Rev Invest Clin 2020 12 22;72(6):386-393. Epub 2020 Dec 22.

epartment of Investigation on Tobacco and Chronic Obstructive Pulmonary Disease, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.

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.
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http://dx.doi.org/10.24875/RIC.20000235DOI Listing
December 2020

Arterial blood gases and ventilation at rest by age and sex in an adult Andean population resident at high altitude.

Eur J Appl Physiol 2020 Dec 16;120(12):2729-2736. Epub 2020 Sep 16.

Fundación Neumologica Colombiana, CR 13B 161-85, Bogota, Colombia.

Purpose: Arterial blood gases (ABG) are influenced by the altitude above sea level, age and sex. Most studies have been conducted at sea level and in small populations ascending to or residents at very high altitudes. Our objective was to evaluate the ventilation and ABG by age and sex in an Andean population resident at high altitude (2640 m).

Methods: Analytical cross-sectional study was done in healthy volunteers. ABG and minute ventilation (VE) were measured. T test and ANOVA for differences by sex and age, and Pearson test for correlations between age, VE and ABG were performed.

Results: We included 374 adults, 55% women from 18 to 83 years and hemoglobin of 15.7 ± 1.6 g/dl. There was a significant decrease in PaO and SaO and an increase in P(A - a)O with age (p < 0.001). Unlike men, with age women had a significant increase in PaCO and a higher decrease in PaO. The correlations between age, the decrease in PaO and the increase in PaCO were greater in women than in men. The VE adjusted to body surface area decreased with age, but this correlation was significantly higher in women.

Conclusions: In this study, with a considerable number of healthy adults living at high altitude (2640 m), we established the physiological impact of altitude, aging and gender in ABG. The PaO and PaCO were significantly lower and the hemoglobin values slightly higher than described at sea level. In addition to PaO decline with age, there was an age-related increase in PaCO in women, associated with a greater reduction of VE.
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http://dx.doi.org/10.1007/s00421-020-04498-zDOI Listing
December 2020

Characterisation of pulmonary function trajectories: results from a Brazilian cohort.

ERJ Open Res 2020 Jul 25;6(3). Epub 2020 Aug 25.

Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.

Background: Pulmonary function (PF) trajectories are determined by different exposures throughout the life course. The aim of this study was to investigate characteristics related to PF trajectories from 15 to 22 years in a Brazilian cohort.

Methods: A birth cohort study (1993 Pelotas Birth Cohort) was conducted with spirometry at 15, 18 and 22 years. PF trajectories were built based on z-score of forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and their ratio using a group-based trajectory model. Associations with exposures reported from perinatal to 22 years were described.

Results: Three trajectories, low (LT), average (AT) and high (HT) were identified in 2917 individuals. Wealthiest individuals belonged to the HT of FEV (p=0.023). Lower maternal pregestational body mass index (BMI) (22.4±0.2; p<0.001 and 22.1±0.14; p<0.001) and lower birth weight (3164.8±25.4; p=0.029 and 3132.3±19.4; p=0.005) were related to the LT of FEV and FVC. Mother's smoking exposure during pregnancy (37.7%; p=0.002), active smoking at ages 18 and 22 years (20.1% and 25.8%; p<0.001) and family history of asthma (44.8%; p<0.001) were related to the LT of FEV/FVC. Wheezing, asthma and hospitalisations due to respiratory diseases in childhood were related to the LT of both FEV and FEV/FVC. Higher BMIs were related to the HT of FEV and FVC at all ages.

Conclusions: PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.
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http://dx.doi.org/10.1183/23120541.00065-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445117PMC
July 2020

Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico.

J Virol 2020 08 31;94(18). Epub 2020 Aug 31.

Instituto de Diagnóstico y Referencia Epidemiológicos, Dirección General de Epidemiología, Mexico City, Mexico

The coronavirus disease 2019 (COVID-19) pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to enabling implementation of effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage A/G, containing mostly sequences from North America, and lineage B/S, containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized 14 independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represented local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified an H49Y amino acid change in the Spike protein. This mutation represents a homoplasy occurring independently through time and space and may function as a molecular marker to follow any further spread of these viral variants throughout the country. Our results provide a general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts. Understanding the introduction, spread, and establishment of SARS-CoV-2 within distinct human populations as well as the evolution of the pandemics is crucial to implement effective control strategies. In this work, we report that the initial virus strains introduced in Mexico came from Europe and the United States and that the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains with a H49Y mutation in the Spike protein, which could be further used as a molecular marker to follow viral spread within the country and the region.
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http://dx.doi.org/10.1128/JVI.01056-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459550PMC
August 2020

Smoke exposure from chronic biomass burning induces distinct accumulative systemic inflammatory cytokine alterations compared to tobacco smoking in healthy women.

Cytokine 2020 07 10;131:155089. Epub 2020 Apr 10.

Research Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Colonia Sección XVI, 14080 Mexico City, Mexico. Electronic address:

Long-term exposure to biomass-burning smoke (BS) is associated with chronic obstructive pulmonary disease (COPD), asthma, and other chronic inflammatory lung diseases. BS results from such processes as the burning of wood for indoor cooking and heating, with women and children having the highest exposure rate. This study aimed to analyze the accumulative alterations in cytokine levels associated with BS (from wood) compared to tobacco smoke (TS) in healthy adult women. The levels of 27 cytokines were analyzed in the serum of 100 women, including 40 tobacco smokers/non-exposed to BS (TS+/BS-), 30 never-smokers/exposed to BS (TS-/BS+) and 30 never-smokers/non-exposed to BS (TS-/BS-) as controls, using 27-Plex immunoassay. The chronic BS exposure index was rated at ≥100 h-years, and the tobacco-smoking index was ≥10 pack-years. Compared to TS-/BS-, TS+/BS- had higher levels of IL-2, IL-9, MCP-1, MIP-1β, and VEGF, while TS-/BS+ showed higher levels of IL-1ra, IL-6, IL-8, Eotaxin, IP-10, RANTES, and VEGF, presenting a distinct inflammatory profile that may favor an eosinophil-derived inflammatory response to BS exposure. Compared to TS+/BS-, TS-/BS+ expressed higher levels of IP-10 and IL-8, but lower levels of IL-2 and MIP-1β. Gene-disease database analysis showed that altered cytokines in both TS+/BS- and TS-/BS+ are associated with asthma, COPD, lung fibrosis, and lung cancer. In conclusion, chronic BS exposure induces distinct systemic inflammatory cytokine alterations compared to tobacco smokers in healthy women. These findings provide new insights into how long-term exposure to BS affects the inflammatory response-and potentially the health-of adult women.
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http://dx.doi.org/10.1016/j.cyto.2020.155089DOI Listing
July 2020

Comparing Spirometric Reference Values From Childhood to Old Age Estimated by LMS and Linear Regression Models.

Arch Bronconeumol 2021 03 1;57(3):172-178. Epub 2020 Mar 1.

Department of Research in Smoking and COPD, National Institute of Respiratory Diseases "Ismael Cosío Villegas", Mexico City, Mexico. Electronic address:

Background: Proper reference values for lung function testing are essential for achieving adequate interpretations. The LMS procedure (lambda, mu, sigma) permits continuous analyses of entire populations avoiding gaps in the transition between childhood and adulthood. It also allows more precise calculations of average values, dispersion, and 5th percentiles, which are usually considered the lower limit of normality. The objective of this study was to compare our results fitted with the LMS method with standard multiple linear regression, and with those from international Global Lung Function Initiative (GLI) equations.

Methods: Data from 9835 healthy residents of the metropolitan area of Mexico City aged 8-80 years were compiled from several studies: EMPECE, PLATINO, adult Mexican workers and two unpublished studies. The LMS procedure and multiple linear regression models were fit to obtain reference equations using R software.

Results: Residuals from the LMS models had a median closer to zero, and smaller dispersion than those from the linear model, but differences although statistically significant were very small and of questionable practical relevance. For example, for females and ln(FEV), median residual was -0.001 with p25 of -0.08 and p75 of 0.08 for LMS, compared with 0.004 (-0.08, 0.09) [p<0.05] for the linear model. Average spirometric values for a given height for our population, were higher than those predicted by the GLI study.

Conclusion: Continuous reference equations for the Mexican population calculated using the LMS technique showed slightly better fit than linear regression models.
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http://dx.doi.org/10.1016/j.arbres.2019.12.033DOI Listing
March 2021

Identification of breath-prints for the COPD detection associated with smoking and household air pollution by electronic nose.

Respir Med 2020 03 12;163:105901. Epub 2020 Feb 12.

Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, Avenida Sierra Leona No. 550, CP 78210, Colonia Lomas Segunda Sección, San Luis Potosí, SLP, Mexico. Electronic address:

Purpose: The analysis of breath-print, has been proposed as an attractive alternative to investigate possible biomarkers of Chronic Obstructive Pulmonary Disease (COPD). The aim of the present study was to discriminate between healthy subjects, patients with COPD associated with smoking (COPD-S) and patients with COPD associated with household air pollution (COPD-HAP).

Methods: A cross-sectional study of 294 participants was conducted, 88 with smoking associated COPD, 28 associated with HAP and 178 healthy subjects. Breath-print analysis was performed by using the Cyranose 320 electronic nose. Group data were evaluated by Principal Component Analysis (PCA), Canonical Discriminant Analysis (CDA) and Support Vector Machine (SVM) and the test's diagnostic power by means of ROC (Receiver Operating Characteristic) curves.

Results: The results indicated that the breath-print of patients with COPD is different from the one of healthy subjects explaining a variability of 93.8% with a correct prediction of 97.8% and correct classification of 100%,also positive and negative predictive value of 96.5 and 100% respectively. Furthermore, the breath-print of exhaled breath from patients with COPD-S and COPD-HAP does not present any difference.

Conclusions: The breath-print of exhaled breath from patients with COPD-S and COPD-HAP does not present any difference, which demonstrates that the breath-print is related to the disease and not to causality. With these results, the analysis of the breath-print of COPD is proposed as an alternative for a screening method in future clinical applications.
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http://dx.doi.org/10.1016/j.rmed.2020.105901DOI Listing
March 2020

Number needed to treat: a useful statistic to evaluate the impact of an intervention.

J Bras Pneumol 2019 Dec 9;45(6):e20190371. Epub 2019 Dec 9.

. Methods in Epidemiologic, Clinical, and Operations Research-MECOR-program, American Thoracic Society/Asociación Latinoamericana del Tórax, Montevideo, Uruguay.

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http://dx.doi.org/10.1590/1806-3713/e20190371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447548PMC
December 2019

Participation of the miR-22-HDAC4-DLCO Axis in Patients with COPD by Tobacco and Biomass.

Biomolecules 2019 12 6;9(12). Epub 2019 Dec 6.

Cellular Biology Laboratory, Department of Research in Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and systemic inflammation. The main causes of COPD include interaction between genetic and environmental factors associated with tobacco smoking (COPD-TS) and/or exposure to biomass smoke (COPD-BS). Several microRNAs (miRNAs) control posttranscriptional regulation of COPD-TS associated gene expression. The miR-22-HDAC4-IL-17 axis was recently characterized. It is still unknown, however, whether this axis, participates in COPD-BS. To investigate, 50 patients diagnosed with severe-to-very severe COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages III/IV, were recruited, 25 women had COPD-BS (never smokers, exposed heavily to BS) and 25 had COPD-TS. Serum levels of miRNA-22-3p were measured by RT (Reverse Transcription)-qPCR, while the concentration of HDAC4 (Histone deacetylase 4) was detected by ELISA. Additionally, we looked for association between serum HDAC4 and DLCOsb (Single-breath diffusing capacity of the lung for carbon monoxide), as % of predicted by age, height, and gender, one of the main differences described between COPD-BS and COPD-TS. Women with COPD-BS were older and shorter and had a higher DLCOsb %P (percent predicted) compared to COPD-TS. Serum miR-22-3p was downregulated in COPD-BS relative to COPD-TS. In contrast, the concentration of HDAC4 was higher in COPD-BS compared to COPD-TS. Furthermore, a positive correlation between serum HDAC4 levels and DLCOsb %P was observed. We concluded that the miR-22-HDAC4-DLCO axis behaves differently in patients with COPD-BS and COPD-TS.
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http://dx.doi.org/10.3390/biom9120837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995507PMC
December 2019

Health Benefits of Air Pollution Reduction.

Ann Am Thorac Soc 2019 12;16(12):1478-1487

School of Earth, Society, and Environment, Department of Atmospheric Sciences, University of Illinois, Urbana, Illinois.

Air pollution is a grave risk to human health that affects nearly everyone in the world and nearly every organ in the body. Fortunately, it is largely a preventable risk. Reducing pollution at its source can have a rapid and substantial impact on health. Within a few weeks, respiratory and irritation symptoms, such as shortness of breath, cough, phlegm, and sore throat, disappear; school absenteeism, clinic visits, hospitalizations, premature births, cardiovascular illness and death, and all-cause mortality decrease significantly. The interventions are cost-effective. Reducing factors causing air pollution and climate change have strong cobenefits. Although regions with high air pollution have the greatest potential for health benefits, health improvements continue to be associated with pollution decreases even below international standards. The large response to and short time needed for benefits of these interventions emphasize the urgency of improving global air quality and the importance of increasing efforts to reduce pollution at local levels.
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http://dx.doi.org/10.1513/AnnalsATS.201907-538CMEDOI Listing
December 2019

Women exposure to household air pollution after an improved cookstove program in rural San Luis Potosi, Mexico.

Sci Total Environ 2020 Feb 14;702:134456. Epub 2019 Nov 14.

Tobacco and COPD Department, National Institute of Respiratory Diseases (INER), Tlalpan 4502, 14080 Mexico City, Mexico.

The state government of San Luis Potosí (SLP), Mexico implemented an improved cookstove (ICS) program in rural areas. As part of the comprehensive program evaluation, we compared fine particulate material (PM) concentrations in kitchens and patios in treated (TH), and non-treated households (NTH), and analyzed pollutant levels according to patterns of fuels and devices use reported by the women. A panel study was conducted in 728 households (357 TH and 371 NTH) in three regions of SLP including two sampling rounds in 2015-16. Data on exposure determinants, ICS conditions and cooking practices were collected. Daily PM in kitchen and patio was measured in a subsample. The average treatment effect was estimated using the double difference method. We constructed a mixed linear model to estimate PM levels for the entire study sample and obtained personal exposure according to time-activity logs. NTH had lower socioeconomic status compared to TH. The average daily PM concentrations in NTH compared to TH were 155.2 and 92.6 μg/m for kitchen and 35.4 and 39.8 μg/m for patio, respectively. PM levels showed significant regional differences but no significant treatment effect. In many cases, the ICS was added to previous open fire and LPG use (stacking). The household size, kitchen ventilation, relative humidity, temperature and the ratio of indoor/outdoor PM concentration were significant predictors of kitchen PM levels. The daily PM personal exposure was significantly reduced using ICS in good conditions or LPG (57 μg/m) compared to the traditional open fire (86 μg/m). This study strengthens the evidence on the potential daily PM exposure reduction for women using an ICS in good conditions or LPG, displacing the polluting open fire. Comprehensive strategies tailored to the sociocultural context of the communities are needed to implement clean energy programs that achieve adoption and sustained use of ICS or LPG.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134456DOI Listing
February 2020

High performance of rapid influenza diagnostic test and variable effectiveness of influenza vaccines in Mexico.

Int J Infect Dis 2019 Dec 4;89:87-95. Epub 2019 Sep 4.

Institutional Influenza Committee, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; Dirección Médica, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.

Objectives: To evaluate the performance of rapid influenza diagnostic tests (RIDT) and influenza vaccines' effectiveness (VE) during an outbreak setting.

Methods: We compared the performance of a RIDT with RT-PCR for influenza virus detection in influenza-like illness (ILI) patients enrolled during the 2016/17 season in Mexico City. Using the test-negative design, we estimated influenza VE in all participants and stratified by age, virus subtype, and vaccine type (trivalent vs quadrivalent inactivated vaccines). The protective value of some clinical variables was evaluated by regression analyses.

Results: We enrolled 592 patients. RT-PCR detected 93 cases of influenza A(H1N1)pdm09, 55 of AH3N2, 141 of B, and 13 A/B virus infections. RIDT showed 90.7% sensitivity and 95.7% specificity for influenza A virus detection, and 91.5% sensitivity and 95.3% specificity for influenza B virus detection. Overall VE was 33.2% (95% CI: 3.0-54.0; p = 0.02) against any laboratory-confirmed influenza infection. VE estimates against influenza B were higher for the quadrivalent vaccine. Immunization and occupational exposure were protective factors against influenza.

Conclusions: The RIDT was useful to detect influenza cases during an outbreak setting. Effectiveness of 2016/17 influenza vaccines administered in Mexico was low but significant. Our data should be considered for future local epidemiological policies.
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http://dx.doi.org/10.1016/j.ijid.2019.08.029DOI Listing
December 2019

Amino acid changes in HA and determinants of pathogenicity associated with influenza virus A H1N1pdm09 during the winter seasons 2015-2016 and 2016-2017 in Mexico.

Virus Res 2019 10 21;272:197731. Epub 2019 Aug 21.

Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.

Biennial H1N1pdm09 influenza A virus (IAV) epidemics have been associated with major severity of respiratory disease in Mexico. Atypically and in contrast with what happened in USA, Canada and Europe during 2017, an increase of infections due to the H1N1pdm09 pandemic virus instead of H3N2 was observed. In order to determine the viral contribution to severe acute respiratory disease, we characterized the pathogenicity determinants of IAV in Mexico during the 2015-2016 and 2016-2017 seasons. The RNA segments of 20 IAV samples were sequenced by NGS platform and phylogenetic analysis was conducted. The analysis of the hemagglutinin (HA) sequences established that all virus samples, except one, belong to clade (6B.1). The IAVs presented the substitution S162 N, which introduces a new glycosylation site in the hemagglutinin. We also found the D222 G substitution, which has been associated with a higher tropism towards the lower respiratory tract, and a non-reported insertion of one Ile in NS1 (Ile113). The IAVs from 2016 to 2017 in Mexico belong to the new clade 6B.1. The new glycosylation site in HA (S162 N) is a major change that may affect the efficacy of the current vaccine. We detected in several patients pathogenicity determinants associated with the severity of the respiratory disease.
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http://dx.doi.org/10.1016/j.virusres.2019.197731DOI Listing
October 2019

Letter from Mexico.

Respirology 2019 12 19;24(12):1224-1225. Epub 2019 Aug 19.

National Institute of Respiratory Diseases, Mexico City, Mexico.

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http://dx.doi.org/10.1111/resp.13680DOI Listing
December 2019

Anthropometric status of individuals with COPD in the city of São Paulo, Brazil, over time - analysis of a population-based study.

J Bras Pneumol 2019 Jul 29;45(6):e20170157. Epub 2019 Jul 29.

. Disciplina de Pneumologia, Escola Paulista de Medicina, Universidade Federal de São Paulo - EPM/UNIFESP - São Paulo (SP) Brasil.

Objective: To evaluate the anthropometric data obtained for residents of the city of São Paulo, Brazil, in a study of Latin America conducted in two phases (baseline, in 2003, and follow-up, in 2012).

Methods: This was an analysis of data obtained for São Paulo residents in a two-phase population-based study evaluating the prevalence of COPD and its relationship with certain risk factors among individuals ≥ 40 years of age. The anthropometric data included values for weight, height, body mass index (BMI), and waist circumference. In the follow-up phase of that study, the same variables were evaluated in the same population sample as that of the baseline phase.

Results: Of the 1,000 São Paulo residents enrolled in the baseline phase of that study, 587 participated in the follow-up phase, and 80 (13.6%) of those 587 subjects had COPD. Comparing the baseline and follow-up phases, we found increases in all anthropometric measures in both groups (COPD and non-COPD), although the differences were significant only in the non-COPD group. The subjects with mild COPD showed increases in weight and BMI (Δweight = 1.6 ± 5.7 and ΔBMI = 0.7 ± 2.2), whereas those with moderate or severe COPD showed reductions (Δweight = -1.7 ± 8.1 and ΔBMI = -0.4 ± 3.0), as did those with severe or very severe COPD (Δweight = -0.5 ± 5.4 and ΔBMI = -0.8 ± 3.3).

Conclusions: Between the two phases of the study, the subjects with mild COPD showed increases in weight and BMI, whereas those with a more severe form of the disease showed reductions.
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http://dx.doi.org/10.1590/1806-3713/e20170157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715159PMC
July 2019

A follow-up study after an improved cookstove intervention in rural Mexico: Estimation of household energy use and chronic PM exposure.

Environ Int 2019 10 25;131:105013. Epub 2019 Jul 25.

Environmental Health Department, Centre for Population Health Research, National Institute of Public Health (INSP), Cuernavaca, Morelos, Mexico; Hubert Department of Global Health, Emory University, Atlanta, GA, USA.

The benefits of improved biomass cookstoves (ICS) depends on their adoption and sustained use. Few studies have documented if and how they are used more than five years after being introduced. We conducted a 9-year prospective cohort study among young rural women in the highlands of Michoacan, Mexico. Participants had received a Patsari ICS during a community trial either in 2005 or 2006. With retrospective information collected in 2012-13, we studied the households' energy use, ICS survival, and cooking practices during the follow-up period. Using an exposure model constructed with personal PM measurements in a subsample of homes at the time of the initial trial in 2005, we estimated the exposure associated with different energy use patterns during the follow-up period. The ICS had a mean lifespan of 4 years, after which more than half of the stoves were not in use; therefore, the use of open fire increased, particularly among the indigenous communities. ICS use peak was achieved two years after the initial trial, either exclusively or combined with open fire. Yearly household energy use and other variables were used to estimate chronic air pollution exposure. Mean PM exposure during the follow-up period ranged from 51 to 319 μg/m; the median was 102 and 146 μg/m for mainly ICS and mainly open fire use, respectively. The ICS has a useful period after which it needs maintenance, repair, or replacement. Unfortunately, many programs have not afforded a follow-up component. Exposure to biomass smoke air pollutants can be reduced by using an ICS instead of the traditional open fire. Household energy strategies should ensure equitable access to clean energy options adapted to local needs and preferences with culturally appropriate technology implemented on a sustainable perspective.
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http://dx.doi.org/10.1016/j.envint.2019.105013DOI Listing
October 2019

Body composition from 18 to 22 years and pulmonary function at 22 years-1993 Pelotas Birth Cohort.

PLoS One 2019 27;14(6):e0219077. Epub 2019 Jun 27.

Federal University of Pelotas, Postgraduate Program in Epidemiology, Pelotas, Brazil.

The objective was to verify the association between body composition from 18 to 22 years and pulmonary function at 22 years of age. This longitudinal analysis was conducted with a Brazilian birth cohort data. The outcomes were the forced expiratory volume in the first second and forced vital capacity (FVC), measured at 22 years follow-up. Main exposures: obesity (body mass index ≥ 30kg/m2), and highest tertiles of fat mass (FM) and fat mass index (air displacement plethysmography) measured at 18 and 22 years-old follow-ups. The reference category (not exposed) was defined by those individuals who were not classified in the highest adiposity categories mentioned, in both ages. Multivariable linear regressions stratified by sex were used. The sample comprised 3,511 participants. Those who belonged to the highest adiposity categories in 18 and 22 years follow-ups showed lower pulmonary function at 22 years when compared to those who were not classified in the higher adiposity categories in both ages (reference category); those in the highest tertile of FM showed a mean FVC -313mL (95%CI -421; -206) and -259mL (95%CI -336; -182) in men and women, compared to the reference category, respectively. Those who changed from the higher to the lower adiposity categories (from 18 to 22 years) showed pulmonary function similar to the reference, and those who presented the opposite body composition trajectory, showed decreased pulmonary function results at 22 years, mainly among women. We concluded that high body adiposity in two follow-ups and especially contemporary adiposity was associated with lower pulmonary function at 22 years.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219077PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597105PMC
February 2020

Quality of Pulmonary Function Tests in Participants with Down Syndrome.

Arch Bronconeumol 2019 10 16;55(10):513-518. Epub 2019 Mar 16.

Department of Epidemiology and Social Science in Health, National Institute of Respiratory Diseases "Ismael Cosío Villegas", Mexico City, Mexico. Electronic address:

Introduction: People with Down syndrome (DS) have high respiratory morbidity, evaluating their respiratory health with standardized, objective tests is desirable. Thus, the objective of this study was to evaluate the technical quality of Pulmonary Function Tests (PFTs) to determine which ones are most suitable for this population.

Methods: Participants included children, teenagers and adults with DS, 5 years of age or older (n=302). The technical quality of the impulse oscillometry system (IOS), forced spirometry, lung-diffusing capacity for carbon monoxide (DL), and 6-min walk test (6MWT) were analyzed by age group. Capnography and pulse oximetry were included in the study. Technical quality was determined on the basis of current international PFTs standards.

Results: Fifty-one percent of participants were males. A total of 184 participants (71%) who completed the IOS fulfilled the quality criteria, while 210 (70%) completed the 6MWT. Performance on forced spirometry and DL was poor. All pulse oximetries and 96% percent heart rates obtained had good quality, but exhaled carbon dioxide (PetCO) and respiratory rate (RR) showed deficient repeatability.

Conclusions: IOS appears to be the most reliable instrument for evaluating lung mechanics in individuals with DS.
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http://dx.doi.org/10.1016/j.arbres.2019.02.010DOI Listing
October 2019

CHRONIC OBSTRUCTIVE PULMONARY DISEASE: PERSPECTIVES FOR PRIMARY HEALTH CARE.

Rev Invest Clin 2019 ;71(1):55-63

Department of Research in Tobacco and COPD, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.

Background: Chronic obstructive pulmonary disease (COPD) has become a major health challenge worldwide due to its increasing incidence and mortality, which have serious repercussions for health-care systems.

Methods: We conducted a review of international efforts to control COPD in primary care.

Results: The WHO created the Alma-Ata declaration which established for the first time, access to health care as a human right. This precept led to the implementation of numerous programs including practical approach to Lung Health and variants in several countries; schemes designed to centralize medical care; and resources to improve attention of respiratory diseases by adapting approaches to the health-care needs of local populations. Primary respiratory health care should include actions for timely detection, health education, and targeted treatment, but the challenge for all health systems is to ensure that their programs function adequately, for they still show shortcomings in terms of their application.

Conclusions: We conclude that offering primary health care based on models that combine opportune diagnoses with suitable treatment can positively influence the course of COPD by treating early stages, thus slowing its progression. However, more extensive education and broader dissemination of information are necessary to achieve this goal.
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http://dx.doi.org/10.24875/RIC.18002630DOI Listing
June 2019

RESPIRATORY IMPACT OF ELECTRONIC CIGARETTES AND "LOW-RISK" TOBACCO.

Rev Invest Clin 2019 ;71(1):17-27

Department of Tobacco Research, Center for Population Health Research, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.

Electronic cigarettes, handheld devices that generate an aerosol that may contain nicotine by heating a solution or e-liquid, have been increasingly used especially in the young population. The aerosol's composition is determined by temperature, and by the substances contained in the heated liquid: glycerin, propylene glycol, nicotine in variable concentrations, flavoring agents, and other non-nicotine compounds. >80 compounds (including known toxics, e.g., formaldehyde, acetaldehyde, metallic nanoparticles, and acrolein) have been found in e-liquid and aerosols. Airway irritation, mucus hypersecretion, and inflammatory response, including systemic changes, have been observed after the exposure to e-cigarettes, leading to an increase in respiratory symptoms and changes in respiratory function and the host defense mechanisms. E-cigarette has been linked with an increase of symptoms in individuals with asthma, cystic fibrosis, and chronic obstructive pulmonary disease. One of the major concerns in public health is the rise in e-cigarette experimentation among never-smokers, especially children and adolescents, which leads to nicotine addiction and increases the chances of becoming with time a conventional smoker. There is an urgent need to regulate e-cigarettes and electronic nicotine delivery systems, at least with the same restrictions to those applied to tobacco products, and not to consider them as harmless products.
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http://dx.doi.org/10.24875/RIC.18002616DOI Listing
June 2019

PREFACE.

Rev Invest Clin 2019 ;71(1):5-6

Research Unit, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City, Mexico.

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May 2020

CONTROVERSIES AND LIMITATIONS IN THE DIAGNOSIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE.

Rev Invest Clin 2019 ;71(1):28-35

Department of Research on Tobacco and COPD, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. While the cut-off point to define airflow obstruction has been controversial, it is widely accepted that the spirometry test is vital, as well as performing it after using a bronchodilator. The 6-second spirometry and the forced expiratory volume in 1 second/forced expiratory volume in 6 seconds (FEV/FEV) have demonstrated validity for defining obstruction, and it would be advisable to incorporate them in the definitions of obstruction. Another relevant issue is that spirometry with borderline obstruction can vary over time, changing to above or below the cut-off point. Thus, surveillance should be considered over time, repeating the spirometry to have a greater certainty in the diagnosis. The objective of this article was to conduct an in-depth review of the controversies in the diagnosis of COPD. During the past years, COPD definition has been updated in different times; however, it is now considered more as a complex syndrome with systemic participation, requiring a multidimensional assessment, and not only a spirometry.
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http://dx.doi.org/10.24875/RIC.18002626DOI Listing
June 2019

Chronic Obstructive Pulmonary Disease in Latin America.

Ann Glob Health 2019 01 22;85(1). Epub 2019 Jan 22.

Federal University of Pelotas, BR.

The PLATINO and PREPOCOL population-based studies documented the prevalence of chronic obstructive pulmonary disease (COPD) in several Latin American (Mexico City, Sao Paulo, Montevideo, Santiago and Caracas) and Colombian (Medellin, Bogota, Barranquilla, Bucaramanga and Cali) cities. COPD ranged between 6.2 and 19.6% in individuals ≥40 years of age, with substantial rates of underdiagnosis (up to 89%) but also overdiagnosis, mostly due to the lack of spirometric confirmation. The main risk factor was tobacco smoking, but male gender and age were also associated with COPD. COPD in never smokers represented about one third of the cases and was associated with previous history of tuberculosis or a diagnosis of asthma. COPD associated with biomass smoke exposure was a common clinical phenotype in Latin America, found as a risk factor in PREPOCOL and other observational studies in the region. Smoking has been decreasing in Latin America and efforts have been made to implement cleaner biomass stoves. Unfortunately, treatment of COPD in Latin America remains highly variable with low rates of smoking cessation counselling, low use of inhaled bronchodilators and influenza vaccination. A primary-care approach to COPD, particularly in the form of integrated programs is lacking but would be critical to improving rates of diagnosis and treatment of COPD.
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http://dx.doi.org/10.5334/aogh.2418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052319PMC
January 2019

Inspiratory Capacity and Vital Capacity of Healthy Subjects 9-81 Years of Age at Moderate-High Altitude.

Respir Care 2019 Feb 15;64(2):153-160. Epub 2019 Jan 15.

Department of Respiratory Physiology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas," Mexico City, Mexico.

Background: Measurements of inspiratory capacity (IC) and vital capacity (VC) are used to recognize dynamic hyperinflation, but appropriate reference values are required to achieve accurate clinical interpretations. Altitude above sea level is a potential determining factor for lung volumes, including IC and VC.

Objective: To describe IC and VC for healthy people who live in Mexico City at an altitude of 2,240 m above sea level.

Methods: Healthy subjects ages 9-81 y completed slow spirometry by following 2005 American Thoracic Society/European Respiratory Society standards. Once associations were explored, linear regression models were constructed and values were compared with those from previously published equations.

Results: A total of 441 healthy subjects (55.1% women) participated. The mean age was 32 y (minimum age, 9 y; maximum age, 81 y). IC and VC measurements were associated with sex, age, height, and weight. An accelerated increase in IC and VC was evident from 9 to 20 y of age, followed by a gradual decrease in both sexes. In general, IC was higher in our population than predicted by previously published reference equations.

Conclusions: IC in healthy people at 2,240 m above sea level was higher than that of previous reports about European and Latin-American subjects of the same height, sex, and age who were at sea level. The present study provided robust reference values for persons who lived at a moderate altitude.
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http://dx.doi.org/10.4187/respcare.06284DOI Listing
February 2019

Diffusing Capacity of the Lung for Carbon Monoxide in Mexican/Latino Children. Quality Control and Reference Values.

Ann Am Thorac Soc 2019 02;16(2):240-247

2 Laboratorio de Función Pulmonar S. de R.L., Ciudad de México, México; and.

Rationale: Single-breath diffusing capacity of the lung for carbon monoxide (Dl) values are used to evaluate gas exchange; however, the quality of maneuvers performed by children has not been evaluated, and reference values for young people living at moderate altitudes are not well established.

Objectives: Our objectives were 1) to determine whether Dl maneuvers performed by a pediatric population would meet 2017 European Respiratory Society/American Thoracic Society (ERS/ATS) quality control standards; and 2) to report normal Dl values for Mexican/Latino children and adolescents living at moderate altitudes.

Methods: This study involved healthy young people 4-20 years of age from the metropolitan area of Mexico City (2,240 m above sea level) who were recruited in schools from July 2014 to August 2017. Dl testing was performed according to the 2005 ATS/ERS standards, and the quality control of each maneuver was analyzed according to the 2017 ERS/ATS standards. We constructed models for Dl with linear and quadratic terms for weight, height, and age as independent variables using shrinkage statistics, variance inflation factors, the Akaike information criterion, and R to compare the results of different models.

Results: Results were obtained for 420 individuals (53% boys) with a mean age of 11.7 ± 4.5 standard deviation (SD) years; 47% of maneuvers from children age 4-6 years were grade A (13% grade B), and 90% of those in children older than 13 years were grade A or B. Forty-six percent of the subjects had a Dl repeatability of <1 ml/min/mm Hg. The mean Dl was higher for boys than for girls (32.4 ± 13.6 [SD] vs. 24.1 ± 7.5 ml/min/mm Hg, respectively). The reference equation for boys was Dl = exp(1.63469 + [0.03251 × age] + [0.00846 × height] + [0.00304 × weight]), R = 0.87; for girls, the best equation was Dl = exp(1.56516 + [0.0193 × age] + [0.00893 × height] + [0.00273 × weight]), R = 0.75. The single-breath transfer coefficient of the lung for carbon monoxide remained constant with age and height, with a lower limit of normal of 6.5 ml/min/mm Hg/L in boys and 5.4 ml/min/mm Hg/L in girls. Measured Dl was higher than predicted by other authors (P < 0.001 by paired t test).

Conclusions: Individuals 4-20 years of age can complete high-quality Dl tests. Children and adolescents living at 2,240 m have higher Dl values than those living at sea level. Reference equations for Dl obtained at sea level are poor predictors of the values measured at moderate altitude.
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http://dx.doi.org/10.1513/AnnalsATS.201712-922OCDOI Listing
February 2019

Women with COPD by biomass show different serum profile of adipokines, incretins, and peptide hormones than smokers.

Respir Res 2018 Dec 4;19(1):239. Epub 2018 Dec 4.

Departamento de Investigación en Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INERICV), Talpan 4502, C.P. 14080, Ciudad de México, Mexico.

Background: The main causes of COPD are tobacco smoking (COPD-TS) and biomass smoke exposure (COPD-BS). COPD-TS is known to induce changes in adipokines, incretins, and peptide hormones, frequent biomarkers of inflammation; however, it is unknown if similar changes occur in COPD-BS.

Methods: Clinical and physiological characteristics, and serum concentration of C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin were measured in women with COPD-BS, COPD-TS, and healthy controls. Data were compared with one-way ANOVA and Tukey's post hoc test; nonparametric were expressed as median (interquartile ranges), with Kruskal-Wallis and Dunn's post-hoc test. Multivariate analysis, age, BMI, MS, and FEV% pred with levels of inflammatory mediators in COPD women.

Results: FEV1% pred, FVC% pred, and FEV1/FVC ratio were decremented in COPD. In COPD-TS increased C-peptide, ghrelin, GIP, GLP-1, and leptin, and reduced glucagon, PAI-1, resistin, and visfatin. In COPD-BS enlarged ghrelin, insulin, leptin, and PAI-1 comparatively with COPD-TS and control, while C-peptide and GLP-1 relatively with controls; conversely, glucagon, and resistin were reduced. Multivariate analysis showed association of ghrelin, insulin, PAI-1, and visfatin with BS exposure.

Conclusions: women with COPD-BS have a distinct profile of adipokines, incretins, and peptide hormones, and specifically with ghrelin, insulin, PAI-1, and visfatin related to BS exposure.
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http://dx.doi.org/10.1186/s12931-018-0943-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280373PMC
December 2018

Macrophage Exposure to Polycyclic Aromatic Hydrocarbons From Wood Smoke Reduces the Ability to Control Growth of .

Front Med (Lausanne) 2018 13;5:309. Epub 2018 Nov 13.

Medica Sur, Clinic and Foundation, Mexico City, Mexico.

Use of solid fuels for cooking or home heating has been related to various diseases of the respiratory tract. Woodsmoke contains a mixture of carcinogenic polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds. Inhalation of these materials induces local and systemic changes in the immune system which may impair critical cell defense mechanisms; however, few studies have investigated the early effects that PAH exposures have on immune cells as macrophages. The aim of this study was to analyze if the pre-exposure to PAHs derived from woodsmoke deteriorates macrophage ability to control the intracellular growth of . By using an experimental model, we analyzed the phenotype and some metabolic changes on THP-1 and monocyte-derived macrophages. Our results demonstrated that exposure to PAHs leads to cell activation and deteriorates mitochondrial function of the macrophage thus facilitating growth of .
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http://dx.doi.org/10.3389/fmed.2018.00309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243050PMC
November 2018

Outcomes for symptomatic non-obstructed individuals and individuals with mild (GOLD stage 1) COPD in a population based cohort.

Int J Chron Obstruct Pulmon Dis 2018;13:3549-3561. Epub 2018 Oct 26.

Federal University of Pelotas, Pelotas, Brazil.

Background: We aimed to study the adverse outcomes of symptomatic and asymptomatic non-obstructed individuals and those with mild COPD longitudinally in participants from three Latin-American cities.

Methods: Two population-based surveys of adults with spirometry were conducted for these same individuals with a 5- to 9-year interval. We evaluated the impact of respiratory symptoms (cough, phlegm, wheezing or dyspnea) in non-obstructed individuals, and among those classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1, COPD on exacerbation frequency, mortality and FEV decline, compared with asymptomatic individuals without airflow obstruction or restriction.

Results: Non-obstructed symptomatic individuals had a marginal increased risk of mortality (HR 1.3; 95% CI 0.9-1.94), increased FEV decline (-4.5 mL/year; 95% CI -8.6, -0.4) and increased risk of 2+ exacerbations in the previous year (OR 2.6; 95% CI 1.2-6.5). Individuals with GOLD stage 1 had a marginal increase in mortality (HR 1.5; 95% CI 0.93-2.3) but a non-significant impact on FEV decline or exacerbations compared with non-obstructed individuals.

Conclusions: The presence of respiratory symptoms in non-obstructed individuals was a predictor of mortality, lung-function decline and exacerbations, whereas the impact of GOLD stage 1 was mild and inconsistent. Respiratory symptoms were associated with asthma, current smoking, and the report of heart disease. Spirometric case-finding and treatment should target individuals with moderate-to-severe airflow obstruction and those with restriction, the groups with consistent increased mortality.
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http://dx.doi.org/10.2147/COPD.S175527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208535PMC
April 2019