Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis

SummaryIdiopathic pulmonary fibrosis (IPF) is a lethal lung disorder of unknown etiology. The disease is likely the result of complex interactions between genetic and environmental factors. Evidence suggests that certain environmental factors, such as cigarette smoking and metal dust exposures, or comorbidities like gastroesophageal reflux, and type 2 diabetes mellitus (DM2) may increase risk to develop IPF. Substantial uncertainty remains, however, regarding these and other putative risk factors for IPF. In this study we performed a case–control analysis including 100 patients with IPF and 263 controls matched for age sex and place of residence. We used a structured questionnaire to identify potential risk factors for IPF, including environmental and occupational exposures as well as the relevance of family history of pulmonary fibrosis. The multivariate analysis revealed that family history of pulmonary fibrosis [OR = 6.1, CI95% 2.3–15.9; p < 0.0001] was strongly associated with increased risk of IPF. Actually, 20% of the cases reported a parent or sibling with pulmonary fibrosis. Gastroesophageal reflux [OR = 2.9, CI: 1.3–6.6; p = 0.007], former cigarette smoking [OR = 2.5, CI: 1.4–4.6, p = 0.003], and past or current occupational exposure to dusts, smokes, gases or chemicals [OR = 2.8, CI: 1.5–5.5; p = 0.002] were also associated with the disease. Despite being a significant risk factor on univariate analysis DM2 was not significant in multivariate analysis. These findings indicate that family history of pulmonary fibrosis is a strong risk factor for IPF. Also, we confirmed that occupational exposures, gastroesophageal reflux and former smoking increase the risk for this disease

Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population

Background: The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence. Methods: We carried out a case–control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts. Results: We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcorr = 0.01, OR= 2.37). The association of the SNP rs352139 was statistically significant after adjustment by age, gender and comorbidities by regression logistic analysis (Dominant model: p value = 0.016, OR = 2.31; Additive model: p value = 0.023, OR = 1.68). The haplotype GAA of TLR9 SNPs was also associated with TB susceptibility (Pcorr = 0.02). Differences in the genotype or allele frequencies of TLR2, TLR4 and TLR6 polymorphisms between TB patients and healthy contacts were not detected. Conclusions: Our study suggests that the allele A of the intronic polymorphism rs352139 on TLR9 gene might contribute to the risk of developing TB in Mexican Amerindians

Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy.

Este articulo ha sido publicado en la revista Oncotarget. Esta versión tiene Licencia Creative Commons CC-BYTriple negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study is to explore the clinical relevance of Lehmann TNBC subtypes by identifying any differences in response to neoadjuvant chemotherapy among them. We determined Lehmann subtypes by gene expression profiling in paraffined pre-treatment tumor biopsies from 125 TNBC patients treated with neoadjuvant anthracyclines and/or taxanes +/- carboplatin. We explored the clinicopathological characteristics of Lehmann subtypes and their association with the pathologic complete response (pCR) to different treatments. The global pCR rate was 37%, and it was unevenly distributed within Lehmann’s subtypes. Basal-like 1 (BL1) tumors exhibited the highest pCR to carboplatin containing regimens (80% vs 23%, p=0.027) and were the most proliferative (Ki-67>50% of 88.2% vs. 63.7%, p=0.02). Luminal-androgen receptor (LAR) patients achieved the lowest pCR to all treatments (14.3% vs 42.7%, p=0.045 when excluding mesenchymal stem-like (MSL) samples) and were the group with the lowest proliferation (Ki-67≤50% of 71% vs 27%, p=0.002). In our cohort, only tumors with LAR phenotype presented non-basal-like intrinsic subtypes (HER2- enriched and luminal A). TNBC patients present tumors with a high genetic diversity ranging from highly proliferative tumors, likely responsive to platinum-based therapies, to a subset of chemoresistant tumors with low proliferation and luminal characteristics.This work was supported by Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) from Instituto de Salud Carlos III (ISCIII) (CB16/12/00241, CB16/12/00471, CB16/12/00481) and by research grants from ISCIII (PI13/00730), Mutua Madrileña 2013 and Sociedad Española de Oncología Médica (SEOM) 2013. The authors acknowledge support through grant TIN2017- 88728-C2-1-R from MICINN-SPAIN. Angela Santonja has a predoctoral grant PFIS-ISCIII (FI12/00489)

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

General and abdominal adiposity and hypertension in eight world regions: a pooled analysis of 837 population-based studies with 7·5 million participants

Background Adiposity can be measured using BMI (which is based on weight and height) as well as indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions and quantified how well these two metrics discriminate between people with and without hypertension. Methods We used data from studies carried out from 1990 to 2023 on BMI, WHtR and hypertension in people aged 20–64 years in representative samples of the general population in eight world regions. We graphically compared the regional distributions of BMI and WHtR, and calculated Pearson’s correlation coefficients between BMI and WHtR within each region. We used mixed-effects linear regression to estimate the extent to which WHtR varies across regions at the same BMI. We graphically examined the prevalence of hypertension and the distribution of people who have hypertension both in relation to BMI and WHtR, and we assessed how closely BMI and WHtR discriminate between participants with and without hypertension using C-statistic and net reclassification improvement (NRI). Findings The correlation between BMI and WHtR ranged from 0·76 to 0·89 within different regions. After adjusting for age and BMI, mean WHtR was highest in south Asia for both sexes, followed by Latin America and the Caribbean and the region of central Asia, Middle East and north Africa. Mean WHtR was lowest in central and eastern Europe for both sexes, in the high-income western region for women, and in Oceania for men. Conversely, to achieve an equivalent WHtR, the BMI of the population of south Asia would need to be, on average, 2·79 kg/m² (95% CI 2·31–3·28) lower for women and 1·28 kg/m² (1·02–1·54) lower for men than in the high-income western region. In every region, hypertension prevalence increased with both BMI and WHtR. Models with either of these two adiposity metrics had virtually identical C-statistics and NRIs for every region and sex, with C-statistics ranging from 0·72 to 0·81 and NRIs ranging from 0·34 to 0·57 in different region and sex combinations. When both BMI and WHtR were used, performance improved only slightly compared with using either adiposity measure alone. Interpretation BMI can distinguish young and middle-aged adults with higher versus lower amounts of abdominal adiposity with moderate-to-high accuracy, and both BMI and WHtR distinguish people with or without hypertension. However, at the same BMI level, people in south Asia, Latin America and the Caribbean, and the region of central Asia, Middle East and north Africa, have higher WHtR than in the other regions

Prevalencia y riesgos asociados con pacientes adultos con asma de 40 años o más de la Ciudad de México: estudio de base poblacional Adult asthma in Mexico City: a population-based study

OBJETIVOS: Determinar la prevalencia de asma y la asociación entre características sociodemográficas, espirométricas, síntomas respiratorios, calidad de vida y sueño en adultos >40 años. MATERIAL Y MÉTODOS: Este informe es parte del estudio PLATINO (Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar), llevado a cabo en la Ciudad de México y área metropolitana en 2003. Se utilizaron modelos de regresión logística ajustados por el diseño del estudio, donde asma fue la variable dependiente y las independientes síntomas respiratorios y características sociodemográficas y clínicas, entre otras. RESULTADOS: La prevalencia de asma diagnosticada por médico fue de 3.3% en hombres y 6.2% en mujeres. La función pulmonar disminuyó en asmáticos. En el análisis multivariado, después de ajustar por confusores potenciales, los asmáticos mostraron un mayor riesgo de ronquido más somnolencia excesiva diurna [RM=3.2 (IC95%1.4-7.4), p=0.008], y mayor frecuencia de inasistencias laborales por problemas respiratorios [RM=5.1 (IC95% 2.5-10.4), p<0.0001]. CONCLUSIONES: La prevalencia de asma fue de 5%. Los asmáticos mostraron menor calidad de vida y función pulmonar.<br>OBJECTIVES: To determine the prevalence of asthma and the association between sociodemographic characteristics, spirometry, respiratory symptoms, quality of life and sleep in adults > 40 years. MATERIALS AND METHODS: This report is part of our study (Latin American Research Project Obstructive Pulmonary), held in Mexico City and the metropolitan area in 2003. We used logistic regression models adjusted for study design, where asthma was the dependent and independent variable respiratory symptoms, sociodemographic and clinical characteristics among others. RESULTS: The prevalence of physician-diagnosed asthma was: 3.3% in men and 6.2% in women. Decreased lung function in asthmatics was observed. In multivariate analysis, after adjusting for potential confounders, asthmatics had a higher risk of excessive daytime sleepiness more snoring [OR = 3.2 (95% CI 1.4-7.4), p= 0.008], and more frequent work absences due to respiratory problems [OR = 5.1 (95% CI 2.5-10.4), p<0.0001]. CONCLUSIONS: The prevalence of asthma was 5%. Asthmatics showed lower quality of life and lung function

Risk factors for idiopathic pulmonary fibrosis in a Mexican population. A case-control study

SummaryThe etiology of idiopathic pulmonary fibrosis (IPF) remains poorly understood, but some studies have suggested that cigarette smoking or other occupational or environmental exposures, diabetes mellitus, or gastroesophageal reflux may play a role. In this study we evaluated the clinical records of a group of 97 consecutive patients with IPF, and 560 patients suffering 5 different respiratory disorders that were examined as controls: asthma (n=111), chronic obstructive pulmonary disease (n=132), squamous cell lung carcinoma (n=118), lung adenocarcinoma (n=101) and patients with otorhinolaryngology problems but without lung disease (n=98). In bivariate analyses male sex, diabetes mellitus and being former cigarette smoker were associated with IPF. After adjusting by these variables, multivariate analysis revealed that type 2 diabetes mellitus [11.3% in IPF patients vs 2.9% in controls, OR=4.3 (95% CI: 1.9–9.8), p<0.0001] was an independent risk factor associated to IPF. Our results provide additional evidence of a putative relationship between DM2 and idiopathic pulmonary fibrosis. Experimental research is necessary for thorough assessment of the pathogenic mechanisms involved in this association

Factors that enable or limit the sustained use of improved firewood cookstoves: Qualitative findings eight years after an intervention in rural Mexico.

The aim of this study was to analyze the factors enabling/limiting the use of improved cookstoves among rural fuel wood users from one mestizo and two indigenous communities eight years after an intervention in the state of Michoacan, in Mexico.A qualitative study with an ethnographic perspective was conducted in 2013/2014 based on 62 interviews with women who had participated in an improved firewood cookstove program in 2005. Thematic qualitative content analysis was performed.Very few women from the indigenous communities were using the improved cookstove at the time of the study; the majority had dismantled or had ceased using it; whereas most of those from the mestizo community were using it for all of their cooking activities. In the indigenous communities, characterized by extended families, uptake of new technology was limited by traditional routine practices, rearrangement of rooms in the house, attachment to the traditional stove, a low- or non-risk perception of woodsmoke; gender relations, insufficient training, non-compliance with program recommendations and design-related aspects. Conversely, in the mestizo community, the uptake of the improved cookstove was favored by routine cooking practices in a nuclear family, a previous use of a raised cookstove and social representations on the health-disease-death effects of woodsmoke vs. the health benefits of cooking with improved stoves. The sociocultural dimension of communities and the cookstove design are aspects that either favor or limit the use of improved cookstoves in indigenous and mestizo populations.Effective cookstove programs must take these elements into account from their early planning stages, and blend them into implementation and follow-up. Project communication, training and differentiated follow-up activities ensuring the operation and maintenance of the cookstove, should be designed according to the specific needs and traditions of each community; they should be based on the preferences and needs of the users

Disgeusia como principal manifestación oral en pacientes con COVID-19 leve en el Instituto Nacional de Enfermedades Respiratorias

Objective. To report the oral manifestations associated with COVID-19 as well as whether these persist over a period of 3 months. Methods. A longitudinal, descriptive study was carried out evaluating 149 individuals positive for SARS-CoV-2 by polymerase chain reaction (PCR), who underwent an initial examination and a control 3 months later. Results. A total of 65% of the participants reported some manifestation in the oral cavity and 24% some sequelae. Within these observed symptoms and oral sequelae, the one with the highest incidence was dysgeusia, which was found in 51% of patients followed by xerostomia (27%), lymph nodes or swollen glands (17%). These manifestations decreased significantly during the follow-up, however they prevailed in some patients. Conclusions. Dysgeusia is the oral manifestation with the highest incidence in this study and was among the 5 most common general manifestations.Objetivo. Reportar las manifestaciones orales más comunes asociadas a COVID-19 así como si estas persisten en un período de 3 meses. Métodos. Se realizó un estudio longitudinal, descriptivo, evaluando a 149 individuos positivos por reacción en cadena de la polimerasa (PCR) para SARS-CoV-2 a los cuales se les realizó un estudio inicial y un control 3 meses después. Resultados. El 65% de los participantes reportó alguna manifestación en cavidad bucal y el 24% alguna secuela. Dentro de estos síntomas y secuelas bucales observados, la de mayor frecuencia fue la disgeusia la cual se encontró en 51% de los pacientes seguida por xerostomía 27%, ganglios o glándulas inflamadas (17%). Dichas manifestaciones disminuyeron de forma importante en el seguimiento, sin embargo, prevalecieron en algunos pacientes. Conclusiones. La disgeusia es la manifestación oral de mayor frecuencia en este estudio y se presentó entre las cinco manifestaciones generales más comunes

Longitudinal Lung Function Growth of Mexican Children Compared with International Studies

<div><p>Introduction</p><p>Our aim was to compare the longitudinal lung function growth of Mexican children and adolescents with the collated spirometric reference proposed for international use and with that of Mexican-Americans from the National Health State Examination Survey III (NHANES) III study.</p> <p>Materials and Methods</p><p>A cohort of Mexican children in third year of primary school was followed with spirometry twice a year through secondary school. Multilevel mixed-effects lineal models separated by gender were fit for the spirometric variables of 2,641 respiratory-healthy Mexican children expressed as Z-scores of tested reference equations. Impact of adjustment by sitting height on differences with Mexican-American children was observed in a subsample of 1,987 children.</p> <p>Results</p><p>At same gender, age, and height, Mexican children had increasingly higher forced expiratory volume in 1 s (FEV₁) and Forced vital capacity (FVC) than the children from the collated reference study (mean Z-score, 0.68 for FEV₁ and 0.51 for FVC) and than Mexican-American children (Z-score, 0.23 for FEV₁ and 0.21 for FVC) respectively. Differences with Mexican-Americans were not reduced by adjusting by sitting height.</p> <p>Conclusions</p><p>For reasons that remain unclear, the gender-, age-, and height-adjusted lung function of children from Mexico City is higher than that reported by several international studies.</p> </div