BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.
BackgroundLung-function decline is one of the possible mechanisms leading to Chronic Obstructive Pulmonary Disease (COPD).MethodsWe analyzed data obtained from two population-based surveys of adults (n = 2026) conducted in the same individuals 5–9 years (y) after their baseline examination in three Latin-American cities. Post BronchoDilator (postBD) FEV1 decline in mL/y, as %predicted/y (%P/y) and % of baseline/y (%B/y) was calculated and the influence of age, gender, BMI, baseline lung function, BD response, exacerbations rate evaluated using multivariate models.ResultsExpressed in ml/y, the mean annual postBD FEV1 decline was 27 mL (0.22%P, 1.32%B) in patients with baseline COPD and 36 (0.14%P, 1.36%B) in those without. Faster decline (in mL/y) was associated with higher baseline lung function, with significant response to bronchodilators, older age and smoking at baseline, also in women with chronic cough and phlegm, or ≥2 respiratory exacerbations in the previous year, and in men with asthma.ConclusionsLung function decline in a population-based cohort did not differ in obstructed and non-obstructed individuals, it was proportional to baseline FEV1, and was higher in smokers, elderly, and women with respiratory symptoms.
BackgroundRadiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predict RP in non-small cell lung cancer (NSCLC) patients.MethodsA prospective multi-institutional study was conducted with locally advanced and oligometastatic NSCLC patients. All participants were evaluated at baseline, end of CCRT, week 6, 12, 24, and 48 post-CCRT. They completed forced spirometry with a bronchodilator, body plethysmography, impulse oscillometry, carbon monoxide diffusing capacity (DLCO), molar mass of CO2, six-minute walk test and exhaled fraction of nitric oxide (FeNO). Radiation pneumonitis was assessed with RTOG and CTCAE. The protocol was registered in www.clinicaltrials.gov (NCT01580579), registered April 19, 2012.ResultsFifty-two patients were enrolled; 37 completed one-year follow-up. RP ≥ Grade 2 was present in 11/37 (29%) for RTOG and 15/37 (40%) for CTCAE. Factors associated with RP were age over 60 years and hypofractionated dose. PFT abnormalities at baseline that correlated with the development of RP included lower forced expiratory volume in one second after bronchodilator (p = 0.02), DLCO (p = 0.02) and FeNO (p = 0.04). All PFT results decreased after CCRT and did not return to basal values at follow-up.ConclusionsFEV1, DLCO and FeNO prior to CCRT predict the development of RP in NSCLC. This study suggests that all patients under CCRT should be assessed by PFT to identify high-risk patients for close follow-up and early treatment.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0775-2) contains supplementary material, which is available to authorized users.
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