Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1) virus infections. Most patients infected with the influenza A (H1N1) ...pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). We propose that single-nucleotide polymorphisms (SNPs) in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1) pdm09 virus infection.
145 patients with influenza A (H1N1) (pA/H1N1), 133 patients with influenza-like illness (ILI), and 360 asymptomatic healthy contacts (AHCs) were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8) using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4) were measured on a Luminex 100.
The IL6 rs1818879 (GA) heterozygous genotype was associated with severe influenza A (H1N1) virus infection (odds ratio OR = 5.94, 95% confidence interval CI 3.05-11.56), and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively). Genetic susceptibility was determined (pA/H1N1 vs. AHC): the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9), and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89). Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007). Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001) and IL-6 (p = 0.007) levels.
The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were associated with influenza A (H1N1) virus infection.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Health care workers are at high risk of being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our aim is to evaluate the efficacy and safety of hydroxychloroquine ...(HCQ) for prophylaxis of coronavirus disease 19 (COVID-19) in health personnel exposed to patients infected by SARS-CoV-2.
Double-blind randomized, placebo-controlled single center clinical trial. Included subjects were health care workers caring for severe COVID-19 patients. Main outcome was time to symptomatic SARS-CoV-2 infection.
127 subjects with a confirmed baseline negative RT-PCR SARS-CoV2 test were included in the trial. 62 assigned to HCQ and 65 to placebo. One subject (1.6%) in the HCQ group and 6 (9.2%) subjects in the placebo group developed COVID-19 (Log-Rank test p = 0.07). No severe COVID-19 cases were observed. The study was suspended because of a refusal to participate and losses to follow up after several trials reported lack of effectiveness of hydroxychloroquine in hospitalized patients with COVID-19.
The effect size of hydroxychloroquine was higher than placebo for COVID-19 symptomatic infection in health personnel, although this was not statistically significant. The trial is underpowered due to the failure to complete the estimated sample size.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Effective therapeutics for respiratory viruses are needed. Early data suggest that nitazoxanide (NTZ) may be beneficial for treating acute respiratory viral illness.
Methods
From ...March 2014 through March 2017, a double-blind, placebo-controlled trial was conducted in 260 participants ≥1 year old hospitalized with influenza-like illness at 6 hospitals in Mexico. Participants were randomized 1:1 to NTZ (age ≥12 years, 600 mg twice daily; age 4–11 years and 1–3 years, 200 or 100 mg twice daily, respectively) or placebo for 5 days in addition to standard of care. The primary endpoint was time from first dose to hospital discharge. Influenza reverse-transcription polymerase chain reaction and Respifinder 22 multiplex test were used for virus detection.
Results
Of 260 participants enrolled, 257 were randomized and took at least 1 dose of study treatment (intention-to-treat population): 130 in the NTZ group and 127 in the placebo group. The Kaplan-Meier estimate of the median duration of hospitalization was 6.5 (interquartile range IQR, 4.0–9.0) days in the NTZ group vs 7.0 (IQR, 4.0–9.0) days in the placebo group (P = .56). Duration of hospitalization between the 2 treatments was similar in children (P = .29) and adults (P = .62), influenza A and B (P = .32), and other respiratory viruses. Seven (5.4%) and 6 (4.7%) participants in the NTZ and placebo groups, respectively, reported serious adverse events.
Conclusions
Treatment with NTZ did not reduce the duration of hospital stay in severe influenza-like illness. Further analyses based on age and evaluations by virus did not reveal any subgroups that appeared to benefit from NTZ.
Clinical Trials Registration
NCT02057757.
Treatment of children and adults hospitalized with severe acute respiratory illness with nitazoxanide in addition to standard of care was safe, but did not reduce hospital stay, complications, nor shedding of influenza and other respiratory viruses.
Th17 profile in COPD exacerbations Ponce-Gallegos, Marco Antonio; Ramírez-Venegas, Alejandra; Falfán-Valencia, Ramcés
International journal of chronic obstructive pulmonary disease,
01/2017, Volume:
12
Journal Article
Peer reviewed
Open access
COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow. It is mainly associated with exposure to cigarette smoke. In addition, it ...is considered, at present, a serious public health problem, ranking fourth in mortality worldwide. Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells. Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways. The aims of these molecules are differentiation, proliferation and recruitment of neutrophils. Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight. In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract. Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity.
Introduction
Lung microbiome dysbiosis affects the immune system balance and promotes lung inflammation. We aimed to characterize and compare the lung bacteriome composition and the cytokine profile ...in women with normal lung function exposed to risk factors for chronic lung diseases (tobacco smoking and biomass‐burning smoke exposure).
Methods
We included women with biomass‐burning smoke exposure (BE, n = 11) and current smokers women (TS, n = 10). The bacteriome composition was performed in induced sputum, sequencing the 16 rRNA gene. Cytokine levels were measured using enzyme‐linked immunosorbent assay multiplex assay in the supernatant of induced sputum. For quantitative variables, we used medians and minimum and maxim values. For the amplicon sequence variants (ASV) differential abundance testing between groups.
Results
At the taxa level, the phylum Proteobacteria was found in a higher proportion in the TS group concerning BE (p = .045); however, after the false discovery rate adjustment, this difference was not retained (p = .288). We found a higher concentration of IL‐1β in the TS group than in the BE group (248.6 vs. 177.9 pg/mL, p = .010). Women with high biomass‐burning smoke exposure in an hour per day had a positive correlation with the abundance of Bacteroidota (ρ = 0.71, p = .014) and Fusobacteriota (ρ = 0.73, p = .011). FEV1/FVC had a positive correlation with an abundance of Bacteroidota, Proteobacteria, and Fusobacteria (ρ = 0.74, p = .009, ρ = 0.85, p = .001, and ρ = 0.83, p = .001, respectively). In tobacco smoking, women had a positive correlation (ρ = 0.77, p = .009) between cigarettes per day and Firmicutes' abundance.
Conclusion
Compared to biomass‐burning smoke‐exposed women, current smokers have poor lung function and high levels of IL‐1β in sputum. Women with biomass‐burning smoke exposure present an increased abundance of Bacteroidota and Fusobacteriota.
This is the first study that evaluates the bacterial composition in exposed women to known risk factors for lung diseases with normal lung function. The pro‐inflammatory mediators play an essential role in the initiation and maintenance of inflammation.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The concepts of susceptibility and vulnerability are intertwined because vulnerability is sometimes a consequence of being susceptible. Women are more likely to be susceptible to chronic obstructive ...pulmonary disease (COPD) than men 1. As many women continue to smoke during pregnancy, the impact of tobacco in women can begin before birth 2, because maternal smoking during pregnancy may increase the risk of childhood respiratory diseases 3 and reduce lung function 2. Indeed, this susceptibility starts before women become smokers. For example, women with specific genotype variants are at a significantly increased risk of becoming heavy smokers 4, while those women with the haplotype TAS2R38 (proline-alanine-valine) have a genetic propensity to experience heightened bitter taste perception and an increased preference for menthol cigarettes 5. Recent findings of the Global Youth Tobacco survey on adolescents aged 13-15years showed that young girls smoke as much as young boys 6. The early onset of smoking may have a greater deleterious impact on lung function among girls 7 because their lungs are smaller than those of males. Accordingly, the same exposure to a given number of cigarettes smoked can lead to more deleterious effects in women 8. In this regard, once young females become smokers, addiction may be reinforced by both nicotine and the sensory and social contexts of smoking. Motivations associated with gender can provoke women to have different cues for smoking compared with males 9; therefore, women are more vulnerable to the social context of smoking and can easily become involved in the nicotine addictive process, along with consequent disease risks.
Background
The relationship between obesity and risk of complications described during the 2009 influenza pandemic is poorly defined for seasonal influenza and other viral causes of influenza‐like ...illness (ILI).
Methods
An observational cohort of hospitalized and outpatient participants with ILI was conducted in six hospitals in Mexico. Nasopharyngeal swabs were tested for influenza and other common respiratory pathogens.
Results
A total of 4778 participants were enrolled in this study and had complete data. A total of 2053 (43.0%) had severe ILI. Seven hundred and seventy‐eight (16.3%) were positive for influenza, 2636 (55.2%) were positive for other viral respiratory pathogens, and 1364 (28.5%) had no respiratory virus isolated. Adults with influenza were more likely to be hospitalized if they were underweight (OR: 5.20), obese (OR: 3.18), or morbidly obese (OR: 18.40) compared to normal‐weight adults. Obese adults with H1N1 had a sixfold increase in odds of hospitalization over H3N2 and B (obese OR: 8.96 vs 1.35, morbidly obese OR: 35.13 vs 5.58, respectively) compared to normal‐weight adults. In adults with coronavirus, metapneumovirus, parainfluenza, and rhinovirus, participants that were underweight (OR: 4.07) and morbidly obese (OR: 2.78) were more likely to be hospitalized as compared to normal‐weight adults. All‐cause influenza‐like illness had a similar but less pronounced association between underweight or morbidly obesity and hospitalization.
Conclusions
There is an increased risk of being hospitalized in adult participants that are underweight or morbidly obese, regardless of their viral pathogen status. Having influenza, however, significantly increases the odds of hospitalization in those who are underweight or morbidly obese.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Biomass exposure is an important risk factor for chronic obstructive pulmonary disease (COPD). However, the time-course behavior of FEV1 in subjects exposed to biomass is unknown.
We undertook this ...study to determine the FEV1 rate decline in subjects exposed to biomass.
Pulmonary function was assessed every year in a Mexican cohort of patients with COPD associated with biomass or tobacco during a 15-year follow-up period.
The mean rate of decline was significantly lower for the biomass exposure COPD group (BE-COPD) than for the tobacco smoke COPD group (TS-COPD) (23 vs. 42 ml, respectively; P < 0.01). Of the TS-COPD group, 11% were rapid decliners, whereas only one rapid decliner was found in the BE-COPD group; 69 and 21% of smokers versus 17 and 83% of the BE-COPD group were slow decliners and sustainers, respectively. A higher FEV1 both as % predicted and milliliters was a predictive factor for decline for BE-COPD and TS-COPD, whereas reversibility to bronchodilator was a predictive factor for both groups when adjusted by FEV1% predicted and only for the TS-COPD group when adjusted by milliliters.
In the biomass exposure COPD group the rate of FEV1 decline is slower and shows a more homogeneous rate of decline over time in comparison with smokers. The rapid rate of FEV1 decline is a rare feature of biomass-induced airflow limitation.
Summary Background Chronic obstructive pulmonary disease (COPD) is a progressive disorder characterized by an inflammatory response to cigarette smoke. A disorder in immune regulation contributing to ...the pathogenesis of COPD has been suggested, however, little is known about the involvement of CD4+ T cells. To determine the distribution of different CD4+ T cell subsets in patients with COPD, current smokers without COPD (CS) and healthy subjects (HS), and its correlation with pulmonary function. Methods Th1, Th2, Th17 and Treg, subsets, were quantified by flow cytometry in peripheral blood (PB) of 39 patients with COPD, 14 CS and 15 HS. Correlations were assessed with Spearman’s rank test. The association between Th17 and lung function was evaluated with a multivariate logistic regression analysis. Results An increase of Th17 cells (median 9.7% range 0.8–22.5%) was observed in patients with COPD compared with CS (median 2.8% range 0.8–10.6) and HS (median 0.6% range 0.4–1%, p < 0.0001). Th1 and Tregs subsets were also increased in COPD and CS compared to HS. Inverse correlations were found between Th17 with FEV1 %p r = −0.57 and with FEV1 /FVC r = −0.60, ( p < 0.0001 for both comparison). In addition, increase of Th17 predicted the presence OR 1.76 (CI 95% 1.25–2.49, p = 0.001) and severity of airflow limitation OR 1.13 (CI95% 1.02–1.25, p = 0.02). Conclusions The increase of Th17 response and the lost of balance between CD4+ T cell subsets, suggest a lack of regulation of the systemic inflammatory response that may contribute to pathogenesis in COPD patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The tobacco industry promotes electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP) as a safer alternative to conventional cigarettes with misleading marketing sustained by ...studies with conflict of interest. As a result, these devices sell without regulations and warnings about their adverse effects on health, with a growing user base targeting young people. This systematic review aimed to describe the adverse effects on the respiratory system in consumers of these devices. We conducted a systematic review and bibliometric analysis of 79 studies without conflict of interest evaluating ENDS and HTP effects in the respiratory system in experimental models, retrieved from the PubMed database. We found that the damage produced by using these devices is involved in pathways related to pulmonary diseases, involving mechanisms previously reported in conventional cigarettes as well as new mechanisms particular to these devices, which challenges that the tobacco industry's claims. The present study provides significant evidence to suggest that these devices are an emerging public health problem and that they should be regulated or avoided.
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