Epigenetics and chromatin remodeling play a role in lung disease

Epigenetics is defined as heritable changes that affect gene expression without altering the DNA sequence. Epigenetic regulation of gene expression is facilitated through different mechanisms such as DNA methylation, histone modifications and RNA-associated silencing by small non-coding RNAs. All these mechanisms are crucial for normal development, differentiation and tissue-specific gene expression. These three systems interact and stabilize one another and can initiate and sustain epigenetic silencing, thus determining heritable changes in gene expression. Histone acetylation regulates diverse cellular functions including inflammatory gene expression, DNA repair and cell proliferation. Transcriptional coactivators possess intrinsic histone acetyltransferase activity and this activity drives inflammatory gene expression. Eleven classical histone deacetylases (HDACs) act to regulate the expression of distinct subsets of inflammatory/immune genes. Thus, loss of HDAC activity or the presence of HDAC inhibitors can further enhance inflammatory gene expression by producing a gene-specific change in HAT activity. For example, HDAC2 expression and activity are reduced in lung macrophages, biopsy specimens, and blood cells from patients with severe asthma and smoking asthmatics, as well as in patients with chronic obstructive pulmonary disease (COPD). This may account, at least in part, for the enhanced inflammation and reduced steroid responsiveness seen in these patients. Other proteins, particularly transcription factors, are also acetylated and are targets for deacetylation by HDACs and sirtuins, a related family of 7 predominantly protein deacetylases. Thus the acetylation/deacetylation status of NF-κB and the glucocorticoid receptor can also affect the overall expression pattern of inflammatory genes and regulate the inflammatory response. Understanding and targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in situations in which current anti-inflammatory therapies are suboptimal

Reduced Phagocytic Capacity of Blood Monocyte/Macrophages in Tuberculosis Patients Is Further Reduced by Smoking.

Tuberculosis (TB) and tobacco use are two major alarming global health issues posing immense threats to human populations. Mycobacterium tuberculosis (MTB) by activation of macrophages could induce the sequences of cells activation and releases of inflammatory cytokines such as CXCL-8, Il-12 and TNF-α which in turn induces the immune system network. However no information is available on other activity of cells by MTB and smoking. In the current study we aimed to investigate the serum levels TNF-a, CXCL-8 and phagocytosis capacity in tuberculosis patients with and without smoking. 103 subjects entered the study including 61 new diagnosed pulmonary TB patients (23 smokers and 38 nonsmokers) and 42 control healthy subjects. The phagocytosis of fluorescein isothiocyanate dextran (FITC-dextran) in blood monocytes/macrophages through flowcytometry was assessed. Serum levels of TNF-a and CXCL-8 were analyzed by ELISA methods. A lower percentage of cells from TB patients who smoked [50.29% (43.4-57.2), p<0.01] took up FITC-dextran after 2h compared to non-smoking TB subjects [71.62% (69.2-74.1)] and healthy cases [97.45% (95.9-99.1). Phagocytic capacity was inversely correlated with cigarette smoking as measured by pack years (r=-0.73, p<0.001). The serum levels of TNF-a and CXCL-8 were significantly higher in the TB patients who smoked compared to the TB non-smoker group (p<0.001, p<0.01 respectively). Blood monocytes/macrophages from TB patients have reduced phagocytic capacity which is further reduced in TB patients who smoke. Smoking enhanced serum levels of TNF-a and CXCL-8 suggesting a greater imbalance between the proinflammatory and anti-inflammatory factors in these patients

The Recent-Transmission of Mycobacterium tuberculosis Strains among Iranian and Afghan Relapse Cases: a DNA-fingerprinting using RFLP and spoligotyping

<p>Abstract</p> <p>Background</p> <p>Relapse of tuberculosis (TB) may develop as the result of reactivation of the endogenous primary infection, or as a result of a exogenous reinfection. This survey evaluated the rate of reactivation versus recent transmission among Iranian and Afghan relapse cases.</p> <p>Methods</p> <p>The sputum specimens were digested, examined microscopically for acid-fast bacilli, and inoculated into Löwenstein-Jensen slants by standard procedures. Thereafter, the susceptibility and identification tests were performed on culture positive specimens. Subsequently, the strains that were identified as <it>Mycobacterium tuberculosis </it>(258 isolates) were subjected to IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping. Additional patient's information was collected for further epidemiological analysis. Patients whose isolates had identical genotyping patterns were considered a cluster with recent transmission episode.</p> <p>Results</p> <p>Out of 258 available isolates, 72(28%) had multi-drug resistant (MDR-TB) in ratio and 42 (16.2%) had other resistant. Notably, 38 of MDR-TB cases (52%) were isolated from Afghan patients. By IS6110-RFLP typing method, 65 patients (25%) were clustered in 29 clusters. In cluster cases, the intra-community transmissions between Iranian and Afghan patients were 41%. All MDR-TB patients in clusters had either Haarlem I or Beijing characteristic. The risk factors like sex, family history, close contact, living condition, PPD test result and site of TB infection were not associated with clustering. Although, the MDR-TB strains were more frequent in non-cluster cases (31%) than cluster one(18%) (P < 0.05). Majority of <it>M. tuberculosis </it>strains isolated from non-cluster cases were belong to EAI3 (51; 30%) and CASI(32;18.6%) superfamilies.</p> <p>Conclusion</p> <p>During the studied period, reactivation of a previous infection remain the more probable cause of recurrence. Although, the evidence of intra- community transmission between Iranian and Afghan TB cases, highlighted the impact of afghan immigrants in national tuberculosis control program (NTP) of Iran.</p

Nutrition and lung cancer: a case control study in Iran

Background: Despite many prospective and retrospective studies about the association of dietary habit and lung cancer, the topic still remains controversial. So, this study aims to investigate the association of lung cancer with dietary factors. Method: In this study 242 lung cancer patients and their 484 matched controls on age, sex, and place of residence were enrolled between October 2002 to 2005. Trained physicians interviewed all participants with standardized questionnaires. The middle and upper third consumer groups were compared to the lower third according to the distribution in controls unless the linear trend was significant across exposure groups. Result: Conditional logistic regression was used to evaluate the association with lung cancer. In a multivariate analysis fruit (Ptrend < 0.0001), vegetable (P = 0.001) and sunflower oil (P = 0.006) remained as protective factors and rice (P = 0.008), bread (Ptrend = 0.04), liver (P = 0.004), butter (Ptrend = 0.04), white cheese (Ptrend < 0.0001), beef (Ptrend = 0.005), vegetable ghee (P < 0.0001) and, animal ghee (P = 0.015) remained as risk factors of lung cancer. Generally, we found positive trend between consumption of beef (P = 0.002), bread (P < 0.0001), and dairy products (P < 0.0001) with lung cancer. In contrast, only fruits were inversely related to lung cancer (P < 0.0001). Conclusion: It seems that vegetables, fruits, and sunflower oil could be protective factors and bread, rice, beef, liver, dairy products, vegetable ghee, and animal ghee found to be possible risk factors for the development of lung cancer in Iran

Completeness and timeliness of tuberculosis notification in Taiwan

Tuberculosis (TB) is a notifiable disease by the Communicable Disease Control Law in Taiwan. Several measures have been undertaken to improve reporting of TB but the completeness and timeliness of TB notification in Taiwan has not yet been systemically evaluated

Delay in diagnosis of tuberculosis in Rawalpindi, Pakistan

<p>Abstract</p> <p>Background</p> <p>Delay in diagnosis and treatment of tuberculosis (TB) may enhance the chances of morbidity and mortality and play a key role in continuous transmission of the bacilli. The objective of this study was to describe health care seeking behavior of suspected TB patients and initial diagnostic work up prior to consultation and diagnosis at National TB Center (NTC).</p> <p>Findings</p> <p>Interviews of 252 sputum smear positive patients were taken from NTC, Rawalpindi. The duration between on-set of symptoms and start of treatment was considered as the total delay and correlated with general characteristics of TB patients. The proportion of males and females were 49.6% and 50.4% with median age of 25 and 24 years respectively. A median delay of 56 days (8 weeks) was observed which was significantly associated with age, cough and fever. More than 50% of the current patients had a history of contact with previously diagnosed TB patients. The majority of patients (63%) visited health care providers within three weeks of appearance of symptoms but only thirty five percent were investigated for TB diagnosis.</p> <p>Conclusion</p> <p>Cough and fever are being ignored as likely symptoms of TB by patients as well as health care providers resulting in delay. Engaging private practitioners through public private mix (PPM) approach for expansion of TB diagnosis and increasing public awareness could be more beneficial to reduce delay.</p

Multidrug-resistant tuberculosis treatment adherence in migrants: a systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a growing concern in meeting global targets for TB control. In high-income low-TB-incidence countries, a disproportionate number of MDR-TB cases occur in migrant (foreign-born) populations, with concerns about low adherence rates in these patients compared to the host non-migrant population. Tackling MDR-TB in this context may, therefore, require unique approaches. We conducted a systematic review and meta-analysis to identify and synthesise data on MDR-TB treatment adherence in migrant patients to inform evidence-based strategies to improve care pathways and health outcomes in this group. METHODS: This systematic review and meta-analysis was conducted in line with PRISMA guidelines (PROSPERO 42017070756). The databases Embase, MEDLINE, Global Health and PubMed were searched to 24 May 2017 for primary research reporting MDR-TB treatment adherence and outcomes in migrant populations, with no restrictions on dates or language. A meta-analysis was conducted using random-effects models. RESULTS: From 413 papers identified in the database search, 15 studies reporting on MDR-TB treatment outcomes for 258 migrants and 174 non-migrants were included in the systematic review and meta-analysis. The estimated rate of adherence to MDR-TB treatment across migrant patients was 71% [95% confidence interval (CI) = 58-84%], with non-adherence reported among 20% (95% CI = 4-37%) of migrant patients. A key finding was that there were no differences in estimated rates of adherence [risk ratio (RR) = 1.05; 95% CI = 0.82-1.34] or non-adherence (RR = 0.97; 95% CI = 0.79-1.36) between migrants and non-migrants. CONCLUSIONS: MDR-TB treatment adherence rates among migrants in high-income low-TB-incidence countries are approaching global targets for treatment success (75%), and are comparable to rates in non-migrants. The findings highlight that only just over 70% of migrant and non-migrant patients adhere to MDR-TB treatment. The results point to the importance of increasing adherence in all patient groups, including migrants, with an emphasis on tailoring care based on social risk factors for poor adherence. We believe that MDR-TB treatment targets are not ambitious enough