Tanaffos Respiration Journal
Volume:10 Issue: 4, Autumn 2011

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-kB 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.

Serological assays for diagnosis of tuberculosis (TB) are very attractive because they are inexpensive, non invasive and simple. Present study was conducted to evaluate the tuberculosis rapid test device in Iran. The tuberculosis rapid test device based on detection of IgM, IgA and IgG antibodies against 6, 16 and 38-kDa antigens of Mycobacterium tuberculosis via chromatography was used in 96 cases of pulmonary and extra pulmonary TB. Fifty four patients with conditions other than TB were selected as the control group. Tuberculin skin test (TST) was performed in two groups. None of the patients were immunodeficient. All of them were evaluated in terms of presence of BCG scar. Tuberculosis rapid test was positive in 75 cases (78.1%) and 15 controls (27.8%). This difference was statistically significant (P-value < 0.001). TST was positive in 66 patients (68.8%) with tuberculosis and 10 (18.5%) controls with no statistically significant difference (P-value = 0.065).Sensitivity, specificity, positive and negative predictive values of the tuberculosis rapid test for diagnosis of tuberculosis were 78.1%, 72.2%, 83.3% and 65%, respectively.These parameters for TST were 31.3%, 81.5%, 75%, and 40%, respectively. Tuberculosis rapid test has better sensitivity than TST and may be helpful in diagnosis of tuberculosis as a complementary test or in epidemiological investigations.

Antigen 85 complex of Mycobacterium tuberculosis includes three immunogenic proteins which are TB vaccine candidates of great importance. As they are very hard to be achieved in natural form, recombinant production of them fuels immunological experiments. Production of such apolar mycobacterial proteins located in the cell wall faces substantial challenges mainly regarding their solubility. This study reports the production of soluble recombinant Ag85B with an efficient yield. Ag85B gene was cloned in pJET1.2 and subsequently in pET32a (+). Both recombinant plasmids were sequenced. Expression of the recombinant protein was induced with 1mM IPTG. Recombinant Ag85B was purified through dissolving inclusions in 8M urea buffer, absorbing to Ni-NTA resins, washing by buffers with decreasing urea concentrations and finally eluted in imidazole. Western blot analysis was performed using anti-6His tag antibody, rabbit anti- M. tuberculosis polyclonal antibody and serum of hospitalized TB patients. Ag85B gene was successfully cloned in both plasmid vectors. The recombinant Ag85B was expressed in E. coli host and purified with significant yield. Western blot results along with those of sequencing ensured accurate production of recombinant Ag85B and retaining of its antigenic structure.

In previous decades several studies have been performed demonstrating that providing appropriate nutritional support to intensive care unit patients affects complications, time of mechanical ventilation, length of ICU stay, and risk of death. In this study we provided a report of nutrition statuses in Masih Daneshvari's ICU as compared to 156 ICUs from 20 countries that participated in an international nutrition survey. All patients admitted to an intensive care unit during a specified one-month period who required artificial nutrition were included in this study. Characteristics of patients, performance of nutrition practices, and ICU outcomes were registered for all patients and compared with data from 156 other intensive care units from various countries around the world. Twenty patients, of which 11(55%) were males and 9(45%) were females, were included in this study. The median age was 50.5 yrs (IQR: 40.5-56.0). Seventeen (85%) of them had EN nutrition only, 2(10%) had PN nutrition only, and 1(5%) had both EN and PN nutrition during their stay in the ICU. The adequacy of calorie intake was 67.6% (vs. 61.1% in all 157 ICUs) and the adequacy of protein intake was 84.9% (vs. 56.7% in 157 ICUs). In our ICU, enteral feeding was superior to parenteral feeding. Also we considered early initiation of enteral feeding within 48 hours following ICU admission. We just used polymeric formula during this study. As a result of formula variation limits, we overestimated calories and protein needs. Glutamine and Selenium supplementations have not been used yet for patient in our ICU, regardless of their proven benefits in oxidative stress conditions like pulmonary diseases. Therefore, limited use of supplementations like selenium is inevitably among the disadvantages of Masih Daneshvari Hospital’s ICU, which is a tertiary-care center for chronic pulmonary diseases.

This study aimed to find an association between the short validated patient-completed questionnaire, the COPD Assessment Test (CAT) and disease severity according to spirometric findings in chemical warfare victims. A total of 55 patients referred to Sasan Hospital (special complex for chemical warfare victims) were included in this survey. They completed CAT questionnaire and then spirometry was performed. According to GOLD criteria, the subjects were divided into four severity groups. All candidates were non-smoker males. They all had FEV1/FVC<70%. CAT scores varied from 5 to 39, with a mean score of 22.25. FEV1 varied from 17.5% to 89% with a mean of 53.14, and FVC ranged from 22.9% to100% with a mean of 61.12. Data analysis revealed a significant relationship between CAT and FEV1 (P=0.01). There was also a significant relationship between CAT and FVC (P=0.05). Our findings show a significant association between CAT and disease severity obtained by lung function in chemical warfare victims.

Evaluation of the lymph nodes in cases with lung cancer for diagnosis or staging has been considered since many years ago. Various methods have been developed for obtaining a sample from lymph nodes. This study was conducted in a research institute with high patient turnover and aimed at evaluating the diagnostic yield of TBNA and effective factors on diagnosis and related complications in patients with pulmonary lesions. Our understudy population included all patients suffering from undiagnosed intrathoracic lymphadenopathies with no accompanying pulmonary lesions on chest CT scan who had been hospitalized in Masih Daneshvari Hospital or referred to its bronchoscopy unit. After determining the anatomic location of lymphadenopathy (LAP), patients underwent fiberoptic bronchoscopy (FOB) and TBNA using 19-gauge eXcelon aspiration needle. Four samples were taken from each patient from the same LAP location. In this study, 39 patients were evaluated. The most common anatomic location of lymph node involvement among our understudy patients was the paratracheal area which was involved in 14 (45.2%) patients followed by subcarinal area in 12 cases (38.7%) and hilar involvement also in 12 cases (38.7%). Five patients (15.6%) had lymphadenopathies in other anatomical locations. Evaluation of the aspirates obtained by TBNA showed that the sample was adequate and diagnostic in 21 patients (55.26%), adequate but non-diagnostic in 9 patients (23.68%) and inadequate in 8 cases (21.06%). Definite diagnosis was made in 22 patients among which the most common diagnosis was atypical and malignant lesions in 11 cases (50%) followed by sarcoidosis in 8 (36.36%), tuberculosis (TB) in 2 (9.09%) and other diagnoses in 1 (4.55%) case. Based on our study results, TBNA was diagnostic in more than half the cases. Various studies have reported a wide range of results in this respect but all of them including ours emphasize on the acceptable diagnostic yield of this technique.

Asthma is a serious global health problem. The lack of a clinical gold standard for evaluation of asthma control, as well as inadequate recognition of uncontrolled asthma by patients and clinicians may contribute to this situation. The Asthma Control Test is an easy and reliable test. The aim of this study was to validate the Persian version of this test with regard to GINA2009 guidelines based on a specialist’s rating of asthma control. Patients (n = 150) completed the Asthma Control Test. Pulmonary function was measured. A chest specialist rated asthma control in line with the Global Initiative for Asthma 2009 guidelines. Patients were divided into well controlled, partly controlled and uncontrolled groups in order to evaluate the reliability and validity of the ACT. The mean age was 41.68 years. The internal consistency reliability of 5-item ACT survey was 0.89%. There were no significant differences in ACT scores between different age, gender, educational status and inhabitancy groups. Between the groups with different GINA-based control levels, a significant difference in ACT score was noted in favor of an ACT-based discrimination of different states of asthma control (F = 305.3, P<0.001). Patient group with poorer lung function (FEV1) scored significantly lower on the ACT than groups with better lung function (F=6.82, P<0.001). Differences in ACT score between treatment recommendation groups were significant (F=50.54, P<0.001). Statistically significant correlations were observed between ACT scores and GINA-based values of asthma control rating by a specialist (r = 0.86, p<0.001) and treatment recommendations (r=0.54, p<0.001). Correlation between ACT score and percentage of FEV1 predicted was moderate (r=0.39, P<0.001). The Persian version of Asthma Control Test is a valid and reliable test for asthma control assessment.

Metal Inert Gas (MIG) welding and Tungsten Inert Gas (TIG) welding are widely used for mild steel segments in basic metal industries. Pulmonary problems such as asthma, pulmonary inflammation, hyper-responsiveness of airways and higher susceptibility to infections are reported as the result of occupational exposure of welders to ozone and nitrogen oxides. Potent oxidizing agents like ozone and nitrogen oxides are also reported to be a precursor for respiratory problems and cause lipid peroxidation of membranes. A total of 43 nonsmoking MIG and TIG welders and 41 nonsmoking workers without appreciable exposure to any chemicals as the control population were chosen to participate in this study. Occupational exposure to ozone was monitored according to the validated methods. Malondialdehyde (MDA) of blood serum as a biomarker for lipid peroxidation was analyzed using Reverse Phase High Performance Liquid Chromatography. Data obtained from this study were analyzed using t-test, Pearson’s correlation coefficient and multiple regression analysis. A total of 88.4% and 74.4% of welders had exposure to ozone and nitrogen dioxide higher than the permissible limit of occupational exposure, respectively. Generally, exposure of MIG welders to ozone was significantly higher than TIG welders (P=0.006). However, exposure to nitrogen dioxide gas was comparable in both groups. Serum MDA of welders was significantly higher than that of the control group (P=0.001). A significant correlation was detected between ozone exposure and level of serum malondialdehyde. Such correlation was not observed for nitrogen dioxide exposure. Considering the high exposure of welders to ozone and nitrogen dioxide, and higher level of serum malondialdehyde in them compared to controls, risk management is recommended for this group of workers.

Since the first rib is protected very well by the overlying soft tissue and bones, its fracture is a major injury and a considerable force is required to do it. Therefore, an isolated fracture of this rib is unusual. A 28-year-old healthy female had an accident while crossing the road and a heavy object fell on her. She had severe pain behind her clavicle region and was immediately hospitalized and examined. Thorough clinical examination and different relevant investigations surprisingly disclosed isolated bilateral first rib fracture which is a very rare clinical condition.

In the modern world, with developed traveling facilities, tourism is an important factor in emerging new infectious diseases in non-endemic areas. Therefore, the epidemiology of infections is a considerable issue for physicians and should be taken into account.We report a case of melioidosis in a 69-year-old Iranian man during his trip to Southeast Asia.On admission, he was febrile with tachycardia and tachypnea and had diabetes mellitus and hypertension since eleven years ago.Bronchoscopy and bronchoalveolar lavage (BAL) were performed. Blood and BAL cultures revealed heavy growth of Burkholderia pseudomallei. According to the aforementioned culture results, the patient was treated with meropenem and TMP-SMX, while other antibiotics were discontinued.After 3 weeks, the patient was discharged with stable status and normal pulmonary function; and eradication therapy with TMP-SMX continued for about 3 months. The control lung CT scan after one month demonstrated significant improvement.

A 60-year-old woman was admitted due to persistent right-sided vague chest pain since two months ago. She also complained of 5 kg weight loss and productive cough. On admission, she was stable and afebrile with mild crackles in both lungs without tachypnea or remarkable respiratory distress.She lived in a rural region in southwest of Iran and was being treated with combined fluticasone-salmeterol and ipratropium bromide due to chronic bronchitis since five years ago. Exposure to biomass fuels used for cooking and heating was a possible etiology for her chronic respiratory symptoms. She denied using systemic corticosteroids in recent months.Laboratory analysis revealed normal complete blood count, arterial blood gases, liver and renal function tests, serum lactate dehydrogenase and angiotensin converting enzyme levels. Human immunodeficiency virus antibody was negative and plasma immunoglobulin revealed no abnormality.Chest roentgenographic studies (Figure 1) revealed multiple nodules in both lung fields.Based on chest computed tomography (CT) findings and negative repeated sputum smears, the patient underwent CT-guided biopsy of lung nodules. Histopathological examination was unremarkable and the procedure was complicated by pneumothorax.Finally, bronchoscopy and bronchoalveolar lavage were performed. No abnormality was detected in the airways.