Subclinical involvement of the heart and its associated factors in patients with sarcoidosis with normal systolic function using 2D speckle tracking.

BACKGROUND: Cardiac involvement by sarcoidosis may affect any part of the heart such as the pericardium, atriums, ventricles, and papillary muscles. In this regard, the use of two-dimensional speckle-tracking strain has been reported to be valuable in detecting heart sarcoidosis and its distinction from cardiomyopathy. The aim of this study was to investigate subclinical cardiac involvement using 2D speckle tracking and its associated factors in patients with normal systolic function by 2D transthoracic echocardiography (TTE). METHODS: In this study, 55 patients with extra-cardiac sarcoidosis and 21 normal people were evaluated by 2D speckle tracking. The mean longitudinal global strain for the left ventricle was calculated as an average of 16 segments per patient. RESULTS: The comparison of the mean 2D speckle-tracking indices including GCS (global circumferential strain) SAXA, GCSSAXM, Average GCS, AP2LS, AP3LS, AP4LS, and also Average GLS (global longitudinal strain) showed a significant difference between the two groups. Also, the evaluation of each of the above indices with a specific cutoff point as well as a high sensitivity and acceptable specificity predicted the presence of sarcoidosis. The occurrence of changes in the above indices was independent of ventricular function by 2D echocardiography in these patients. CONCLUSIONS: The marked changes in the 2D speckle-tracking parameters in patients with extra-cardiac sarcoidosis can be of great value in the prediction of cardiac involvement. The occurrence of the abovementioned cardiac changes can be completely independent of the involvement of left ventricular function and is therefore predictable in patients with normal ventricular function.

Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran.

The Coronavirus Disease 2019 (COVID-19) pandemic has killed many people worldwide since December 2019, and Iran has been among the most affected countries. In this retrospective study, we aimed to determine the prognostic factors associated with mortality in COVID-19 patients by analyzing 396 survived and 63 non-survived patients in Shahid Modarres Hospital, Tehran, Iran, from January 30th until April 5th, 2020. As the results, the BMI > 35 (p = 0.0003), lung cancer (p = 0.007), chronic kidney disease (p = 0.002), Immunocompromised condition (p = 0.003), and diabetes (p = 0.018) were more frequently observed in the expired group. The history of statins use was more common in the discharged group (p = 0.002), while there was no significant difference in the drug history of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs, aspirin, and/or steroids, and in the past-year influenza vaccination. Multivariable regression demonstrated rising odds of in-hospital death related with age (odds ratio (OR) = 1.055, p = 0.002), levels of C-reactive protein (CRP) (OR = 2.915, p < 0.001), creatinine (OR = 1.740, p = 0.023), lymphocyte count (OR = 0.999, p = 0.008), and magnesium level (OR = 0.032, p < 0.001) on admission. In conclusion, the patients with older age and higher BMI with lymphopenia, hypomagnesemia, elevated CRP and/or raised creatinine on admission are at higher risk of mortality due to the COVID-19 infection, which requires the physicians to use timely and strong therapeutic measures for such patients.

The association of radiologic right heart strain indices with the severity of pulmonary parenchymal involvement and prognosis in patients with COVID-19.

Introduction: It has been demonstrated that an increase in the diameter of the right ventricle or pulmonary artery in COVID-19 patients could be associated with the severity of lung involvement and may lead to unfavorable outcomes, particularly in the presence of pulmonary vascular diseases. This study investigated the relationship between these right heart strain features, the extent of lung involvement, and their prognostic values in patients without vascular comorbidities. Methods: This study selected 154 consecutive patients with positive chest computed tomography (CT) findings and no evidence of concurrent pulmonary disease. Clinical characteristics and adverse outcomes in in-hospital settings were collected retrospectively. Diameters of cardiac ventricles and arteries, along with lung opacification scores, were obtained using CT pulmonary angiography (CTPA) findings, and the association of these variables was evaluated. Results: An increase in pulmonary artery (PA) to ascending aorta (AO) diameter ratio and lung parenchymal damage were significantly and positively correlated (P=0.017), but increased right ventricle (RV) to left ventricle (LV) diameter ratio showed no association with the extent of chest opacification (P=0.098). Evaluating the prognostic ability of both ratios using logistic regression and receiver operating characteristic (ROC) analysis proved no significant class separation in regards to predicting adverse outcomes (PA/AO: OR:1.081, P Value:0.638, RV/LV: OR:1.098, P Value:0.344). Conclusion: In COVID-19 patients without vascular comorbidities, a higher PA/AO diameter ratio was significantly associated with increased lung involvement severity on CT imaging but not with adverse in-hospital outcomes. Conversely, an increased RV/LV ratio on CTPA did not correlate significantly with adverse outcomes or the severity of parenchymal lung damage.

Efficacy and safety of a proposed omalizumab biosimilar compared to the reference product in the management of uncontrolled moderate-to-severe allergic asthma: a multicenter, phase III, randomized, double-blind, equivalency clinical trial.

Background and aims: Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil®, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations. Methods: Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks. Results: Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV1) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, "dyspnea" and "headache" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies. Conclusion: P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters. Clinical trial registration: www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).

Investigation of the effects of Chlorella vulgaris supplementation on the modulation of oxidative stress in apparently healthy smokers.

BACKGROUND: Smoking is among the established yet modifiable risk factors for cancers, cardiovascular diseases, and pulmonary disorders. Oxidative stress has been proposed as a key mechanism mediating the deleterious consequences of smoking. The present study evaluated the effect of supplementation with Chlorella vulgaris, a nutrient and bioactive green microalgae with proven antioxidant capacity, on the burden of oxidative stress in Iranian smokers. METHODS: Thirty-eight smokers (mean age: 37.11 +/- 1.69 years; females: 18.4%) were administered C. vulgaris extract (3600 mg/day) for a period of 6 weeks. Fasted serum samples collected at baseline and after the completion of study were analyzed for the concentrations of vitamin C, vitamin E, glutathione, and malonedialdehyde (MDA) as well as activities of superoxide dismutase, glutathione peroxidase, and catalase. Total antioxidant capacity of serum was also determined by the ability of serum to inhibit the formation of ferryl myoglobin radical species. RESULTS: Six-week supplementation with C. vulgaris extract in smokers was associated with marked elevation of all assessed serum antioxidant measures (p < 0.001) and significant reduction of MDA levels (p = 0.002). After gender segregation, a similar pattern of changes was observed for both male and female subjects apart from lack of significant change in serum vitamin E status in females. Although the magnitude of change in serum vitamin E was significantly greater in males compared to females (p = 0.014), there was no significant change in the magnitude of changes for other assessed parameters between the genders. CONCLUSIONS: Supplementation with C. vulgaris extract significantly improves antioxidant status and attenuates lipid peroxidation in chronic cigarette smokers. Hence, C. vulgaris might prevent the disease burden and mortality rate associated with smoking.

Effect of Pneumococcal Conjugate 13 Valent and Polysaccharide 23 Valent Vaccination on Anti-Pneumococcal Antibody Titer of Hemodialysis Patients: A Randomized Clinical Trial.

Background: Pneumococcal infections are a life- threatening disease in hemodialysis patients and vaccination against pneumococcus is an effective prevention. The current study aims to evaluate the immune response and maintenance of the anti-pneumococcal antibody titer in hemodialysis patients to the 23 valent pneumococcal polysaccharide vaccine alone and 13 valent conjugated with 23 valent polysaccharide vaccine. Materials and Methods: This study is a randomized clinical trial that was performed at Loghman Hakim Hospital in Tehran, Iran in 2017. A total of 70 patients undergoing hemodialysis were randomly assigned to intervention (22 patients) and control (23 patients). In the control group, only one dose of the PPSV23 vaccine while patients in the intervention group were injected initially with PCV13, and then after at least 8 weeks PPSV23 vaccine. The outcome of this study is first and sixth-month antibody titer after injection of the PPSV23 vaccine. Results: The obtained result showed no significant difference between the two groups in the first month and sixth months. The results indicate that both the intervention group (treated with PCV13+PPSV23) and the control group (treated with PPSV23 only) experienced a significant impact from the first to the sixth month. Additionally, there was a noticeable effect on the levels of anti pneumococcal antibodies during the first to sixth month between the intervention and control groups. In addition, the difference between the antibody titer of the first month and the sixth month was not significant in the two groups. Conclusion: The anti-pneumococcal antibody titer in hemodialysis patients does not show a clear difference after two vaccine injections and one vaccination.

Prognostic implications of biventricular strain measurement in COVID-19 patients by speckle-tracking echocardiography.

BACKGROUND: Recent reports have indicated the beneficial role of strain measurement in COVID-19 patients. HYPOTHESIS: To determine the association between right and left global longitudinal strain (RVGLS, LVGLS) and COVID-19 patients' outcomes. METHODS: Hospitalized COVID-19 patients between June and August 2020 were included. Two-dimensional echocardiography and biventricular global longitudinal strain measurement were performed. The outcome measure was defined as mortality, ICU admission, and need for intubation. Appropriate statistical tests were used to compare different groups. RESULTS: In this study 207 patients (88 females) were enrolled. During 64 ± 4 days of follow-up, 22 (10.6%) patients died. Mortality, ICU admission, and intubation were significantly associated with LVGLS and RVGLS tertiles. LVGLS tertiles could predict poor outcome with significant odds ratios in the total population (OR = 0.203, 95% CI: 0.088-0.465; OR = 0.350, 95% CI: 0.210-0.585; OR = 0.354, 95% CI: 0.170-0.736 for mortality, ICU admission, and intubation). Although odds ratios of LVGLS for the prediction of outcome were statistically significant among hypertensive patients, these odds ratios did not reach significance among non-hypertensive patients. RVGLS tertiles revealed significant odds ratios for the prediction of mortality (OR = 0.322, 95% CI: 0.162-0.640), ICU admission (OR = 0.287, 95% CI: 0.166-0.495), and need for intubation (OR = 0.360, 95% CI: 0.174-0.744). Odds ratios of RVGLS remained significant even after adjusting for hypertension when considering mortality and ICU admission. CONCLUSION: RVGLS and LVGLS can be acceptable prognostic factors to predict mortality, ICU admission, and intubation in hospitalized COVID-19 patients. However, RVGLS seems more reliable, as it is not confounded by hypertension.

The Effect of Exogenous Surfactant on Moderate and Severe Stages of COVID-19 Induced ARDS: the Pilot Study of a Clinical Trial.

COVID-19 pandemic has created a global health challenge. Many pharmaceuticals have been repurposed as potential treatments, though many have not been promising. Due to the inflammatory and destructive effects of the virus on alveolar cells, the effect of exogenous surfactant was assessed as a potential treatment of lung dysfunction in COVID-19 patients. In this pilot study of the clinical trial, 49 patients aged 35-80 years with COVID-19 admitted in ICU entered the study (22 patients intubated and 23 had face masks; 4 patients in the control arm). The treatment arm patients received two consecutive doses of surfactant. P/F ratio (based on serial blood gas analyses before and 12 hours after 2 doses of surfactant) and also, clinical outcomes were assessed.in COVID-19 adult patients, surfactant significantly improved pulmonary P/F ratio both in intubated and face mask COVID-19 patients (increasing from 119.2 ± 51.7 to 179.4 ± 115.5). The rate of extubation was much better than similar country-wide studies. Surfactant significantly alleviates the respiratory status in moderate to severe COVID-19 ARDS with two consecutive 100 mg doses of surfactant (with 6 hours' interval) though previous studies have been controversial, regarding the effect of surfactant in general forms of ARDS. Higher doses might have better effects, mandating more trials.

The effect of surfactant on clinical outcome of patients with COVID-19 under mechanical ventilation: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Assessing the effect of surfactant on clinical outcome in patients with COVID-19 under mechanical ventilation TRIAL DESIGN: Single centre, two arm, parallel group (1:1 allocation ratio), randomised superiority trial with blinded care and outcome assessment. PARTICIPANTS: Inclusion criteria: Adult COVID-19 patients admitted to the ICU in Modarres hospital, Tehran, Iran (age range of 18 to 99 years) with moderate to severe ARDS (based on definition of P/F ratio) requiring auxiliary respiratory devices (either intubation or face mask). EXCLUSION CRITERIA: ● Existence of a major underlying pulmonary disease in addition to COVID-19 ● Underlying congenital heart disease ● Patients needing extracorporeal membrane oxygenation (ECMO) ● ARDS primarily due to any other reason rather than COVID-19 ● The primary source of pulmonary involvement was bacterial pneumonia or any other etiology except for COVID-10 induced lung involvement ● Those who refused to continue the study (either the patient or their family) ● any patient had any sign of healing before entering the study leading to discharge from ICU in less than 12 hours INTERVENTION AND COMPARATOR: In the intervention group, the dose of the drug is a vial containing 4 ml, equivalent to 100 mg, which is prescribed for an adult weighing about 70 kg each time, and if the patient's weight is much lower or higher, it will be adjusted accordingly. Surfactant is prescribed inside the trachea in two doses, starting on the day of intubation with a second dose 6 hours later. The control group will receive the same volume of normal saline, based on weight, administered into the trachea with the same time schedule. MAIN OUTCOMES: 30 days mortality; patient mortality during stay in ICU up to 30 days; ICU length of stay up to 30 days; Time under mechanical ventilation up to 30 days. RANDOMISATION: After the participant enters the study, i.e. after the qualification of the patients in the trial is confirmed and their informed written consent is taken, we will use a simple randomisation method using a table of random numbers. In order to hide the random allocation process, a central randomisation approach will be used and the random sequence will be at the disposal of one of the researchers, excluding the principal investigator. BLINDING (MASKING): Participants, healthcare providers and the principal investigator assessing the outcomes will all be blinded to the group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 60 participants will be randomised in a 1:1 allocation ratio (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. TRIAL REGISTRATION: IRCT registration number: IRCT20091201002804N12 Registration date: 1st June 2020, 1399/03/12 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The Effect of Renal Transplantation on Respiratory Muscle Strength in Patients with End Stage Renal Disease.

BACKGROUND: There is evidence of musculoskeletal and respiratory involvement in patients with chronic kidney disease (CKD). This is attributed to protein calorie imbalance that is caused by the disease process, and hemodialysis and is generally referred to as uremic myopathy. This results in calcification of respiratory muscles such as diaphragm and intercostal muscles. There are limited data about respiratory muscle strength in patients with CKD. We intended to evaluate the effect of kidney transplantation on respiratory muscles strength in patients with CKD. MATERIALS AND METHODS: Spirometry was used to measure maximal inspiratory mouth pressure (PIMAX), which was calculated by using the lung residual volume and maximal respiratory pressures at the mouth (PEMAX), 2 days before and again 30 days after kidney transplantation in 26 patients with ESRD. PIMAX and PEMAX values less than 60% of the predicted value were considered abnormal. RESULTS: Mean ± SD PIMAX values showed significant increase from 31.88 ± 8.58 cmH2O before kidney transplantation to 37.65 ± 13.39 cmH2O after transplant (P < 0.001). Similarly, a significant increase in PEMAX values was observed from 33.04 ± 16.12 cmH2O to 39.19 ± 20.34 cmH2O (P < 0.001). Nineteen patients (73.1%) showed significant increases in PIMAX and PEMAX values. Mean serum creatinine decreased from 6.94 to 1.32 (P < 0.001) after transplant. CONCLUSION: Although both PIMAX and PEMAX values increased significantly after kidney transplant, these measurements were still below lower limit of normal. This suggests that factors other than uremic myopathy may contribute to respiratory muscle weakness in patients CKD.

Effect of Dialysis on Maximum Inspiratory and Expiratory Pressures in End Stage Renal Disease Patients.

BACKGROUND: Muscle weakness especially weakness of the respiratory muscles is a complication of chronic kidney disease. The cause of muscle weakness is the accumulation of excessive amounts of urea and other toxins. The aim of this study was to assess the effect of hemodialysis on respiratory muscle strength by measuring maximum inspiratory (PI max) and expiratory pressure (PE max). MATERIALS AND METHODS: A cross sectional study was carried out on 31 patients with chronic kidney disease at Modarres hospital in 2012. Before hemodialysis, patients had their PI max and PE max taken by using a manovacuometer. After that, the patients were connected to the dialysis machine. At the end of the hemodialysis, the patients had their PI max measured again. Data were assessed by the multivariate regression test. RESULTS: Before dialysis, PI max and PE max were lower than normal levels. After the hemodialysis session, repeat PFT revealed an increase in PE max and no significant change in PI max. There were strong correlations between hypoalbuminemia, anemia, hypercalcemia, hyperphosphatemia, hyperparathyroidism and decreased respiratory muscle strength. Also, the respiratory muscle strength decreased in the elderly and women. CONCLUSION: Respiratory muscle weakness is a complication of chronic kidney disease; hemodialysis can improve muscle strength and PI max.

Pulmonary and extra-pulmonary manifestations of sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic multi-organ granulomatous disease of unknown etiology that is characterized by the presence of granuloma in various organs. The clinical features of sarcoidosis are heterogeneous but pulmonary involvement is cardinal manifestations. The aim of this study was to determine radiologic, clinical and laboratory findings of patients with sarcoidosis. PATIENTS AND METHODS: In a cross-sectional study, all patients visiting sarcoidosis clinic were enrolled in the study. Computed tomography (CT) scan was obtained and lab exams were obtained from patient and reports were recorded in data sheet. RESULTS: Total of 55 patients with sarcoidosis were enrolled in the study. The average of age was 44.6 (range 25-62) years. Thirty-seven patients were male and 18 were female. The most common extra-pulmonary manifestation was arthritis (in 18% of cases) and then lupus pernio (12.8%) and uveitis (10.9%). Bilateral hilar adenopathy and para tracheal lymphadenopathy was observed in 39(70%) and 22 (40%) of patients. Parenchymal nodules (30%), bronchiectasia (25%), ground-glass opacification (18%) were the most common findings. Percentages of patients with dyspnea were 29% and percentages of patients with cough were 21%. Among abnormal lab tests, high urine calcium (Ca) were positive in 21% and high angiotensin-converting enzyme (ACE) in 16% of patients. CONCLUSION: Pulmonary involvements are both fibrosis and granulomatosis and the most common manifestations are parenchymal nodules, bronchiectasia and high-grade fibrosis. The most common extra-pulmonary involvement is arthritis. Lab tests are non-specific and have no correlation with duration or severity of disease.

Approach to Patients with Severe Asthma: a Consensus Statement from the Respiratory Care Experts' Input Forum (RC-EIF), Iran.

Challenges in the assessment, diagnosis and management of severe, difficult-to-control asthma are increasingly regarded as clinical needs yet unmet. The assessments required to determine asthma severity, comorbidities and confounding factors, disease phenotypes and optimal treatment are among the controversial issues in the field. The respiratory care experts' input forum (RC-EIF), comprised of an Iranian panel of experts, reviewed the definition, appraised the available guidelines and provided a consensus for evaluation and treatment of severe asthma in adults. A systematic literature review followed by discussions during and after the forum, yielded the present consensus. The expert panel used the appraisal of guidelines for research and evaluation-II (AGREE-II) protocol to define an initial locally-adapted strategy for the management of severe asthma. Severe asthma is considered a heterogeneous condition with various phenotypes. Issues such as assessment of difficult-to-control asthma, phenotyping, the use of blood and sputum eosinophil count, exhaled nitric oxide to guide therapy, the position of anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty as well as the use of established, recently-developed and evolving treatment approaches were discussed and unanimously agreed upon in the panel. A systematic approach is required to ensure proper diagnosis, evaluate compliance, and to identify comorbidities and triggering factors in severe asthma. Phenotyping helps select optimized treatment. The treatment approach laid down by the Global Initiative for Asthma (GINA) needs to be followed, while the benefit of using biological therapies should be weighed against the cost and safety concerns.

Impact of Adjunctive Therapy with Chlorellav ulgaris Extract on Antioxidant Status, Pulmonary Function, and Clinical Symptoms of Patients with Obstructive Pulmonary Diseases.

This present trial investigated the efficacy of supplementation with Chlorella vulgaris, a bioactive microalga rich in macro- and micronutrients, in the improvement of biochemical and clinical symptoms in patients with obstructive pulmonary disorders. Ninety-seven patients with chronic obstructive pulmonary disease (COPD) or asthma who were under conventional treatment regimens were randomly assigned to C. vulgaris extract (CVE) (n=48; 2700 mg/day) or no adjunctive therapy (n=49) for eight weeks. Serum levels of antioxidants along with spirometric parameters and clinical symptoms were evaluated pre- and post-trial. The magnitude of increases in the concentrations of glutathione, vitamin E, and vitamin C, and activities of glutathione peroxidase, catalase, and superoxide dismutase enzymes were all significantly greater in the CVE vs. control group (p<0.05). In spite of increases, none of the assessed spirometric parameters (FVC, FEV1, FEV1/FVC, and FEF(25-75%)) did significantly differ by the end of the trial in the study groups, apart from a significant elevation of FEV1 in the control group (p=0.03). The frequency of coughing, shortness of breath, wheezing, and sputum brought up were all significantly reduced in both CVE and control groups (p<0.05). The rate of improvement for sputum brought up and wheezing were significantly greater in the CVE group compared to the control group (p<0.05). Although CVE was found to ameliorate serum antioxidant status, its supplementation was not associated with any bronchodilatory activity. The results of the present trial do not support any clinical efficacy for CVE in patients with obstructive pulmonary disorders.

Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety.

BACKGROUND: Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to various antigens. Although influenza vaccination is recommended in pulmonary sarcoidosis, its efficacy and safety has not been investigated. OBJECTIVES: To evaluate safety and immunogenicity of influenza vaccine in patients with sarcoidosis. PATIENTS/METHODS: Influenza vaccination was performed in 23 eligible patients with sarcoidosis (SP) and 26 healthy controls (HC). Antibody titers against H1N1, H3N2, and B influenza virus antigens were evaluated just before and 1 month after vaccination. Patients were followed for 6 months to assess vaccine safety. RESULTS: Serological response and magnitude of changes in antibody titers against influenza vaccine antigens were comparable between SPs and HCs. Women showed a better serological response against B antigen (P = 0·034) than men. Twenty-four-hour urine calcium was associated with antibody response against H1N1 [correlation coefficient (CC) = 0·477, P = 0·003] and H3N2 (CC = 0·352, P = 0·028) antigens. Serum angiotensin-converting enzyme correlated negatively with antibody response against B antigen (CC = -0·331, P = 0·040). Higher residual volume was associated with fewer rises in antibody titer against H3N2 antigen (CC = -0·377, P = 0·035). No major adverse events or disease flare-up was observed during follow-up. CONCLUSIONS: In this study, influenza vaccination did not cause any major adverse event in SPs, and their serological response was equal to HCs. Studies with larger sample size and a broader selection of subjects could help validate the results of this study.

The Role of Fas-FasL Signaling Pathway in Induction of Apoptosis in Patients with Sulfur Mustard-Induced Chronic Bronchiolitis.

Sulfur mustard (SM) is an alkylating agent that induces apoptosis and necrosis in cells. Fas-Fas ligand (FasL) interaction could induce apoptosis as well. In this study, it was hypothesized that apoptosis might play an important role in the pathogenesis of SM-induced lung injury via Fas-FasL signaling pathway. In a case-control study, Fas and FasL levels, caspase-3 activity and percent of apoptotic cells were measured in bronchoalveolar lavage (BAL) fluid of patients 20 years after exposure to sulfur mustard and compared with the control group. Results show that Fas and FasL levels were significantly higher in BAL fluid cells in patients group compared with the control (P = .001). No significant differences were observed between mild and moderate-severe groups. BAL fluid cells caspase-3 activity was not significantly different among the mild, moderate-severe, and control groups. The data suggest that Fas-FasL-induced apoptosis was impaired in BAL fluid cells of SM-exposed patients which might be one of the initiators of pathogenesis in SM-induced lung injury in these patients.

E-selectin S128R polymorphism leads to severe asthma.

The E-selectin mediates the interaction of activated endothelial cells with leukocytes and plays a fundamental role in the pathogenesis of asthma. It has been suggested that an S/R (Serine128Arginine) polymorphism of E-selectin alters ligand binding function. Our purpose in this study was to determine whether this Serine128Arginine polymorphism influences the risk of asthma and also to analyze the possible correlation of disease severity in Iranian patients with polymorphism of E-selection. We studied human E-selectin gene polymorphism in 172 asthmatic patients and 173 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). To determine the severity of the asthma's situation, a questionnaire was prepared requesting the following information: age, sex, clinical signs and symptoms and past medical history. After the participants filled in the questionnaire, all active or ex-smoker patients were excluded. A trained observer assessed airway reversibility, peak flowmetry and spirometry in asthmatic patients. We found increased serum levels of soluble E-selectin (sE-selectin) in asthmatic patients compared with healthy subjects (P<0. 0001). Frequencies of the SS, SR, and RR genotypes were found as 66.3%, 31.4%, and 2.3% in the patients and 91.9%, 8.1%, and 0.0% in control subjects, respectively. The 128Arg allele was more prevalent in patients than controls (OR 5.78; 95% CI, 3.07-10.86, P<0.0001). However, in this study the polymorphism was not associated with circulating sE-selectin levels. We found a direct correlation between the level of sE-selectin and the severity of asthma (P=0.001). On the other hand, there was a close relation between 128Arginine carriage and disease severity (P<0.0001). These results suggest that the Ser128Arg polymorphism of the E-selectin gene is a genetic factor that may be associated with the severity of asthma.