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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). [ABSTRACT FROM AUTHOR]

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 antipneumococcal 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. [ABSTRACT FROM AUTHOR]

Background: An increase in the serum levels of creatine phosphokinase (CPK) could be associated with an unfavorable clinical outcome in coronavirus disease (COVID-19) patients; however, detailed information on this association is scarce. The aim of this study was to investigate upon admission CPK serum level and its relationship with the degree of involvement in chest computed tomography (CT) scans and hypoxia in patients with COVID-19. Methods: This cross-sectional survey was conducted on 191 COVID-19 patients who were referred to a major respiratory referral center in Tehran, Iran, in 2019. CPK serum level, oxygen saturation, blood pressure, temperature, and severity of lung involvement (based on lung CT scan) were measured. The severity of lung involvement in cuts of CT imaging was reported with a score between 1 and 4. The descriptive and relational statistics were conducted using Pearson's correlation coefficient and one-way analysis of variance. Results: The average age of the patients was 55.22 ± 15.39 years, and the male was predominant in gender (65.4%). There was a statistically significant relationship between CPK serum level and the severity of lung involvement in patients with COVID-19 (P = 0.04). Furthermore, a significant and reverse correlation was observed between CPK serum level and oxygen saturation in the patients (r = –0.160, P = 0.04). Conclusion: The results of this study showed that COVID-19 patients with elevated CPK levels upon admission are prone to more severe lung involvement, worsening oxygenation, and respiratory failure. Hence, considering the initial critical care strategies for such patients could be of the essence. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD), as an autoimmune disorder, is associated with chronic relapsing inflammation of intestine. UC and CD are associated with gastrointestinal and extra-intestinal symptoms, which may vary in severity of clinical presentation. This study was designed to evaluate airway resistance and pulmonary volumes and capacities in the active phase of UC and CD. Materials and Methods: Patients who had IBD and referred to Shahid Modarres Hospital from February 2016 to December 2017 were assessed for enrollment in our study. Diagnosis of Crohn's disease or ulcerative colitis was confirmed by colonoscopic and pathological evaluations. Pulmonary respiratory parameters including first second of forced expiration (FEV1), forced vital capacity (FVC), residual volume (RV), total lung capacity (TLC), forced expiratory flow between 25% and 75% (FEF25-75%), and airway resistance were measured by plethysmography in the first days of admission in patients with stable IBD and also immediately after an initial stabilization of the vital signs in patients with unstable IBD. Data were analyzed using SPSS software (v.21. IBM Inc. IL). P value less than 0.05 was considered as statistically significant. Results: Of 75 patients with IBD, 65 had UC and 10 had CD. The mean ages of the patients with UC and CD were 37.81 ± 13.31 and 34.20 ± 8.53 years, respectively. Of all the participants, approximately 54.7% and 45.3% of the patients were male and female, respectively. The duration of disease for patients with UC and CD was 43.09 ± 45.86 and 44.40 ± 15.45 months, respectively. Based on the Pearson correlation analysis, there were significant associations between FEV1, TLC, and FEF25-75% with the duration of UC and also between FEV1, RV, and airway resistance with the duration of CD. In patients with CD but not in the patients with UC, there were statistical relationships between FEV1, FVC, FEV1/FVC, RV, RV/TLC, FEF25-75% and increased airway resistance with severity and activation of IBD. Conclusion: According to our findings, pulmonary involvements were found often in patients with IBD with and without the presence of clinical pulmonary symptoms. The duration and also activation and severity of IBD can be associated with increased risk for pulmonary involvements. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 extrapulmonary 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%), groundglass 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 FEF25-75%) 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 broncho-dilatory activity. The results of the present trial do not support any clinical efficacy for CVE in patients with obstructive pulmonary disorders. [ABSTRACT FROM AUTHOR]

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 showthat 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. [ABSTRACT FROM AUTHOR]

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.

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.