Background: Coronavirus disease 2019 (COVID-19) is associated with significant morbidity and mortality, particularly in patients with underlying conditions such as diabetes mellitus. Zinc is an essential trace element with important immunomodulatory and antiviral properties, and zinc deficiency has been suggested to worsen outcomes in viral respiratory infections. However, the relationship between serum zinc levels and clinical outcomes in diabetic patients with COVID-19 remains insufficiently explored. Methods: This retrospective descriptive–analytical study was conducted on 158 diabetic patients hospitalized with confirmed COVID-19 at Shahid Sadoughi Hospital, Yazd, Iran. COVID-19 diagnosis was confirmed using RT-PCR and/or chest CT scan. Serum zinc levels were obtained from medical records, and patients were categorized into low zinc (<50 µg/dL) and normal zinc (50–70 µg/dL) groups. Clinical outcomes including ICU admission, intubation, length of hospital stay, and mortality were compared. Statistical analysis was performed using SPSS version 26. Results: Patients with low serum zinc levels were significantly older than those with normal zinc levels (p = 0.001). ICU admission (26.3% vs. 12.8%, p = 0.034) and mortality (27.5% vs. 7.7%, p = 0.001) were significantly higher in the low zinc group. Low serum zinc was associated with increased odds of ICU admission (OR = 2.42) and death (OR = 4.55). No significant differences were observed in intubation rates or length of hospital stay. Conclusion: Low serum zinc levels were associated with worse clinical outcomes, including higher ICU admission and mortality rates, in diabetic patients hospitalized with COVID-19. Assessment and correction of zinc deficiency may be beneficial in this high-risk population.

Background: This study aimed to evaluate the effect of pirfenidone on lung CT scan lesions in patients with severe COVID-19. Methods: In this cross-sectional study, data were extracted from the electronic medical records of patients with severe COVID-19 who received one of the following treatments: pirfenidone alone (n= 40), prednisolone alone (n= 55), pirfenidone combined with methylprednisolone (n= 18), or supportive care only (n= 32). Chest CT images taken at baseline and two months post-treatment were assessed by a trained radiologist. p< 0.05 was considered statistically significant. Results: The distribution of initial CT scan findings, Comparison of CT scan findings at admission and two months post-discharge, as well as the extent of pulmonary fibrosis and ground-glass opacity (GGO) grades across the groups, showed no statistically significant differences. However, significant differences were observed in CT scan findings and GGO grades between the four study groups at two months post-discharge. Moreover, in both the pirfenidone (p= 0.00) and supportive care (p= 0.01) groups, the extent of pulmonary fibrosis between admission and two months post-discharge showed statistically significant changes. Conclusion: In summary, although antifibrotic agents such as pirfenidone may not lead to significant improvement in lung CT scan findings in patients with severe COVID-19, they may help slow the progression of pulmonary fibrosis following the acute phase of the disease.

Host genetic variation influencing interferon-γ (IFN-γ) regulation is a critical determinant of immune heterogeneity in COVID-19. We investigated the functional IFNG +874T/A polymorphism (rs2430561), a key regulator of IFN-γ transcription, in 255 PCR-confirmed COVID-19 patients stratified as Outpatient (n = 103), Severe (n = 84), and Critical (n = 68). In parallel, systems-level transcriptomic analyses were conducted using publicly available GEO datasets, including pseudobulk RNA-sequencing of 406 peripheral blood mononuclear cell (PBMC) samples from GSE196198, GSE221066, and GSE300696, categorized into Outpatient (n = 162), Mild–Moderate (n = 140), and Severe–Critical (n = 104) groups, as well as single-nucleus RNA-sequencing of lung tissue from 20 COVID-19 decedents and 7 controls (GSE171524). Genotype-based analyses revealed no significant differences across clinical severity groups under multiple inheritance models. However, the IFNG +874T/A polymorphism showed significant associations with erythrocyte sedimentation rate under the co-dominant model (p = 0.03) and with hematological parameters, including an increased risk of leukopenia associated with the A allele (p = 0.006) and the AA genotype (p = 0.015). At the systemic level, PBMC-derived transcriptomes from Severe–Critical patients demonstrated coordinated upregulation of IFNG, its regulatory antisense transcript IFNG-AS1, and both IFN-γ receptor subunits (IFNGR1 and IFNGR2), indicating preserved transcriptional competence of the IFN-γ signaling axis as disease severity increased. In contrast, lung tissue transcriptomes from COVID-19 decedents did not exhibit parallel activation of the IFN-γ pathway and instead showed modest downregulation of IFNGR1, suggesting impaired tissue-level responsiveness to IFN-γ in advanced disease.

This study presents a detailed histopathological analysis of lung tissue from 44 deceased COVID19 patients, aiming to elucidate the mechanisms driving severe disease progression. Postmortem biopsies were systematically examined, revealing diffuse alveolar damage in 95.5% of cases, predominantly in the acute/exudative phase. Characteristic features included extensive hyaline membrane formation, alveolar septal thickening, fibrin deposition, and red blood cell extravasation. Notably, advanced fibrosis, indicative of ongoing tissue remodeling, was observed in 86.4% of cases, highlighting the chronic pathological impact of the disease. Patient demographics showed a predominance of older males with comorbidities such as hypertension and diabetes, aligning with known high-risk profiles. The methodology involved meticulous autopsy procedures and standardized histopathological assessments to ensure the reliability of findings. This study provides key insight into histological changes in the lungs of COVID-19 patients, helping to clarify the disease's progression. It provides valuable insights that may contribute to a better understanding of long COVID and the potential long-term pulmonary complications in these patients. These findings may ultimately support improved management approaches and therapeutic strategies for COVID-19 care.

Pulmonary trichomoniasis is an underdiagnosed disease. In most cases, there is an underlying clinical condition related to immunosuppression. The results of molecular biology techniques indicate that trichomonad infections have been significantly underestimated. A 7-year-old girl with a medical history of suspected juvenile rheumatoid arthritis presented with a fever, chills, and a productive cough. Her chest computed tomography scan indicated a pericardial effusion and consolidation in the left lower lobe. In direct microscopy of the bronchoalveolar lavage fluid, we identified a motile and flagellated organism. Based on the morphology, size, and rolling motility, we identified this organism as Trichomonas hominis. The patient's fever stopped after 3 days of intravenous metronidazole administration. In immunocompromised patients with evidence of pneumonia, sputum or bronchial samples should be examined more carefully. The possibility of unusual pathogens should be considered if they do not respond to antibacterial treatments.

PURPOSE:The study aimed to investigate the connection between an intronic variant in the ABO gene (rs657152) and the severity of COVID-19 in terms of clinical symptoms, haematological complications, inflammatory markers, and lung lesions. METHODS:After applying exclusion criteria, the study included 240 patients divided into 3 groups: 88 Outpatients, 84 Ward-hospitalized, and 68 ICU-admitted/failed patients. The tetra-ARMS PCR method was used to genotype ABO polymorphism in the patient. Paraclinical tests of patients at the time of admission (before receiving conventional treatments) included levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as a complete blood count (CBC). Also, the severity of lung lesions was evaluated based on the results of spiral computed tomography (CT) of the chest during admission. RESULTS:The statistical analysis using the ANOVA test revealed significant differences in the mean values of allele frequencies (p-value = 0.0020) and genotype proportions (p-value = 0.0017) among clinical groups. The study also found a notable difference in ABO polymorphism across different levels of the inflammatory marker CRP, but not with the ESR levels. Furthermore, the study showed a significant difference in the distribution of lung lesion severity and ABO polymorphism among different clinical groups. CONCLUSION:To conclude, our findings supported the substantial impact of ABO polymorphism rs657152 on the severity of COVID-19 in Iranian patients, specifically concerning haematological complications, inflammatory markers, and lung lesions. The study underscored the protective effect of the AC genotype and the detrimental impact of the CC genotype on clinical manifestations.

Background and aimsAllergic 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.MethodsExacerbation 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.ResultsExacerbation 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.ConclusionP043 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 registrationwww.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).

The study was designed to assess the association of ACE I/D polymorphism with the severity and prognosis of COVID-19 in the Iranian population. Hence, 186 adult patients were categorized into three clinical groups based on the severity of COVID-19: 1) Outpatients or mildly symptomatic patients as control ( n = 71); 2) Hospitalized patients or severe symptomatic cases ( n = 53); 3) Inpatients led to ICU/death or critically ill patients needed mechanical ventilation ( n = 62). The possible association of ACE I/D polymorphism with the risk of comorbidities and serum level of C-reactive protein was evaluated in two severe cases. The results showed that the frequency of D and I alleles are 69.35% and 30.65%, respectively, in the total population. The analysis of allelic frequencies via Fisher's exact test confirmed significantly higher frequency of D allele in both severe groups than that in the mild one, 78.31% in Hospitalized patients (OR = 2.56; 95% CI 1.46 to 4.46; p -value = 0.0011) and 74.19% in Inpatients led to ICU/death (OR = 2.04; 95% CI = 1.22 to 3.43; p -value = 0.0094) compared to 58.45% in Outpatients . The results of genotype proportions displayed an association between COVID-19 severity and DD genotype. Overall, our findings in Iranian patients supported the undeniable role of the DD genotype in the intensity of the disease, comparable to other populations. Furthermore, there is no definite evidence regarding the protective effect of the I allele in our inquiry.

Background:Asthma is one of the respiratory disorders caused by chronic airway inflammation. IL-4 has been identified as one of the participating interleukins in the severity of asthma.Objective:A case-control study was conducted to determine the association of rs1805010, a single nucleotide polymorphism in the interleukin 4 receptor α chain, with asthma and immunoglobulin E and IL-17A serum levels in Iranian populations.Methods:ELISA was used to investigate the relationship between three different varieties of SNP I50V and serum IL-17A levels, as well as total IgE levels. Based on GINA criteria, patients were classified into mild, moderate, and severe groups based on the association between SNP I50V, IL-17A, and total IgE. In order to analyze the data, the student-t-test and the one-way ANOVA were used.Results:The SNP I50V was associated with asthma in a significant way (p = 0.001). IL-17A and total IgE levels were significantly higher in asthmatic patients than in control participants (p 0.05 and p 0.021, respectively), but neither showed any association with SNP I50V in the asthmatic patients.Conclusion:Asthma patients have a higher prevalence of the I allele, reflecting the significance of Th2 cells. Although total IgE and IL-17A levels increased in both disease subgroups, total IgE level augmentation correlates directly with disease severity, while IL-17A level enhancement does not.

Desquamative interstitial pneumonia (DIP) is a form of interstitial lung disease that is directly related to smoking. In addition to smoking, other factors have been implicated in its etiology, including: systemic disorders, dangerous materials in the environment, drugs and infectious agents. By reviewing the literature, we find that there are very rare cases that indicate infections as causing DIP. Here the author report on a 58-year-old male who was addict and complained of a dry cough with dyspnea for one month. TBLB was performed and pathology result was consistent with DIP. He received prednisolone 5 mg twice a day, but his symptoms persisted. Open-lung biopsy was performed and it illustrated Aspergillus pneumonia (Chronic necrotizing aspergillosis). He was treated with corticosteroids combined with antifungal agents.

Introduction: Most mortality in COVID-19 cases was due to the increased inflammatory cytokines and cytokine storm. As mesenchymal stem cells (MSCs) possess immunomodulatory properties, this study assessed the therapeutic effects of placental MSC-derived extracellular vesicles on the inflammation and pulmonary injury caused by COVID-19. Methods: The study was carried out in phases I (safety study, 101 patients) and II (efficacy study, 80 patients) in a randomized, double-blind study at four hospital centers from April 2021 to August 2021. In addition to standard treatments, 15 mL of normal saline solution containing 15×109 vesicles was injected intravenously for five consecutive days. Results: No reaction or adverse events were observed in any patients. In the intervention group, after 5 days of treatment, patients’ clinical status and oxygenation improved, and 75% of patients presented an increased SpO2 after 5 days. Besides, inflammatory parameters assessment indicated a 21% decrease in neutrophil-lymphocyte ratio and a 54% reduction in C-reactive protein after day five of the intervention. Conclusion: PMSC-derived extracellular vesicles were safe and well-tolerated, down-regulated cytokine storms, and restored oxygenation. Thus, they can be considered a promising therapeutic candidate for severe COVID-19.

Background:Exposure to toxic materials predisposes the lungs to infectious agents and inflammatory responses. The present study was performed on patients with anthracosis caused by exposure to fossil fuels in previous years, and histopathological features of airways' normal-appearing tissue were compared with histopathological features of anthracotic plaques in these patients.Methods:Bronchoscopic evaluations were performed on bakery workers who were directly in contact with fossil fuels. Samples were taken from anthracotic plaques (Group A) or seemingly intact tissues at their periphery (Group B). Pathological evaluations were done after hematoxylin and eosin staining. Then, microbiological cultures were performed for the diagnosis of Mycobacterium tuberculosis. Data obtained from bronchoscopy, pathology, and cultures were compared between anthracotic and normal-appearing peripheral tissues using chi-square and analysis of variances (ANOVA) at a 95% confidence level.Results:Sixty-eight patients were diagnosed with anthracotic plaques. The mean ± SD of the patients' age was 72.12 ± 13.74 years. Females comprised 58.8% of the sample, and 85.3% of the patients were Iranian. The frequency rates of disseminated plaques and obstructive types were 86.8% and 48.5%, respectively. Ten patients (14.70%) were diagnosed with tuberculosis, and 4.41% (3 of 68) had granuloma, which was detectable only in samples gathered from Group A. Fibrosis was more common in Group A (10.3%, p = 0.03), and most of the evaluated samples in both groups exhibited inflammatory features.Conclusion:Inflammatory changes and tissue damage can be seen in anthracotic plaques and the surrounding normal-appearing tissue, even after removing the triggering factors. So, it is suggested to take a biopsy from seemingly intact tissue at the periphery of the anthracotic plaque when a biopsy is needed in a patient with anthracosis to reduce the risk of bleeding. Besides, medical treatment should be done to control inflammation.

Introduction: Over the past 20 years, seven coronaviruses have caused more or less severe respiratory diseases in humans. Among these, the most important ones are SARS-CoV and the coronavirus, a similar virus that has created a pandemic called Covid-19 since 2019, belonging to the b-category of beta-coronaviruses called Sarbecovirus. This virus is due to a kind of spike-like structure to the ACE2 receptor (angiotensin converting enzyme 2) bind to the surface of host cells. Often, dysfunction of ACE2 protease after viral infection leads to dysfunction of the RAAS (renin-angiotensin-aldosterone) pathway and, as a result, by affecting blood pressure, it upsets the balance of fluids and electrolytes in the body, a process that results in increased inflammation and permeability of arteries in the airways. Furthermore, the widespread release of cytokines by the immune cells in response to viral and/or secondary infections can lead to cytokine storms along with symptoms of sepsis. In these cases, uncontrolled inflammation causes multiple organ damage that leads to organ failure, particularly in cardiovascular, hepatic, and renal systems. Conclusion: Despite the findings of the pathogenic mechanism of SARS-CoV-2, there is still no specific drug to treat COVID-19. Therefore, achieving proper therapeutic strategies against COVID-19 requires a comprehensive understanding of its pathogenesis in the host for developing new drugs and/or using approved drugs.

Peripheral neuropathy may be reversible or permanent. Hence, we would like to present a 38-years-old man without any previous medical history admitted to ShahidSadoughi Hospital in Yazd in terms of reduced force of all four limbs, shortness of breath, cough and hemoptysis. Electromyography and nerve conduction velocity study was performed after the para-clinical examinations and Guillain–Barré syndrome was considered first diagnosis. Regarding the pulmonary symptoms, sinusitis and bilateral alveolar opacities, and positive anti-neutrophil cytoplasmic antibodies, Wegener's granulomatosis was suggested as a potential diagnosis and more steps were performed. This patient has been verified to have concurrent increasing limb weakness, also known as Guillain-Barré syndrome.

BACKGROUND:Asthma is a major source of global social and economic burden; thus, its early detection is important. Measurement of fractional exhaled nitric oxide (FENO) has been used recently considered a good indicator of asthma and also a sensitive and non-invasive method for monitoring airway inflammation. This study was conducted to determine the cut-off point of FENO for the diagnosis of asthma in the studied population.MATERIALS AND METHODS:The subjects of this cross-sectional diagnostic study were assessed by the FENO test, spirometry, and methacholine challenge test. The best cut-off point of the FENO for the diagnosis of asthma was determined. The data were analyzed by SPSS 20 using student t-test, and Chi-square test and the ROC curves were also drawn.RESULTS:The mean FENO in asthmatic and non-asthmatic subjects was 43.5±33.41 and 17.5±21.48 ppb, respectively (P <0.001). The best cut-off point of the FENO based on the overall sensitivity and specificity was 39.5 ppb.CONCLUSION:According to the results of this study, symptomatic patients with FENO higher than 39.5 ppb could be considered as asthmatic.

Objectives: Gold standard of anthracosis diagnosis is bronchoscopy. Many patients suffer from progressive pulmonary disease for many years after discontinuation of exposure to fossil fuel. We hypothesized that smoke inhalation of fossil fuels causes diffuse bronchi involvement and it acts like a foreign body inside the bronchi therefore the inflammation process will continue even in absence of exposure to fossil fuels. The goal of the study was to compare histopathological features of healthy appearing tissue of airways with anthracotic plaques in patients with anthracosis. Methods: Patients with anthracotic plaques during the bronchoscopy were included. Biopsies from anthracotic plaque and healthy appearance tissue of airway were taken. Histopathologic features of biopsies were evaluated. Data were analyzed by SPSS statistical software. Results: Mean age of 68 patients was 72.12± 13.74. Most of the patients were female. Acute inflammation was not significantly different in anthracotic and healthy appearance tissue. (P=0.368) Also, metaplasia was the same in both areas (P= 0.687). Fibrosis considerably was seen in anthracotic plaques (P=0.03). Conclusions: We have identified spreading involvement is present in whole part of airway in patients with anthracosis. Hence, treatment and control should be considered for preventing the progression of disease in patients with normal appearance airway.

Background: Black dust deposited in the lungs is called anthracosis. By damaging bronchial mucosa, anthracosis can affect the mucociliary cleaning function. Initial reports indicate that there is a relationship between anthracosis and pulmonary tuberculosis. Due to obstructive effects of anthracosis on distal airways and disruption in a proper sampling of bronchoalveolar lavage (BAL), other diagnostic methods are necessary for estimating the tuberculosis prevalence in these patients. The aims of this study was to evaluate tissue samples adjacent to an anthracotic plaque for acid-fast bacilli smear and culture. Methods: his is a cross-sectional analysis study on 100 patients referred to Shahid Sadoughi Hospital who required bronchoscopy and anthracotic plaque based on bronchoscopy results. Bronchial fluid lavage, two biopsy samples for culture, and a smear of Mycobacterium tuberculosis from the surrounding of these plaques were prepared. Data analyses were carried out using SPSS (version 18). Results: One-hundred patients og the age range 46-91years were studied. The patients with tuberculosis diagnosis based on the smear of BAL and bronchial tissue samples and culture of BAL and bronchial tissue samples were 7%, 13%, 6% and 8% respectively. The presence of granuloma in histopathology was seen in 15 patients infected with tuberculosis. (κ > 0.04, p-value <0.05). In patients with positive tuberculosis, culture of bronchoalveolar lavage was superior to other methods. Conclusions: Diagnostic value of BAL method and tissue biopsy in anthracosis patients with tuberculosis did not show a statistically significant difference. As compared with other methods, BAL culture was more positive. Therefore, tissue biopsy is not a good alternative to BAL.

Introduction: About 50% of patients with metastatic cancers suffer from malignant pleural effusion. The goals of treatment for these patients should be to relieve pain, restore normal function, reduce or eliminate hospitalization, and make efficient use of medical care resources. Objectives: This study aimed to evaluate the effect of negative pressure suction on the success rate of pleurodesis with bleomycin on malignant pleural effusion. Patients and Methods: This study was conducted as before-after interventional study, without randomization. For all patients, 1 mg/kg bleomycin diluted with 50 mL distilled water, was injected into the chest tube. After changing the position of the patient, the clamp was opened and the tube was connected to the central suction with two chest bottles. The negative pressure suction was 20 cmH2O. Before intervention and four weeks after the intervention, a simple decubitus lateral chest X-ray was taken and the amount of malignant pleural effusion was assessed and compared with the amount of pleural effusion before the insertion of the chest tube. If the pleural effusion level was greater than 10 mm from the outer part of the chest, pleurodesis was considered unsuccessful Results: The mean age of patients was 60.44 ± 10.48 years (32-79 years); of which 12 patients (48%) were male. The most common cancer was lung cancer (48%). The success rate of treatment with bleomycin accompanied by negative pressure suction was 80% without a significant relationship with age, gender and type of cancer. Additionally, the results showed the improvement of the respiratory status and the pain level after the pleurodesis. The only side effect after bleomycin injection was fever in 84% of patients. Conclusion: Bleomycin treatment accompanied by negative pressure suction can improve malignant pleural effusion and this method is recommended for these patients.

OBJECTIVE:To evaluate the action of 2% lidocaine on the culture results of bronchial fluid in patients suspected of having lower respiratory tract infections.STUDY DESIGN:Cross-sectional analytical study.PLACE AND DURATION OF STUDY:Shahid Sadoughi Hospital, Yazd, Iran, from November 2014 to November 2015.METHODOLOGY:Patients suspected of lower respiratory tract infections referred to bronchoscopy unit of the Hospital were included. Those with incomplete questionnaire and bronchoscopy contraindication were excluded. Bronchial fluid was aspirated before and after local application of 2% lidocaine and cultured, according to the suspected clinical diagnosis. Finally, statistical analysis was performed using SPSS software, version 17.0. For statistical comparisons, McNemar's test was used. Level of significance was kept at p <0.05.RESULTS:The mean age of the study population was 51.83 ±15.93 with a range of 25 - 80 years. Out of 130 patients, 60 patients had positive culture results. Nineteen (31.7%) cases had positive culture for tuberculosis and 41 (63.3%) cases had positive results for other bacteria before intervention that did not change after using 2% lidocaine (p=1). In 70 (53.84%) cases, results were negative before and after use of 2% lidocaine.CONCLUSION:No significant difference was found between culture results before and after the use of lidocaine. Therefore, lidocaine can be used during bronchoscopy to increase patient tolerance.

Article history Received 2 Feb 2015 Accepted 18 Apr 2015 Available online 11 May 2015