Elevated interleukin (IL)-6 as a predictor of disease severity among Covid-19 patients: a prospective cohort study.

BACKGROUND: accompanied to the spreading of coronavirus disease 2019 (Covid-19) in the world, identifying factors related to the severity of the disease is one of the interests of physician and medical researchers. We hypothesized that interleukin 6 serum level is associated with severe outcome. METHODS: In this longitudinal prospective cohort study we enrolled 208 confirmed COVID-19 patients who were admitted to the Tohid Hospital (Sanandaj, Iran). Patients were classified into two groups based on IL-6 value in the first day of admission, elevated (n = 107) or not elevated/normal (n = 101), and followed until the occurrence of final outcome (death or discharge from the hospital). Data were analyzed using univariate methods, Chi-squared and independent two sample T test. The relationship between the independent variables and our interesting outcomes were investigated by multiple linear and penalized logistic regression modeling. RESULTS: A total of 208 patients, 51% female and mean age 53.6 ± 16.3 years, including 107 elevated and 101 non-elevated IL-6 patients, were followed. No significant difference was observed between the two groups in demographic and clinical characteristics. Although not significant, logistic regression results showed that the chance of death occurrence among patients with elevated IL-6 are 3.91 times higher. According to the multiple linear regression modeling, elevated IL-6 significantly increased the duration of hospital stay (P = 0.02). Frequency of ICU admission (P = 0.04) and mean of ICU stay (P = 0.8) are also higher in elevated IL-6 group. CONCLUSION: This study revealed that elevated IL-6 is significantly related to prolongation of hospital stay in Covid-19 patients. Although not significant, the occurrence of death among patients who had increased IL-6 in the time of admission was higher than patients with normal or lower serum levels of IL-6.

The risk profile of patients with COVID-19 as predictors of lung lesions severity and mortality-Development and validation of a prediction model.

Objective: We developed and validated a prediction model based on individuals' risk profiles to predict the severity of lung involvement and death in patients hospitalized with coronavirus disease 2019 (COVID-19) infection. Methods: In this retrospective study, we studied hospitalized COVID-19 patients with data on chest CT scans performed during hospital stay (February 2020-April 2021) in a training dataset (TD) (n = 2,251) and an external validation dataset (eVD) (n = 993). We used the most relevant demographical, clinical, and laboratory variables (n = 25) as potential predictors of COVID-19-related outcomes. The primary and secondary endpoints were the severity of lung involvement quantified as mild (≤25%), moderate (26-50%), severe (>50%), and in-hospital death, respectively. We applied random forest (RF) classifier, a machine learning technique, and multivariable logistic regression analysis to study our objectives. Results: In the TD and the eVD, respectively, the mean [standard deviation (SD)] age was 57.9 (18.0) and 52.4 (17.6) years; patients with severe lung involvement [n (%):185 (8.2) and 116 (11.7)] were significantly older [mean (SD) age: 64.2 (16.9), and 56.2 (18.9)] than the other two groups (mild and moderate). The mortality rate was higher in patients with severe (64.9 and 38.8%) compared to moderate (5.5 and 12.4%) and mild (2.3 and 7.1%) lung involvement. The RF analysis showed age, C reactive protein (CRP) levels, and duration of hospitalizations as the three most important predictors of lung involvement severity at the time of the first CT examination. Multivariable logistic regression analysis showed a significant strong association between the extent of the severity of lung involvement (continuous variable) and death; adjusted odds ratio (OR): 9.3; 95% CI: 7.1-12.1 in the TD and 2.6 (1.8-3.5) in the eVD. Conclusion: In hospitalized patients with COVID-19, the severity of lung involvement is a strong predictor of death. Age, CRP levels, and duration of hospitalizations are the most important predictors of severe lung involvement. A simple prediction model based on available clinical and imaging data provides a validated tool that predicts the severity of lung involvement and death probability among hospitalized patients with COVID-19.

Serum level of stem cell factor and its soluble receptor in aspirin-exacerbated respiratory disease.

Aim: Stem cell factor (SCF) may be associated with inflammatory processes leading to aspirin-induced asthma. This study evaluated the relationship between serum level of SCF and its soluble receptor with aspirin-induced asthma. Methods & materials: Twenty-five patients and 25 healthy controls were enrolled in this study. The concentration of SCF and mast/stem cell growth factor receptor (C-kit) was determined in serum samples. Spirometry and rhinometry were performed to determine the severity of the disease. p < 0.05 were considered significant. Results: The serum levels of SCF and C-kit receptor were significantly higher in the case group. The serum SCF and C-kit level had a significant positive correlation with the severity of asthma, disease duration and nasal obstruction. Conclusion: Our findings suggest that SCF and C-kit receptors have a direct effect on the severity of aspirin-induced asthma.

Comparative Network Analysis of Patients with Non-Small Cell Lung Cancer and Smokers for Representing Potential Therapeutic Targets.

Cigarette smoking is the leading cause of lung cancer worldwide. In this study, we evaluated the serum autoantibody (AAb) repertoires of non-small cell lung cancer (NSCLC) patients and smokers (SM), leading to the identification of overactivated pathways and hubs involved in the pathogenesis of NSCLC. Surface- and solution-phase biopanning were performed on immunoglobulin G purified from the sera of NSCLC and SM groups. In total, 20 NSCLC- and 12 SM-specific peptides were detected, which were used to generate NSCLC and SM protein datasets. NSCLC- and SM-related proteins were visualized using STRING and Gephi, and their modules were analyzed using Enrichr. By integrating the overrepresented pathways such as pathways in cancer, epithelial growth factor receptor, c-Met, interleukin-4 (IL-4) and IL-6 signaling pathways, along with a set of proteins (e.g. phospholipase D (PLD), IL-4 receptor, IL-17 receptor, laminins, collagens, and mucins) into the PLD pathway and inflammatory cytokines network as the most critical events in both groups, two super networks were made to elucidate new aspects of NSCLC pathogenesis and to determine the influence of cigarette smoking on tumour formation. Taken together, assessment of the AAb repertoires using a systems biology approach can delineate the hidden events involved in various disorders.

What Do We Know about Anthracofibrosis? A Literature Review.

Recently, the significance of anthracosis in the tracheobronchial tree, lung parenchyma, and even non-respiratory organs has been postulated and discussed in association with other diseases, especially tuberculosis. We reviewed the current literature by using the following key words in Medline/PubMed, Embase, and Google Scholar databases: anthracosis, anthracofibrosis, anthracotic bronchitis, biomass fuels, and mixed-dust pneumoconiosis. The bibliographies of eligible papers were also reviewed for further relevant articles. A total of 37 studies were assessed. The content of these studies was then divided into specific categories. Considering the pathogenesis, along with histopathological, radiological, and bronchoscopic results regarding anthracotic lesions, we suggest these findings be defined as "ANTHRACOSIS SYNDROME". For the first time, we describe a syndrome involving black pigmentation, which was previously thought to involve only the tracheobronchial tree. Until recently, it was not considered to be a single syndrome with different sites of involvement.

Soluble CD93 as a Novel Biomarker in Asthma Exacerbation.

Asthma research is shifting from studying symptoms and lung functions to the narrow-focus cellular profiles protein analysis, biomarkers, and genetic markers. The transmembrane glycoprotein CD93 is involved in endothelial cell migration, angiogenesis, leukocytes extravasation, apoptosis, innate immunity and inflammation. Relationships between the serum level of soluble CD93 (sCD93) and acute myocardial infarction/premature MI/inflammatory arthritis/skin sclerosis have recently been reported. We hypothesized that sCD93 would be elevated during the acute phase of asthma. We measured the serum level of sCD93 in 57 patients with asthma exacerbation and 57 age-and gender-matched healthy controls. Additionally, sCD93 was reassessed at the time of discharge from the hospital. Clinical characteristics and peak expiratory flow (PEF) of the patients were assessed. The primary outcome was the comparison of serum level of sCD93 between asthmatics and healthy subjects. The sCD93 values ranged from 128 to 789 ng/mL in asthmatics (345.83±115.81) and from 31 to 289 ng/mL in control subjects (169.46±62.43). The difference between the 2 groups was statistically significant (P<0.001). The association between sCD93 and asthma remained significant after adjusting for age, sex, and BMI. The differences between asthmatics and controls remained significant on the last day of hospital stay. The association between sCD93 and PEF was not significant. In conclusion, the serum level of soluble CD93 is increased in patients with asthma exacerbation. It also showed that serum levels of sCD93 decreased with treatment of asthma attack. The clinical usefulness of determination of sCD93 as a biomarker of asthma requires further studies.

Bronchoalveolar galactomannan in invasive pulmonary aspergillosis: a prospective study in pediatric patients.

BACKGROUND: Elevations in the number of immunocompromised patients in the past decade has lead to progressive increase in the incidence of Invasive Pulmonary Aspergillosis (IPA) among children; however, early diagnosis remains a challenge. Detection of galactomannan (GM) in the bronchoalveolar lavage (BAL) fluid appears to possess higher sensitivity and specificity than serum in immunocompromised adult patients but, it rarely has been investigated in pediatric patients. METHODS: We performed a prospective case-control study to evaluate the efficacy of BAL GM in immunocompromised pediatric patients. Cases were subjects fulfilling the host factor criteria as defined by the EORTC/MSG and met established definitions for proven or probable IPA. Control group was patients with possible IPA in whom diagnoses other than IPA were confirmed and patients without risk factors of IPA who underwent bronchoscopy for other diagnostic purpose. Galactomannan testing was performed on BAL fluid samples using platelia Aspergillus seroassay. RESULTS: Sixteen cases of IPA (4 proven, 12 probable) and 54 controls (6 possible IPA and 48 no IPA) were documented according to EORTC/MSG definitions. The sensitivity and positive predictive values of BAL GM using an OD index of ≥0.5 were 87.5% and 93.33% respectively. We found seven cases of IPA with negative serum GM while their BAL GM was positive. CONCLUSION: We found high diagnostic value of BAL GM in immunocompromised pediatric patients with IPA. The lower OD index is necessary in children to avoid missing the cases of IPA in children.

Anti-cyclic citrullinated peptide (CCP) antibody in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) without rheumatoid arthritis.

Citrullination, a post-translational modification of proteins, is increased in inflammatory processes and is known to occur in smokers. It can induce anti-cyclic citrullinated peptide (CCP) antibodies, the most specific serologic marker for rheumatoid arthritis. Thus far, the incidence of autoimmunity in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) resulting in anti-CCP production has not been examined. We hypothesise that anti-CCP antibody level in these patients should be higher than that in healthy subjects. A total of 112 non-rheumatoid arthritis patients, including 56 patients with wood-smoke-induced COPD and 56 patients with tobacco-induced COPD, and 56 healthy non-smoker controls were included. The serum anti-CCP antibody levels were measured and compared between the groups and against smoke exposure and clinical characteristics. The mean anti-CCP antibody levels in wood-smoke-induced COPD group were significantly higher than those in tobacco-induced COPD group (p = 0.03) and controls (p = 0.004). Furthermore, 8 (14.2 %) patients with wood-smoke-induced COPD, 4 (7.14 %) with tobacco-induced COPD and 2 (3.57 %) controls exceeded the conventional cut-off of anti-CCP antibody positivity. No relationship was found between the anti-CCP antibody level and age, gender, duration of disease, Pack-years of smoking, and duration of exposure to wood smoke. Moreover, correlations between anti-CCP antibodies and severity of airflow limitation, CAT scores, mMRC scores of dyspnoea, and GOLD staging of COPD severity were not significant. Wood-smoke-induced COPD could significantly increase the anti-CCP antibody level in non-rheumatoid arthritis patients when compared with that in patients with tobacco-induced COPD and healthy controls.

Reliability and validity of Persian version of perceived stress scale (PSS-10) in adults with asthma.

BACKGROUND: Asthma is a major public health problem in the world, and recent findings suggest that stress influences asthma and asthma morbidity. The 10-item Perceived Stress Scale (PSS-10) is one of the most frequently used instruments to measure psychological stress. This study was conducted to evaluate the psychometric properties of the Persian versions of the PSS-10 in adults with asthma. METHODS: In this descriptive cross-sectional study as a methodological research, 106 asthmatic patients referring to several clinics in Sanandaj (western Iran) were selected through convenience sampling. The PSS-10 and the 21-item Depression anxiety and stress scale (DASS-21) were administrated to all patients. Cronbach's alpha was used to evaluate reliability of PSS-10, and confirmatory factor analysis (CFA) and convergent validity were used to evaluate its validity. RESULTS: The results of confirmatory factor analysis indicated that a two-factor structure of PSS-10 provided a good fit to data. The Cronbach's alpha coefficients for negative factor, positive factor and total score (PSS-10) were 0.86, 0.83, and 0.90, respectively. The PSS-10 was positively correlated with the DASS-21 and its subscales, indicating an acceptable convergent validity. Female asthmatic patients scored higher on PSS-10 in comparison with male asthmatic patients. CONCLUSION: The Persian version of PSS-10 is a valid and reliable instrument to measure perceived stress in adults with asthma.

Determination of the best prognostic value of serum tumor markers in patients with suspected lung cancer in an Iranian population.

BACKGROUND: Finding a suitable marker with high sensitivity and specificity for early diagnosis of cancer is very desirable. This study was aimed to determine the diagnostic value of serum CYFRA21-1, carcinoembryonic antigen (CEA), and neuron-specific enolase (NSE) for screening of lung cancer patients in western Iran. METHODS: This descriptive analytical case-control study was performed on 30 subjects with malignant and 81 with benign lung cancer. Serum levels of CYFRA21-1, CEA, and NSE were determined. RESULTS: The concentration of serum tumor markers was significantly higher in the malignant group than in the benign subjects. The highest sensitivity was obtained by measurement of serum NSE (73%). The highest specificity was obtained by measurement of serum CYFRA21-1 (95%). CONCLUSIONS: Our results demonstrate the usefulness of measuring CYFRA21-1 and NSE together for early screening of lung cancer in western Iran.

First presentation of a case of pulmonary alveolar microlithiasis with spontaneous pneumothorax.

Pulmonary Alveolar Microlithiasis (PAM) is a rare disease of unknown origin. It is characterized by the presence of small calculi within the alveolar spaces, and has various clinical manifestations. Some patients may be asymptomatic for a long period of time with subsequent occurrence of dyspnea, dry cough, chest pain, and eventually, respiratory failure. Recurrent spontaneous pneumothorax episodes are a late complication of the disease. We report the case of an alveolar microlithiasis episode in a 42-year-old male, admitted to Tohid Hospital, Iran, whose first clinical presentation was symptoms of pneumothorax. He was admitted with sudden onset dyspnea and right-sided pleuretic chest pain. Following treatment of pneumothorax after chest tube placement, the pulmonary function revealed normal indices, and chest radiograph demonstrated diffuse confluence of dense micronodular infiltrate. High-resolution computerized tomography scan showed diffuse ground glass attenuation and calcifications along the interlobular septa and subpleural regions. Transbronchial lung biopsy confirmed the diagnosis of PAM.

Diagnostic value of serum adenosine deaminase level in pulmonary tuberculosis.

BACKGROUND: In some studies, the level of adenosine deaminase (ADA) in sputum and effusion liquids was used for the diagnosis of tuberculosis (TB). But it is not always possible to access these materials. The goal of this study is to assess the diagnostic value of serum ADA levels in pulmonary TB patients. MATERIALS AND METHODS: In this study, 40 sputum smear-positive TB patients who were hospitalized and 40 non-TB patients who referred for surgeries were selected. A serum sample was collected and serum ADA level was measured by ADA kit. RESULTS: The average (SD) of serum ADA in TB and non-TB patients were 20.88 (±5.97) and 10.69 (±2.98) U/L, respectively (P value < 0.05). The best cut-off point was 14 U/L. The calculated area under the receiver operating characteristic (ROC) curve was 0.955 (95% CI, 0.914-0.995); sensitivity was 92.7% (95% CI, 84.7-100) and specificity was 88.1% (95% CI, 78.3-97.8) (P < 0.001). CONCLUSION: Serum ADA level may be proposed as a proper index for TB diagnosis.

Correlation between hs-CRP and Asthma Control Indices.

BACKGROUND: Local and systemic inflammation occur at the same time in asthma and high sensitive CRP may play a role in the pathogenesis of this disease. Conventional approaches to monitor and control asthma involve no direct assessment of airway inflammation. There are some recent data postulating a discrepancy between the markers of airway and systemic inflammation and asthma control test (ACT) scores. In this study we evaluate the correlation between the serum levels of hs-CRP in patients with different levels of asthma control based on ACT scores and spirometric indices. MATERIALS AND METHODS: The validated Persian version of ACT was administered to one-hundred asthmatic patients. Spirometry was performed and prebronchodilatory FEV1 was measured. Blood samples for CRP measurement were taken and hs-CRP levels were analyzed. Fifty age-matched healthy volunteers comprised the control group. RESULTS: A total of 100 asthmatic patients (57 females and 43 males) and 50 controls were participated. hs-CRP in asthmatics was higher than in controls. No significant differences were found in hs-CRP levels in patients with different levels of asthma control based on ACT (≥20, 16-19, ≤15), GINA classification of asthma control (well controlled, partly controlled, uncontrolled) or FEV1. CONCLUSION: We found no correlation between degree of systemic inflammation estimated by hs-CRP and other clinical indices of asthma control such as ACT scores, FEV1 and GINA classification of asthma control and even in patients with clinical and spirometric indices of controlled asthma, markers of systemic inflammation were still present.

Validation of Persian Version of Asthma Control Test Based on new Global Initiative for Asthma Guidelines.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: The Persian version of Asthma Control Test is a valid and reliable test for asthma control assessment.

Anthracosis and anthracofibrosis.

OBJECTIVE: To define the clinical, radiographic, and bronchoscopic features, and to describe the occupations of the largest group of patients with anthracosis. METHODS: All patients who underwent flexible bronchoscopy at 2 Iranian hospitals (Imam Hospital [Tehran], and Tohid Hospital [Sanandaj]), Iran, between April 1982 and June 2006 were considered for inclusion in the study. The demographic data, clinical, and radiographic findings of anthracotic and anthracofibrotic patients were recorded. RESULTS: Of the 14,300 patients, 487 cases of simple anthracosis, and 291 of anthracofibrosis were found. A total of 98.4% female patients were housewives, and 86.4% lived in rural areas. Of the male patients, 40.6% were farmers, 29.6% were manual workers, and 7.5% were miners. Of these, 96% of patients had abnormal chest radiography. On bronchoscopic examination, bilateral bronchial involvement was found in 62.5% of the patients. The condition was confined to the trachea in 0.38% of patients, the bronchi involved were the main bronchus in 37%, the lobar bronchi in 83.2%, and segmental bronchi in 35%. Bronchial narrowing and obstruction was observed in 37.4% of the patients. CONCLUSION: Anthracosis and anthracofibrosis are neglected conditions that are a common finding on routine bronchoscopic examination. Given the demographic findings, and a review of other reports from developing countries, exposure to combustion of biomass fuel in rural areas is a possible risk factor.

Prevalence of asthma and rhinitis in bakery workers in the city of Sanandaj, Iran.

Baker's asthma is one of the most common forms of occupational asthma. This study was conducted to determine prevalence of asthma and rhinitis among bakery workers in the city of Sanandaj, the provincial center of Kurdistan province in the west of Iran in the in Summer 2006. In this study 776 bread bakery workers were included. These subjects were selected randomly among 1620 bakery workers. The diagnosis of asthma was based on a medical history of episodic symptoms of cough, chest tightness, and dyspnea and spirometry. Airflow obstruction was determined with spirometry, the definition of airflow obstruction which was used in this study was an FEV1/FVC ratio < 0.8, and FEV1 or FVC increases of > or = 12 percent and at least 200 mL after using a short-acting inhaled beta2-agonist. Rhinitis was diagnosed by typical history of work related symptoms. Analyses were performed on 776 subjects (all were men) without missing data for asthma and rhinitis. All of subjects were male with mean age of 33.69+/-11.09 years. Mean duration of bakery working for these subjects was 13.91+/-9.37 years. Prevalence of asthma at the time of study was 11.9%. 93 subjects were diagnosed as asthma with history, physical and spirometry findings. 31 (33.3%) of asthmatic workers were diagnosed as asthma previously and 62 (66.6%) workers were known as new asthmatic patients which were diagnosed in this study program. The prevalence of rhinitis was (9.9%). Subjects with asthma had longer history of working at bakery than others (P=0.001). Asthma prevalence among these bakery workers that were included in our study was similar and in some instances the prevalence was lower than other studies.