Tanaffos Respiration Journal
Volume:21 Issue: 2, Spring 2022

The 2019 novel coronavirus (SARS-CoV-2) causes severe pneumonia called COVID-19 and leads to severe acute respiratory syndrome with a high mortality rate. The SARS-CoV-2 virus in the human body leads to jumpstarting immune reactions and multi-organ inflammation, which has poorer outcomes in the presence of predisposing conditions, including hypertension, dyslipidemia, dysglycemia, abnormal adiposity, and even endothelial dysfunction via biomolecular mechanisms. In addition, leucopenia, hypoxemia, and high levels of both cytokines and chemokines in the acute phase of this disease, as well as some abnormalities in chest CT images, were reported in most patients. The spike protein in SARS-CoV-2, the primary cell surface protein, helps the virus anchor and enter the human host cells. Additionally, new mutations have mainly happened for spike protein, which has promoted the infection's transmissibility and severity, which may influence manufactured vaccines’ efficacy. The exact mechanisms of the pathogenesis, besides molecular aspects of COVID-19 related to the disease stages, are not well known. The altered molecular functions in the case of immune responses, including T CD4+, CD8+, and NK cells, besides the overactivity in other components and outstanding factors in cytokines like interleukin-2, were involved in severe cases of SARS-CoV-2. Accordingly, it is highly needed to identify the SARS-CoV-2 bio-molecular characteristics to help identify the pathogenesis of COVID-19. This study aimed to investigate the bio-molecular aspects of SARS-CoV-2 infection, focusing on novel SARS-CoV-2 variants and their effects on vaccine efficacy.

Considering the increased prevalence of asthma and its consequences for individuals and society, its effective management and close monitoring is essential. Awareness of the effects of telemedicine can improve asthma management. The present study aimed to systematically review articles examining the effect of telemedicine on the management of asthma, including control of the symptom, patients’ quality of life, costs, and adherence to treatment programs.

A systematic search was performed on four databases: PubMed, Web of Science, Embase, and Scopus. English language clinical trials investigating the effectiveness of telemedicine in asthma management published from 2005 to 2018 were selected and retrieved. The present study was designed and conducted based on the PRISMA guidelines.

Out of 33 articles included in this research, telemedicine was employed by 23 studies for the promotion of patient adherence to treatment in the form of reminders and feedback, by 18 for telemonitoring and communicating with healthcare providers, by six for offering remote patient education, and by five for counseling. The most frequently used telemedicine approach was asynchronous (used in 21 articles), and the most commonly utilized tool was Web-based (utilized in 11 articles).

Telemedicine can improve symptom control, patients’ quality of life, and adherence to treatment programs. However, little evidence exists confirming the effectiveness of telemedicine in decreasing costs.

Considering the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, which causes coronavirus disease 2019 (COVID-19), we aimed to report the clinical features of 427 patients with COVID-19 and the outcomes after one-month admission to major teaching hospitals in the northeast of Iran. Data of patients hospitalized with COVID-19 from 20 February 2020 to 20 April 2020 was analyzed using the R software. The cases and their outcomes were monitored up to one month following their admission. Among 427 patients with a median age of 53 years (50.8% male), 81 (19%) were directly admitted to the ICU ward, and 68 (16%) died during the study. The mean (SD) lengths of hospital stay were significantly higher in the non-survivors (6 (9) days) than survivors (4 (5) days) (P = 0.018). Ventilation need was reported in 67.6% of the non-survivors and 0.8% of the survivors (P < 0.001). Cough (72.8%), fever (69.3%), and dyspnea (64.0%) were the most common symptoms. There were more comorbidities in the severe cases (73.5%) and non-survivor (77.5%). Liver and kidney damage were significantly more common in non-survivors. Ninety percent of the patients had at least one abnormal chest CT scan finding, including crazy paving and consolidation patterns (27.1%), followed by the ground-glass opacity (24.7%). Results showed that the patients’ age, underlying comorbidities, levels of SpO2, and laboratory findings at the time of admission may predict the progress of the disease and can be considered mortality-related factors.

Ecological studies showed that countries with national Bacillus Calmette-Guerin (BCG) vaccination programs for tuberculosis prevention reported lower incidences of severe and fatal COVID-19 than countries without such programs. Several studies have demonstrated that the BCG vaccine can induce long-term trained Immunity in bone marrow progenitor cells. In this study, we tried to evaluate the relationship between tuberculin skin test results, BCG scar, and COVID-19 outcomes among patients with confirmed COVID-19.
This was a cross-sectional study. Cases included 160 patients with confirmed COVID-19 in Zahedan hospitals (southeast Iran) in 2020, selected by convenient sampling. PPD test was performed for all patients through the intradermal technique. Collected data included demographic information, underlying conditions, PPD test results, and COVID-19 outcome. Analysis was conducted utilizing ANOVA, χ2 test, and multivariate analysis (logistic regression).
The univariate analysis showed a positive relationship between older age, having underlying diseases, and positive tuberculin skin test results with the outcome of COVID-19. We also found a lower frequency of BCG scar among patients with death outcomes than recovered ones. In the multivariate analysis by logistic regression through the backward method, only age and underlying diseases remained predictors of death.
Tuberculin test results might be dependent on age and underlying conditions. Our study did not show relationship between BCG vaccine and mortality in COVID-19 patients. Further investigations in different settings are required to reveal the efficacy of the BCG vaccine in preventing this devastating disease.

The risk for transmission of COVID-19 to people in close contact with infected people, especially healthcare workers, has not been well estimated. Therefore the present study was conducted to assess the household secondary attack rate (SAR) of COVID-19 among healthcare workers and related factors.
The present prospective case-ascertained study was conducted on 202 healthcare workers with confirmed COVID-19 in Hamadan, diagnosed from March 1, 2020, to August 20, 2020. For households with close contact with the index case, RT-PCR was performed regardless of symptoms. We defined SAR as the proportion of secondary cases from the total contacts that live in the index case household. SAR was reported as a percentage and 95% confidence interval (CI). Multiple logistic regression was performed to explore the predictors of COVID-19 transmission of index cases to their households.
We found 36 secondary cases out of 391 household contacts with laboratory confirmation (RT-PCR), representing a household SAR of 9.2% (95% CI: 6.3, 12.1). Among factors related to the family member, female gender (OR: 2.9, 95% CI: 1.2, 6.9), being the patient's spouse (OR: 2.2, 95% CI: 1.0, 4.6), and living in the apartment (OR: 2.78, 95% CI: 1.24, 6.23), and among factors related to index cases, hospitalization (OR: 5.9, 95% CI: 1.3, 26.9) and caught (OR: 2.4, 95% CI: 1.1, 5.2) were the significant predictors of disease transmission to other family members (P<0.05).
The findings of this study suggest that the SAR is remarkable in household contacts of infected healthcare workers. Some characteristics of family members of the index case, including female gender, being the patient's spouse, and living in the apartment, and some characteristics of the index case, including hospitalization and caught, were associated with the increased SAR.

Many individuals with chronic obstructive pulmonary disease (COPD) report suffering from chronic pain, which affects their quality of life. This study aimed to determine the prevalence, characteristics and impact of chronic pain in patients with COPD, and to explore its possible predictive and aggravating factors.
It was a cross-sectional study. Male individuals with COPD responded to a questionnaire, including mMRC, CAT, Brief Pain Inventory (BPI) (composed of Worst pain, Pain Severity Score (PSS) and Pain Interference Score (PIS)), and Hospital Anxiety and Depression Scale. Patients were divided into group 1 (G1) with chronic pain, and group 2 (G2) without chronic pain.
Sixty eight patients were included. The general prevalence of chronic pain was 72.1% (CI95%:10.7%). The most common site of pain was the chest (54.4%). Analgesics were used in 38.8%. Patients from G1 had more hospital admissions in the past (OR=6.4[1.7–23.4]). Three variables were associated to pain in the multivariate analysis: socio-economic level (OR=4.6[1.1–19.2]), hospital admissions (OR=0.087[0.017–0.45]), and CAT (OR=0.18[0.05– 0.72]). Dyspnea was associated to PIS (p<0.005). A correlation was found between PSS and PIS (r=0.73). Six patients (8.8%) retired because of pain. Patients who had CAT≥10 were more in G1 (OR=4.9[1.6–15.7]). CAT was correlated to PIS (r=0.5). G1 demonstrated higher anxiety scores (p<0.05). There was a moderate positive correlation between depression symptoms and PIS (r=0.33).
Pain should be systematically assessed in COPD patients, regarding its high prevalence. New guidelines should take into consideration pain management to ameliorate patients' quality of life.

Many efforts were made to determine the uncommon clinical complications after lung transplantation and treatment options to tackle them; however, many of these rare complications have not been mentioned in recent publications. Evaluating and recording adverse effects after organ transplantation can significantly prevent post-transplant mortality. This study aimed to examine rejection factors by examining individuals undergoing lung transplantation surgery. In a prospective longitudinal study, we followed up on complications of 60 lung recipients post lung-transplantation surgery for six years from 2010 to 2018. All complications were recorded in follow-up visits or hospital admissions during these years. Finally, the patients' information was categorized and evaluated by designing a questionnaire. From a total of 60 transplant recipients, from 2010 to 2018, 58 patients were initially enrolled in our study, but two were lost to follow-up. Uncommon complications witnessed in the post-transplantation period included endogenous endophthalmitis, herpetic keratitis, duodenal strongyloidiasis, intestinal cryptosporidiosis, myocardial infarction, diaphragm dysfunction, Chylothorax, thyroid nodule, and necrotizing pancreatitis. Meticulous postoperative surveillance is crucial for managing lung transplant patients for early detection and treatment of common and uncommon complications. Therefore, it is necessary to establish procedures for assessing the patients' constancy until complete recovery.

The outcome of coronavirus disease 2019 (COVID-19) is complicated by various comorbidities; asthma, a common chronic disease, may be considered one of these conditions. This study aimed to investigate the effect of asthma as a potential comorbid condition on the COVID-19 prognosis.
This retrospective study included all RT-PCR confirmed COVID-19 cases recorded on the Shiraz health department's electronic database from January to May 2020. A questionnaire was designed to collect information about patients' demographics, their history of asthma and other comorbidities, and the severity of COVID-19 by contacting them by phone.
Of 3163 COVID-19 patients, 109 (3.4%) had self-reported asthma with a mean age of 42.7 ± 19.1 years. Most patients (98%) had mild-to-moderate asthma, while 2% had severe disease. Among asthmatic patients, fourteen (12.8%) were admitted to the hospital, and five (4.6%) died. Univariate logistic regression results showed that asthma had no significant effect on hospitalization (OR 0.95, 95% CI: 0.54-1.63) and mortality (OR 1.18, 95% CI: 0.48-2.94) in patients with COVID-19. Compared living and deceased patients with COVID-19, the pooled OR was 18.2 (95% CI: 7.3–40.1) for cancer, 13.5 (95% CI: 8.2–22.5) for age 40-70 years, 3.1 (95% CI: 2–4.8) for hypertension, 3.1 (95% CI: 1.8–5.3) for cardiac disease and 2.1 (95% CI: 1.3–3.5) for diabetes mellitus.
This study showed that asthma is not associated with an increased risk of hospitalization and mortality in patients with COVID-19. Further studies are needed to investigate the risk of different asthma phenotypes on the severity of COVID-19 disease.

The two main pillars of asthma management include regular follow-up and using guidelines in the treatment process. Patient portals enable regular follow-up of disease, and guideline-based decision-support-systems can improve the use of guidelines in the treatment process. Based on the Global Initiative for Asthma (GINA) and Snell’s drug interaction, asthma management system in primary care (AMSPC) includes the capabilities of both mentioned systems. This system was developed to improve regular follow-up and use GINA in the asthma management process. This study aimed to assess the accuracy and usability of the AMSPC based on the GINA and Snell’s drug interaction. To assess the accuracy of the system, kappa test was used to calculate the degree of agreement between the suggestions made by the system and the physician’s decision for a total of 64 patients selected through convenience sampling method. To assess usability, the Questionnaire for User Interface Satisfaction (QUIS) was used. The scores of the Kappa for the agreements between the system and the physician in determining “drug type and dosage”, “follow-up time”, and “drug interactions” were 0.90, 0.94, and 0.94, respectively. The average score of the QUIS was 8.6 out of 9. Due to the high accuracy of the system in computerizing the GINA and Snell’s drug interaction, as well as its proper usability, it is expected that the system be widely used to improve asthma management and reduce drug interactions.

Cancer is one of the leading causes of morbidity and mortality around the world. Caregivers of these patients are affected by various physical, emotional, social, spiritual, and financial factors that can affect their quality of life (QoL). This study aimed to compare the QoL and general health status of thoracic cancer patients with their family caregivers in Iranian population.
Using the City of Hope-Quality of Life (COH-QOL) questionnaire and the General Health Status (GHQ) questionnaire, this cross-sectional study compared the QoL and general health status in 71 thoracic cancer patients with their family members as the primary caregivers. The study was conducted in Masih Daneshvari Hospital of Tehran, Iran from 2017 to 2018. Demographic data and results of the questionnaires were analyzed using the Statistical Package for the Social Sciences (SPSS v.20). Student’s t-test, Chi square test, and Pearson’s correlation were used to compare the results.
In patients and their caregivers, 53.5% (N=38) and 36.6% (N=26) were male, respectively (P=0.043). While the average score of physical wellbeing was 6.12 ± 1.95 in caregivers, it was 5.32 ± 2.08 in patients (P=0.021). In case of psychological wellbeing, the average score in caregivers was 4.14 ± 1.50 and in patients was 5.7 ± 1.54 (P=0.000). We observed no significant difference between caregivers and patients regarding social concerns (4.62 ± 1.50 vs. 4.90 ± 1.74) and spiritual wellbeing (7.03 ± 1.17 vs. 7.2 ± 1.53). Also, the mean scores of GHQ-12 were 5.06 ± 2.5 and 4.17 ± 2.53 in caregivers and patients, respectively (P=0.04). A significant negative correlation was observed between GHQ-12 and QoL scores (r=-0.593, P<0.001). The probability of acquiring mental disorders in female caregivers was two times higher than male caregivers (P=0.05).
Our findings demonstrated that family caregivers of thoracic cancer patients suffer from physical and psychological distress, sometimes even more than the patients. This highlights the important role of family caregivers in the process of approaching a patient with thoracic cancer.

Flexible bronchoscopy is an aerosol-generating procedure (AGP), which increases the risk of transmission of SARS-CoV-2 infection. We aimed to find COVID-19 symptoms among healthcare workers (HCWs) involved in flexible bronchoscopies for non-COVID-19 indications during the SARS-CoV-2 pandemic.
The participants of this hospital-based single-center descriptive study were HCWs of our hospital involved in flexible bronchoscopies of patients with non-COVID-19 indications. These patients had no clinical features of COVID-19 and were tested negative for SARS-CoV-2 by the real-time polymerase chain reaction of nasopharyngeal and throat swabs before the procedure. The study outcome was the occurrence of COVID-19 in study participants after exposure to bronchoscopies.
Thirteen HCWs performed 81 bronchoscopies on 62 patients. Indications for bronchoscopies included malignancy (61.30%), suspected infections (19.35%), non-resolving pneumonia (6.45%), mucus plug removal (6.45%), central airway obstruction (4.84%), and hemoptysis (1.61%). The mean age of patients was 50.44 ± 15.00 years, and the majority was males (72.58%). Bronchoscopic procedures included 51 bronchoalveolar lavages, 32 endobronchial ultrasound- transbronchial needle aspiration (EBUS-TBNA), 26 endobronchial biopsies, 10 transbronchial lung biopsy (TBLB), 3 mucus plug removals, 2 conventional TBNA, and 2 radial EBUS-TBLB. Except for two HCWs who complained of transient throat irritation of non-infectious cause, none of the cases developed any clinical features suggestive of COVID-19.
A dedicated bronchoscopy protocol helps in minimizing the risk of transmission of SARS-CoV-2 infection among HCWs involved in flexible bronchoscopies for non-COVID-19 indications during the SARS-CoV-2 pandemic.

Reviewing the laboratory studies, we observe some drugs with other specified applications, which cause serious inhibitory immune responses in the body. Selective Serotonin Reuptake Inhibitors (SSRIs) are among these drugs. Therefore, the current research aimed to evaluate the effectiveness of one of the SSRI drugs called fluvoxamine on the cytokine levels in COVID-19 patients.
The current research included 80 patients with COVID-19 hospitalized in ICU in Massih Daneshvari Hospital. They were entered into the research by an accessible method of sampling and then divided into two groups randomly. One of the groups underwent the treatment with fluvoxamine as the experimental group and the other group did not receive fluvoxamine as the control group. Interleukin-6 (IL-6) and CRP levels were measured before the onset of fluvoxamine consumption and when discharging from the hospital in all members of the sample group.
The current study showed that IL-6 levels increased, while CRP levels decreased in the experimental group significantly (P-value≤ 0.01). After consuming fluvoxamine, IL-6 and CRP levels were higher and lower in the females compared to the males, respectively.
Considering the effectiveness of fluvoxamine on IL-6 and CRP in COVID-19 patients, it may ultimately come true to use this drug to improve both psychological and physical conditions simultaneously and leave the COVID-19 pandemic behind with less pathology.

Tuberculosis is the most common worldwide cause of death from microbial diseases. Extra-pulmonary tuberculosis accounts for 20% to 25% of all cases. In this study, we used generalized estimation equations to investigate the trend of changes in extra-pulmonary tuberculosis incidence.
The recorded data of all patients with extra-pulmonary tuberculosis from 2015 to 2019 in Iran’s National Tuberculosis Registration Center were included. The trend of standardized incidence changes in provinces of Iran was calculated and reported linearly. Also, we identified the risk factors related to the extra-pulmonary tuberculosis incidence in five consecutive years using generalized estimating equations.
We studied the data of 12,537 patients with extra-pulmonary tuberculosis, of whom 50.3% were female. The mean age of the subjects was 43.61±19.88 years. Around 15.4% of all patients had a history of contact with a tuberculosis patient, 43% had a history of hospital stay, and 2.6% had a human immunodeficiency virus infection. Regarding disease types, 25% were lymphatic, 22% were pleural, and 14% were bone. Golestan province had the highest (average of 28.50 ± 8.65 cases), and Fars province had the lowest (average of 3.06 ± 0.75 cases) standardized incidences in these five years. Also, time trend (P ˂ 0.001), employment rate (P = 0.037), and average annual rural income (P = 0.001) had a significant effect on reducing extra-pulmonary tuberculosis incidence.
Extra-pulmonary tuberculosis has a decreasing trend in Iran. Still, Golestan, Sistan and Baluchestan, Hormozgan, and Khuzestan provinces have a higher incidence rate compared to the other provinces.

Asthma is one of the most common chronic diseases that cause respiratory problems. Different training programs can effectively alleviate its symptoms and minimize the complications. This study aimed to determine the effect of a training program on asthma control.
This interventional study was performed on patients referred to clinics affiliated with Shiraz University of Medical Sciences. Cases were selected by convenience sampling and divided into two intervention and control groups, each consisting of 29 patients. Before the training program, data were collected using an asthma control questionnaire and a spirometry test, and they were analyzed using statistical tests and software.
The results showed that after the intervention, the mean of all spirometry test indices and asthma control scores of the questionnaire increased in the experimental group. Alterations in the mean scores of the clinical manifestations and spirometry indices (FEV1, FVC, FEV1/FVC, and FEF25%-75%) before and after the intervention in the experimental group were significant. After the intervention, all spirometry indices were increased in the experimental group compared to the control group (p<0.05).
The results showed the effectiveness of teach-back training in managing asthmatic patients. Therefore, this intervention can be used as an effective method to control asthma along with other methods such as exercise and medications.

Anabolic-androgenic steroids (AAS) are one of the ingredients of herbal and dietary supplements that are popular among sports trainers. AAS abuse predisposes everyone to several complications. Reviews of the literature on AAS users have shown mainly skin, renal, and hepatic complications. In this case report, we presented a case with simultaneous complications, including diffuse alveolar hemorrhage (DAH), acute respiratory distress syndrome (ARDS), pericardial effusion, gastrointestinal bleeding (GIB), and acute kidney injury (AKI). Given the potential for lethal complications and the consequences of ethical, civil, and criminal law, it seems that specific policies will be considered for the use of bodybuilding drugs. It is also suggested that this approach be added as a new part of the medical curriculum. Also, ARDS and DAH are unreported side effects in other studies, which is suggested to be considered by specialists.

Pulmonary artery sling is a rare condition in which the left pulmonary artery anomalously originates from a normally positioned right pulmonary artery. The left pulmonary artery arises anterior to the right main bronchus, courses between the trachea and esophagus then enters the left hilum. Respiratory symptoms such as wheezing, stridor, cough, and dysphasia are common in this anomaly.

We describe a 16-month-old male infant presenting recurrent cough, stridor, and wheezing from early infancy. He underwent computed tomography angiography, bronchoscopy, and transthoracic echocardiography, confirming the left pulmonary artery sling diagnosis. Surgical correction of pulmonary artery sling was successfully performed as a new anastomosis between the main pulmonary artery and the left pulmonary artery, as well as tracheoplasty. The infant was discharged without any complications. Follow-up after two years revealed no respiratory symptoms and feeding difficulty.

In the presence of chronic cough, stridor, recurrent wheezing, and other prolonged respiratory symptoms, investigation for possible detection of pulmonary artery sling is recommended.

Bleomycin is a unique antibiotic agent with cytotoxic activity and is used successfully in various malignant diseases, such as Hodgkin lymphoma and germ cell tumors. Drug-induced lung injury (DILI) is one of the major limitations of bleomycin administration in particular clinical settings. The incidence varies among patients and depends on a variety of risk factors, such as cumulative drug dose, underlying malignant disease, and concurrent radiation. The clinical presentations are non-specific for bleomycin-induced lung injury (BILI), depending on the onset and severity of symptoms. There is no established guideline for the best treatment of DILI and the treatment is based on the time and severity of pulmonary symptoms. It is important to consider BILI in any patient with pulmonary clinical manifestations who has been treated with bleomycin. 
Here, we report a 19-year-old woman who is a known case of Hodgkin lymphoma. She was treated with a bleomycin-containing chemotherapy regimen. On the 5th month of therapy, she was admitted to hospital with severe acute pulmonary symptoms and decreased oxygen saturation. She was treated successfully with high-dose corticosteroid without any significant sequelae.

The SARS-CoV-2 invades the cells by attachment of virus spike proteins (S1, S2) to cell membrane and engages angiotensin-converting enzyme 2 (ACE2), which is highly expressed in the epithelium of cerebral vasculature. Here, we describe a patient with encephalitis following SARS-CoV-2 infection.

A 77-year-old male patient presented with mild cough and coryza lasting for eight days without a prior history of underlying disease or neurologic disorder. Oxygen saturation (SatO2) was decreased and behavioral changes, confusion, and headaches were started within three days prior to admission. Bilateral ground glass opacifications and consolidations were noted on chest CT scan. Lymphopenia, highly elevated D-Dimer and ferritin were noted in laboratory results. Brain CT and MRI showed no changes regarding encephalitis. Cerebrospinal fluid was collected as the symptoms persisted. The results of SARS-CoV-2 RNA RT-PCR from CSF and nasopharyngeal samples were positive. The combination therapy with remdesivir, interferon beta-1alpha and methylprednisolone was started. Due to deterioration of the patient’s status and SatO2, he was admitted to the ICU and intubated. Tocilizumab, dexamethasone, and mannitol were started. The patient was extubated on the 16th day of ICU admission. The patient’s level of consciousness and SatO2 were improved. He was discharged from the hospital a week later.

RT-PCR of CSF sample along with brain imaging can help with diagnosis when encephalitis due to SARS-CoV-2 is suspected. However, no changes regarding encephalitis may be seen on brain CT or MRI. Combination therapy with antivirals, interferon beta, corticosteroids, and tocilizumab can help patients recover in these conditions.