Tanaffos Respiration Journal
Volume:21 Issue: 3, Summer 2022

Idiopathic Pulmonary Fibrosis (IPF) is a lung disease characterized by formation of fibroblast foci and honeycomb lesions in the pulmonary parenchyma. The physiopathological mechanisms involved in the development of fibrosis and architectural disorganization are still imperfectly elucidated. In fact, lesion formation is irreversible and no treatment, to date, has been shown to be effective (30% of patients die within 5 years of the onset of the disease). The long-held concept of chronic inflammation leading to fibrosis is still controversial. Indeed, recent data suggest that the physiopathology of this disease is the product of fibroblast dysfunction rather than the result of an inflammatory imbalance. This concept supports the parallel involvement of three main factors:  epithelial damage, angiogenesis and oxidative stress. In this review we highlighted the different factors and the ethiopathogenic pathways involved in the fibrotic process, in order to increase our understanding of the mechanisms involved in this pulmonary pathology.

Smoking is a preventable cause of morbidity and mortality with an increasing prevalence in developing countries. The present systematic review and meta-analysis aimed to estimate the prevalence of smoking among college and high school students in Iran.

Databases of Scopus, PubMed, Web of Science, Google Scholar, SID, and MagIran were searched with no time limitation. Observational studies published in Persian or English were included in the analysis. Time frame of the searches was from inception until 1 January 2021. The data was analyzed using random effects model, subgroup analysis, and meta-regression analysis. Heterogeneity among studies was examined using Cochran's Q test and I2 statistic.

A total of 63 articles with a sample size of 58742 were analyzed. The pooled smoking prevalence was found to be 13.56% (95% CI: 11.65-15.47). There was a significant increase in the prevalence of smoking among female students between 1998 and 2020. Regions 1 of Iran had the highest prevalence rates of smoking (Provinces of Alborz, Tehran, Qazvin, Mazandaran, Semnan, Golestan, and Qom). Smoking was more prevalent among college students (15.62%, 95% CI: 13.14-18.10) than in high school students (9.77%, 95% CI: 7.19-12.35).

Given the relatively high prevalence of smoking among Iranian college and high school students, it is necessary to inform them about the harmful effects of smoking through training programs.

This review aimed to identify the features of coronavirus disease 2019 (COVID-19) in pediatric patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. According to the literature, the incidence of COVID-19 was reported to be 1-5% among children. However, the incidence of infection with the new variant of the virus is higher in children. The most common features were fever and respiratory manifestation. The milder severity and lower mortality of COVID-19 among children are related to their less contact, immature immune system, and different features of angiotensin-converting enzyme 2 (ACE2), an important receptor of the virus to invade the host cells. Several complications were observed in severe pediatric patients, such as coinfections, encephalitis, multisystem inflammatory syndrome, and multiorgan failure. The most frequent laboratory data were the procalcitonin elevation. The enhanced inflammatory factors and lymphocytopenia were less common among this population. In the CT findings, the ground‐glass opacities, pulmonary consolidation, fine mesh shadow, and tiny nodules were most common. While some children were admitted to the ICU, mechanical ventilation was rarely reported. The vertical intrauterine transmission from mother to child has not been proven. The treatment mainly focuses on maintaining balance in the fluids and electrolytes, nutritional support, and oxygen therapy for this vulnerable population.

Although many aspects of the COVID-19 disease have not yet been clarified, dysregulation of the immune system may play a crucial role in the progression of the disease. In this study, the lymphocyte subsets were evaluated in patients with different severities of COVID-19. In this prospective study, the frequencies of peripheral lymphocyte subsets (CD3+, CD4+, and CD8+ T cells; CD19+ and CD20+ B cells; CD16+/CD56+ NK cells, and CD4+/CD25+/FOXP3+ regulatory T cells) were evaluated in 67 patients with confirmed COVID-19 on the first day of their admission. The mean age of patients was 51.3 ± 14.8 years. Thirty-two patients (47.8%) were classified as severe cases, and 11 (16.4%) were categorized as critical. The frequencies of blood lymphocytes, CD3+ cells, CD25+FOXP3+ T cells, and absolute count of CD3+ T cells, CD25+FOXP3+ T cells, CD4+ T cells, CD8+ T cells, and CD16+56+ lymphocytes were lower in more severe cases compared to the milder patients. The percentages of lymphocytes, T cells, and NK cells were significantly lower in the deceased patients. (p= 0.002 and p= 0.042, p=0.006, respectively). Findings of this cohort study demonstrated that the frequencies of CD4+, CD8+, CD25+FOXP3+ T cells, and NK cells differed in the severe cases of COVID-19. Moreover, lower frequency of T cells and NK cells could be predictors of mortality in these patients.

The therapeutic options for patients with interstitial lung disease (ILD) are limited. On the other hand, the role of noninvasive ventilation (NIV) in ILD management is not clear. This study investigated the effect of nighttime NIV in hypercapnic ILD patients.
In this unblinded randomized clinical trial, we included a total of 20 ILD patients admitted in a specialized center with hypoxia, PaCO2>45, and HCO3>27. Participants were randomly allocated into two groups; intervention (nighttime NIV plus standard treatment) and control (standard treatment). The severity of dyspnea and the quality of life (QoL) was evaluated at beginning of the trial and after 30 days through Modified medical research council (mMRC) dyspnea scale and the SF-36 health survey questionnaire. Paired or Wilcoxon Signed rank tests and independent samples t-test or Mann-Whiney U test were used for between and within groups analyses, respectively.
The mean age of 20 patients enrolled was 62.57±6.67 and 40% were male. Although, a clinical significant improvement of dyspnea was detected in NIV group (P=0.046) after intervention, it was not statistically different from control group. Significant improvement was observed in physical functioning (P<0.001), social functioning (P=0.004) and pain (P=0.003) detected after 30 days in NIV group and the observed improvement in QoL was significantly higher than control group for physical functioning (P=0.042) and general health (0.049).
Our results suggest NIV treatment in patients with ILD and hypercapnic respiratory failure could be advised in order to improve physical functioning.

Acute exacerbation events, which can develop during the natural course of chronic obstructive pulmonary disease (COPD) can lead to worsening quality of life, increased hospital costs, and higher rates of morbidity and mortality. In recent years, individuals at heightened risk of COPD exacerbations have been said to display a so-called "frequent exacerbator (FE)" phenotype, defined as having two or more exacerbation events (or ≥ 1 exacerbation with a hospitalization) within 1 year.
We conducted a retrospective study involving 299 patients with COPD. Patients were divided into 2 groups as non-exacerbator phenotype (group-1, n=195) and FE phenotype (group-2, n=104).
FE phenotype was identified in 35.1% of patients. There were no significant differences between these two phenotypes in terms of gender, smoking status, or leukocyte count. However, FEs were found to be older (p=0.04), with more frequent detection of emphysema (p=0.02) and lower eosinophil levels (p=0.02). FEs also demonstrated worse pulmonary function parameters.
COPD patients with the FE phenotype likely require a different treatment algorithm due to differing clinical features such as poorer respiratory function, lower eosinophil levels, and more frequent emphysema.

The objective of this research is to analyze influenza-induced complications, symptoms, and the interaction of morbidity and mortality rates in hospitalized influenza cases based on age-sex dispersion, influenza virus subtype, prescribed medications, and underlying conditions.
We performed this retrospective study using a dataset of 10,517 hospitalized individuals, including 3,101 laboratory-confirmed influenza cases from patients of all ages who had attended hospitals in the Northwest of Iran due to respiratory complications.
The most prevalent strain which circulated annually was influenza A/H3N2. In contrast to previous studies, our findings suggested that influenza A/H1N1 has the highest mortality rate and the most severe complications.
Regardless of virus type/subtype, the most susceptible age group for influenza was 0-9 years old in both males and females. Meanwhile the high-risk age group among males was 50-59 years old and among females were over 80 age group (mortality rate ≈ 20%). Chronic obstructive pulmonary disease (COPD) (32%) and cardiovascular disease (CVD) (30%) were the most prevalent active underlying diseases among the patients who died, with the latter being more prevalent in males over the age of 70. Patients with a history of chemotherapy had the highest mortality rate. Patients who were prescribed a combination of antibiotics and antivirals had better outcomes with lowest mortality rate.
Our findings demonstrated that annual influenza seasons are often marked by changes in influenza types and subtypes, with variations in the severity. Development of a standardized set of arrays that best correspond with infections, can be useful in guiding diagnostic and therapeutic decisions.

Unmeasured confounding is the primary obstacle to causal inference in observational research. We aimed to illuminate the association between exposure to influenza vaccination (IV) within six months before contracting the coronavirus disease (COVID-19) and COVID-19 hospitalization in relation to unmeasured confounding using the E-value method.

Information about 367 patients, 103 of whom (28.07 %) had received IV, and confounders included sex, age, occupation, cigarette smoking, opium, and comorbidities were collected. We estimated the interest association using the inverse probability weighted (IPW) method. There was no information on some potential unmeasured confounders, such as socio-economic status. Therefore, we computed E-value as a sensitivity analysis, which is the minimum strength of unmeasured confounding to explain away an exposure-outcome association beyond the measured confounders completely.

IPW denoted 1.12 (95% CI: 0.71 to 1.29) times greater risk of COVID-19 hospitalization in patients exposed to IV than in unexposed individuals. Sensitivity analysis demonstrated that an E-value (95% CI) of 1.49 (1.90 to 2.15) is required to shift the RR and the corresponding confidence Interval (CI) lower and upper limits toward the null. Moreover, if they had been omitted, the most computed E-values for measured confounders were relatively larger than for unmeasured confounders.

According to the context of the measured confounders, if they had been omitted, an E-value of 1.16 to 1.76, a weaker confounding could fully explain away the reported association, suggesting that no relationship exists between IV and COVID-19 hospitalization.

Chronic obstructive pulmonary disease (COPD) as one of the health-threatening problems imposes many economic costs on health systems. Today, there is a greater tendency to use complementary and alternative therapies in the treatment of diseases. This study aimed to evaluate the efficacy of a Persian herbal formulation in patients with COPD.
This randomized clinical trial was conducted on 76 patients with mild-severe COPD assigned to 2 groups (in each group n=38) for 8 weeks. The interventional group received Compound Honey Syrup (CHS), consisting of combination of honey and extracts of five medicinal plants (i.e., ginger, cinnamon, saffron, cardamom, and galangal) and the control group received a placebo. The COPD Assessment Test (CAT), St George's Respiratory Questionnaire (SGRQ), and lung function test were used before and after.
Seventy-six patients, 88.6% male and 55.7% under 60 years of age, completed the course of treatment. At the end of the study, the overall score of the CAT questionnaire was significantly different between the first and fourth week (P=0.029). Meanwhile the findings of SGRQ questionnaire were significantly different between the interventional and control groups at other times (P=0.001). FEV1 and FEV1/FVC were found to be significantly different between two groups in weeks 4 and 8 (P <0.05). At the end of the study, no side effects of CHS were reported.
Based on the data presented herein, CHS could be effective as a complementary and safe drug in increasing the quality of life of with COPD.

Patients undergoing bronchoscopy often suffer from pain, coughing, and suffocation. Therefore, lidocaine is prescribed through various methods to induce local anesthesia. This study aimed to compare nebulized lidocaine and intratracheally injected lidocaine in pain and cough reduction during bronchoscopy.

This clinical trial was performed on 96 patients, divided into two groups of intervention (receiving lidocaine via a nebulizer before bronchoscopy) and control (receiving lidocaine through the working channel of bronchoscope). Then, the patients᾽ cough frequency was recorded during the procedure, and the pain level was measured using a numerical rating scale at the end of the procedure. The data were analyzed with SPSS software (version 16) using the chi-square and Fisher's exact tests. Moreover, the linear and Poisson regression tests were applied to analyze the main variables in this study.

There was no significant difference between the two groups regarding demographic characteristics (P>0.05). Moreover, the linear regression test revealed that the intervention (nebulized lidocaine) group had significantly lower pain scores (1.54±0.08) than the control (intratracheally injected lidocaine) group (2.5±0.26) (P=0.013). In addition, the Poisson regression test showed a statistically significant difference between the intervention (35.22±2.93) and control (48.85±5.96) groups in terms of cough frequency (P<0.0001).

This study indicated that nebulized lidocaine has higher efficacy in reducing the patients᾽ pain and cough during bronchoscopy than intratracheally injected lidocaine.

Foreign body aspiration can be a life-threatening incidence amongst children. The aim of this study was to evaluate the usefulness and outcomes of foreign body removal with emphasis on accuracy of flexible fiberoptic bronchoscopy and the predictors of post- procedure complications in children.

Records of patients who had undergone flexible fiberoptic bronchoscopy for foreign body extraction in Namazi Hospital affiliated to Shiraz University of Medical Sciences from 2012 to 2017 were retrospectively reviewed.

109 patients in whom foreign body were detected by flexible fiberoptic bronchoscopy were enrolled. The patients' age range was between 10 days to 16 years, with the male predominance and the peak incidence amongst toddlers aged 1 to 2 years. The majority of foreign body were situated in the left main bronchus (22.9%). Coughing (37.5%) and chocking (20.8%) were the most commonly recorded symptoms. Hyperinflation (63.5%) and lung collapse (19.2%) were the most radiological findings. The duration of the procedure for 50.5% of the patients was 5-8 minutes. No complications were recorded during the flexible fiberoptic bronchoscopy procedure. Ninety-five percent of the patients had more than one visit before their admission for bronchoscopy with incorrect diagnosis of asthma/reactive airway disease and pneumonia, 74 and 20%, respectively.

Although rigid bronchoscopy is still considered as the gold standard and preferred method in managing the airways foreign bodies, flexible fiberoptic bronchoscopy also can be used as an effective diagnostic and therapeutic tool with high success.

Difficult Intubation (DI) is a constant concern for anesthesiologists and being able to predict it will improve patient safety. Different tests have been presented in anesthesiology practice to increase the accuracy of the DI prediction. Since there is no single sensitive and specific test, most of the practitioners use a combination of them. Here we report a new and novel index of ratio of height to rhinion-mentum distance (RHRMD) to improve the prediction.
Four hundred adult patients’ candidate for elective surgery were enrolled into the study. Initially, patients’ data such as weight, height and rhinion-mentum distance (RMD) were recorded by the first anesthesiologist. After anesthesia induction, the second anesthesiologist performed laryngoscopy and recorded the Cormack-Lehane (CL) score. CL score III or higher was considered as DI. Finally, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for RHRMD was calculated.
DI was reported in 7.75% of patients. RHRMD is related with CL grade: as the former increased, the latter decreased. RHRMD with cut-off point 25.4 has 90.6% sensitivity, 29.9% specificity, 10.1% PPV and 97.3% NPV in predicting DI.
RHRMD with 90.6% sensitivity and 97.3% NPV could be a valuable tool for prediction of DI.

Weaning of the patient from mechanical ventilator is one of important stages of treatment in patients undergoing mechanical ventilation. Therefore, this study was done to determine the effect of family presence on weaning success in patients admitted to intensive care units (ICUs).

The present interventional quasi-experimental study was performed on 154 patients undergoing mechanical ventilation who were selected through available sampling method and based on inclusion criteria and were randomly divided into intervention and control groups. For the intervention group, the presence of one of the family members was used in process of weaning from the mechanical ventilator. A questionnaire of patients҆ demographic information, family satisfaction of patients admitted to ICU, and a checklist of recording the patient's vital signs were used to collect the required information.

Based on the results, After the intervention, the patients in the intervention group were in a better condition than the control group in terms of vital signs, time spent for intubation and number of re-intubation, as well as family satisfaction (P<0.05).

The results showed that the presence of family in the process of weaning of patients admitted to the intensive care unit is effective in improving vital signs and physiological indicators and reduces the time spent for intubation and the number of re-intubation in these patients while promoting family satisfaction. Therefore, the use of this method can be used in coordination with members of the treatment team to help patients admitted to the intensive care unit.

Activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to tyrosine kinase inhibitors (TKIs), but responses to TKIs is not permanent and drug resistance eventually happens for almost all patients. Subsequent studies found different resistance mechanisms, among which (EGFR) T790M mutation is the most important mechanism of TKI treatment failure. Using cell- free DNA (cfDNA) is a new way for diagnosing resistance mutations in EGFR. The aim of present study is to determine cfDNA-identified recurrence mutation rate and their association with clinical outcome in lung Adenocarcinoma patients.
Patients who were diagnosed with metastatic adenocarcinoma of the lung and acquired resistance to TKIs were enrolled. The incidence of T790M positivity, overall survival (OS) and median duration of TKI treatment before progression was calculated. Polymerase chain reaction (PCR) and sequencing were used to identify the T790M mutation in cfDNA.
The incidence of T790M mutations was higher in men, younger cases (<59 years), in patients with L858R primary mutation and never smokers although they were not significantly different (P-values= 041, 0.316, 0.316 and 0.158, respectively). There was significant longer OS in the Del19 subgroup than the L858R subgroup (p = 0.014). In multivariable analysis, significant longer OS was associated with younger age (<59 years) and primary EGFR mutation exon 19 (P- values= 0.028 and 0.050, respectively).
T790M mutations frequency may differ by ethnicity, genetic factors and EGFR primary mutations. Detecting T790M mutations in plasma is considered as an indicator of treatment with third generation EGFR-TKIs.

Increased vascular permeability is one of the main mechanisms in the production of pleural effusion (PE) and vascular endothelial growth factor (VEGF) has a significant role in its pathogenesis. This study aimed to compare pleural levels of VEGF in transudative and exudative PEs besides the other pleural markers.
In this prospective cross-sectional study, 80 patients with PE were divided into 4 groups as transudative (N=15), parapneumonic (N=15), tuberculosis (N=25), and malignant (N=25) PE. Biochemical tests measured the pleural protein, LDH, cholesterol, glucose, polymorphonuclear cell (PMN), and lymphocyte. ELISA measured the pleural VEGF level.
Out of 80 patients, 51 were male, and the total mean age was 55.34±18.53. There were significant differences in pleural VEGF between exudative and transudative effusion (P<0.001) and between malignant and benign effusion (P=0.014). The highest mean difference in pleural VEGF levels was seen in the comparison of transudative and malignant groups (Mean difference=-136.56; P<0.002). The VEGF level in 3 groups was not significantly different; transudative vs tuberculous, parapneumonic vs tuberculous, and parapneumonic vs malignant. Furthermore, VEGF higher than 73.09 pg/ml had a 64% sensitivity and 82% specificity for the diagnosis of malignancy. Among pleural markers (VEGF, protein, LDH, and glucose), VEGF had the highest area under curve (AUC=0.734). Moreover, pleural protein, LDH, and glucose levels significantly correlated with pleural VEGF; however, pleural cholesterol, PMN, and lymphocyte were not correlated.
VEGF is assumed as an important factor in the pathogenesis of exudative PE, especially malignant effusion. It can distinguish between lymphocytic exudative PEs.

Carbon-based nanomaterials (CBNs) are the key elements in nanotechnology. The main challenge presented by CBNs is their relationship with the toxicity exposed in the biological systems, because of the incomplete information on their toxicity. This study is aimed to compare the cytotoxicity of graphite nanoparticles (GRNPs), graphene nanoparticles (GNPs), and multi-walled carbon nanotubes (MWCNTs) in A549 cells.
The physicochemical properties of nanomaterials were determined by instrumental techniques. CBNs were dispersed by the nongenotoxic standard procedure. After the cells were cultured, they were exposed to different concentrations of CBNs. Cellular viability was determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Moreover, toxicological indicators were obtained using linear probit regression.
The degree of cytotoxicity of CBNs in A549 cells was related to the time and, particularly, dose. At the concentrations of lower than 300 μg/mL, GNPs had stronger toxicity than MWCNTs, but the cytotoxic effects were reversed with the increase of the concentrations. The no-observed-adverse-effect concentration (NOAEC) of GRNPs, GNPs, and MWCNTs was 1.76, 0.06, and 0.65 μg/mL, respectively.
The results indicated that CBNs were toxic and GNPs had stronger toxicity than the others. The experimental results can be useful in increasing the knowledge about the toxicity and health risk management of CBNs.

Behçet's disease (BD) is a multisystem, progressive, and inflammatory disorder of unknown etiology. Vasculitis is believed to underlie various clinical manifestations of BD and is known to be one of the main causes of death due to BD, in cases of large vessel involvement. The current study is done in order to examine the effects of rituximab on the patient’s debilitating clinical manifestations, as a result of not responding to the standard treatment regimens. The present case is a 28-year-old female patient with BD associated vasculitis. She was referred to the respiratory referral center, chiefly complaining of intermittent episodes of massive hemoptysis. She had also recurrent oral and genital ulcers, and difficulty in walking, despite considering the common treatment approaches for BD. Our patient received two courses of rituximab in combination with intravenous methylprednisolone. Over six months follow-up period from the date of treatment initiation with rituximab, symptoms of BD such as recurrent hemoptysis and aphthous ulcers were reduced in both frequency and severity. Lower limb weakness and difficulty in walking were improved as well. To summarize, rituximab appears to be an effective alternative for treatment-resistant vasculitis in BD patients.