Epithelial cells/progenitor cells in developing human lower respiratory tract: Characterization and transplantation to rat model of pulmonary injury.

Introduction: For cell-based therapies of lung injury, several cell sources have been extensively studied. However, the potential of human fetal respiratory cells has not been systematically explored for this purpose. Here, we hypothesize that these cells could be one of the top sources and hence, we extensively updated the definition of their phenotype. Methods: Human fetal lower respiratory tissues from pseudoglandular and canalicular stages and their isolated epithelial cells were evaluated by immunostaining, electron microscopy, flow cytometry, organoid assay, and gene expression studies. The regenerative potential of the isolated cells has been evaluated in a rat model of bleomycin-induced pulmonary injury by tracheal instillation on days 0 and 14 after injury and harvest of the lungs on day 28. Results: We determined the relative and temporal, and spatial pattern of expression of markers of basal (KRT5, KRT14, TRP63), non-basal (AQP3 and pro-SFTPC), and early progenitor (NKX2.1, SOX2, SOX9) cells. Also, we showed the potential of respiratory-derived cells to contribute to in vitro formation of alveolar and airway-like structures in organoids. Cell therapy decreased fibrosis formation in rat lungs and improved the alveolar structures. It also upregulated the expression of IL-10 (up to 17.22 folds) and surfactant protein C (up to 2.71 folds) and downregulated the expression of TGF-ß (up to 5.89 folds) and AQP5 (up to 3.28 folds). Conclusion: We provide substantial evidence that human fetal respiratory tract cells can improve the regenerative process after lung injury. Also, our extensive characterization provides an updated phenotypic profile of these cells.

Effects of supplementation of vitamins D, C and E on Idiopathic Pulmonary Fibrosis (IPF): A clinical trial.

BACKGROUND & AIMS: Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a growing prevalence. We aimed to evaluate the effects of co-supplementation with vitamins C, E, and D on respiratory, inflammatory, and oxidative stress outcomes in IPF patients. METHODS: Thirty-three patients participated in this quasi-experimental study and were supplemented with vitamins E, C, and D with 200 IU/daily, 250 mg/every other day and 50000 IU/Weekly, respectively for 12 weeks. Anthropometric indices, dietary recall, physical activity, Saint George questionnaire were assessed along with the biochemical measures of inflammation and oxidative stress, and respiratory parameters. Data were analyzed by SPSS version 21, and P-value ≤ 0.05 was considered significant. RESULTS: Results of spirometry and plethysmography tests showed a significant increase in FEV1 (P-value = 0.016), IRV (P-value = 0.001), RV (P-value = 0.002) and TLC (P-value = 0.003). But no significant change was observed in FVC, VC, FEV1/FVC, and ERV. We also found that ESR, hs-CRP, TGFß, and PrC remarkably reduced after the supplementation (P-value ≤ 0.05), while the GPx level remained unchanged. CONCLUSIONS: It is concluded that three months of supplementation with a combination of D, C, and E vitamins in IPF patients may positively affect the respiratory function and alleviate the inflammation and oxidative stress.

Microextraction on a screw for determination of trace amounts of hexanal and heptanal as lung cancer biomarkers.

Solid phase microextraction on a screw was utilized for the extraction of hexanal and heptanal as lung cancer biomarkers from urine samples. Reduced graphene oxide (rGO) was coated on the surface of a stainless-steel set screw by electrophoretic deposition method. The screw was located inside a glass cover, and the created channel acted as the sample solution flow pass. A 5 mL glass syringe was connected to a syringe pump to direct the sample and the eluent through the channel. The extraction procedure was followed by gas chromatography/mass spectrometry (GC/MS) for separation and determination of the extracted aldehydes. The effective parameters on the extraction efficiencies of the analytes were identified and optimized. Under the optimal extraction conditions, the extraction time was as short as 10 min. The calibration curves indicated good linearity (R2 > 0.97) within the concentration range of 1.0-50 µg L-1. The obtained limits of detection (LODs) for hexanal and heptanal were down to 0.4 and 0.3 µg L-1, respectively. Considering the repeatability, simplicity, and eco-friendliness of this simple extraction method, it can be efficiently used for preconcentration of aldehydes in different samples.

Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients.

PURPOSE: Lung cancer is the deadliest known cancer in the world, with the highest number of mutations in proto-oncogenes and tumor suppressor genes. Therefore, this study was conducted to determine the status of hotspot regions in DDR2 and KRAS genes for the first time, as well as in TP53 gene, in lung cancer patients within the Iranian population. EXPERIMENTAL DESIGN: The mutations in exon 2 of KRAS, exon 18 of DDR2, and exons 5-6 of TP53 genes were screened in lung cancer samples, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) using PCR and sequencing techniques. RESULTS: Analysis of the KRAS gene showed only a G12C variation in one large cell carcinoma (LCC) patient, whereas variants were not found in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) cases. The Q808H variation in the DDR2 gene was detected in one SCC sample, while no variant was seen in the ADC and LCC subtypes. Variations in the TP53 gene were seen in all NSCLC subtypes, including six ADC (13.63%), seven SCC (15.9%) and two LCC (4.54%). Forty-eight variants were found in the TP53 gene. Of these, 15 variants were found in coding regions V147A, V157F, Q167Q, D186G, H193R, T211T, F212L and P222P, 33 variants in intronic regions rs1625895 (HGVS: c.672+62A>G), rs766856111 (HGVS: c.672+6G>A) and two new variants (c.560-12A>G and c.672+86T>C). CONCLUSIONS: In conclusion, KRAS, DDR2, and TP53 variants were detected in 2%, 2.17% and 79.54% of all cases, respectively. The frequency of DDR2 mutation is nearly close to other studies, while KRAS and TP53 mutation frequencies are lower and higher than other populations, respectively. Three new putative pathogenic variants, for the first time, have been detected in Iranian patients with lung cancer, including Q808H in DDR2, F212L, and D186G in coding regions of TP53. In addition, we observed five novel benign variants, including Q167Q, P222P and T211T in coding sequence, and c.560-12A>G and c.672+86T>C, in intronic region of TP53. Mutations of KRAS and DDR2 were found in LCC and SCC subtypes, respectively, whereas mutations of TP53 were seen in SCC and ADC subtypes with higher frequencies and LCC subtype with lower frequency. Therefore, Iranian lung cancer patients can benefit from mutational analysis before starting the conventional treatment. A better understanding of the biology of these genes and their mutations will be critical for developing future targeted therapies.

Chitosan-alginate nano-carrier for transdermal delivery of pirfenidone in idiopathic pulmonary fibrosis.

Pirfenidone (PFD) is one of the pyridine family components with anti-inflammatory, antifibrotic effects and US FDA approved for the treatment of idiopathic pulmonary fibrosis (IPF). Presently, PFD is administered orally and this has setbacks. Hence, it is important to eliminate the pharmacotherapeutic limitations of PFD. This research was carried out to study the possibility of transdermal delivery of PFD using chitosan-sodium alginate nanogel carriers. In order to synthesize chitosan-sodium alginate nanoparticles loaded with PFD, the pre-gelation method was used. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR) analyses were used for the characterization. Drug encapsulation and release manner were studied using UV spectroscopy. Ex vivo permeation examinations were performed using Franz diffusion cell and fluorescence microscopy. The results showed that nanoparticles having spherical morphology and size in the range of 80 nm were obtained. In vitro drug release profile represents sustained release during 24 h, while 50% and 94% are the loading capacity and efficiency, respectively. Also, the skin penetration of PFD loaded in nanoparticles was significantly increased as compared to PFD solution. The obtained results showed that synthesized nanoparticles can be considered as promising carriers for PFD delivery.

Arterial blood gas and spirometry parameters affect the length of stay in hospitalized asthmatic patients.

BACKGROUND: Asthma is a common condition in general medical practice, and it accounts for about 1% of all ambulatory hospital visits. Nowadays, hospitalization rates for asthma have actually been increased in some demographic subgroups despite recent advances in treatment. Understanding the underlying factors that contribute to hospitalization and especially duration of the hospitalization of asthmatics could help elucidate the recent rise in morbidity and also reduce the high demand on health care systems of the disease. The aim of this study was to evaluate factors affecting the duration of hospitalization for Iranian patients with asthma. METHODS: This study was conducted on 55 asthmatic patients (diagnosis of asthma was in accordance with the criteria of the American Thoracic Society). The study was performed on patients hospitalized in Rasoul-e-Akram hospital in Tehran, Iran during the period 2005-2006. During hospitalization, the patients' most common complaints were recorded as the symptoms and signs of the medical condition, results of physical examinations, spirometry, arterial blood gas analysis (ABG), and ICU admission. RESULTS: There were 18(32.7%) male and 37(67.3%) female patients with a mean age of 54.96 (SD=17.54) years. The mean duration of hospitalization was 8.31(SD=4.69) days that ranged between 2 and 23 days. The mean baseline arterial PH (p=0.039, RPearso = -0.362), baseline arterial [HCO3] (p=0.042, RPearson = 0.361), changes of FEV1 after bronchodilator (p=0.041, RPearson= -0.363) and patient's age (p=0.002, RPearson=0.0433) were determined as factors affecting duration of hospitalization. CONCLUSION: Our results showed that more attention needs to be given to the findings of arterial blood gas and spirometry which can potentially affect the duration of hospitalization of asthmatic patients.

Helicobacter pylori in patients suffering from pulmonary disease.

BACKGROUND: Recently, research of indirect evidence suggested a possible association between Helicobacter pylori and pulmonary disease. This study aimed to determine if H. pylori could be detected in endobronchial specimens collected from patients undergoing bronchoscopy. MATERIALS AND METHODS: This prospective study was conducted on 34 consecutive patients with any type of lung disease undergoing bronchoscopy in which biopsy was required for their diagnosis. A written informed consent was obtained from all participants. Three bronchial mucosa biopsy samples were obtained using fenestrated biopsy forceps. One sample was used to determine urease activity, the second one for histopathological examination, and the third one for diagnosis. All subjects were fully informed regarding the gastroesophageal reflux disorder (GERD) Questionnaire. RESULTS: There were 34 patients with pulmonary diseases (12 males and 22 females, mean age 58.2±18.2 years) out of which, 11 (32.4%) had GERD. No significant difference was found between the histopathological assay and GERD. CONCLUSION: Our study found no direct evidence supporting the theory that H. pylori may cause pulmonary disease and no relation with GERD was detected. However, a possible indirect role could not be excluded. Further studies in patients with GERD and lung disease may reveal a potential pathogenic link between H. pylori and pulmonary disease.

Effects of combination of fluticasone propionate and salmeterol xinafoate on lung function improvement in patients with bronchiectasis.

INTRODUCTION: Bronchiectasis is defined as bronchial abnormal and permanent dilation with destructive and inflammatory changes of bronchial wall. Bronchodilators are used to treat the disease in order to improve lung functions. Seretide is the combination of fluticasone propionate and salmeterol xinafoate (FLU/SAL). The effect of each has been proved in the improvement of bronchiectasis, while their synthetic effect as FLU/SAL on bronchiectasis improvement has not been studied yet. AIM: The aim of this study was to investigate the effects of FLU/SAL on the lung function improvement in bronchiectasis patients, comparing and interpreting pulmonary function tests before and after FLU/SAL inhalation. METHODS AND MATERIALS: Twelve patients with bronchiectasis who referred to Rasoul-e-Akram Hospital, Tehran, Iran in 2008 participated in this prospective quasi-experimental trial. The patients were treated with 2 puffs of fluticasone 125 µg and salmeterol 50 µg (Seretide) twice a day for one month. Beside recording demographic variables, the results of pulmonary function tests (PFT) including vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and FEV1/FVC ratio were recorded before and after the treatment. Data were analyzed using SPSS v.16 and Pearson correlation and paired T-test were performed. RESULTS: Among 12 patients with bronchiectasis, there were 4 men and 8 women with the mean age of 47.58 (SD=18.32) yr. The mean increase in the ratios of VC, FVC and FEV1 to predicted values and also patients FEV1/FVC after treatment were 15.50% (SD=14.40), 49.83% (SD=8.19) 8.17% (SD=12.07) and 7.17% (SD=12.68), respectively. The results of paired T-test indicated that VC (P=0.008) and FEV1(P=0.039) have increased significantly after treatment. CONCLUSION: This study is one of the first studies investigating the FLU/SAL effect on bronchiectasis. Results of this study have indicated that using FLU/SAL has a significant effect on the improvement of lung function parameters in these patients, while the attention was been focused on antibiotic therapy or other bronchodilators.

Evaluation of the simvastatin effects in the treatment of pulmonary hypertension (PH).

BACKGROUND: Pulmonary hypertension (PH) is a rare but life-threatening disease characterized by significant increases in pulmonary arterial pressure (PAP) and right ventricular hypertrophy (RVH), therefore early diagnosis and proper treatment of PH is very important. Statins confer cardiovascular benefits beyond the reduction of serum cholesterol through antiproliferative and antiinflammatory mechanisms and induction of endothelial nitric oxide expression. In pneumonectomized rats injected with monocrotaline, simvastatin reversed established pulmonary hypertension and conferred a 100% survival advantage. OBJECTIVE: The aim of this study was to evaluate the potential effect of simvastatin treatment in patients with pulmonary hypertension (PH). PATIENTS AND METHODS: In this prospective before-after pilot trial, 19 patients with primary and secondary causes of PH referred to Khorrami Hospital in Qom, Iran were recruited. Patients were treated with simvastatin, beginning at 20 mg/daily for 2 months, then increasing to 40 mg/daily for another 4 months. Echocardiographic Doppler estimates of systolic pulmonary artery pressures (SPAP) were measured for each patient before prescribing simvastatin and at the end of treatment. Also demographic data, history of smoking and heart functional class (NYHA) before and after treatment were recorded. RESULTS: Out of 19 patients with PH, fifteen were males (78.95%) and four were females (21.1%) with the mean age of 66 (SD=15.28) yr, range between 18 to 83 years. The commonest cause of PH was chronic obstructive pulmonary disease (COPD) in 15 patients (78.9%). Simvastatin significantly ameliorated PH from 74.79 (SD=23.52) mmHg to 67.21 (SD=20.55) mmHg (P<0.001). Whereas, heart functional class changes were not statistically significant (P=0.157). CONCLUSION: In this study, we demonstrated that simvastatin treatment decreased SPAP in patients with PH. As the pathogenesis of PH involves inappropriate proliferation and constriction of vascular smooth-muscle cells, and deficiencies of endogenous vasodilators such as prostacyclin and endothelial-derived nitric oxide, the antiproliferative, antiinflammatory and antithrombogenic effect of simvastatin seems to be useful. This study has led physicians to believe that simvastatin may be beneficial for the treatment of PH.