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.

Diagnostic sensitivity of impulse oscillometry in early detection of patients exposed to risk factors chronic obstructive pulmonary diseases.

Background: Impulse oscillometry (IOS) is a method that does not depend on the cooperation of the patient and can detect small airway diseases with higher sensitivity than spirometry. However, the clinical application value of IOS in the screening of patients exposed to risk factors COPD and early diagnosis remains unclear. The aim of this study is to evaluate diagnostic sensitivity of IOS in the early detection of patients exposed to risk factors COPD. Methods: A prospective cross-sectional study was conducted in Rasoul Akram Hospital, Tehran, Iran, from 2013 to 2015. 28 patients with COPD risk factors and normal spirometry participated in the study. The IOS was performed. We obtained the respiratory resistance and impedance of 5 Hz (R5) and 20 Hz (R20) and 5 Hz (Z5), respectively. The data were analyzed using SPSS version 17 using Chi-square and two independent sample t-test. Spearman correlation test was used to measure the correlation of oscillometry parameters in the diagnosis of COPD. P-value <0.05 was considered significantfor all statistical analyses. Results: The mean patient age was 55.50±11.27 years. In this study, the sensitivity of Z5, R5, and R20 was respectively 28.5%, 25%, and 31.5%. All oscillometry parameters were significantly correlated with each other but none of the oscillometry parameters showed significant correlations with FEV1/FVC (rZ5=0.018, rR5=0.082, rR20=0.041 and PZ5=0.932, PR5=0.711, P R20=0.850). According to the results, only 9 patients (32.5%) with normal values of FEV1/FVC had abnormal values of oscillometry. Conclusion: IOS has a low sensitivity and cannot be used in the screening of early-stage chronic obstructive pulmonary disease.

CovidCTNet: an open-source deep learning approach to diagnose covid-19 using small cohort of CT images.

Coronavirus disease 2019 (Covid-19) is highly contagious with limited treatment options. Early and accurate diagnosis of Covid-19 is crucial in reducing the spread of the disease and its accompanied mortality. Currently, detection by reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard of outpatient and inpatient detection of Covid-19. RT-PCR is a rapid method; however, its accuracy in detection is only ~70-75%. Another approved strategy is computed tomography (CT) imaging. CT imaging has a much higher sensitivity of ~80-98%, but similar accuracy of 70%. To enhance the accuracy of CT imaging detection, we developed an open-source framework, CovidCTNet, composed of a set of deep learning algorithms that accurately differentiates Covid-19 from community-acquired pneumonia (CAP) and other lung diseases. CovidCTNet increases the accuracy of CT imaging detection to 95% compared to radiologists (70%). CovidCTNet is designed to work with heterogeneous and small sample sizes independent of the CT imaging hardware. To facilitate the detection of Covid-19 globally and assist radiologists and physicians in the screening process, we are releasing all algorithms and model parameter details as open-source. Open-source sharing of CovidCTNet enables developers to rapidly improve and optimize services while preserving user privacy and data ownership.

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.

Downhill walking influence on physical condition and quality of life in patients with COPD: A randomized controlled trial.

Background: Chronic Obstructive Pulmonary Disease (COPD), in addition to its respiratory problems, is accompanied by several musculoskeletal consequences. The aim of this study is to investigate the effectiveness of eccentric exercise in the form of downhill walking (DW) on respiratory capacity, physical function and quality of life (QOL) in patients with COPD. Methods: The randomized controlled trial was carried out during 2014 - 2015 in Hazrat-e-Rasool Hospital in Tehran, Iran. The study design was as an assessor blind RCT on 32 patients with COPD that randomly assigned to the eccentric training (ET) and control (CON) groups. Patients in ET group received a 12-week DW exercise on the treadmill while the patients in the control group were only treated by COPD conventional medications and walked on paved surfaces. Functional tests, FEV1, FEV1 to FVC and St. George's Respiratory Questionnaire (SGRQ) were used to assess the subject's physical status and QOL pre and post-intervention. Results: The FEV1 (p=0.008), FEV1/FVC (p=0.002), six-minute walk test (p=0.029), timed up & go test (p=0.023), SGRQ symptom (p=0.022), SGRQ activity (p=0.007), SGRQ impact (p=0.033) and total score of SGRQ (p=0.013) improved significantly in the ET group compare to the CON group. Conclusion: DW could have positive influence on physical status and QOL of patients with COPD.

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.

Does Downhill Walking on Treadmill Improve Physical Status and Quality of Life of A Patient With COPD?

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is accompanied by several extra-pulmonary consequences, such as skeletal muscle weakness and atrophy which will have a negative impact on daily life in patients and lead to their debilitation; therefore, when treating COPD patients, protocols should be taken into account to improve function and quality of life (QoL). CASE PRESENTATION: The case was a 71- year-old woman suffering from chronic bronchitis and bronchiectasis for 30 years that has been faced with increased musculoskeletal disorders in recent months. The case was managed by downhill treadmill walking for four months with the aim of improving her functional ability and QoL. Functional tests, thigh girth measurement and St. george's respiratory questionnaire (SGRQ) were used to assess the physical status and QoL of the patient. The outcomes measures confirmed the improvement of the studied case. The improvements continued three months after the beginning of the treatment. CONCLUSIONS: The eccentric exercise therapy in the form of downhill walking had positive effects on functions and QoL of studied case, especially had an augmenting effect on the thigh muscles size.

Genetic Profile Variation in Vaccine Strains and Clinical Isolates of Bordetella pertussis Recovered from Iranian Patients.

BACKGROUND: Re-emergence of pertussis has been reported in Iran despite a high rate of vaccination coverage. Low efficacy of the vaccine might be due to the genetic divergence between clinical versus vaccine strains. In the current study, the genetic profiles of clinical isolates and vaccine strains of Bordetella pertussis (B. pertussis) were assessed by using Pulsed Field Gel Electrophoresis (PFGE). METHODS: Following phenotypic and molecular identification of isolates, XbaI-digested genomic DNA of 5 clinical isolates, 2 vaccine strains and a Tohama I strain were analyzed by PFGE along with B. parapertussis as a control. RESULTS: Seven distinct PFGE profiles were found among all examined isolates/strains. In 5 clinical isolates, 4 profiles were identified whereas the vaccine strains displayed 2 distinct profiles. The reference strain, Tohama I had a distinct profile. Vaccine and clinical profiles had low similarity, with relatedness of approximately 40%. CONCLUSION: The genetic profiles of B. pertussis were different between circulating isolates and vaccine strains used in the national vaccination programs. Since new genetic profiles of B. pertussis can be disseminated periodically, the profiles of isolates circulating in the population should be monitored over the course of the re-emergence.

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.

Determination of alpha-1 antitrypsin level in patients with severe asthma.

BACKGROUND: This descriptive study aimed to determine the serum level of alpha-1 antitrypsin (AAT) in patients with severe asthma. MATERIALS AND METHODS: The serum level of AAT was determined in 43 patients with severe asthma. Pulmonary function tests were performed and data were analyzed by SPPS version 19 software. RESULT: The mean age of patients was 41±13.8 years (range 14 to 78 years). The AAT level was within the normal range (90-200 mg/dl) in 38 patients (88.4%) and less than normal in 2 patients (4.7%). CONCLUSION: No association was observed between the serum level of AAT and lung function in severe persistent asthmatic patients. The prevalence of AAT deficiency was low in patients with severe persistent asthma. These results must be confirmed by further longitudinal investigations using larger cohort studies.

Relationship between Serum Levels of Testosterone and the Severity of Chronic Obstructive Pulmonary Disease.

BACKGROUND: This cross-sectional study aimed to investigate the relationship between the levels of serum testosterone and the severity of chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Using GOLD criteria, 140 male patients with COPD were categorized into mild, moderate, severe and very severe COPD groups of 35 each. Then, serum levels of testosterone, prolactin and LH of patients were compared and the data were analyzed using SPSS version 18 software. RESULTS: Average age of patients was 67.4±10.1 years (range 41 to 90 years). The prevalence of the secondary hypogonadism was 58.6%. It was shown that the level of serum testosterone was directly correlated with the severity of COPD (P= 0.04). CONCLUSION: This study found that the prevalence of the secondary hypogonadism in COPD patients was high. The forced expiratory volume in 1 second (FEV1) was correlated with the level of serum testosterone. Further investigations are required to better evaluate the pathology and treatment of secondary hypogonadism in COPD patients.

Comparison of the Serum Electrolyte Levels among Patients Died and Survived in the Intensive Care Unit.

BACKGROUND: This study aimed to evaluate the prevalence of serum sodium and potassium disorders and assess their effects on mortality rate in hospitalized patients in the ICU and also to identify prognosis and predictors of survival. MATERIALS AND METHODS: A retrospective case-control study was conducted on 457 hospitalized patients in the ICU of Rasoul-e-Akram Hospital (Tehran, Iran). There were two groups: 239 patients who died in the ICU(cases) and 218 patients who were discharged from the ICU(controls). Normal serum concentrations of sodium and potassium were considered as 135-150 and 3-5.5 mEq/L, respectively. Data were analyzed using Chi square test, Independent t-test, One Way ANOVA, Correlation and Receiver Operating Characteristic (ROC) curve. RESULTS: The mean serum sodium concentration in patients who died and discharged patients was 137.56(SD=8.56) and 137.17(SD=5.11) mEq/L, respectively. Whereas, hyponatremia was significantly more common in expired patients (39.7% vs. 28%, P<0.001). On the other hand, the mean serum potassium concentration in expired and discharged patients was 4.42(SD=0.90) and 4.16(SD=0.59)mEq/L, respectively. Hyperkalemia was significantly more common in expired patients (9.2% vs. 0.9%, P<0.001). There was a significant negative correlation between serum sodium concentration and patient's age (P=0.029, R Spearman = - 0.123). In addition, ROC analysis showed that serum potassium concentration could potentially be a predictor of death in ICU patients (P=0.003, Area Under Curve (AUC) = 0.581). CONCLUSION: Hyponatremia and hyperkalemia are highly prevalent in expired ICU patients which is compatible with the findings of some other studies. Mortality of ICU patients is linked, in greater part, to organ dysfunction, but the severity of serum sodium and potassium disturbances remains a significant predictor of mortality. Thus, correcting electrolyte disturbances in ICU patients is important.

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.