Cytokine gene polymorphisms and serum cytokine levels in patients with idiopathic pulmonary fibrosis

BACKGROUND: Studies have demonstrated associations between cytokine gene polymorphisms and the risk of idiopathic pulmonary fibrosis (IPF). We therefore examined polymorphisms in the genes encoding interleukin (IL)-6, IL-10, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and transforming growth factor-beta 1 (TGF-β(1)), and compared the serum levels of these cytokines in IPF patients and healthy controls. Furthermore, we examined the association of the studied genotypes and serum cytokine levels with physiological parameters and the extent of parenchymal involvement determined by high-resolution computed tomography (HRCT). METHODS: Sixty patients with IPF and 150 healthy controls were included. Cytokine genotyping was performed using the polymerase chain reaction sequence specific primer (PCR-SSP) method. In a subset of patients and controls, serum cytokine levels were determined by enzyme-linked immunosorbent assay. RESULTS: There was no difference between IPF patients and controls in the genotype and allele distributions of polymorphisms in TNF-α, IFN-γ, IL-6, IL-10, and TGF-β(1) (all p > 0.05). The TNF-α (−308) GG, IL-6 (−174) GG and CG, and IL-10 (−1082, -819, -592) ACC ATA genotypes were significantly associated with HRCT scores (all p < 0.05). IL-10 (−1082, -819, -592) ACC haplotype was associated with the diffusion capacity of the lung for carbon monoxide, and ATA haplotype was associated with the partial pressure of oxygen (PaO(2)) (all p < 0.05). The TGF-β(1) (codons 10 and 25) TC GG, TC GC, CC GG and CC GC genotypes were significantly associated with the PaO(2) and HRCT scores (p < 0.05). The TGF-β(1) (codons 10 and 25) CC GG genotype (5 patients) was significantly associated with higher PaO(2) value and less parenchymal involvement (i.e., a lower total extent score) compared to the other TGF-β(1) genotypes (81.5 ± 11.8 mm Hg vs. 67.4 ± 11.1 mm Hg, p = 0.009 and 5.60 ± 1.3 vs. 8.51 ± 2.9, p = 0.037, respectively). Significant differences were noted between patients (n = 38) and controls (n = 36) in the serum levels of IL-6 and IL-10 (both, p < 0.0001), but not in the levels of TNF-α and TGF-β(1) (both, p > 0.05). CONCLUSION: The studied genotypes and alleles do not predispose to the development of IPF but appear to play an important role in disease severity. Our results suggest that the TGF-β(1) (codons 10 and 25) CC GG genotype could be a useful genetic marker for identifying a subset of IPF patients with a favorable prognosis; however, validation in a larger sample is required

Pirfenidone treatment in idiopathic pulmonary fibrosis: A Saudi experience

Background: Recent trials involving pirfenidone suggest a beneficial effect in the treatment of idiopathic pulmonary fibrosis (IPF). Objective: To report on the efficacy and safety of pirfenidone in the treatment of patients with IPF, at a tertiary care hospital in Saudi Arabia. Methods: The study included 58 patients with IPF who were evaluated from March 2012 to March 2013. During the study period, 33 patients received pirfenidone, and the remaining patients (n = 25) served as a control group. Baseline clinical characteristics, physiological parameters and the results of a 36-Item Short Form Health Survey (SF-36) were compared between the groups. Furthermore, we compared changes in forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLco), six-minute walk distance (6MWD) and SF-36 for both groups during follow-up. The last follow-up period ended in January 2014. Results: There were no significant differences in baseline clinical characteristics between the groups. Furthermore, we found no differences in FVC, DLco and SF-36 during follow-up (median, 12 months). However, patients receiving pirfenidone treatment were less likely to experience reductions in 6MWD compared with the control group (13% vs. 52%, respectively; P = 0.001). Although adverse events were more frequently reported by the pirfenidone group compared with the control group (85 vs. 56%, respectively; P = 0.015), these patients did not require discontinuation of treatment. Conclusion: Pirfenidone treatment preserves functional capacity, as reflected by the 6MWD. Adverse events associated with pirfenidone treatment were generally well tolerated by the patients

The six-minute walk test in patients with pulmonary sarcoidosis

<b>Background:</b> The 6-min walk test (6MWT) is a useful tool to assess prognosis and functional impairment in various pulmonary diseases.<b> Aims: </b> To evaluate functional capacity during various stages of pulmonary sarcoidosis and develop a scoring system clinical radiological physiological score (CRP) that can potentially be used to assess the functional status among patients with sarcoidosis.<b> Materials and Methods:</b> We performed a retrospective study on 26 patients diagnosed with pulmonary sarcoidosis from 2001 to 2007. All patients completed the 6MWT. The parameters assessed during the test included spirometry, arterial blood gas, 6-min walk distance (6MWD), Borg dyspnea score, and initial and end oxygen saturation. <b> Results:</b> Females covered a significantly shorter distance than males (343 m (223-389) vs. 416.5 m (352-500); <i> P </i> &lt; 0.0001). In addition, females had a significantly lower SpO₂ at the end of the 6MWT than males (90.5 (61-99) vs. 96 (75-98); <i> P</i> &lt; 0.03). The 6MWD was inversely correlated with the final Borg score (r = &#8722;0.603, <i> P</i> = 0.004) and the CRP score (r = -0.364, <i> P</i> = 0.047) and positively correlated with forced expiratory volume in 1 s (FEV₁ ) &#x0025; (r = 0.524, <i> P</i> = 0.006) and forced vital capacity (FVC) &#x0025; (r = 0.407, <i> P</i> = 0.039). <b> Conclusions:</b> Female gender, FEV₁ &#x0025;, final Borg score, FVC&#x0025;, CRP score, and SpO₂ at the end of the 6MWT are associated with reduced 6MWD. It appears that Saudi patients diagnosed with sarcoidosis have a markedly reduced walking distance compared with other races. The effect of race and ethnicity and the utility of the CRP score as a potential marker to assess functional status require further exploration

Clinical characteristics and computed tomography findings in Arab patients diagnosed with pulmonary sarcoidosis

<b>Background and Objective</b> : Sarcoidosis is prevalent worldwide with significant heterogeneity across different ethnic groups. We aimed To describe the clinical characteristics and computed tomography findings among Arab patients with pulmonary sarcoidosis. <b> Methods</b> : A retrospective study of patient demographics, symptoms, co-morbid illness, sarcoidosis stage, treatment, pulmonary function and CT results. <b> Results</b> : Of 104 patients, most (77&#x0025;) were 40 years of age or older at diagnosis, and females in this category (&#899;40 years ) significantly outnumbered male patients (69/104 (66.3&#x0025;) vs. 35/104 (33.7&#x0025;), <i>P</i>=.003). The most common complaints were dyspnea (76&#x0025;), cough (72.1&#x0025;) and weight loss (32.7&#x0025;). The majority of patients displayed impairment in lung function parameters at presentation. However, significant impairment in forced vital capacity, percentage predicted (FVC&#x0025;) (&lt; 50&#x0025;) was present in only 17&#x0025; of patients. The most frequent CT finding was mediastinal lymph node enlargement in 49 patients (73.1&#x0025;). Parenchymal abnormalities indicating lung fibrosis were noted in 31 patients (46.3&#x0025;), and traction bronchiectasis was the most common (35.8&#x0025;) fibrotic pattern detected on CT scans. <b>Conclusion</b> : At presentation, clinical manifestations of sarcoidosis among this sample of Arab patients were similar to reports from other nations. Further studies are needed to explore the effects of race and ethnicity on disease severity in the Middle East

Pulmonary hypertension in Saudi Arabia: A single center experience

Context: Several international studies have described the epidemiology of pulmonary hypertension (PH). However, information about the incidence and prevalence of PH in Saudi Arabia is unknown. Aims: To report cases of PH and compare the demographic and clinical characteristics of PH due to various causes in a Saudi population. Methods: Newly diagnosed cases of PH [defined as mean pulmonary artery pressure >25 mmHg at right heart cauterization (RHC)] were prospectively collected at a single tertiary care hospital from January 2009 and June 2012. Detailed demographic and clinical data were collected at the time of diagnosis, along with hemodynamic parameters. Results: Of the total 264 patients who underwent RHC, 112 were identified as having PH. The mean age at diagnosis was 55.8 ± 15.8 years, and there was a female preponderance of 72.3%. About 88 (78.6%) of the PH patients were native Saudis and 24 (21.4%) had other origins. Twelve PH patients (10.7%) were classified in group 1 (pulmonary arterial hypertension), 7 (6.2%) in group 2 (PH due to left heart disease), 73 (65.2%) in group 3 (PH due to lung disease), 4 (3.6%) in group 4 (chronic thromboembolic PH), and 16 (14.3%) in group 5 (PH due to multifactorial mechanisms). PH associated with diastolic dysfunction was noted in 28.6% of group 2 patients, 31.5% of group 3 patients, and 25% of group 5 patients. Conclusions: These results offer the first report of incident cases of PH across five groups in Saudi Arabia