Chien-Hung Chin

Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts

BackgroundTo investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.MethodsA total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.ResultsWe newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004).ConclusionsTLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.

Prognostic factors of tracheobronchial mucoepidermoid carcinoma--15 years experience.

Background and objectives:  Mucoepidermoid carcinoma of the tracheobronchial tree is a rare tumour which displays a variable degree of clinical aggressiveness and malignancy. The relationship between the patients prognosis and the tumours histological features and clinical behaviour is uncertain. The aim of this study was to identify the clinicopathological features and analyse the outcomes of patients with this type of cancer.

Prognostic values of serum IP-10 and IL-17 in Patients with Pulmonary Tuberculosis

Objective: To identify patients at high risk of relapse after anti-tuberculosis (TB) therapy or with poor long-term outcomes. Methods: Fifty-one patients with pulmonary TB: 7 were classified as high association with both cavitations on initial chest radiography and positive sputum smear/cultures after two months of anti-TB treatment (HA group); 19 medium association (MA, one risk alone); and 25 low association (LA, neither risk). Serum interferon (IFN)-γ-inducible protein 10 (IP-10), interleukin-17 (IL-17), and C-reactive protein levels were investigated. Results: There was a trend towards higher serum IP-10 levels (p = 0.042) for HA patients throughout the 6-month treatment period. Month-2 IP-10 levels were higher in the HA than in the MA/LA group (656.2 ± 234.4 vs. 307.6 ± 258.5 pg/ml, adjusted p = 0.005). Receiver operating characteristic curves showed that the risk of relapse was well-captured by month-2 IP-10 levels at a cut-off value of 431 pg/ml (AUC=0.857, 95% CI 0.75–0.97, p = 0.003). Month-2 serum IL-17 levels were lower in non-survivors than survivors (15.7 ± 2.9 pg/ml vs. 24.6 ± 8.2 pg/ml, p = 0.001). Multivariate analysis demonstrated that a month-2 serum IL-17 level of ≤ 17 pg/ml (p = 0.026) was independently associated with all-cause mortality. Conclusions: Serum IP-10 and IL-17 levels after 2 months of anti-TB treatment may be biomarkers for estimating risk of both cavitation and delayed sputum conversion, and for predicting long-term mortality, respectively.

Factors influencing short-term re-admission and one-year mortality in patients with chronic obstructive pulmonary disease.

Background and objectives:  Fourteen day re‐admission rates are deemed to be an important indicator of the quality of medical care for COPD in Taiwan. This study identified the characteristics of patients with COPD who required short‐term re‐admission and analysed the risk factors for 1‐year mortality.

Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.

STUDY OBJECTIVES We hypothesized that DNA methylation patterns may contribute to disease severity or the development of hypertension and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA). METHODS Illuminas (San Diego, CA, USA) DNA methylation 27-K assay was used to identify differentially methylated loci (DML). DNA methylation levels were validated by pyrosequencing. A discovery cohort of 15 patients with OSA and 6 healthy subjects, and a validation cohort of 72 patients with sleep disordered breathing (SDB). RESULTS Microarray analysis identified 636 DMLs in patients with OSA versus healthy subjects, and 327 DMLs in patients with OSA and hypertension versus those without hypertension. In the validation cohort, no significant difference in DNA methylation levels of six selected genes was found between the primary snoring subjects and OSA patients (primary outcome). However, a secondary outcome analysis showed that interleukin-1 receptor 2 (IL1R2) promoter methylation (-114 cytosine followed by guanine dinucleotide sequence [CpG] site) was decreased and IL1R2 protein levels were increased in the patients with SDB with an oxygen desaturation index > 30. Androgen receptor (AR) promoter methylation (-531 CpG site) and AR protein levels were both increased in the patients with SDB with an oxygen desaturation index > 30. Natriuretic peptide receptor 2 (NPR2) promoter methylation (-608/-618 CpG sites) were decreased, whereas levels of both NPR2 and serum C type natriuretic peptide protein were increased in the SDB patients with EDS. Speckled protein 140 (SP140) promoter methylation (-194 CpG site) was increased, and SP140 protein levels were decreased in the patients with SDB and EDS. CONCLUSIONS IL1R2 hypomethylation and AR hypermethylation may constitute an important determinant of disease severity, whereas NPR2 hypomethylation and SP140 hypermethylation may provide a biomarker for vulnerability to EDS in OSA. COMMENTARY A commentary on this article appears in this issue on page 723.

Il13 promoter (-1055) polymorphisms associated with chronic obstructive pulmonary disease in Taiwanese.

Interleukin-13 (IL13) −1055 polymorphism has been implicated in the development of chronic obstructive pulmonary disease (COPD) in various studies with conflicting results. The aims of this study are to investigate whether IL13 −1055 polymorphism is associated with the development of COPD in Taiwanese smokers; and to determine if IL13 −1055 polymorphism is associated with the severity of COPD. A case-control study was conducted on COPD patients (n = 85) and healthy smoker (n = 72). Genomic DNA was extracted for genotyping of IL13 sequencing and serum IL-13 was measured using by enzyme-linked immunosorbent assay (ELISA). After adjusting smoking index and age confounding, the T-allelic frequencies of the IL13 −1055 gene polymorphisms in COPD group are significantly higher than those in control group (18.8% versus 1.4%; P < .001; odds ratio [OR] = 29.3; 95% confidence interval [CI]: 5.9–145.3); and the frequencies of CT/TT genotypes in COPD group are significantly higher than those in control group (27.1% versus 2.8%; P < .001; OR = 20.0; 95% CI: 3.9–100.8). In COPD patients, stepwise linear regression shows IL13 −1055 T allele is the independent factor associated with forced expiratory volume in 1 second (P = .007), but not associated with serum IL-13. In conclusion, IL13 −1055 T allele is associated with the development and severity of COPD in Taiwanese smokers.

Clinical predictors of effective continuous positive airway pressure in patients with obstructive sleep apnea/hypopnea syndrome.

To identify standard clinical parameters that may predict the optimal level of continuous positive airway pressure (CPAP) in adult patients with obstructive sleep apnea/hypopnea syndrome (OSAHS).

Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea

We aimed to identify novel molecular associations between chronic intermittent hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea (OSA). We analyzed gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients on long-term continuous positive airway pressure treatment (VSOC). Comparisons of the microarray gene expression data identified eight genes up-regulated with OSA and down-regulated with CPAP treatment, and five genes down-regulated with OSA and up-regulated with CPAP treatment. Protein expression levels of two genes related to endothelial tight junction (AMOT P130, and PLEKHH3), and three genes related to anti-or pro-apoptosis (BIRC3, ADAR1 P150, and LGALS3) were all increased in the VSO group, while AMOT P130 was further increased, and PLEKHH3, BIRC3, and ADAR1 P150 were all decreased in the VSOC group. Subgroup analyses revealed that AMOT P130 protein expression was increased in OSA patients with excessive daytime sleepiness, BIRC3 protein expression was decreased in OSA patients with hypertension, and LGALS3 protein expression was increased in OSA patients with chronic kidney disease. In vitro short-term intermittent hypoxia with re-oxygenation experiment showed immediate over-expression of ADAR1 P150. In conclusion, we identified a novel association between AMOT/PLEKHH3/BIRC3/ADAR1/LGALS3 over-expressions and high severity index in OSA patients. AMOT and GALIG may constitute an important determinant for the development of hypersomnia and kidney injury, respectively, while BIRC3 may play a protective role in the development of hypertension.

Blood absolute T cell counts may predict 2-month treatment response in patients with pulmonary tuberculosis.

Background and objective: Little is known about the usefulness of lymphocyte subsets as early predictors of anti-tuberculosis (TB) treatment response in immuno-competent patients. Methods:Among a total of 64 patients with culture positive pulmonary TB, 29 remained sputum smear/culture positive or had delayed resolution on CXR (slow responders (SR)), and 35 had sputum culture conversion to negative and rapid resolution on CXR (fast responders (FR)) after two months of anti-tuberculosis treatment. Clinical parameters and lymphocyte subsets were investigated. Results: A larger proportion of patients in the SR group had cavities on CXR, bilateral lung involvement, positive acid-fast bacilli stains, and complaint of cough at diagnosis than those in the FR group. Absolute counts of CD3+ T cells (p = 0.016) and CD8+ T cells (p = 0.012) at diagnosis were both significantly higher in the SR group. This trend was present throughout the 6-month treatment course. Absolute T cell counts (odds ratio (OR) 1.002, 95% confidence interval (CI) 1.0–1.004), positive sputum acid fast bacilli stain (OR 6.69, 95% CI 1.37–32.77) and bilateral lung involvemment on CXR (OR 13.114, 95% CI 1.87–92.14) at diagnosis were independent predictors for a slow response. Combining these three predictors, a prediction score (PS) could be calculated to display an optimal discrimination for slow response (area under the curve (AUC) = 0.855, p < 0.001) whereas absolute T cell counts yielded the highest discriminative value on an individual level (AUC = 0.676, p = 0.015). Conclusions: A higher T cell count at diagnosis in patients with TB may predict a slow response to two months of treatment. The calculation of a PS further increased predictive accuracy and performance.

Occult Thyroid Cancer Presenting as Endotracheal Invasion Report of Two Cases and Literature Review

Occult thyroid cancer presenting initially as endotracheal invasion is extremely rare. Two patients presented to our chest clinic with hemoptysis and cough. The chest radiograph showed a filling defect in the tracheal air column. Physical examination of the neck and thyroid revealed unremarkable findings. An endotracheal tumor was noted by bronchoscopy. The pathologic examination of the surgical specimens confirmed the diagnosis of occult papillary thyroid carcinoma with transmural tracheal invasion. One patient had longterm survival after radical surgery, while the other expired because of the complication of progressive upper airway obstruction. No similar cases have been described in the literature. We believe endotracheal invasion by occult thyroid cancer should be considered in the differential diagnosis of endotracheal tumor. The absence of a clinically detectable thyroid abnormality does not exclude the possibility of locally advanced thyroid cancer. Aggressive surgical resection of the primary tumor and the involved trachea can provide the opportunity for long-term survival.