[Show abstract][Hide abstract] ABSTRACT: This study presents a rule-based method for automated, real-time snoring detection using nasal pressure recordings during overnight sleep. Although nasal pressure recordings provide information regarding nocturnal breathing abnormalities in a polysomnography (PSG) study or continuous positive airway pressure (CPAP) system, an objective assessment of snoring detection using these nasal pressure recordings has not yet been reported in the literature. Nasal pressure recordings were obtained from 55 patients with obstructive sleep apnea. The PSG data were also recorded simultaneously to evaluate the proposed method. This rule-based method for automatic, real-time snoring detection employed preprocessing, short-time energy and the central difference method. Using this methodology, a sensitivity of 85.4 % and a positive predictive value of 92.0 % were achieved in all patients. Therefore, we concluded that the proposed method is a simple, portable and cost-effective tool for real-time snoring detection in PSG and CPAP systems that does not require acoustic analysis using a microphone.
[Show abstract][Hide abstract] ABSTRACT: This study proposes a method of automatically classifying sleep apnea/hypopnea events based on sleep states and the severity of sleep-disordered breathing (SDB) using photoplethysmogram (PPG) and oxygen saturation (SpO2) signals acquired from a pulse oximeter. The PPG was used to classify sleep state, while the severity of SDB was estimated by detecting events of SpO2 oxygen desaturation. Furthermore, we classified sleep apnea/hypopnea events by applying different categorisations according to the severity of SDB based on a support vector machine. The classification results showed sensitivity performances and positivity predictive values of 74.2% and 87.5% for apnea, 87.5% and 63.4% for hypopnea, and 92.4% and 92.8% for apnea + hypopnea, respectively. These results represent better or comparable outcomes compared to those of previous studies. In addition, our classification method reliably detected sleep apnea/hypopnea events in all patient groups without bias in particular patient groups when our algorithm was applied to a variety of patient groups. Therefore, this method has the potential to diagnose SDB more reliably and conveniently using a pulse oximeter.
[Show abstract][Hide abstract] ABSTRACT: The shape of the flow-volume (F-V) curve is known to change to showing a prominent plateau as stenosis progresses in patients with tracheal stenosis. However, no study has evaluated changes in the F-V curve according to the degree of bronchial stenosis in patients with unilateral main bronchial stenosis.
We performed an analysis of F-V curves in 29 patients with unilateral bronchial stenosis with the aid of a graphic digitizer between January 2005 and December 2011.
The primary diseases causing unilateral main bronchial stenosis were endobronchial tuberculosis (86%), followed by benign bronchial tumor (10%), and carcinoid (3%). All unilateral main bronchial stenoses were classified into one of five grades (I, ≤25%; II, 26%-50%; III, 51%-75%; IV, 76%-90%; V, >90% to near-complete obstruction without ipsilateral lung collapse). A monophasic F-V curve was observed in patients with grade I stenosis and biphasic curves were observed for grade II-IV stenosis. Both monophasic (81%) and biphasic shapes (18%) were observed in grade V stenosis. After standardization of the biphasic shape of the F-V curve, the breakpoints of the biphasic curve moved in the direction of high volume (x-axis) and low flow (y-axis) according to the progression of stenosis.
In unilateral bronchial stenosis, a biphasic F-V curve appeared when bronchial stenosis was >25% and disappeared when obstruction was near complete. In addition, the breakpoint moved in the direction of high volume and low flow with the progression of stenosis.
[Show abstract][Hide abstract] ABSTRACT: Two adipokines, leptin and adiponectin regulate metabolic and inflammatory systems reciprocally. The role of adiponectin in chronic obstructive pulmonary disease (COPD) has been studied. However, there are few data evaluating the relationship of plasma leptin with COPD severity or progression.
The objective of this study is to evaluate the relationship of leptin, adiponectin, and leptin/adiponectin ratio with the COPD severity and progression according to COPD phenotypes.
Plasma leptin and adiponectin levels were measured in 196 COPD subjects selected from the Korean Obstructive Lung Disease cohort. Using a linear regression model and mixed linear regression, we determined the relationship of plasma leptin and adiponectin levels and leptin/adiponectin ratio with COPD severity and progression over 3 years.
The concentration of adiponectin in plasma positively correlated with percent (%) emphysema on initial computed tomography (CT) (adjusted P = 0.022), while plasma leptin concentrations and leptin/adiponectin ratio exhibited an independent inverse correlation with initial forced expiratory volume in 1 second (FEV1) (adjusted P = 0.013 for leptin and adjusted P = 0.041 for leptin/adiponectin ratio). Increased plasma leptin and leptin/adiponectin ratio were significantly associated with change in % emphysema over 3 years (adjusted P = 0.037 for leptin and adjusted P = 0.029 for leptin/adiponectin ratio), while none of the adipokines demonstrated an association with FEV1 decline over the 3 year period.
Plasma adiponectin and leptin vary according to COPD phenotypes. Plasma leptin and leptin/adiponectin ratio, but not adiponectin, were significantly associated with changes in CT-assessed emphysema, suggesting a potential role as a biomarker in emphysema progression in COPD patients.
Annals of the American Thoracic Society 05/2015; 12(7). DOI:10.1513/AnnalsATS.201501-005OC
[Show abstract][Hide abstract] ABSTRACT: There are no accurate data on the diagnostic value of preoperative flexible bronchoscopy (FB) for persistent ground-glass nodule (GGN) of the lung. We evaluated the value of preoperative FB in patients with suspected GGN-type lung cancer. We retrospectively searched a database for subjects who had 'ground-glass opacity', 'non-solid nodule', 'part-solid nodule', or 'sub-solid nodule' on chest computed tomography reports between February 2004 and March 2012. Patients who had infiltrative ground-glass opacity lesions, mediastinal lymphadenopathy, or pleural effusion, focal ground-glass opacity lesions >3 cm, and were lost to follow-up were excluded. We assessed the diagnostic value of preoperative FB in patients with persistent GGNs who underwent surgical resection. In total, 296 GGNs were evaluated by FB in 264 patients with persistent GGNs who underwent preoperative FB and surgical resection. The median size of the GGNs was 18 mm; 135 (46%) were pure GGN and 161 (54%) were part-solid GGN. No visible tumor or unsuspected endobronchial metastasis was identified by preoperative FB. Only 3 (1%, 3/208) GGNs were identified preoperatively as malignant by bronchial washing cytology; all were part-solid GGNs. No other etiology was identified by FB. Of the GGNs, 271 (91%) were subsequently confirmed as malignant and 25 (9%) were confirmed as benign at surgical resection. Consequently, the overall diagnostic sensitivity and negative predictive value of preoperative FB on a per-nodule basis was 1% (3/271) and 8% (25/293), respectively. The preoperative FB did not change the surgical strategy. Preoperative FB did not add much to the evaluation of persistent GGNs of the lung. Routine preoperative FB may have limited value in surgical candidates with small persistent pure GGNs.
PLoS ONE 03/2015; 10(3):e0121250. DOI:10.1371/journal.pone.0121250 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Correct mediastinal staging is critical for determination of the most appropriate management strategy in patients with non-small-cell lung cancer (NSCLC). The purpose of this study was to compare the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with that of mediastinoscopy in patients with NSCLC.
A prospective trial was conducted in a tertiary referral center in Korea. Patients with histologically proven NSCLC and suspicion for N1, N2, or N3 metastasis were enrolled. Each patient underwent EBUS-TBNA followed by mediastinoscopy. Surgical resection and complete lymph node dissection were conducted in patients for whom no evidence of mediastinal metastasis was apparent after mediastinoscopy.
In total, 138 patients underwent EBUS-TBNA and 127 completed both EBUS-TBNA and mediastinoscopy. N2/N3 disease was confirmed in 59.1% of the patients. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) of EBUS-TBNA on a per-person analysis were 88.0%, 100%, 92.9%, 100%, and 85.2%, respectively. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and NPV of mediastinoscopy on a per-person analysis were 81.3%, 100%, 89.0%, 100%, and 78.8%, respectively. Significant differences in the sensitivity, accuracy, and NPV were evident between EBUS-TBNA and mediastinoscopy (p < 0.005).
EBUS-TBNA was superior to mediastinoscopy in terms of its diagnostic performance for mediastinal staging of cN1-3 NSCLC. Because EBUS-TBNA is both less invasive and affords superior diagnostic sensitivity, it should be the first-line procedure performed in patients with NSCLC.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2015; 10(2):331-7. DOI:10.1097/JTO.0000000000000388 · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Recent reports have suggested the association between emphysema and cardiovascular disease (CVD); however, there are few reports regarding association of emphysema severity with metabolic syndrome and its components representing CVD risk factors.
A retrospective cross-sectional study was performed in 2814 adult male subjects over age 40 who visited the Health Promotion Center in Samsung Medical Center for a health checkup program.
We classified patients according to the quintiles of forced expiratory volume in 1 sec (FEV1) and emphysema index (EI). FEV1 percentage predicted values (% pred) was inversely associated with prevalence of metabolic syndrome and most of its components, such as abdominal obesity, hypertension, fasting hyperglycemia, and low high-density lipoprotein cholesterol. Although there was no association between prevalence of metabolic syndrome and EI, hypertension was positively associated with EI (P<0.001) and high triglycerides (TGs) were inversely associated with EI (P=0.021). These associations persisted after adjustment of other variables (P<0.001 in hypertension and P=0.039 in high TGs).
The computed tomography-determined EI has a complex association with components of metabolic syndrome that is associated with increased prevalence of hypertension but decreased prevalence of high TGs, whereas FEV1 (% pred) has an inverse association with metabolic syndrome and most of its components with consistent direction.
Metabolic Syndrome and Related Disorders 01/2015; 13(3). DOI:10.1089/met.2014.0117 · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated whether sonographic findings can provide additional diagnostic yield in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), and can more accurately predict nodal metastasis than chest computed tomography (CT) or positron emission tomography (PET)/CT scans. EBUS-TBNA was performed in 146 prospectively recruited patients with suspected thoracic lymph node involvement on chest CT and PET/CT from June 2012 to January 2013. Diagnostic yields of EBUS finding categories as a prediction model for metastasis were evaluated and compared with findings of chest CT, PET/CT, and EBUS-TBNA. In total, 172 lymph nodes were included in the analysis: of them, 120 were malignant and 52 were benign. The following four EBUS findings were predictive of metastasis: nodal size ≥10 mm, round shape, heterogeneous echogenicity, and absence of central hilar structure. A single EBUS finding did not have sufficient diagnostic yield; however, when the lymph node had any one of the predictive factors on EBUS, the diagnostic yields for metastasis were higher than for chest CT and PET/CT, with a sensitivity of 99.1% and negative predictive value of 83.3%. When any one of predictive factors is observed on EBUS, subsequent TBNA should be considered, which may provide a higher diagnostic yield than chest CT or PET/CT.
Journal of Korean Medical Science 12/2014; 29(12):1632-8. DOI:10.3346/jkms.2014.29.12.1632 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patient- and procedure-related factors associated with postoperative pulmonary complications (PPCs) have changed over the last decade. Therefore, we sought to identify independent risk factors of PPCs and to develop a clinically applicable scoring system. We retrospectively analyzed clinical data from 2,059 patients who received preoperative evaluations from respiratory physicians between June 2011 and October 2012. A new scoring system for estimating PPCs was developed using beta coefficients of the final multiple regression models. Of the 2,059 patients studied, 140 (6.8%) had PPCs. A multiple logistic regression model revealed seven independent risk factors (with scores in parentheses): age ≥70 years (2 points), current smoker (1 point), the presence of airflow limitation (1 point), American Society of Anesthesiologists class ≥2 (1 point), serum albumin <4 g/dL (1 point), emergency surgery (2 points), and non-laparoscopic abdominal/cardiac/aortic aneurysm repair surgery (4 points). The area under the curve was 0.79 (95% CI, 0.75-0.83) with the newly developed model. The new risk stratification including laparoscopic surgery has a good discriminative ability for estimating PPCs in our study cohort. Further research is needed to validate this new prediction rule.
PLoS ONE 12/2014; 9(12):e113656. DOI:10.1371/journal.pone.0113656 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and objective:
Radiotherapy is usually administered to the central airway in patients with unresectable adenoid cystic carcinoma (ACC). The purpose of this study was to describe the outcomes of endobronchial intervention in patients with airway stenosis following radiotherapy for ACC. Moreover, we investigated the incidence and contributing factors for airway stenosis following radiotherapy for ACC.
Forty-seven patients with ACC, who underwent radiotherapy of the tracheobronchial tree from January 1995 to December 2011, were reviewed retrospectively. Fibrotic airway stenoses were diagnosed using three-dimensional computed tomography, flexible bronchoscopy or both.
Eleven (23%) of the 47 patients with ACC suffered fibrotic airway stenosis following radiotherapy and received bronchoscopic intervention. The median interval from radiotherapy to diagnosis of fibrotic airway stenosis was 7 months. Low forced expiratory volume in 1 s (FEV1), FEV1 /forced vital capacity and brachytherapy were verified as factors contributing to radiotherapy-induced airway stenosis. Bronchoscopic intervention provided both symptomatic relief and improvement of lung function, and no procedure-related death or major complication was observed. Insertion of a straight silicone stent was required in 10 patients (91%), and 4 (36%) eventually received Y-shaped silicone stents. The stents, once implanted, could not be removed in any of the patients; stents were well-tolerated for a prolonged period in all patients.
Fibrotic airway stenosis following radiotherapy in patients with ACC is often found. Bronchoscopic intervention, including silicone airway stenting, was a safe and useful method for treating radiotherapy-induced fibrotic airway stenosis in patients with ACC.
[Show abstract][Hide abstract] ABSTRACT: Primary tracheal amyloidosis (PTA) can lead to airway obstructions, and patients with severe PTA should undergo bronchoscopic interventions in order to maintain airway patency. Focal airway involvements with amyloidosis can only be treated with mechanical dilatation. However, the PTA with diffused airway involvements and concomitant cartilage destructions requires stent placement. Limited information regarding the usefulness of silicone stents in patients with PTA has been released. Therefore, we report a case of diffused PTA with tracheomalacia causing severe cartilage destruction, which is being successfully managed with bronchoscopic interventions and silicone stent placements.
Tuberculosis and Respiratory Diseases 06/2014; 76(6):292-4. DOI:10.4046/trd.2014.76.6.292
[Show abstract][Hide abstract] ABSTRACT: We evaluated the prognostic value of volume-based metabolic positron emission tomography (PET) parameters in patients with small cell lung cancer (SCLC) compared with other factors.
The subjects were 202 patients with pathologically proven SCLC who underwent pretreatment 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT). Volumetric metabolic parameters of intrathoracic malignant hypermetabolic lesions, including maximum and average standardized uptake value, sum of metabolic tumor volume (MTV), and sum of total lesion glycolysis (TLG) were measured.
164 patients had died during follow-up (median 17.4 months) and median overall survival was 14 months. On univariate survival analysis, age, stage, treatment modality, sum of MTV (cutoff = 100 cm3), and sum of TLG (cutoff = 555) were significant predictors of survival. There was a very high correlation between the sum of MTV and the sum of TLG (r = 0.963, P < 0.001). On multivariate survival analysis, age (HR = 1.04, P < 0.001), stage (HR = 2.442, P < 0.001), and sum of MTV (HR = 1.662, P = 0.002) were independent prognostic factors. On subgroup analysis based on limited disease (LD) and extensive disease (ED), sum of MTV and sum of TLG were significant prognostic factors only in LD.
Both sum of MTV and sum of TLG of intrathoracic malignant hypermetabolic lesions are important independent prognostic factors for survival in patients with SCLC, in addition to age and clinical stage. However, it may be more useful in limited disease rather than in extensive disease.
Cancer imaging : the official publication of the International Cancer Imaging Society 04/2014; 14(1):2. DOI:10.1186/1470-7330-14-2 · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the utility of a combined approach using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-FNA-B/E) for mediastinal staging of lung cancer.
An EBUS-TBNA database was analyzed retrospectively. EUS-FNA-B/E was performed after EBUS-TBNA when mediastinal lymph nodes were not accessible using EBUS-TBNA or when tissue sampling using EBUS-TBNA alone was inadequate.
During the study period, 44 patients were enrolled. EBUS-TBNA and EUS-FNA-B/E were performed on 79 and 52 lymph nodes, respectively. The sensitivity, specificity, and accuracy of mediastinal N-staging using EBUS-TBNA alone were 79%, 100%, and 84%, respectively. The sensitivity, specificity, and accuracy of mediastinal N-staging using a combination of EBUS-TBNA and EUS-FNA-B/E were 100%, 100%, and 100%, respectively. Significant differences in sensitivity (P = 0.008) and accuracy (P = 0.004) of mediastinal N-staging were evident when EBUS-TBNA alone and the combined procedure were compared. The nodal stage shifted higher after use of the EUS-FNA-B/E procedure in six cases (13%). No serious complication associated with the procedures was noted.
Use of a combination of EBUS-TBNA and EUS-FNA-B/E can afford better sensitivity and accuracy of mediastinal N-staging compared with use of EBUS-TBNA alone. Such combined procedures should be considered for examination of lesions that are inaccessible or difficult to access by EBUS-TBNA.
PLoS ONE 03/2014; 9(3):e91893. DOI:10.1371/journal.pone.0091893 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
Epithelial myoepithelial carcinoma (EMC) of the lung is a very rare tumor that is characterized by biphasic differentiation of epithelial and myoepithelial cells. Current discussion about this entity focuses on the malignant potential of the tumor and the role of myoepithelial cells in diagnosis and patient prognosis. This study reports five EMC cases in the lung and discusses issues related to EMC prognosis.
Materials and methods
The five EMC cases were diagnosed and collected at the Samsung Medical Center (Seoul, Korea) from 1998 to 2012. Four patients with EMC were received a lobectomy and one patient was given a bronchoscopy to excise the tumor. All cases were evaluated with hematoxylin and eosin and immunohistochemical staining, which included S-100 protein, smooth muscle actin, TTF-1, cytokeratin, vimentin, and p27 analysis.
Results and Conclusion All cases revealed biphasic differentiation of epithelial and myoepithelial tumor cells with various stromal patterns. One of the cases contained predominantly myoepithelial and focal epithelial differentiation, and the tumor showed recurrence and metastasized to the chest wall. This was the first case of metastatic pulmonary EMC. Therefore, we suggest that EMC of the lung has a malignant potential, and that myoepithelial tumor cells may be associated with a pulmonary EMC prognosis
[Show abstract][Hide abstract] ABSTRACT: Purpose
We evaluated the characteristics of and treatment outcomes in patients with benign tracheobronchial tumors.
Materials and Methods
We reviewed the records of patients with benign tracheobronchial tumors who underwent bronchoscopic intervention with mechanical removal and Nd: YAG laser cauterization, and evaluated the characteristics and treatment outcomes of 55 patients with hamartomas, leiomyomas, papillomas, typical carcinoids, or schwannomas seen between April 1999 and July 2012.
The most common tumors were hamartoma (n=24), leiomyoma (n=16), papilloma (n=7), typical carcinoid (n=5), and schwannoma (n=3). Forty-one patients (75%) had symptoms. On chest computed tomography, 35 patients (64%) had round or ovoid lesions, accompanied by atelectasis (n=26, 47%) or obstructive pneumonia (n=17, 31%). Fatty components (n=9, 16%) and calcifications (n=7, 13%) were observed only in hamartomas, leiomyomas, and typical carcinoids. At bronchoscopy, the typical findings were categorized according to tumor shape, surface, color, and visible vessels. Fifty (91%) patients underwent complete resection. Forty patients (73%) achieved successful bronchoscopic removal defined as complete resection without complications or recurrence. Recurrences occurred in four papillomas, one leiomyoma, and one typical carcinoid. The proportions of tumor types (p=0.029) differed between the successful and unsuccessful removal groups, and a pedunculated base (p<0.001) and no spontaneous bleeding (p=0.037) were more frequent in the successful removal group.
We described clinical, radiological, and typical bronchoscopic findings in patients with benign tracheobronchial tumors; these findings might help to differentiate such tumors. Bronchoscopic intervention was a useful treatment modality, and tumor type, pedunculated base, and vascularity may influence successful tumor removal.
Yonsei medical journal 01/2014; 55(1):84-91. DOI:10.3349/ymj.2014.55.1.84 · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite the key role of mutational analysis in targeted therapy, the difficulty in acquisition of adequate tumor tissues for molecular genotyping in advanced non-small cell lung cancer (NSCLC) has led to the need for a fast and efficient method for detecting genetic alterations for targeted therapy.
We analyzed tissue specimens of advanced NSCLC. A mass spectrometry-based assay was used to investigate 471 oncogenic mutations. All tumor specimens were prepared from fresh-frozen tissues.
In total, there were 59 hotspot mutations in 67% of the entire patient group (41 out of 61 patients). The most frequent mutation was in TP53 (n=24, 39.3%), followed by EFGR (n=19, 31.1%). Others included MLH1, KRAS, PIK3CA, ERBB2, ABL1 and HRAS.
Our results suggest that molecular genotyping using high-throughput technology such as OncoMap v4 is feasible, even with small biopsied specimens from patients with advanced NSCLC.
Anticancer research 11/2013; 33(11):5127-33. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate and minimally invasive technique used routinely for investigation of mediastinal and hilar lymphadenopathy. However, few studies have addressed its role in comparison to the traditional diagnostic approaches of transbronchial lung biopsy (TBLB), endobronchial biopsy (EBB), and bronchoalveolar lavage (BAL) in the diagnosis of sarcoidosis. We evaluated the usefulness of EBUS-TBNA in the diagnosis of sarcoidosis compared to TBLB, EBB, and BAL.
Materials and Methods
Consecutive patients with suspected sarcoidosis (stage I and II) on chest radiography and chest computed tomography were included. All 33 patients underwent EBUS-TBNA, TBLB, EBB, and BAL during the same session between July 2009 and June 2011. EBUS-TBNA was performed at 71 lymph node stations.
Twenty-nine of 33 patients, were diagnosed with histologically proven sarcoidosis; two patients were compatible with a clinical diagnosis of sarcoidosis during follow-up; and two patients were diagnosed with metastatic carcinoma and reactive lymphadenopathy, respectively. Among 29 patients with histologically proven sarcoidosis in combination with EBUS-TBNA, TBLB, and EBB, only EBUS-TBNA and TBLB revealed noncaseating granuloma in 18 patients and one patient, respectively. The overall diagnostic sensitivities of EBUS-TBNA, TBLB, EBB, and BAL (CD4/CD8 ≥3.5) were 90%, 35%, 6%, and 71%, respectively (p<0.001). The combined diagnostic sensitivity of EBUS-TBNA, TBLB, and EBB was 94%.
EBUS-TBNA was the most sensitive method for diagnosing stage I and II sarcoidosis compared with conventional bronchoscopic procedures. EBUS-TBNA should be considered first for the histopathologic diagnosis of stage I and II sarcoidosis.
Yonsei medical journal 11/2013; 54(6):1416-21. DOI:10.3349/ymj.2013.54.6.1416 · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
Haptoglobin (Hp) subunits have been suggested as a potential serum marker for lung cancer. Research is intense on the application of Hp subunits to predict the cancer earlier. Nevertheless, it remains difficult to accurately measure the content of Hp subunits. We developed stable isotope dilution-multiple reaction monitoring mass spectrometry (SID-MRM-MS) capable of measuring Hp subunits (alpha and beta chains). Three isotopic analogs (NPANPVQ, TEGDGVYTLNDK and ILGGHLDAK for alpha, alpha2 and beta chain, respectively) were used as internal standard (IS) for SID-MRM-MS. Serum levels of each Hp subunit were measured in 210 clinical samples using SID-MRM-MS. A concentration ratio of each Hp subunit to total Hp was investigated. Secretion levels of alpha and beta chains were significantly increased in non-small cell lung cancer (NSCLC) compared to controls (P<0.0001). Alterations of the alpha chain ratio were more apparent than beta chain between controls and NSCLC (P=0.0001 and 0.338 for alpha and beta chains, respectively). In conclusion, this study provides not only an efficient quantitative method to determine each Hp subunit in crude sera, but also evidence that Hp alpha chain is a more prospective biomarker to diagnose NSCLC than beta chain.
Recent several studies have reported Hp as a potential biomarker for diagnosis of lung cancer. However a successful evaluation of the value of Hp subunits was not achieved on clinical samples. To evaluate the diagnostic performance of each Hp subunit, the development of an accurate quantitative assay of Hp subunits is necessary. In this regard, we employed a new analytical method using stable isotope dilution-multiple reaction monitoring mass spectrometry (SID-MRM-MS), capable of measuring Hp subunits in 210 clinical specimens. In this article, we measured the Hp subunit concentrations and Hp subunits/total Hp ratios in patients with NSCLC using SID-MRM-MS. This is the first report on the evaluation of each Hp subunit as a lung cancer marker using SID-MRM-MS. Consequently, we evaluated specific three tryptic peptides (e.g. NPANPVQ, TEGDGVYTLNDK and ILGGHLDAK for alpha, alpha2 and beta chain, respectively) with high specificity and sensitivity for determination of Hp subunits. Through future large prospective cohort studies, the clinical application of Hp subunits as complementary markers, especially Hp alpha, would be useful for the diagnosis of NSCLC.
Journal of proteomics 10/2013; 94. DOI:10.1016/j.jprot.2013.09.019 · 3.89 Impact Factor