[Show abstract][Hide abstract] ABSTRACT: Background:
Conventional spirometric parameters have shown poor correlation with symptoms and health status of chronic obstructive pulmonary disease (COPD). While it is well-known that the pattern of the expiratory flow-volume curve (EFVC) represents ventilatory dysfunction, little attempts have been made to derive quantitative parameters by analyzing the curve. In this study, we aimed to derive useful parameters from EFVC via graphic analysis and tried to validate them in patients with COPD.
Using Graphical Analysis 3.4 Vernier Software, we derived from the EFVC such parameters as area of obstruction (Ao), area of triangle (AT), area of rectangle (AR) and ratio of volume at 75 and 25 % peak expiratory flow (PEF) (0.25/0.75 V). For validation, we reviewed clinical and spirometric data of 61 COPD patients from Seoul National University Airway Registry (SNUAR) and Korean obstructive Lung Disease (KOLD) cohorts.
Of all parameters, only RV/TLC significantly correlated with scores from St. George's Respiratory Questionnaire (SGRQ) (r = 0.447, p = 0.037). Six-minute walking distance (6MWD) highly correlated with Ao/AR (r = -0.618, p = 0.005) and Ao/PEF (r = -0.581, p = 0.009) whereas neither FEV1 nor FEV1/FVC had significant correlation with 6MWD.
Ao/AR and Ao/PEF are promising parameters which correlate well with the exercising capacity of COPD patients.
Preview · Article · Dec 2016 · BMC Pulmonary Medicine
[Show abstract][Hide abstract] ABSTRACT: Background:
Sodium-potassium-chloride cotransporter isoform 1 (NKCC1) is an active ions cotransporter and modulates cellular volume and migration. NKCC1 blockers can inhibit cancer cell growth.
We aimed to elucidate the expression and prognostic significance of NKCC1 in non-small cell lung cancer (NSCLC).
We retrospectively analyzed 788 NSCLC patients with either adenocarcinoma (n = 503) or squamous cell carcinoma (n = 285) by immunohistochemistry to correlate NKCC1 expression with clinicopathologic and survival outcomes.
In adenocarcimoma, high NKCC1 expression was associated with larger tumor size (p = 0.013), vascular invasion (p < 0.001), lymphatic invasion (p < 0.001), perineural invasion (p = 0.019) and advanced pathologic stage (p < 0.001), but there are no significant correlations between NKCC1 expression and clinicopathological parameters in squamous cell carcinoma. Patients with high NKCC1 expression had significantly shorter disease-free survival (DFS; p < 0.001) and shorter overall survival (OS; p < 0.001) than those with low NKCC1 expression in adenocarcinoma. In squamous cell carcinoma, NKCC1 expression was not associated with prognosis. Multivariate analysis revealed that high NKCC1 expression was an independent prognostic factor for DFS in lung adenocarcinomas (HR, 1.709; 95% CI, 1.029 to 2.130; p = 0.033) and for OS in EGFR-mutated adenocarcinoma patients (HR, 3.165; 95% CI, 1.424 to 7.035; p = 0.005).
NKCC1 high expression predicted a bad clinical outcome for lung adenocarcinoma patients and EGFR-mutated subgroup. Therefore, NKCC1 may play a role in lung adenocarcinoma and novel therapeutic tactics could be developed by targeting NKCC1 protein.
No preview · Article · Nov 2015 · QJM: monthly journal of the Association of Physicians
[Show abstract][Hide abstract] ABSTRACT: Background and objective:
Development of CPE in CAP is associated with prolonged hospital stay and it may increase the morbidity and mortality. We aimed to identify microbiological and clinical factors that predicate a prolonged hospital admission in patients treated with a tube thoracostomy to control CPE.
This retrospective cohort included patients with CPE requiring chest tube drainage in a tertiary referral Korean hospital from 1 January 2004 to 30 July 2012. After dichotomous grouping according to the mean duration of hospital stay, clinical, laboratory and microbiological parameters were compared.
The final analysis included 158 patients with CPE. The majority were male (130, 85.0%), and the mean age was 62.8 years. The mean duration of hospital stay was 17.7 (±10.2) days. The mean duration of chest tube drainage was 9.6 (±6.7) days. Streptococcus viridans (48.4%) was the most common pathogen. Intrapleural fibrinolysis was performed in 85 (53.8%); additional tube insertion was needed in 40 (25.3%) patients. In the multivariate analysis after adjusting for covariates, a prolonged hospital stay was associated with fever (aOR: 3.42, P = 0.02), lower PaO2 (aOR: 4.89, P = 0.007) and haemoglobin (aOR: 4.90, P = 0.003) levels, and an increased blood neutrophil fraction (aOR: 3.83, P = 0.01) on admission as well as the identification of microbes in CPE (aOR: 4.14, P = 0.03), and ineffective pleural drainage (aOR: 3.28, P = 0.03).
This study suggests that physicians should note the clinical symptoms and laboratory findings of severe infection and effectiveness of pleural drainage to predicate which patients with a CAP needing thoracostomy for CPE will have a prolonged hospital stay.
[Show abstract][Hide abstract] ABSTRACT: Excessive dynamic airway collapse (EDAC) is a disease entity of excessive reduction of the central airway diameter during exhalation, without cartilage collapse. An 80-year-old female presented with generalized edema and dyspnea at our hospital. The patient was in a state of acute decompensated heart failure due to pneumonia with respiratory failure. We accordingly managed the patient with renal replacement therapy, mechanical ventilation and antibiotics. Bronchoscopy confirmed the diagnosis of EDAC. We scheduled extubation after the improvement of pneumonia and heart condition. However, extubation failure occurred due to hypercapnic respiratory failure with poor expectoration. Her EDAC was improved in response to high flow nasal oxygen therapy (HFNOT). Subsequently, the patient was stabilized and transferred to the general ward. HFNOT, which generates physiologic positive end expiratory pressure (PEEP) effects, could be an alternative and effective management of EDAC. Further research and clinical trials are needed to demonstrate the therapeutic effect of HFNOT on EDAC.
Preview · Article · Oct 2015 · Tuberculosis and Respiratory Diseases
[Show abstract][Hide abstract] ABSTRACT: Therapeutic drug monitoring in tuberculosis remains controversial. We evaluated the relationship between anti-tuberculosis drug levels in blood and clinical outcome.Serum concentrations of first-line anti-tuberculosis drugs were measured in tuberculosis patients between March 2006 and April 2013. Venous blood was drawn 2 h after drug ingestion and analyzed using high-performance liquid chromatography/tandem mass spectrometry. We retrospectively reviewed the data and determined the association of serum drug levels with clinical outcome.Among 413 patients, the prevalence of low serum concentrations of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA) was 59.3%, 27.8%, 12.8%, and 8.0%, respectively. The low INH group had a greater percentage of patients with a history of tuberculosis treatment (19.2% vs. 11.0%; P = .026) and was more likely to present with drug-resistant strains (17.6% vs. 8.8%; P = .049) than the normal INH group; however, low levels of INH, RMP, EMB, and PZA were not related to treatment outcome. Low INH level had a tendency to be associated with 2-month culture positivity, but it was not statistically significant (P = .072) in multivariate analysis. Seventeen (4.1%) patients experienced a recurrence. However, the recurrence rate was not statistically different between the low and normal INH groups.Low-serum INH may play a role both in recurrence and in acquired drug resistance. However, the serum level of INH was not directly related to either treatment response or recurrence rate. The role and usefulness of therapeutic drug monitoring should be evaluated in further prospective studies.
No preview · Article · Oct 2015 · Antimicrobial Agents and Chemotherapy
[Show abstract][Hide abstract] ABSTRACT: Background:
Radiogenomic features are predictive of anaplastic lymphoma kinase (ALK) rearrangement in surgically resected non-small cell lung cancer (NSCLC).
ALK rearrangement was screened by fluorescent in situ hybridization in 497 patients with resected NSCLC. Of these, 198 patients screened for both ALK and epidermal growth factor receptor (EGFR) mutation were enrolled. Clinicopathologic findings, survival after surgical procedure, computed tomographic (CT) features, and maximum standardized uptake value according to different genotypes were investigated with univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors.
The prevalence of ALK positivity in resected NSCLC was 5.0% (25 of 497). Patients with ALK rearrangement showed significant differences in terms of patient's age (p = 0.006 for ALK versus EGFR, and 0.04 for ALK versus wild type [WT]/WT, respectively), solid lesion (p = 0.0074 for ALK versus EGFR), degree of contrast enhancement (p = 0.0006 for ALK versus EGFR), and lesion margin (p = 0.0011 for ALK versus EGFR, and 0.0314 for ALK versus WT/WT, respectively) compared with EGFR mutant and WT/WT cohorts. Multivariate analysis revealed that young age, solid lesion, lobulated margin, and hypoattenuation at contrast-enhanced CT scan were independent predictors of ALK positivity (p = 0.027, 0.046, 0.001, 0.021, respectively). The area under the ROC curve of the predictive model was 0.832, which suggests good discrimination.
ALK-rearranged lung cancer has characteristic clinical and imaging features compared with EGFR mutant or WT/WT cohorts. Our findings suggest that young age, lobulated margin, solid lesion, and hypoattenuation at contrast-enhanced CT scan are important predictors of ALK-rearranged lung cancer.
Full-text · Article · Oct 2015 · The Annals of thoracic surgery
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Some non-small-cell lung cancer patients have preserved pulmonary function after surgery. Compared with open thoracotomy, video-assisted thoracic surgery (VATS) is widely performed and preserves pulmonary function. Patients with non-small-cell lung cancer have an extremely poor prognosis without surgery. Clinicians should therefore decide which patients can safely tolerate lung resection. This study aimed to identify factors associated with preserving pulmonary function after VATS in non-small-cell lung cancer patients.
Three hundred and fifty-one patients with non-small-cell lung cancer underwent VATS and preoperative and 12-month postoperative pulmonary function tests. Patients with and patients without preserved forced expiratory volume in 1 s (FEV1) and diffusing capacity of carbon monoxide were compared.
The FEV1 was preserved after VATS in 142 (40.5%) patients. In multivariable analysis, this group was significantly associated with VATS sublobar resection (P < 0.001) and resection at the right upper lobe or right middle lobe (vs right lower lobe, P = 0.048; vs left upper lobe, P = 0.003; vs left lower lobe, P = 0.015). Diffusing capacity of carbon monoxide was preserved in 129 (36.8%) patients. Multivariable analysis showed that VATS sublobar resection (P < .001), lower baseline diffusing capacity of carbon monoxide (P < 0.001) and right upper lobe or right middle lobe resection (vs right lower lobe, P = 0.0014; vs left upper lobe, P = 0.029, vs left lower lobe, P = 0.014) were significantly associated with preserved diffusing capacity of carbon monoxide.
For preserving pulmonary function after non-small-cell lung cancer surgery, VATS sublobar resection was superior to VATS lobectomy, and surgery on the right upper lobe or right middle lobe was superior to that at other sites.
No preview · Article · Sep 2015 · European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery
[Show abstract][Hide abstract] ABSTRACT: : Insulin-like growth factor-1 receptor (IGF1R) is a membrane receptor-type tyrosine kinase that has attracted considerable attention as a potential therapeutic target, although its clinical significance in non-small cell lung cancer (NSCLC) is controversial. This study aimed to clarify the clinical significance of IGF1R expression in human NSCLC.
: IGF1R protein expression was evaluated using immunohistochemistry in 372 patients with NSCLC who underwent curative surgical resection (146 squamous cell carcinomas [SqCCs] and 226 adenocarcinomas [ADCs]). We then analyzed correlations between expression of IGF1R and clinicopathological and molecular features and prognostic significance.
: Membranous and cytoplasmic IGF1R expression were significantly higher in SqCCs than in ADCs. In patients with SqCC, membranous IGF1R expression was associated with absence of vascular, lymphatic, and perineural invasion; lower stage; and better progression-free survival (PFS) (hazard ratio [HR], 0.586; p= .040). In patients with ADC, IGF1R expression did not have a significant prognostic value; however, in the subgroup of epidermal growth factor receptor ( EGFR )-mutant ADC, membranous IGF1R expression was associated with lymphatic and perineural invasion, solid predominant histology, and higher cancer stage and was significantly associated with worse PFS (HR, 2.582; p= .009).
: Lung ADC and SqCC showed distinct IGF1R expression profiles that demonstrated prognostic significance. High membranous IGF1R expression was predictive of poor PFS in EGFR -mutant lung ADC, while it was predictive of better PFS in SqCC. These findings will help improve study design for subsequent investigations and select patients for future anti-IGF1R therapy.
[Show abstract][Hide abstract] ABSTRACT: In carcinogenesis of peripheral pulmonary carcinomas, multiple genetic and epigenetic alterations are involved. In this study, we quantified methylation levels of repetitive DNA elements (L1 and Alu) and six CpG island methylator phenotype (CIMP)-panel markers in various lesions representing steps in the development of lung adenocarcinoma (ADC), including atypical adenomatous hyperplasia, adenocarcinoma in situ, and invasive ADC. We then assessed methylation levels in an independent set of stage I ADCs (n = 100) and correlated methylation status with clinicopathological findings and clinical outcome. The pattern of changes in the methylation levels of L1 and Alu was different during progression of the lesion along the process of multistep carcinogenesis. A methylation level of >52.4 % of L1 and of >19.7 % of Alu in stage I ADC was associated with shorter cancer-specific survival in univariate but not in multivariate analysis. A tumor to normal lung tissue methylation ratio of >0.693 of L1 was an independent parameter heralding poor prognosis for stage I ADC patients. Methylation of CIMP-related genes was found in ADC. Stage I ADC cases without methylation of any of the six markers had a significantly shorter cancer-specific survival than ADC with methylation of one or more markers. The combination of tumor to normal L1 methylation ratio > 0.693 and absence of methylation of CIMP markers correlated independently with shorter cancer-specific survival. In conclusion, our findings suggest that Alu hypomethylation is an early and L1 hypomethylation a later event during multistep pulmonary carcinogenesis. The prognostic significance of the combination of methylation status of L1 and CIMP markers must be validated in large-scale studies of pulmonary ADC.
No preview · Article · Mar 2015 · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
[Show abstract][Hide abstract] ABSTRACT: The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.
[Show abstract][Hide abstract] ABSTRACT: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IκBα)/nuclear factor-kappa B (NF-κB) pathway in RAW 264.7 cells.
[Show abstract][Hide abstract] ABSTRACT: Acute respiratory distress syndrome (ARDS) remains an unsolved problem in the intensive care unit (ICU) that can be treated with venovenos extracorporeal membrane oxygenation (VV-ECMO). We summarized retrospectively collected data from an institutional experience with VV-ECMO in patients with severe acute respiratory failure and identified the clinical parameters associated with successful ECMO weaning. Among the 45 cases who received ECMO for pneumonia(n=19), exacerbation of interstitial lung disease (n=11), ARDS secondary to sepsis(n=8), aspiration pneumonitis(n=2), postoperative ARDS (n=3), and others(n=2), 21(46.7%) were successfully weaned from ECMO. In a univariate analysis median platelet (PLT) count at ICU admission(162 vs. 97 × 10/L, p=0.046) and pre-day 1(118.5 vs. 62.5 × 10/L, p = 0.046) were higher in the ECMO-weaned group than those in the weaning failure group. Using a PLT level of 70 × 10/L, the odds ratio for successful ECMO weaning was 11.0(95% CI 1.34-87.16, p=0.023) in the multivariate analysis. Bleeding complication rates were similar between the two groups. High PLT counts at ICU admission and the day immediately prior to initiating ECMO might play a key role in successful weaning of VV-ECMO for severe acute respiratory failure. Further studies should evaluate the proper target PLT level to enhance ECMO outcomes.
No preview · Article · Nov 2014 · ASAIO journal (American Society for Artificial Internal Organs: 1992)
[Show abstract][Hide abstract] ABSTRACT: Percutaneous needle aspiration or biopsy (PCNA or PCNB) is an established diagnostic technique that has a high diagnostic yield. However, its role in the diagnosis of nodular ground-glass opacities (nGGOs) is controversial, and the necessity of preoperative histologic confirmation by PCNA or PCNB in nGGOs has not been well addressed.
We here evaluated the rates of malignancy and surgery-related complications, and the cost benefits of resecting nGGOs without prior tissue diagnosis when those nGGOs were highly suspected for malignancy based on their size, radiologic characteristics, and clinical courses. Patients who underwent surgical resection of nGGOs without preoperative tissue diagnosis from January 2009 to October 2013 were retrospectively analyzed.
Among 356 nGGOs of 324 patients, 330 (92.7%) nGGOs were resected without prior histologic confirmation. The rate of malignancy was 95.2% (314/330). In the multivariate analysis, larger size was found to be an independent predictor of malignancy (odds ratio, 1.086; 95% confidence interval, 1.001-1.178, p =0.047). A total of 324 (98.2%) nGGOs were resected by video-assisted thoracoscopic surgery (VATS), and the rate of surgery-related complications was 6.7% (22/330). All 16 nGGOs diagnosed as benign nodules were resected by VATS, and only one patient experienced postoperative complications (prolonged air leak). Direct surgical resection without tissue diagnosis significantly reduced the total costs, hospital stay, and waiting time to surgery.
With careful selection of nGGOs that are highly suspicious for malignancy, surgical resection of nGGOs without tissue diagnosis is recommended as it reduces costs and hospital stay.