Correlation of fractional exhaled nitric oxide (FeNO) and clinical outcomes in patients with chronic obstructive pulmonary disease: A prospective cohort study.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is an acceptable and noninvasive marker for defining eosinophilic airway inflammation. Further study is necessary to clarify the role of FeNO in patients with chronic obstructive pulmonary disease (COPD). This study aimed to determine the association between FeNO levels and clinical outcomes. METHODS: A prospective observational study was conducted at Songklanagarind Hospital from October 2020 to November 2022. FeNO testing and spirometry were performed at the initial visit and 12-month follow-up. Exacerbation, hospitalization, lung function decline, and all-cause mortality were analyzed to determine the association between FeNO levels and clinical outcomes. RESULTS: A total of 60 patients with COPD were enrolled, 88.3 % of whom were male, with a mean age of 71.3 ± 9.5 years. There were 18 patients (30 %) in the high FeNO group (≥25 ppb) and 42 patients (70 %) in the low (<25 ppb) FeNO group. The mean blood eosinophil count (BEC) was significantly higher in the high FeNO group (p < 0.001). After a 12-month follow-up period, high FeNO group had higher exacerbation events (HR of 1.26, 95 % confidence interval (CI), 1.10-1.97, p= 0.025). Hospitalization and mortality rates were significantly higher in the high FeNO group. Regardless of the inhaled corticosteroids used, patients with high BEC and FeNO levels tended to have a greater risk of exacerbation. CONCLUSION: In patients with COPD, FeNO levels are strongly correlated with BEC. Poor clinical outcomes were reported in patients with high FeNO levels. FeNO may be a useful biomarker for predicting clinical outcomes in patients with COPD.

Prevalence, predictors, dynamic bone change, and treatment efficacy of osteoporosis among chronic obstructive pulmonary disease patients: a prospective cohort study.

Background: Osteoporosis is a silent chronic obstructive pulmonary disease (COPD) comorbidity that is often under-detected. We aimed to study the prevalence and potential predictors of osteoporosis in COPD. Dynamic changes in bone mass density (BMD) and treatment efficacy of bisphosphonate were also assessed. Methods: This prospective cohort study included COPD patients between January 2017 and January 2019. Demographics data, spirometric parameters, and C-reactive protein (CRP) were collected. Bone mineral density (BMD) at the lumbar spine (L2-4) and both femoral necks were measured after enrollment and the 12-month follow-up. Participants were categorized into three groups per the baseline BMD T-score: normal (≥ - 1.0), osteopenia (between -1.0 and - 2.5), and osteoporosis (≤ - 2.5). In the osteoporosis group, alendronate 70 mg/week with vitamin D and calcium was prescribed. Results: In total, 108 COPD patients were enrolled. The prevalence of osteoporosis and osteopenia were 31.5 and 32.4%, respectively. Advanced age, lower body mass index (BMI), history of exacerbation in the previous year, and high CRP levels were significant predictors of osteoporosis. After 12 months, 35.3% in the osteoporosis group reported new vertebral and femoral fractures, compared to none in the non-osteoporosis group (p < 0.001). In the normal BMD and osteopenia groups showed a further decline in BMD after 12-month. Conversely, the osteoporosis group showed a statistically significant improvement in BMD after anti-resorptive treatment (p < 0.001). Conclusion: The prevalence of osteoporosis was high in Thai COPD patients. Advanced age, lower BMI, history of exacerbation, and high CRP levels were potential predictors. A rapid decline in BMD was observed in COPD patients without treatment.

Prevalence, associated factors, and clinical consequences of metabolic syndrome in chronic obstructive pulmonary disease patients: a 5-year prospective observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by multiple systemic comorbidities, not only airflow limitation. Metabolic syndrome (MetS) is a common comorbidity. Patients with COPD have a higher risk of MetS than do healthy individuals. OBJECTIVES: We aimed to investigate the prevalence of and explore the factors associated with MetS in Thai COPD patients and to assess the clinical consequences of MetS after a 5-year follow-up period. METHODS: A prospective observational study was conducted in patients with stable COPD at Songklanagarind Hospital between June 2015 and November 2019. MetS was defined according to the International Diabetes Federation 2005 criteria. The patients were followed-up for 5 years. The prevalence, associated factors, and consequences of MetS were analyzed. RESULTS: A total of 115 patients with COPD were enrolled, of whom 95.3% were male. The overall prevalence of MetS was 37.4% (43 patients). Chronic bronchitis and high C-reactive protein (CRP) levels were independently and significantly associated with MetS in patients with COPD (p = 0.036 and 0.044, respectively). After following patients for 5 years, the incidence of cardiovascular disease and stroke, exacerbation rate, and mortality rate were significantly higher in the COPD with MetS group [relative risk (RR) = 15.36, 95% confidence interval (CI) = (2.13-110.67), RR = 45.43, 95% CI = (4.61-447.07), RR = 1.94, 95% CI = (1.40-2.70), and RR = 48.01, 95% CI = (1.12-2049.43), respectively]. CONCLUSION: The prevalence of MetS is high in patients with COPD. Chronic bronchitis and high CRP levels are associated with MetS in COPD. The incidence of clinical consequences was significantly higher in patients with COPD and MetS after a 5-year follow-up. Screening for MetS is strongly recommended for all patients with COPD.

Diagnostic and prognostic value of serum miR-145 and vascular endothelial growth factor in non-small cell lung cancer.

Previous studies have reported the diagnostic and prognostic value of serum microRNA (miR)-145 and vascular endothelial growth factor (VEGF) levels in various types of cancer; however, their clinical use in non-small cell lung cancer (NSCLC) remains unclear. The present study included 215 patients, 106 with NSCLC and 109 with other lung diseases (OLDs). miR-145 expression levels were determined using reverse transcription-quantitative PCR (RT-qPCR) and VEGF levels were measured using an ELISA. The diagnostic performance was assessed using a receiver operating characteristic curve and area under the curve (AUC) analysis. A Kaplan-Meier survival curve and Cox regression analysis were employed to evaluate the prognostic significance of the markers. The biological function of miR-145 was examined in A549 and H1792 cell lines. The effects of miR-145 on cell proliferation of NSCLC cells were evaluated by flow cytometry, and the expression levels of miR-145 and cell cycle-related genes were determined by RT-qPCR. The results revealed that miR-145 and VEGF exhibited fair diagnostic performance [AUC, 0.61 (95% CI, 0.55-0.68) and AUC, 0.64 (95% CI, 0.57-0.71), respectively]. Combining age and smoking status with miR-145 and VEGF provided the best model for differentiating patients with NSCLC from those with OLDs (AUC, 0.76; 95% CI, 0.69-0.83). Furthermore, low serum miR-145 levels were associated with poor overall survival [hazard ratio (HR), 0.48; 95% CI, 0.27-0.85], whereas high VEGF levels were not associated with poor overall survival (HR, 1.47; 95% CI, 0.81-2.68). In addition, the results of the in vitro experiments indicated that miR-145 decreased cell proliferation via the induction of cell cycle arrest. In conclusion, the findings of the present study suggested that combining miR-145 and VEGF levels with clinical risk factors may be a potential diagnostic scheme for NSCLC. In addition, serum miR-145 may be used as a prognostic marker. These results indicated that miR-145 may function as a tumor suppressor in NSCLC.

Serum miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer.

Tumor-promoting cytokines are a cause of tumor progression; therefore, identifying key regulatory microRNAs (miRNAs) for controlling their production is important. The aim of this study is to identify promising miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer (NSCLC). We identified circulating miRNAs from 16 published miRNA profiles. The selected miRNAs were validated in the serum of 32 NSCLC patients and compared with 33 patients with other lung diseases and 23 healthy persons using quantitative real-time PCR. The cytokine concentration was investigated using the enzyme-linked immunoassay in the same sample set, with clinical validation of the miRNAs. The correlation between miRNA expression and cytokine concentration was evaluated by Spearman's rank correlation. For consistent direction, one up-regulated miRNA (miR-145) was found in four studies, and seven miRNAs were reported in three studies. One miRNA (miR-20a) and four miRNAs (miR-25-3p, miR-223, let-7f, and miR-20b) were reported in six and five studies. However, their expression was inconsistent. In the clinical validation, serum miR-145 was significantly down-regulated, whereas serum miR-20a was significantly up-regulated in NSCLC, compared with controls. Regarding serum cytokine, all cytokines [vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and transforming growth factor ß (TGF-ß)], except tumor necrosis factor-α (TNF-α), had a higher level in NSCLC patients than controls. In addition, we found a moderate correlation between the TGF-ß concentration and miR-20a (r = -0.537, p = 0.002) and miR-223 (r = 0.428, p = 0.015) and a weak correlation between the VEGF concentration with miR-20a (r = 0.376, p = 0.037) and miR-223 (r = -0.355, p = 0.046). MiR-145 and miR-20a are potential biomarkers for NSCLC. In addition, the regulation of tumor-promoting cytokine, through miR-20a and miR-223, might be a new therapeutic approach for lung cancer.

Serum miR-339-3p as a potential diagnostic marker for non-small cell lung cancer.

Objective: MicroRNA (miRNA), a short noncoding RNA, is claimed to be a potential blood-based biomarker. We aimed to identify and evaluate miRNAs as diagnostic biomarkers for non-small cell lung cancer (NSCLC). Methods: Profiles of 745 miRNAs were screened in the serum of 8 patients with NSCLC and 8 age- and sex-matched controls using TaqMan low-density arrays (TLDAs) and validated in 25 patients with NSCLC and 30 with other lung diseases (OLs) as well as in 19 healthy persons (HPs). The diagnostic performance of the candidate miRNAs was assessed in 117 cases of NSCLC and 113 OLs using quantitative real-time polymerase chain reaction (qRT-PCR). Differences in miRNA expression between patients with NSCLC and controls were assessed using the Mann-Whitney U test. The area under receiver operating characteristic (ROC) curve (AUC) was obtained based on the logistic regression model. Results: Ten miRNAs were found to be differentially expressed between patients with NSCLC and controls, including miR-769, miR-339-3p, miR-339-5p, miR-519a, miR-1238, miR-99a#, miR-134, miR-604, miR-539, and miR-342. The expression of miR-339-3p was significantly higher in patients with NSCLC than in those with OLs (P < 0.001) and HPs (P = 0.020). ROC analysis revealed an miR-339-3p expression AUC of 0.616 [95% confidence interval (CI): 0.561-0.702]. The diagnostic prediction was increased (AUC = 0.706, 95% CI: 0.649-0.779) in the model combining miR-339-3p expression and other known risk factors (i.e., age, smoking status, and drinking status). Conclusions: MiR-339-3p was significantly upregulated in patients with NSCLC compared with participants without cancer, suggesting a diagnostic prediction value for high-risk individuals. Therefore, miR-339-3p expression could be a potential blood-based biomarker for NSCLC.

A new and easily used modified myasthenia gravis score.

We developed a new modified quantitative myasthenia gravis (mQMG) score which can be easily used in the condition of limited access to specific equipment.  Substitution peak expiratory flow rate for forced vital capacity, and removal of handgrip strength and speech test items were the major modifications. The new mQMG score was tested for content validity and test-retest reliability. Then 45 Myasthenia Gravis Foundation of America (MGFA) grade II-III outpatients who had been clinically stable ≥ 3 months were enrolled to analyze correlations between the mQMG score and the original quantitative myasthenia gravis (QMG) score, the mQMG score and the previously validated Thai-version myasthenia gravis quality of life score (MGQOL 15-Thai version), and the QMG score and MGQOL15-Thai version score by Spearman correlation (p < 0.05). The positive correlation coefficient between the mQMG and QMG score was very strong (r = 0.96, 95% CI, 0.93-0.98, p < 0.001), between the mQMG and MGQOL15-Thai version score was moderate (r = 0.44, 95% CI, 0.17-0.65, p = 0.003), and between the QMG and MGQOL15-Thai version score was moderate (r = 0.41, 95% CI, 0.14-0.63, p = 0.005). We thus conclude that the new mQMG score is practical for use in research and clinical care.

Efficacy and safety profile of autologous blood versus talc pleurodesis for malignant pleural effusion: a randomized controlled trial.

BACKGROUND: Autologous blood is a novel, high-efficacy sclerosant for treatment of malignant pleural effusion (MPE), similar to tetracycline. There has been no comparative data between autologous blood and a worldwide sclerosant like talc. We aimed to compare the effectiveness of autologous blood versus talc pleurodesis. METHODS: A prospective study was conducted at Songklanagarind Hospital, Songkhla, Thailand. A total of 123 symptomatic MPE cases were randomized to receive autologous blood pleurodesis (ABP) versus pleurodesis with talc slurry. In the ABP group, 100 ml of autologous venous blood was instilled through a chest drain, followed by 50 ml of sterile normal saline (NSS). In the talc group, 20 ml of 1% lidocaine diluted in 30 ml NSS was instilled, followed by 4 g of sterile talc (Steritalc®, a non-small particle size talc) suspended in 100 ml of NSS. A 30-day pleurodesis efficacy (according to Paladine's criteria), along with the adverse events, was evaluated. RESULTS: Fifty-six cases in the ABP, and 54 cases in the talc group completed the study. There was no difference between the two groups in the demographic data. The overall pleurodesis success rate at 30 days was 82.0% in the ABP group, comparable to the talc pleurodesis group (87.0%, p = 0.12). The percentage of fever (9.0% versus 28.0%, p = 0.04), amount of acetaminophen required by each participant (2.2 ± 0.7 versus 4.6 ± 0.9 tablets, p = 0.03), pain score and percentage of cases who needed opioids (9.0% versus 26.0%, p = 0.02) and hospital stay (10.2 ± 2.7 versus 12.8 ± 3.4, p = 0.04) were significantly lower in the ABP group; no infectious or serious events occurred. CONCLUSIONS: ABP had an equivalent efficacy compared to talc pleurodesis for MPE treatment. ABP offered less fever and pain and could shorten hospital stays, and neither produced means ABP did not produce clotted drainage, pulmonary or systemic adverse events.

Methylation of 14-3-3σ gene and prognostic significance of 14-3-3σ expression in non-small cell lung cancer.

Loss of 14-3-3σ expression through DNA methylation has been associated with carcinogenesis and the prognosis for various cancer types. Detection of methylation of the gene in serum may be useful for diagnostic utility. The present study aimed to investigate the correlation between 14-3-3σ methylation level in 36 paired tumor tissues of non-small cell lung cancer (NSCLC) and matched serum using methylation-specific polymerase chain reaction. The prognostic significance of 14-3-3σ expression in 167 NSCLC was also evaluated using immunohistochemistry. Methylation of the 14-3-3σ gene was identified in all samples. The methylation level in the serum (mean 87.7%, range 64.6-100%) was higher compared with tumor (mean 46.7%, range 25.3-56.3%). However, no significant correlation between methylation levels in tissues and serums was observed (Spearman's correlation, -0.036; P=0.837). In the 167 tumor tissues, the majority of the cases (83.8%) exhibited negative expression. Adenocarcinoma is more likely to exhibit negative expression (91.4%) compared with squamous cell carcinoma (70.2%). No significant difference was identified in the overall survival according to 14-3-3σ expression status and 14-3-3σ expression did not demonstrated independent prognostic significance. In conclusion, NSCLC harbors certain levels of 14-3-3σ methylation in the tumor and the sera of patients. The clinical value of serum 14-3-3σ methylation should be further elucidated. Immunohistochemical expression 14-3-3σ protein has limited value on prognostic significance.

Pulmonary Cryptococcosis Presenting With Lung Mass: Report of 7 Cases and Review of Literature.

Pulmonary cryptococcosis is commonly found in immunocompromised patients. This microorganism rarely infects immunocompetent individuals, and when it does, it causes mild symptoms. The radiological findings of this disease may involve an intrapulmonary mass that mimics lung tumor. The objective of this study was to review the clinicopathological information, radiological findings, and treatment of patients who presented with intrapulmonary mass due to cryptococcosis. This study collected data from 7 patients who were treated at Songklanagarind Hospital, Songkhla, Thailand, between 2009 and 2014. Their clinical data, radiological findings, pathological results, and treatment protocols were reviewed. The patients were 2 women and 5 men, ranging in age from 37 to 79 years old. One case was an immunocompromised host. Four cases experienced the chest symptoms of dyspnea, hemoptysis, and chronic cough. The most common location of mass was the left lower lobe (71%). Four cases had a history of bird contact. Lung lobectomy was performed in 3 cases (42%), and all of the patients were treated with oral fluconazole. An intrapulmonary mass caused by this microorganism is mainly found in immunocompetent patients. Treatment with the antifungal drug fluconazole is very effective.

Value of preoperative 6-minute walk test for predicting postoperative pulmonary complications.

OBJECTIVES: The objective of this study was to determine the performance of preoperative 6-minute walk test (6MWT) for predicting postoperative pulmonary complications (PPC) in high risk patients undergoing elective surgery under general anesthesia. METHODS: A prospective cohort study was conducted in patients scheduled to undergo elective thoracic or nonthoracic surgery and indicated for preoperative pulmonary evaluation in Songklanagarind Hospital, Songkhla, Thailand. Preoperative spirometry, 6MWT were done and 30-day PPC were recorded. The multiple regression analysis and receiver operating characteristic (ROC) curves were used to analyze the variables and to compare the performance of 6MWT and spirometry tests. RESULTS: A total of 78 participants were recruited into the study. 6MWT was done completely in all cases without any complications. Among these tests, 14 cases (17.9%) had contraindications to spirometry and two cases were unable to achieve the criteria for acceptable efforts. PPC developed in 17 cases (21%) with a high mortality (17.7%). A multiple regression analysis showed elderly, poor general health status, smoking history, low level of the mean value of forced expiratory volume in 1 second (FEV1) % predicted (by spirometry) and shorter 6-minute walk distance (6MWD) were the independent factors associated with PPC. Patients developing PPC had a significantly lower preoperative 6MWD compared with patients without PPC (256.0 ± 48.0 versus 440.0 ± 117.1 meters, p < 0.001). 6MWD of ⩽325 meters was a threshold for predicting PPC with 77% sensitivity and 100% specificity, and had a good predictive value for PPC similar to that for the FEV1 %. CONCLUSIONS: Preoperative 6MWT is a very useful alternative test for predicting PPC in high risk patients scheduled to undergo surgery under GA.

Diagnostic yield and safety of sputum induction with nebulized racemic salbutamol versus hypertonic saline in smear-negative pulmonary tuberculosis.

OBJECTIVES: The aim of the study was to compare the diagnostic yield and safety profile of sputum induction (SI) with nebulized racemic salbutamol solution versus hypertonic saline in smear-negative pulmonary tuberculosis (TB). METHODS: The prospective study was conducted at Songklanagarind Hospital, Thailand. Suspected smear-negative pulmonary TB cases were recruited and randomized to receive SI with either nebulized racemic salbutamol solution or 3% sodium chloride (NaCl) solution. Induced sputum was examined with the acid-fast bacilli (AFB) smear test and cultured for Mycobacterium tuberculosis. The efficacy and adverse events of SI were analyzed. RESULTS: A total of 59 patients received SI with nebulized racemic salbutamol solution and 53 received 3% NaCl solution. There was no significant difference between the two groups in the average quantity of induced sputum (1.3 ± 0.1 versus 1.2 ± 0.2 ml, p = 0.5). The percentages of positive AFB smear and TB cultures in the salbutamol group were 15% and 22%, and 13% and 17% in the 3% NaCl group (p = 0.5), respectively. Racemic salbutamol solution could increase the TB diagnostic yield similarly to 3% NaCl, but incurred less chest tightness (5% versus 15%) and bronchospasm (0% versus 11.3%, p = 0.02) compared with 3% NaCl. CONCLUSIONS: SI by nebulized racemic salbutamol solution offers equal benefits to 3% NaCl solution in increasing both sputum quantity and diagnostic yield in smear-negative patients suspected of having pulmonary TB. Nebulized racemic salbutamol does not produce bronchospasm and chest tightness occurs less frequently than with 3% NaCl. Therefore, SI with nebulized racemic salbutamol solution should be considered as a good alternative noninvasive diagnostic tool for the diagnosis of pulmonary TB when hypertonic saline is unavailable or contraindicated.

Efficacy and safety profile of autologous blood versus tetracycline pleurodesis for malignant pleural effusion.

OBJECTIVES: Autologous blood pleurodesis (ABP) is used for the treatment of pneumothorax with a good efficacy. The aim of this study is to determine the efficacy and safety of ABP in the treatment of malignant pleural effusion (MPE). METHODS: A prospective study was conducted at Songklanagarind Hospital, Thailand. Symptomatic MPE patients were randomized to receive pleurodesis with either autologous blood or tetracycline. In the ABP group, 100 ml of autologous venous blood was instilled via chest tube followed by 50 ml of sterile normal saline (NSS). In the tetracycline group, 20 ml of 1% lidocaine diluted in 30 ml NSS was instilled followed by 1 g of tetracycline diluted in 100 ml of NSS. The chest tube was clamped for 2 hours, then reconnected to suction and removed. Pleurodesis effectiveness was evaluated according to Paladine's criteria and adverse events were recorded. RESULTS: A total of 48 symptomatic MPE patients were recruited. Of these, 24 cases were randomized to receive ABP and 24 cases received tetracycline. There was no difference between the two groups in baseline characteristics. The overall success rate of pleurodesis was the same in both the autologous blood group and the tetracycline group (83.4% versus 87.5%, p = 0.36). In the ABP group, the pain score and fever were significantly lower (8.3% versus 29.1%, p = 0.003) and there was a small percentage of cases that needed analgesia (4.2% versus 75%, p < 0.001); no serious events occurred. CONCLUSIONS: ABP was as effective as tetracycline in the treatment of MPE. ABP produced less pain and fever, and could shorten the hospital stay.

Cuff leak volume as a clinical predictor for identifying post-extubation stridor.

BACKGROUND: Post-extubation stridor occurs after translaryngeal intubation results to re-intubation in a number of patients. OBJECTIVE: To determine the cut-off value of the cuff leak volume test among Thai patients as a predictor for post-extubation stridor MATERIAL AND METHOD: Demographic data and cuff leak volume were collected from patients who had been intubated with planned extubation. Clinical stridor was observed and identified after extubation. RESULTS: Among 115 patients, the cuff leak volume of less than 114 ml was used to predict post-extubation stridor with the sensitivity of 89%, specificity of 90%, positive predictive value of 65%, and negative predictive value of 98%, respectively. Among the stridor group, 12 of 19 cases (63.2%) needed re-intubation. CONCLUSION: The cuff leak volume of less than 114 ml can be used as a clinical predictor for identifying post-extubation stridor