Exploring the evolution of T cell function and diversity across different stages of non-small cell lung cancer.

The immune system plays a key role in detecting and fighting cancerous tumors. T cells are a crucial component in both natural and therapeutic cancer immunoediting responses, but it is unclear if they are the primary agents of these processes. In this study, patients with lung lesions detected by CT scan were selected, and their peripheral blood samples were analyzed for T cell population and serum cytokines/chemokines. T cell subtypes (CD3, CD4, CD8, CD27, CD28, CD45, CD45RA, CD57, CCR7, and PD1) and serum cytokines/chemokines (IL-2, IL-6, IL-10, IFN-γ, TGF-ß, TNFα, CXCL1, CXCL9, and CXCL12) were measured by flow cytometry and analysis before surgical resection or other cancer treatments. The frequency of T cell subpopulations in patients with lung cancer (n = 111) corresponded to those seen in patients with T cell exhaustion. As lung cancer progressed, the proportion of effector memory T cells decreased, while the proportion of naive T cells, PD-1, CD57+, CD28+CD27+, CD45RA+, and CD3+CD4+CCR7 increased. Circulating CD8+PD1+ T cells were positively correlated with intra-tumoral PD-L1 expression. Concurrently, serum levels of IL-2, TGF-ß, and CXCL9 decreased, while IL-6, IL-10, IFN-γ, and CXCL12 increased during the progression of lung cancer. In conclusion, T cell dysfunction is associated with cancer progression, particularly in advanced-stage lung cancer, and cancer immunoediting will provide early-stage cancer detection and further therapeutic strategies.

Environmental pollutants increase the risks of acute exacerbation in patients with chronic airway disease.

Objective: Respiratory infections are a common cause of acute exacerbations in patients with chronic airway disease, however, environmental factors such as air pollution can also contribute to these exacerbations. The study aimed to determine the correlation between pollutant levels and exacerbation risks in areas exposed to environmental pollution sources. Methods: From 2015 to 2016, a total of 788 patients with chronic airway diseases were enrolled in a study. Their medical records, including hospital visits due to acute exacerbations of varying severity were analyzed. Additionally, data on daily pollutant levels from the Air Quality Monitoring Network from 2014 to 2016 was also collected and analyzed. Results: Patients with chronic airway disease and poor lung function (FEV1 < 50% or obstructive ventilatory defect) have a higher risk of severe acute exacerbations and are more likely to experience more than two severe acute exacerbations within a year. The study found that in areas exposed to environmental pollution sources, there is a significant correlation between NO2, O3, and humidity with the main causes of severe acute exacerbation. When the levels of NO2 were higher than 16.65 ppb, O3 higher than 35.65 ppb, or humidity higher than 76.95%, the risk of severe acute exacerbation in patients with chronic airway disease increased. Conclusion: Acute exacerbations of chronic airway disease can be triggered by both the underlying disease state and the presence of air pollution. Computer simulations and early warning systems should be developed to predict acute exacerbations of chronic airway disease based on dynamic changes in air pollution.

Haemothorax due to intercostal artery injury after thoracentesis.

We present a rare case of haemothorax complication post thoracentesis. Contrast computed tomography was used to locate the bleeding site, and transarterial embolization was performed to stop intercostal artery bleeding.

Major comorbidities lead to the risk of adverse cardiovascular events in chronic obstructive pulmonary disease patients using inhaled long-acting bronchodilators: a case-control study.

BACKGROUND: While inhaled bronchodilators reduce symptoms and acute exacerbations of chronic obstructive pulmonary disease (COPD), their use is associated with increased cardiovascular events in some studies. This study investigates the risk of adverse events associated with the use of inhaled bronchodilators in COPD patients with multimorbidity. METHODS: A case-control study was conducted between January 2015 and December 2017, and patients with spirometry-confirmed diagnosis of COPD (N = 1565) using inhaled long-acting bronchodilators were enrolled. Medical records were reviewed and clinical data, including age, gender, smoking status, major comorbidities, lung function stage, history of exacerbations, bronchodilator regimens, and treatment duration were analyzed. Major adverse cardiovascular events occurring during long-acting bronchodilator use were recorded. RESULTS: The most common comorbidities were cardiovascular disease (CVD) (53.6%) and chronic kidney disease (CKD) (25.8%). We observed that CVD (odds ratio [OR], 5.77), CKD (OR, 2.02) and history of frequent exacerbations (OR, 2.37) were independent risk factors for cardiovascular events, regardless of the type of bronchodilators use. Moreover, COPD patients with both CKD and CVD had higher risk (6.32-fold) of adverse cardiovascular effects than those with neither comorbidity. Eighty-seven of 1565 (5.56%) COPD patients died during this study period. Of them, 21.8% (19/87) were cardiovascular-related and 73.6% (64/87) patients were respiratory-related mortality. Among COPD patients using long-acting bronchodilators, CKD was the only risk factor to predict cardiovascular events and cardiovascular-related mortality (OR, 4.87; 95% confidence interval [CI], 1.75-13.55]. CONCLUSIONS: COPD patients had higher risk of cardiovascular events were associated with their CVD and/or CKD comorbidities and history of frequent exacerbations, rather than associated with their use of inhaled bronchodilators.

Pulmonary infection caused by nontuberculous mycobacteria in a medical center in Taiwan, 2005-2008.

The aim of this study was to investigate the epidemiology and clinical characteristics of pulmonary infections caused by nontuberculous mycobacteria (NTM) in a university hospital in Taiwan from 2005 to 2008. During the study period, a total of 312 patients with NTM pulmonary infection were identified. Most patients with NTM pulmonary infection had preexisting pulmonary diseases or malignancies. The incidence (per 100,000 inpatients and outpatients) of patients with NTM isolations (6.67 in 2005 and 9.28 in 2008, P < .0001) from respiratory specimens and the incidence of patients with NTM pulmonary infection (3.54 in 2005 and 4.45 in 2008, P < .0141) increased significantly annually. The most common pathogens in patients with NTM-associated pulmonary infections were Mycobacterium avium complex (n = 110, 35.3%), followed by M. abscessus (n = 66, 21.2%). Incidence (per 100,000 inpatients and outpatients) of patients with pulmonary infections caused by rapidly growing mycobacteria (RGM) also increased significantly (1.06 in 2005 and 2.00 in 2008, P = .008). In conclusion, RGM, especially M. abscessus, had an increasingly important role in NTM pulmonary infections.

Successful treatment of bronchoesophageal fistula with esophageal and bronchial stenting.

Bronchoesophageal fistula is reported in 5-10% of patients with esophageal cancer. In most of these cases, the insertion of a single stent, either a tracheobronchial or an esophageal stent, is sufficient to seal off the fistula. In this case we describe a 67-year-old man with esophageal cancer and complications of bronchoesophageal fistula, which resulted in repeated pneumonia and acute respiratory failure. Initially, two expandable metallic membranous esophageal stents were placed to cover the fistula. However, the esophageal stent failed to stop the air leak and dislodged into the stomach. Thereafter, a bronchial stent was placed at the right intermediate bronchus and successfully stopped the air leak. The patient was then weaned from the ventilator 1 week after the insertion of a bronchial stent. In conclusion, stenting in both the esophagus and airways should be considered when both are severely invaded by malignancy, when the airway is compressed, or when the fistula is insufficiently sealed by an esophageal stent.

Clinical features and outcomes of disseminated infections caused by non-tuberculous mycobacteria in a university hospital in Taiwan, 2004-2008.

This retrospective study investigated the clinical characteristics and prognostic factors of patients with disseminated infections caused by non-tuberculous mycobacteria (NTM) in Taiwan. Forty patients who fulfilled the criteria for disseminated NTM infection at a medical centre from January 2004 to December 2008 were analyzed. More than half of the patients (n = 22, 55%) were HIV-infected and fever was the most common initial presentation (n = 21, 52.5%). There were 13 episodes of co-infection with other bacterial pathogens in 11 patients (30%). The most common site of NTM isolation from culture was blood (62.5%), followed by respiratory tract (52.5%). Mycobacterium avium complex was the most common species (70%). The overall mortality rate due to disseminated NTM infection was 30%. Univariate survival analysis showed significantly higher mortality rates in female patients, patients without anti-NTM treatment and patients co-infected with other bacterial pathogens. Multivariate analysis showed that lack of anti-NTM treatment was the only prognostic factor for a poor outcome (p = 0.001). In conclusion, maintaining a high level of suspicion and starting appropriate anti-NTM treatment promptly after diagnosis are crucial to improve outcome in patients with disseminated NTM infection.

Identification of nontuberculous mycobacterial infection by IS6110 and hsp65 gene analysis on lung tissues.

The clinical, histologic, and radiographic presentations of nontuberculous mycobacterial (NTM) lung disease are usually indistinguishable from those of reactivated pulmonary tuberculosis (TB), so it remains a great challenge for the clinician to make treatment decisions for patients with old TB and a positive culture result for NTM. This study investigated whether the mycobacterial specific heat shock protein 65 (hsp65) and Mycobacterium tuberculosis (MTB)-specific IS6110 gene would present in pulmonary lesions of patients with NTM pulmonary infection. Formalin-fixed and paraffin-embedded (FFPE) tissue blocks of 24 patients with NTM infections treated at the hospital from 1998 to 2008 were included. Mycobacterial hsp65 gene was amplified in 20 of the 24 patients, and the species identified by sequencing was consistent with corresponding culture results in 12 of these patients. MTB-specific IS6110 gene was detected in 3 of the 7 patients who had old TB and a subsequent diagnosis of fibrocavitary NTM lung disease. Polymerase chain reaction (PCR) analysis of hsp65 gene also confirmed the presence of MTB genes in 2 of these 3 patients. Our results indicate that PCR amplification and sequencing of the mycobacterial hsp65 gene is a sensitive assay for identification of NTM species in FFPE materials. However, consistent results of PCR analysis, microbiology study, histologic manifestations, radiology, and clinical presentation are important for correct diagnosis of NTM pulmonary infection. The presence of MTB gene in patients with fibrocavitary NTM lung lesions poses a clinical dilemma for deciding concurrent treatment TB and NTM infection.

Enzyme-linked immunospot assay for interferon-gamma to support the diagnosis of tuberculosis in diabetic patients.

The aim of this study was to evaluate the support to tuberculosis diagnosis of a new immunological tool, an enzyme-linked immunospot (ELISPOT) assay for interferon-γ, in diabetic patients. From March 2007 to January 2008, diabetic patients with suspected pulmonary tuberculosis were enrolled in a tertiary care hospital. Data on clinical characteristics of the patients and conventional laboratory results were collected and blood samples were obtained for ELISPOT assay (T SPOT-TB; Oxford Immunotec Ltd, Oxford, UK). A total of 84 patients with suspected pulmonary tuberculosis were recruited. Fifty-one (60.7%) of these patients were considered to have pulmonary tuberculosis, including 42 (50%) with confirmed tuberculosis and 9 (10.7%) with probable tuberculosis. The overall (confirmed and probable tuberculosis) sensitivity, specificity, positive predictive value and negative predictive value of the ELISPOT assay were 84.3%, 66.7%, 79.6%, and 73.3%, respectively. The negative predictive value of the ELISPOT assay was significantly higher in patients with adequate glycaemic control (90% vs 56.3%). In conclusion, the ELISPOT assay can provide useful support in diagnosing pulmonary tuberculosis in diabetic patients, especially those with adequate glycaemic control.

Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000-2008.

To assess the species distribution and epidemiologic trends of nontuberculous mycobacteria, we examined isolates from patients in Taiwan. During 2000-2008, the proportion increased significantly from 32.3% to 49.8%. Associated disease incidence increased from 2.7 to 10.2 cases per 100,000 patients. Mycobacterium avium complex and M. abscessus were most frequently isolated.

Molecular evidence of false-positive cultures for Mycobacterium tuberculosis in a Taiwanese hospital with a high incidence of TB.

BACKGROUND: Isolation of Mycobacterium tuberculosis (MTB) from the clinical specimens of patients with suspected TB remains the gold standard for diagnosis of TB. However, false-positive MTB cultures can occur as a result of laboratory contamination. METHODS: After reviewing the medical records of 400 TB cases identified during January 2008 to January 2009 by the infection control unit of a university-affiliated hospital in Taipei, Taiwan, five patients were considered as clinically suspected false-positive cases and were referred to a mycobacteriology laboratory for confirmation. Spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeat analyses were performed for all the suspected isolates and all other isolates cultured on the same day as the five suspected isolates. RESULTS: Three cases were confirmed as false-positive culture cases based on the laboratory investigation. The culture from one of these cases (index case 1) grew multidrug-resistant TB. Another patient (index case 2) received an extended course of anti-TB treatment after he was considered to have failed treatment because of the false-positive MTB culture result. No anti-TB medication was given for index case 3. All three cases with false-positive cultures had only one positive culture specimen among multiple consecutive specimens submitted for cultures. In addition, specimens of the false-positive cultures were all negative for acid-fast smears. CONCLUSIONS: False-positive MTB cultures should be suspected in the following situations: when growth is observed on only one specimen among multiple specimens submitted; when it is positive in only one culture medium, especially in broth; or when there is only one specimen submitted. False-positive MTB cultures can be further confirmed with modern molecular typing techniques.

Comparison of 2 interferon-gamma assays and Roche Cobas Amplicor Mycobacterium tuberculosis assay for rapid diagnosis of tuberculosis among patients with suspected tuberculosis in Taiwan.

BACKGROUND AND PURPOSE: Two commercial interferon-gamma (IFN-gamma) assays, which are commonly used for diagnosing latent tuberculosis (TB), are also useful for diagnosis of active TB. In this study, the IFN-gamma assays and polymerase chain reaction (PCR) for diagnosis of TB were compared. METHODS: A prospective comparison of the performance of 2 commercial IFN-gamma assays - QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB (T SPOT) - and PCR using the Roche Cobas Amplicor Mycobacterium tuberculosis (RCA-TB) assay for the rapid diagnosis of TB was conducted from January 2007 to December 2007 at a university-affiliated hospital in Taiwan. RESULTS: Of 187 patients enrolled in the study, results from both T SPOT and QFT-G were available for 154, including 109 patients with active TB and 45 with no TB. The sensitivity of T SPOT (89.0%) was higher than that of QFT-G (71.4%). RCA-TB had the highest sensitivity (90.2%) and specificity (100%), but was usually performed in patients with positive acid-fast bacilli smear test. In patients with extrapulmonary TB, T SPOT had a high diagnostic value (sensitivity, 81.3%). A significant discordance between the 2 IFN-gamma assays was also noted. IFN-gamma assays provided a more rapid diagnosis for tuberculosis than the conventional culture method (mean +/- standard deviation, 8.23 +/- 12.86 days; p < 0.001). CONCLUSIONS: Use of IFN-gamma may shorten the time to diagnosis of TB, especially for smear-negative patients and those with extrapulmonary disease.

Comparative in vitro activities of nemonoxacin, doripenem, tigecycline and 16 other antimicrobials against Nocardia brasiliensis, Nocardia asteroides and unusual Nocardia species.

OBJECTIVES: The aim of this study was to assess the in vitro activities of nemonoxacin (a novel non-fluorinated quinolone), doripenem, tigecycline and 16 other antimicrobial agents against the Nocardia species. METHODS: MICs of 19 antimicrobial agents for 125 clinical isolates of the Nocardia species were determined by the broth microdilution method. RESULTS: Nocardia brasiliensis (n = 61), Nocardia asteroides (n = 45), Nocardia flavorosea (n = 5), Nocardia otitidiscaviarum (n = 4), Nocardia farcinica (n = 3), Nocardia beijingensis (n = 2), Nocardia puris (n = 2) and one each of Nocardia nova, Nocardia jinanensis and Nocardia takedensis were identified based on a 16S rRNA gene sequencing analysis. For N. brasiliensis isolates, the MIC(90)s of the tested quinolones were in the order nemonoxacin < gemifloxacin = moxifloxacin < levofloxacin = ciprofloxacin, and the MIC(90)s of the tested carbapenems were in the order doripenem = meropenem < ertapenem < imipenem. Tigecycline had a lower MIC(90) (1 mg/L) than linezolid (8 mg/L). For N. asteroides isolates, the MIC(90)s of the tested quinolones were in the order nemonoxacin < gemifloxacin = moxifloxacin < levofloxacin < ciprofloxacin, and the MIC(90)s of the tested carbapenems were in the order doripenem = meropenem = imipenem < ertapenem. For the other 19 Nocardia species isolates, nemonoxacin showed good activity with the lowest MIC(90) of the tested quinolones. Among the four tested carbapenems, doripenem and meropenem had comparatively lower MIC(90)s. CONCLUSIONS: The results of this in vitro study suggest that nemonoxacin, linezolid and tigecycline show promise as treatment options for nocardiosis. Further investigation of their clinical role is warranted.