Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer.

Lung cancer is a major cause of death in Western countries. Current screening methods are invasive and still lead to a high percentage of false positives. There is, therefore, a need to find biomarkers that increase the probability of detecting lung cancer early. MicroRNAs (miRNAs) are stable molecules in blood plasma and exhaled breath condensate (EBC). We quantified miRNA-21 and miRNA-486 expression from plasma and EBC samples from patients with a diagnosis of non-small-cell lung cancer (NSCLC) and controls. miRNA-21 was significantly higher in plasma and in EBC of the NSCLC patients and miRNA-486 was significantly lower. This difference indicates a significantly improved diagnostic value, and suggests that these miRNAs could be clinically used as a first-line screening test in high-risk subjects.

Competence in pleural procedures.

Diseases of the pleura and pleural space are common and present a significant contribution to the workload of respiratory physicians, with most cases resulting from congestive heart failure, pneumonia, and cancer. Although the radiographic and ultrasonographic detection of pleural abnormalities may be obvious, the determination of a specific diagnosis can often represent a challenge. Invasive procedures such as pleural drainage, ultrasound/CT-guided pleural biopsy or medical thoracoscopy can be useful in determining specific diagnosis of pleural diseases. Management of primary and secondary spontaneous pneumothorax is mandatory in an interventional pulmonology training program, while the medical or surgical treatment of the recurrence is still a matter of discussion. Pleural drainage is a diagnostic and therapeutic procedure used in the treatment of pneumothorax and pleural effusions of different etiologies and even in palliation of symptomatic in malignant pleural effusion. Medical thoracoscopy (MT) is a minimally invasive procedure aimed at inspecting the pleural space. It could be a diagnostic procedure in pleural effusions (suspected malignant pleural effusion, infective pleural disease such as empyema or tuberculosis) or therapeutic procedure (chemical pleurodesis or opening of loculation in empyema). Diagnostic yield is 95% in patients with pleural malignancies and higher in pleural tuberculosis. In parapneumonic complex effusion, MT obviates the need for surgery in most cases. Thoracoscopy training should be considered being as important as bronchoscopy training for interventional pulmonology, although prior acquisition of ultrasonography and chest tube insertion skills is essential.

Pleural tuberculosis: medical thoracoscopy greatly increases the diagnostic accuracy.

Our objective was to evaluate the efficacy of a standardised work-up in the diagnosis of pleural tuberculosis (TB) that included fibreoptic bronchoscopy and medical thoracoscopy. A consecutive series of 52 pleural TB patients observed during the period 2001-2015 was evaluated retrospectively. 20 females, mean (range) age 39.7 (18-74) years, and 32 males, mean (range) age 45.75 (21-83) years, were included (28 non-EU citizens (53.8%)). The diagnosis of TB infections was established by identification (using stains, culture or molecular tests) of Mycobacterium tuberculosis in the pleura, sputum and/or bronchial specimens, or by evidence of caseous granulomas on pleural biopsies. Patients with and without lung lesions were considered separately. The diagnostic yield of the microbiological tests on pleural fluid was 17.3% (nine out of 52 patients). Among the 18 patients with lung lesions, bronchial samples (washing, lavage or biopsy) were positive in 50% of cases (nine patients). Cultures of pleural biopsies were positive in 63% of cases (29 out of 46 patients); pleural histology was relevant in all patients. Without pleural biopsy, a diagnosis would have been reached in 15 out of 52 patients (28.6%) and in four of them only following culture at 30-40 days. An integrated diagnostic work-up that includes all the diagnostic methods of interventional pulmonology is required for a diagnosis of pleural TB. In the majority of patients, a diagnosis can be reached only with pleural biopsy.

Pulmonary metastases from low grade sarcoma in a patient with pulmonary sarcoidosis. Sarcoidosis or sarcoid-like reaction?

An asymptomatic man with previous histopatological diagnosis of pulmonary sarcoidosis in radiological follow-up (stable for about 4 years) presented massive right pleural effusion. After drainage, CT of the chest showed an increase in number and size of pulmonary nodules compared to the last check (8 months before). Surgical pulmonary biopsies were performed with the diagnosis of metastases from low grade sarcoma. The primary tumor was localized to the right buttock. Given the absence of symptoms, the extent of disease and many comorbidities the patient underwent only treatment with gemcitabine that was not tolerated and discontinued after the first few cycles 1 year ago. At the present the patientis still asymptomatic even if the CT of the chest shows a slow but continuous progression of the disease. The question is: is this an association between sarcoidosis and malignancy? or was this a sarcoid-like reaction during malignancy?

Conventional transbronchial needle aspiration with 23 gauge needle: a preliminary study.

BACKGROUND: Conventional transbronchial needle aspiration (cTBNA) is a safe and minimally invasive procedure with a high yield for the diagnosis of large lymph nodes (LNs) in favourable locations (LNs >1.5 cm in stations #4R and/or #7). However, it is usually underutilized by pulmonologist. One of the main reasons given for not performing cTBNA is the risk of puncturing vascular structures of the mediastinum. Recently, with the twofold objective of minimize the risk of bleeding and reduce the cTBNA cost, a thinner and less expensive needle has been commercialized. It is a 23 gauge (G) needle that costs 34, 37 €. The aim of our study was to analyze the sample adequacy, diagnostic accuracy and safety of this needle in comparison with 21 and 22 G needles (average cost: 6,400 €). METHODS: We retrospectively analysed medical records from patients who underwent bronchoscopy with cTBNA for the diagnosis of LNs >1.5 cm in stations #4R and/or #7 at the Thoracic Endoscopy Unit of the University Hospital of Parma from January 1st, 2007 to October 31(st), 2011. Five hundred patients underwent cTBNA from January 1(st), 2007 to October 31(st), 2011. In order to reduce the technical and personal bias for sampling procedure we analyzed only cases sampled by a single well-trained bronchoscopist, particularly skilful at cTBNA. RESULTS: A total of 222 patients (186 men; mean age 63 years±12, range 6-89) with LNs >1.5 cm in stations #4R and/or #7 were identified. A 23 G needle was used in 84 patients (38%), a 21 G needle in 88 patients (40%) and a 22 G needle in 50 patients (22%). No statistically significant differences between the 23 G group and the 21 or 22 G group in sample adequacy (P=0.78 and P=0.12, respectively) and diagnostic accuracy (P=0.9 and P=0.4, respectively) were found. There were no intraprocedural or postprocedural complications irrespective of the size of needle used. CONCLUSIONS: Transbronchial 23 G needle is as safe and effective as the 21 and 22 G needle for the sampling of LNs >1.5 cm in stations #4R and/or #7. For this reason, to obtain cytology specimens from large LNs in favourable locations, the 23 G needle may represent an alternative and less expensive choice compared to 21 and 22 G needles, even if our observation needs to be confirmed in a larger prospective study.

Lipoid pneumonia as a complication of Lorenzo's oil therapy in a patient with adrenoleukodystrophy.

Lipoid pneumonia (LP) is a rare exogenous condition caused by inhalation or aspiration of lipid material into the lungs. It is often associated with the therapeutic use of different types of oil, and the diagnosis is based on the demonstration of lipid-laden macrophages in bronchoalveolar lavage fluid. We reported the case of a 39-year-old male with X-linked adrenoleukodystrophy who developed LP secondary to the use of Lorenzo's oil. To our knowledge, the association between the use of Lorenzo's oil and LP has never been reported in literature.

YKL-40 and mesothelin in the blood of patients with malignant mesothelioma, lung cancer and asbestosis.

BACKGROUND/AIM: In the diagnosis of malignant mesothelioma (MM) there still is a lack of specific and sensitive screening biomarkers: this study examined the discriminatory power of a panel of serum/plasma biomarkers. PATIENTS AND METHODS: The study involved four groups: (a) individuals previously exposed to asbestos with asbestosis; (b) patients with MM; (c) patients with non-small cell lung cancer; and (d) controls without any evidence of malignancy. The concentrations of mesothelin, chitinase-3-like-1 (YKL-40), vascular endothelial growth factor (VEGF), endothelin-1, interleukin-8 (IL-8) and fibulin-3 in the serum of patients were determined. RESULTS: Patients with MM had significantly higher serum levels of mesothelin (p<0.001), YKL-40 (p<0.001), IL-8 (p<0.001) and VEGF (p<0.01) than controls. The cut-off point for MM was 1.26 nM for mesothelin alone, and 167 pg/ml for YKL-40 alone; the presence of both markers above these cut-off levels improved diagnostic specificity. CONCLUSION: The addition of YKL-40 may improve the specificity of mesothelin measurements alone for detecting patients with MM.

Foreign body aspiration in adults and in children: advantages and consequences of a dedicated protocol in our 30-year experience.

BACKGROUND: Foreign body (FB) inhalation is a potentially life-threatening emergency also in clinically stable patients as the situation could worsen at any moment. There is varying opinion regarding the urgency for removal of inhaled FBs, and there are no guidelines in the literature. The aim of our study was to present our experience with FB aspiration in children and adults from 1993, when we introduced our Thoracic Endoscopy Service with the availability "on call" of a bronchologist 24 hours a day, 7 days a week, defining a dedicated protocol together with our anaesthesiologists for prompt intervention in this situation. METHODS: We consulted our database and examined the records of all patients undergoing bronchoscopy for suspected FB aspiration from 1993 onwards; our previous experience of 11 children and 14 adults with FBs from 1981 to 1992 was also included to compare the results obtained. RESULTS: In this period, we removed 159 FBs (in 70 children and 89 adults) and performed 23 negative bronchoscopies in children and 6 in adults for suspected aspiration. All FBs were removed successfully. We were able to intervene immediately also in critical situations: in 60/70 children within 24 hours of admission to hospital, in 44 of these 60 on the actual day of admission, thus avoiding a potentially dangerous delay between aspiration and removal. We had no complications, and no patients needed surgery. CONCLUSIONS: We conclude that an efficient organization involving a dedicated protocol of intervention, trained staff available 24 hours a day, 7 days a week, appropriate setting, and the right instrumentation enabled us to tackle this important emergency.

Immune response to Mycobacterium tuberculosis infection in the parietal pleura of patients with tuberculous pleurisy.

The T lymphocyte-mediated immune response to Mycobacterium tuberculosis infection in the parietal pleura of patients with tuberculous pleurisy is unknown. The aim of this study was to investigate the immune response in the parietal pleura of tuberculous pleurisy compared with nonspecific pleuritis. We have measured the numbers of inflammatory cells particularly T-cell subsets (Th1/Th2/Th17/Treg cells) in biopsies of parietal pleura obtained from 14 subjects with proven tuberculous pleurisy compared with a control group of 12 subjects with nonspecific pleuritis. The number of CD3+, CD4+ and CCR4+ cells and the expression of RORC2 mRNA were significantly increased in the tuberculous pleurisy patients compared with the nonspecific pleuritis subjects. The number of toluidine blue+ cells, tryptase+ cells and GATA-3+ cells was significantly decreased in the parietal pleura of patients with tuberculous pleurisy compared with the control group of nonspecific pleuritis subjects. Logistic regression with receiver operator characteristic (ROC) analysis for the three single markers was performed and showed a better performance for GATA-3 with a sensitivity of 75%, a specificity of 100% and an AUC of 0.88. There was no significant difference between the two groups of subjects in the number of CD8, CD68, neutrophil elastase, interferon (IFN)-γ, STAT4, T-bet, CCR5, CXCR3, CRTH2, STAT6 and FOXP3 positive cells. Elevated CD3, CD4, CCR4 and Th17 cells and decreased mast cells and GATA-3+ cells in the parietal pleura distinguish patients with untreated tuberculous pleurisy from those with nonspecific pleuritis.

Determination of aldehydes in exhaled breath of patients with lung cancer by means of on-fiber-derivatisation SPME-GC/MS.

A number of volatile organic compounds (VOCs) have been identified and used in preliminary clinical studies of the early diagnosis of lung cancer. The aim of this study was to evaluate the potential of aldehydes (known biomarkers of oxidative stress) in the diagnosis of patients with non-small cell lung cancer (NSCLC). We used an on-fiber-derivatisation SPME sampling technique coupled with GC/MS analysis to measure straight aldehydes C3-C9 in exhaled breath. Linearity was established over two orders of magnitude (range: 3.3-333.3×10(-12) M); the LOD and LOQ of all the aldehydes were respectively 1×10(-12) M and 3×10(-12) M. Accuracy was within 93% and precision calculated as % RSD was 7.2-15.1%. Aldehyde stability in a Bio-VOC(®) tube stored at +4°C was 10-17 h, but this became >10 days using a specific fiber storage device. Finally, exhaled aldehydes were measured in 38 asymptomatic non-smokers (controls) and 40 NSCLC patients. The levels of all of the aldehydes were increased in the NSCLC patients without any significant effect of smoking habits and little effect of age. The good discriminant power of the aldehyde pattern (90%) was confirmed by multivariate analysis. These results show that straight aldehydes may be promising biomarkers associated with NSCLC, and increase the sensitivity and specificity of previously identified VOC patterns.