Search

Background: Systemic sclerosis is associated with an increased incidence of malignancies, in particular solid neoplasms. Hematological cancers have been also observed in autoimmune diseases, though rarely present with lung involvement. The latter may be misdiagnosed in systemic sclerosis patients, due to the frequent concomitant interstitial lung disease. Case description: Here, we present the case of a 63-year-old man affected by systemic sclerosis presenting with an atypical lung imaging and splenomegaly, who was diagnosed with splenic marginal zone lymphoma, thus raising the suspicion of lung secondarism. We discuss the diagnostic challenge of differential diagnosis in interstitial lung presentation and briefly review the available literature on this topic. Conclusion: Several reports have demonstrated an increased risk of malignancy in patients with systemic sclerosis. Still, the lack of concretely defined guidelines for systemic sclerosis, along with systemic sclerosis multifaceted organ involvement at presentation, may challenge diagnosis and management. Here, we remark the importance of clinical work-up and a multidisciplinary approach in systemic sclerosis, to early detect and treat concomitant hematological malignancies, especially during the first years of the disease.

Cytopathological analyses of bronchial washings (BWs) collected during fibre‐optic bronchoscopy are often inconclusive for lung cancer diagnosis. To address this issue, we assessed the suitability of conducting molecular analyses on BWs, with the aim to improve the diagnosis and outcome prediction of lung cancer. The methylation status of RASSF1A, CDH1, DLC1 and PRPH was analysed in BW samples from 91 lung cancer patients and 31 controls, using a novel two‐colour droplet digital methylation‐specific PCR (ddMSP) technique. Mutations in ALK, BRAF, EGFR, ERBB2, KRAS, MAP2K1, MET, NRAS, PIK3CA, ROS1 and TP53 and gene fusions of ALK, RET and ROS1 were also investigated, using next‐generation sequencing on 73 lung cancer patients and 14 tumour‐free individuals. Our four‐gene methylation panel had significant diagnostic power, with 97% sensitivity and 74% specificity (relative risk, 7.3; odds ratio, 6.1; 95% confidence interval, 12.7–127). In contrast, gene mutation analysis had a remarkable value for predictive, but not for diagnostic, purposes. Actionable mutations in EGFR, HER2 and ROS1 as well as in other cancer genes (KRAS, PIK3CA and TP53) were detected. Concordance with gene mutations uncovered in tumour biopsies was higher than 90%. In addition, bronchial‐washing analyses permitted complete patient coverage and the detection of additional actionable mutations. In conclusion, BWs are a useful material on which to perform molecular tests based on gene panels: aberrant gene methylation and mutation analyses could be performed as approaches accompanying current diagnostic and predictive assays during the initial workup phase. This study establishes the grounds for further prospective investigation., Diagnostic and predictive assessment remains major challenges in lung cancer management. In this work, we investigate the importance of molecular investigations applied to bronchial washings collected during fibre‐optic bronchoscopy for lung lesions. Using a cancer‐specific DNA methylation panel and gene mutations analyses, we demonstrated that bronchial washing represents a useful material for performing molecular tests in lung cancer patients.

Introduction: Lung cancer is a deathly cancer, associated with cigarette smoke. Targeted therapies require molecular characterization of tumors, mostly on histological samples. We hypothesized that less invasive techniques such as bronchial lavage (BL) could give suitable material for such analysis. Aims: to evaluate feasibility and accuracy of molecular testing on BL samples from high risk patients with suspect lung lesions. Methods: we enrolled consecutive smokers or ex smokers undergoing bronchoscopy at our site, as a part of diagnostic investigation of a radiologically proven lung opacity. BL samples for genetic analysis were collected from all patients. Testing was performed through Next Generation Sequencing (NGS) on a 9 gene panel: EGFR, KRAS, ALK, ROS1, MET, BRAF, ERBB2, p53, PI3KCA. Pathology was used as reference standard for diagnosis and molecular analysis. We regarded benign diagnosis and/or no evidence of clinical/radiological disease progression after a 6 months follow up as negative controls. Results: We enrolled 91 neoplastic patients (33 with endoscopically visible lesions, 58 without visible lesions) and 21 negative controls. Whole panel analysis with NGS was feasible on 100% of BL samples. Overall concordance with available pathological tests was 92.4%. Sensitivity and specificity were 76.9% and 28.6%, respectively. The most frequently mutated gene was p53 (42%), also in controls (42%). No complications were related to BL. Conclusions: BL seems a valuable material for genetic analysis with NGS in lung cancer, and has a low complication risk. Larger studies are needed to define the appropriate role for such analysis, also as a screening test.

Introduction: Interstitial lung diseases (ILD) are a heterogeneous group of diseases characterized by inflammation and/or fibrosis. Small airways ( Objectives: Assess small airways involvement through IOS in patients with ILD. Assess a possible correlation between small airways resistance, reactance and symptoms. Assess a possible correlation between the values R5-R20 and the degree of small airways involvement in HRTC. Methods: A single-center prospective cohort study. Patients with different diagnoses of ILD were divided in two subgroups: fibrosing ILD and non-fibrosing ILD. They underwent spirometry, HRTC and IOS. Parameters collected were: R5 (total airway resistance), R20 (central airway resistance); R5-R20 (small airway resistance), AX (reactance area), X5 (reactance measured at a 5 Hertz frequency). Results: 70 patients with a diagnosis of ILD have been enrolled: 33 with fibrosing ILD, 37 with non-fibrosing ILD. The fibrosing ILD group has R5-R20 higher than non-fibrosing ILD group statistically significant and in fibrosing ILD group R5-R20 increases with the age of patients. In fibrosing ILD there is a inverse statistically significant correlation of X5 with the FVC % predicted. In non-fibroing ILD, the thickening of the bronchiolar walls is associated with an increase in R5-R20 statistically significant. Conclusion: IOS could be useful in ILD to value the small airways involvement together with HRCT. Reactance could have a role in the functional follow-up of fibrosing ILD patients.

The opportunity of a multidisciplinary evaluation for the diagnosis of interstitial pneumonias highlighted a major change in the diagnostic approach to diffuse lung disease. The new American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society guidelines for the diagnosis of idiopathic pulmonary fibrosis have reinforced this assumption and have underlined that the exclusion of connective tissue disease related lung involvement is mandatory, with obvious clinical and therapeutic impact. The multidisciplinary team discussion consists in a moment of interaction among the radiologist, pathologist and pulmonologist, also including the rheumatologist when considered necessary, to improve diagnostic agreement and optimize the definition of those cases in which pulmonary involvement may represent the first or prominent manifestation of an autoimmune systemic disease. Moreover, the proposal of classification criteria for interstitial lung disease with autoimmune features (IPAF) represents an effort to define lung involvement in clinically undefined autoimmune conditions. The complexity of autoimmune diseases, and in particular the lack of classification criteria defined for pathologies such as anti-synthetase syndrome, makes the involvement of the rheumatologist essential for the correct interpretation of the autoimmune element and for the application of classification criteria, that could replace clinical pictures initially interpreted as IPAF in defined autoimmune disease, minimizing the risk of misdiagnosis. The aim of this review was to evaluate the available evidence about the efficiency and efficacy of different multidisciplinary team approaches, in order to standardize the professional figures and the core set procedures that should be necessary for a correct approach in diagnosing patients with interstitial lung disease.

Rationale: In patients with suspected lung cancer fibrobronchoscopy (FBS) has a key role in the diagnostic process, but its performance is variable (from 90% in the presence of visible lesions to less than 30% for distal ones). DNA methylation analysis emerged as a promising approach for cancer detection. Aberrantly methylated DNA sequences are present in tumour cells and represent cancer specific biomarkers that can be detected in biological fluids. Our study attempts to improve the diagnostic power of BW through the use of cancer specific DNA methylation biomarkers. METHODS: We performed a retrospective case-control study in which we investigated the methylation status of a panel of genes (RASSF1A, CDH1, DLC1 and PRPH) in BWs samples from 91 lung cancer patients and 31 non-cancer controls (current or former smokers). We analysed the methylation status of DNAs from BWs fluids by using a novel highly sensitive two-colour droplet digital methylation-specific PCR. Results: The 4-gene panel exhibited a significant diagnostic power, with a 97% sensitivity and 74% specificity (overall diagnostic accuracy = 0.88), conferring a relative risk of 7.3, at an odds ratio of 76.1 (95% CI from 12.7 to 127). The ROC curve analysis (AUC=0.93) confirmed the excellent diagnostic power of the 4-genes panel. In addition the methylation assay was positive in 35 of the 36 BW samples with negative cytological analyses. CONCLUSIONS. Our results indicate that the aberrant methylation of this panel of genes could represent a helpful support to current diagnostic strategies for lung cancer detection.

In 1963, the first bronchoscopic lung biopsy was performed. Less than 10 years later, the technique of transbronchial lung biopsy using a flexible bronchoscope was introduced into clinical practice, significantly reducing the rate of major complications and the rate of surgical lung biopsies in patients with diffuse parenchymal lung diseases. The diagnostic yield of transbronchial lung biopsy varies among various parenchymal lung diseases. In pulmonary sarcoidosis and lymphangitis carcinomatosa, a diagnosis can be obtained in up to 80% of patients. This method is considered inadequate, however, in identifying more complex histological patterns such as usual interstitial pneumonitis or nonspecific interstitial pneumonitis. Introduction of the 'jumbo forceps' and of a more 'surgically oriented' procedural setting (patients deeply sedated and intubated) allowed larger and more numerous lung specimens to be obtained without a significant increase of complications such as pneumothorax or bronchial bleeding. However, the possibility to obtain enough parenchymal tissue for a morphological diagnosis of complex patterns remained unmet. Recently, the use of cryoprobes has achieved a significant impact on this issue allowing to obtain large quantity of tissue. Recent studies document that with transbronchial cryobiopsies the diagnosis of usual interstitial pneumonitis can be made confidently by pathologists with a good inter-observer agreement. Pneumothorax is the main complication (reported in up to one fourth of cases in some series); bronchial bleeding is easily controlled using Fogarty balloon. Transbronchial cryobiopsy is a promising new technique that may become a valid alternative to surgical lung biopsy in the near feature.

A non-invasive test to facilitate the diagnosis of non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) is still not available and represents an important goal. Forty-eight patients with stage I NSCLC, 45 with IPF, 30 with other idiopathic interstitial pneumonias (IIPs) including idiopathic non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (HP), 35 with diffuse non-malignant disease and 30 healthy donors were enrolled onto the study. Free circulating (fc)DNA and MMP-7 levels were evaluated by Real Time PCR and ELISA, respectively. Median fcDNA levels were similar in NSCLC (127 ng/mL, range 23.6–345 ng/mL) and IPF (106 ng/mL, range 22–224 ng/mL) patients, and significantly lower in IIPs patients, in individuals with other diseases and in healthy donors (p &lt, 0.05). Conversely, median MMP-7 values were significantly higher in IPF patients (9.10 ng/mL, range 3.88–19.72 ng/mL) than in those with NSCLC (6.31 ng/mL, range 3.38–16.36 ng/mL, p &lt, 0.0001), NSIP (6.50 ng/mL, range 1.50–22.47 ng/mL, p = 0.007), other diseases (5.41 ng/mL, range 1.78–15.91, p &lt, 0.0001) or healthy donors (4.35 ng/mL, range 2.45–7.23, 0.0001). Serum MMP-7 levels seem to be capable of distinguishing IPF patients from those with any other lung disease. fcDNA levels were similar in NSCLC and IPF patients, confirming its potential role as a biomarker, albeit non-specific, for the differential diagnosis of NSCLC.

Background: Pleural empyema can be subdivided into 3 stages: exudative, multiloculated, and organizing. In the absence of clear septation, antibiotics plus simple drainage of pleural fluid is often sufficient treatment, whereas clear septation often requires more invasive treatment. Objectives: The aim of this study was to report our experience and analyze the safety and efficacy of medical thoracoscopy in patients with multiloculated and organizing empyema. Methods: We performed a retrospective study reviewing the files of patients referred for empyema and treated by medical thoracoscopy at our department from July 2005 to February 2011. Results: A total of 41 patients with empyema were treated by medical thoracoscopy; empyema was free flowing in 9 patients (22%), multiloculated in 24 patients (58.5%), and organized in 8 patients (19.5%). Medical thoracoscopy was considered successful without further intervention in 35 of 41 patients (85.4%): all of the 9 patients with free-flowing fluid, 22 of the 24 patients with multiloculated empyema (91.7%), and only 4 of the 8 patients with organizing effusion (50%). Conclusions: Our study confirms that multiloculated pleural empyema could safely and successfully be treated with medical thoracoscopy while organizing empyema can be resistant to drainage with medical thoracoscopy, requiring video-assisted thoracic surgery or open surgical decortications; among this population, the presence of separate ‘pockets’ not in apparent communication with each other often leads to a surgical approach.

Rare diffuse infiltrative lung diseases are a challenge for clinicians, radiologists, and pathologists for at least three reasons: (a) their low incidence and prevalence hamper the acquisition of expertise and frequently the diagnosis is delayed; (b) therapeutic actions are mainly empirical and based on steroid use, and (c) pathogenetic events are difficult to explain and only recently new therapeutic measures taking advantage of innovative genetic and/or immunopathogenetic studies have been suggested. In this review rare diffuse lung disorders are briefly discussed (pulmonary alveolar proteinosis, inherited lipidoses, acute eosinophilic pneumonia, amyloidosis, pulmonary ossification, pulmonary alveolar microlithiasis). The list is obviously not exhaustive and arbitrarily chosen. The intent is, however, to emphasize that in this difficult field multidisciplinary expertise and the knowledge of the most recent pathogenetic mechanisms have the main role in diagnosis and treatment.

In 1963, the first bronchoscopic lung biopsy was performed. Less than 10 years later, the technique of transbronchial lung biopsy using a flexible bronchoscope was introduced into clinical practice, significantly reducing the rate of major complications and the rate of surgical lung biopsies in patients with diffuse parenchymal lung diseases. The diagnostic yield of transbronchial lung biopsy varies among various parenchymal lung diseases. In pulmonary sarcoidosis and lymphangitis carcinomatosa, a diagnosis can be obtained in up to 80% of patients. This method is considered inadequate, however, in identifying more complex histological patterns such as usual interstitial pneumonitis or nonspecific interstitial pneumonitis. Introduction of the 'jumbo forceps' and of a more 'surgically oriented' procedural setting (patients deeply sedated and intubated) allowed larger and more numerous lung specimens to be obtained without a significant increase of complications such as pneumothorax or bronchial bleeding. However, the possibility to obtain enough parenchymal tissue for a morphological diagnosis of complex patterns remained unmet. Recently, the use of cryoprobes has achieved a significant impact on this issue allowing to obtain large quantity of tissue. Recent studies document that with transbronchial cryobiopsies the diagnosis of usual interstitial pneumonitis can be made confidently by pathologists with a good inter-observer agreement. Pneumothorax is the main complication (reported in up to one fourth of cases in some series); bronchial bleeding is easily controlled using Fogarty balloon. Transbronchial cryobiopsy is a promising new technique that may become a valid alternative to surgical lung biopsy in the near feature.

Idiopathicpulmonary fibrosis (IPF) has a sporadic occurrence in most instances,but can also occasionally occur in familial form. While clinicalfeatures of sporadic IPF are well defined, clinical presentation,complications, and outcome of familial IPF are still undefined. Thisretrospective study was undertaken to establish clinical parametersand survival time in a consecutive series of patients with familialIPF and to establish whether the phenomenon of anticipation could beobserved.30 patients had received a diagnosis of familial IPF at ourinstitution over the period from January 2005 and December 2011; in7 of them there was a parent-child relation.Clinical features and patient outcome were analyzed and contrasted toa well characterized cohort of 127 patients with non familial IPF.there was no significant difference in presenting symptoms and theoverall outcomes were quite similar in the two groups, but thefamilial group was much more enriched for females and we found astatistically significant lower age at onset in the youngergenerations (mean age 57,8 years versus 74,2 years, p 0,001). Acuteexacerbations, IPF progression and lung cancer were more frequent inthe familial IPF group as a cause of death (p0,005).familial IPF seems indistinguishable from sporadic IPF with respectto most clinical and physiologic findings; however the age of onsetwas slightly lower among the familial cases than in the sporadiccases of IPF and the phenomenon of anticipation could be observed.

Background Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC). Methods 100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method. Results Free circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p

Background Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited. Objectives To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD. Method Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features. Results Safety: pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm2 (range, 11.94–76.25). Diagnostic yield: among adequate TBLC the pathologists were confident (“high confidence”) that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis–interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident (“low confidence”). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69–0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable. Conclusions TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD.

Background Usual interstitial pneumonia (UIP), is a necessary feature pathologically or radiologically for the diagnosis of idiopathic pulmonary fibrosis (IPF). The predictive value of transbronchial biopsy (TBB) in identifying UIP is currently unknown. The objective of this study is to assess the accuracy with which histopathologic criteria of usual interstitial pneumonia (UIP) can be identified in transbronchial biopsy (TBB) and to assess the usefulness of TBBx in predicting a the diagnosis of UIP pattern. We conducted a retrospective blinded and controlled analysis of TBB specimens from 40 established cases of UIP and 24 non-UIP interstitial lung diseases. Results Adequate TBB specimens were available in 34 UIP cases (85% of all UIP cases). TBB contained histopathologic criteria to suggest a UIP pattern (ie. at least one of three pathologic features of UIP present; patchy interstitial fibrosis, fibroblast foci, honeycomb changes) in 12 cases (30% of all UIP cases). Sensitivity, specificity, positive and negative predictive values for the two pathologists were 30% (12/40), 100% (24/24), 100% (12/12), 46% (24/52) and 30% (12/40), 92% (22/24), 86% (12/14), 55% (22/40) respectively. Kappa coefficient of agreement between pathologists was good (0.61, 95% CI 0.31-0.91). The likelihood of identifying UIP on TBB increased with the number and size of the TBB specimens. Conclusion Although sensitivity is low our data suggest that even modest amount of patchy interstitial fibrosis, fibroblast foci, honeycomb changes detected on TBB can be highly predictive of a UIP pattern. Conversely, the absence of UIP histopathologic criteria on TBB does not rule out UIP.

In non-small cell lung cancer (NSCLC) patients, somatic EGFR and K-ras mutations predict therapeutic effectiveness and resistance, respectively, to EGFR tyrosine kinase inhibitors (TKIs). Transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) is a validated technique for diagnosis and staging of NSCLC. In the present study, we compared the feasibility and reliability of EGFR and K-ras gene mutation analysis in fixed and fresh mediastinal lymph nodes and extra-lymph nodal samples obtained by EUS-FNA in patients suspicious for NSCLC. Thirty-six patients were enrolled into the study. For each patient, DNA was extracted from both fresh samples and fixed cytological smears. Exons 18-21 of EGFR and exon 2 of K-ras were amplified by PCR and mutation status was determined by direct sequencing and pyrosequencing. All cases were eligible for analysis. NSCLC was diagnosed in 32 patients (25 adenocarcinomas and 7 squamous cell carcinomas) and 4 patients were free of malignancy. Of the 25 patients with adenocarcinoma, EGFR mutations were detected in 2 (8%) fresh tumor samples and in 3 (12%) fixed cytological smears. K-ras mutations were detected in 8 (32%) fresh samples, and in 9 (36%) fixed cytological smears. Fixed and stained cytological samples seem to be more reliable than fresh material for molecular analysis.

At present, no studies have evaluated the role of bronchoscopic transbronchial lung biopsy (TBLB) in the diagnosis of diffuse drug-induced lung disease (DILD), and there is no consensus for a definite diagnostic workup approach for this rare clinical entity. The aim of the present study was to evaluate the clinical usefulness of TBLB in diffuse DILD. This study was a retrospective analysis of patients with diffuse DILD, who underwent bronchoscopy. The role of TBLB was assessed to determine whether the histological results are useful for the final diagnosis. Over a 5-yr period, 44 patients underwent bronchoscopy, and all had a bronchoalveolar lavage (BAL). Thirty-three of the 44 patients underwent TBLB (75%), and the results of TBLB were diagnostically helpful in 25 (75.7%) of the procedures. No histopathologic abnormality was identified in 6 (18%) of the 33 patients. In 2 patients (6%) the obtained samples were not adequate, since no lung parenchyma was obtained. No severe complications related to bronchoscopic procedures occurred. In conclusion, TBLB is a safe procedure, and is diagnostically helpful in the majority of cases of patients with diffuse DILD. Histological data obtained by TBLB further corroborate clinical, laboratory, radiologic and BAL results for a definitive diagnosis of diffuse DILD.

Lung cancer is the most frequently diagnosed tumour type and the leading cause of cancer mortality throughout the world. The prognosis of patients is strongly correlated with tumour stage,1 hence the importance of an accurate, easily usable diagnostic tool for early detection. Low-dose spiral computed tomography (CT) has opened up interesting prospects for early diagnosis but is expensive, invasive and presents some limitations, especially in terms of specificity.2 Free circulating DNA levels have been shown to be higher in patients with lung cancer than in healthy individuals (including heavy smokers), suggesting that this marker could be an important tool to identify lung cancer in screening programmes.3 More recently, our group4 and other researchers5 have shown that plasma or serum free DNA is also significantly higher in patients with other cancer histotypes than in healthy donors. …

Previous studies have shown an increased number of inflammatory cells and, in particular, of CD8+ T lymphocytes, in central airways, peripheral airways, lung parenchyma and pulmonary arteries of smokers with COPD. In this study we investigated whether this inflammatory process is restricted to the lung tissue or whether a similar process is also present in the lymph nodes of these subjects. We examined paratracheal lymph nodes obtained from 6 smokers with COPD (FEV1/VC88% predicted and FEV1/FVC70% both before and after 200 microg of inhaled salbutamol) and 6 smokers without COPD (FEV1/VC88% predicted and FEV1/FVC70%) undergoing lung resection for localised pulmonary lesions. By immunohistochemistry we quantified CD4+ and CD8+ T-lymphocytes in the lymph nodes. Smokers with COPD had a decreased ratio CD4/CD8 compared to smokers without COPD. When all subjects were considered together, the ratio CD4/CD8 showed a positive correlation with the values of FEV1/VC and a negative correlation with cigarette consumption. In conclusion, smokers with COPD have an increased proportion of CD8+ cells in the lymph nodes, indicating that a T-lymphocyte pattern similar to that present in the lung tissue is also present in the lymph nodes of these subjects. This finding suggests that, in COPD, the polarisation of the immune response may occur in the regional lymph nodes, possibly as a consequence of the presentation of an endogenous antigen that remains unknown.

This study investigated the relationships between pathological changes in small airways (1/FVC) < 70%] in 12 subjects and normal lung function in 10. When all subjects were considered together, total airway wall thickness was significantly correlated with FEV1/FVC ( r2 = 0.25), reactivity to methacholine ( r2 = 0.26), and slope of linear regression of FVC against FEV1 values recorded during the methacholine challenge ( r2 = 0.56). Loss of peribronchiolar alveolar attachments was significantly associated ( r2 = 0.25) with a bronchoconstrictor effect of deep inhalation, as assessed from a maximal-to-partial expiratory flow ratio

A 42-year-old woman was referred to our department with a 5 months history of intermittent fever and fatigue. Her past medical history included a consolidated diagnosis of sarcoidosis (obtained 7 years before with a sub-carinal lymph node biopsy) and in the previous years she had been treated with steroids, hydroxychloroquine, methotrexate and azathioprine with persistent and progressive enlargement of mediastino-hilar adenopathies and bilateral nodular infiltrates. Her symptoms progressed despite a course of antibiotics prescribed for presumed community-acquired pneumonia and a course of corticosteroids. The patient lived in Italy and there was no history of travels or other additional risk factors for infections. At the time of admission, the patient had a temperature of …

Few cases of catamenial pneumothorax with complete or partial diaphragmatic hernias are reported in the literature. We present herein the case of a 38-year-old woman affected by recurrent right-sided spontaneous pneumothorax during menstrual periods. CT scan revealed normal lung parenchyma and multiple diaphragmatic nodes suspected for endometrial implants. The patient underwent right thoracoscopy and the presence of multiple diaphragmatic perforations of the tendinous part was observed as well as partial hepatic hernia. Through a video-assisted procedure, pleural biopsies and diaphragmatic plication containing the tendinous part with total pleural abrasion and talc pleurodesis were performed. No endometrial implants were found on histologic examination of pleural biopsies. The surgical procedure was uneventful and totally successful. On the basis of the clinical data and endoscopic view, we consider our case as catamenially recurring pneumothorax.

A 58-year-old man with alcoholic liver cirrhosis and signs related to portal hypertension (such as esophageal varices) was admitted to the GB Morgagni hospital (Forli, Italy) because of acute-onset breathlessness and weakness. His blood pressure was 90/55 and laboratory values showed anemia (hemoglobin 7.9 g/dl, hematocrit 23.5%). Packed red cells (2 units) were immediately administered intravenously, after which the blood pressure rose to 110/65. Meanwhile, a posterioanterior chest radiograph demonstrated a massive right pleural effusion. A thoracentesis was performed and approximately 700 ml of hemorrhagic pleural effusion was evacuated. The day after the thoracentesis the patient underwent medical thoracoscopy for evacuation of the pleural effusion and for diagnosis. After aspiration of 2,200 ml of hemorrhagic pleural fluid (with hematocrit of 8%), the exploration of the thoracic cavity revealed at the 9th and 10th posterior intercostal space the presence of intercostal varicose veins with recent signs of bleeding ( fig. 1 a, b). A chest tube was placed. Twenty minutes after placement of the chest tube, the patient became more breathless and examination rePublished online: August 6, 2009

In a recent issue of CHEST (January 2011), Gounant et al 1 showed that dedicated linear echoendoscope endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needles are able to release metal particles, probably by friction between the stylet and the needle, with a potential risk of injecting particles into nodes. After reading this article, we are a bit confused for several reasons. First, we do not understand the primum movens and the intrinsic aim of designing a study like this. Logically, we should perform similar investigations on all surgical, endoscopic, and radiologic procedures in which metal tools are used. Indeed, a simple blood test with a needle could release metal particles. Therefore, we do not understand the need to focus specifi cally on dedicated EBUS-TBNA needles. Second, the article does not indicate the concentrations of iron, titanium, nickel, and chromium that can be potentially harmful to the body. This is important information, considering how many times a patient may undergo EBUS-TBNA over a lifetime (one, maybe two times). Accordingly, we have some doubts that the concentrations released in the lymph nodes are so high as to be potentially harmful to the body. In conclusion, we completely agree with the authors that transbronchial needle aspiration using a fl exible bronchoscope (conventional transbronchial needle aspiration) or linear echoendoscope (endobronchial ultrasound) allowing real-time guided lymph node aspiration are minimally invasive procedures for the diagnosis of mediastinal lymphadenopathy, with a very high sensitivity, a very low morbidity, and no reported mortality. 2 , 3 Although the release of metal particles by an EBUS-TBNA needle may be reported to the manufacturers of these needles, this must not lead to a reduction in, or questioning of, the use of EBUS-TBNA in the diagnosis of mediastinal lymphadenopathy.

Summary A 64-year-old male was diagnosed with malignant pleural mesothelioma (MPM) in June 2006 after complaining of dyspnoea and a persistent cough. In July 2006 the patient underwent talc pleurodesis and started first-line chemotherapy with cisplatin associated with pemetrexed (Alimta ® ). At the end of the third chemotherapy cycle the disease was stable and no significant drug toxicity was recorded. The patient progressed through another three cycles under the same treatment schedule. Restaging at the end of the sixth cycle confirmed a stable disease and the patient started follow-up. In January 2007, further restaging showed disease progression and the patient was enrolled in a phase I clinical trial involving a continuous infusion of pemetrexed until at a dose of 100 mg m −2 at day one. After 8 days the patient was referred to the Accident and Emergency Department for acute dyspnoea and a fever of 38.5 °C. A high resolution CT-scan of the thorax showed diffuse, bilateral areas of ground glass attenuation with a patchy distribution. A 13-day broad-spectrum antibiotic therapy did not achieve any clinical and/or radiological improvement of respiratory abnormalities, and for this reason a bronchoscopy, with a fluoroscopic-guided transbronchial lung biopsy (TBB), and a bronchoalveolar lavage (BAL), were performed. BAL cultures for common bacteria, acid fast bacilli and fungi, as well as vial cultures and/or immunofluorescent tests for viruses (cytomegalovirus, adenovirus, herpes simplex virus, syncytial respiratory virus, influenzae and parainfluenzae viruses) and Legionellae, proved negative. Examination of BAL cytospin preparations, stained by both Diff-Quick and Papanicolaou methods, showed cuboidal hyperplastic/dysplastic cells (diffuse alveolar damage cells) whilst no malignant cells, viral inclusions, fungi, or Pneumocystis jiroveci cysts were identified. The TBB showed remnants of jaline membranes in the alveolar spaces along with granulation tissue partly obliterating the alveolar spaces, and slight thickening of the interalveolar septa. Plump elongated reactive type II pneumocytes covering the alveolar septa were also numerous. A regimen of 200 mg methylprednisolone once a day was started and a partial remission of clinical and radiological abnormalities was achieved. Based on our clinical and radiological findings we therefore conclude a possible diagnosis of drug-induced toxicity by pemetrexed chemotherapy in continuous infusion.

Idiopathic pulmonary fibrosis (IPF) is difficult to diagnose because of numerous interstitial lung diseases with similar symptoms. As serum DNA has proven useful for early lung cancer detection, we aimed to define the relevance of this marker in discriminating IPF from other fibrotic and nonfibrotic/nonmalignant lung diseases. DNA was quantified in 191 subjects: 64 healthy individuals, 58 patients with IPF, 17 patients with nonspecific pulmonary fibrosis (13 idiopathic nonspecific interstitial pneumonia, 4 chronic hypersensitivity pneumonitis), and 52 patients with other diffuse/nonmalignant lung diseases. The median value of free DNA in IPF patients was 61.1 ng/mL (range 7.1–405), which was significantly higher than that of healthy donors (median 6.8, range 2.2–184) (p

intravascular large B-cell lymphoma is a distinct subtype of mature B-cell neoplasms, with uncommon primary presentation in the lungs. Diagnosis could be very difficult due to the lack of detectable tumor masses and it is usually made by surgical lung biopsy or autopsy examination.two patients occurred primarily with interstitial lung disease and underwent a pulmonary biopsy using cryoprobes.the pathological analysis of the lung biopsies revealed in both cases a conclusive diagnosis of intravascular large B-cell lymphoma with primary lung involvement and patients have been safely diagnosed using transbronchial cryobiopsy for the first time in the literature.transbronchial cryobiopsy could be used as valid surrogate for surgical lung biopsy in lymphoprolipherative lung disorders (including intravascular lymphomas), as allows larger samples of tissue, greater diagnostic yield, no crush artifacts and much less complications than surgical biopsy.