Gianluca Casoni

The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics

In vitro polarized human Th2 cells preferentially express the chemokine receptors CCR3, CCR4, and CCR8 and migrate to their ligands: eotaxin, monocyte-derived chemokine (MDC), thymus- and activation-regulated chemokine (TARC), and I-309. We have studied the expression of chemokines and chemokine receptors in the airway mucosa of atopic asthmatics. Immunofluorescent analysis of endobronchial biopsies from six asthmatics, taken 24 hours after allergen challenge, demonstrates that virtually all T cells express IL-4 and CCR4. CCR8 is coexpressed with CCR4 on 28% of the T cells, while CCR3 is expressed on eosinophils but not on T cells. Expression of the CCR4-specific ligands MDC and TARC is strongly upregulated on airway epithelial cells upon allergen challenge, suggesting an involvement of this receptor/ligand axis in the regulation of lymphocyte recruitment into the asthmatic bronchi. In contrast to asthma, T cells infiltrating the airways of patients with chronic obstructive pulmonary disease and pulmonary sarcoidosis produce IFN-gamma and express high levels of CXCR3, while lacking CCR4 and CCR8 expression. These data support the role of CCR4, of its ligands MDC and TARC, and of CCR8 in the pathogenesis of allergen-induced late asthmatic responses and suggest that these molecules could be considered as targets for therapeutic intervention.

COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma

Background: Squamous cell carcinoma has a stronger association with tobacco smoking than other non-small cell lung cancers (NSCLC). A study was undertaken to determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for the squamous cell carcinoma histological subtype in smokers with surgically resectable NSCLC. Methods: Using a case-control design, subjects with a surgically confirmed diagnosis of squamous cell carcinoma were enrolled from smokers undergoing lung resection for NSCLC in the District Hospital of Ferrara, Italy. Control subjects were smokers who underwent lung resection for NSCLC in the same hospital and had a surgically confirmed diagnosis of NSCLC of any histological type other than squamous cell. Results: Eighty six cases and 54 controls (mainly adenocarcinoma, n = 50) were enrolled. The presence of COPD was found to increase the risk for the squamous cell histological subtype by more than four times. Conversely, the presence of chronic bronchitis was found to decrease the risk for this histological subtype by more than four times. Among patients with chronic bronchitis (n = 77), those with COPD had a 3.5 times higher risk of having the squamous cell histological subtype. Conclusions: These data suggest that, among smokers with surgically resectable NSCLC, COPD is a risk factor for the squamous cell histological subtype and chronic bronchitis, particularly when not associated with COPD, is a risk factor for the adenocarcinoma histological subtype.

Neutrophilic infiltration within the airway smooth muscle in patients with COPD

Background: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. Methods: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. Results: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). Conclusions: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation.

Diagnosis of pulmonary thromboembolism with endobronchial ultrasound

To the Editors: Endobronchial ultrasound (EBUS) is a new addition to the diagnostic armamentaria of the pneumologist. Its properties allow for excellent visualisation of structures surrounding the airways and, as such, have significant potential to add to diagnostic bronchoscopies. EBUS has a definitive role in detection and biopsy of mediastinal lymph nodes or masses 1, 2. However, we believe that the potential use of this procedure is still underestimated. For this reason, in this letter we report on the …

EBUS-TBNA in mediastinal/hilar lymphadenopathies and/or masses: an Italian case series.

Introduction:  Transbronchial needle aspiration (TBNA) is an established method to diagnose hilar/mediastinal lymphadenopathies and/or masses. Real‐time endobronchial ultrasound (EBUS) is a method that involves TBNA, and has been shown to increase the diagnostic yield in this context.

A Case of Amiodarone-induced Acute Fibrinous and Organizing Pneumonia Mimicking Mesothelioma

A 79-year-old man who was a nonsmoker, ex–truck driver, and metalworker (20 years) was admitted to our hospital. He had a diagnosis of pleural and parenchymal asbestos-related lesions with bilateral, partly calcified, pleural plaques (Figure 1B, blue arrow) and bilateral round atelectasis in both lower lobes (Figure 1C, yellow arrows). He had already undergone bronchoalveolar lavage (BAL) that did not show any asbestos bodies. Treatment with amiodarone (200 mg four times daily for 5 d/wk) was started 8 months before for a paradoxical atrial fibrillation. He was admitted to the hospital for recent appearance of dyspnea, dry cough, and low-grade fever persisting despite antibiotics treatment. A computed tomography scan detected unilateral, circumferential right pleural effusion, pleural thickening, and right upper lobe ground glass attenuation (Figures 2A and 2B). Moreover, right hemithorax volume was reduced. Mediastinal adenopathies, right lower lobe consolidation (Figure 2C), and peripheral consolidation in the left lower lobe were also observed (Figure 2C). A neoplastic lesion (mesothelioma, adenocarcinoma) was considered. Vacuolated macrophages and asbestos bodies were not identified in BAL fluid (Figure 2D). In the transbronchial lung biopsy specimens (Figures 3A and 3B), intraalveolar fibrin balls (arrow), chronic inflammatory interstitial infiltrate, and myofibroblasts embedded in the alveolar proteinaceous exudate and extracellular matrix were observed (acute fibrinous and organizing pneumonia [AFOP] pattern) (1). The patient was treated with methylprednisolone 40 mg twice daily, and amiodarone was withdrawn. Three months later, computed tomography scan showed complete remission of the pleural effusion and of alveolar consolidations (Figures 4A and 4B). Figure 1. Multiple bilateral pleural plaques (A and B; blue arrow) associated with bilateral round atelectasis (C; yellow arrows) and huge bilateral basal calcified plaques (D).

Endothelial cell activity in chronic obstructive pulmonary disease without severe pulmonary hypertension.

Pulmonary hypertension is common in patients with chronic obstructive pulmonary disease (COPD), but the precise mechanism of vascular impairment in these patients is unknown. We, therefore, decided to investigate whether endothelial cell dysfunction is present in patients with COPD with a wide range of chronic airflow obstruction before the development of severe pulmonary hypertension. Selected plasma markers of endothelial cell activity were studied: nitrate+nitrite (NO-2/NO-3), thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), soluble selectins (endothelium sES, leukocyte sLS, platelet sPS), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1). Twenty-five patients with COPD (forced expiratory volume in one second/vital capacity [FEV1/VC] < 88% predicted) and 29 healthy control subjects were recruited to the study. Among patients nine had a pulmonary artery systolic pressure (PASP) between 15 and 30 mmHg, 13 between 32 and 38 mmHg, 2 had a PASP of 41 and 42 mmHg, respectively. One patient had severe pulmonary hypertension with a PASP of 70 mmHg. The average FEV1 of patients with COPD was 46 ± 4% predicted. As compared to control subjects, patients with COPD showed a significant increase in plasma levels of TM and TFPI, indicating that their endothelial cells are still able to produce potent coagulation inhibitors. Levels of NO-2/NO-3were similar in the two groups of subjects examined, further suggesting preserved endothelial function in patients with COPD. In regard to adhesion molecules, patients with COPD showed a reduction in sLS, sPS, and sPECAM-1, and an increase in sICAM-1. This study shows that endothelial cell activity is largely preserved in patients with COPD without severe pulmonary hypertension, suggesting that these patients, despite quite severe airway obstruction, retain reasonably normal endothelial function until they develop severe pulmonary hypertension.

Reducing agents inhibit the contractile response of isolated guinea‐pig main bronchi

Background Oxidants are involved in many respiratory disorders, including asthma and chronic obstructive pulmonary diseases. Reduced glutathione (GSH), one of the most important antioxidant compounds against oxidant free radicals, is particularly abundant in the respiratory epithelial lining fluid, where its concentration is increased in inflammatory disorders.

Lymphoproliferative lung disorders: clinicopathological aspects

Lymphoproliferative disorders are rarely observed as primary lesions in the lung, representing only 0.3% of all primary pulmonary malignancies, <1% of all the cases of non-Hodgkin lymphoma and 3–4% of all the extra nodal manifestations of non-Hodgkin lymphoma. The earliest comprehensive studies of pulmonary lymphomas were those of Saltzstein [1] and Papioannou and Watson [2], which were published in the 1960s. These investigators made important observations: low-grade neoplasms were more frequent than higher grade lymphomas (reticulum cell sarcomas) and both tumours had better clinical outcomes than their nodal-based counterparts. The authors also concluded that the majority of neoplasms with a low-grade cytological appearance should be considered as reactive proliferations, introducing the term “pseudo-lymphoma”. This hypothesis showed significant weak points and, approximately 20 years later, Addis et al. [3] concluded that “most if not all the cases of pseudo-lymphoma can be classified, when re-evaluated, as malignant lymphoma”. Knowledge of these entities expanded rapidly after the advent of new investigative tools such as immunohistochemistry and molecular biology techniques. The World Health Organization (WHO) classification of lymphoid neoplasm recently emphasised the importance of clinical features [4]. table 1 provides an overall classification of lymphoproliferative disorders, which are described as: reactive/non-neoplastic lymphoid lesions, malignant parenchymal lymphoproliferative lesions (primary or secondary) and post-transplant lymphoproliferative disorders. View this table: Table 1. Classification system for the pulmonary lymphoproliferative disorders ### Reactive pulmonary lymphoid diseases Three rare forms of benign hyperplasia of pulmonary lymphoid tissue, namely follicular bronchiolitis, pulmonary nodular lymphoid hyperplasia and lymphocytic interstitial pneumonia, are regarded as part of the spectrum of lymphoid hyperplasia of the bronchus-associated lymphoid tissue (table 1) [5, 6]. Follicular bronchiolitis is characterised by lymphoid follicular hyperplasia, often with reactive germinal centres, in the walls of bronchioles with narrowing of the lumen. Pulmonary nodular lymphoid hyperplasia (pulmonary pseudo-lymphoma) is a distinct form of reactive …

Fever, splenomegaly and lymphopenia in sarcoidosis. Visceral leishmaniasis.

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 …