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Venerino Poletti

Publications and source records attributed to Venerino Poletti.

At least 19 recordsLinked to original sources
PubMed2026

Idiopathic pulmonary fibrosis risk loci in East Asian populations mirror those of European populations.

RATIONALE: Common and rare variants that are associated with the risk of developing idiopathic pulmonary fibrosis (IPF) have been identified predominantly in European ancestry populations. OBJECTIVES: To better understand the genetic variants that contribute to IPF in individuals with Asian ancestry, we conducted a genome-wide association study of IPF in East Asian populations. METHODS: We included 1026 patients with IPF and compared them to 1723 unaffected controls of Japanese and Korean ancestry. Genome-wide association analysis was conducted in the Japanese and Korean ancestry cohorts separately and combined using meta-analysis. Restricted maximum likelihood was used to estimate the SNP-based heritability and local ancestry of chromosome 11 was inferred for each subject. MEASUREMENTS AND MAIN RESULTS: We identified loci on chromosomes 4 (FAM13A; rs7690839), 5 (TERT; rs7734992), 6 (DSP; rs2076295), and 11 (MUC5B; rs35705950) that were significantly associated with risk of IPF. Importantly, the sentinel variants in each of these loci are the same as, or in strong linkage disequilibrium with, the risk variants that have been observed in studies of European ancestry populations. In aggregate, common variants (not including the MUC5B promoter variant) account for approximately 25% of the risk of developing IPF in these East Asian ancestry cohorts. Moreover, local ancestry analysis indicates that the presence of MUC5B promoter variant in the East Asian population is not a result of admixture with European ancestry populations. CONCLUSIONS: We conclude that the IPF risk loci in East Asian populations are shared with those of European ancestry populations, although their risk allele frequencies and effect sizes differ. These findings indicate shared genetic risk factors of IPF across ancestries.

Aged↗
PubMed2005

CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalations of finely dispersed organic particles or low molecular weight chemicals. The disease is characterized by an alveolitis sustained by CD8(+) cytotoxic T lymphocytes, granuloma formation, and, whenever antigenic exposition continues, fibrosis. Although it is known that T-cell migration into the lungs is crucial in HP reaction, mechanisms implicated in this process remain undefined. METHODS: Using flow cytometry, immunohistochemistry, confocal microscopy analysis and chemotaxis assays we evaluated whether CXCL10 and its receptor CXCR3 regulate the trafficking of CD8(+) T cells in HP lung. RESULTS: Our data demonstrated that lymphocytes infiltrating lung biopsies are CD8 T cells which strongly stain for CXCR3. However, T cells accumulating in the BAL of HP were CXCR3(+)/IFNgamma(+) Tc1 cells exhibiting a strong in vitro migratory capability in response to CXCL10. Alveolar macrophages expressed and secreted, in response to IFN-gamma, definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3(+) T-cell line. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the BAL in individuals with HP. CONCLUSION: These data indicate that IFN-gamma mediates the recruitment of lymphocytes into the lung via production of the chemokine CXCL10, resulting in Tc1-cell alveolitis and granuloma formation.

Adult↗
PubMed2005

High-resolution CT in diagnosis of diffuse infiltrative lung disease.

The chest radiograph remains the first imaging modality for the approach to diffuse infiltrative lung disease (DILD), but, 23 years after its introduction, high-resolution CT (HRCT) is still considered the best imaging tool for the evaluation of the pulmonary interstitium and to diagnose and assess DILD. The introduction of multidetector computed tomography (MDCT) has provided the thoracic radiologist with a powerful tool with which to image the lung. Moreover MDCT has enabled radiologists to understand better the functional information contained within CT images of DILD. By focusing on the HRCT signs, patterns, and distributions of abnormalities, and mentioning the clinical aspects and the new recent advances in pulmonary imaging, in this article we provide an overview of a practical approach to the interpretation of the DILD.

Humans↗
PubMed2005

Pulmonary complications in patients with hematological disorders: pathobiological bases and practical approach.

Pulmonary complications occur in up to 40 to 60% of patients with hematological disorders during the disease course and considerably influence morbidity and mortality. The main factors making the lung a clinically significant targeted organ in these patients may be summarized as follows. In the lung parenchyma a variety of inflammatory cells whose precursors are in the bone marrow pass through, park in, proliferate, and release microbicidal and cytohistotoxic substances. Constitutive parenchymal lung cells (bronchiolar and alveolar epithelial cells, endothelial cells, "interstitial" cells) may be a distinctive target for toxic substances or may have an important part in the inflammatory/reactive and reparative processes after an injury event. Pathogenic agents are allowed to reach the lung very easily through either or both the airways and the vascular bed and accumulate there in large amounts. Inflammatory/immunologic reactions may be particularly weak or, on the contrary strong, in the lungs either spontaneously or due to toxic action of drugs and radiation or to the immunodeficiency induced by hematological disorders, and finally to the presence of immunomodulatory viruses. The distinctive anatomical structure and function of the lung parenchyma (interactions between air spaces and capillary bed-gas exchange units) may render localized parenchymal damage clinically relevant. Allogeneic reactions may be overexpressed in the lung or the kinetics of the developing of graft versus host disease (GVHD)-related lung injury may be markedly different from the kinetics of GVHD in other organs. Hematological disorders may harbor in lung parenchymal structures at the onset (i.e., lympho-/myeloproliferative disorders primary in the lung) or during the disease course. Genetic predisposition, although probably involved, is not yet well understood. This article reviews the pathobiological bases of lung injury occurring in subjects with hematological disorders and suggests a practical diagnostic approach to these pulmonary complications.

Disease Susceptibility↗
PubMed2005

Lymphoproliferative lung disorders.

Although the lung is frequently involved by disseminated lymphoma, isolated pulmonary lymphoma is rare, accounting for less than 1% of all extranodal localized disease. Three broad categories of lymphoma of the lung require recognition: in rare instances, large B cell type lymphoma can present primarily in the lung; a second variant is by T cell lymphoma presenting as an angiocentric process. However, the most common histologic subtype is represented by low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, often in the past considered as a pseudotumor because of its long indolent natural history. Common presenting features include cough, dyspnea, pain, fever, recurrent infections, hemoptysis, or an asymptomatic finding on routine chest radiograph. Precise pathological diagnosis and molecular characterization are required in all cases, following World Health Organization classification criteria. Radiological features include pulmonary consolidation, solid pulmonary opacities, hilar adenopathy, or pleural effusion. Principles of treatment vary with the different histology.

Diagnosis, Differential↗
PubMed2005

HHV-8 and EBV are not commonly found in idiopathic pulmonary fibrosis.

BACKGROUND AND AIM OF THE WORK: Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia (IPF/UIP) is a diffuse and progressive lung disease whose pathogenesis is incompletely understood. Recently, the presence of Herpesvirus-specific DNA was detected in the large majority of cases of a series of IPF/UIP and other lung interstitial diseases. We have therefore tested our own IPF/UIP series for the presence of HHV-8 and EBV proteins. METHODS: We used a variety of sensitive technologies including immunohistochemistry with NCL-HHV8-LNA and EBV-LMP1 antibodies, as well as of EBV RNA (EBER) by in-situ hybridisation; the presence of HHV-8 and EBV DNA was also investigated by means of PCR and subsequent analysis using a microfluidic apparatus. RESULTS: Despite the good sample quality, immunohistochemical, in-situ hybridisation and PCR results were negative for both EBV and HHV-8. CONCLUSIONS: We conclude that EBV and HHV-8 are not involved in the pathogenesis of IPF/UIP.

Adult↗
PubMed2004

Disseminated basidiobolomycosis in an immunocompetent woman.

Basidiobolomycosis is a chronic subcutaneous infection of the trunk and limbs due to Basidiobolus ranarum. The disease is well known in tropical areas, although recent cases of gastrointestinal basidiobolomycosis have also been reported in Arizona. We describe a young immunocompetent women who had presented with eosinophilia and lung infiltrates. She subsequently died, and diagnosis of disseminated basidiobolomycosis was made on the basis of histological features at autopsy.

Adult↗
PubMed2004

Diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease, largely restricted to Japan, that is characterized by progressive suppurative and obstructive airway disease, which, if left untreated, progresses to bronchiectasis, respiratory failure, and death. The lesion was first described in the early 1960s. In 1969 the name diffuse panbronchiolitis (DPB) was proposed to distinguish it from chronic bronchitis. Diffuse refers to the distribution of the lesions throughout both lungs, and pan refers to the involvement of inflammation in all layers of the respiratory bronchioles. Its distinctive imaging and histologic features, the coexisting sinusitis, and the isolation of Haemophilus influenzae and Pseudomonas aeruginosa in the sputum should enhance disease recognition. Neutrophils and T-lymphocytes, particularly CD8- cells, together with cytokines IL-8 and macrophage inflammatory protein-1 are believed to play key roles in the development of this disease. Significant improvement in the prognosis of this potentially fatal disease has been reported after the use of long-term therapy with macrolide antibiotics, the effect of which is attributed to an anti-inflammatory and immunoregulatory action.

Bronchiolitis↗
PubMed2004

Transbronchial needle aspiration improves the diagnostic yield of bronchoscopy in sarcoidosis.

BACKGROUND AND AIM: Transbronchial needle aspiration (TBNA) is a minimally invasive bronchoscopic procedure that allows sampling of hilar and mediastinal lymph nodes in close contact with the airways. We undertook this study to assess the value of TBNA in the diagnosis of sarcoidosis manifesting with intrathoracic lymphadenopathies (stages I and II), and to compare its yield with that of transbronchial lung biopsy (TBLB). METHODS: The results of bronchoscopy with combined TBNA and TBLB in 32 patients with stage I or II sarcoidosis were retrospectively analyzed. RESULTS: Sensitivity was 65.6% for TBNA (stage I, 82.3 %; stage II, 46.6%), and 62.5% for TBLB (stage 1, 52.9%; stage II, 73.3%). The combination of the two methods was associated with the highest diagnostic yield (93.7% overall sensitivity), and allowed significantly better results over both TBNA alone (93.7% vs 65.6%; p = 0.011) and TBLB alone (93.7% vs 62.5%; p = 0.005). CONCLUSIONS: The results of our study suggest that a diagnostic approach combining TBNA and TBLB is safe and effective in the setting of stage I and II sarcoidosis. It also confirmed the value of TBNA, with excellent diagnostic yields especially in stage I of the disease.

Adult↗
PubMed2003

Complement receptor 1 gene polymorphisms are associated with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrotic disorder underlain by aberrant wound healing of repeated lung injury. Environmental triggers and genetic background are likely to act as modifiers of the fibrotic response. Erythrocyte complement receptor 1 is a membrane protein mediating the transport of immune complexes to phagocytes. Three gene polymorphisms are related to the erythrocyte surface density of complement receptor 1 molecules, which in turn are related to the rate of immune complexes' clearance. There is evidence of association between sarcoidosis and the complement receptor 1 gene. We wondered whether IPF is associated with the complement receptor 1 gene alleles coding for a reduced molecule/erythrocyte ratio. We studied 74 patients and 166 control subjects. Three polymorphic sites of the gene, A3650G exon 22, HindIII RFLP intron 27, and C5507G exon 33, were analyzed and found to be in linkage disequilibrium. The GG genotype for the C5507G exon 33 polymorphism was significantly more common in patients with IPF than in control subjects (odds ratio = 6.232, 95% confidence interval = 2.198-18.419, p = 0.00023). The significant difference was found in both sexes. These findings agree with speculations on the role of the complement receptor 1 gene in idiopathic pulmonary fibrosis.

Aged↗
PubMed2003

Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis.

To investigate the molecular events that may underpin dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we analyzed the expression patterns of beta-catenin on 20 IPF/UIP lung samples, together with two downstream target genes of Wnt signaling, cyclin-D1, and matrilysin. In 18 of 20 cases of IPF/UIP investigated on serial sections, nuclear beta-catenin immunoreactivity and abnormal levels of cyclin-D1 and matrilysin were demonstrated in proliferative bronchiolar lesions (basal-cell hyperplasia, squamous metaplasia, bronchiolization, honeycombing). The nature of these lesions was precisely defined using specific markers (DeltaN-p63, surfactant-protein-A, cytokeratin-5). Interestingly, nuclear beta-catenin accumulation was also demonstrated in fibroblast foci in most (16 of 20) IPF/UIP samples, often associated with bronchiolar lesions. Similar features were not observed in normal lung and other fibrosing pulmonary diseases (diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, desquamative interstitial pneumonia). Sequence analysis performed on DNA extracted from three samples of IPF/UIP did not reveal abnormalities affecting the beta-catenin gene. On the basis of these findings new models for IPF/UIP pathogenesis can be hypothesized, centered on the aberrant activation of Wnt/beta-catenin signaling, with eventual triggering of divergent epithelial regeneration at bronchiolo-alveolar junctions and epithelial-mesenchymal-transitions, leading to severe and irreversible remodeling of the pulmonary tissue.

Adult↗
PubMed2003

Bronchiolar disorders: classification and diagnostic approach.

Bronchiolitis is a process in which inflammatory cells and mesenchymal tissue are both present, mainly centered in and around membranous and/or respiratory bronchioles, with sparing of a considerable portion of the other parenchymal structures. The distribution and amounts of the cellular and mesenchymal components vary from case to case, which accounts for the variety of histopathologic, radiographic, and clinical aspects of bronchiolitis. The clinical classification of bronchiolar diseases considers the causes or the clinical settings in which bronchiolitis develops: inhalation of toxic fumes, irritant gases or organic dusts, infectious and postinfectious bronchiolitis, collagen-vascular disease-associated bronchiolitis, posttransplant bronchiolitis, or rarer associations. A morphological classification based on histologic characteristics takes into account four main histologic patterns: cellular bronchiolitis, bronchiolitis with inflammatory/intraluminal polyps, constrictive or cicatritial bronchiolitis, peribronchiolar fibrosis, and bronchiolar metaplasia. High-resolution computed tomographic scanning (HRCT) is currently the best imaging technique for the evaluation of patients suspected of having bronchiolitis. HRCT findings in bronchiolar diseases with a good correlation with histopathologic changes are classified as follows: centrilobular tubular branching or nodular opacities; ground-glass attenuation or consolidation; mosaic perfusion; a mixed pattern. This article presents and briefly discusses the diagnostic approach to these diseases.

Journal Article↗
PubMed2003

Extranodal marginal zone B-cell lymphoma of MALT-type of the lung: single-center experience with 12 patients.

The lung is a relatively rare site for mucosa-associated lymphoid tissue (MALT) lymphomas: we report the largest available single-center series of patients with this presentation. From August 1992 to October 2000, 12 patients with untreated primary low-grade MALT lymphoma of the lung were submitted either to chemotherapy alone (n = 8), surgery alone (n = 2) or surgery plus chemotherapy (n = 2). At diagnosis, 6 (50%) were asymptomatic and 6 (50%) had nonspecific pulmonary symptoms. The most common radiologic findings were a pulmonary infiltrate (7 cases) and a mass lesion (5 cases). Histological diagnosis was obtained with transbronchial lung biopsy/bronchoalveolar lavage (BAL) (6 cases), with transthoracic needle biopsy (1 case), or an open thoracotomy (5 cases). All patients had stage IE. All 12 (100%) achieved complete remission; 3 (25%) local recurrences were observed. The global 6-year survival rate was 100% with a relapse-free survival rate of 50%. In conclusion, these data underline the diagnostic utility of BAL and the therapeutic efficacy of a chemotherapeutic strategy based on regimens such as N-CVP in the context of localized MALT lymphoma of the lung.

Aged↗
PubMed2003

Recent advances in the diagnosis and management of nonspecific interstitial pneumonia.

Idiopathic interstitial pneumonia is a heterogeneous group of diseases. Recently, the importance of a detailed differentiation of nonspecific interstitial pneumonia from other idiopathic interstitial pneumonias has been demonstrated. Most critical appeared to be a proper classification based on clinical presentation, high-resolution CT findings, bronchoalveolar lavage fluid cell findings, and histopathology. This classification may guide the most appropriate therapeutic approach and has significant implications regarding prognosis. Recent advances in the diagnosis and management of nonspecific interstitial pneumonia, cellular and fibrosing variants, are discussed.

Adrenal Cortex Hormones↗
PubMed2003

The value of flexible transbronchial needle aspiration in the diagnosis of stage I sarcoidosis.

STUDY OBJECTIVES: Transbronchial lung biopsy (TBLB) during flexible bronchoscopy (FB) is the recommended procedure for diagnosing sarcoidosis in most cases, although its yield in stage I disease is reported to be not as high as when parenchymal involvement is radiologically evident. We undertook this study to assess the diagnostic value of transbronchial needle aspiration (TBNA) in sarcoidosis presenting with hilar and/or mediastinal lymphadenopathy (stage I). DESIGN: Retrospective review of bronchoscopy procedures performed over a 6-year period for the diagnostic workup of hilar and/or mediastinal lymphadenopathy, as detected by chest radiographs. SETTING: Urban academic hospital. PATIENTS: Fifty-five patients with hilar and/or mediastinal lymphadenopathy without pulmonary abnormalities were included in the analysis. INTERVENTIONS: After chest CT and physical examinations, all patients underwent FB with TBNA. Patients thought to have clinicoradiologic findings highly consistent with sarcoidosis, as assessed by the bronchoscopists performing the procedures, underwent combined TBNA and TBLB. RESULTS: A diagnosis of sarcoidosis was established in 32 patients. In the remaining 23 patients, other diseases were pathologically diagnosed. Overall, TBNA was diagnostic in 23 of 32 patients with sarcoidosis (72%) by showing nonnecrotizing granulomas in 28 of 39 lymph node stations sampled (72%). Among the 15 patients who were submitted to both TBNA and TBLB, TBNA exclusively established the diagnosis in 7 of 15 patients (47% increase in the diagnostic rate) and its yield exceeded that of TBLB (11 of 15 patients [73%] vs 6 of 15 patients [40%], respectively). The association of TBNA and TBLB increased the diagnostic yield to 87%. CONCLUSIONS: TBNA may be of great value in the diagnostic evaluation of patients with suspected stage I sarcoidosis, and its use in association with TBLB should be strongly encouraged. TBNA may also preclude the need for further surgical diagnostic procedures in several patients with hilar and/or mediastinal adenopathy due to causes other than sarcoidosis.

Biopsy, Needle↗
PubMed2003

Idiopathic bronchiolitis mimicking diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a distinct sinobronchial syndrome which has been almost exclusively reported in East Asia; only a few cases have been observed in non-Asians so far. Since 1990, when one of us described the first European case, we have screened all patients presenting with a clinical, physiopathological and radiological pattern compatible with DPB, in order to assess if the paucity of proven cases in Europe could reflect a lack of awareness of this disease among both pulmonologists and pathologists. Over a 10-years period we identified four additional DPBs, but also interestingly observed five cases of "idiopathic" bronchiolitis (IB) that had both clinical symptoms and high-resolution computed tomography (HRCT) findings indistinguishable from those of DPB, but did not show the typical histological changes. All these patients were Caucasians and presented with dyspnea, productive cough, an obstructive or mixed impairment on pulmonary function tests and chest HRCT features strongly suggesting a grade II to IV DPB. We suggest that diseases classified as IB in this study might be homogeneous entities which are clinically and radiologically similar to DPB.

Adult↗
PubMed2002

Role of fiberscopic transbronchial needle aspiration in the staging of N2 disease due to non-small cell lung cancer.

BACKGROUND: Transbronchoscopic needle aspiration (TBNA) can offer a unique opportunity to identify surgically unresectable lung cancer and to avoid surgical mediastinal exploration in many patients with mediastinal lymph node extension of the tumor. The aim of this study was to assess the yield of TBNA performed with either histology or cytology needles in mediastinal staging of N2 disease due to non-small cell lung cancer (NSCLC). METHODS: Retrospective chart review was carried out on 194 TBNA procedures performed between January 1997 and September 2000 at a single institution. Inclusion criteria were pathologic evidence of NSCLC; contrast enhancement computed tomography scan of the chest suggesting N2 disease; and negative bronchoscopic examination for possible neoplastic lesions at the site of RESULTS: Overall sensitivity and diagnostic accuracy were 71% and 73%, respectively, with no significant differences between 19-gauge and 22-gauge cytology needles. Procedures performed for right paratracheal and subcarinal lymph node stations had a significantly higher yield than those for the left paratracheal station. CONCLUSIONS: TBNA mediastinal staging, performed during the initial diagnostic evaluation of NSCLC, can spare costs and risks of more invasive procedures in patients with inoperable tumors, in patients who are not candidates for operation because of coexistent significant comorbidities, and in patients with N2 disease.

Biopsy, Needle↗