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Biomedical subjects

V Poletti

Publications and source records attributed to V Poletti.

At least 19 recordsLinked to original sources

Diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease, well recognised in Japan and principally affecting the respiratory bronchioles, causing a progressive suppurative and severe obstructive respiratory disorder. If left untreated, DPB progresses to bronchiectasis, respiratory failure and death. It was first described in the early 1960s. Subsequently, in 1969, the disease was named DPB 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. The distinctive imaging and histological features, the coexisting sinusitis, and the isolation of Haemophilus influenzae and Pseudomonas aeruginosa in the sputum enhance disease recognition. Histologically, DPB is characterised by chronic inflammation, localised mainly in the respiratory bronchioles and adjacent centrilobular regions, with characteristic interstitial accumulation of foamy histiocytes, neutrophils and lymphocyte infiltration. Neutrophils and T-lymphocytes, particularly CD8+ cells, together with the cytokines interleukin-8 and macrophage inflammatory protein-1, are believed to play key roles in the development of DPB. A significant improvement in the prognosis of this potentially fatal disease has been recently reported thanks to the use of long-term therapy with macrolide antibiotics, the effect of which is attributed to an anti-inflammatory and immunoregulatory action.

Anti-Bacterial Agents↗

Fire-eater's pneumonitis.

The authors report a case of acute respiratory failure that fulfils the diagnostic criteria for fire-eater's pneumonitis; pathological features, usually described only in experimental works on animals, are also discussed.

Adult↗

Acute exacerbation of idiopathic pulmonary fibrosis: report of a series.

This study describes five cases presenting an acute clinical course of pulmonary fibrosis, in the absence of specific precipitating factors. A retrospective chart review of five patients with histologically proved usual interstitial pneumonia was carried out in 2001-2002. Clinical data, bronchoalveolar lavage (BAL) findings, high resolution computed tomography and histological features were reported. On admission all cases presented hypoxemia and dyspnoea, while some showed an increase of carbohydrate antigen 19.9 or laboratory tests typical of infection, although appropriate cultures were all negative. Altogether, four subjects died and only one is on follow-up. A pattern of diffuse ground-glass or alveolar opacification superimposed on reticular and linear findings was evident on lung imaging in all cases. Marked neutrophilia, together with type II reactive cells hyperplasia, was detected on BAL. Histological findings, from open lung biopsy or autopsy, showed all the aspects of usual interstitial pneumonia with superimposed features of acute lung injury, such as diffuse alveolar damage, with or without hyaline membranes, type II reactive cells hyperplasia and numerous fibroblastic foci. This study also underlines the diagnostic value of bronchoalveolar lavage versus open lung biopsy.

Acute Disease↗

Acute interstitial pneumonia: report of a series.

Four cases of acute interstitial pneumonia (AIP) are described with special emphasis on clinical background, lung imaging and bronchoalveolar lavage findings. A retrospective chart review of four patients with histologically-proven AIP, diagnosed between 1998 and 2000, was carried out. Clinical data, bronchoalveolar lavage (BAL) findings, high-resolution computed tomography (HRCT) and histological features were analysed. Three patients died and only one is in follow-up. HRCT showed areas of ground glass attenuation and alveolar consolidation in all patients. Histology, documented by open lung biopsy or autopsy specimens, was consistent with the organising form of diffuse alveolar damage pattern. BAL findings were characteristic, with a huge neutrophilia associated with scattered atypical type II pneumocytes collected in clusters with extracellular amorphous material (fragments of hyaline membranes) observed in two out of three cases. In this paper, four cases of acute interstitial pneumonia are reported in detail. The poor prognosis associated with this entity has been confirmed and the possible diagnostic role of the bronchoalveolar lavage is emphasised.

Bronchoalveolar Lavage Fluid↗

Respiratory failure due to micronodular type II pneumocyte hyperplasia.

AIMS: To report the first case of respiratory failure due to micronodular type II pneumocyte hyperplasia. METHODS AND RESULTS: Biopsy, explant and autopsy material from a 16-year-old girl, a smoker, with no personal or family history of tuberous sclerosis, who died following lung transplantation necessitated by progressive respiratory failure, was evaluated histologically. Micronodular pneumocyte hyperplasia was identified histologically as the cause of the respiratory failure. Foci of hyperplastic type II pneumocytes measuring up to 4 mm were widely scattered through the lungs. The hyperplastic cells had abundant eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli. Immunohistochemistry showed that they stained for cytokeratins AE1, AE3 and CAM 5.2 and for epithelial membrane antigen (EMA), but not for carcinoembryonic antigen (CEA), S100, smooth muscle actin, CD68 and HMB-45. CONCLUSIONS: Although micronodular type II pneumocyte hyperplasia is usually of no clinical significance, in our patient the process was so florid as to cause respiratory failure, which was severe enough to necessitate lung transplantation.

Adolescent↗

Morphologic changes leading to bronchiolitis obliterans in a patient with delayed non-infectious lung disease after allogeneic bone marrow transplantation.

A 37-year-old man developed delayed non-infectious lung disease after undergoing bone marrow transplantation (BMT) for acute myeloid leukaemia. Over a 15-month period, the progression of morphologic changes from cellular interstitial pneumonia to bronchiolitis obliterans organizing pneumonia and cicatricial bronchiolitis obliterans was documented. Pulmonary function tests, high-resolution CT, bronchoalveolar lavage, lung biopsy and extensive microbiological studies were used as diagnostic tools either at onset and during the follow-up. This represents the first reported case in which a model--supported by longitudinal biopsy results--for the evolution of histologic lesions toward bronchiolitis obliterans after BMT is suggested; therapeutic implications are discussed.

Adult↗

Delayed non-infectious lung disease in allogeneic bone marrow transplant recipients.

BACKGROUND AND AIM OF THE WORK: The studies on late-onset non-infectious respiratory complications after allogeneic bone marrow transplantation (allo-BMT) have been mainly focused on bronchiolitis obliterans to date. The aim of this work was to analyze the incidence, clinico-pathologic characteristics and outcome of the entire spectrum of entities falling into the group of delayed non-infectious lung disease (DLD). METHODS: Retrospective chart review was carried out of 112 patients who underwent allo-BMT for hematologic malignancies between April 1995 and November 1998 at a single Institution. The categorization of the pulmonary disease was made by analyzing clinical data, bronchoalveolar lavage (BAL), high-resolution computed tomography (HRCT) and histology when possible. RESULTS: DLD occurred in 10 (10%) out of 97 recipients who survived at least 100 days following allo-BMT and was defined as bronchiolitis obliterans (BO; 4 cases), acute lung injury (ALI; 1 case) and subacute cellular interstitial pneumonia (SCIP; 5 cases). The BAL-profile was characterized by a marked increase of the neutrophil percentage in BO cases and of the lymphocyte (predominantly CD8+) percentage in parenchymal DLDs (SCIP, ALI). HRCT proved to be helpful to correctly identify BO cases, whereas histology was always needed to better define DLD presenting with an interstitial and/or alveolar pattern. The predominant airway involvement as well as the acute-onset of a respiratory illness with histological evidence of diffuse alveolar damage were associated with a worse prognosis because of a poor response to the immunosuppressive treatment. CONCLUSIONS: DLDs represent a group of entities heterogeneous in regard to variables such as onset and clinical behaviour (acute, subacute or chronic), predominant pattern of lung involvement (airway or parenchymal), response to treatment. Although immunopathologic mechanisms related to c-GVHD probably have a relevant pathogenic importance in this setting, the possible role of associated events (eg, drug toxicity and infections) at least in priming the lung damage need to be better clarified for its therapeutical implications.

Adolescent↗

Acute lung injury associated with 5-fluorouracil and oxaliplatinum combined chemotherapy.

Diarrhoea, T-CD4+ lymphopenia and bilateral patchy pulmonary infiltrates developed in a male 60 yrs of age, who was treated with oxaliplatinum and 5-fluorouracil for unresectable rectum carcinoma. The findings from transbronchial lung biopsy and bronchoalveolar lavage (BAL) were consistent with an organizing diffuse alveolar damage pattern. Once extensive microbiological studies proved negative, corticosteroids were given and a complete remission of clinical and radiological abnormalities was achieved. It is concluded that the aforementioned pathological manifestations were due to chemotherapy and included a pulmonary adverse reaction, a feature never previously associated with oxaliplatinum and 5-fluorouracil regimens.

Acute Disease↗

First report of the Italian register for diffuse infiltrative lung disorders (RIPID).

RIPID was established in 1998 as a joint project of the major Italian scientific societies for Respiratory Medicine, with the aim to create an Italian Register on diffuse infiltrative lung disorders that can provide the basis for epidemiological and clinical studies of adequate sample size. In the period from May 1998 to December 2000, 1,382 cases were submitted from 54 Centers in 15 regions of Italy, 54.2% males (mean age +/- SD 50.5 +/- 16.8 years) and 45.8% females (50.2 +/- 15.3 years). A current smoking habit emerges in 18% of subjects; former smokers and never-smokers represent 26% and 56% of the total case series, respectively. The most frequent disease registered is idiopathic pulmonary fibrosis (37.6%), followed in decreasing order by sarcoidosis (29.2%), and Langherans' cell hystiocytosis (6.6%). High resolution computed tomography (HRCT) was considered as the most important tool for final diagnosis in the majority of cases (74.4%); 39.4% of patients underwent transbronchial biopsies, 39.2% bronchoalveolar lavage (BAL). A surgical biopsy was performed in 20.5% of patients. A web site has been activated from December 2000 (www.pneumonet.it/ripid), allowing prompt access to all information and scientific material concerning the project and to an electronic form for data collection that can be completed on-line.

Adult↗

Comparison of registries of interstitial lung diseases in three European countries.

Few published studies have compared epidemiological data on the prevalence, incidence or relative frequency of the different interstitial lung diseases. In this review, the data of such registries from three countries in Europe (Belgium, Germany and Italy) are compared with those in the USA (Bernalillo County, NM). These registries show some striking similarities, but also discrepancies, which in part may be real, but may also be due to selection bias. Indeed, the registries in the European countries encompass the patients seen by pulmonologists, while the registry in Bernalillo County is based on a general population study in a limited area. In addition, in some studies, prevalences and incidences were registered, while in others, only prevalences or incidences were registered. Finally, most, but not all studies were prospective. Nonetheless, the different studies showed that sarcoidosis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, interstitial lung diseases due to collagen vascular diseases and not-defined (or postinflammatory) fibrosis were most frequent. In the majority of disease entities a male predominance was found. Surprisingly large differences in the use of diagnostic techniques, such as high-resolution computed tomography, bronchoalveolar lavage, open lung biopsy and transbronchial lung biopsy, were noted between the different studies.

Adult↗

Interstitial lung diseases: an epidemiological overview.

Epidemiological studies on interstitial lung diseases (ILDs) may be schematically subdivided into the following major types: 1) quantifications of disease, broken down into incidence, prevalence and mortality data; 2) identification of aetiological factors; and 3) clinical epidemiological studies. Epidemiological data may be obtained from different sources or population groups, using different study designs such as systematic national statistics, population-based data and registries, and large case series of specific diseases. Differences in results between epidemiological studies may be due to real differences in incidence, but may also be due to changes in disease definitions and classifications, differences in the epidemiological design of the studies, or even registration bias. Comparative epidemiological data of different ILDs are almost limited to the general population study in Bernalillo County and to national mortality statistics, which should be interpreted with great caution. Also, some, mostly national registries of the different ILDs have been carried out by specific medical profession groups (especially pulmonologists), which clearly underestimate the real incidence of ILDs, but in which the comparison of the relative frequencies is probably accurate. Based on all these comparative studies, sarcoidosis and idiopathic pulmonary fibrosis appear to be the most frequent ILDs, followed by hypersensitivity pneumonitis and ILD in collagen vascular disease, when classical pneumoconioses are not included. There is also a relatively large group of nonspecific fibrosis. Much more data have been published on the epidemiology of specific forms of interstitial lung disease. Most information is available on the epidemiology of sarcoidosis, and those data are probably the most accurate. Data on idiopathic pulmonary fibrosis have the disadvantage of the recent changes in definition and classification of this disease. Hypersensitivity pneumonitis has been studied epidemiologically, especially in some exposure groups such as farmers and pigeon breeders, and in some regions in North America, UK, France and Scandinavia. Estimates of frequencies of interstitial lung disease in collagen vascular disease or of drug-induced interstitial lung disease are less accurate and more variable, depending on diagnostic criteria. Notwithstanding the aforementioned problems, this report tries to provide a balanced overview of the epidemiology of different interstitial lung diseases.

Humans↗

Bronchoalveolar lavage in bronchiolitis obliterans organizing pneumonia primed by radiation therapy to the breast.

BACKGROUND: Growing evidence indicates that unilateral lung irradiation for breast cancer may "prime" the development of migratory lung infiltrates with histologic features of bronchiolitis obliterans organizing pneumonia. OBJECTIVE: Our purpose was to evaluate the cytologic and immunocytologic features of bronchoalveolar lavage in this condition. METHODS: We analyzed the profile bronchoalveolar lavage cell differentials and lymphocyte subpopulations of 11 women with bronchiolitis obliterans organizing pneumonia syndrome after radiation therapy for breast cancer in comparison to 9 healthy women. RESULTS: The bronchoalveolar lavage analysis demonstrated a significant increase in the percentage of lymphocytes (36.7% +/- 5.4% vs 8.6% +/- 1.1%, P =.0002), neutrophils (3.8% +/- 1.2% vs 0.6% +/- 0.2%, P =.005), eosinophils (2.4% +/- 1% vs 0.3% +/- 0.1%, P =.01), and mast cells (1.4% +/- 0.6% vs 0.1% +/- 0.02%, P =.05) with a significant decrease in the percentage of macrophages (56.1% +/- 6% vs 90.3% +/- 1.4%, P =.0002) in patients with bronchiolitis obliterans organizing pneumonia compared with the control subjects. The percentage of CD3(+) cells was significantly increased in patients with bronchiolitis obliterans organizing pneumonia (93.7% +/- 1.3% vs 70.9% +/- 4%, P =.0004), with a significant decrease in CD4(+) cells (32.7% +/- 4.7% vs 55.4% +/- 2. 6%, P =.002) and a significant increase in CD8(+) cells (61.2% +/- 4. 8% vs 37.5% +/- 2.9%, P =.003) in comparison to control subjects. The CD4/CD8 ratio was significantly reduced in patients with bronchiolitis obliterans organizing pneumonia compared with control subjects (0.6% +/- 0.1% vs 1.5% +/- 0.1%, P =.001). CONCLUSION: These data add to the view that unilateral lung irradiation for breast cancer may "prime" the development of a syndrome quite similar to idiopathic bronchiolitis obliterans organizing pneumonia.

Aged↗

Bronchiolitis obliterans-organizing pneumonia: an Italian experience.

The purpose of this study was to describe the clinical features at onset and outcome and the diagnostic approach in subjects with bronchiolitis obliterans-organizing pneumonia (BOOP). Over a 7-year period we observed 78 cases of biopsy-proven bronchiolitis obliterans-organizing pneumonia, in which well documented clinical and radiographic data were available. The final diagnosis of BOOP was validated when patients presented: (i) negative microbiological analysis on BAL fluid; (ii) a well documented improvement either spontaneous, or after steroid treatment or (iii) cases with progressive respiratory failure and increasing radiographic shadows, an open lung biopsy or autopsy that excluded other entities. There were 42 males and 36 females; the mean age was 61+/-12 years (range 12-85 years). Forty-two (54%) patients were current smokers, 25 (32%) had never smoked and 11 (14%) were ex-smokers. The clinical pattern at presentation of BOOP was more frequently similar to classical acute or sub-acute infectious pneumonia. Fever (63%), dyspnoea (58%) and dry cough (53%) were the typical symptoms on admission. A flu-like syndrome preceeding BOOP was observed in 21 cases (27%). Inspiratory crackles (78%) were the most typical finding at physical examination. However, 13% of the patients were asymptomatic and an abnormal chest X-ray film was the reason for seeking medical attention. Radiographically the most frequent pattern of BOOP was a unilateral consolidation (44%) with lower field predominance. A migratory behaviour was present in 22% of the cases. High-resolution computed tomographic (HR-CT) scan when performed, was more sensitive in detecting ground glass infiltrates, sub-pleural or peri-bronchovascular distribution or the presence of nodules or cavitation. Most patients (68%) were classified as having idiopathic BOOP. However, the same clinical-roentgenological pattern was observed in patients after radiotherapy for ductal breast carcinoma (6%), in collagen-vascular diseases (6%), related to drugs (9%), to infections serologically documented (4%), and to graft vs. host disease (4%). Four patients (all of whom had idiopathic BOOP) presented a rapid progressive respiratory failure needing mechanical ventilation. In another two cases respiratory failure appeared after a long period during which patients experienced exertional dyspnoea and low grade fever. BAL profile was characterized by lymphocytosis with a reduction of the CD4/CD8 ratio, associated with a slight increase of neutrophils and eosinophils and scattered mast cells. However in two cases we had an increased CD4/CD8 ratio and in one case the presence of a significant 12% of polyclonal B cells. In a few cases atypical (cytokeratin-positive cells) epithelial cells were detected: these cells were constantly present in the BAL fluid of patients with rapidly progressive respiratory failure. From the diagnostic point of view this series documents that transbronchial lung biopsy (coupled with BAL) can be the first diagnostic step. However, therapy can be started on the basis of BAL data (when a characteristic morphological and phenotypical profile is evident) in cases in which the clinical presentation is suggestive and a biopsy cannot be made. Most patients showed a rapid and good response to steroid therapy. However, three patients died (4%) in spite of steroid therapy (two cases) and steroid and cyclophosphamide therapy (one case). In conclusion, although clinical findings, chest X-ray film and CT Scan findings usually suggest the diagnosis a definite confirmation requires transbronchial lung biopsy and BAL and, less frequently, open lung biopsy.

Adolescent↗

The lung as a target organ in patients with hematologic disorders.

The lung is one of the organs most severely affected by complications during the course of hematologic disorders. In the last years an impressive amount of progress has been made in clarifying the pathogenesis of lung diseases, particularly those occurring in conditions of severe immunosuppression such as bone marrow transplantion, acquired immunodeficiency syndrome or leukemia. Peculiar anatomical characteristics render the lung parenchyma highly susceptible to infections, but the clinical outcome is due not only to the injury induced by the pathogens but also to their interactions with inflammatory cells and particularly to the effects of a wide network of secreted cytokines. Polymorphonuclear cells, macrophages, lymphocytes and structural pulmonary cells (epithelial cells, interstitial cells) generate a variety of cytokines and growth factors which, in turn, may be responsible for the majority of the clinical effects in response to infections, such as those of Pneumocystis carinii and cytomegalovirus, but also to certain drugs or to radiation. The pathogenesis of graft-versus-host disease (GVHD) is still poorly understood, but animal models seem to demonstrate the involvement of a number of cytokines and growth factors, together with toxic effects induced by conditioning regimens.

Chemotaxis, Leukocyte↗