Giuseppina Bertorelli

Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis

Background: Eosinophils and T lymphocytes represent constant features in the airways of subjects with exacerbated chronic bronchitis. Eotaxin is the most potent and selective eosinophil chemoattractant which can also attracts lymphocytes. The aim of the study was to evaluate the expression of eotaxin and its receptor, CCR3, in bronchial airways during exacerbation of chronic bronchitis.

Individual exposure to particulate matter and the short-term arrhythmic and autonomic profiles in patients with myocardial infarction

AIMS Epidemiological studies show that peak exposure to air pollution is associated with increased morbidity and mortality from cardiovascular events. Panel and controlled exposure studies show that particulate matter (PM) may influence the parasympathetic regulation of the heart. The aim of this study was to concurrently measure individual exposure to PM of various sizes, heart rate variability (HRV), and electrical instability in patients with myocardial infarction. METHODS AND RESULTS Personal exposures to PM(10), PM(2.5), and PM(0.25) was measured over 24 h in 39 patients (36 males, 3 females; mean age 60.3 years) with prior myocardial infarction (>6 months). Simultaneously, a 24 h ECG was recorded and then analysed for HRV and ventricular arrhythmias. Breath condensate and blood samples also were collected at the end of monitoring to measure several indexes of inflammation. Negative correlation was found between HRV and exposure to PM(0.25) in a group of patients not taking beta-blockers. More severe ventricular arrhythmias were observed at the highest concentrations of PM(10) and PM(2.5). Indexes of inflammation in either breath condensate or blood did not correlate with PM exposures. CONCLUSION Our study shows that exposure to ultrafine particles is associated with autonomic dysregulation in selected patients with myocardial infarction. More severe arrhythmias occur at the highest exposures to larger particles. Nevertheless, the underlying mechanisms remain hypothetical because inflammation may be evoked by PM or be related to the disease itself.

Dendritic cell number is related to IL-4 expression in the airways of atopic asthmatic subjects.

Background: Airway dendritic cells are essential for stimulating naive T cells in response to inhaled antigen and for the development of allergic sensitization. IL‐4 in vitro can distinguish dendritic cell lines from peripheral blood mononuclear cells. Our study had the following aims:

Pulmonary Involvement in Sjögren’s Syndrome

In this study we tried to value the frequency and the characteristics of the physiological abnormalities affecting the lungs in Sjögrens syndrome (SS). We studied 18 female nonsmokers (average age 53 years). The diagnosis has been made on the presence of at least two of the following abnormalities: keratoconjunctivitis sicca (Schirmers test), xerostomia (scanning of the salivary glands, lip biopsy) and collagen vascular disease. We made the following tests: clinical examination, chest roentgenogram, spirometry, TGV, RAW and SAW valuation, study of the flow-volume curves, diffusion capacity test, bronchoalveolar lavage, bronchial biopsy. The physiological results have demonstrated the presence of a restrictive syndrome affecting above all the small airways (MEF25-32.7%) and a decrease of the diffusion capacity (DLCO-25%). There is, moreover, a constant lymphocytic infiltration of the bronchial mucosa and of the lungs interstitium. In conclusion the pulmonary involvement in SS seems to be constant, unpredictable and of remarkable clinical-physiological importance.

Study of immune complexes in bronchoalveolar lavage fluids.

Immune complexes (IC) were investigated in the bronchoalveolar lavage fluid (BAL) of 5 patients with hypersensitivity pneumonitis (HP), 11 with idiopathic pulmonary fibrosis (IPF) and 16 with sarcoidosis (S) by three different methods: C1Q-BA, KgB, AKgB-MA. Using AKgB-MA, it is possible to identify the class of antibodies forming the IC. IC were present in all cases of HP, in 8/11 (73%) of IPF and in 10/16 (62%) of S. However, the three tests showed discordant results for the three different diseases: C1Q-BA and KgB-SP were both positive in 40%, AKgB-MA in 80% of HP cases; C1Q-BA in 73%, KgB-SP in 9% and AKgB-MA in 46% of IPF cases; C1Q-BA in 31%, KgB-SP in 12% and AKgB-MA in 31% of S cases. In all of the diseases, the IC were mostly composed of IgG; moreover, in HP IgA was also frequently present. The determination of IC in different fractions obtained from BAL ultracentrifugation, confirmed the simultaneous presence of IC of different molecular weights and antibody composition. Lung transbronchial biopsy with immunofluorescence showed immunoglobulin, prevalently IgG, and C, in all HP cases, the majority of IPF cases and 50% of S cases. This confirms the importance of IC in the pathogenesis and/or evolution of some pulmonary diseases.

Bronchoalveolar Lavage in Chronic Eosinophilic Pneumonia

We describe 6 patients with chronic eosinophilic pneumonia (CEP) investigated clinically and by bronchoalveolar lavage (BAL). The BAL findings of these 6 patients were compared with those of 293 patie

Eosinophilic alveolitis in immunologic interstitial lung disorders.

To analyze the role of eosinophils in alveolitis due to immunological interestitial lung disorders, 568 bronchoalveolar lavage (BAL) from 537 patients affected by 13 types of interstitial lung disease involving immunologic mechanisms were considered. An arbitrary cut-off of 4% of eosinophils in BAL was assumed. In five (idiopathic pulmonary fibrosis (IPF), allergic bronchopulmonary aspergillosis (ABPA), amiodarone-induced pneumonitis (AIP), chronic eosinophilic pneumonia (CEP), Churg-Strauss syndrome (CSS)) out of the thirteen groups we took into consideration, the level of eosinophils was >4%. In CEP and CSS in particular, the arbitrary cut-off of 4% was greatly exceeded (28.9%±27.4,p<0.01 and 33.6%±14.5,p<0.01, respectively). In the same two groups the increase of eosinophils in BAL was isolated with a direct correlation to the number of eosinophils in blood. By contrast, the increase of eosinophils in BAL of IPF, AIP and ABPA was of lesser extent (4.7%±5.7p<0.01, 5.0%±3.0p<0.01 and 6.1%±10.4p<0.01, respectively) and was accompanied by an increase of neutrophils in IPF, of lymphocytes in AIP and both in ABPA. These patterns are generally defined as “mixed alveolitis.” On the basis of these data we conclude that the term “eosinophilic alveolitis” should be reserved for CEP and CSS.

The increased number of very late activation antigen-4-positive cells correlates with eosinophils and severity of disease in the induced sputum of asthmatic patients

BACKGROUND Lymphocyte function associate-1 (LFA-1), macrophage antigen-1 (Mac-1), and very late activation antigen-4 (VLA-4) are involved in the infiltration of leukocytes into the tissues. Experimental models of allergic inflammation suggest that VLA-4 could determine the selective recruitment of eosinophils into the inflamed airways. OBJECTIVE Our purpose was to evaluate the involvement of integrins in eosinophil recruitment in asthma. METHODS We evaluated by immunocytochemistry the expression of VLA-4, LFA-1, and Mac-1 and their relationship with inflammatory cells and severity of disease in the induced sputum of 20 mild to moderate atopic asthmatic subjects and in 8 healthy subjects. RESULTS The number of VLA-4+ cells is increased in asthmatic patients and VLA-4 is mainly localized on eosinophils. Furthermore, VLA-4+ cells are significantly related to eosinophils. In contrast, LFA-1 and Mac-1 cellular expressions do not differ between asthmatic and control subjects and are not related to any specific cell type. Eosinophils and VLA-4+ cells are significantly higher in moderately compared with mildly asthmatic patients (P <.01, P <.05) and with healthy control subjects (P <.0005, P <.001). Eosinophils and VLA-4+ cells are also higher in mildly asthmatic patients compared with control subjects (P <.001, P <.005). CONCLUSION This is the first report demonstrating, by a noninvasive method in humans, that VLA-4+ cells are increased and correlate with the eosinophils in the induced sputum of atopic patients with mild to moderate asthma and that VLA-4 expression is related to the severity of disease.

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

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

Evaluation of some immunological parameters in interstitial lung disease by discriminant analysis.

In 37 subjects affected by interstitial lung diseases (19 patients with pulmonary sarcoidosis, 11 with hypersensitivity pneumonitis, 7 with idiopathic pulmonary fibrosis), we have compared by discriminant analysis (Statistical Package for the Social Sciences, version 8.3) 17 biological parameters derived from bronchoalveolar lavage analysis, gallium-67 scanning and lung biopsy. The aim of the study was to analyze the parameters of these three groups by forming one or more linear combinations of the discriminant variables. In particular, we tried to define the ability of such parameters to define these interstitial lung diseases and the relative importance of the data examined. The functions obtained are highly discriminant, so that the three groups are well distinguished among themselves; it means that the variables employed discriminate among the diseases studied. Among the variables considered, differential cell count, immune complex determination, gallium-67 lung scanning have the most important discriminant capacity. Discriminant analysis emphasizes that the three diseases are mediated by different immune mechanisms and underlines the role of each mechanism in determining the disease.