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A Pesci

Publications and source records attributed to A Pesci.

At least 37 records · Page 2Linked to original sources

Clinical and subclinical alveolitis in connective tissue diseases assessed by bronchoalveolar lavage.

Subclinical alveolitis, as assessed by bronchoalveolar lavage (BAL) cell analysis, may be present in the lower respiratory tract of a high proportion of symptomless patients with connective tissue diseases (CTDs) with normal chest roentgenograms. The distribution of BAL cell types, mainly macrophages, lymphocytes, and polymorphonuclear neutrophils, varies according to type of CTD and to the presence of associated interstitial lung disease (ILD). Nevertheless, subclinical alveolitis can be classified into two major groups: lymphocyte and neutrophil alveolitis. A mixed, lymphocyte and neutrophil alveolitis may be detected as well. Subclinical alveolitis, particularly in systemic sclerosis, frequently is associated with abnormalities of lung parenchyma as assessed by computed tomography (CT) scan, supporting the hypothesis that it may be associated with the development of overt ILD. Close follow-up of these patients is needed to better determine whether subclinical alveolitis precedes ILD and whether early detection of subclinical alveolitis in CTDs may identify those patients who are at risk for the development of ILD in the future.

Bronchoalveolar Lavage Fluid↗

Inhaled beclomethasone dipropionate downregulates CD4 and CD8 T-lymphocyte activation in peripheral blood of patients with asthma.

BACKGROUND: Previous studies demonstrated a downregulation of T-lymphocyte (CD3+ cells) activation in peripheral blood after treatment with inhaled corticosteroids in patients with asthma. OBJECTIVE: This study was carried out to evaluate the effect of inhaled corticosteroids on CD4 and CD8 T-lymphocyte activation, respectively. METHODS: We examined the expression of three surface activation markers (CD25, HLA-DR, and very late activation antigen 1) on circulating CD4+ and CD8+ T-cell subsets in subjects with asthma (n = 23) before and 8 weeks after treatment with inhaled beclomethasone dipropionate dry powder (daily dose, 800 microg). RESULTS: Beclomethasone dipropionate treatment had a marked effect in reducing the expression of the activation marker CD25 (p < 0.01) in both CD4+ and CD8+ T-cell subsets in peripheral blood of patients with asthma. However, no correlation was found between the downregulation of CD4 and CD8 T-lymphocyte activation and the improvement in physiologic indices of disease activity. CONCLUSIONS: These data add to the view that CD4+ and CD8+ T lymphocytes in peripheral blood of patients with asthma are in an activated state that is downregulated by inhaled corticosteroids.

Administration, Inhalation↗

Lymphocyte activation markers in peripheral blood before and after natural exposure to allergen in asthmatic patients.

Activated T cells and their cytokine products are involved in the pathogenesis of asthma. However, little is known about changes in circulating T cell subsets in allergic asthma during natural exposure to allergens. We examined whether natural allergen exposure of patients with atopic asthma is associated, in vivo, with changes of lymphocyte subtypes and activation markers in peripheral blood. Ten patients with atopic mild asthma sensitized only to grass pollen had peripheral venous blood lymphocyte analyses before and during the pollen season. No significant changes were observed. There was an inversion in the CD4/CD8 ratio in the peripheral blood both before (p < 0.05) and during (p < 0.01) seasonal exposure when compared to a group of healthy, age-matched control subjects. Evaluation of T cells expressing CD25 activation marker also demonstrated a significant reduction of CD4+25+ cells and a significant increase of CD+25+ cells compared to the controls. CD23+ cells (B lymphocytes with low affinity Fc IgE receptor) in the asthmatic group out of the pollen season correlated negatively with hyperreactivity to methacholine (p < 0.05). We conclude that in mild allergic asthmatic patients sensitized to grass pollen, blood lymphocyte subsets and their activation markers do not reflect seasonal exposure. Moreover, our findings show that these patients have higher proportions of CD8+ cells expressing higher levels of CD25 in their blood compared to normal subjects both before and during the pollen season.

Adult↗

Selection of T lymphocytes bearing limited TCR-Vbeta regions in the lung of hypersensitivity pneumonitis and sarcoidosis.

Hypersensitivity pneumonitis (HP) and sarcoidosis are interstitial lung disorders (ILD) characterized by a lymphocytic alveolitis that, in the active phase of the disease, is sustained by different T-cell subsets, i.e., CD8+ cells in HP and CD4+ lymphocytes in sarcoid patients. To address the question of whether a bias in T-cell selection occurs in the lung of patients with HP and sarcoidosis, we analyzed the T-cell receptor beta chain variable region (TCR-Vbeta) repertoire by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 14 HP and 25 sarcoid patients. To verify whether these cells can be activated in vitro through the TCR, blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins, including SEA, SEB, SEC1, SEC2, SED, and SEE. Flow cytometry and PCR analyses demonstrated an overexpression of cells bearing Vbeta2, Vbeta3, Vbeta5, Vbeta6, and Vbeta8 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments were overrepresented in the lung rather than in the blood. Both in HP and sarcoid patients almost all T cells bearing the dominant Vbeta segment belonged to the T-cell subset that sustains the alveolitis, i.e., CD8 in HP patients and CD4 in sarcoid subjects. Follow-up studies demonstrated that the recovery of the alveolitis was characterized by the disappearance of cells bearing a limited T-cell repertoire. Interestingly, T-lymphocyte response to different superantigens demonstrated that the proliferation elicited by different staphylococcal toxins was more pronounced in the lung than in the blood. Taken together, our findings indicate a compartmentalization of cells bearing discrete Vbeta gene products in the pulmonary microenvironment and suggest that the expansion of specific Vbeta region subsets occurring in the lung might result from triggering by a specific antigen. In fact, the removal from exposure in HP patients or specific treatment in sarcoidosis resulted in the decrease of the overrepresented cell population accounting for the lymphocytic alveolitis.

Adult↗

Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study.

In a double-blind, parallel-group study, we examined the effect of short-term treatment with inhaled fluticasone propionate (FP) in a group of 20 nonsmoking asthmatic patients who required only beta2-agonists to control their symptoms. We administered FP (250 microg twice daily) or matched placebo for 6 wk. Methacholine challenge was performed before treatment, after 3 wk, and at the end of treatment. Each patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy before and after treatment. Eight patients in the placebo group and nine patients in the FP group completed the study. Bronchial responsiveness to methacholine decreased significantly only after 6 wk of treatment with FP (p < 0.05). When we compared the FP group with the placebo group, we observed a significant decrease only in the number of cells expressing intracellular adhesion molecule-1 (ICAM-1) and MAC-1 (p < 0.04 and p < 0.03, respectively). Moreover, we saw that the tryptase level in BAL decreased (p < 0.001), whereas the eosinophil cationic protein (ECP) level did not change significantly. Additionally, the number of eosinophils and mast cells in the lamina propria in bronchial biopsies specimens was significantly smaller in the FP group than in the placebo group (p < 0.02 and p < 0.01, respectively). Additionally, in the FP group, we found that basement-membrane thickness was significantly decreased when compared with that of the placebo group (p < 0.05). In conclusion, our results show that short-term treatment with low-dose FP reduces inflammatory cell infiltration into the lamina propria in bronchial biopsy specimens. Moreover, short-term low-dose FP treatment might control the intensity of airway remodeling in mild asthma.

Administration, Inhalation↗

Airways remodeling is a distinctive feature of asthma and is related to severity of disease.

PURPOSE: Airways remodeling, evaluated as the subepithelial layer thickness, was compared in asthmatic patients with that of healthy subjects, and was related to clinical grading of disease, presence of atopy, and length of asthmatic history. SUBJECTS AND METHODS: Thirty-four patients with stable asthma (mean age+/-SD: 26.5+/-9.2 years; 10 female) treated with only inhaled beta2-agonists and eight healthy volunteers (mean age+/-SD: 24.6+/-2.5 years; four female) were recruited for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patients had newly diagnosed conditions (duration of disease < or = 1 year), nine patients had long asthmatic history (> 1 year and < or = 10 years), and 14 had prolonged asthmatic history (> 10 years). Bronchial responsiveness to methacholine (M) was expressed as provocative concentration of M causing a 20% fall in FEV1 (PC20) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-point score based on symptoms, bronchodilator use, and daily peak expiratory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelial layer thickness, in biopsy samples, was measured from the base of bronchial epithelium to the outer limit of reticular lamina. RESULTS: In asthmatics, baseline FEV1 values (percent of predicted) ranged from 75.7 to 137.0%, and PC20 M ranged from 0.15 to 14.4 mg/mL. According to the asthma severity score, 14 asthmatics were classified as having mild disease, 14 as having moderate disease, and six as having severe disease. The mean values of subepithelial layer thickness were 12.4+/-3.3 microm (range, 6.8 to 22.1 microm) in asthmatics, and 4.4+/-0.5 microm (range, 3.8 to 5.2 microm) in healthy subjects (p<0.001). Subepithelial layer thickness of those with severe asthma differed significantly from that of patients with moderate and mild asthma (16.7+/-3.1 microm vs 12.1+/-2.7 microm and 10.8+/-2.4 microm, p<0.01 and p<0.003, respectively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coefficient [rs]=0.581; p<0.001), and negatively correlated with baseline FEV1 (rs=-0.553; p<0.001) and PC20 M (rs=-0.510; p<0.01). No difference was found between degree of thickening observed in atopic asthmatics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. Lastly, multiple regression analysis revealed that asthma severity score was the significant predictive factor for thickness of subepithelial layer. CONCLUSIONS: We confirmed that airways remodeling is a very distinctive and characteristic pathologic finding of asthma. We also demonstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.

Adolescent↗

Increased bronchoalveolar granulocytes and granulocyte/macrophage colony-stimulating factor during exacerbations of chronic bronchitis.

Although inflammatory changes are found throughout the airways of patients with chronic bronchitis, the mechanisms of the pathogenesis of chronic bronchitis are still unclear. The aim of this study was to investigate airways inflammation in patients with and without an exacerbation of bronchitis. Thirteen chronic bronchitic patients and nine normal subjects were studied. Eight of the patients were studied under baseline conditions (B), and five during an exacerbation of bronchitis (E). Bronchoscopy and bronchoalveolar lavage (BAL) with cytological analysis were performed, and the levels of granulocyte/macrophage colony-stimulating factor (GM-CSF) were determined in sera and in BAL supernatants by a solid phase enzyme immunoassay. Compared with patients under baseline conditions, chronic bronchitic patients with an exacerbation had increased numbers of BAL neutrophils (10+/-3 and 83+/-18x10(3) cells x mL(-1), respectively; p<0.0001) and of BAL eosinophils (1.9+/-0.5 and 6.7/-1.9x10(3) cells x mL(-1), respectively; p=0.014). Patients with chronic bronchitis, as a whole, had significantly increased levels of BAL GM-CSF compared to control subjects (36+/-5 and 19+/-4 pg x mL(-1), respectively; p=0.035), and similar levels of serum GM-CSF. Serum levels of GM-CSF were markedly increased in chronic bronchitic patients with an exacerbation, as compared with patients under baseline conditions (1.4+/-0.4 and 13+/-1 pg x mL(-1), respectively; p <0.0001). BAL levels of GM-CSF were also increased in chronic bronchitic patients with an exacerbation (25+/-5 and 54+/-8 pg x mL(-1), respectively; p=0.009). During exacerbations of chronic bronchitis there are changes in the cell populations in bronchoalveolar lavage of patients consistent with a recruitment of polymorphonuclear leucocytes in the airway lumen. The increased levels of granulocyte/macrophage colony-stimulating factor might suggest a role for this cytokine in the inflammatory processes of chronic bronchitis.

Adult↗

Bronchoalveolar lavage in mixed cryoglobulinaemia associated with hepatitis C virus.

In order to evaluate the presence of an inflammatory process of the lower respiratory tract in patients with mixed cryoglobulinaemia (MC) associated with hepatitis C virus (HCV), bronchoalveolar lavage (BAL) was performed in 16 non-smoking females free of clinical pulmonary symptoms and with normal chest roentgenograms. Pulmonary function tests including diffusion capacity for carbon monoxide (DLCO) were also carried out. Thirteen healthy subjects were evaluated as the control group. Patients with MC had a lower percentage of alveolar macrophages (75% vs 92%, P = 0.001) and a higher percentage of lymphocytes (19.7% vs 7%, P = 0.001) than healthy controls. The percentage of CD3+ lymphocytes was higher in MC patients than in controls (86.5% vs 70%, P = 0.004). No significant differences in the percentage of CD4+, CD8+ and CD19+ lymphocytes, neutrophils and eosinophils were found. Pulmonary function tests showed significantly lower values of forced expiratory flow (FEF) 25-75 (P = 0.05) and DLCO (P = 0.05) in MC patients than in healthy controls. No correlations between BAL results and pulmonary function tests were found. The 5 yr follow-up of five patients did not demonstrate deterioration in lung function. Thus, BAL results indicate a subclinical T-lymphocytic alveolitis in MC HCV+ patients that is not associated with a risk of deterioration in lung function.

Adult↗

Bronchial responsiveness to distilled water and methacholine and its relationship to inflammation and remodeling of the airways in asthma.

Although bronchial hyperresponsiveness in asthma is associated with inflammation within the airways, it is not known whether the degree and type of inflammation influence the response to different stimuli and whether pathologic changes of airway structure influence the bronchoconstrictive responses. Therefore, number of inflammatory cells in the epithelium and the lamina propria and the basement membrane thickness were estimated from bronchial biopsies taken in 27 asthmatic subjects (range percent predicted FEV1: 75.6 to 132.1, range of daily PEF variability: 1.9% to 20%) and related to the degree of bronchial responsiveness to ultrasonically nebulized distilled water (UNDW) and methacholine (M). PD20UNDW (provocative dose) was measurable in 15 of 27 patients and ranged between 1.01 and 20.4 ml. PC20M (provocative concentration) ranged between 0.15 and 31.7 mg/ml. In the 15 responders to UNDW, total inflammatory cells (p<0.04) and eosinophils (p<0.015) within the epithelium were higher than in 12 nonresponders to UNDW (PD20 > 34.8 ml). There was no correlation between PD20UNDW and any cell counts whereas negative correlations were found between PC20M and both total inflammatory cells (rs = -0.57; p<0.005) and eosinophils (rs = -0.63; p< 0.0015) within the epithelium. The degree of thickening of subepithelial layer ranged between 7 and 16 micrometers+ (n=26). Thickness correlates both with total inflammatory cells (rs = 0.49; p<0.025) and eosinophils (rs = 0.61; p< 0.003) within the epithelium. Moreover, it was correlated with baseline FEV1 (rs = -0.57; p<0.003) and daily peak expiratory flow (PEF) variability (rs = 0.51; p<0.01). A weak but significant correlation was also found between subepithelial layer thickness and PC20M (rs = -0.42; p<0.04). The results of this study demonstrate that eosinophilic inflammation of bronchial epithelium plays a role in determining UNDW and M responsiveness in asthma. Moreover, they suggest that remodeling of the airways such as thickening of subepithelial layer correlates with indices of asthma severity and could contribute to the degree of M but not to UNDW responsiveness.

Adolescent↗

Mast cells in bronchiolitis obliterans organizing pneumonia. Mast cell hyperplasia and evidence for extracellular release of tryptase.

Idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) is characterized by air space inflammation and fibrosis of unknown origin. The pathogenesis of the inflammatory reaction and fibrosis in fibrotic lung disorders remains unclear; however, recent attention has focused on the potential role of the mast cell in the genesis of fibrosis. To determine whether mast cells are implicated in the pathogenesis of BOOP, mast cells were identified in BAL fluid and in transbronchial lung biopsy specimens from 11 patients affected by BOOP and 17 control subjects. Mast cells and tryptase were significantly increased in BAL fluid of patients with BOOP (p = 0.001 and p = 0.03, respectively). In lung tissue of patients with BOOP, there was an increased number of mast cells per square millimeter of lung tissue with respect to control group (p = 0.001). Seventy-three percent of mast cells were found in the alveolar septa, 18% within alveoli often plunged in organizing pneumonia, 4% among alveolar lining cells, and 6% along blood vessels. No mast cells were located within alveoli in control subjects. Mast cell degranulation was evident in lung tissue specimens of patients with BOOP but not in those of control subjects (p = 0.01). This study shows the importance of mast cells and mast cell activation in the pathogenesis of BOOP.

Aged↗

Mast cells in the airway lumen and bronchial mucosa of patients with chronic bronchitis.

In order to evaluate the degree of mast cell infiltration and determine their granulation state in the airways of patients with chronic bronchitis, bronchoscopy was performed in 25 chronic bronchitis subjects (10 smokers and 15 ex-smokers) with mucoid sputum production and in seven normal nonsmoking control subjects. Bronchoalveolar lavage and bronchial biopsies were examined using histochemical techniques. Subjects with chronic bronchitis had higher numbers of mast cells both in the epithelium (1.22 +/- 1 versus 0.22 +/- 0.2 mast cells per mm) and in the bronchial glands (137.4 +/- 37.9 versus 38 +/- 5.1 mast cells per mm2) than did control subjects (p < 0.01 and p < 0.001, respectively), whereas the numbers of mast cells in bronchoalveolar lavage (0.21 +/- 0.1 versus 0.18 +/- 0.1 mast cells percentage, nonsignificant [NS]) and in the lamina propria (87.5 +/- 66.4 versus 87.2 +/- 61.8 mast cells per mm2, NS) were similar in the two groups. In the smoking group of bronchitics an increase in mast cell numbers was observed in epithelium (1.6 +/- 1.3 versus 0.95 +/- 0.7 mast cells per mm, NS), in lamina propria (112.2 +/- 86.5 versus 71.7 +/- 45.7 mast cells per mm2), and in BAL (0.26 +/- 0.21 versus 0.16 +/- 0.17 mast cell percentage of total cells, NS) in comparison with the ex-smoker's group of bronchitics.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗

Mast cell and histamine involvement in farmer's lung disease.

The aim of this study was to evaluate the cellular and biochemical characteristics of the bronchoalveolar lavage (BAL) fluid in patients with farmer's lung disease (FLD). Total cell numbers in BAL fluids from patients with FLD (n = 30) were significantly higher than in normal subjects (n = 7; p < 0.01), and differential cell counts were significantly different. Lymphocytes were the most numerous cell type in BAL fluids from patients with FLD (65.4 +/- 2.5 percent vs 6.8 +/- 0.5 percent), and analysis of lymphocyte subsets revealed increased percentages of CD3+ and CD8+ cells (91.8 +/- 0.9 percent vs 68.8 +/- 3 percent, p < 0.01, and 54.3 +/- 3.1 percent vs 30.1 +/- 3.2 percent, p < 0.01, respectively). A marked increase in mast cell numbers, as revealed by the specific alcian blue/safranin staining, was observed in patients with FLD (4.2 +/- 0.57 percent, n = 12, vs 0.18 +/- 0.04 percent, n = 7, p < 0.001). Histamine levels in BAL supernatants were increased in patients with FLD (mean = SEM, 4.4 +/- 0.8 ng/ml vs 0.9 +/- 0.1 ng/ml; median, 2.4 ng/ml vs 0.9 ng/ml, p < 0.01), and correlated positively with mast cell numbers and percentages (r = +0.63, p < 0.03, and r = +0.69, p < 0.02, respectively); conversely, a negative correlation was found between histamine levels and CD8+ lymphocyte percentages (r = -0.48, p < 0.01). Raised neutrophil percentages (5.1 +/- 0.8 vs 0.5 +/- 0.18, p < 0.05) and albumin concentrations (29.2 +/- 3.9 mg/dl vs 3.4 +/- 1.3 mg/dl, p < 0.01) were also found in patients with FLD. These findings show that increased numbers of mast cells, lymphocytes, and neutrophils can be found in BAL fluids of patients with FLD. The increased histamine levels in the supernatants of BAL fluids indicate that mast cells are activated. These data allow us to postulate a role for mast cell accumulation and histamine release in the inflammatory process of FLD.

Adult↗

Lower respiratory tract inflammation in chronic bronchitis. Evaluation by bronchoalveolar lavage and changes associated with treatment with Immucytal, a biological response modifier.

Chronic bronchitis (CB) is characterized by inflammatory changes in the bronchial tissue and by recurrent bronchitis exacerbations. In addition, defective systemic and local immune mechanisms have been demonstrated and biologic response modifiers (BRMs) have been recently introduced for clinical use in patients with CB. We studied 24 patients with CB by bronchoalveolar lavage (BAL), before and after a 4-week treatment protocol with inhaled Immucytal (Pierre-Fabre Pharma Srl, Milan, Italy), a BRM composed of bacterial ribosomal fractions and membrane proteoglycans. Compared with normal controls (NC), before treatment BAL in patients with CB contained increased proportions of neutrophils (NC, 0.8 +/- 0.2 percent; CB, 3 +/- 1 percent), of eosinophils (NC, 0.1 +/- 0.02 percent; CB, 0.6 +/- 0.2 percent); and of lymphocytes (NC, 6 +/- 1 percent; CB, 13 +/- 2 percent; p < 0.01 each comparison) with higher percentages of CD3+ and CD8+ lymphocytes (p < 0.01 each comparison). In BAL from patients with CB there were also higher levels of albumin and of the ratio IgG/albumin (p < 0.01 and p < 0.05, respectively, compared with NC). After Immucytal treatment, the proportions of lymphocytes in BAL in patients with CB were decreased (13 +/- 2 percent before, 6 +/- 1 percent after; p < 0.01). In addition, the posttreatment BAL samples contained significantly fewer neutrophils per milliliter of BAL (3.7 +/- 0.8 x 10(3) neutrophils per milliliter of BAL before, 1.5 +/- 0.5 x 10(3) neutrophils per milliliter after; p < 0.05). No differences were seen for the proportions of lymphocyte subpopulations and for the protein levels between the BAL obtained before and after Immucytal treatment. These data demonstrate the presence of a lower respiratory tract inflammation in patients with CB and suggest that treatment of patients with CB with a BRM may change the proportions of inflammatory cells present in BAL.

Aerosols↗

Eosinophils and the lung.

An increase in the number of eosinophils in blood, tissues or sputum is found in many pulmonary disorders, although the review is mainly concerned with the association of eosinophilia with bronchial asthma and pulmonary eosinophilia. In this review, the morphology and life cycle of eosinophils is discussed. The role played by eosinophil secretions and eosinophil chemoattractants in the pathophysiology of the lung is also reviewed.

Asthma↗

Histochemical characteristics and degranulation of mast cells in epithelium and lamina propria of bronchial biopsies from asthmatic and normal subjects.

We examined the staining characteristics and degranulation of mast cells in bronchial biopsy specimens taken by fiberoptic bronchoscopy from 13 stable asthmatic patients and eight normal nonsmoking subjects. Specimens were fixed in periodate-lysine-paraformaldehyde, embedded in glycol methacrylate, and stained with toluidine blue (2%) for 30 min (pH 2.7) and 7 days (pH 0.5). The number of mast cells in the epithelium and in the lamina propria was counted under light microscopy. In addition, the distribution of mast cells with different granule contents, arbitrarily defined as degranulated or partly degranulated and fully granulated, was estimated at the two levels. In asthmatic subjects, the number of mast cells in the epithelium after either staining method was significantly higher compared with that in control subjects. The number of mast cells in the lamina propria, but not in the epithelium, was significantly higher after 7 days compared with 30-min toluidine blue stain both in asthmatic (135.6/mm2 versus 74.8/mm2; p < 0.001) and control subjects (121.5/mm2 versus 71.5/mm2; p < 0.01). There was evidence of a progressive mast cell degranulation when moving toward the airway lumen in both groups. However, degranulation was more evident in asthmatic subjects. In both groups, granulated mast cells were absent in the epithelium, whereas in the lamina propria granulated mast cells were approximately one-third of total in asthmatic and two-thirds of total in normal subjects. These observations suggest that mast cells in human bronchial mucosa are heterogeneous with respect to histochemical characteristics. They provide evidence that degranulation of mast cells occurs in both asthmatic and normal subjects and that degranulation is greater in asthmatics.

Adult↗

Mast cells in fibrotic lung disorders.

Fibrotic lung disorders are chronic inflammatory diseases in which inflammatory processes in the lower respiratory tract injure the lung and modulate the proliferation of mesenchymal cells that form the basis of the fibrotic scar. The pathogenesis of fibrosis in fibrotic lung disorders remains unclear; however, recent attention has focused on the potential role of the mast cell in the genesis of fibrosis. To determine whether mast cells are implicated in the pathogenesis of lung fibrosis, mast cells were compared with the degree of fibrosis in transbronchial lung biopsy specimens from 49 patients with fibrotic lung disorders (16 sarcoidosis, 15 farmer's lung disease, 9 cryptogenic fibrosing alveolitis, 6 bronchiolitis obliterans organizing pneumonia, 3 histiocytosis X). In lung tissue of patients with fibrotic lung disorders, there was an increased number of mast cells in respect to the control group (98.6 +/- 7.7 vs 27.8 +/- 5.1 mast cells per square millimeter, p < 0.01). Mast cell counts in lung biopsy specimens were significantly correlated with the degree of fibrosis (r = 0.87, p < 0.001); 80.8 percent of mast cells were found in the alveolar septa, 9.6 percent within alveoli, 1.9 percent among alveolar lining cells, and 5 percent along blood vessels. No mast cells were located within alveoli in controls. Our data suggest that mast cells participate in chronic inflammation and that their presence is related to interstitial fibrosis in a much broader spectrum of fibrotic lung disorders.

Adult↗

Lung function and bronchial responsiveness after bronchoalveolar lavage and bronchial biopsy performed without premedication in stable asthmatic subjects.

We evaluated tolerance, safety, and effects on lung function and bronchial responsiveness of BAL (4 x 50 ml) combined with BB (three to five specimens) performed without premedication in 13 mild and stable asthmatics and eight healthy volunteers. All subjects tolerated bronchoscopy procedures well and without serious side effects. During procedures, no supplemental oxygen was administered and no ECG abnormalities were noted. The PEFR was measured before and immediately after bronchoscopy and at 5-min intervals up until recovery. The maximal percentage fall in PEFR after bronchoscopy was significantly greater in asthmatics (23.1 +/- 13.9 percent) compared to normal subjects (7.8 +/- 8.2 percent, p less than 0.01). Changes in PEFR returned to baseline values within 120 min in all asthmatics. The tcPO2 was recorded at baseline, during and after bronchoscopy. In both groups, a significant change in tcPO2 was measured during the infusion of BAL aliquots, and persisted throughout the procedure. A significant difference in asthmatics compared to healthy subjects was evident during BB and at the end of the procedure (p less than 0.05). In asthmatics, M challenge was performed on three different days over a three-week period prior to bronchoscopy, and was repeated at intervals of 2, 6, and 24 h following procedure. The PC20 M values measured before bronchoscopy were found to have a very high reproducibility (intraclass correlation coefficient = 0.93). The PC20 values measured during experiment times after bronchoscopy were not significantly different from baseline values. These data demonstrate that in mild and stable asthmatics, BAL combined with BB can be safely performed following administration of only local anesthesia. In carefully selected asthmatic subjects, transient bronchoconstriction and a lowering of oxygen tension can be induced by BAL and BB, whereas changes in bronchial responsiveness are more unlikely to occur.

Adolescent↗