Maintenance therapy: the compliance issue.
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Biomedical subjects
Publications and source records attributed to D Olivieri.
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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)
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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.
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.
A case of primitive lymphoma non-Hodgkin of parotid gland in a patient seventy three's years-old is presented. A total parotidectomy was effected. Subsequently the patient, owing to a good old age, was subjected to a regional-local radiant therapy.
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.
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.
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We conducted a randomized, double-blind, placebo-controlled study on the effect of disodium cromoglycate (DSCG) and nedocromil sodium (NED) on propranolol-induced bronchoconstriction (PIB) in 12 asthmatic subjects 10 to 53 years of age. Placebo (saline solution) and active drugs (10 mg) were aerosolized 30 minutes before bronchoprovocation with inhaled propranolol. Bronchial response to propranolol was expressed as the cumulative dose provoking a 20% fall in FEV1 (PD20P) and given in mumol. Reproducibility of PD20P was estimated before and after the days of study. PD20P varied within two doubling doses. Disodium cromoglycate and NED had no significant effect on baseline lung function. Although, geometric mean PD20P values (+/- GSEM) recorded after DSCG (7.24 mumol +/- 1.31) and after NED (9.22 mumol +/- 1.26) were higher than values recorded after placebo (6.55 mumol +/- 1.31), these differences were not statistically significant. A greater than 2-fold increase in PD20P was noted after NED in three subjects and in one subject after DSCG. We conclude that both DSCG and NED only modestly alter PIB, with some between subject differences.
The tolerability and the duration of effect of 12 micrograms of formoterol and 25 micrograms of procaterol administered via metered-dose aerosol to 12 stable asthmatic patients were evaluated in a double-blind, placebo controlled trial. FEV1, pulse rate, and blood pressure were measured at baseline and every two hours after dosing for 12 hours. The bronchodilation peak was observed after two hours for both drugs. Formoterol induced a significant bronchodilating effect for 12 hours compared with both baseline and placebo values. With procaterol, significant bronchodilation occurred for six hours compared with baseline values and four hours compared with placebo. No significant changes were observed in pulse rate and blood pressure with either drug. Four subjects complained of muscle tremor after procaterol administration. We conclude that in subjects with stable asthma, inhaled formoterol at a dose of 12 micrograms maintains significant bronchodilation for 12 hours after dosing and is very well tolerated. Further studies are required to evaluate effectiveness and tolerability of high dose formoterol treatment in acute severe asthma therapy.
Inhaled propranolol (P) was administered to a population which included asthmatic children (30 subjects) and adults (43 subjects): 1) to investigate the determinants of induced bronchial response; 2) to examine the relationship with treatment requirements; 3) to determine the relationship with responsiveness to methacholine (M) and ultrasonically nebulized distilled water (UNDW) (50 subjects); and 4) to establish the short-term repeatability of bronchial response to propranolol compared with methacholine (22 subjects). Bronchial response to propranolol and methacholine was expressed as the cumulative provocative dose (PD20 in mumol) and responsiveness to UNDW as the provocative output (PO20 in ml.min-1) producing a 20% fall in forced expiratory volume in one second (FEV1). Response to propranolol was significantly related to the degree of responsiveness to methacholine, but not to age, gender, presence of atopy, age at asthma onset, or baseline FEV1. PD20P was measurable in all but three subjects. A significant difference in mean PD20M but not in PD20P was found between subjects requiring more anti-asthmatic treatments compared to those without therapy. The difference between geometric mean PD20P and geometric mean PD20M was 14.1. PO20UNDW was measurable in only 21 out of 50 subjects. Both PD20P and PD20M were significantly lower in responders to UNDW than in nonresponders. Reproducibility of PD20P was comparable to that of PD20M (coefficients of repeatability: 1.17 and 1.09). We conclude that bronchial responsiveness to propranolol is safely measurable in most children and adults with asthma. Repeatability of bronchial response to propranolol is comparable to that of methacholine. Moreover, responsiveness to propranolol is not a predictor of treatment requirement.(ABSTRACT TRUNCATED AT 250 WORDS)
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We have recently examined the relationship between cell content of bronchoalveolar lavage (BAL) fluid and lung histology in a group of 13 asthmatic subjects during clinical remission. Inflammatory cells in BAL appeared to reflect the severity of the overall inflammatory process of the bronchial mucosa. In the present report we examined whether in asthma the presence of a thickened basement membrane is associated with inflammation of the bronchial mucosa. There was a significantly higher number of inflammatory cells (p less than 0.01) and eosinophils (p less than 0.005) in the submucosa of subjects showing a thickened basement membrane (greater than 7 microns) compared to those having normal basement membrane (less than or equal to 7 microns). These findings seem to support the hypothesis that the degree of thickening of basement membrane in asthma is related to mucosal inflammation.
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.
We examined the pattern and degree of the inflammatory process in bronchial biopsy specimens taken by fiberoptic bronchoscopy in eight asthmatic subjects (two women aged 19-38 years) after 5 years of specific immunotherapy (SIT) to mite extracts (SIT group). At the time of study, they received a maintenance dose of mite-extracts (last subcutaneous administration 3 weeks before bronchoscopy). Results were compared with those found in eight matched mite-sensitive subjects with stable asthma (two women aged 19-36 years; non-SIT group) and in eight healthy individuals (four women aged 22-29 years; control group). Bronchial biopsy specimens were fixed in periodate-lysine-paraformaldehyde, embedded in glycol methacrylate, and stained with hematoxylin-eosin and 2% toluidine blue. Number of eosinophils, mast cells, and total nucleated cells were counted separately in the epithelium and lamina propria by light microscopy and expressed as cells/high power field. Within the epithelium, eosinophil and mast cell counts in SIT and non-SIT groups were significantly higher compared to controls, whereas total cell counts were not statistically different. Within the lamina propria, total cell count in SIT and non-SIT groups was significantly higher compared with the control group, whereas mast cells were similar. The number of eosinophils in both SIT and non-SIT groups was higher compared with controls; however this reached statistical significance only in SIT-groups. Comparison between the two groups of asthmatics did not show any significant difference for any cell counts.(ABSTRACT TRUNCATED AT 250 WORDS)