摘要:

When neutrophils are recruited to tissue sites and exposed to phagocytosable targets, they release oxidants which may be responsible for the local inactivation of alpha-1-proteinase inhibitor (AlPI). Consequently, AlPI becomes incapable of inhibiting the proteolytic activity of elastase, released at the same time by neutrophils as a result of leakage from phagocytic vacuoles. In the present paper we show that phagocytosing neutrophils inactivate AlPI via a process inhibitable by chemical agents known to interfere with the hypochlorous acid (HOCl)-generating myeloperoxidase pathway. The anti-inflammatory drug nimesulide (NMS), which is able to efficiently limit the extracellular availability of HOCl in the neutrophil surroundings, was found to prevent the inactivation of AlPI by neutrophils. The results provide evidence for a possible way to control neutrophil elastase activity by rescuing its natural inhibitor (AlPI) at inflamed tissue sites during infectious and noninfectious processes.

ISSN:0025-7931    

DOI:10.1159/000196015

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

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 < 0.01) and eosinophils (p 7 μm) compared to those having normal basement membrane (≤7 μm). These findings seem to support the hypothesis that the degree of thickening of basement membrane in asthma is related to mucosal inflammat

ISSN:0025-7931    

DOI:10.1159/000196091

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The objective of this study was to evaluate the yield of transbronchial needle aspiration (TBNA) in a clinical routine setting of a teaching hospital for the diagnosis and staging of bronchogenic carcinoma in comparison to the results of controlled clinical studies. We reviewed our results with Wang retractable needle catheters during a 9-month period. The needle catheters were used in 72 patients. 43 patients had a final diagnosis of bronchogenic carcinoma. Classical bronchial washes, brushings and forceps biopsies led to the diagnosis in 28 patients (65%). The addition of TBNA increased the diagnostic yield by 14% (6 patients) to 79% overall. In 32 patients staging of mediastinal lymph nodes was attempted. Positive TBNA proved inoperability in 9 patients. In 7 patients TBNA was used to investigate peripheral masses. Two patients had a malignant tumor, of which one was diagnosed by TBNA. Overall, TBNA revealed important information with clinical consequences in 16 of 72 patients (22%). There were no complications. We conclude that TBNA significantly increases the diagnostic yield of fiberoptic bronchoscopy and carries only a minimal risk. Our results, obtained in the clinical routine setting of a teaching hospital, are comparable to the reported results of controlled studies.

ISSN:0025-7931    

DOI:10.1159/000196016

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Different technical aspects concerning bronchoalveolar lavage (BAL) are still controversial: optimal instillation volume for airway sampling, processing of lavage cells and measurement of solutes are all matter of debate. Data from BAL must then be interpreted cautiously. In asthma and bronchial hyperresponsiveness different studies with BAL seem to agree on a few points such as the presence in the airways of inflammatory cells, predominantly eosinophils and mononuclear cells, and epithelial cells. Macrophages and polymorphs from asthmatic airways are more active in terms of oxygen radical release, this activity being correlated with methacholine responsiveness. In our studies we found a positive correlation between PD20 and lymphocyte numbers. Inflammatory mediators such as arachidonic acid derivatives and PAF have been assessed in BAL fluids in different studies but the precise meaning of those data still remains to be clarified. Corticosteroid treatment can significantly modify the cellular profile in BAL: eosinophils, epithelial cells and mast cells decrease, but lymphocyte numbers increase. Though in its infancy, direct sampling of airways fluids is likely to lead to a much greater understanding of pathophysiological mechanisms in asthma with important therapeutic implications.

ISSN:0025-7931    

DOI:10.1159/000196092

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

There are two suitable methods for estimating the ventilatory response to CO2: the steady state or the Read method. The latter is usually applied because of its shorter duration and its stimulus, near to tissue PCO2. From recent studies on a physiological model but also on the dynamics of the ventilatory CO2 response (G liters min-1 kPa-1), it can be shown, both theoretically and experimentally, that the Read method markedly overestimates the steady-state estimate of the ventilatory CO2 response (Gss). We have, therefore, applied two ramp approaches: one with an initial end-tidal PCO2 (PetCO2) step of 0.5 kPa and a mean PetCO2 ramp slope of 0.41 kPa/min (step-ramp method, SR) and one without an initial step and a mean ramp slope of 0.21 kPa/min (ramp method; R). As predicted by theory, the ventilatory CO2 response from the R method (GR) during the second 4-min interval of the 8-min procedure and the ventilatory CO2 response from the SR method (GSR) from the whole 6-min procedure, except for the first 30 s, should yield a good approximation of Gss. In a group of 12 normal volunteers we indeed found no differences between these estimates, and, as predicted by theory, we found both estimates to be larger than GR from the first 4-min interval. From the interindividual spread, only the difference with respect to GSR was significant (p < 0.02). The volunteers preferred the R approach because of the lower PetCO2 attained and the smaller ventilation increase. Our results are, from the theoretical point of view, in accordance with recent direct comparisons of the steady state and rebreathing approaches, using different ramp slopes and initial PetCO2 steps. The re-breathing approaches, however, lasted only 3-4 min with a markedly steeper PetCO2 rise. We conclude that the R approach we used is a possible substitute for the more cumbersome steady state approaches applied until now.

ISSN:0025-7931    

DOI:10.1159/000196017

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Bronchial asthma has been defined as a bronchial disease inducing an airway obstruction. Recently a renaming was proposed: eosinophilic desquamative chronic bronchitis. This is very interesting as it outlines the importance of inflammation in the pathogenesis of the disease. Until recently it was assumed that the narrowed airways were preferentially located centrally, that is to say in the large bronchi. However, evidence now exists that deep lung is also involved in bronchial asthma: 1) indeed it is well known that many aeroallergens are able to reach the alveoli; 2) assessment of flow volume curves and of ventilation/perfusion abnormalities showed the airway obstruction is often located on peripheral airways, especially in the chronic stages of the disease; 3) bronchoalveolar lavage (BAL) has been used extensively in asthmatics and results support this hypothesis. Alveolar macrophages (AM) are the principal resident phagocytes in the bronchoalveolar lumen, but these cells have been observed in more central airways by segmental bronchial wash and bronchial biopsy using conventional staining or monoclonal antibodies; we propose to name them airway macrophages. They play a major role in local defence against environmental agents. In a very elegant and important piece of work, R. Patterson demonstrated that bronchoalveolar cells obtained by BAL in sensitized monkeys and injected into the trachea of unsensitized syngenic monkeys were able to promote bronchial asthma after specific inhalation challenge. Since AM accounted for about 90 to 95% of the cells recovered by BAL, potential role for AM could be suggested. We would like to overview the lines of evidence which suggest that macrophages play an important role in the pathophysiology of human bronchial asthma. 1) AM are able to synthesize and release chemical mediators involved in the pathophysiology of bronchial asthma; they can be activated by an IgE dependent mechanism, phagocytosed particles (zymosan and opsonized zymosan) or soluble stimuli such as a chemoattractant peptide (fMLP) or a potent activator of protein kinase C (PMA); and these mechanisms appear to be relevant to bronchial asthma; 2) AM are activated in vivo in asthmatic patients and their activation correlates with the severity of the disease (as assessed by either the Aas’ clinical score, or airway obstruction or nonspecific airway reactivity); the concept of releasability seems to be very important; 3) AM play a central role in the immune response; they act in cooperation with lymphocytes in allergic asthmatics, AM suppressive activity is decreased and interleukin-1 (11-1) production is increase

ISSN:0025-7931    

DOI:10.1159/000196095

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Asthma and chronic obstructive pulmonary disease (COPD) are complex conditions with imprecise definitions which make definitive morphological comparisons difficult. Broadly, the airways in asthma are occluded by tenacious plugs of exudate and mucus, there is fragility of airway surface epithelium, thickening of the reticular layer beneath the epithelial basal lamina and bronchial vessel congestion and oedema. There is increased inflammatory infiltrate comprising ‘activated’ lymphocytes and eosinophils with release of granular content in the latter, and there is enlargement of bronchial smooth muscle particularly in medium sized bronchi. Three conditions contribute to COPD. In chronic bronchitis there is mucous hypersecretion with enlargement of tracheo-bronchial submucosal glands and a disproportionate increase of mucous acini. In small (peripheral) airways disease, there is inflammation of bronchioli, mucous metaplasia and hyperplasia, with increased intralumenal mucus, increased wall muscle, fibrosis and airway stenoses. Respiratory bronchiolitis is a critically important early lesion which may predispose to the development of centrilobular emphysema. The severity of destruction of alveolar wall in emphysema appears to be the most important determinant of chronic deterioration of airf

ISSN:0025-7931    

DOI:10.1159/000196096

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

SO2 exposure (50-500 ppm) of isolated, perfused and ventilated guinea pig lungs, via the air passages, caused a concentration-related reduction in dynamic compliance and conductance. No changes in pulmonary perfusion flow was noted at any SO2 concentration. Formed sulfite was detected in lung lavage fluid as well as in the perfusate. Pretreatment of the lungs with a low concentration of SO2 (10 ppm) for 30 min protected against bronchoconstriction by a high concentration of SO2 (250 ppm). A similar protective effect was noted by pretreatment with sodium sulfite (3 mM) in the lung perfusate.

ISSN:0025-7931    

DOI:10.1159/000196018

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Bronchoalveolar lavage (BAL) may have a potential role in contributing to a more precise definition of COPD disorders, but at present little is known about the cellular and biochemical changes that occur in BAL in the different stages of COPD. On the contrary, BAL features due to smoking habits, a well-known risk factor for COPD, have been widely investigated. We submitted to BAL 15 normal nonsmokers, 15 asymptomatic smokers and 11 smokers affected by chronic bronchitis. In this latter group BAL fluid recovery was significantly reduced and cellularity increased, but less prominently than in asymptomatic smokers. The CD4/CD8 ratio was significantly decreased in smokers with and without bronchitis, the CD8 percentage being positively correlated with the smoking history. NK cells were decreased in patients with chronic bronchitis. BAL neutrophils were increased in both smoker groups and a correlation was seen with smoking history and degree of airflow obstruction. Neutrophils are markedly involved in the oxidation of BAL proteins, as we could determine with the evaluation of the methionine sulphoxide/methionine ratio in BAL fluids. This finding may be relevant to better understand COPD pathogenesis and progression.

ISSN:0025-7931    

DOI:10.1159/000196097

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Several reactive oxygen intermediates are generated in biological processes involved in cellular respiration and during the respiratory burst of phagocytic cells. Exogenous insult of free radicals to respiratory tract may derive from polluting environmental agents, cigarette smoke, drugs, toxic compounds, and hyperoxia. Oxidizing radicals cause damage to proteins, lipids, carbohydrates, enzymes, nucleic acids, and other biological constituents. They are counterbalanced by different defensive mechanisms present in the body, whose action may be enhanced by exogenous antioxidant supply. Oxidants may have a role in patients with COPD, since the majority of these subjects are heavy smokers and show increased amount of highly activated phagocytes in their respiratory tract. This determines inactivation of the antiprotease system, increase in elastase production, and impairment of the connective tissue repair, so leading to structural changes that characterize chronic obstructive pulmonary disease.

ISSN:0025-7931    

DOI:10.1159/000196098

出版商:S. Karger AG    

年代:1992

数据来源: Karger