Asthma: a disease remodeling the airways.
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Asthma↗
Biomedical subjects
P Chanez
Publications and source records attributed to P Chanez.
Immunohistochemical characterization of the cellular infiltration in asthmatic bronchi.
Bronchial biopsies obtained from 16 asthmatic patients and six normal subjects were analyzed by immunohistochemistry. In the asthmatic patients, the total numbers of macrophages infiltrating the airway mucosa were increased. Many of the macrophages had the phenotypic characteristics of blood monocytes. HLA Class II antigen was expressed on infiltrating cells and airway epithelial cells. In biopsies from the asthmatics there was a significant increase in activated eosinophils, but not in neutrophils. There was also a significant increase in the numbers of T-lymphocytes in the asthmatics, but very few B-lymphocytes were detected. These results suggest that lung macrophages may have a central role to play in the mechanisms of the chronic immune-mediated inflammatory response seen in the airway mucosa of asthmatic patients.
Adult↗
Safety of bronchoalveolar lavage and bronchial biopsies in patients with asthma of variable severity.
The safety of fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), and bronchial biopsies has been questioned in asthma, and current recommendations indicate that bronchoscopies should only be performed in mild to moderate asthma. Moreover, in most studies patients receive premedication with nebulized bronchodilators that may enhance the safety of the procedures. The purpose of this study was to determine (1) whether the overall safety of fiberoptic bronchoscopy, BAL, and bronchial biopsies in mild to moderate asthma could be extended to patients with more severe asthma and (2) whether these procedures are safe without premedication with nebulized bronchodilators. A group of 50 patients with asthma of variable severity (FEV1 ranging from 37 to 107% of predicted values) and 25 healthy volunteers were studied. Bronchoscopy, BAL (250 ml), and four bronchial biopsies were performed in a standardized manner, without premedication with a nebulized bronchodilator, by the same investigator. Safety was assessed by clinical follow-up, continuous recording of arterial oxygen saturation during the procedure with a digital oximeter, and measuring FEV1, FEF25-75, and FVC just before and 5 min after bronchoscopy. Arterial oxygen saturation decreased in asthmatic patients from 97% (range 91 to 99%) (T1) to 92% (range 79 to 98%) (T8) (ANOVA, Fisher's PLSD) and in control subjects from 97% (range 94 to 99%) (T1) to 93% (range 88 to 98%) (T8) (ANOVA, Fisher's PLSD). The fall in arterial oxygen saturation was not significantly different between asthmatic and normal subjects, and there was no correlation between arterial oxygen desaturation and the severity of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Chest radiography and high resolution computed tomography of the lungs in asthma.
CT scans have been studied only in asthmatics who were smokers, and no such study has been performed in patients with chronic uncomplicated asthma where a permanent bronchial destruction is likely to occur after a long course of the disease. The object of the study was to characterize CT-scan abnormalities and determine whether bronchial destructive lesions may be observed. Fifty-seven adults with chronic asthma of variable severity and etiology and 10 normal subjects were studied. None of the subjects smoked. Chest radiographs and HR-CT scans were performed in all patients. To discriminate between reversible and irreversible CT-scan abnormalities, two examinations were made in 10 patients with acute asthma both before and 2 wk after parenteral high dose corticosteroid treatment. The chest radiographs showed the expected abnormalities of asthma in 37.8% of the asthmatics. CT scans were abnormal in 71.9% of the asthmatics. Reversible abnormalities included mucoid impactions, acinar pattern, and lobar collapse. Irreversible abnormalities included bronchiectasis, bronchial wall-thickening, sequellar line shadows, and emphysema. Most of these abnormalities are likely to be related to bronchial destruction.
Adult↗
Increased oxygen species generation in blood monocytes of asthmatic patients.
Besides eosinophils, inflammatory processes in asthma are characterized by an infiltration of inflammatory cells, including mononuclear phagocytes, such as alveolar macrophages (AM) and blood monocytes, in the airways. Monocyte activation has been observed in the blood after exercise or allergen-induced asthma. Stimulated AM in chronic and stable asthmatic patients have been shown to release oxygen species. We thus investigated the intensity of the activation of monocytes from 18 asthmatic patients compared with 18 healthy subjects. Oxygen species release was analyzed for monocytes in suspension by chemiluminescence using a luminometer and for monocytes maintained in adherence using conventional assay and video imaging camera. Circulating blood monocytes in suspension from asthmatic patients and control subjects showed the same baseline free radical release. Monocytes in suspension from asthmatic patients were more stimulatable by PMA: specifically, monocytes release more H2O and peaks of O2-. are sooner; moreover, peaks of total free radical release are higher, and this plateau is sustained. Compared with monocytes from control subjects, those from asthmatic patients evaluated after adherence show a higher baseline for O2-. and higher total free radical release. Monocytes from asthmatic patients spontaneously release more O2-. over time in nonstimulated cells and release more O2-. with PMA stimulation; they show the same peak level total free radical release as those from control subjects after stimulation. SOD activity analysis on adherent monocytes was lower in asthmatic compared with control subjects. These data show that monocytes from asthmatic patients were activated compared with control monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Acridines↗
c-fos proto-oncogene expression in bronchial biopsies of asthmatics.
c-fos, a proto-oncogene regulating the transcription of many genes, plays a critical role in the cell cycle and differentiation and may be involved in the regulation of inflammation in asthma. Very low levels of c-fos are detectable in most human cells, and its expression is rapidly and transiently increased by multiple factors, some of which are involved in the airways inflammation of asthma (histamine, eicosanoids, and cytokines). The presence of c-fos protein, as detected by immunofluorescence, and the immunoreactivity of PCNA, a cell proliferation marker, were examined in bronchial biopsies obtained from 12 asthmatics and 10 normal subjects. Biopsies of eight of 12 asthmatics expressed c-fos versus none of 10 normal subjects. The expression was heterogeneous and localized to cells positive for anti-cytokeratin monoclonal antibody, indicating their epithelial origin. On the other hand, PCNA immunoreactivity was only observed in one asthmatic and one control subject but it was not related with c-fos expression. This study demonstrates the induction of c-fos in epithelial cells of asthmatics, suggesting a role for this proto-oncogene in activation rather than in proliferation.
Adult↗
Comparison between bronchial and alveolar samples of bronchoalveolar lavage fluid in asthma.
BACKGROUND: Cell content of BALF may vary according to the segment of the lung washed. It was proposed to separate BALF into several aliquots, the first sample being more related to bronchi. The present study compared bronchial and alveolar samples by fractionating aliquots of BALF in normal and asthmatic subjects. METHODS: One hundred asthmatic subjects (mean +/- SEM: 37 +/- 1.5 yr in age) were compared with 31 normal subjects (mean +/- SEM: 32 +/- 2.2 yr in age). None of the subjects was a smoker and none was taking drugs that might interfere with the results. The severity of asthma was defined by the clinical score of Aas examining the chronic severity of asthma and ranging from 1 to 5 (range: 1 to 4; mean +/- SEM: 2.2 +/- 0.1) and FEV1 (range: 45 to 130 percent; mean +/- SEM: 82 +/- 1.8 percent of predicted values). Bronchoscopy was done in a standardized manner. A first aliquot of 50 ml of saline each were instilled and the BALF recovered was pooled (alveolar sample). After centrifugation, total and differential cell counts (May Grünwald-Giemsa) were carried out on bronchial and alveolar samples. RESULTS: The alveolar sample contained significantly more cells per milliliter of BALF than the bronchial sample in normal (p less than 0.0077, Wilcoxon test) and in asthmatic subjects (p = 0.0001, Wilcoxon test). Both in normal and asthmatic subjects, bronchial samples contained significantly more neutrophils and epithelial cells and fewer macrophages and lymphocytes than alveolar samples. In asthmatic subjects, the bronchial sample contained a significantly greater percentage of eosinophils than the alveolar sample. Eosinophils were significantly increased in asthmatic subjects for both the bronchial and alveolar samples. Bronchial and alveolar eosinophilia both were correlated with the Aas score (r = 0.25, p = 0.024 and r = 0.38, p = 0.0006, respectively, by Spearman Rank test). CONCLUSIONS: This study shows in a large number of subjects that the cell content of bronchial and more distal segments of the lung is not comparable, indicating that studies should not give pooled data in asthmatic subjects. Moreover, it confirms the presence of BALF eosinophilia in asthmatic subjects.
Adolescent↗
In vitro activation of bronchoalveolar lavage cells by house dust mite allergens.
Mast cells represent a small but important proportion of bronchoalveolar lavage cells and are directly exposed to environmental triggers including allergens. Histamine and PGD2 are mediators released during the activation of mast cells. Fourteen patients allergic to Dermatophagoides pteronyssinus were studied. After bronchoalveolar lavage the unfractionated cell pellet containing metachromatic cells was submitted to allergen challenge using three concentrations of a standardized Dermatophagoides pteronyssinus extract and one concentration of A23187 (2.5 microM). The release of histamine was measured by radioimmunoassay using a monoclonal antibody against acylated histamine and PGD2 was measured by enzyme immunoassay using a polyclonal antibody against methoxamine-PGD2. Histamine was released in 13/14 patients following stimulation of the cells with A23187 and 12/14 patients after stimulation with Dermatophagoides pteronyssinus extract. The release of histamine was 3.5-fold greater when cells were stimulated by the Dermatophagoides pteronyssinus extract than with A23187. PGD2 was released in 10/12 patients when cells were stimulated with A23187 and 6/14 patients in the case of Dermatophagoides pteronyssinus extract stimulation. In the latter case, the mean release was not significantly greater than baseline. For histamine, the maximum release usually occurred with the more concentrated extract whereas in the experiments where PGD2 was released, maximal generation usually occurred with the lowest concentration used. There was no correlation between the severity of asthma and the release of mediators. This study confirms the activation of metachromatic cells by allergen and shows some heterogeneity in the release of granule and membrane-derived mediators.
Adult↗
Airway macrophages releasability in bronchial asthma.
Asthma is a multifactorial disease on genetic basis. Its development is influenced by maternal and environmental factors, i.e. allergens and adjuvants. Early identification of candidates at high risk for development of asthma will enable giving recommendations on preventive measures focussing on exposure to tobacco smoke and other pollutants, indoor and outdoor allergens and possibly viral infections during infancy.
Asthma↗
Functional assessment of viability of epithelial cells. Comparison of viability and mediator release in healthy subjects and asthmatics.
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Asthma↗
Indirect evidence of bronchial inflammation assessed by titration of inflammatory mediators in BAL fluid of patients with asthma.
Bronchial inflammation is a characteristic of asthma that may be examined indirectly by bronchoalveolar lavage (BAL). Nine normal individuals were compared with 38 age-matched adults with asthma of variable severity to appreciate the importance of cell activation in the severity of asthma. The severity of asthma was appreciated by the clinical score of Aas and the pulmonary function of the patients. FEV1 ranged between 35% and 130% of predicted. The indirect activation of eosinophils (EOSs), mast cells, fibroblasts, and neutrophils was examined by the titration of eosinophil cationic protein (ECP), tryptase, hyaluronan (HA), and myeloperoxidase (MPO) by radioimmunoassay in BAL fluid (BALF) and cytology of BALF. In the adults with asthma, there was a significantly increased number of EOSs and a significantly increased level of all mediators but MPO. MPO levels were increased in seven patients only; three of these patients were previous smokers. Only ECP and HA levels were significantly correlated with the severity of asthma. These results demonstrate EOSs, mast cells, and fibroblasts are activated in asthma, whereas the involvement of neutrophils is less clear. There was a significant correlation between ECP and HA levels, suggesting a common activation of EOSs and fibroblasts.
Adult↗
Unexplained CD4-positive T-cell deficiency in non-HIV patients presenting as a Pneumocystis carinii pneumonia.
Three cases of Pneumocystis carinii pneumonia occurring in adults with unexplained T-cell defects are reported. No HIV markers were found during the follow up, and neither was any immunosuppressive disease. The authors emphasize the possibility that Pneumocystis pneumonia may occur and may be treated successfully in previously healthy subjects.
Adult↗
Inflammatory processes in asthma.
Bronchial inflammation is a characteristic of asthma, but, although postmortem and rare bronchoscopic studies had been performed, it is only after 1980 that many experiments were done. Electron microscopy, immunohistochemistry and molecular biology have enhanced our knowledge. As bronchial biopsies and bronchoalveolar lavage present drawbacks, it is favorable to combine both to obtain the best insights into inflammation. The epithelium is rarely intact in asthmatic patients, the cells being both 'fragile' and activated. Eosinophil inflammation is highly important and likely involved in the damage of the epithelium and submucosa. Airway macrophages and monocytes are present in greater amounts and are activated in the bronchi, and they are certainly involved in the pathogenesis of asthma. Mast cells are activated and some emphasis has been put on lymphocytes. Therefore, asthma appears to be a desquamative bronchitis with mixed cell infiltrate.
Acute Disease↗
Releasability of airway macrophages in bronchial asthma.
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Airway Obstruction↗
Increased numbers of hypodense alveolar macrophages in patients with bronchial asthma.
Alveolar macrophages (AM) are among the cells involved in the bronchial inflammation of asthma. It has been shown that AM are a heterogeneous cell population in normal subjects. The heterogeneity of AM from 36 asthmatic patients and 23 normal subjects was studied using Percoll density fractionation. AM recovered from asthmatic patients are mainly in the lower density fractions (1.03 and 1.04 g/ml), whereas AM from normal subjects are in the higher density fractions (1.05 and 1.07 g/ml). Electron microscopic studies showed that low density AM of both asthmatic and normal subjects appear to have morphologic characteristics of activated cells by comparison with high density AM that present characteristics of quiescent cells in both asthmatic and normal subjects. The functional activity of AM fractions of asthmatic and control subjects was assessed using the release of the oxygen free radicals induced by opsonized zymosan and TxB2 generation by A23187. There was no difference between the five fractions of asthmatic or control subjects with regard to oxygen species release. The TxB2 generation was increased in the low density AM from asthmatics when compared with the same fractions of normal subjects. The hypodense cells produced less TxB2 than did cells of higher density in both asthmatic and normal subjects. The density of AM was correlated with the recent instability of the asthma but not with the severity of it. This study shows that AM from asthmatic subjects, when compared with those from control subjects, are heterogeneous, hypodense cells and that they predominate. Hypodense AM did not appear to be hyperresponsive in vitro and may have been already committed into the airways.
Adolescent↗
Neutrophil chemotactic activity of PAF, histamine and neuromediators in bronchial asthma.
Human blood polymorphonuclear neutrophils (PMN) are thought to be involved in the pathogenesis of asthma through their recruitment into the bronchoalveolar lumen and the lung by local release of chemotactic factors. Therefore chemotactic activities of several mediators (PAF, histamine and three neuropeptides substance P, VIP and a somatostatin analog) were compared on blood PMN from both healthy subjects (HS) and asthmatic patients (AP). The maximal response to PAF was significantly different (P less than 0.05) with cells from both groups. Moreover activity for the HS peaked at 10(-6) M, whereas the AP showed peak chemotactic activity at 10(-8) M. Histamine had no chemoattractant effect on PMN. Substance P did not induce PMN locomotion, whereas VIP induced a chemotactic response in a dose-dependent manner, particularly with cells from HS as compared to those from AP. BIM 23014 (a somatostatin analog) exhibited chemotactic activity which was also more pronounced with PMN from HS as compared to those from AP. Our findings showed that blood PMN could be involved in asthma through their heightened locomotor reactions to mediators which are known to be released locally by activated cells in bronchoalveolar lumen.
Adolescent↗
[An unusual miliary pattern].
Syndromes presenting with interstitial radiological signs are often difficult to diagnose aetiologically. Surgical biopsy prevents certain rare cases being neglected notably when there are atypical manifestations. We describe a case of bronchiolitis obliterans with an organising pneumonia which was classical as regards the histology and its response to treatment but unusual as regards the clinical presentation and the aetiology.
Adult↗
[Bronchial inflammation in asthma. Evaluation by bronchial biopsies].
Our understanding of the pathogenesis of asthma has benefitted as a result of bronchial endoscopic techniques linked to studies of bronchoalveolar lavage (LBA) and bronchial biopsy. By using modern biochemical and immunohistochemical methods as well as ultrastructural studies we are better able to specify the importance of bronchial inflammation. Currently we underline the role of epithelial lesions and of intraepithelial lesions and sub-basal inflammation. The responsibility of eosinophils in the epithelial disorder has been proved in vivo by the evidence of cationic protein found both in the LBA liquid and by the tissue localisation thanks to immunological markers. An understanding of the infiltrates and of the state of cellular activation in situ constitutes an initial step in the comprehensive of inflammation; however, these studies do not yet allow us to fully understand the mechanisms of regulation and also the trigger factor in cellular dysfunction which may be the cause. The pseudo-thickening of the basal membrane and sub-epithelial fibrosis are poorly understood, but is probably involved in epithelial repair. The histopathological mechanisms which underly the bronchial aging are equally poorly understood. In the future a better understanding of these problems of neuro-inflammatory disturbances and of epithelial permeability should facilitate the therapeutic approach.
Asthma↗