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Biomedical subjects

C E Mapp

Publications and source records attributed to C E Mapp.

At least 55 records · Page 3Linked to original sources
PubMed1996

In vivo exposure to nitrogen dioxide (NO2) induces a decrease in calcitonin gene-related peptide (CGRP) and tachykinin immunoreactivity in guinea-pig peripheral airways.

The mammalian respiratory tract is densely innervated by sensory and autonomic fibres. Subsets of the nerves contain bioactive regulatory peptides, such as substance P, calcitonin gene-related peptide (CGRP), and neurokinins. The sensory nervous system responds to inhaled irritants, resulting in a release of neuropeptides and, thus, a decrease in the peptide immunoreactivity of the fibres. We examined the effects of inhaled nitrogen dioxide (NO2), a well-known indoor and outdoor air pollutant, on pulmonary sensory neuropeptides. Guinea-pigs were exposed for 4 h to 18 parts per million (ppm) NO2 or to air (n = 5 each). At the end of the exposure, they were killed with urethane and their lungs were fixed in 1% paraformaldehyde in phosphate-buffered saline. Cryostat sections were stained with antisera to an anatomical nerve marker, protein gene product (PGP) 9.5, and to CGRP and tachykinins, utilizing the avidin-biotinylated peroxidase method. In the noncartilaginous airways (diameter < 250 microns) of NO2-exposed animals, less tachykinin- and CGRP-immunoreactive nerve fibres were found compared with controls. No change was seen in the total nerve fibre distribution (PGP 9.5). It is concluded that the peptidergic nerves of guinea-pig peripheral airways are a sensitive indicator of exposure to nitrogen dioxide.

Administration, Inhalation↗
PubMed1996

Isotonic smooth muscle response in human bronchi exposed in vitro to nitrogen dioxide.

Exposure to nitrogen dioxide (NO2), a common oxidant airborne pollutant, has been shown to cause reversible effects on lung function and airway responsiveness, in addition to airways inflammation. However, there have been conflicting reports concerning NO2-induced airway hyperresponsiveness. In the present study, we investigated the isotonic smooth muscle response in isolated human bronchi previously exposed in vitro to NO2. Bronchial segments were obtained from 12 patients who had undergone thoracotomy for lung cancer. Bronchial segments from each patient were exposed to air and to 2.5 parts per million (ppm) NO2 for 4 h. The contractile response of bronchial rings to acetylcholine, neurokinin A (NKA), and substance P was then studied under isotonic conditions. The response to NKA was also studied in rings, with or without epithelium, exposed either to air or 7 ppm NO2. No NO2-induced alteration of the bronchial smooth muscle isotonic response was found under any of the experimental conditions. We conclude that in vitro exposure to up to 7 ppm nitrogen dioxide does not cause alterations of the human bronchial smooth muscle shortening capacity.

Acetylcholine↗
PubMed1996

Airway eosinophilia and expression of interleukin-5 protein in asthma and in exacerbations of chronic bronchitis.

BACKGROUND: An increased number of eosinophils in the bronchial mucosa has been demonstrated both in asthma and in exacerbations of chronic bronchitis. OBJECTIVE: To investigate whether the airway eosinophilia present in asthma and in chronic bronchitis during exacerbations is associated with interleukin (IL)-5 protein expression in the bronchial mucosa. METHODS: We obtained bronchial biopsies in 18 subjects with asthma (four intrinsic, seven extrinsic and seven occupational) and in 11 subjects with chronic bronchitis examined during an exacerbation. The findings were compared with those of bronchial biopsies from 10 subjects with chronic bronchitis examined under baseline conditions and from seven normal subjects, taken as controls. By immunohistochemistry, we assessed the expression of IL-5 protein and the number of eosinophils (EG2), mast cells (tryptase), and T-lymphocytes (CD3) in the submucosa. RESULTS: As compared with controls, the number of eosinophils was increased to a similar degree in both asthma (P < 0.001) and in exacerbations of chronic bronchitis (P < 0.001), whereas the number of IL-5 immunopositive cells was increased significantly only in asthma (P < 0.01). No differences were observed in the number of mast cells and T-lymphocytes between the four groups of subjects examined. CONCLUSIONS: This study shows that the degree of airway eosinophilia is similar in asthma and in exacerbations of chronic bronchitis, but only in asthma is it associated with an increased expression of IL-5 protein in the bronchial mucosa.

Adult↗
PubMed1995

In-vitro exposure of guinea pig main bronchi to 2.5 ppm of nitrogen dioxide does not alter airway smooth muscle response.

In order to investigate whether the oxidant airborne pollutant nitrogen dioxide (NO2) affects airway smooth muscle responsiveness, the contractile response of guinea pig main bronchi after in vitro exposure to 2.5 ppm of nitrogen dioxide was studied. Main bronchi were cannulated and exposed for 2 or 4 h to a constant flow of either NO2 or air. After exposure, bronchial rings were obtained and placed in a 37 degrees C jacketed organ bath filled with Krebs-Henseleit solution. Concentration-response curves were performed for acetylcholine (10(-9)-10(-3) M), substance P (10(-9)-10(-4) M), and neurokinin A (10(-10)-10(-5) M), and voltage-response curves (12-28 V) were performed for electrical field stimulation. There was no significant difference in either the smooth muscle maximal contractile response, or sensitivity between the bronchi exposed to NO2 and those exposed to air. We conclude that in vitro exposure to 2.5 ppm of NO2 does not alter airway smooth muscle responsiveness in guinea pigs.

Acetylcholine↗
PubMed1995

Airway wall remodeling after cessation of exposure to isocyanates in sensitized asthmatic subjects.

To determine whether the cessation of exposure to isocyanates is associated with structural changes of the airway wall in sensitized subjects, we studied bronchial biopsies from 10 subjects with occupational asthma induced by toluene diisocyanate (TDI). Bronchial challenges with TDI and methacholine were performed and biopsies were taken on two occasions, at diagnosis and 6 to 21 mo after cessation of exposure to TDI. After bronchoscopy, biopsies were formalin-fixed or snap-frozen in liquid nitrogen and then processed for a quantitative histochemical and immunohistochemical analysis. After cessation of exposure, we observed a significant decrease of the sensitivity to TDI (p < 0.05), of the thickness of subepithelial fibrosis (p < 0.007), and of the numbers of subepithelial fibroblasts (p < 0.05), mast cells (p < 0.02), and lymphocytes (p < 0.03) as compared with values at diagnosis. By contrast, the nonspecific bronchial hyperresponsiveness and the numbers of macrophages and eosinophils did not change. In conclusion, in patients with occupational asthma induced by TDI, the cessation of exposure to the sensitizing agent is associated with a reduced thickness of subepithelial fibrosis and with a reduced number of subepithelial fibroblasts, mast cells, and lymphocytes in the bronchial mucosa, suggesting a remodeling of the airway wall with the avoidance of the specific stimulus.

Adolescent↗
PubMed1995

Cytokines in the airway mucosa of subjects with asthma induced by toluene diisocyanate.

To determine the status of activation of lymphocytes and the role of cytokines on the inflammatory response of the bronchial mucosa in toluene diisocyanate (TDI) asthma, we performed a quantitative analysis of bronchial biopsies obtained from 15 subjects with TDI-induced asthma and seven normal control subjects. Markers of activation of lymphocytes (CD25 and Very Late activation Antigen-1, VLA-1) and expression of Tumor Necrosis Factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) were determined by immunohistology in the submucosa. Moreover, expression of adhesion molecules on endothelium of submucosal vessels was assessed. Asthmatic subjects had increased numbers of cells expressing CD25 and VLA-1 compared with the control group (p < 0.05). TNF alpha and IL-1 beta immunoreactivity was increased in asthmatics compared with control subjects (p < 0.01), whereas the expression of adhesion molecules, ICAM-1 and E-selectin, on vascular endothelium was not significantly different. No significant differences in the morphologic quantifications were observed between the asthmatics who had biopsies taken 2 d after TDI challenge (n = 7) and those with longer interval (21 +/- 8 d) between TDI challenge and biopsy (n = 8), suggesting that the increase in CD25, VLA-1, TNF alpha, and IL-1 beta was not due to an acute effect, but could be considered a part of the chronic inflammatory process of the airways. We conclude that the inflammatory response of the airways in TDI-induced asthma is characterized by persistent activation of lymphocytes and by chronic expression of proinflammatory cytokines.

Adult↗
PubMed1995

Effect of smoking cessation on airway inflammation in chronic bronchitis.

To investigate the effect of smoking cessation on the airway inflammatory process present in nonatopic subjects with chronic bronchitis, we obtained bronchial biopsies from nine current smokers and seven exsmokers, all with symptoms of chronic bronchitis at the time of the study, and from seven healthy nonsmoking subjects. The exsmokers had stopped smoking on average 13 yr before the study, yet cough and production of sputum had persisted. Bronchial biopsies were assessed using immunohistochemical techniques to investigate the number of inflammatory cells, the markers of mononuclear cell activation, and the expression of endothelial adhesion molecules and cytokines in the subepithelium. Current smokers and exsmokers had an increased number of macrophages, IL-2R-positive cells, VLA-1-positive cells, ICAM-1-positive vessels, and E-selectin-positive vessels compared with normal nonsmoking subjects, but the number of cells positive for neutrophils, EG-2, CD3, CD4, CD8, TNF-alpha and IL-1 beta were similar among the three groups. No differences were observed between current smokers and exsmokers for any parameter examined. In conclusion, the inflammatory process present in the airway mucosa of current smokers may persist after smoking cessation in subjects who continue to have symptoms of chronic bronchitis.

Aged↗
PubMed1995

Comparison of leukocyte counts in sputum, bronchial biopsies, and bronchoalveolar lavage.

To determine the relationship between inflammatory cells in sputum, bronchoalveolar lavage (BAL), and bronchial mucosa, we counted the number of leukocytes in sputum, BAL, and bronchial biopsies obtained from subjects with asthma and with chronic bronchitis in stable condition or during exacerbations. Sputum was induced by inhalation of hypertonic saline in the asthma group. Spontaneous sputum was collected in the chronic bronchitis groups. Differential counts of leukocytes were performed on cytospin preparations of sputum and BAL. Eosinophils, macrophages, neutrophils, and lymphocytes were quantified in the submucosa of the bronchial biopsies. In asthma and in stable chronic bronchitis, the percentages of neutrophils were significantly higher in sputum than in BAL, whereas the opposite was true of the percentages of macrophages and lymphocytes. The lymphocyte was the predominant cell infiltrating the bronchial submucosa in all groups. BAL eosinophils correlated with submucosal and sputum eosinophils in the asthma and exacerbated chronic bronchitis groups. A similar trend was observed between submucosal and sputum eosinophils. In conclusion, the relative proportion of inflammatory cells was different in sputum, BAL, and bronchial mucosa. However, there was a fairly good agreement between the number of eosinophils counted with the three techniques in asthmatics and in exacerbated chronic bronchitics, suggesting that sputum cell analysis may be used for a noninvasive assessment of airway eosinophilia.

Adult↗
PubMed1995

Effect of oxidant air pollutants on the respiratory system: insights from experimental animal research.

In the present paper, we have reviewed experimental animal studies on the effects of the two most important oxidant airborne pollutants, nitrogen dioxide and ozone, on the respiratory system. The toxic effects depend on concentration and length of exposure, and are generally similar for both oxidants, with ozone operative at lower concentrations. High doses of both oxidants cause death due to lung oedema. Exposure to sublethal levels causes functional alterations such as airflow limitation and airway hyperresponsiveness to bronchoconstrictor stimuli. These effects, which are generally reversible, are associated with epithelial injury, oedema and airway and parenchymal infiltration by inflammatory cells. Loss of cilia of airway epithelium and necrosis of type I alveolar epithelial cells are the most prominent consequences at the epithelial level. Inflammation is characterized by early neutrophilic infiltration, followed by an increased number of mononuclear cells, predominantly alveolar macrophages. After long-term exposure, whilst nitrogen dioxide causes predominantly emphysema, ozone produces mainly pulmonary fibrosis. Biochemical effects include lipid peroxidation, increased antioxidant metabolism, and alteration of enzyme activity. Nitrogen dioxide and ozone may also alter the immunological response and reduce the defence against infections, increasing the susceptibility of exposed animals to infections.

Animals↗
PubMed1994

The effects of toluene diisocyanate and of capsaicin on human bronchial smooth muscle in vitro.

Toluene diisocyanate contracts guinea-pig bronchial smooth muscle through a mechanism involving capsaicin-sensitive sensory nerves. In the present study, we investigated the effects of toluene diisocyanate, capsaicin and tachykinins on isolated human bronchi. In 44 rings, toluene diisocyanate (0.3 mM) produced a relaxation which averaged 16.9 +/- 1.1%, in ten rings it produced a shortening that was 15.1 +/- 3.3% and in ten preparations it gave no response. A second administration of toluene diisocyanate (0.3 mM) always produced a relaxation (n = 13, 18.1 +/- 3.9%). Capsaicin (0.03 mM) produced shortening in 15 (35 +/- 6.6%) and relaxation in 11 preparations (41 +/- 6.8%), whereas a second administration caused shortening in nine (25.1 +/- 6.1%) and relaxation in 16 rings (36.4 +/- 4.9%). When toluene diisocyanate was given after two consecutive capsaicin administrations, we observed shortening in two rings (10.0 +/- 3.6%), relaxation in ten rings (15.9 +/- 3.6%), and no response in four preparations. To test the role of NK1 and NK2 receptors in these conflicting responses, we performed concentration-response curves to different tachykinins. Substance P, neurokinin A and neurokinin A-(4-10), a specific NK2 receptor agonist, gave a concentration-dependent shortening, with neurokinin A being the most effective and neurokinin A-(4-10) the least. The specific NK1 receptor agonist, [Sar9, Met(O2)11]substance P, produced both shortening and relaxation. We conclude that toluene diisocyanate and capsaicin may produce both shortening and relaxation in isolated human bronchi through NK1 receptors.

Acetylcholine↗
PubMed1994

Sputum eosinophilia after asthmatic responses induced by isocyanates in sensitized subjects.

To assess the nature and the time-course of the cellular component of airway inflammation induced by isocyanates, we examined nine subjects with occupational asthma induced by toluene- or methylene diphenyl-diisocyanate (TDI, MDI) and four control subjects never exposed to isocyanates. Sputum was induced by inhalation of ultrasonically nebulized hypertonic saline (3-4% NaCl) before and 8, 24, 48 h after inhalation challenge with TDI or MDI. Expectorated samples were incubated with dithiothreitol, washed and cytocentrifuged. Differential cell counts were obtained on slides stained with May-Grünwald-Giemsa. Metachromatic cells (mast cells and basophils) were counted on slides stained with toluidine blue at pH 0.1. One occupational asthmatic exhibited a dual reaction to TDI, two exhibited a single early asthmatic reaction to MDI, six exhibited a late asthmatic reaction to TDI (n = 5) or MDI (n = 1), whereas no reactions were observed in control subjects after TDI challenge. In sensitized subjects eosinophils increased from a median value (interquartile range) of 5 (15)% before challenge to 29 (29)% (P = 0.014) and to 30 (31)% (P = 0.031) 8 and 24 h after TDI/MDI challenges, respectively. Sputum eosinophilia was observed both in early and late reactors and declined to near to baseline values 48 hr after challenge. Percentages of eosinophils in control subjects did not exceed 7% during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Eosinophil cationic protein (ECP), histamine and tryptase in peripheral blood before and during inhalation challenge with toluene diisocyanate (TDI) in sensitized subjects.

To determine whether the measurement of specific markers of inflammatory cells in peripheral blood might be used to detect the inflammatory activity in the airways in asthma induced by toluene diisocyanate (TDI), we measured the levels of eosinophil cationic protein (ECP), histamine and tryptase in peripheral blood before and during inhalation challenge with TDI or methacholine in two groups of subjects who exhibited or did not exhibit an asthmatic reaction after exposure to toluene diisocyanate in the laboratory. When the subjects developed a late asthmatic reaction after exposure to TDI, they showed an increase in their ECP serum levels. By contrast, there were no significant changes in serum ECP levels after exposure to TDI in the control group or after methacholine challenge in either group. Tryptase levels in serum were not detectable before or during inhalation challenge with TDI or methacholine. There was no significant increase in plasma histamine levels during inhalation challenge with TDI or methacholine. These results suggest that eosinophils are 'activated' in subjects who develop a late asthmatic reaction after exposure to TDI and that the measurement of ECP levels in peripheral blood may be a useful marker to monitor airway inflammation.

Administration, Inhalation↗
PubMed1994

Upregulation of adhesion molecules in the bronchial mucosa of subjects with chronic obstructive bronchitis.

To determine whether adhesion molecules and cytokines are upregulated in the bronchial mucosa of chronic bronchitics, we obtained bronchial biopsies in 16 chronic bronchitics, in eight asymptomatic smokers, and in seven normal nonsmoking subjects. Bronchial biopsies were examined by immunohistochemistry to identify the expression of E-selectin and intercellular adhesion molecular-1 (ICAM-1) on vessels and on bronchial epithelium, and the expression of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), neutrophil elastase, and eosinophil cationic protein (EG-2) on cells in the submucosa. Chronic bronchitics had an increased number of E-selectin-positive vessels when compared with both asymptomatic smokers (p < 0.05) and normal subjects (p < 0.01). The numbers of ICAM-1-positive vessels, neutrophils, and IL-1 beta, TNF-alpha-, and EG-2-positive cells were not significantly different in the three groups of subjects examined. When the bronchitic group was divided according to the presence or absence of airway obstruction, the increased number of E-selectin-positive vessels persisted only in bronchitics with airway obstruction, who also had an increased expression of ICAM-1 on basal epithelial cells. We concluded that in the bronchial mucosa of chronic bronchitics with airway obstruction, there is an increased expression of E-selectin on vessels and of ICAM-1 on basal epithelial cells, suggesting the involvement of these adhesion molecules in the pathogenesis of the disease.

Adult↗
PubMed1994

Predictive value of airways hyperresponsiveness and circulating IgE for identifying types of responses to toluene diisocyanate inhalation challenge.

Development of asthma after exposure to toluene diisocyanate (TDI) has been recognized in a variety of occupational settings. However, the pathogenesis of isocyanate-induced asthma remains controversial. In particular, the role of IgE in the development of TDI-induced asthma has remained uncertain. To investigate predictive factors for response to inhalation challenge with TDI, we analyzed data from 63 subjects referred for evaluation of respiratory symptoms thought to be related to TDI sensitization. All subjects underwent interview, routine phlebotomy, spirometry, methacholine challenge, and allergy skin testing prior to TDI challenge. Spirometry and methacholine challenge were repeated 1 day after TDI challenge. The cumulative dose of methacholine needed to produce a 20% decrease in FEV1 (PD20) was determined. A PD20 of 1.4 mg or more was considered normal. Subjects were challenged by exposure to 5 to 10 ppb TDI for up to 30 min in a 9 m3 exposure chamber. A positive response was a 20% or more decrease in FEV1 within 1 h (early) or beyond 1 h (late) after TDI exposure. Thirty-four subjects (54%) had a positive response, of whom 12 (35% of responders) had isolated early responses, 13 (38%) had isolated late responses, and the remainder had dual responses. Thirty-two individuals (51%) had a positive response to methacholine (AR+) prior to TDI challenge. AR+ was strongly associated with a positive TDI challenge: 23 AR+ subjects (72%) had a positive TDI challenge, compared with only 11 AR- subjects (35%) (p < 0.01). AR positivity did not predict the time of onset of TDI response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Airway eosinophilia in chronic bronchitis during exacerbations.

To examine the nature and the degree of airway inflammation in chronic bronchitis during exacerbations, bronchial biopsies and sputum were obtained in 11 subjects with chronic bronchitis examined during an exacerbation, and in 12 subjects with chronic bronchitis examined under baseline conditions. All subjects were nonatopic. Lobar bronchial biopsies were assessed using histochemical and immunohistochemical techniques, and sputum was examined for differential cell counts of leukocytes. Subjects with bronchitis during exacerbations had, on average, 30-fold more eosinophils in their bronchial biopsies than did those examined under baseline conditions (p < 0.001). Although to a lesser extent, the numbers of neutrophils (p < 0.01), T-lymphocytes (CD3) (p < 0.05), VLA-1-positive cells (p < 0.01), and TNF-alpha positive cells (p < 0.05) were also increased during exacerbations. By contrast, the T-lymphocyte subpopulations (CD4 and CD8) and the numbers of macrophages, mast cells, IL-2R-positive cells, and IL-1 beta-positive cells were similar in the two groups of subjects, as well as the percentages of ICAM-1- and E-selectin-positive vessels. Eosinophils were also increased in sputum of subjects with exacerbations when compared with those examined under baseline conditions (p < 0.05). In conclusion, exacerbations of chronic bronchitis are associated with a marked airway eosinophilia and with a milder increase in the number of neutrophils, activated T-lymphocytes, and TNF-alpha-positive cells in the bronchial mucosa.

Aged↗
PubMed1994

Mechanisms and pathology of occupational asthma.

Since the pathogenesis and the pathological features of occupational asthma are similar to those of nonoccupational asthma, the former represents a very useful model for the investigation of the pathogenesis of asthma in general. More than one mechanism may be operative in occupational asthma. Among the mechanisms proposed, immunological mechanisms and airway inflammation play an important role. There is evidence to confirm that T-lymphocyte activation and local accumulation in the bronchial wall of activated eosinophils occurs in asthma of diverse aetiology, i.e. immunoglobulin E (IgE)-mediated, occupational and intrinsic. Neurogenic pathways should be further investigated as a potential mechanism of modulation and amplification of airway inflammation in occupational asthma.

Adult↗