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M Boutet

Publications and source records attributed to M Boutet.

At least 19 recordsLinked to original sources
PubMed2003

Variability of inflammatory cell counts on bronchial biopsies of normal subjects.

Bronchial biopsies are currently used to study the pathophysiology of airway diseases, and comparisons are often made with biopsies from healthy volunteers. It is therefore important to evaluate the variability in each parameter analyzed in bronchial biopsies of healthy volunteers in order to be able to discriminate significant changes. We analyzed bronchial biopsies of 31 nonsmoking, nonatopic healthy subjects who volunteered as normal controls for studies on pathophysiology of asthma. Mean % epithelial desquamation was 23.7% of observed total epithelial length. No subepithelial fibrosis was observed. Inflammatory cell counts (/mm(2) connective tissue surface) were variable among subjects but not different between small (<or=0.25 mm(2)) and large biopsies. Medians (range) of positive cells were for CD3: 20.5 (0-530.0), CD4: 6.2 (0-124.4), CD8: 1.8 (0-81.5), CD25: 0 (0-62.3), HLA-DR: 80.0 (3.5-524.2), EG1: 5.3 (0-180.6), EG2: 6.4 (0-48.8), AA1: 51.3 (0-286.4), CD45: 39.7 (0-448.5) and CD45ro: 28.6 (0-425.2). Subjects living in an urban area had significantly higher CD8-positive cell counts than those from suburban areas ( p = 0.0001). The presence of an animal at home was associated with lower positive cell counts for CD4 ( p = 0.02), CD45 ( p = 0.02) and HLA-DR ( p = 0.01). In conclusion, the variability in the number and expression of markers of activity of bronchial immune cells in normal subjects likely reflects variable host responses to environmental exposures and must be taken into account when compared to specimens obtained in subjects with airway diseases.

Adolescent↗
PubMed2001

Effect of salmeterol on allergen-induced airway inflammation in mild allergic asthma.

A previous study suggested that the long-acting beta2-adrenergic agonist salmeterol (SM) had inhibitory effects on bronchial mucosal inflammation 6 hours after allergen exposure. To further evaluate the influence of SM on allergen-induced airway inflammation. We studied, in a randomized, double-blind, cross-over trial, 16 mild asthmatic patients who had a dual asthmatic response to allergen inhalation. Subjects received 50 microg of SM or placebo (P), twice daily for 1 week each, separated by a 2-week wash-out period. At the end of each treatment period, after withholding SM for 24 h, they had a methacholine inhalation test (medication was resumed after the test), followed 24 h later by an AC with the concentration of allergen that had induced a LAR at baseline. Airway inflammation was assessed 24 h after the AC by bronchoalveolar lavage (BAL) (n = 16) and bronchial biopsies (n = 13). As expected, SM improved baseline FEV1 and PC20 (P < or = 0.009) and decreased the allergen-induced early bronchoconstrictive response. There were no significant differences in BAL cell counts after the two treatments. On bronchial biopsies, numbers (median, mm2) of submucosal CD45 (P: 43 +/- 23; SM: 161 +/- 43, P = 0.031), CD45Ro (P: 37 +/- 19; SM: 126 +/- 41, P = 0.047) and AA1 positive cells (P: 38 +/- 6, SM: 65 +/- 17, P = 0.006) were significantly higher after SM than P treatment. The numbers of CD4 (P: 11 +/- 10; SM: 32 +/- 7, P = 0.085), HLA-DR (P: 65 +/- 30; SM: 116 +/- 36, P = 0.079) and EG2 positive cells (P: 25 +/- 15; SM: 38 +/- 26, P = 0.09) tended to increase with SM treatment. In summary, compared to placebo, 1 week of regular use of SM is associated with an increase in bronchial inflammatory cells 24 h after AC. This is in keeping with the recommendation that salmeterol should only be used with an anti-inflammatory agent, particularly in the context of significant allergen exposure.

Adolescent↗
PubMed2000

Cytokine expression in the lower airways of nonasthmatic subjects with allergic rhinitis: influence of natural allergen exposure.

BACKGROUND: Natural exposure to pollen provokes an increase in airway responsiveness in nonasthmatic subjects with seasonal allergic rhinitis. This natural exposure may induce inflammatory cell recruitment and cytokine release, leading to lower airway inflammation. OBJECTIVE: The aim of this study was to characterize lower airway inflammation in nonasthmatic pollen-sensitive subjects. METHODS: We performed immunohistochemical tests on bronchial biopsy specimens from subjects with rhinitis who had no past or current history of asthma to evaluate cytokine expression and inflammatory cell numbers and activation both in and out of the pollen season. RESULTS: The number of CD4(+), CD8(+), and CD45RO(+) lymphocyte subpopulations were significantly higher during the pollen season compared with the out-of-season period (P <.04). Furthermore, EG1(+) cells tended to increase after natural pollen exposure (P =.06). The number of IL-5(+) cells increased significantly after natural exposure to pollen compared with out-of-season numbers (P <.01). This increase in IL-5 expression was correlated with the numbers of CD3(+), CD4(+), CD45RO(+), and EG1(+) cells. The numbers of tryptase-positive, IFN-gamma(+), and IL-4(+) cells did not change after natural exposure. CONCLUSION: This study showed that natural pollen exposure was associated with an increase in lymphocyte numbers, eosinophil recruitment, and IL-5 expression in the bronchial mucosa of nonasthmatic subjects with allergic rhinitis.

Adult↗
PubMed1999

Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodelling.

To study the physiopathology and significance of asymptomatic airway hyperresponsiveness (AHR), the clinical and bronchial immunohistological parameters were evaluated in subjects with asymptomatic and symptomatic AHR. Asymptomatic subjects with AHR (eight females/two males, no respiratory symptoms, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) <8 mg x mL(-1) and no treatment) were compared with asthmatic subjects paired for age, sex and PC20, and with nonatopic, nonasthmatic controls paired for age and sex. All three groups were evaluated once at baseline, whilst the asymptomatic AHR subjects were re-evaluated after 1 and 2 yrs. Measurements included spirometry, methacholine challenge, serum immunoglobulin (Ig)E, blood eosinophils, and bronchoscopy (at baseline and after 2 yrs only). At first evaluation, the mean blood eosinophil count, total serum IgE level, atopic index, baseline forced expiratory volume in one second (FEV1) and the degree of bronchial epithelial desquamation of the asymptomatic AHR subjects were similar to those of asthmatic subjects. However, they presented focal rather than the continuous bronchial subepithelial fibrosis observed in asthmatics. Their mucosal CD3, CD4, CD25, EG1 and EG2-positive cell counts were intermediate between those of the control subjects and asthmatics. At the end of the 2-yr follow-up, four of them had developed asthma symptoms. At this time, bronchial biopsies revealed an increase in the extent of subepithelial fibrosis and in the number of CD25 and CD4-positive cells, and a decrease in the number of CD8+ cells, particularly in subjects who developed asthma symptoms. These data suggest that asymptomatic airway hyperresponsiveness is associated with airway inflammation and remodelling, and that the appearance of asthma symptoms is associated with an increase in these features, particularly the CD4/CD8 ratio and airway fibrosis. Consequently, this study proposes an association between asymptomatic airway hyperresponsiveness and airway inflammation, structural changes and asthma although these relationships remain to be further evaluated.

Adolescent↗
PubMed1998

In vitro procollagen synthesis and proliferative phenotype of bronchial fibroblasts from normal and asthmatic subjects.

Asthma is characterized histologically by a bronchial subepithelial fibrosis. Cytokines and other mediators released in the asthmatic chronic inflammatory microenvironment can activate the repair process that leads to fibroblast proliferation and collagen synthesis. To our knowledge, there are no data regarding the effect of a chronic inflammatory microenvironment on the phenotype of human bronchial fibroblasts. In the present study, we address this issue by comparing bronchial fibroblasts isolated from normal and asthmatic subjects in terms of: (a) proliferation over cell passage; (b) in vitro lifespan; (c) proliferative response to transforming growth factor-beta 1, platelet-derived growth factor-BB, dexamethasone, and retinoic acid; and (d) base-line synthesis of procollagens I and III. Bronchial fibroblasts from asthmatic subjects demonstrated lower DNA synthesis with cell passage than bronchial fibroblasts from normals. The in vitro lifespan of asthmatic bronchial fibroblasts was lower than in those from normal subjects and was significantly correlated with airway responsiveness. Platelet-derived growth factor-BB and dexamethasone increased 3H-thymidine incorporation in asthmatic bronchial fibroblasts without having any significant effect on normal fibroblast proliferation. Transforming growth factor-beta 1 and retinoic acid had no significant effect on bronchial fibroblast proliferation. Base-line procollagens I and III synthesis measurements showed no differences between normal and asthmatic fibroblasts. Taken together, these results indicate that the chronic inflammatory microenvironment found in asthma can modulate some aspects of bronchial fibroblast phenotype.

Adult↗
PubMed1997

Reactive airways dysfunction syndrome due to chlorine: sequential bronchial biopsies and functional assessment.

Very little information is available on the acute histopathological bronchial alterations caused by reactive airways dysfunction syndrome (RADS). We had the opportunity to carry out sequential bronchial biopsies in a subject with RADS due to chlorine (60 h, 15 days, 2 and 5 months after the acute exposure), and also to assess spirometry and bronchial responsiveness to methacholine. A 36 year old worker in a water-filtration plant (nonsmoker) abruptly inhaled high concentrations of chlorine on September 12, 1994. He experienced immediate nasal and throat burning, retrosternal burning and wheezing, and these symptoms persisted during and after the workshift. Two days later, he complained of retrosternal burning, dyspnoea and wheezing. Inspiratory wheezing was documented. His forced expiratory volume in one second (FEV1) was 66% of predicted and the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) was slightly abnormal (2.5 mg.mL-1). On the following day, the patient underwent bronchial biopsies, which showed almost complete replacement of the epithelium by a fibrinohaemorhagic exsudate. The subject was prescribed inhaled steroids. Fifteen days after the accident, the PC20 was improved to 6 mg.mL-1. Bronchial biopsies showed considerable epithelial desquamation with an inflammatory exudate and swelling of the subepithelial space. Five weeks after the accident, the PC20 was normal (57 mg.mL-1). Inhaled steroids were stopped. Two months after the accident, the PC20 deteriorated to 4 mg.mL-1. Biopsies then showed regeneration of the epithelium by basal cells and there was still a pronounced inflammatory infiltrate. Inhaled steroids were restarted. Three and five months later, the PC20 was normal (24 mg.mL-1). Bronchial biopsies showed a greatly improved epithelium and reduction of the inflammatory infiltrate. This case report shows that reactive airways dysfunction syndrome can cause acute, marked, though partially reversible, histological abnormalities. Inhaled steroids may modulate changes in bronchial responsiveness in this condition.

Adult↗
PubMed1997

Bronchial subepithelial fibrosis correlates with airway responsiveness to methacholine.

OBJECTIVES: To evaluate the relationships between airway subepithelial collagen deposition and epithelial desquamation with airflow obstruction and hyperresponsiveness in different types of asthma and other respiratory conditions such as chronic cough and allergic rhinitis. DESIGN AND PARTICIPANTS: We compared the histopathologic features observed on bronchial biopsy specimens obtained from 80 subjects: 38 with different types of asthma, 19 with chronic cough, 13 with allergic rhinitis, and 10 normal control subjects. Each subject had a questionnaire on respiratory symptoms and medication needs, measurements of expiratory flows and methacholine responsiveness, allergy skin prick tests, and a bronchoscopy with bronchial biopsies. None of the subjects studied used bronchial anti-inflammatory agents. RESULTS: Different degrees of bronchial subepithelial fibrosis were present in asthmatic subjects, the most intense being observed in occupational asthma; a subepithelial deposition of collagen was also found in subjects with allergic rhinitis, although it was less intense than in asthma and irregularly distributed under the basement membrane. On global analysis, we found a significant correlation between individual provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) and subepithelial fibrosis intensity (rs=-0.70, p<0.001). The degree of epithelial desquamation was correlated with that of subepithelial fibrosis (rs=0.36, p=0.02) in subjects with normal airway responsiveness, but it was not correlated with the PC20 (rs=0.10, p>0.05). Neither the degree of subepithelial fibrosis nor epithelial desquamation was correlated with the FEV1. CONCLUSION: These results suggest that structural airway changes such as subepithelial collagen deposition may be significant determinants or markers of a process that results in airway hyperresponsiveness.

Adult↗
PubMed1996

Dexamethasone and cyclosporin A modulation of cytokine expression and specific antibody synthesis in an allergic bronchopulmonary aspergillosis murine model.

We previously demonstrated that, in C57B1/6 mice, cyclosporin A enhanced and dexamethasone inhibited the Aspergillus fumigatus-induced pulmonary eosinophilia and total IgE levels. To evaluate whether these effects were related to the modulation of T-lymphocyte recruitment and activation and cytokine expression, we performed immunohistochemical staining for T-cell surface marker CD3 and CD4, cell activation marker CD25, and cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and interleukin-5 (IL-5) on lung tissue sections from mice exposed to Aspergillus fumigatus and treated or not with dexamethasone or cyclosporin A. Dexamethasone significantly inhibited Aspergillus fumigatus-induced increased number of activated T cells and cytokine-expressing cells in parallel with a decrease in pulmonary eosinophils. In contrast, cyclosporin A did not decrease these immunological events but enhanced the lung eosinophil recruitment. Moreover, dexamethasone prevented the production of immunoglobulins against 76 and 36 kD antigen proteins and cyclosporin A against 76 and 18 kD antigen proteins. These results indicate that dexamethasone down-regulates and cyclosporin A up-regulates lung eosinophil recruitment and total IgE production, probably via the modulation of T-lymphocyte activation and GM-CSF, IL-4 and IL-5 expression. Both drugs inhibit Aspergillus fumigatus-specific antibody synthesis, but their suppressive actions are selective to different antigenic components.

Animals↗
PubMed1996

Immunohistochemical detection of GM-CSF, IL-4 and IL-5 in a murine model of allergic bronchopulmonary aspergillosis.

BACKGROUND: Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and IL-5 are important in tissue eosinophil accumulation and high IgE production in allergic inflammatory reaction. OBJECTIVE: We examine lung GM-CSF, IL-4 and IL-5 expression in a murine model of allergic bronchopulmonary aspergillosis (ABPA) characterized by eosinophil and lymphocyte lung infiltration and elevated serum IgE level. METHODS: C57BL/6 mice were intranasally treated three times a week for 1, 2 or 3 week(s) with Aspergillus fumigatus (Af) antigen or saline and were sacrificed on days 7, 14 and 21. Immunohistochemical analyses for GM-CSF, IL-4 and IL-5 were performed on lung sections. RESULTS: Af treatment induced a remarkable pulmonary eosinophil influx. Increased numbers of lung T lymphocytes and GM-CSF positive cells were observed on days 14 and 21. IL-4 and IL-5 positive cells were increased significantly only on day 14. Immunostained serial sections showed that most (> or = 98%) cytokine positive cells were CD3 positive. Few eosinophils (< 2% of cytokine positive cells) were immunoreactive for GM-CSF and IL-5. Significant correlations were found between the number of GM-CSF and IL-5 positive cells, and the number of eosinophils in Af-treated lung (r = 0.62, P < 0.05 and r = 0.52, P < 0.05 respectively), and between the number of IL-4 positive cells and the serum total IgE level (r = 0.64, P < 0.01). CONCLUSIONS: Our data suggest a role for T lymphocyte GM-CSF, IL-4 and IL-5 in Af-induced mouse pulmonary eosinophilia and increased serum IgE production and further support the importance of T helper (TH2) cells in the pathogenesis of ABPA.

Animals↗
PubMed1996

Reactive airways dysfunction syndrome induced by exposure to a mixture containing isocyanate: functional and histopathologic behaviour.

A 31-year-old machinist experienced acute symptoms of rhinoconjunctivitis, coughing, shortness of breath, and wheezing after sudden exposure to fumes containing isocyanates and solvents. Lung function tests carried out 11 days after the event showed reduced flow rates. Forty days after the acute inhalational injury, expiratory flows improved, and the PC20 was 0.8 mg/ml, showing moderate bronchial hyperresponsiveness. Six days later, the subject underwent bronchoscopy. Bronchial biopsies showed a marked loss of epithelial cells, severe subepithelial oedema, and inflammatory cells infiltrate (mainly lymphocytes). The subject was given inhaled steroids. The PC20 was back to normal 42 days later. Bronchial biopsies then showed incomplete regeneration of the epithelial layer with few ciliated cells and persistence of inflammation (lymphocyte infiltrate) in epithelia and connective tissue. We conclude that irritant exposure to a mixture of isocyanates and solvents can cause occupational asthma without a latency period, i.e., reactive airways dysfunction syndrome.

Adult↗
PubMed1996

Morphologic and functional properties of bronchial cells isolated from normal and asthmatic subjects.

Recent advances in biomedical sciences have led to the development of various methods for the evaluation of the physiopathology of respiratory diseases. This study reports morphologic and functional features of cells isolated by a new method from bronchial biopsies of normal and asthmatic subjects. Both epithelial and fibroblastic cells were isolated from the same biopsies using collagenase. The cells were cultured for several passages and stored frozen. Two selective culture media were used in order to obtain pure epithelial and fibroblastic cell populations. Immunofluorescence analysis of intermediate filaments, keratins, and vimentin confirmed the type of the isolated cells. The proportions of alpha-actin-expressing cells varied among the fibroblastic cell populations isolated from normal and asthmatic subjects. Interestingly, the population containing high numbers of alpha-actin-expressing cells and presenting the fastest collagen contraction kinetic was isolated from bronchial biopsies of an asthmatic subject. Moreover, the fibroblastic cells that showed the best contractile properties 24 h after their seeding in floating collagen gels were isolated from bronchial biopsies of asthmatic patients having PC20 values below 1 mg/ml. On the basis of these data, we propose a new approach to isolate, culture and characterize human bronchial cells in vitro.

Adult↗
PubMed1996

Tumor necrosis factor-alpha and interleukin-1 alpha expression in a murine model of allergic bronchopulmonary aspergillosis.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) are two important proinflammatory cytokines that may be involved in allergic inflammatory processes. We recently developed a murine model of allergic bronchopulmonary aspergillosis characterized by eosinophilic and lymphocyte lung infiltration and increased serum and bronchoalveolar lavage immunoglobulin E concentration. In this study we examined the expression of TNF-alpha and IL-1 alpha in the lung tissue sections of C57BL/6 mice that were intranasally challenged with Aspergillus fumigatus antigen or saline on the first 3 days of each week and sacrificed on days 4, 7, 14, and 21. Compared with the control mice, A. fumigatus treated mice had a remarkable increase of TNF-alpha and IL-1 alpha expression in the lung on days 4, 14, and 21, with a slight increase on day 7. The major types of cells expressing TNF-alpha and IL-1 alpha included alveolar macrophages, endothelial cells, and bronchiolar and alveolar epithelial cells. Consistent with increased expression of TNF-alpha and IL-1 alpha, intercellular adhesion molecule-1 expression also was upregulated in the lung of A. fumigatus treated mice; its time course and cell types were similar to those of TNF-alpha and IL-1 alpha expression. These results suggest that TNF-alpha and IL-1 alpha may be involved in the A. fumigatus induced inflammatory process and that upregulated intercellular adhesion molecule-1 expression may represent one of the roles played by TNF-alpha and IL-1 alpha in this murine model.

Animals↗
PubMed1996

Lower airways remodeling in nonasthmatic subjects with allergic rhinitis.

We analyzed by immunohistochemistry the distribution of types I, II, III, IV, V, and VII collagens, laminin, and fibronectin in the bronchial biopsy specimens of nonasthmatic subjects with seasonal allergic rhinitis (n = 8) and compared these results with those found in mild stable allergic asthmatics (n = 6) and normal controls (n = 5). The content of type I and III collagens was increased in rhinitic subjects compared with controls. These collagens were focally deposited in the reticular basement membrane area. Three subjects with allergic rhinitis had no fibronectin deposition in their basement membrane, as in controls, whereas the other five had a focal fibronectin deposition. In asthmatic patients, type I and III collagens and fibronectin were more abundant and more uniformly distributed underneath the basement membrane than they were in rhinitic subjects. Expression of type II, IV, V, and VII collagens and laminin were similar in the three groups. Electron microscopic and immunohistochemical analyses of bronchial mucosa showed a network of myofibroblasts beneath the epithelium in rhinitis as in asthma subjects. These data show that the irregularly distributed subepithelial fibrosis observed in subjects with allergic rhinitis results from the deposition of type I and III collagens and fibronectin, probably produced by bronchial myofibroblasts. These results suggest the presence of an active structural remodeling in the lower airways of allergic rhinitic subjects that is similar in nature to that seen in asthma, although less marked.

Adult↗
PubMed1995

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in a murine model of pulmonary eosinophilia and high IgE level.

T lymphocytes and eosinophils are probably involved in the pathogenesis of allergic bronchopulmonary aspergillosis (ABPA), a disease characterized by pulmonary eosinophilia and high serum and lavage IgE levels. We recently developed a murine model of ABPA. To investigate the mechanisms of T lymphocyte and eosinophil recruitment to the lung in this disease, we examined the expression of ICAM-1 in the lung tissue of mouse challenged with Aspergillus fumigatus (Af) antigen. C57B1/6 mice were intranasally exposed to Af (Af group) or saline (control group) three times a week for 1, 2 or 3 weeks. On days 4, 7, 14 and 21, mice were killed and lung tissue was fixed in acetone and embedded in glycol methacrylate. Serial 2-microns sections were stained with chromotrope 2R and MoAbs against ICAM-1, CD11a/CD18 (LFA-1) and CD3. Af-challenged mice presented significant increases in eosinophil, T lymphocyte and LFA-1-positive cell count and up-regulated expression of ICAM-1 in the lung tissue at all the time points examined. ICAM-1 expression intensity correlated with the number of T lymphocytes (r = 0.59, P < 0.01), LFA-1-positive cells (r = 0.68, P < 0.001), but not of eosinophils (r = -0.24, P > 0.05). These findings suggest that up-regulation of ICAM-1 expression is involved in the inflammatory process of this murine model of ABPA, and that this up-regulation may be more relevant to the the T lymphocyte accumulation in the lung.

Animals↗
PubMed1995

Increased maximal airway response to methacholine during seasonal allergic rhinitis in nonasthmatic subjects: relationships with airway wall thickness and inflammation.

This study was carried out to determine whether the increase in airway responsiveness induced by natural antigenic exposure in nonasthmatic subjects is associated with an increase in maximal bronchoconstrictor response (MBR), and if these changes could be due to an increase in airway wall thickness from allergen-induced increase in airway inflammation. In 11 nonasthmatic subjects with seasonal allergic rhinitis, a methacholine challenge was obtained monthly, during and out of pollen exposure. Each subject had a high-resolution chest tomography in and out of the pollen season, to determine the relative thickness of the right intermediary bronchus over its total diameter (T/D), as well as inflammatory cell counts, apparent basement membrane thickness as an indication of subepithelial fibrosis and epithelial desquamation in bronchial biopsy specimens. In season, the mean provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in one second (PC20) decreased from 51.5 to 25.8 mg.mL-1, and the maximal post-methacholine fall in forced expiratory volume in one second (delta FEV1,max) or forced vital capacity (delta FVC) and the slope of the dose response curve (DRS) increased compared with out of season: delta FEV1,max 44 +/- 5 vs 25 +/- 5%; delta FVC 34 +/- 5 vs 16 +/- 4%; and slope of DRS 14.1 +/- 2.8 vs 6.9 +/- 1.3%/mg.mL-1. No significant change was observed in T/D ratio. The seasonal change in delta FVC was positively correlated with the delta FEV1,max (rs = 0.891) and the change in DRS (rs = 0.909), but not with the change in PC20, nor with changes in bronchial biopsy inflammatory features or T/D ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Is reactive airways dysfunction syndrome a variant of occupational asthma?

BACKGROUND: Reactive airways dysfunction syndrome (RADS) or irritant-induced asthma is a syndrome that leaves subjects with asthma-like symptoms after one or more exposures to a high concentration of an irritant substance. The degree of reversibility of airway obstruction in subjects with RADS is nevertheless unknown, as is the degree of associated lesions at the airway level. METHODS: We compared the acute reversibility of forced expiratory volume in 1 second (FEV1) after inhalation of albuterol (200 micrograms) in 15 subjects with RADS (12 cases caused by chlorine inhalation) with that of 30 subjects with occupational asthma (OA) caused by various agents. They were paired according to baseline airway obstruction (61% and 63% of predicted value in the RADS and OA groups), requirement for medication (bronchodilator only--7 of 15 subjects with RADS and 14 of 30 subjects with OA--as compared with bronchodilator + inhaled steroids in 8 of 15 subjects with RADS and 16 of 30 subjects with OA, respectively), and interval since removal from exposure (means of 30 and 24 months in the RADS and OA groups). In addition, five nonsmokers with RADS who had not received inhaled steroids underwent bronchoscopy with lavage and bronchial biopsies less than 2 years after the exposure. RESULTS: The percentage increase in FEV1 over baseline after inhalation of albuterol was 10% +/- 9% in the RADS group and 19% +/- 16% in the OA group (p = 0.005). Only 2 of 15 subjects (13%) with RADS and 12 of 30 subjects (40%) with OA showed an improvement in FEV1 of 20% or greater after inhalation of albuterol. Bronchoalveolar lavage showed an increased number of cells with a predominance of lymphocytes, and biopsy specimens showed increased basement membrane thickness in the five subjects with RADS who underwent bronchoscopy. CONCLUSION: Subjects with RADS are generally left with less airway reversibility than those with OA. We suggest that this difference is secondary to distinct pathologic changes.

Adult↗
PubMed1994

Airway inflammation in nonasthmatic subjects with chronic cough.

The physiopathology of chronic cough remains obscure. We evaluated the possibility that chronic cough in nonasthmatic subjects is associated with airway inflammation, and if this is so, what the relationship between this inflammation and the possible etiology of cough might be, as well as its response to inhaled steroids. Nineteen nonsmoking, nonasthmatic subjects referred for a persistent cough (mean: 3.8 yr) were evaluated and compared with 10 normal subjects. The evaluation included a respiratory questionnaire, a physical examination, allergy skin-prick tests, chest and sinus radiographs, esophageal pH monitoring, measurements of expiratory flows, methacholine and citric acid challenges, and flexible bronchoscopy for bronchoalveolar lavage (BAL) and bronchial biopsies. Fourteen subjects further accepted participation in a randomized, double-blind crossover trial of inhaled beclomethasone (500 micrograms four times daily) and a placebo for 1 mo each. Four groups of subjects were identified according to the presence of postnasal discharge (n = 4), gastroesophageal reflux (n = 6), both conditions (n = 5), or neither (n = 4). Subjects with chronic cough had an increased number of inflammatory cells in their bronchoalveolar lavage fluid (BALF), but there was no significant difference between the four subgroups of coughers. As compared with control subjects, the bronchial biopsies of subjects with chronic cough showed increased epithelial desquamation (p = 0.004) and inflammatory cells (p = 0.005), particularly mononuclear cells (p < 0.01), in addition to submucosal fibrosis, squamous-cell metaplasia, and loss of cilia. These findings were not significantly different between the different etiologic groups. In subjects with chronic cough, basement-membrane thickness was normal and not different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗