Bronchoalveolar Lavage Cell Profiles Research Articles

Nebulized caffeine alleviates airway hyperresponsiveness in a murine asthma model.

The clinical definition of "difficult asthma" has expanded recently to include an ever-growing subset of patients with symptoms that cannot be controlled by conventional means, forcing the medical community to develop innovative therapeutics. Beneficial effects of coffee for subjects with asthma, primarily the effect of methylxanthine components, have long been described. Methylxanthines, including theophylline and caffeine, inhibit phosphodiesterases and downstream cAMP signaling to prevent mast cell degranulation while promoting immunomodulation (Peleman RA, Kips JC, Pauwels RA. Clin Exp Allergy 28: 53-56, 1998; Deshpande DA, Wang WCH, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JSK, Liggett SB. Nat Med 16: 1299-1304, 2010). Caffeine is also a bitter taste receptor agonist, binding to taste-sensing type 2 receptors (TAS2R) before releasing calcium to hyperpolarize airway smooth muscle membranes, inducing bronchodilation (Workman AD, Palmer JN, Adappa ND, Cohen NA. Curr Allergy Asthma Rep 15: 72, 2015; Devillier P, Naline E, Grassin-Delyle S. Pharmacol Ther 155: 11-21, 2015). Theophylline is conventionally used to treat asthma, whereas, according to the literature, the dosage required for orally administered caffeine has yielded modest improvement (Alfaro TM, Monteiro RA, Cunha RA, Cordeiro CR. Clin Respir J 12: 1283-1294, 2018). We sought to determine whether aerosolization of ultrafine caffeine particles (2.5-4 μm) directly to the lungs of susceptible A/J mice challenged with methacholine would improve pulmonary function via forced oscillation technique. In addition, we assessed whether nebulization of caffeine leads to changes in lung pathophysiology and bronchoalveolar lavage cell profiles. We found that mice that received aerosolized caffeine had statistically significant decreases in maximum airway resistance [6.3 vs. 3.9 cmH2O·s/mL at 62.5 mg/mL caffeine; confidence interval (CI) = -4.3, -0.4; P = 0.02] and significant delays in the time required to reach maximum resistance compared with that of controls (64.7 vs. 172.1 sec at 62.5 mg/mL caffeine, CI = 96.0, 118.9; P < 0.0001). Nebulized caffeine yielded a consistent effect on airway hyperresponsiveness at a range of doses without evidence of significant pathology relative to vehicle control.NEW & NOTEWORTHY For decades, coffee has been shown to improve symptoms in patients with asthma. One component, theophylline, is conventionally used to treat asthma, whereas the dosage required for orally administered caffeine has yielded modest improvement. We sought to determine whether aerosolization of caffeine directly to the lungs of susceptible A/J mice challenged with methacholine would alter pulmonary function via forced oscillation technique. We found nebulized caffeine yielded a consistent improvement on murine AHR.

BAL biomarkers' panel for differential diagnosis of interstitial lung diseases.

Bronchoalveolar lavage (BAL) is a useful procedure for differential diagnosis of interstitial lung diseases (ILDs) and for identification of granulomatous lung diseases. We investigated a panel of biomarkers from BAL fluid of ILD patients to evaluate their utility in differentiating ILDs. Bronchoscopy with BAL was performed in 100 consecutive patients with suspected ILD (41 sarcoidosis, 11 cHP and 24 other ILDs); the 24 patients negative for ILD diagnosis were included as control group. BAL phenotypes and cell profiles (CD4+/CD8+ ratio, NK and CD103+ cell counts, chitotriosidase and KL-6 levels in BAL) were determined by flow cytometry. A decision-tree statistical algorithm was applied. Sarcoidosis was discriminated by a higher BAL CD4+/CD8+ ratio (p = 5.8E-05), a lower BAL CD103+CD4+ count (p = 5.0E-02) and lower BAL NK percentages (p = 8.8E-03) than the other groups. BAL KL-6 concentrations were higher in sarcoidosis than in other ILDs (p = 1.5E-02) and were directly correlated with CD4+/CD8+ ratio. We used decision-tree statistical analysis to combine our biomarkers into two diagnostic algorithms for differential diagnosis of ILDs. A panel of BAL biomarkers for diagnosis of ILDs is proposed; CD4+/CD8+ ratio, KL-6 concentrations, and NK and CD103+CD4+ cell percentages in BAL could improve the identification and differential diagnosis of sarcoidosis.

Expression analysis of extracellular microRNA in bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis.

MicroRNA (miRNA) are transcriptional regulators implicated in pulmonary sarcoidosis and packaged in extracellular vesicles (EV) during cellular communication. We characterized EV and investigated miRNA expression in bronchoalveolar lavage (BAL) fluid from sarcoidosis patients. EV were characterized for size(s) using dynamic light scattering and transmission electron microscopy (TEM) analysis and protein markers by immunoblotting. Twelve extracellular and 5 cellular miRNA were investigated in BAL from 16 chest X-ray stage-I (CXR-I) and 17 CXR stage-II (CXR-II) sarcoidosis patients. Associations between miRNA and disease characteristics (extrapulmonary involvement, pulmonary function and BAL cell profile) were statistically analysed. BAL from sarcoidosis patients contained exosomes and microvesicles (MV) as EV. In these EV, expression of miR-146a (P = 0.007), miR-150 (P = 0.003) and BAL cellular miR-21 (P = 0.01) was increased in CXR-II compared with CXR-I. Other detected EV (miR-21 and miR-26a) and cellular (miR-31, miR-129-3p, miR-146a and miR-452) miRNA were not differentially expressed. The investigated miRNA did not reflect extrapulmonary involvement, but EV miR-146a and miR-150 were negatively correlated with pulmonary function (miR-146a with vital capacity (VC; Spearman's correlation coefficient (rs ), P = -0.657, 0.007), percent predicted forced expiratory volume in 1 s (FEV1 ; -0.662, 0.006) and FEV1 /forced vital capacity (FVC) ratio (-0.649, 0.008); miR-150 correlated negatively with VC (-0.584, 0.019) and FEV1 /FVC ratio (-0.746, 0.001) in CXR-II cases). Our data provide evidence that exosomes and microvesicles as extracellular vesicles are present in the bronchoalveolar space of sarcoidosis patients and they differentially express EV miRNA (miR-146a and miR-150), the expression of which correlates negatively with pulmonary function indices. The significance of these findings for disease pathophysiology and clinical course require further investigation.

Pneumopathies interstitielles diffuses médicamenteuses au cours des maladies systémiques

Immunosuppressants and immunomodulators are designed to regulate excessive immune response responsible for inflammatory lesions and are prescribed more and more in internal medicine. These drugs are known for their efficiency but with a significant toxicity including interstitial lung disease (ILD). Some factors liable to pulmonary toxicity include advanced age, genetic polymorphism and the existence of prior pulmonary disease. Cytotoxicity and hypersensitivity are the main mechanisms of pulmonary toxicity. There is no universal classification of drug induced-lung disease. Theoretically, drugs may be responsible for all histological aspects of ILD. Methotrexate is the most well-known drug as a provider of ILD with a prevalence of 0.3 to 11.6%. Some cases of ILD have also been reported with the new biologics used in systemic diseases. The diagnostic approach to the suspicion of drug ILD is to eliminate non-medicinal causes of pneumonia including infections and tumors before exploring the clinical symptomatology and the results of imaging and bronchoalveolar lavage cell profile. The analysis of the clinical symptomatology check the compatibility of the chronology of clinical and/or radiological pneumonia with the medication suspected. Subsequently, data from the clinical case are compared with those of the literature. Treatment involves stopping the suspected drug. The use of corticosteroids may be required in case of signs of severity or a lingering evolution.

18F-FDG PET patterns and BAL cell profiles in pulmonary sarcoidosis

Bronchoalveolar lavage (BAL) and (18)F-fluorodeoxyglucose ((18)F-FDG) PET can both demonstrate sarcoid activity. To assess whether metabolic activity imaged by (18)F-FDG PET represents signs of disease activity as reflected by BAL, (18)F-FDG PET patterns were compared with BAL cell profiles. In this retrospective analysis, 77 newly diagnosed pulmonary sarcoidosis patients underwent BAL and (18)F-FDG PET. Based on (18)F-FDG PET, patients were diagnosed with exclusively mediastinal/hilar activity (group A) and activity in the lung parenchyma (group B). Per group, BAL lymphocytes (%), CD4/CD8 ratio, CD103(+)CD4(+)/CD4(+) ratio and neutrophils (%) were compared with the extent of metabolic activity expressed as the maximum standardized uptake value (SUV(max)). Additionally, SUV(max) and BAL parameters per radiographic stage were analysed. Overall, the SUV(max) in the lung parenchyma correlated with neutrophils and SUV(max) of the mediastinum/hila correlated with the CD4/CD8 ratio. In both groups, a significant, negative correlation between the SUV(max) of the mediastinum/hila and the CD103(+)CD4(+)/CD4(+) ratio was found. In group B, the SUV(max) of the mediastinum/hila correlated with the CD4/CD8 ratio, while the SUV(max) in the lung parenchyma correlated with the CD103(+)CD4(+)/CD4(+) ratio and neutrophils. Significant differences were found in the SUV(max), CD4/CD8 ratio, CD103(+)CD4(+)/CD4(+) ratio and neutrophils between the radiographic stages. The SUV(max) of the lung parenchyma was positively related to the radiographic stage, while the SUV(max) of the mediastinum/hila and CD4/CD8 ratio were inversely related. (18)F-FDG PET correlates with the CD4/CD8 ratio and neutrophils, suggesting that (18)F-FDG PET represents this specific cell profile in BAL. High SUV(max) values of the lung parenchyma may therefore correlate with more severe parenchymal involvement, particularly when accompanied by a low SUV(max) of the mediastinum/hila.

Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis

BackgroundNo effective treatment for acute lung injury and fibrosis currently exists. Aim of this study was to investigate the time-dependent effect of bone marrow-derived mesenchymal stem cells (BMDMSCs) on bleomycin (BLM)-induced acute lung injury and fibrosis and nitric oxide metabolites and inflammatory cytokine production.MethodsBMDMSCs were transferred 4 days after BLM inhalation. Wet/dry ratio, bronchoalveolar lavage cell profiles, histologic changes and deposition of collagen were analyzed.ResultsNitrite, nitrate and cytokines were measured weekly through day 28. At day 7, the wet/dry ratio, neutrophilic inflammation, and amount of collagen were elevated in BLM-treated rats compared to sham rats (p = 0.05-0.002). Levels nitrite, nitrate, IL-1β, IL-6, TNF-α, TGF-β and VEGF were also higher at day 7 (p < 0.05). Degree of lymphocyte and macrophage infiltration increased steadily over time. BMDMSC transfer significantly reduced the BLM-induced increase in wet/dry ratio, degree of neutrophilic infiltration, collagen deposition, and levels of the cytokines, nitrite, and nitrate to those in sham-treated rats (p < 0.05). Fluorescence in situ hybridization localized the engrafted cells to areas of lung injury.ConclusionSystemic transfer of BMDMSCs effectively reduced the BLM-induced lung injury and fibrosis through the down-regulation of nitric oxide metabolites, and proinflammatory and angiogenic cytokines.

High-resolution computed tomography patterns and immunopathogenetic findings in drug-induced pneumonitis

We tried to determine whether high-resolution computed tomography (HRCT) patterns correlate with the immunopathogenetic findings and whether they could provide helpful information for predicting the outcomes in non-neoplastic drug-induced pneumonitis. The HRCT images were classified as most suggestive of pneumonitis, diffuse alveolar damage (DAD), non-specific interstitial pneumonia, organizing pneumonia (OP), hypersensitivity pneumonitis, and acute eosinophilic pneumonia (AEP) in 34 patients with non-neoplastic drug-induced pneumonitis. The patients were analyzed for the bronchoalveolar lavage (BAL) cell findings and for the circulating levels of interferon-inducible protein 10 (IP-10) and macrophage-derived chemokine (MDC), which were measured by an enzyme-linked immunosorbent assay. The cumulative dose of corticosteroids received by the patients and the day when they required supplemental oxygen were calculated as outcome markers. There were no differences in the circulating chemokine levels and the BAL cell profiles except for the eosinophil percentages among the HRCT patterns. Most of the cases with pulmonary eosinophilia belonged to the OP and AEP groups, and the circulating MDC levels correlated with BAL eosinophil percentages. We could not find any relationship between the BAL cell profiles or the chemokine levels and the outcome markers. In contrast, the HRCT patterns rather predicted the outcomes because larger cumulative dose of steroids and longer oxygen supply were required for the patients in the DAD and OP groups. In contrast, all patients with AEP recovered without steroid administration. The present study suggests that HRCT does not predict cellular pathophysiology but it may predict the corticosteroid use in non-neoplastic drug-induced pneumonitis.

Comparison of atopic and nonatopic children with chronic cough: Bronchoalveolar lavage cell profile

Chronic cough is a common complaint in children and its relationship with asthma is controversial. The aim of the present study was to determine the pattern of airway inflammation in atopic and nonatopic children with chronic cough, and to investigate whether atopy is a predictive factor for eosinophilic inflammation in cough. Bronchoalveolar lavage (BAL; three aliquots of 1 ml/kg saline) was performed in the right middle lobe of 24 (11 atopic and 13 nonatopic) children with persistent cough (8 females, 16 males), mean age 4.7 years (range: 1–11). Atopy was defined as an elevated total serum IgE or a positive RAST test. Both atopic and nonatopic children with persistent cough had an increase in total cells/ml in BAL (atopic: median 39 × 104, range: 20–123; nonatopic: median 22 × 104, range: 17–132) compared to nonatopic controls (median 11 × 104, range 9–30). The increases were mainly in neutrophils (atopic: median 17%, range 2.5–88.5%; nonatopic: median 6%, range 1.0–55.0%) compared to controls (median 1.55%, range 0.5–7.0%; atopics vs. controls, P < 0.005). There were no significant increases in eosinophils, lymphocytes, epithelial cells, or mast cells. Eosinophils were elevated in only 5/11 atopic and none of the nonatopic children. The increased percentage of neutrophils in the BAL fluid of atopic and nonatopic children with persistent cough could be due to an underlying inflammatory process driving the cough, or even conceivably, due to the effect of coughing itself. In this highly selected series, the absence of eosinophilic inflammation in the majority suggests that most would be predicted not to respond to inhaled corticosteroid therapy. This study underscores the need to be cautious about treating coughing children with inhaled corticosteroids, even in the context of a tertiary referral practice. Pediatr Pulmonol. 2007;42:857–863. © 2007 Wiley‐Liss, Inc.

CHARACTERIZATION OF LOWER RESPIRATORY TRACT INFLAMMATION AND ITS RELATIONSHIP WITH COMPUTERIZED TOMOGRAPHIC (CT) FINDINGS IN BRONCHIAL ASTHMA

PURPOSE: T cells in the airways are considered to play a key role in orchestrating the inflammatory response of asthma. Though radiological and broncho-alveolar lavage (BAL) changes have been reported in asthma, there are not many studies that have investigated the relationship of BAL cell profile with changes on CT scan (which may suggest airway remodeling).

TGF-β and Smad3 Signaling Link Inflammation to Chronic Fibrogenesis

Transient adenovirus-mediated gene transfer of IL-1beta (AdIL-1beta), a proinflammatory cytokine, induces marked inflammation and severe and progressive fibrosis in rat lungs. This is associated with an increase in TGF-beta1 concentration in bronchoalveolar lavage (BAL) fluid. TGF-beta1 is a key cytokine in the process of fibrogenesis, using intracellular signaling pathways involving Smad2 and Smad3. In this study we investigate whether inflammation induced by IL-1beta is able to independently induce lung fibrosis in mice deficient in the Smad3 gene. Seven days after AdIL-1beta administration, similar levels of IL-1beta transgene are seen in BAL in both wild-type (WT) and knockout (KO) mice, and BAL cell profiles demonstrated a similar marked neutrophilic inflammation. Phospho-Smad2 staining was positive in areas of inflammation in both WT and KO mice at day 7. By day 35 after transient IL-1beta expression, WT mice showed marked fibrosis in peribronchial areas, quantified by picrosirius red staining and morphometry. However, there was no evidence of fibrosis or collagen accumulation in IL-1beta-treated KO mice, and peribronchial areas were not different from KO mice treated with the control adenovector. TGF-beta1 and phospho-Smad2 were strongly positive at day 35 in fibrotic areas observed in WT mice, but no such staining was detectable in KO mice. The IL-1beta-induced chronic fibrotic response in mouse lungs is dependent on Smad3. KO and WT animals demonstrated a similar inflammatory response to overexpression of IL-1beta indicating that inflammation must link to the Smad3 pathway, likely through TGF-beta, to induce progressive fibrosis.

Bronchial hyperresponsiveness and the bronchiolitis obliterans syndrome after lung transplantation

Because bronchial hyperresponsiveness has been linked to the bronchiolitis obliterans syndrome (BOS), we determined PD 20 methacholine (PD 20(M)), PD 15 hypertonic saline (PD 15(HS)) and their dose-response slopes (DRS M and DRS HS) in 8 single and 18 double lung transplant recipients within 1 year of lung transplantation and examined the relationship to bronchoalveolar lavage cell profiles and subsequent development of BOS. Twenty-two patients (81%) had a positive methacholine and 6 (25%) a positive hypertonic saline challenge. A positive PD 15(HS) was associated with an increased risk for BOS at 2 years (odds ratio 12.6, 95% confidence interval 1.3–123.5, p < 0.05), and time to BOS was significantly and negatively related to DRS HS ( r = −0.5, p < 0.05) — that is, the greater the response, the shorter the time to BOS. Interestingly, DRS HS correlated positively with recipient:donor total lung capacity ratio ( r = 0.5, p < 0.05), but there was no relationship between either challenge result and airway inflammation. Methacholine hyperresponsiveness is common after lung transplantation but is not prognostic, whereas response to hypertonic saline may reflect recipient:donor size matching and provide useful information regarding the potential for BOS development.

Interstitial lung disease in polymyositis and dermatomyositis: Clinical course and response to treatment

Objectives: To assess the prevalence, clinical characteristics, and treatment options of patients with interstitial lung disease (ILD) in polymyositis and dermatomyositis (PM/DM). Patients and Methods: Sixty-three consecutive patients with PM/DM underwent standardized screening. Patients with ILD were monitored prospectively, and graded immunosuppression was administered according to the rate of clinical progression. Results: ILD was diagnosed in 20 of 63 patients (32%). Generally, the clinical and serologic findings of the anti-Jo1 syndrome were present. Follow-up evaluation disclosed either a progressive or a nonprogressive course. The 10 patients with progressive ILD were distinguished from the nonprogressive group by extensive ground-glass opacities on high-resolution computed tomography (HRCT) and by bronchoalveolar lavage (BAL) neutrophilia. Intravenous pulse cyclophosphamide prevented further progression in all 10 patients and led to some functional improvement. In the 10 patients without rapidly progressive lung disease, immunosuppression of moderate intensity stabilized pulmonary findings during a median 35 months of follow-up. Conclusions: The prevalence of ILD in our patients with PM/DM was 32%; this emphasizes the need for pulmonary screening in all PM/DM patients. Progressive disease, featuring ground-glass opacities on HRCT and an inflammatory BAL cell profile, is amenable to intensive immunosuppression. Conversely, patients who do not have these HRCT and BAL features appear to have a low risk of pulmonary deterioration. Relevance: Because the treatment for ILD seems to depend on the rate of clinical progression, future therapeutic trials of lung disease in PM/DM should stratify patients accordingly. Semin Arthritis Rheum 32:273-284. Copyright 2003, Elsevier Inc. All rights reserved.

Clinical utility of bronchoalveolar lavage cell phenotype analyses in the postoperative monitoring of lung transplant recipients.

Bronchoalveolar lavage (BAL) fluid provides a crucial tool for investigation of the cellular component of the deep lung spaces and hence to approach the alloreactive response following lung transplantation. This study investigated whether BAL cell profiles can assist for the diagnosis of certain postoperative complications. We conducted a retrospective analysis of both transbronchial biopsy and bronchoalveolar lavage materials in a series of 26 consecutive lung transplant recipients (LTR) in relationship with their clinical status at the time of the procedure. BAL fluid was subjected to cell morphology as well as flow cytometric phenotypic analyses. The samples were labeled as follows: normal transplant in clinically stable and healthy recipients, n=58; acute rejection (AR), n=58; infection (INF), n=31; and obliterative bronchiolitis/bronchiolitis obliterans syndrome (OB/BOS) n=27. Total BAL cell counts were the highest in INF. Lymphocytic alveolitis was suggestive of both acute allograft rejection and CMV viral infection, with a combined significant increased HLA-DR positive cells in AR. Alveolar neutrophilia with an increased CD4/CD8 ratio was correlated with the diagnosis of OB. The neutrophil percentages, HLA-DR and CD57 positive cells were significantly higher when an infection was present. These findings suggest that BAL cell analysis could give complementary information of histological data and further insight into immunologic events after lung allograft. A longitudinal surveillance of BAL cell profiles in an individual patient may be suggestive for a preclinical state of posttransplant acute rejection, bacterial infection and obliterative bronchiolitis.

Inflammatory cells and cellular activation in the lower respiratory tract in Churg-Strauss syndrome

BACKGROUNDTo obtain insight into the mechanisms of tissue injury in lung disease due to Churg-Strauss syndrome (CSS), the bronchoalveolar lavage (BAL) cell profile and the levels in the BAL fluid...

Bronchoalveolar lavage cell profiles in Wegener's granulomatosis

Pulmonary involvement due to Wegener's granulomatosis (WG) can present radiologically either as diffuse infiltrates or as nodular and linear opacities. Clinical experience suggests that these radiological patterns are associated with different bronchoalveolar lavage (BAL) cell profiles, but this has not been examined formally. We compared the BAL cell profile in eight WG patients with diffuse infiltrates on chest X-ray, indicative of highly active pneumonitis, with corresponding findings in 37 patients with nodular, linear and focal low-attenuation infiltrates on high-resolution computed tomography (HRCT) which reflected low-grade, mainly interstitial disease. A control group was composed of 11 patients with pulmonary sarcoidosis. Diffuse infiltrates occurred in association with high systemic disease activity and featured a neutrophilic BAL profile in the presence of generally normal BAL lymphocytes. HRCT findings suggestive mainly of interstitial disease were associated with either a lymphocytic BAL cell profile or a normal cell pattern. Patients with a lymphocytic cell profile generally had a preferential elevation of CD4 + cells in the BAL in the presence of a normal CD4 CD8 ratio in the blood. This was a common feature of WG and pulmonary sarcoidosis. In conclusion, highly active pneumonitis and pulmonary disease of low or moderate activity in WG are associated with disparate BAL cell profiles. It remains to be examined whether the preferential elevation of CD4 + cells in the latter condition reflects a common pathogenetic role of this subset of cells in WG and pulmonary sarcoidosis.

Bronchoalveolar cell profiles in children with asthma, infantile wheeze, chronic cough, or cystic fibrosis.

Differential cell counts of bronchoalveolar lavage (BAL) have been reported in normal children but few data on cellular profiles in bronchial diseases in childhood are available. We determined the BAL cell profiles of 72 children divided into 5 groups: asthma (n = 14), chronic cough (n = 12), infantile wheeze (n = 26), cystic fibrosis (n = 10), and control (n = 10). The highest total cell, eosinophil, and neutrophil counts were found in children with cystic fibrosis. The cell profile of children with chronic cough was similar to that of control children. Asthma and infantile wheeze were characterized by a high median ratio of eosinophils (3%) and neutrophils (12%), respectively. In both diseases, epithelial shedding was suggested by an elevated epithelial cell count, 13.5 and 12%, respectively. Lymphocyte subset analysis showed a higher proportion of CD8 cells (58 versus 40%) and therefore a lower CD4/CD8 ratio (0.266 versus 0. 455) in children with asthma compared with infantile wheezers (p = 0. 02). Irrespective of the presence or absence of radiological abnormalities, a proportion of neutrophils > 10%, was found in one-third of the children with asthma and in half of the infantile wheezers, and was related to symptom severity. We suggest that neutrophil-mediated inflammation, with or without bacterial infection, may contribute to symptoms of asthma in childhood. Chronic cough, however, is not associated with the cell profiles suggestive of asthma and in isolation should not be treated with prophylactic antiasthma drugs.

Bronchoalveolar lavage cell profile in methotrexate induced pneumonitis.

BACKGROUND: Pneumonitis is a rare but potentially life threatening side effect of methotrexate treatment for rheumatoid arthritis which needs to be distinguished from interstitial lung disease due to rheumatoid arthritis....

Bronchoalveolar lavage in extrinsic allergic alveolitis: effect of time elapsed since antigen exposure

The aim of the present study was to investigate whether bronchoalveolar lavage (BAL) cell profile and immunoglobulin levels from patients with extrinsic allergic alveolitis (EAA) were related to the time elapsed between last antigen exposure and BAL. For this purpose, an analysis was performed of BAL fluid (BALF) obtained from 59 nonsmoking EAA patients at various time-points after termination of antigen exposure and BAL. BALF early after antigen provocation (group 1: < 24 h) contained high absolute and relative numbers of lymphocytes, neutrophils, eosinophils and mast cells, and a low relative number of alveolar macrophages. When obtained after recent antigen exposure (group 2: 2-7 days), BALF showed high numbers of lymphocytes, plasma cells and mast cells, and high levels of immunoglobulins M, G and A (IgM, IgG and IgA). In BAL obtained one week or more after the final antigen exposure, (Group 3: 8-30 days; Group 4: 1-12 months) the distribution of all constituents showed a tendency to return to normal values, with the exception of the lymphocytes. These results demonstrate that BAL cell profile and immunoglobulin levels in EAA are highly dependent on the time-point at which the material is obtained in relation to the last exposure to the causative antigen.

Elevated Levels of Bronchoalveolar Lavage Vitronectin in Hypersensitivity Pneumonitis

Vitronectin is an adhesive glycoprotein that is present in plasma and the extracellular matrix. Hypersensitivity pneumonitis (HP) is characterized by pulmonary inflammation and damage to the extracellular matrix. Perhaps reflecting this, fibronectin has been found to be elevated in the lower respiratory tract of subjects with HP. Vitronectin, like fibronectin, binds to both extracellular matrix components and cells and may mediate tissue remodeling. Thus, it was investigated whether vitronectin might be increased in bronchoalveolar lavage (BAL) fluid of patients with HP. Vitronectin and, for comparison, fibronectin were measured in BAL fluid from 16 patients with HP and nine healthy control subjects by enzyme-linked immunosorbent assay. Vitronectin was significantly increased in the HP group (658.4 +/- 121.8 ng/ml) compared with the controls (58.4 +/- 11.1 ng/ml, p < 0.001) and was found to be positively correlated with fibronectin. Patients whose last antigenic exposure was 4 or fewer days before the BAL had statistically significantly higher BAL vitronectin and fibronectin than did patients whose last exposure was 5 or more days before the BAL. The serum vitronectin levels did not differ. There was no significant relationship between the lavage fluid vitronectin and fibronectin levels and the BAL cell profile in HP. This study confirms that vitronectin, like fibronectin, is a normal constituent of the lower respiratory tract, and demonstrates that vitronectin is elevated in the lower respiratory tract of patients with HP and may play a role in tissue remodeling and fibrosis in this disease.

Characteristics of Bronchoalveolar Leukocytes from the Lungs of Rats Inhaling 0.2–0.8 ppm OF Ozone

AbstractThe study was aimed at investigating the likely role of the bronchoalveolar leukocytes in the epithelial injury arising from exposure to ozone at low concentrations. Rats were exposed to 0.2–0.8 ppm of ozone for 7 hr/day for up to 4 days. At the selected time points the lungs were lavaged and the bronchoalveolar lavage cell profile was assessed by differential counting. Selected activities of the bronchoalveolar leukocytes, which could contribute to epithelial injury in vivo, were assessed in vitro, including (1) spontaneous and phorbol-stimulated release of superoxide anion, (2) proteolysis of fibronectin, and (3) ability to damage epithelial cells. Exposure to ozone at the highest concentrations caused inflammation in the bronchoalveolar region as shown by an increase in the proportion of neutrophils in the lavage. There was adaptation to the ozone-induced injury as shown by the fact that this inflammation was reduced as the time of exposure increased. No increases in any of the indicators of ab...