Immunoglobulins and cellular constituents of the BAL fluid of patients with sulfur mustard gas-induced pulmonary fibrosis.

STUDY OBJECTIVE: The acute heavy exposure to sulfur mustard gas can lead to pulmonary fibrosis (PF). This study was performed to determine the cellular and protein content of BAL fluid in 24 patients with sulfur mustard gas-induced PF. PATIENTS: Twenty-four veterans with sulfur mustard gas-induced PF and 18 nonexposed veterans serving as control subjects were enrolled into the study. MEASUREMENTS: Chest roentgenograms, pulmonary function tests (PFTs), tests for carbon monoxide diffusing capacity of the lung (DLCO), high-resolution CT scans of the chest, BAL via fiberoptic bronchoscopy, analyses of BAL fluids for cellular and protein constituents, and determinations of serum albumin and Ig levels were performed in all cases. A transbronchial lung biopsy was done in all patients following BAL. RESULTS: Neutrophilic alveolitis was the predominant feature. Neutrophils (p = 0.0001) and eosinophils (p = 0.0001) were the predominant cell types in the BAL fluid of patients with PF. There was a strong correlation between the BAL fluid neutrophil count (p = 0.76; p = 0.0003) or its percentage (p = 0.77; p = 0.0003) and the degree of fibrosis. Of the BAL fluid Ig levels, only the IgG level in the study group was significantly higher than the IgG level of the control group (p = 0.0001). Of the PFT physiologic parameters, only the percentage of DLCO showed a significant correlation with the degree of fibrosis (p = -0.76; p < 0.001). CONCLUSION: The cellular constituents of BAL fluid in patients with sulfur mustard gas-induced PF are very similar to the cellular constituents seen in patients with idiopathic PF, and this finding indicates the presence of an ongoing active alveolitis in PF.     

The effects of chronic bronchitis and chronic air-flow obstruction on lung cell populations recovered by bronchoalveolar lavage

Bronchoalveolar lavage is used to evaluate parenchymal inflammation in patients with diffuse lung disease. Normal values for lavage cell counts and proteins are derived primarily from young subjects who are free from lung disease; however, older patients who undergo bronchoalveolar lavage often have used cigarettes for long periods of time and have developed variable degrees of chronic bronchitis and/or chronic air-flow obstruction. Therefore, we evaluated the effects of cigarette use, chronic bronchitis, and chronic air-flow obstruction on lavage cell populations by performing bronchoalveolar lavage in 48 male patients who were undergoing diagnostic fiberoptic bronchoscopy. Sixteen patients (33%) had elevated percentages of neutrophils (greater than or equal to 10%) in lavage fluid. Fourteen of these (87.5%) had chronic cough and/or phlegm production, but only 9 (64.3%) met criteria for definite chronic bronchitis. Patients with moderate or severe air-flow obstruction, defined spirometrically, had significantly greater percentages of lavage neutrophils and lower percentages of macrophages than did patients with mild or no air-flow obstruction. The first lavage aliquot contained the greatest proportion of neutrophils and the smallest proportion of macrophages. The percentage of neutrophils declined and the percentage of macrophages increased in sequential aliquots. The data indicate that patients with chronic cough and/or phlegm production and chronic air-flow obstruction may have increased proportions of neutrophils in bronchoalveolar lavage fluid in the absence of diffuse parenchymal lung disease or infections. These variables must be taken into account when interpreting lavage cellular analyses.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo evaluation of bronchoalveolar lavage (BAL) fluid in atopic bronchial asthma, chronic bronchitis and sarcoidosis patients

The intensity of inflammatory response was evaluated in skin test on guinea pig using bronchoalveolar lavage (BAL) fluid obtained from patients with some diseases of the respiratory tract. The results of skin test were verified with activities of proteases in BAL fluid. The study was performed on 24 patients with atopic bronchial asthma, 21 with chronic bronchitis, 13 with sarcoidosis (II phase) and 18 control subjects. All patients were undergoing fiberoptic bronchoscopies and BAL fluid was obtained. The results of skin test on guinea pig using BAL fluid were correlated with the activities of acid and neutral proteases. The highest activity of proteases and intensity of skin reactions were noted in patients with atopic bronchial asthma and sarcoidosis. Authors suggest that the skin test on guinea pig with BAL fluid may be useful tool for total evaluation of inflammatory response in patients with atopic bronchial asthma, chronic bronchitis and sarcoidosis.     

Increased in CD8 T lymphocytes in the BAL fluid of patients with sulfur mustard gas-induced pulmonary fibrosis

OBJECTIVE: In an attempt to understand better the potential role of the T cell in the pathogenesis of pulmonary fibrosis (PF) due to sulfur mustard gas inhalation, this study was designed to analyze bronchoalveolar lavage (BAL) lymphocyte subsets and to determine the ratio of CD4 to CD8 lymphocytes in BAL fluid. SETTING: University hospital. PATIENTS: Twenty-one veterans with mustard gas-induced pulmonary fibrosis and 20 normal veterans as control group. INTERVENTION: Chest roentgenograms, pulmonary function tests (PFTs), tests for carbon monoxide diffusing capacity of the lung (DLCO), high-resolution CT scans of the chest, BAL via fiberoptic bronchoscopy, analyses of BAL fluids for cellular and Flow-cytometric analysis of the phenotype of bronchoalveolar cells were performed in all cases. A transbronchial lung biopsy was done in all patients following BAL. RESULTS: Neutrophilic alveolitis was the predominant feature. Neutrophils (P<0.0001) and eosinophils (P=0.0006) were the predominant cell types in the BAL fluid of patients with PF. CD8 lymphocytes expressed as percentage or absolute number were significantly higher in patients with PF than in healthy controls (22.96+/-7.48% vs. 14.16+/-7.73%, respectively; P=0.0006; and 2.28+/-0.84 vs. 1.10+/-0.55 x 10(3) cells/ml, respectively; P<0.0001). The CD4/CD8 ratio was significantly lower in patients with PF than in healthy controls (0.73+/-0.25 vs. 1.58+/-0.67; P<0.0001). Except for the percentage and the absolute number of the BAL fluid neutrophils (r=0.70, P=0.001: r=-0.62, P=0.005; respectively), no correlation was found between DLCO% and the other BAL cells. A significant negative correlation was observed between the percentage of DLCO and both the percentage and the absolute number of CD8 lymphocytes in BAL fluid in patients with PF (r=-0.81, P=0.0003; r=-0.61, P=0.006; respectively). A significant correlation was also seen between the percentage of DLCO and the CD4/CD8 ratio (r=-0.60, P=0.006) in our patients. CONCLUSION: CD8 T cells in BAL fluid were significantly elevated in patients with pulmonary fibrosis. Patients with higher grades of pulmonary fibrosis expressed as percentage of DLCO, revealed higher percentages and the absolute number of CD8 T cells and a lower CD4/CD8 ratio.     

Lactoferrin and secretory IgA in the bronchoalveolar lavage fluid from patients with a stable asthma.

We have measured lactoferrin and secretory IgA (sIgA) in the unconcentrated bronchoalveolar lavage fluid (BALF) from nonsmoking healthy volunteers (n = 10) and nonsmoking patients with stable asthma (n = 14). The median concentrations and the ranges of lactoferrin were controls, 0.13 mg/L (0.01-0.43 mg/L); asthma, 0.41 mg/L (0.07-7.51 mg/L). For sIgA the results were controls, 0.48 mg/L (0.12-1.47 mg/L); asthma, 1.29 mg/L (0.65-14.6 mg/L). The concentrations in the epithelial lining fluid (ELF) were calculated on the basis of urea in BALF and serum. SIgA and lactoferrin levels in the BALF and ELF from the patients with asthma were higher than in controls (Mann-Whitney U-test, p less than 0.03). Our results indicate that in patients with stable asthma the airway epithelial cells are activated, resulting in an enhanced secretion of lactoferrin and enhanced secretory transport of sIgA into the airway lumen.     

Increased MCP-1 and MIP-1beta in bronchoalveolar lavage fluid of chronic bronchitics.

CC-chemokines are chemotactic factors expressed in a wide range of cell types and tissues. The aim of this study was to evaluate the involvement of CC-chemokines in the airways inflammation of patients affected by chronic bronchitis. The study evaluated, with an immunoassay, the concentrations of monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage inflammatory protein-1beta (MIP-1beta), in the bronchoalveolar lavage fluid (BALF) of 12 smokers affected by chronic bronchitis and 14 smoking, 15 nonsmoking and six exsmoking healthy subjects. MCP-1 was significantly increased in patients with chronic bronchitis ((mean+/-SD) 10.75+/-4.04 pg x mL(-1)) and in the smoker control group (12.39+/-5.87 pg x mL(-1)) compared with healthy exsmokers: (7.12+/-1.60 pg x mL(-1), p=0.035 and p=0.045, respectively) and nonsmokers (6.41+/-3.87 pg x mL(-1), p=0.003 and p=0.006, respectively). MIP-1alpha concentrations were undetectable. A significant difference was observed in MIP-1-beta levels in BALF of chronic bronchitics (8.11+/-5.97 pg x mL(-1)) compared to smoker (3.57+/-2.90 pg x mL(-1), p=0.018), exsmoker (3.43+/-0.68 pg x mL(-1), p=0.025) and nonsmoker (3.39+/-3.73 pg x mL(-1), p=0.008) control groups. A negative correlation was observed between MIP-1beta levels and forced expiratory volume in one second values (p=-0.64, p=0.035) in chronic bronchitics. An increase of monocyte chemotactic protein-1 is related to smoking habit and seems consistent with a lung inflammatory reaction. On the contrary, an increase in macrophage inflammatory protein-1beta levels is restricted to smokers developing chronic obstructive pulmonary disease. These data suggest a role of CC-chemokines in the pathogenesis of chronic bronchitis.     

Lactoferrin and secretory IgA in the bronchoalveolar lavage fluid from patients with a stable asthma

We have measured lactoferrin and secretory IgA (sIgA) in the unconcentrated bronchoalveolar lavage fluid (BALF) from nonsmoking healthy volunteers (n=10) and nonsmoking patients with stable asthma (n=14). The median concentrations and the ranges of lactoferrin were controls, 0.13 mg/L (0.01–0.43 mg/L); asthma, 0.41 mg/L (0.07–7.51 mg/L). For sIgA the results were controls, 0.48 mg/L (0.12–1.47 mg/L); asthma, 1.29 mg/L (0.65–14.6 mg/L). The concentrations in the epithelial lining fluid (ELF) were calculated on the basis of urea in BALF and serum. SIgA and lactoferrin levels in the BALF and ELF from the patients with asthma were higher than in controls (Mann-Whitney U-test, p<0.03). Our results indicate that in patients with stable asthma the airway epithelial cells are activated, resulting in an enhanced secretion of lactoferrin and enhanced secretory transport of sIgA into the airway lumen.     

Increased exhaled nitric oxide in chronic bronchitis: comparison with asthma and COPD

STUDY OBJECTIVES: To test the hypothesis that exhaled nitric oxide (NO) is increased in patients with chronic bronchitis, and to compare the results with exhaled NO in patients with asthma and COPD. STUDY DESIGN: Cross-sectional survey. SETTING AND PATIENTS: Veterans Administration pulmonary function laboratory. Patients (n = 179) were recruited from 234 consecutive patients. Two nonsmoking control groups of similar age, with normal spirometry measurements and no lung disease, were used (18 patient control subjects and 20 volunteers). MEASUREMENTS: Participants completed questionnaires and spirometry testing. Exhaled NO was measured by chemiluminescence using a single-breath exhalation technique. RESULTS: Current smoking status was associated with reduced levels of exhaled NO (smokers, 9. 2 +/- 0.9 parts per billion [ppb]; never and ex-smokers, 14.3 +/- 0. 6 ppb; p < 0.0001). Current smokers (n = 57) were excluded from further analysis. Among nonsmokers, the levels of exhaled NO were significantly higher in patients with chronic bronchitis (17.0 +/- 1. 1 ppb; p = 0.035) and asthma (16.4 +/- 1.3 ppb; p = 0.05) but not in those with COPD (14.7 +/- 1.0 ppb; p = 0.17) when compared with either control group (patient control subjects, 11.1 +/- 1.6 ppb; outside control subjects, 11.5 +/- 1.5 ppb). The highest mean exhaled NO concentration occurred in patients with both chronic bronchitis and asthma (20.2 +/- 1.6 ppb; p = 0.005 vs control subjects). CONCLUSIONS: Exhaled NO is increased in patients with chronic bronchitis. The increase of exhaled NO in patients with chronic bronchitis was similar to that seen in patients with asthma. The highest mean exhaled NO occurred in patients with both chronic bronchitis and asthma. Exhaled NO was not increased in patients with COPD. Although chronic bronchitis and asthma have distinct histopathologic features, increased exhaled NO in patients with both diseases suggests common features of inflammation.     

Intraluminal airway inflammation in chronic bronchitis. Characterization and correlation with clinical parameters

In order to characterize intraluminal airway inflammation in subjects with chronic bronchitis, bronchoscopy and bronchoalveolar lavage were performed in 28 subjects with chronic bronchitis with fixed airway obstruction and, for comparison, 15 asymptomatic smokers and 25 normal nonsmoking volunteers. The chronic bronchitics had a cough productive of sputum on most days of the month for 6 months in the preceding 2 yr, had at least one exacerbation requiring medical intervention in each of the previous 2 yr, and had an FEV1 less than 76% of predicted without response to bronchodilator. During bronchoscopy the airways were assessed for visual evidence of inflammation by assigning them a score, the bronchitis index, that graded the airways according to the apparent severity of airway edema, erythema, friability, and secretions. Bronchoalveolar lavage was performed by sequentially instilling and retrieving with gentle suction five 20-ml aliquots of sterile normal saline into each of three separate lobes. The first aliquots, the "bronchial" sample, were pooled and processed separately from the final four aliquots, the "distal" sample. Cell counts, cell differentials, and albumin were determined for both the bronchial and distal samples. In order to correlate inflammation with clinical parameters, sputum was collected for 24 h prior to bronchoscopy; spirometry was performed just prior to bronchoscopy, and smoking histories were obtained. Visual inspection of the airways, as quantified by the bronchitis index, demonstrated significantly more evidence for inflammation in the chronic bronchitics than in either the asymptomatic smokers or the normal subjects. The bronchial sample lavage fluids from the chronic bronchitics tended to contain more cells (6.1 +/- 2.2 x 10(6) cells) than the bronchial sample fluids from the asymptomatic smokers (3.6 +/- 0.6 x 10(6) cells) or normal subjects (3.7 +/- 0.5 x 10(6) cells). Furthermore, the chronic bronchitics had a higher percentage of neutrophils in their bronchial lavage fluid (35.8 +/- 5.6%) than did either the asymptomatic smokers (20.7 +/- 2.6%, p = 0.0001) or the normal subjects (10.3 +/- 5.6%). The distal sample lavage fluid also recovered more neutrophils from both the chronic bronchitics (15.0 +/- 4.2%, p = 0.0012) and asymptomatic smokers (5.7 +/- 1.3%, p = 0.002) than from the normal subjects (2.8 +/- 0.4%). The chronic bronchitics were divided into two groups: those with low (less than 20%) and those with high (greater than 20%) bronchial sample neutrophils. Those with higher bronchial sample neutrophils had significantly more sputum production and lower FEV1, FEV1/FVC, and FEF25-75 than did the subjects with lower bronchial sample neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)     

Assessment of airways inflammation utilizing bronchoalveolar lavage

Pathologic correlations and examination of expectorated sputum have suggested that chronic bronchitis is an inflammatory disorder of the airways. Bronchoscopy and bronchoalveolar lavage provide a means for sampling airway epithelial lining fluid. Application of bronchoscopy and bronchoalveolar lavage to a group of patients with chronic bronchitis confirms the association of airways inflammation and chronic bronchitis.     

Serum IgA and secretory IgA levels in bronchial lavages from patients with a variety of respiratory diseases.

The secretory immunoglobulin A (IgA) system plays an important role in the protection of epithelial surfaces. The aim of this study was to evaluate whether the measurement of the primary airway Ig (sIgA) concentration in bronchial washings is clinically useful in patients with airway epithelial injury or inflammation. We measured serum IgA levels and sIgA concentrations in the bronchial lavages of patients with chronic bronchitis (n = 10), bronchiectasis (n = 15), lung cancer (n = 15) and in healthy control subjects (n = 10). Absolute sIgA levels of bronchial lavage fluids in the chronic bronchitis, bronchiectasis and lung cancer groups were higher than the controls, but there was no significant difference between the groups. sIgA/ml recovered bronchial fluid ratios were similar in the all groups. Standardisation of samples by means of albumin concentration ratios (sIgA/alb) showed that the bronchial lavages of the patients with lung cancer, chronic bronchitis and bronchiectasis were generally similar and demonstrated a significantly decreased sIgA/alb ratio compared to that of control subjects (p = 0.001, p < 0.05 and p < 0.05). sIgA/alb ratios in bronchial lavages recovered from involved lung of the patients with lung cancer and bronchiectasis were lower as compared to uninvolved lung (p < 0.001 and p < 0.05). There was no significant difference in serum IgA levels between all groups. As a result, although our findings seem partly to confirm the hypothesis that local bronchial IgA secretion is impaired in areas of bronchial epithelial injury or inflammation, we thought that sIgA would be useless as a marker of respiratory epithelial injury or inflammation in patients with chronic bronchitis, bronchiectasis and lung cancer.     

Adult bronchiolitis. Evaluation by bronchoalveolar lavage and response to prednisone therapy

Four adult patients with biopsy-proven bronchiolitis were identified and prospectively evaluated. Each patient presented with the rapid onset (weeks to months) of severe respiratory disease that was clinically distinct from asthma, chronic bronchitis, bronchiectasis, cystic fibrosis, and emphysema. Bronchiolitis patients were evaluated by pulmonary function testing and bronchoalveolar lavage (BAL) before and after two months of treatment with 1 mg/kg/day of prednisone. Initial BAL results of bronchiolitis patients were compared to those of cigarette smokers with chronic bronchitis (n = 4), asymptomatic cigarette smokers (n = 5), and normal nonsmoking volunteers (n = 5). Neutrophils comprised 53 +/- 13 percent of the cells recovered by BAL in bronchiolitis patients but only 3 +/- 2 percent of the cells in chronic bronchitis patients, 1.5 +/- 0.6 percent of the cells in asymptomatic smokers, and 0.3 +/- 0.3 percent of the cells in normal volunteers (p less than 0.01, all comparisons). Moreover, prednisone produced a striking decrease in lower respiratory tract neutrophils (53 +/- 13 percent to 8 +/- 3 percent, p less than 0.05) in all bronchiolitis patients while lung function either improved (two patients) or remained unchanged (two patients). These findings suggest a central role for the neutrophil in bronchiolitis and argue that BAL may be clinically useful in the diagnosis and management of these patients.     

BAL Fluid 8-Isoprostane Concentrations in Eosinophilic Bronchitis and Asthma

Background. Oxidative stress has an important role in the pathophysiology of asthma. But oxidative stress of airway has not been assessed in patients with nonasthmatic eosinophilic bronchitis (EB). 8-epi-prostaglandin F2alpha (8-isoprostane) is a biomarker of oxidative stress. Objectives. We sought to determine whether oxidative stress (measured by 8-isoprostane) occurs in EB and whether 8-isoprostane is associated with airway function in EB and asthma. Methods. We measured 8-isoprostane concentrations in the bronchoalveolar lavage (BAL) fluid from 11 subjects with EB, 10 subjects with asthma, and 9 healthy control subjects. 8-isoprostane was measured by enzyme immunoassays. Results. We found that BAL fluid 8-isoprostane concentrations were raised both in EB and asthma. The median concentrations of 8-isoprostane in BAL fluid were significantly higher in subjects with asthma (12.78 pg/mL) when compared with EB (8.34 pg/mL) and healthy control subjects (5.07 pg/mL). Conclusions. Our study shows that oxidative stress is increased significantly in asthmatic subjects and the degree of oxidative stress in EB subjects is milder than that in asthma, as reflected by 8-isoprostane concentrations in the BAL fluid. The difference in airway function observed in subjects with EB and asthma could be associated with different elevation in 8-isoprostane concentration in the airways.     

Effect of filtration and concentration on the composition of bronchoalveolar lavage fluid

The effects of filtration and concentration on the cellular and protein composition of bronchoalveolar lavage fluids were examined in ten normal subjects and 11 patients with asthma. Filtration of lavage fluid preferentially removed bronchial epithelial cells, resulting in a relative increase in the proportion of alveolar macrophages. Concentration of the lavage fluid results in a significant loss of proteins, with a greater loss of large molecular weight proteins. A similar loss was not observed when diluted sera form the same subjects were concentrated in the same manner. Our results suggest that when studying the cellular composition of bronchoalveolar lavage fluid, the aspirated fluid should not be filtered through cotton gauze if changes in the bronchial epithelium may be of importance because it will remove a significant proportion of these cells. Proteins in lavage fluids should be quantitated in unconcentrated lavage fluid whenever possible.     

Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease

To determine whether patients with fixed airflow obstruction have distinct pathologic and functional characteristics depending on a history of either asthma or chronic obstructive pulmonary disease (COPD), we characterized 46 consecutive outpatients presenting with fixed airflow obstruction by clinical history, pulmonary function tests, exhaled nitric oxide, sputum analysis, bronchoalveolar lavage, bronchial biopsy, and high-resolution computed tomography chest scans. Subjects with a history of COPD (n = 27) and subjects with a history of asthma (n = 19) had a similar degree of fixed airflow obstruction (FEV1: 56 +/- 2 versus 56 +/- 3% predicted) and airway hyperresponsiveness (PC20FEV1: 2.81 [3.1] versus 1.17 [3.3]). Subjects with a history of asthma had significantly more eosinophils in peripheral blood, sputum, bronchoalveolar lavage, and airway mucosa; fewer neutrophils in sputum and bronchoalveolar lavage fluid; a higher CD4+/CD8+ ratio of T cells infiltrating the airway mucosa; and a thicker reticular layer of the epithelial basement membrane. They also had significantly lower residual volume, higher diffusing capacity, higher exhaled nitric oxide, lower high-resolution computed tomography scan emphysema score, and greater reversibility to bronchodilator and steroids. In conclusion, despite similar fixed airflow obstruction, subjects with a history of asthma have distinct characteristics compared with subjects with a history of COPD and should be properly identified and treated.     

Angiotensin-converting enzyme in serum and in bronchoalveolar lavage in sarcoidosis

Angiotensin-converting enzyme (ACE) determinations were made in serum and in bronchoalveolar lavage fluid in 20 controls and in 28 patients with sarcoidosis. Serum ACE was significantly higher in patients with active sarcoidosis (54.3 +/- 19.0 SD nmol/ml/ min; n = 24) compared to controls (25.7 +/- 8.2; n = 20) or to patients with inactive sarcoidosis (23.6 +/- 7.3; n = 4). In contrast, ACE in bronchoalveolar lavage fluid was similar in nonsmoking controls (16.4 +/- 7.3 nmol/ml/min/macrophage; n = 8), smoking controls (10.4 +/- 11.9; n = 7); nonsmoking active sarcoidosis patients (16.7 +/- 14.6; n = 10), smoking sarcoidosis patients (17.9 +/- 8.4; n = 6) and inactive sarcoidosis patients (14.5 +/- 8.2; n = 3). Since ACE has been demonstrated by immunofluorescence in mononuclear phagocytes in granulomas, the authors speculate that macrophages recovered by alveolar lavage are not activated and do not reflect sarcoid alveolitis at the tissue level.     

Chemokine concentrations and mast cell chemotactic activity in BAL fluid in patients with eosinophilic bronchitis and asthma, and in normal control subjects

BACKGROUND: Asthma and eosinophilic bronchitis share many immunopathologic features including increased numbers of eosinophils and mast cells in the superficial airway. The mast cell chemotactic activity of airway secretions has not been assessed in patients with eosinophilic bronchitis. OBJECTIVES: To investigate the concentration of chemokines in bronchial wash samples and BAL fluid, and the mast cell chemotactic activity in BAL fluid from subjects with asthma and eosinophilic bronchitis, and from healthy control subjects. METHODS: We measured the concentrations of CCL11, CXCL8, and CXCL10 in bronchial wash samples and BAL fluid from 14 subjects with eosinophilic bronchitis, 14 subjects with asthma, and 15 healthy control subjects. Mast cell chemotaxis to BAL fluid from these subjects was examined using the human mast cell line HMC-1. RESULTS: The bronchial wash sample and BAL fluid concentrations of CXCL10 and CXCL8 was increased in subjects with eosinophilic bronchitis compared to those in subjects with asthma and healthy control subjects (p < 0.05). The CCL11 concentration was below the limit of detection in most subjects. BAL fluid from subjects with eosinophilic bronchitis was chemotactic for mast cells (1.4-fold migration compared to a control, 95% confidence interval, 1.1 to 1.9; p = 0.04) and was inhibited by blocking CXCR1 (45% inhibition; p = 0.002), CXCR3 (38% inhibition; p = 0.034), or both (65% inhibition; p = 0.01). BAL fluid from the subjects with asthma and healthy control subjects was not chemotactic for mast cells. Mast cell migration to BAL fluid was correlated with the concentration of CXCL8 (r = 0.42; p = 0.031) and CXCL10 (r = 0.52; p = 0.007). CONCLUSION: In subjects with eosinophilic bronchitis, CXCL8 and CXCL10 concentrations were elevated in airway secretions. These chemokines may play a key role in mast cell recruitment to the superficial airway in this condition.     

Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype

Rationale: Obesity is associated with increased prevalence and severity of asthma. Adipose tissue macrophages can contribute to the systemic proinflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese patients with asthma. Objectives: We hypothesized that leptin levels would be increased in the bronchoalveolar lavage fluid from overweight/obese subjects and, furthermore, that leptin would alter the response of alveolar macrophages to bacterial LPS. Methods: Forty-two subjects with asthma and 46 healthy control subjects underwent research bronchoscopy. Bronchoalveolar lavage fluid from 66 was analyzed for the level of cellular inflammation, cytokines, and soluble leptin. Cultured primary macrophages from 22 subjects were exposed to LPS, leptin, or leptin plus LPS. Cytokines were measured in the supernatants. Measurements and Main Results: Leptin levels were increased in overweight/obese subjects, regardless of asthma status (P = 0.013), but were significantly higher in overweight/obese subjects with asthma. Observed levels of tumor necrosis factor-α were highest in overweight/obese subjects with asthma. Ex vivo studies of primary alveolar macrophages indicated that the response to LPS was most robust in alveolar macrophages from overweight/obese subjects with asthma and that preexposure to high-dose leptin enhanced the proinflammatory response. Leptin alone was sufficient to induce production of proinflammatory cytokines from macrophages derived from overweight/obese subjects with asthma. Conclusions: Ex vivo studies indicate that alveolar macrophages derived from overweight/obese subjects with asthma are uniquely sensitive to leptin. This macrophage phenotype, in the context of higher levels of soluble leptin, may contribute to the pathogenesis of airway disease associated with obesity.     

曹梦园)高迁移率族蛋白B1在香烟暴露大鼠模型中的表达

目的 探讨高迁移率族蛋白B1(HMGB1)在香烟诱导的慢性支气管炎大鼠模型中的表达及作用.方法 雄性SD大鼠随机分为正常对照组、吸烟模型组,每组14只.采用烟熏法建立慢性支气管炎大鼠模型.光镜下观察支气管肺组织病理形态学改变,分析支气管肺泡灌洗液(BALF)细胞计数和分类,用ELISA 法检测大鼠血清中HMGB1的浓度,免疫组化法检测HMGB1在肺组织的表达.结果 模型组大鼠肺组织的病理形态改变与人类慢性支气管的特点相一致.BALF中模型组细胞总数、单核巨噬细胞及中性粒细胞百分比与健康对照组比较,差异有显著性(P<0.05).与对照组相比,模型组大鼠血清HMGB1的含量显著升高(P<0.05).免疫组化染色可见HMGB1主要分布于支气管及肺泡上皮细胞,与对照组比较,模型组大鼠肺组织HMGB1的表达强度明显增强(P<0.05).结论 吸烟是慢性支气管炎的一个重要危险因素,HMGB1可能在慢性支气管炎的发病中起到一定的作用.     

Bronchiolitis in adults. A reversible cause of airway obstruction associated with airway neutrophils and neutrophil products

In the past 4 yr, 16 adult patients were identified who had accelerated onset of a severe respiratory disorder (usually obstructive in nature) that was clinically distinct from the more commonly encountered chronic obstructive disorders (e.g., chronic bronchitis, emphysema, asthma, bronchiectasis, cystic fibrosis, and alpha 1-antitrypsin deficiency). These patients, termed patients with "bronchiolitis," underwent pulmonary function testing, bronchoscopy with bronchoalveolar lavage (BAL), and open lung biopsy. Although lung biopsy findings varied somewhat among the patients, each biopsy contained a prominent component of bronchiolitis. Pulmonary function testing and BAL were also repeated after 3 months of treatment with oral prednisone (1 mg/kg/day). Initial BAL neutrophil percentages were significantly higher in the bronchiolitis group (54 +/- 10%) than in smokers with chronic bronchitis (3.9 +/- 1.0%) or in normal nonsmoking volunteers (0.8 +/- 0.5%) (p less than 0.01, both comparisons). Eleven of 15 patients with bronchiolitis had significant improvement (greater than or equal to 15% increase in FEV1) in their lung function after prednisone treatment. Furthermore, this "responder" subgroup had a significant reduction in BAL neutrophil percentages after treatment with prednisone (46 +/- 15% to 6 +/- 3%, p less than 0.05). Finally, the neutrophil products collagenase and myeloperoxidase were detected in the BAL fluid of patients with bronchiolitis. These findings suggest a central role for the neutrophil in the pathogenesis of bronchiolitis and emphasize the utility of BAL in the identification of these patients.