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PubMed1984

Evaluation of the effect of BAL (2,3-dimercaptopropanol) on arsenite-induced teratogenesis in mice.

The effect of the chelating agent dimercaprol (BAL) on the embryotoxic and teratogenic effects of arsenite (As3+) was determined. BAL (sc, 30 mg/kg) was administered to pregnant CD-1 mice, either 8 and 4 hr prior to or 4 and 8 hr after a 12-mg/kg ip dose of arsenite; other females received a single sc injection of 60 mg/kg BAL concurrently with the arsenite. Treatments were given on Gestation Day 9 or 12 (copulation plug = Day 1). Controls received sc corn oil or ip H2O, with or without arsenite or BAL. Arsenite treatment caused gross and skeletal malformations and prenatal deaths, while controls were unaffected. When BAL was given prior to arsenite on Day 9, incidences of prenatal mortality and skeletal malformation were significantly diminished, and on Day 12, BAL protected against fetocidal effects of arsenite when given concurrently with the arsenite. No other significant protective effects against arsenite toxicity were seen due to BAL; however, concurrent BAL treatment on Day 9 appeared to result in decreased fetal mortality and a decline in skeletal malformations. BAL given following arsenite on Day 9 afforded no significant protection against the arsenic, although an apparent decrease in gross and skeletal malformations was suggestive of such an effect. According to these results, BAL is unlikely to have a practical beneficial effect on the arsenite exposed conceptus, because it must be administered prior to the teratogen (or perhaps simultaneously with it) to be effective.

Animals↗
PubMed2006

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.

Adult↗
PubMed2004

Effect of inhaled fluticasone propionate on BAL TGF-beta(1) and bFGF concentrations in clinically stable lung transplant recipients.

BACKGROUND: Inhaled fluticasone propionate (FP) therapy decreases inflammation and sub-basement membrane thickness in asthmatic airways. Bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTRs) involves progressive airway fibrosis and obliteration. Therefore, augmented immunosuppression may be of some benefit in treating BOS. In this study, we examined the effect of 3 months of treatment with high-dose inhaled FP on the concentrations of 2 fibrogenic factors, transforming growth factor (TGF)-beta(1) and beta fibrogenic growth factor (bFGF) in bronchoalveolar lavage (BAL) fluid from clinically stable LTRs. METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel group study with inhaled FP (750 microg, twice/day for 3 months) in 28 LTRs (15 FP and 13 placebo). We recruited 23 healthy controls. We performed spirometry, bronchoscopy, and bronchoalveolar lavage procedures before treatment and after 3 months of treatment. We used commercially available enzyme-linked immunosorbent assay kits to measure BAL fluid TGF-beta(1) and bFGF concentrations. RESULTS: In LTRs before treatment, BAL TGF-beta(1) concentrations (but not bFGF concentrations), total cell counts, and neutrophil percentage increased compared with controls (p < 0.05). We found no significant differences between FP and placebo groups at baseline measurements. After treatment, BAL TGF-beta(1) concentrations significantly increased in the FP group (p = 0.03), but we found no difference between FP and placebo groups; BAL bFGF concentrations increased during treatment in both groups compared with controls (p < 0.05), but not significantly within either patient group (p > 0.05). We found a reverse correlation between forced expiratory volume in 1 second (FEV(1)) and BAL TGF-beta(1) concentration in the FP group (r = -0.53, p = 0.04), and between FEV(1) and BAL TGF-beta(1) concentration in the placebo group (r = -0.74, p = 0.004). Multivariable analysis indicated no significant independent effects of inhaled FP in either BAL TGF-beta(1) or bFGF concentrations. CONCLUSIONS: Bronchoalveolar fluid TGF-beta(1) concentrations increased in LTRs after transplantation and may correlate with the decrease in lung function. Inhaled FP added to conventional immunosuppression had no effect on TGF-beta(1) or bFGF production in BAL fluid.

Administration, Inhalation↗
PubMed2003

Interleukin-18 expression in BAL cells of sarcoidosis patients is decreased in vivo but protein secretion is not impaired in vitro.

Recently, increased expression of interleukin-18 (IL-18) has been shown in sarcoid airway epithelium. However, IL-18 expression has not been investigated extensively in bronchoalveolar lavage (BAL) cells in sarcoidosis yet. Expression of IL-18 and tumour necrosis factor-alpha (TNFalpha) mRNA in cells of the BAL of 23 patients with sarcoidosis and nine healthy volunteers was determined using semiquantitative RT-PCR. IL-18 protein in BAL cells was investigated by immunocytochemistry (ICC). IL-18 protein levels in BAL cell culture supernatants from patients and controls with and without LPS stimulation were measured by enzyme-linked immuno-sorbent assay. BAL cells from patients were stimulated with either IL-10 or IL-13 and IL-18 protein levels were determined. IL-18 mRNA expression was significantly decreased in BAL cells of patients compared to control subjects (1.62 +/- 0.27 vs. 4.29 +/- 0.77, P < 0.05). TNFalpha mRNA expression was significantly increased in BAL cells of patients in comparison to control subjects (0.63 +/- 0.09 vs. 0.11 +/- 0.08, P < 0.05). ICC showed less positive alveolar macrophages in sarcoidosis patients than in control subjects (26 vs. 53%). IL-18 protein levels did not differ significantly between both groups. Stimulation with IL-10 significantly reduced IL-18 protein concentration in sarcoidosis patients. Our results suggest that BAL cells may not be the main source of IL-18 production in sarcoidosis in vivo. Since IL-18 production of BAL cells was not impaired in culture antiinflammatory cytokines might contribute to decreased IL-18 expression in vivo.

Adult↗
PubMed2007

Small airways dysfunction and neutrophilic inflammation in bronchial biopsies and BAL in COPD.

BACKGROUND: The single-breath N(2) test (sbN(2)-test) is closely related to small airways pathology in resected lung specimens of smokers. We investigated whether uneven ventilation and airway closure are associated with specific markers of airway inflammation as obtained by bronchial biopsies, BAL, and induced sputum in patients with manifest COPD. METHODS: Fifty-one patients with stable COPD not receiving corticosteroids were examined in a cross-sectional study (43 men; mean [SD] age, 63 +/- 8 years; exsmokers and smokers; median pack-years, 41 [interquartile range, 31 to 51 pack-years]). Postbronchodilator spirometry (FEV(1), 63 +/- 8% of predicted) and sbN(2)-test (slope of phase III [DeltaN(2)], closing capacity [CC]/total lung capacity [TLC] percentage of predicted) were performed. Inflammatory cell counts were assessed in bronchial biopsies, BAL (only in the first half of patients), and induced sputum. Neutrophil elastase (NE), secretory leukocyte proteinase inhibitor (SLPI), and interleukin-8 levels were determined in BAL fluid. RESULTS: DeltaN(2) increased with subepithelial neutrophil numbers in bronchial biopsies (rs = 0.337, p = 0.017) and with NE levels (rs = 0.443, p = 0.039), NE/neutrophil ratio (rs = 0.575, p = 0.005) and SLPI levels (rs = 0.484, p = 0.022) in BAL. CC/TLC was associated with BAL neutrophil numbers (rs = 0.448, p = 0.048). The sbN(2)-test was not associated with any other inflammatory cell type in BAL or biopsies, nor with inflammatory cell counts in sputum. Of importance, the correlations between DeltaN(2) and BAL NE/neutrophil ratio, and between CC/TLC and BAL neutrophil numbers remained significant when adjusting for FEV(1) percentage of predicted. CONCLUSIONS: The results of the sbN(2)-test are associated with neutrophilic inflammation in bronchial biopsies and BAL in patients with COPD. Our findings support a role of neutrophilic inflammation in the pathogenesis of small airways dysfunction in COPD.

Biopsy↗
PubMed1995

Kinetic retrieval of eosinophil cationic protein, hyaluronan, secretory IgA, albumin, and urea during BAL in healthy subjects.

Determination of absolute concentrations of various soluble components of the epithelial lining fluid (ELF) may be valuable to estimate inflammatory activities within the underlying lung tissue. Internal standards may then be used as markers of dilution of bronchoalveolar lavage (BAL). The aim of this study was to determine whether different dwell times would affect the relationship between the concentrations of any of the three potential internal standards (secretory IgA [SIgA], albumin, and urea), and the concentrations of two potential markers of inflammation (eosinophil cationic protein [ECP] and hyaluronan [HA]) in BAL. A series of aliquots of BAL fluid were aspirated every 60 s up to 8 min after a bolus instillation of saline solution in 20 healthy subjects (10 smokers). The BAL concentrations of albumin and urea increased with time, consistent with continuous diffusion from the body water pool, absorption of the BAL fluid, or both. The rate constant of diffusion was 1,000 times higher for urea than for albumin (3.38 x 10(-1) and 3.64 x 10(-4), respectively), reflecting the difference in molecular weights, and in agreement with the notion that albumin and urea appeared in BAL fluid by a rate-limited procedure related to osmotic transfer. Biexponential increases of SIgA were recorded, suggesting a two-compartmental origin of this compound, normally located to mucosal membranes and presumed to be dissolved in ELF. Time-dependent increases in BAL fluid of HA also were recorded, but on the other hand, the ECP concentrations tended to level off after an initial increase, suggesting that the bulk of ECP appeared in BAL by a nonosmotic mechanism. We conclude that the kinetics of these three internal standards in BAL fluid differs greatly from each other and from the kinetics of the two selected markers of inflammation. Consequently, internal standards for determination of absolute concentrations of markers of inflammation in ELF should be carefully selected because of the requirement of matched kinetics of the markers.

Adult↗
PubMed1998

Cytomegalovirus pneumonia in AIDS patients: value of cytomegalovirus culture from BAL fluid and correlation with lung disease.

OBJECTIVES: To verify the value of cytomegalovirus (CMV) cultures of BAL fluid vs postmortem lung histopathology in detecting CMV pneumonia, and to correlate the BAL viral dose with the number of CMV inclusion bodies (CMV-IB) in the lung tissue of AIDS patients. DESIGN: Retrospective analysis of 434 BALs and 40 autopsies involving 307 AIDS patients; clinical follow-up lasted 10 months. PATIENTS AND METHODS: The 40 patients who died within 20 days of undergoing BAL were divided on the basis of histopathologic findings into subjects with and without CMV-IB in the lung tissue. The relationship between the BAL viral dose and CMV lung infection was evaluated by counting the early antigen (CMV-EA) positive cells/200 microL of BAL and the number of CMV-IB/mm2 of lung tissue. RESULTS: The predictive value of BAL virus isolation for the diagnosis of CMV pneumonia was 61% for positive and 100% for negative results. The patients with the largest number of CMV-IB had CMV-EA counts from 2 to 840; in those with a moderate and small number, the CMV-EA counts were, respectively, from 11 to 700 and 2 to 300. Among the patients surviving up to 10 months after the BAL index sample, the frequency of recurrent extrapulmonary CMV abnormalities was 27% in those with positive and 7% in those with negative cultures. CONCLUSIONS: BAL CMV cultures from AIDS patients have a very high negative and relatively low positive predictive value for CMV pneumonia. The presence and replication of CMV in the lung may lead to systemic dissemination as suggested by the higher probability of CMV extrapulmonary diseases. Viral titers do not seem to be related to the degree of lung damage.

AIDS-Related Opportunistic Infections↗
PubMed2005

Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: a role for routine endotracheal aspirate cultures.

STUDY OBJECTIVES: To test whether routine quantitative cultures of endotracheal aspirates obtained before the onset of ventilator-associated pneumonia (VAP) could help to predict the causative microorganisms and to select early appropriate antimicrobial therapy before obtaining BAL culture results. DESIGN: Prospective observational study. SETTING: French medical ICU. PATIENTS: A total of 299 patients received mechanical ventilation for at least 48 h. INTERVENTIONS: Endotracheal aspiration (EA) was performed twice weekly in all mechanically ventilated patients. A diagnosis of VAP was made by BAL culture. Only the EA performed just before the suspicion of VAP (EA-pre) were evaluated. This strategy (ie, the EA-pre-based strategy) was compared with an antibiotic therapy that would have been prescribed if the recommendations of both the American Thoracic Society (ATS) and Trouillet et al (Am J Respir Crit Care Med 1998; 157:531-539) had been applied. MEASUREMENTS AND RESULTS: VAP was diagnosed (by BAL culture) in 41 of the 75 patients in whom BAL was performed. Among the 41 BAL specimens that were positive for VAP, EA-pre had identified the same microorganisms (with the same antibiotic resistance patterns) in 34 cases (83%). In one case, EA-pre was not available at the time BAL was performed (a case of early-onset VAP), but the empiric antibiotic therapy was adequate. While EA-pre did not give the same results as the BAL culture, the antibiotic therapy based on the results of the EA-pre was adequate in four other cases. Finally, antibiotic therapy was delayed in only two cases. Antibiotic treatment was therefore adequate in 38 of the 40 assessable cases (95%). If the Trouillet-based strategy had been used, the antibiotic treatment would have been adequate in 34 of the 41 cases (83%; p = 0.15 [vs EA-pre strategy]). Based on the ATS classification, the antibiotic treatment would have been adequately prescribed in only 28 of the 41 cases (68%; p = 0.005 [vs EA-pre strategy]). CONCLUSIONS: Routine EA performed twice a week makes it possible to prescribe adequate antibiotic therapy (while waiting for BAL culture results) in 95% of the patients in whom a VAP is ultimately diagnosed by BAL culture.

Adult↗
PubMed1989

Elevated BAL fluid histamine levels and parenchymal pulmonary disease in rheumatoid arthritis.

To determine the amount of histamine in BAL fluid in subjects with RA and to ascertain if elevated histamine levels were associated with parameters of active pulmonary disease, we measured BAL fluid histamine levels in 31 subjects with RA and 36 normal subjects. The subjects with RA had a significantly greater mean BAL histamine level than the normal subjects, (313 +/- 154 pg/ml vs 18 +/- 8 pg/ml; p less than 0.05). When the subjects with RA were divided into three groups based on chest radiograms (1 = normal; 2 = pleural disease only; 3 = interstitial or nodular disease), we found that subjects in group 3 had significantly lower values for TLC and D. Subjects in group 3 also had higher percentages of BAL neutrophils and eosinophils and higher BAL histamine levels (group 1, 115 +/- 52 pg/ml; group 2, 30 +/- 30 pg/ml; and group 3, 1,182 +/- 709 pg of histamine per milliliter). Moreover, BAL histamine levels were negatively correlated with TLC (r = -0.46; p = 0.01) and FVC (r = -0.45; p = 0.01) and positively correlated with BAL neutrophils (r = 0.6; p = 0.0003) and BAL eosinophils (r = 0.89; p = 0.0001). These data suggest that the BAL histamine level may be a useful marker to determine the activity of pulmonary disease in RA.

Arthritis, Rheumatoid↗
PubMed1999

Eosinophilic alveolitis in BAL after lung transplantation.

Lung transplantation has become a therapeutic option for patients with end stage lung disease. However, outcome after transplantation is complicated by episodes of rejection and infections. Bronchoalveolar lavage is a valuable tool in monitoring patients after transplantation, since it allows the detection of pathogens. A marker specifically indicating rejection from changes in BAL fluid has not been found yet. Especially changes in differential cell count, like lymphocytosis or an increase in polymorphnuclear granulocytes, are unspecific. The role of high eosinophil levels in BAL has not been elucidated yet. We analyzed 25 BAL samples and clinical data of 4 patients who underwent lung transplantation and presented with recurrent episodes of eosinophilic alveolitis in BAL. All patients demonstrated a deterioration of clinical condition, lung function, and blood gas analysis during times of eosinophilia in BAL, compared to previous examinations. In all cases, eosinophilia in BAL was accompanied by rejection. All patients were finally treated with high doses of steroids, resulting in improvement of all parameters. Eosinophilia was not associated with significant changes in the IL-5 concentration in BAL or the pattern of IL-5 expression in BAL cells. In conclusion, eosinophilic alveolitis may indicate acute rejection in patients after lung transplantation, if other causes of eosinophilia are excluded.

Bronchoalveolar Lavage Fluid↗
PubMedDate not supplied

The ortho backbone amide linker (o-BAL) is an easily prepared and highly acid-labile handle for solid-phase synthesis.

The tris(alkoxy)benzyl backbone amide linker (BAL) has found widespread application in solid-phase synthesis. The key intermediate for preparation of para BAL (p-BAL) is 2,6-dimethoxy-4-hydroxybenzaldehyde; several reports on its synthesis have appeared. However, the ortho analogue of the handle (o-BAL) has successfully been used by us for the synthesis of C-terminal-modified peptides, oligosaccharides, and substituted anilines. Here, we present a new and convenient synthesis of the key intermediate for o-BAL, 4,6-dimethoxy-2-hydroxybenzaldehyde, by a highly regioselective demethylation with BBr3, followed by purification through steam distillation. Cleavage studies of Leu-enkephalin anchored to either o-BAL or p-BAL handles revealed that both handles were surprisingly acid-labile and released the peptide with dilute TFA (5% and even 1% TFA in CH2Cl2). This useful property allowed the synthesis of fully protected Leu-enkephalin. The very convenient synthesis of 4,6-dimethoxy-2-hydroxybenzaldehyde combined with the benign properties of the o-BAL handle may make it the preferred regioisomer.

Acids↗
PubMed2002

TCR usage and cytokine expression in peripheral blood and BAL T cells.

T cells are thought to play an important regulatory role in atopic asthma. We hypothesized that human blood and BAL T cell subsets bearing various TCR-Vbeta genes might show selective differences in their cytokine profile. Peripheral blood (PB) and bronchoalveolar lavage (BAL) T cells from seven atopic asthmatic and six non-atopic non-asthmatic subjects were stimulated with PMA and ionomycin in the presence of monensin and analysed for TCR-Vbeta expression and production of cytokines at the single cell level. The percentage of IFN-gamma- and IL-2-producing BAL T cells was elevated compared with PB T cells from both the asthmatic subjects and the non-atopic, non-asthmatic controls. A small percentage of PB and BAL T cells produced IL-4 and IL-5, in asthmatic and normal subjects. In peripheral blood, the percentage of T cells expressing each cytokine was similar in the various TCR-Vbeta subsets and in total CD3+ T cells in all normal and six of seven asthmatic subjects. However, there was a substantial degree of heterogeneity in the cytokine profile of BAL TCR-Vbeta subsets compared with the total CD3+ T cells. This was more obvious in the asthmatic subjects with a reduction in the percentage of IFN-gamma- and IL-2-expressing T cells (five of seven asthmatic subjects) and an increase in the percentage of IL-4- and IL-5-expressing T cells (two of seven asthmatic subjects). These data confirm previous findings of an elevated proportion of IFN-gamma- and IL-2-producing BAL T cells while only a small proportion of PB and BAL T cells produce IL-4 and IL-5. Moreover, subsets of BAL T cells, defined by their TCR-Vbeta usage, may differ in their cytokine profile compared with the total CD3+ T cells, implying that T cells expressing different Vbeta elements may play different roles in regulating the airway inflammation in asthma.

Asthma↗
PubMed1997

Usefulness of quantitative cultures of BAL fluid for diagnosing nosocomial pneumonia in ventilated patients.

STUDY OBJECTIVE: To evaluate the role of quantitative cultures of BAL for diagnosing nosocomial pneumonia in mechanically ventilated patients. DESIGN: Cohort study. SETTING: Medical ICU, Hôpital Bichat, Paris, France, an academic tertiary care center. PATIENTS: A total of 141 episodes of suspected lung infection in 84 consecutive patients mechanically ventilated for 48 h or more. MEASUREMENTS AND RESULTS: Microbiologic findings obtained using BAL were compared with those obtained with protected specimen brush (PSB) samples and their operating characteristics were determined. The level of qualitative agreement between BAL and PSB specimen cultures was high, with 83% of the organisms isolated in PSB specimens being recovered simultaneously from BAL fluid. In addition, the results of quantitative BAL and PSB cultures were significantly correlated (rho = 0.46, p < 0.0001). Fifty-seven cases of pneumonia were diagnosed based on the following criteria: PSB sample yielding > or = 10(3) cfu/mL of at least one microorganism and/or > or = 5% of cells containing intracellular bacteria on direct examination of BAL. The operating characteristics of BAL fluid cultures were determined using different ways to report the results and over a range of values. The discriminative value of 10(4) cfu/mL was found to be an optimal threshold, with a sensitivity of 82% (95% confidence interval [CI], 76 to 88) and a specificity of 84.5% (95% CI, 79 to 90). CONCLUSIONS: These results indicate that BAL fluid cultures can offer a sensitive and specific means to diagnose pneumonia in ventilated patients and may provide relevant information about the causative pathogens.

Adult↗
PubMed1998

The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia.

STUDY OBJECTIVE: To determine the influence of mini-BAL culture results on subsequent changes in antibiotic therapy and patient outcomes. DESIGN: Prospective, single-center, cohort study. SETTING: Medical ICU of Barnes-Jewish Hospital, St. Louis, a university-affiliated teaching hospital. PATIENTS: One hundred thirty mechanically ventilated patients undergoing mini-BAL for suspected ventilator-associated pneumonia (VAP). INTERVENTIONS: Mini-BAL, prospective patient surveillance, and data collection. MEASUREMENTS AND RESULTS: Sixty (46.2%) patients had mini-BAL cultures that yielded at least one pathogen potentially accounting for the clinically suspected episode of VAP (64 bacterial, 3 viral, 2 fungal). Among the 60 patients with microbiologically positive mini-BAL cultures, 44 (73.3%) were classified as receiving inadequate antibiotic therapy (ie, identification of a microorganism resistant to the prescribed antibiotic regimen). Prior antibiotic administration or its absence remained unchanged in 51 (39.2%) patients based on the mini-BAL culture results, while in another 51 (39.2%) patients, antibiotic therapy was either begun (n=7) or the existing antibiotic regimen was changed (n=44), and in the remaining 28 (21.6%) patients, antibiotic therapy was discontinued altogether. The hospital mortality rates of these three groups were statistically different: 33.3%, 60.8%, and 14.3%, respectively (p<0.001). The most common pattern of antibiotic resistance resulting in an antibiotic change following mini-BAL was the identification of a Gram-negative bacteria resistant to a prescribed third-generation cephalosporin in 23 of 44 (52.3%) patients. Twenty-one of these 23 patients (91.3%) received prior therapy with a cephalosporin class antibiotic during the same hospitalization. Having an immunocompromised state (adjusted odds ratio [OR]=2.45; 95% confidence interval, 1.56 to 3.85; p=0.047) and the presence of a pathogen in the mini-BAL culture resistant to the empirically prescribed antibiotic regimen (adjusted OR=3.28; 95% confidence interval, 2.12 to 5.06; p=0.006) were identified as risk factors independently associated with hospital mortality by logistic regression analysis. CONCLUSIONS: These data suggest that antibiotic selection prior to obtaining the results of lower airway cultures is an important determinant of outcome for patients with suspected VAP. A delay in initiating adequate antibiotic therapy was associated with a greater mortality. Therefore, the initial selection of antibiotics for the empiric treatment of VAP should be broad enough to cover all likely pathogens, including antibiotic-resistant bacteria. This appears to be especially important in patients having received prior antibiotics.

Adult↗
PubMed1999

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.

Adult↗
PubMed2005

Relationship of BAL and lung tissue CD4+ and CD8+ T lymphocytes, and their ratio in idiopathic pulmonary fibrosis.

BACKGROUND: Surgical biopsy specimens have shown that T lymphocytes (TLs) infiltrate lung parenchyma in patients with idiopathic pulmonary fibrosis (IPF) and might play a pathogenetic role. BAL, a far less invasive technique, has also been used for the investigation of IPF pathogenesis. However, controversy exists whether the BAL fluid cellular profile reflects the cellular composition of the lung parenchyma. STUDY OBJECTIVE: To compare infiltrating TLs subpopulations (CD4+, CD8+, and CD4+/CD8+ ratio) in lung tissue and BAL fluid. PATIENTS AND METHODS: Immunohistochemistry was performed according to the streptavidin-biotin method on the surgical biopsy specimens of 12 untreated patients with IPF. The number of CD3+, CD4+, and CD8+ TLs was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor; Meylan, France). In BAL fluid, the same TLs subpopulations were evaluated by flow cytometry. RESULTS: In lung tissue, CD3+ TLs accounted for a mean (+/- SEM) of 28.8 +/- 7% of total cells, CD4+ TLs accounted for 14.5 +/- 4% of total cells (50.1 +/- 4% of CD3+ TLs), and CD8+ TLs accounted for 13.8 +/- 4% of total cells (47.4 +/- 4% of CD3+ TLs). In BAL fluid, lymphocytes accounted for 9.8 +/- 2.5% of total cells, CD4+ TLs accounted for 51.8 +/- 4% of CD3+ TLs, and CD8+ TLs accounted for 42.2 +/- 4% of CD3+ TLs. Tissue CD4+ and CD8+ TLs (expressed as a percentage of CD3+ TLs) correlated significantly with the number of CD4+ and CD8+ TLs in BAL fluid (r = 0.846 and p = 0.001 vs r = 0.692 and p = 0.013, respectively). A significant positive correlation was also found between the mean CD4+/CD8+ ratio found in tissue and BAL fluid (1.05 +/- 0.21 and 1.5 +/- 0.27, respectively; r = 0.832; p = 0.01). CONCLUSION: The results suggest that in patients with IPF, the TL subpopulations in BAL fluid reflect the pattern of lymphocytic infiltration in pulmonary parenchyma.

Bronchoalveolar Lavage Fluid↗
PubMed2006

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.

Adult↗
PubMed2000

BAL is a novel risk-related gene in diffuse large B-cell lymphomas that enhances cellular migration.

Clinical risk factor models such as the International Prognostic Index are used to identify diffuse large B-cell lymphoma (DLB-CL) patients with different risks of death from their diseases. To elucidate the molecular bases for these observed clinical differences in outcome, differential display was used to identify a novel gene, termed BAL (B-aggressive lymphoma), which is expressed at significantly higher levels in fatal high-risk DLB-CLs than in cured low-risk tumors. The major BAL complementary DNA encodes a previously uncharacterized 88-kd nuclear protein with a duplicated N-terminal domain homologous to the nonhistone portion of histone-macroH2A and a C-terminal alpha-helical region with 2 short coiled-coil domains. Of note, the BAL N-terminus and secondary structure resemble those of a recently identified human protein, KIAA1268. In addition, both BAL and KIAA1268 map to chromosome 3q21, further suggesting that these genes belong to a newly identified family. BAL is expressed at increased levels in DLB-CL cell lines with an activated peripheral B cell, rather than a germinal center B cell, phenotype. This observation and the characteristic dissemination of high risk DLB-CLs prompted studies regarding the role of BAL in B-cell migration. In classical transwell assays, stable BAL-overexpressing B-cell lymphoma transfectants had significantly higher rates of migration than vector-only transfectants, indicating that the risk-related BAL gene promotes malignant B-cell migration. (Blood. 2000;96:4328-4334)

Amino Acid Sequence↗