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Biomedical subjects

A B Thompson

Publications and source records attributed to A B Thompson.

At least 37 records · Page 2Linked to original sources

Quantitative culture of bronchoalveolar lavage fluid for the diagnosis of bacterial pneumonia.

PURPOSE: A prospective study to determine the usefulness of quantitative bacterial cultures of fluid obtained via fiberoptic bronchoscopy and bronchoalveolar lavage as an aid in the diagnosis of bacterial pneumonia. PATIENTS AND METHODS: All patients undergoing fiberoptic bronchoscopy with bronchoalveolar lavage during a 6 1/2-month period. Presence of pneumonia was determined using clinical, radiographic, laboratory, and histologic data. Quantitative bacterial cultures of bronchoalveolar lavage fluid were determined using a 1-microL culture loop. RESULTS: Quantitative bacterial cultures of bronchoalveolar lavage (BAL) fluid were sensitive and specific predictors of bacterial pneumonia. Using 10(3) colony-forming units (cfu)/mL as the threshold value for a positive culture, we determined the sensitivity and specificity to be 90% and 97%, respectively. The data were also analyzed for the subgroups of patients who were intubated or were receiving antibiotics. The sensitivity and specificity were 78% and 96% for the group of patients receiving antibiotics and 100% and 82% for the group of patients intubated for more than 24 hours at the time of BAL. Values for the area under the receiver operating characteristic curve for the 3 groups were 0.94, 0.88, and 0.96, respectively. CONCLUSIONS: Quantitative bacterial cultures of BAL fluid are sensitive and specific in the diagnosis of bacterial pneumonia. The use of antibiotics at the time of BAL reduces the sensitivity of the test, and prolonged intubation reduces the specificity of the test.

Bacterial Infections↗

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.

Adult↗

The bronchitis index. A semiquantitative visual scale for the assessment of airways inflammation.

Flexible fiberoptic bronchoscopy has been proven to be an effective tool for the assessment and characterization of airway inflammation. Visual inspection of airways affected by chronic bronchitis discloses an abnormal appearance characterized by erythema, edema, secretions, and friability. It was hypothesized that the visual appearance of airway inflammation could be assessed in a semiquantitative manner. A bronchitis index (BI) was developed that scores the visual appearance of airways according to the presence or absence of abnormal edema, erythema, secretions, and friability (0 = normal, 3 = remarkably abnormal). The BI was determined in three study groups: 86 subjects with chronic bronchitis, 15 subjects who smoked cigarettes, but did not have chronic bronchitis, and 25 normal, nonsmoking control subjects. The reproducibility of the BI was determined by comparing the results from pairs of two independent observers assessing 249 subjects undergoing fiberoptic bronchoscopy under various investigative protocols. In total, nine investigators scored the airways. For the three observer pairs with more than six observations, there were no differences noted in the BI (p = 0.43, 0.67, 0.82). To control for the effect of cough upon the BI, lidocaine usage was recorded. No correlation was found between lidocaine usage and BI. As previously noted for a smaller group of subjects, the BI was found to be elevated in those with chronic bronchitis (13.2 +/- 0.53) compared with both asymptomatic smokers (8.5 +/- 0.89, p < 0.0005) and normal volunteers (2.3 +/- 0.55, p < 0.0001); the latter two groups also differed significantly (p < 0.0001). The BI was also found to correlate significantly with bronchial sample lavage fluid neutrophil content in lavage fluid obtained after determination of the BI and with cigarette smoking as quantitated by pack years. Conversely, the BI correlated negatively with the spirometric measures of airway obstruction, FEV1, FEV1/FVC, FEV25-75, and FEFmax. Thus, the BI appears to be a reproducible, semiquantitative assessment of the visual appearance of airway inflammation. It may be a useful bronchoscopic adjunct for the assessment of airway inflammation in clinical investigations.

Adult↗

General vs local anesthesia. Effect on bronchoalveolar lavage findings.

Bronchoalveolar lavage (BAL) can be performed with the patient undergoing either local or general anesthesia (GA). This study investigates whether the type of anesthesia affects BAL fluid and cell recovery. Eighty patients, were selected for study. Fluid recoveries were significantly less in the GA group for both the bronchial and alveolar lavages. The differences were confirmed for BAL fluid recovery in a subsequent group of 120 unselected patients. Bronchoscope size did not appear to affect recovery, nor did anesthesia time; BAL fluid recovery from patients with respiratory failure who were intubated and mechanically ventilated was similar to that in the GA group, suggesting that lower recovery rates may be due to mechanical ventilation. The BAL fluid cell counts were related to fluid recovery, but airway neutrophils represented a higher percentage of BAL lavage fluid cells in the GA lavages, independent of differences in the volume of lavage fluid recovered.

Adult↗

Bronchoalveolar lavage procollagen-III-peptide in recent onset hypersensitivity pneumonitis: correlation with extracellular matrix components.

Hypersensitivity pneumonitis (HP) is characterized by the accumulation of inflammatory cells in the lung parenchyma, and may progress to fibrosis. The content of the fibroblast derived collagen metabolite procollagen-III-peptide (PCP-III) in bronchoalveolar lavage (BAL) fluid of HP patients has been found to be increased. Previous studies have shown elevation of the fibroblast adhesion molecules, vitronectin and fibronectin in the BAL fluid of recent onset HP. In view of these observations, it was hypothesized that increases in PCP-III would be associated with increases in vitronectin and fibronectin in the BAL fluid of subjects with untreated recent onset HP. BAL was performed in 14 patients with HP and nine normal controls. The aminoterminal domain of PCP-III was measured by radioimmunoassay, and vitronectin and fibronectin by enzyme-linked immunosorbent assay. Detectable amounts of BAL PCP-III were seen in all HP patients but not in the normal controls (mean +/- SEM 5.1 +/- 1.2 versus < 0.2 ng.ml-1; i.e. below the limit of detection of the PCP-III assay). The BAL fluid concentration of PCP-III correlated well with the amount of vitronectin (r = 0.638) and fibronectin (r = 0.710). Except for PCP-III and mast cells, no significant correlations were found between PCP-III, vitronectin, fibronectin and the cellular parameters. The findings suggest that an increased turnover of collagens and proteoglycans is present in the lower respiratory tract of patients with recent onset HP, possibly reflecting remodelling of the extracellular matrix.

Adult↗

Altered epithelial lining fluid parameters in old normal individuals.

Pneumonia is a leading cause of morbidity and death in older patients, and immunosenescence is believed to contribute to their susceptibility. In order to investigate whether age-related changes occur on the epithelial surfaces of the lung, bronchoscopy and bronchoalveolar lavage (BAL) were performed without complication in 19 young (27.7 +/- 4.2 yrs), 6 middle-aged (49.8 +/- 3.5 yrs), and 8 old (74.1 +/- 4.3 yrs) normal, nonsmoking subjects. BAL was performed by instilling and retrieving five 20 ml aliquots of normal saline into three sites. The returns from the first aliquots (the bronchial sample) were analyzed separately from the returns from the subsequent aliquots (the distal sample). Lavage fluid cellularity was characterized and IgA, IgG, and albumin were measured by ELISA. Lavage fluid returns were lower in the elderly group and correlated with spirometric parameters. Significantly elevated numbers of neutrophils were recovered by the bronchial sample fluid from the old group. In contrast, no consistent difference in macrophage recovery by either the bronchial or distal sample was noted. In both the bronchial and distal samples, IgG, but not IgA or albumin, was elevated in the group of old subjects. Alterations occurring in BAL fluid with aging may reflect changes in local host defenses.

Adult↗

Serum procollagen III peptide levels in subjects with sarcoidosis. A 5-year follow-up study.

In a prospective study, Type III procollagen N-terminal peptide was measured in the sera of 38 subjects with biopsy-proven pulmonary sarcoidosis at 6-month intervals over a period of 5 yr. The subjects were divided into four groups according to their radiologic presentation and clinical course: Group A (n = 10) subjects with sarcoidosis Type I without radiologic progression over 5 yr; Group B (n = 5) subjects with sarcoidosis Type I with radiologic progression to Stage II or III; Group C (n = 9) subjects with sarcoidosis Types II and III without progression over 5 yr; and Group D (n = 14) subjects with sarcoidosis Types II and III with radiologic progression. Lung function tests (FVC, FEV1, and DLCO), chest roentgenograms, and measurements of serum angiotensin converting enzyme (S-ACE) were performed concurrently with the S-PCP-III levels. Significantly higher levels of S-PCP-III were found in group B (Type I, progressive) (18.2 +/- 1.09 ng/ml) and in group D (Type II/III, progressive) (13.9 +/- 1.2 ng/ml) compared with those of Group A (Type I, stable) (9.1 +/- 1.09 ng/ml) and Group C (Type II/III, stable) (7.6 +/- 1.1 ng/ml) or normal volunteers (9.4 +/- 4 ng/ml) (p less than 0.001 for all comparisons). Changes in S-PCP-III levels tended to parallel the clinical course, and steroid treatment resulted in a significant decrease in S-PCP-III concentrations (p less than 0.001). In contrast, serum angiotensin converting enzyme (S-ACE) levels did not correlate with either the clinical course or radiologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Aerosolized beclomethasone in chronic bronchitis. Improved pulmonary function and diminished airway inflammation.

Chronic bronchitis is associated with airways obstruction and inflammation. In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction, subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage (BAL) before and after receiving 6 wk of therapy (five puffs four times a day) with either aerosolized beclomethasone (n = 20) or placebo (n = 10) in a double-blinded, randomized fashion. All subjects received aerosolized albuterol before each use of the study medications. Before BAL, the airways were visually assessed for the appearance of inflammation and assigned a score, the bronchitis index. BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a "bronchial sample." The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis. The fluid was prepared for cytologic examination by cytocentrifugation. Albumin (as a measure of epithelium permeability) and lactoferrin and lysozyme (as measures of serous cell activity) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay, and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution. After treatment, the beclomethasone group, but not the placebo group, showed improvement in FVC (p = 0.02), FEV1 (p = 0.002), and 25 to 75% forced expiratory flow (p = 0.006). Associated with the improvement in spirometry, the bronchitis index fell (13.5 +/- 1.0 versus 10.75 +/- 1.1, p = 0.02) in the beclomethasone-treated group, but not the placebo-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Airway inflammation predicts diffuse alveolar hemorrhage during bone marrow transplantation in patients with Hodgkin disease.

We determined risk factors present in patients with Hodgkin disease that predicted the development of diffuse alveolar hemorrhage syndrome (DAH) during autologous bone marrow transplantation (BMT). One hundred twenty-three patients with Hodgkin disease prospectively underwent bronchoscopy with bronchoalveolar lavage (BAL) before receiving BMT. The bronchitis index (BI) of the airways and bronchial and alveolar cell counts and differentials were determined in all patients and compared with 20 normal nonsmoking volunteers. Logistic regression analysis was used to determine factors that predicted for the development of DAH. Visual evidence of bronchial injury was observed regardless of smoking history (BI = 7.8 +/- 0.5 for BMT versus 2.3 +/- 0.5 for volunteers, p = 0.001). BMT patients who developed DAH (n = 14) had significantly greater numbers of bronchial neutrophils and eosinophils compared with DAH-negative (n = 109) patients (bronchial polymorphonuclear leukocytes (PMN), 33 +/- 7% versus 14 +/- 2%, p = 0.006; bronchial eosinophils, 0.9 +/- 0.3% versus 0.4% +/- 0.07%, p = 0.02). Logistic regression analysis revealed that the presence of bronchial PMN > 20% or bronchial eosinophils > zero% were predictive of DAH (p = 0.005 and 0.05, respectively). When both predictors were positive, the rate of DAH was 10 times greater than when both predictors were negative (43% versus 4% DAH occurrence). Survival was also significantly reduced when these predictors were positive. This study demonstrates that bronchial inflammation is present with or without intraluminal inflammatory cells in the majority of patients with Hodgkin disease before BMT. The subgroup of these patients with increased bronchial inflammatory cells are at greatly increased risk for development of DAH and death.

Academic Medical Centers↗

Immunomodulatory therapies for cystic fibrosis.

Progressive pulmonary disease is the primary cause of morbidity and mortality in adult patients with cystic fibrosis (CF). The decrease in lung function associated with infection with Pseudomonas aeruginosa has been related to the severity of pulmonary inflammation. Thus therapies that reduce pulmonary inflammation may prove to be clinically efficacious. Therapeutic interventions that target pulmonary inflammation may be directed either at the infecting organism, especially P aeruginosa, or at host responses. Eradication of P aeruginosa from the airways of patients with CF has not been accomplished. However, reduction of the burden of P aeruginosa or modification of virulence factors are practical goals. Normalization of the host response ultimately depends on correction of the molecular defect. Until then, therapies are being investigated that may modulate pulmonary inflammation. These include therapies aimed at compensating for the defect in ion transport, down-regulating inflammatory cell responses, inhibiting host inflammatory products, or altering airway secretions. Preliminary data suggest that each of these approaches may have clinical efficacy. Large, multicenter trials addressing these issues are presently ongoing and hold the promise for continued improvement in the clinical course of patients with CF.

Anti-Bacterial Agents↗

Pathogenesis, evaluation, and therapy for massive hemoptysis.

Massive hemoptysis is a rare, but life-threatening event. Death from massive hemoptysis is usually due to aspiration of blood. Thus, the initial evaluation should occur simultaneously with efforts to control the patient's airway and respiratory status. Therapeutic interventions can be directed with an understanding of the underlying pathophysiology and estimated rate of blood loss. Surgery remains the definitive therapy. However, more conservative measures can usually control acute bleeding and provide therapeutic alternatives for patients who are not surgical candidates.

Adult↗

Protease injury in airways disease.

In summary, proteases are present in the airway in inflammatory airways disease. These enzymes can damage the airway epithelium. As a consequence, airway function can be altered, and long-term changes in airway anatomy can result. Although the exact cellular and biochemical mechanisms that lead to these changes are incompletely described, it seems likely that they will play important roles in clinical airways disease. As such, these pathways may represent novel opportunities for therapeutic intervention.

Animals↗

Gcglobulin functions as a cochemotaxin in the lower respiratory tract. A potential mechanism for lung neutrophil recruitment in cigarette smokers.

Activation of the complement pathway with generation of the potent chemotaxin C5a may play a significant role in the neutrophil accumulation seen in the lungs of patients with smoking-associated diseases. Although C5a is rapidly degraded to the less potent chemotaxin C5a des Arg, binding of this peptide with its cochemotaxin Gcglobulin (GcG) can restore its chemotactic potency. Therefore, modulation of Gcglobulin levels in smoking-induced lung disease could affect the accumulation of neutrophils seen in this disorder. To test this hypothesis GcG was measured by an enzyme-linked immunosorbent assay in bronchoalveolar lavage fluids (BALF) obtained from non-smokers, asymptomatic smokers, and patients with chronic obstructive pulmonary disease (COPD). Antigenic amounts of GcG in BALF were increased in COPD patients and asymptomatic smokers compared with nonsmokers (6.35 +/- 1.02 and 5.15 +/- 1.07 versus 2.82 +/- 0.37 micrograms/mg albumin, p less than 0.05). In addition, we found that BALF enhanced C5a des Arg-mediated chemotaxis (48.3 +/- 5.6 versus 11.2 +/- 1.6 cells/high power field, p less than 0.05), an effect that was not seen in the presence of GcG antibody. Furthermore, BALF GcG was similar to serum GcG using Western blot analysis, and the interaction of GcG with C5a des Arg was not inhibited by cigarette smoke. These data demonstrate that elevation of BALF GcG levels occurs in smoking-associated lung disease and that this protein is biologically active and capable of increasing C5a des Arg-mediated chemotaxis. This suggests that modulation of GcG levels may be important in smoking-associated lung diseases.

Adult↗