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Biomedical subjects

A B Thompson

Publications and source records attributed to A B Thompson.

At least 19 recordsLinked to original sources
PubMed1995

Immunological functions of the pulmonary epithelium.

The mature pulmonary epithelium forms a continuous lining to the airspace. Recent data suggest that this specialized epithelium may also contribute to host defence via interactions with inflammatory cells. Pulmonary epithelial cells can serve as part of the local immune system, providing structures and functions crucial for the maintenance of normal pulmonary function. This article will briefly review the morphology and development of the pulmonary epithelial cells, their function with regard to host defence, alterations of the pulmonary epithelium associated with airway diseases, and potential therapeutic implications for the treatment of respiratory diseases.

Epithelium↗
PubMed1994

Smoking reduction: an alternative approach for smokers who cannot quit.

Cigarette smoking is the foremost cause of death in the United States and is a major health problem worldwide. Clearly, the best way to eliminate the risk of smoking-related diseases, is to quit smoking. Smoking cessation has immediate and long-term benefits and substantially reduces the risk of many smoking-related diseases. Unfortunately, quitting smoking is rarely easy. For those smokers who cannot or do not wish to quit, reduction in their total smoking may represent a potential health benefit. Reduction in total smoking can, theoretically, be achieved by: 1) reducing the number of cigarettes smoked daily; and/or 2) switching to a low tar/low nicotine cigarette. Smokers, however, tend to self-adjust nicotine to maintain relatively constant levels. Reduction in tar/nicotine content or number of cigarettes, therefore, may not produce health benefits. Smoking reduction with alternative nicotine delivery, however, may represent an alternative option for smokers who cannot, or do not, wish to quit.

Humans↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Vitronectin in bronchoalveolar lavage fluid is increased in patients with interstitial lung disease.

Vitronectin, also known as S-protein, is a 75,000-dalton serum glycoprotein that has a variety of functions, including the capacity to interact with the terminal components of the complement cascade, the coagulation system, and cell surfaces. By virtue of its ability to interact with cells, vitronectin is capable of mediating cell-spreading and adhesion and may also influence cell differentiation and cell growth. To investigate the possibility that vitronectin might contribute to the pathogenesis of interstitial lung disease, vitronectin was measured in bronchoalveolar lavage fluid from patients with sarcoidosis, idiopathic pulmonary fibrosis, and, for comparison, normal volunteers. Vitronectin was detected in lavage fluid and serum of all study subjects. Increased lavage fluid concentrations were found in patients with interstitial lung disease when compared with normal subjects (p less than 0.005), and glucocorticoid-treated patients with interstitial lung disease had lower vitronectin levels than did untreated patients. Furthermore, on SDS-PAGE and Western blot analysis lavage fluid vitronectin comigrated with serum vitronectin, suggesting similar molecular size. Thus, vitronectin is a normal constituent of the epithelial lining fluid, and lavage fluid vitronectin is similar to serum vitronectin. The increase of vitronectin concentrations in the epithelial lining fluid of patients with interstitial lung disease suggests that vitronectin may contribute to the pathogenesis of interstitial lung disease.

Blood Proteins↗
PubMed1991

Bronchoscopy with bronchoalveolar lavage causes neutrophil recruitment to the lower respiratory tract.

Bronchoscopy with bronchoalveolar lavage (BAL) is a technique now widely utilized for both clinical and investigational purposes. At times, it is useful to perform bronchoscopy with BAL in a serial fashion. However, previous work in animals indicates that bronchoscopy with BAL can cause lower respiratory tract inflammation. To determine if BAL also causes lower respiratory tract inflammation in humans, sequential bronchoscopy with BAL was performed in 30 human subjects. Inflammation was evaluated using a quantitative visual assessment of bronchitis and by BAL. BAL was performed by instilling and aspirating five 20-ml aliquots of saline in each of three areas of the lung. The fluid returned from the first aliquot from each site was pooled as the bronchial fraction, and that from the remaining four aliquots was pooled as the alveolar fraction. Each volunteer was restudied at 2, 7, 24 or 72 h. Findings at the second bronchoscopy with BAL included an elevation in visual signs of large airways inflammation, which was greatest at 24 h. Bronchial neutrophils increased significantly, with the greatest effect seen at 7 h (5.3 +/- 2.0 versus 59.5 +/- 11.0%, SEM). The effect was most pronounced in the area of the lung previously lavaged, but was also seen in lobes that had not received BAL at the first bronchoscopy. Alveolar neutrophils also increased, with the maximal effect also seen at 7 h. Visible bronchial inflammation, bronchial neutrophils, and alveolar neutrophils returned to the normal range by 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Chronic inflammation is associated with an increased proportion of goblet cells recovered by bronchial lavage.

To evaluate the possibility that bronchoalveolar lavage could provide sufficient respiratory epithelial cells to quantify changes in epithelial cell types associated with chronic inflammation, we examined the epithelial cells obtained in the first infused (20 ml) aliquots that were processed separately from later aliquots, a process known to enrich for bronchial contents. Epithelial cells, including ciliated cells, goblet cells, and fragments of desquamated epithelium, were easily identified after preparation by cytocentrifugation and staining with a modified Giemsa stain. Quantification of the columnar cell types revealed that those with chronic bronchitis and asymptomatic smokers have increased goblet cells as a percentage of the total columnar epithelial cells (chronic bronchitics 36 +/- 2 percent, asymptomatic smokers 22 +/- 2 percent) compared with normal subjects (9 +/- 1 percent, p less than 0.001, ANOVA). Significantly, the goblet cell percentage was strongly correlated with other measures of bronchitis and measures of airflow obstruction such as the bronchitis index, a visually derived score at bronchoscopy of airway inflammation (r = 0.72, p less than 0.001), the percent neutrophils in the first infused aliquots (r = 0.44, p less than 0.05), and the FEV1 percent (r = -0.74, p less than 0.001). Thus, bronchoalveolar lavage is capable of providing sufficient bronchial epithelial cells for analysis, and the changes seen in the spectrum of columnar epithelial cells may reflect important underlying pathologic changes.

Airway Obstruction↗