American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 1998
Comparative StudyCD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease.
To investigate whether the inflammatory process in peripheral airways is different in smokers who develop symptoms of chronic bronchitis and chronic airflow limitation and in asymptomatic smokers who do not develop chronic airflow limitation, we examined surgical specimens obtained from 16 smokers undergoing lung resection for localized pulmonary lesions. Nine had symptoms of chronic bronchitis and chronic airflow limitation and seven were asymptomatic with normal lung function. ⋯ The number of CD8+ T-lymphocytes and the smooth muscle area were increased in smokers with symptoms of chronic bronchitis and chronic airflow limitation as compared with asymptomatic smokers with normal lung function, while the number of neutrophils, macrophages, and CD4+ T-lymphocytes were similar in the two groups of subjects examined. We concluded that smokers who develop symptoms of chronic bronchitis and chronic airflow limitation have an increased number of CD8+ T-lymphocytes and an increased smooth muscle area in the peripheral airways as compared with asymptomatic smokers with normal lung function, supporting the important role of CD8+ T-lymphocytes and airway remodeling in the pathogenesis of chronic obstructive pulmonary disease.
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Am. J. Respir. Crit. Care Med. · Mar 1998
Antibody to E- and L-selectin does not prevent lung injury or mortality in septic baboons.
Recruitment of polymorphonuclear leukocytes (PMN) through upregulation of cellular adhesion molecules is a proposed mechanism of injury in sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that pretreatment of baboons with a monoclonal antibody to human E- and L-selectin (EL-246) during sepsis would decrease PMN influx into tissues and result in less organ injury during gram-negative sepsis. We studied 14 anesthetized, ventilated adult baboons; six animals received 1 mg/kg of EL-246 before infusion of an LD100 of live Escherichia coli and six received the E. coli infusion without antibody therapy. ⋯ The antibody partly blocked PMN migration, but there were few significant physiologic or biochemical differences between the EL-246-treated and untreated animals. In the antibody-treated animals, UOP was decreased, metabolic acidosis was worsened, and median survival time was decreased significantly. We conclude that treatment with an antibody to E- and L-selectin in gram-negative sepsis does not improve gas exchange or protect against lung injury, and is associated with decreased survival time in primates.
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Interest has recently been renewed in lung volume reduction surgery (LVRS) for end-stage emphysema. However, numerous questions about its role in the treatment of emphysema remain, including the clinical characteristics of optimal candidates and its mechanism of improvement in pulmonary function. In this report, we develop a mathematical analysis and graphic depiction of the mechanism of improvement in expiratory airflow and vital capacity. ⋯ Moreover, RV/TLC is found to be the single most important determinant of the improvement in pulmonary function after LVRS. Regardless of the specific underlying lung disease, the impairment of airflow is due primarily to mismatch between the sizes of the lung and the chest wall, and the effects of LVRS are almost exclusively due to improvement of that match. This analysis can be used to develop testable hypotheses to guide patient selection for this procedure.
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Am. J. Respir. Crit. Care Med. · Mar 1998
Comparative StudyImproved clearability of cystic fibrosis sputum with dextran treatment in vitro.
Most patients with cystic fibrosis (CF) are infected by Pseudomonas aeruginosa. Dextran exhibits anti-adhesive effects in preventing attachment of P. aeruginosa to epithelial cells (1). The initial purpose of this study was to evaluate the potential of dextran to alter the rheology and ciliary transportability of CF sputum prior to initiation of a clinical trial in patients with CF. ⋯ There was a significant positive correlation between spinnability and viscoelasticity, and negative relationships between spinnability and both forms of clearability as predicted from viscoelastic measurements. This study suggests that treatment with Dextran 4000 can reduce the crosslink density and cohesiveness of CF and improve mucociliary and cough clearability. Dextran 4000 is an inexpensive and nontoxic agent that may be of benefit in patients with CF lung disease and perhaps in other respiratory disease where mucus retention is an important feature.
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Am. J. Respir. Crit. Care Med. · Mar 1998
Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice.
Erythromycin (EM) is an antibiotic with potent antiinflammatory effects that is used for treating chronic lower respiratory tract infections. It has been shown that free radicals, such as the superoxide anion and nitric oxide (NO), are pathogenic molecules in viral disease. Much attention has been given to a critical role of NO in the pathologic events of various inflammatory diseases. ⋯ Simultaneously, the number of inflammatory cells recovered in lung lavage fluid 6 d after virus infection was significantly reduced by the treatment with EM. The EM treatment resulted in a dose-dependent decrease in the level of nitrite/nitrate (metabolites of NO) in the serum and the NO synthase (NOS)-inducting potential in the lungs of the virus-infected mice. These results indicate that EM may have substantial therapeutic value for various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing NO overproduction in the lung.