American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2001
Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome.
Because experimental studies have shown that intact alveolar epithelial fluid transport function is critical for resolution of pulmonary edema and acute lung injury, we measured net alveolar fluid clearance in 79 patients with acute lung injury or the acute respiratory distress syndrome. Pulmonary edema fluid and plasma were sampled serially in the first 4 hours after intubation. Net alveolar fluid clearance was calculated from sequential edema fluid protein measurements. ⋯ Endogenous and exogenous catecholamines did not correlate with alveolar fluid clearance. Patients with maximal alveolar fluid clearance had significantly lower mortality and a shorter duration of mechanical ventilation. In summary, in contrast to hydrostatic pulmonary edema, alveolar fluid clearance in patients with acute lung injury and the acute respiratory distress syndrome is impaired in the majority of patients, and maximal alveolar fluid clearance is associated with better clinical outcomes.
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Am. J. Respir. Crit. Care Med. · May 2001
Comparative StudyIncreased expression of transforming growth factor-beta1 in small airway epithelium from tobacco smokers and patients with chronic obstructive pulmonary disease (COPD).
Tobacco smoke is believed to cause small airway disease and then chronic obstructive pulmonary disease (COPD), but the molecular mechanisms by which small airway obstruction occurs remain unknown. To study the gene expression levels of transforming growth factor (TGF)-beta1, a potent fibrogenic factor, in small airway epithelium from smokers and patients with COPD, we harvested highly pure samples of epithelial cells from small airways under direct vision by using an ultrathin bronchofiberscope BF-2.7T (outer diameter 2.7 mm with a biopsy channel of 0.8 mm in diameter). The expression levels of TGF-beta1 were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). ⋯ Spontaneously released immunoreactive TGF-beta1 levels from cultured epithelial cells were more elevated in subjects with a history of smoking and patients with COPD than in nonsmokers. Our study showed a close link between smoking and expression of TGF-beta1 in small airways. Our results also suggested that small airway epithelial cells might be involved in obstructive changes found in smokers and patients with COPD.
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Am. J. Respir. Crit. Care Med. · May 2001
Comparative StudyPulmonary edema fluid from patients with acute lung injury augments in vitro alveolar epithelial repair by an IL-1beta-dependent mechanism.
Efficient alveolar epithelial repair is crucial for the restoration of the injured alveolar epithelial barrier in patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). We hypothesized that pulmonary edema fluid from patients with ALI /ARDS would inhibit alveolar epithelial repair as measured in an in vitro epithelial wound-repair model using the human alveolar epithelial-like cell line A549. In contrast to our initial hypothesis, pulmonary edema fluid from patients with ALI/ARDS increased alveolar epithelial repair by 33 +/- 3% compared with pooled plasma from healthy donors (p < 0.01). ⋯ Inhibition of interleukin-1beta (IL-1beta) activity by IL-1 receptor antagonist reduced alveolar epithelial repair induced by ALI/ARDS edema fluid by 46 +/- 4% (p < 0.001), indicating that IL-1beta contributed significantly to the increased epithelial repair. In summary, pulmonary edema fluid collected early in the course of ALI/ARDS increased alveolar epithelial repair in vitro by an IL-1beta-dependent mechanism. These data demonstrate a novel role for IL-1beta in patients with ALI/ARDS, indicating that IL-1beta may promote repair of the injured alveolar epithelium.