American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 1998
Randomized Controlled Trial Clinical TrialProcollagen types I and III aminoterminal propeptide levels during acute respiratory distress syndrome and in response to methylprednisolone treatment.
Ineffective lung repair in patients with unresolving acute respiratory distress syndrome (ARDS) is accompanied by progressive fibroproliferation, inability to improve lung injury score (LIS), progressive multiple organ dysfunction syndrome (MODS), and an unfavorable outcome. Our aim was to investigate the relationship between fibrogenesis, pulmonary and extrapulmonary organ dysfunction, and outcome during the natural course of ARDS and in response to prolonged methylprednisolone treatment. We investigated 29 patients with ARDS. ⋯ In early ARDS, plasma PINP and PIIINP levels are elevated and continue to increase over time in those not improving. Among nonimprovers, those randomized to prolonged methylprednisolone treatment had a rapid and significant reduction in plasma and BAL aminoterminal propeptide levels and similar changes in lung injury and MODS scores. These findings provide additional evidence of an association between biological efficacy and physiologic response during prolonged methylprednisolone treatment of unresolving ARDS.
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Am. J. Respir. Crit. Care Med. · Nov 1998
A lung computed tomographic assessment of positive end-expiratory pressure-induced lung overdistension.
The aim of this study was to assess positive end-expiratory pressure (PEEP)-induced lung overdistension and alveolar recruitment in six patients with acute lung injury (ALI) using a computed tomographic (CT) scan method. Lung overdistension was first determined in six healthy volunteers in whom CT sections were obtained at FRC and at TLC with a positive airway pressure of 30 cm H2O. In patients, lung volumes were quantified by the analysis of the frequency distribution of CT numbers on the entire lung at zero end-expiratory pressure (ZEEP) and PEEP. ⋯ PEEP induced a mean alveolar recruitment of 320 +/- 160 ml and a mean lung overdistension of 238 +/- 320 ml. In conclusion, overdistended lung parenchyma of healthy volunteers is characterized by a CT number below -900 HU. This threshold can be used in patients with ALI for differentiating PEEP-induced alveolar recruitment from lung overdistension.
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Am. J. Respir. Crit. Care Med. · Nov 1998
Comparative StudyPolymorphisms of the beta chain of the high-affinity immunoglobulin E receptor (Fcepsilon RI-beta) in South African black and white asthmatic and nonasthmatic individuals.
We used amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) to document the prevalence of three mutations in the beta chain of the high-affinity IgE receptor (Fcepsilon RI-beta): I181L, V183L, and E237G in a sample of black and white asthmatic and control subjects in South Africa to determine whether these variants contribute to the enhanced IgE responses in these groups and also to determine whether the discrepancy in the prevalence of atopy in these groups could be attributed to these variants, as whites tend to be more atopic than blacks. There was a significant difference in the frequency of I181L between white asthmatics (28%) and white control subjects (3%) (p = 0.00001), and between black control subjects (16%) and white control subjects (p = 0.002); no difference in the frequency of I181L was observed between black asthmatics (22%) and black control subjects (16%). V183L was found in one black asthmatic who was also positive for I181L and E237G. ⋯ E237G was more prevalent in blacks (20%) than in whites (8.5%) (p = 0.001). I181L might predispose to atopy in the white population, but not in the black population. The significantly higher prevalence of E237G in blacks than in whites might explain why blacks tend to have more severe asthma than whites and might offer more insight into the higher asthma mortality rate in the black population as compared with the white population.
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Am. J. Respir. Crit. Care Med. · Nov 1998
Comparative StudyEffects of dipyridamole and inhaled nitric oxide in pediatric patients with pulmonary hypertension.
Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation by increasing pulmonary vascular levels of cyclic guanosine monophosphate (cGMP). Dipyridamole, a drug with several putative vasodilator mechanisms, is an inhibitor of cGMP-specific phosphodiesterases (PDE5); it therefore has the potential to increase pulmonary vascular cGMP levels, lower pulmonary vascular resistance, augment iNO-induced pulmonary vasodilation, and attenuate excessive pulmonary vasoreactivity. To test dipyridamole in the pulmonary circulation, we studied pediatric patients undergoing cardiac catheterization who had severe resting pulmonary hypertension (Group 1; n = 11) or exaggerated acute hypoxia-induced pulmonary vasoconstriction (Group 2; n = 4). ⋯ In Group 2, Ppa and the pulmonary-to-systemic resistance ratio (Rp/Rs) increased to suprasystemic levels during acute hypoxia. Pretreatment with dipyridamole blunted the increase in Ppa and Rp/Rs during repeat hypoxia, keeping Ppa at a subsystemic level and Rp/Rs < 1. We conclude that: (1) dipyridamole nonselectively reduces PVRI, primarily through an increase in CI; (2) in combination with iNO, dipyridamole augments the decrease in PVRI in some patients; and (3) dipyridamole blunts the severity of acute hypoxic pulmonary vasoconstriction in children with exaggerated hypoxic pressor responses.
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Am. J. Respir. Crit. Care Med. · Nov 1998
ReviewCellular and molecular mechanisms regulating airway smooth muscle proliferation and cell adhesion molecule expression.
Asthma as well as bronchiolitis obliterans and chronic bronchitis are chronic lung diseases characterized by airflow obstruction and airway inflammation. Although asthma typically induces reversible airflow obstruction, in some patients airflow obstruction becomes irreversible. The irreversible airway remodeling that occurs in asthma has been attributed in part to increased smooth muscle mass. ⋯ In addition, new evidence reveals that direct cell- cell interaction between immunocytes and airway smooth muscle may also modulate airway smooth muscle cell function. Studies have shown that activated T lymphocytes can adhere to cultured airway smooth muscle, and the functional consequence of this adherence is the upregulation of cell adhesion molecules and the stimulation of DNA synthesis in human airway smooth muscle cells. The identification of the critical regulatory sites that mediate airway smooth muscle cell proliferation or modulate cell adhesion molecule expression in these cells may improve our understanding of the mechanisms that regulate airway inflammation and possibly provide new therapeutic approaches to alter airway remodeling seen in patients with chronic airflow obstruction.