Dexamethasone inhibits endotoxin-induced coagulopathy in human lungs.

Essentials Glucocorticoids are associated with an increased risk of thrombosis. Healthy volunteers received dexamethasone or placebo in an endotoxin lung instillation model. Dexamethasone suppressed thrombin generation in bronchoalveolar lavage. Glucocorticoids inhibit endotoxin induced pulmonary coagulopathy. SUMMARY: Background Activation of local and systemic coagulation is a common finding in patients with pneumonia. There is evidence that glucocorticoids have procoagulant activity in the circulation, particularly in the context of inflammation. The effects of glucocorticoids on local pulmonary coagulation have not yet been investigated. Objective To use a human model of lung inflammation based on the local instillation of endotoxin in order to investigate whether glucocorticoids alter pulmonary coagulation. Methods Twenty-four healthy volunteers were randomized to receive either dexamethasone or placebo in a double-blind trial. Endotoxin was instilled via bronchoscope into right or left lung segments, followed by saline into the contralateral site. Six hours later, a bilateral bronchoalveolar lavage (BAL) was performed and coagulation parameters were measured. Results Endotoxin induced activation of coagulation in the bronchoalveolar compartment: the level of prothrombin fragment 1 + 2 (F1 + 2 ) was increased three-fold (248 pmol L-1 , 95% confidence interval [CI] 43-454 versus 743 pmol L-1 , 95% CI 437-1050) and the level of thrombin-antithrombin complex (TATc) was increased by ~ 50% (31 µg L-1 , 95% CI 18-45 versus 49 µg L-1 , 95% CI 36-61) as compared with saline-challenged segments. Dexamethasone reduced F1 + 2 (284 pmol L-1 , 95% CI 34-534) and TATc (9 µg L-1 , 95% CI 0.7-17) levels almost to those measured in BAL fluid from the saline-instilled segments in the placebo group. Dexamethasone even profoundly reduced F1 + 2 levels (80%) in saline-instilled lung segments (50 pmol L-1 , 95% CI 12-87). In contrast, dexamethasone had no effect on systemic F1 + 2 levels. Conclusions Dexamethasone inhibits endotoxin-induced coagulopathy in lungs. This trial is the first to provide insights into the effects of glucocorticoids on pulmonary coagulation in response to endotoxin.

[Idiopathic interstitial pneumonias: from classification to diagnostic work-up]. / Idiopathische interstitielle Pneumonien : Von der Klassifikation zur Diagnostik.

Idiopathic interstitial pneumonias (IIP) comprise seven entities with distinct histologic patterns. In their idiopathic form IIP are rare diseases. They are, nevertheless, considered prototypes of the much more common secondary interstitial pneumonias. The advent of high-resolution computed tomography (HRCT) has had a profound impact on the imaging of IIP, because the detailed delineation of the lung anatomy allows a close correlation between the histologic patterns of IIP and the CT features. On the basis of CT morphology and in the correct clinical context, the radiologist can achieve an accurate diagnosis in many cases. However, due to overlap between the various entities, complementary lung biopsy is recommended in virtually all cases. This article reviews the CT pattern of IIP and offers relevant clinical and histological information for the purpose of enabling the radiologist to understand and participate in the multidisciplinary concept of IIP.

[T1 maps and O2-enhanced MRT of the diseased lung. Emphysema, fibrosis, mucoviscidosis]. / T1-Maps und O2-verstärkte MRT der erkrankten Lunge. Emphysem, Fibrose, Mukoviszidose.

PURPOSE: Gas exchange is the primary function of the lung and the transport of oxygen plays a key role in pulmonary physiology and pathophysiology. MATERIALS AND METHODS: Molecular oxygen is weakly paramagnetic, so that an increase in oxygen concentration results in shortening T1 relaxation time and thus increasing signal intensity in T1 weighted images. The calculation of parameter maps may allow deeper insights into relaxation mechanisms. T1 maps based on a snapshot FLASH sequence obtained during the inhalation of various oxygen concentrations allow the creation of an oxygen transfer function, providing a measurement of local oxygen transfer. T1 weighted single shot TSE sequences demonstrate the signal changing effects during inhalation of pure oxygen. RESULTS: The average of the mean T1 values over the entire lung during inspiration was 1,199+/-117 ms, the average of these values during expiration was 1,333+/-167 ms. T1 maps of patients with emphysema and lung fibrosis show fundamentally different values and respiratory dependence compared to healthy individuals. Oxygen enhanced MR has the potential to assess reduced diffusion capacity and decreased transport of oxygen in patients with emphysema and cystic fibrosis. DISCUSSION: Results published in the literature indicate that T1 mapping and oxygen enhanced MR are promising new methods in functional imaging of the lung.

Controlled prospective randomised trial on the effects on pulmonary haemodynamics of the ambulatory long term use of nitric oxide and oxygen in patients with severe COPD.

BACKGROUND: Pulmonary hypertension is a frequent complication of severe chronic obstructive pulmonary disease (COPD) and a major cause of morbidity and mortality in this condition. Based on the improved survival of these patients due to long term oxygen therapy and the potent and selective pulmonary vasodilation by inhaled nitric oxide, the safety and effectiveness of the combined inhalation of these two gases over a 3 month period was assessed. METHODS: Forty patients with secondary pulmonary hypertension due to COPD were randomly assigned to receive either oxygen alone or "pulsed" inhalation of nitric oxide with oxygen over a period of 3 months. "Pulsed" inhalation of nitric oxide was used to reduce pulmonary ventilation-perfusion mismatch and formation of toxic reaction products of nitric oxide and oxygen. RESULTS: Compared with oxygen alone, the combined inhalation of nitric oxide and oxygen caused a significant decrease in mean (SE) pulmonary artery pressure (from 27.6 (4.4) mm Hg to 20.6 (4.9) mm Hg, p<0.001) and pulmonary vascular resistance index (from 569.7 (208.1) to 351.3 (159.9) dyne x s(-1) x cm(-5) x m(-2), p<0.001) without decreasing arterial oxygenation. Cardiac output increased by 0.5 litres (from 5.6 (1.3) l/min to 6.1 (1.0) l/min, p=0.025). Systemic haemodynamics and left heart function remained unchanged during this period and no increase in toxic reaction products of nitric oxide was observed. CONCLUSIONS: This is the first controlled trial indicating that the "pulsed" inhalation of nitric oxide together with oxygen may be safely and effectively used for the long term treatment of severe COPD.

Aerosolised iloprost improves pulmonary haemodynamics in patients with primary pulmonary hypertension receiving continuous epoprostenol treatment.

BACKGROUND: Continuous intravenous treatment with epoprostenol significantly improves pulmonary haemodynamics and survival in patients with primary pulmonary hypertension (PPH). Its beneficial effect, however, may be blunted due to adverse effects such as catheter sepsis and systemic hypotension. Recent investigations have shown that inhaled iloprost is effective in the treatment of PPH. Based on their different pharmacokinetics, we hypothesised that the combination of intravenous epoprostenol and inhaled iloprost would be more efficacious than epoprostenol alone during acute testing in patients with PPH. METHODS: The effect of a single dose of inhaled iloprost (30 microg total over 15 minutes) on pulmonary haemodynamics was examined in eight patients with PPH (initial non-responders to nitric oxide) who had considerable adverse effects during treatment with epoprostenol. RESULTS: The combination of inhaled iloprost and intravenous epoprostenol significantly improved mean pulmonary artery pressure (MPAP), cardiac index (CI), mixed venous oxygen saturation (SvO2), and systemic arterial oxygen pressure (PaO2) compared with epoprostenol treatment alone. Mean systemic arterial pressure (MSAP) and pulmonary capillary wedge pressure (PCWP) remained unchanged. CONCLUSIONS: The pulmonary vasoreactivity shown by additional iloprost inhalation during effective epoprostenol treatment suggests that an improvement of treatment for pulmonary hypertension may be possible by combining vasoactive substances.

Treatment with epoprostenol reverts nitric oxide non-responsiveness in patients with primary pulmonary hypertension.

OBJECTIVE: To assess whether long term treatment with epoprostenol might restore primary non-responsiveness to nitric oxide (NO) in patients with primary pulmonary hypertension. METHODS: Seven patients with primary pulmonary hypertension receiving intravenous epoprostenol continuously because of failure of NO to influence pulmonary haemodynamics during initial testing were followed over a period of 13-29 months. Afterwards, acute vascular reactivity towards NO was tested again during right heart catheterisation. RESULTS: Administration of NO after continuous epoprostenol treatment for a mean period of 18 months improved arterial oxygen saturation (p < 0.01) and cardiac index (p < 0.05), and decreased mean pulmonary artery pressure (p < 0.01) and total pulmonary vascular resistance (p < 0.01) in patients previously unresponsive to NO. CONCLUSIONS: Long term treatment with epoprostenol reverts initial refractoriness to NO in patients with primary pulmonary hypertension. Thus the addition of NO to epoprostenol treatment might cause further improvement in the course of the disease.

Lung endothelial cell proliferation in normal and pulmonary hypertensive neonatal calves.

Tremendous changes in pressure and flow occur in the pulmonary and systemic circulations after birth, and these hemodynamic changes should markedly affect endothelial cell replication. However, in vivo endothelial replication rates in the neonatal period have not been reported. To label replicating endothelial cells, we administered the thymidine analog bromodeoxyuridine to calves approximately 1, 4, 7, 10, and 14 days old before they were killed. Because we expected the ratio of replicating to nonreplicating cells to vary with vascular segment, we examined the main pulmonary artery, a large elastic artery, three sizes of intrapulmonary arteries, the aorta, and the carotid artery. In normoxia for arteries < 1,500 micron, approximately 27% of the endothelial cells were labeled on day 1 but only approximately 2% on day 14. In the main pulmonary artery, only approximately 4% of the endothelial cells were labeled on day 1 and approximately 2% on day 14. In contrast, in the aorta, approximately 12% of the endothelial cells were labeled on day 1 and approximately 2% on day 14. In chronically hypoxic animals, only approximately 14% of the endothelial cells were labeled on day 1 in small lung arteries and approximately 8% were still labeled on day 14. We conclude that the postnatal circulatory adaptation to extrauterine life includes significant changes in endothelial cell proliferation that vary dramatically with time and vascular location and that these changes are altered in chronic hypoxia.

Aerobic endurance training program improves exercise performance in lung transplant recipients.

STUDY OBJECTIVE: To determine whether an aerobic endurance training program (AET) in comparison to normal daily activities improves exercise capacity in lung transplant recipients. PATIENTS AND STUDY DESIGN: Nine lung transplant recipients (12+/-6 months after transplant) were examined. All patients underwent incremental bicycle ergometry with the work rate increased in increments of 20 W every 3 min. Identical exercise tests were performed after 11+/-5 weeks of normal daily activities and then after a 6-week AET. The weekly aerobic training time increased from 60 min at the beginning to 120 min during the last week. Training intensity ranged from 30 to 60% of the maximum heart rate reserve. RESULTS: Normal daily activities had no effect on exercise performance. The AET induced a significant decrease in resting minute ventilation from 14+/-5 to 11+/-3 L/min. At an identical, submaximal level of exercise, a significant decrease in minute ventilation from 47+/-14 L/min to 39+/-13 L/min and heart rate from 144+/-12 to 133+/-17 beats/min, before and after the AET, was noted. The increase in peak oxygen uptake after AET was statistically significant (1.13+/-0.32 to 1.26+/-0.27 L/min). CONCLUSIONS: These data demonstrate that normal daily activities do not affect exercise performance in lung transplant recipients > or = 6 months after lung transplantation. An AET improves submaximal and peak exercise performance significantly.