The dual endothelin receptor antagonist bosentan has been approved in several countries for pulmonary arterial hypertension, and patients with portopulmonary hypertension (PPHTN) have not specifically been excluded. However, no data have been published on the efficacy and safety of bosentan in this patient population. Here, the first clinical experiences with bosentan in patients with Child A cirrhosis and severe PPHTN are reported.In total, 11 consecutive patients with cirrhosis and severe PPHTN in New York Heart Association Functional Classes III and IV were treated for .1 yr with bosentan.After 1 yr of treatment with bosentan, all patients showed improved symptoms and exercise capacity. The 6-min walking distance increased from 310¡102 m at baseline to 388¡81 m at 1 yr. Cardiopulmonary exercise testing disclosed a significant increase in peak oxygen uptake, from 12.6¡3.5 to 16.6¡2.8 mL?min -1 ?kg -1 . Pulmonary vascular resistance fell from 944¡519 to 635¡321 dynes?s?L -1. The medication was well tolerated by all patients, and there was no evidence of drug-related liver injury.In conclusion, bosentan proved to be efficacious and safe in a small number of patients with portopulmonary hypertension.

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Lung injury in ventilated lungs may occur due to local or systemic disease and is usually caused by or accompanied by inflammatory processes. Recently, acidification of exhaled breath condensate pH (EBC-pH) has been suggested as marker of inflammation in airway disease. We investigated pH, ammonia, Lactate, pCO2, HCO3-, IL-6 and IL-8 in EBC of 35 ventilated patients (AECC-classification: ARDS: 15, ALI: 12, no lung injury: 8). EBC-pH was decreased in ventilated patients compared to volunteers (5.85 +/- 0.32 vs. 7.46 +/- 0.48; P < 0.0001). NH4+, lactate, HCO3-, pCO2, IL-6 and IL-8 were analyzed in EBC and correlated with EBC-pH. We observed correlations of EBC-pH with markers of local (EBC IL-6: r = -0.71, P < 0.0001, EBC IL-8: r = -0.68, P < 0.0001) but not of systemic inflammation (serum IL-6, serum IL-8) and with indices of severity of lung injury (Murray's Lung Injury Severity Score; r = -0.73, P < 0.0001, paO2/FiO2; r = 0.54, P < 0.001). Among factors potentially contributing to pH of EBC, EBC-lactate and EBC-NH4+ were found to correlate with EBC-pH. Inflammation-induced disturbances of regulatory mechanisms, such as glutaminase systems may result in EBC acidification. EBC-pH is suggested to represent a marker of acute lung injury caused by or accompanied by pulmonary inflammation.

Analysis of breath condensate (BC) has received interest recently due to the need for easy and repetitive monitoring or airway and pulmonary disease. While many authors have used custom built systems, commercial systems are now available and will probably be used more widely. Early studies of markers and mediators in BC have reported concentrations following varying periods of sampling time. However, factors that influence the generation of BC have not been analysed and it is unclear whether breathing rate, tidal volume, lung function, body weight, height or age influence the amount of BC collected. We therefore studied the influence of these factors on breath condensate volume and breath condensate urea and protein concentrations in 22 healthy volunteers and 23 COPD patients. A strong correlation of total respired volume and breath condensate volume was observed for both groups (volunteers: r=0.952, p < 0.0001, COPD: r=0.883, p < 0.001) while no significant correlation existed for breath condensate volume and TLC, RV, Vc, FEV1, R(tot), height or body weight, As long as ventilation remained fairly constant, breath condensate volume increased linearly with time. The fraction of breath condensate extracted from total vapour contained in the exhalate was estimated by measuring relative atmospheric humidity before and after the collecting tube. The amount calculated by the change in temperature and saturation corresponded closely to the amount actually collected. We conclude from these results that breath condensate volume is primarily dependent on V(E), and does not seem to depend on lung function parameters. For standardisation it is suggested to report breath condensate measurements per volume respired. Both, urea and protein are present in measurable quantities in breath condensate and protein as well as BCV may be helpful denominators for comparison with e.g. cytokines in lung disease.

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