Objectives of this European Respiratory Society task force were to summarise current studies, to develop strategies for future research and to increase availability and awareness of exercise training for pulmonary hypertension (PH) patients.An evidence-based approach with clinical expertise of the task force members, based on both literature search and face-to-face meetings was conducted. The statement summarises current knowledge and open questions regarding clinical effects of exercise training in PH, training modalities, implementation strategies and pathophysiological mechanisms.In studies (784 PH patients in total, including six randomised controlled trials, three controlled trials, 10 prospective cohort studies and four meta-analyses), exercise training has been shown to improve exercise capacity, muscular function, quality of life and possibly right ventricular function and pulmonary haemodynamics. Nevertheless, further studies are needed to confirm these data, to investigate the impact on risk profiles and to identify the most advantageous training methodology and underlying pathophysiological mechanisms.As exercise training appears to be effective, cost-efficient and safe, but is scarcely reimbursed, support from healthcare institutions, commissioners of healthcare and research funding institutions is greatly needed. There is a strong need to establish specialised rehabilitation programmes for PH patients to enhance patient access to this treatment intervention.

The multiple inert gas elimination technique (MIGET) was first described by Wagner et al in 1974.' It allows quantitation of the ventilationperfusion (VA/Q) distribution and a precise analysis of the intrapulmonary and extrapulmonary factors that govern gas exchange in humans. This review discusses how this technique has facilitated a better understanding of the mechanisms underlying gas exchange in two common chronic lung diseases -chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. The methodological aspects ofthe MIGET are not discussed, and the interested reader is referred to the first review in this series (Thorax 1994;49:815-824) or to some comprehensive reviews published recently on this subject.2

TIPS neither improved nor worsened pulmonary gas exchange in patients with portal hypertension. This data does not support the use of TIPS as a specific treatment for HPS. However, it does reinforce the view that TIPS can be safely performed for the treatment of other complications of portal hypertension in patients with HPS.

Abstractsistent pulmonary hypertension of the newborn. 5 In many patients with acute respiratory Background -Inhaled nitric oxide (NO) is a selective pulmonary vasodilator which distress syndrome (ARDS) inhaled NO reduces the pulmonary artery pressure and increases can improve gas exchange in acute lung injury. However, it is uncertain that this arterial oxygenation by lessening intrapulmonary shunt. 6 Experimentally, inhaled NO effect on arterial oxygenation can be generalised to all lung diseases.reverses hypoxic pulmonary vasoconstriction. 7Inhaled NO, however, can worsen gas exchange Methods -The effects of inhaled NO on gas exchange were studied in nine patients by overcoming the usual physiological mechanisms of matching ventilation (V) and perwith chronic obstructive pulmonary disease (COPD), 11 patients with severe pul-fusion (Q). Whilst inhaled NO acts as a selective pulmonary vasodilator in some monary hypertension, and 14 healthy volunteers. A randomised sequence of patients with chronic obstructive pulmonary disease (COPD), it fails to improve 40 ppm of NO or air was inhaled for 20 minutes through an orofacial mask.oxygenation. 8 9 It is important to establish in which diseases inhaled NO fails to improve Results -Inhaled NO reduced mean (SE) transcutaneous arterial oxygen tension gas exchange. We have studied the change in arterial oxygenation during NO inhalation in (TcPO 2 ) from 9.6 (0.3) to 8.9 (0.4) kPa in healthy volunteers and from 7.4 (0.6) to patients with COPD and compared it with normal volunteers and patients with severe pul-7.0 (0.5) kPa in patients with COPD. There was no change in TcPO 2 in patients with monary hypertension. severe pulmonary hypertension. During inhalation of NO and air no change occurred in transcutaneous arterial carbon Methods dioxide tension (TcPCO 2 ), arterial oxygen Nine patients with COPD, 11 with severe pulsaturation (SaO 2 ) measured by pulse oxi-monary hypertension, and 14 healthy vometer, or cardiac output determined by lunteers were studied. All gave their informed the transthoracic impedance method. consent and the study was approved by the Conclusions -Inhaled NO does not im-local hospital ethics committee. The diagnosis prove TcPO 2 nor increase cardiac output in of COPD was established from a history of normal subjects and patients with COPD, clinical and physiological evidence of irsuggesting that inhaled NO worsens gas reversible airway obstruction. All patients with exchange. This could represent inhaled Section of Respiratory COPD ceased bronchodilators 12 hours before NO overriding hypoxic pulmonary vasoMedicine, the study. The diagnosis of severe pulmonary

Micronuclei, comet and chromosome alterations assays are the most widely used biomarkers for determining the genotoxic damage in a population exposed to genotoxic chemicals. While chromosome alterations are an excellent biomarker to detect short-and long-term genotoxic effects, the comet assay only measures early biological effects, and furthermore it is unknown whether nuclear abnormalies, such as those measured in the micronucleus test, remain detectable long-term after an acute exposure. In our previous study, an increase in structural chromosome alterations in fishermen involved in the clean-up of the Prestige oil spill, two years after acute exposure, was detected. The aim of this study is to investigate whether, in lymphocytes from peripheral blood, the nuclear abnormalies (micronucleus, nucleoplasmic bridges and nuclear buds) have a similar sensitivity to the chromosome damage analysis for genotoxic detection two years after oil exposure in the same non-smoker individuals and in the same peripheral blood extraction. No significant differences in nuclear abnormalies frequencies between exposed and non-exposed individuals were found (p > 0.05). However, chromosome damage, in the same individuals, was higher in exposed vs. non-exposed individuals, especially for chromosome lesions (p < 0.05). These findings, despite the small sample size, suggest that nuclear abnormalities are probably less-successful biomarkers than are chromosome alterations to evaluate genotoxic effects two or more years after an exposure to oil. Due to the great advantage of micronucleus automatic determination, which allows for a rapid study of hundreds of individuals exposed to genotoxic chemical exposure, further studies are needed to confirm whether this assay is or is not useful in long-term genotoxic studies after the toxic agent is no longer present.

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IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is an infrequent but important complication of acute pulmonary embolism (PE). Thrombophilias and non-O blood groups are genetic risk factors for venous thromboembolism (VTE), however they are not independently associated with CTEPH. Identifying genetic risk factors for CTEPH would provide important insights into pathobiology and might allow risk-stratification following PE. We undertook a genome-wide association study (GWAS) in CTEPH to identify novel disease loci.MethodsTo date, 1457 Caucasian CTEPH patients were enrolled from 10 European and US Centres and compared to 1536 healthy Caucasian controls from the Wellcome Trust Case Control Consortium. Genotyping was performed using the HumanOmniExpressExome-8 array. Quality control criteria and statistical analysis are summarised in figure 1.Results1250 CTEPH cases, 1492 controls and 7 million single-nucleotide polymorphisms (SNPs) were included after quality control exclusions. Two loci, in chromosomes 4 and 9 were significantly associated with CTEPH (figure 1). The lead SNP in chr9 (rs532436, OR=2.38, p=4.6x10-32) is highly correlated with the tagging SNP for the A1 blood group (rs507666, R2=0.99). Reconstructing genetic ABO groups confirmed an over-representation of the A1A1 group in CTEPH compared to controls (7% vs. 2.9%, OR 4.5). Additionally, there were 11 significant SNPs in the chr9 ADAMTS13 gene locus that is moderately correlated with ABO (R2=0.33).The lead SNP in chr4 (rs13130318, OR=1.4, p=5.6x10-8) is highly correlated with a missense variant in FGG (rs6050, R2=0.89) associated with decreased fibrinogen protein and increased resistance to fibrinolysis in CTEPH. There were no associations at the F5 locus, which is highly significant in VTE.ConclusionsWe report the first GWAS in CTEPH, identifying at least 2 genetic loci associated with the disease. The ABO association is driven by the A1 blood group and represents the largest population attributable genetic risk factor for CTEPH, which is higher than previously reported for VTE. The potential ADAMTS13 association is a plausible biological candidate, and further work will establish whether it is independent from ABO. The lack of associations with other loci found in VTE suggests that ABO might have a pathobiological role in CTEPH in addition to its contribution to VTE.Abstract S108 Figure 1Manhattan plot of significant loci in chromosome 4 and 9 associated with CTEPH. Quality control exclusion thresholds and chromosome 9 regional association plot shown within figure. Dotted line represents a Genome-wide significance threshold of p=5x10-8 (Bonferroni). Imputaton was performed from the HapIotype Reference Consortium (Sanger imputation service). An additive model of association was applied using logistic regression with gender and 1 principal component as covariates. HWE (Hardy-Weinberg equilibrium), IBD (iderity by descent), MAF (minor allele frequency), PCA (principal component analysis), SNP (single nucleotide polymorphism).