The impairment of pulmonary function is related to the development of pulmonary hypertension in patients with cystic fibrosis?

Purpose: Cystic Fibrosis has been recently included in group 3 of Dana Point classification of Pulmonary Hypertension. However the prevalence of PH in CF and its impact on the outcome is still unclear. The purpose of the study is to analyze prevalence, characteristics and determinants of PH and its effects on exercise capacity in end-stage CF patients awaiting lung transplantation. Methods: We have retrospectively examined the prevalence of PH in a large cohort of CF patients followed by our centre between 2000 and 2012. All our patients underwent right heart catheterization during the evaluation for lung transplantation. Echocardiographic and electrocardiographic features have been evaluated too. Respiratory function has been studied with spirometry and arterial blood gas analysis. Exercise capacity has been tested with 6mwt. We included 122 patients. Age was 28±9 years and 72 (59%) were women. We excluded all patients in which the time between catheterization and other examinations was > 30 days. Furthermore we excluded all patients who were clinically instable during the examination period. Results: The prevalence of PH in the studied population is 57.4%. 59 patients (48.3%) present elevation of pulmonary artery pressure (PAP) of mild degree (mPAP 25-35 mmHg) whereas only 11 patients (9%) present level of mean pulmonary artery pressure (mPAP) > 35 mmHg. Patients with PH show more severe respiratory function impairment. The levels of FEV1 (p<0.001), FVC (p<0.001), paCO2 (p=0.002) and paO2 (p=0.015) correlates with PAP in univariate analysis. When evaluated in multivariate analysis, only FEV1 remains significantly associated with PH (p=0.0002; HR 1.1; 1.05, 1.17). Exercise capacity is compromised in patients with PH awaiting lung transplantation and this group has significantly worse results at 6mwt (p=0.01). A lower distance at 6mwt is predictive for a poor prognosis in the studied population even when inserted in multivariate analysis (p=0.007; HR = 0.267; 0.096, 0.747). Conclusion: Pulmonary Hypertension is frequently associated with end-stage CF. A severe decrease of FEV1 is strongly correlated with development of PH. The presence of PH is related to a reduction of the exercise capacity evaluated by 6mwt, which is predictive for adverse outcome in CF patients awaiting lung transplantation. Although our results are still preliminary, this study suggests that pulmonary vasodilators may be used for the treatment of PH in CF patients with advanced lung disease.