Estudio de la afección pulmonar asociada a esclerodermia sistémica: biomarcadores pronósticos y detección precoz

Abstract

The systemic sclerosis (SSc) is a systemic autoimmune disease, with a low prevalence in the population. The pulmonary involvement related to SSc is the leading cause of death, as interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH). Then, it is very important the study of factors associated to the prognostic of pulmonary involvement and a screening of them. _x000D_ It is well known that patients with SSc-ILD and anti-Scl-70 antibodies have a more aggressive fibrosis outcome and a reduced survival. However, the outcome of patients with SSc-ILD and anti-PM/Scl has not been established, neither the prognostic value of non-invasive biomarkers in EBC and EB. The aims of the two first works were study the outcome of ILD associated to the anti-PM/Scl antibodies compared with patients with anti-Scl-70, and analyse the biomarkers in EBC and EB to evaluate their correlation with the pulmonary function test and their prognostic value. _x000D_ The first study showed that the patients with anti-PM/Scl had different clinic characteristics than anti-Scl-70 group, with higher frequency of limited cutaneous SSc, inflammatory myopathy, and lower prevalence of peripheral vascular disease and gastrointestinal disease. The patients with anti-PM/Scl antibodies presented stabilization in forced vital capacity (FVC) during the follow-up, a greater progression-free survival and lower severe restrictive free survival. _x000D_ In the second study was identified that in the EBC pH values lower than 7.88 were related with reduced progression-free survival. Moreover, FeNO values in the EB lower than 10.75 ppb were associated with a worse progression-free survival. In the patients with SSc-ILD was documented an inverse correlation between elevated values of CO in EB and diminished FVC at baseline and the end of follow-up. _x000D_ In the case of PAH, it has been determined the relevance of screening methods for the increase of the survival secondary to the initiation of early vasodilator specific treatment. Recently, a new algorithm for the early diagnosis of PAH in SSc patients has been published, although it has not widely validated in external cohorts. SSc patients with borderline pulmonary hypertension (PH) have a high risk to develop PAH and higher mortality. Patients with PH related with ILD or left heart disease also has worse prognosis. In this way, it would be relevant study the capacity of this algorithm in the early diagnosis of borderline PH and other groups of PH. The aims of the third study were to validate the DETECT algorithm in an external cohort, determine the capacity of the algorithm for an early identification of borderline PH and PAH, and finally to value the DETECT algorithm capacity to an early identification of any sort of PH._x000D_ A validation of DETECT algorithm was performed, objectifying that in our cohort presented a high sensibility and negative predictive value, reducing the number of false negative improving the diagnostic capacity than the previous recommendations. With the DETECT algorithm also were identified the group of patients with borderline PH and HAP, and also the patients with group 2 and 3 PH of the WHO classification.

Date of Award	1 Jul 2017
Original language	Undefined/Unknown
Awarding Institution	Vall d'Hebron University Hospital (HUVH)
Supervisor	Vicente Fonollosa Pla (Tutor), Miquel Vilardell Tarres (Director) & Carmen Pilar Simeón Aznar (Director)