Role of Gastro-oesophageal reflux in systemic sclerosis and other advancements in interstitial lung diseases: preliminary data

Abstract

Background The management of interstitial lung disease in the context of systemic sclerosis (ILD-SSc) and pleuroparenchymal fibro-elastosis PPFE associated to other ILD has important unmet clinical needs. Symptomatic gastro-oesophageal reflux [GORD] is reported in up to 90% of systemic sclerosis [SSc]. PPFE is a rare interstitial lung disease (ILD) entity characterized by pleural and parenchymal fibrosis with a striking upper-lobe predominance. PPFE can occasionally coexist with other ILDs. Material and methods We present preliminary baseline results of the first 44 enrolled patients (median age 52, female 70%, median FVC=74%, median DLCO= 37%, diffuse SSc 33%) of a prospective study (NCT02136394), with regards to oesophageal manometry/24hr impedance (carried out off PPIs), respiratory(K-BILD and Leicester cough questionnaires) and GORD symptoms (UCLA SCTC GIT 2.0 Questionnaire, Reflux Disease Questionnaire RDQ) and lung function: time to decline for FVC drop of 10% or DLco 15% drop from Visit 1 was calculated using cox proportional hazard models. Furthermore, a retrospective analysis of 284 IPF patients (mean age 66±1.1, males 77%, ever smokers 66%, mean FVC% 68.4±2.5, mean DLco% 36.3±1.6, average CT extent % 38.4±1.6) regarding the prevalence of PPFE is presented: average disease extent on HRCT was used as a measure of disease severity; mortality, time to irreversible decline in FVC levels of > 10% and irreversible decline in DLco levels of > 15% from baseline, were quantified from the date of the HRCT using proportional hazards analysis. Results Foe the ILD-SSc study: proximal reflux was detected in 50% of patients, median DeMeester score was 5. FVC% showed significant correlations (p<0.01) with pH recumbent clearance (r=0.46) and K-BILD total score (r=0.45). DLCO% showed significant correlations (p<0.01) with hiatal hernia (r=0365), pH recumbent clearance (r=0.45) and K-BILD total score (r=0.65).. RDQ score was significantly correlated with DeMeester(r=59,p<0.01) and Time of acid pH in upright position (r=0.48, p<0.01); among respiratory questionnaires, Leicester total score showed significant correlations (p<0.01) with time of acid impedance in upright position (r=0.62), total time of acid pH (r=0.68). At the univariate analysis, DeMeester score, % time of acid pH on recumbent position were the strongest predictor of lung function decline (respectively, p=0.005 and p=0.004). For the PPFE study: 94 (33%) IPF patients met the HRCT criteria for PPFE. Compared to patients without PPFE, subjects with PPFE were less likely to be ever smokers (p=0.02), had lower FVC measurements (p=0.0005) and more extensive ILD on HRCT (p=0.03). Freestanding bronchiectasis were found in 34% of PPFE versus < 2% of patients without PPFE (p<0.0001). PPFE was significantly associated with increased mortality (HR: 1.54 CI: 95% 1.16-2.05, p=0.003), decreased time to decline in FVC (HR: 1.82 CI: 95% 1.28-2.6, p=0.001) and DLco (HR: 2.29 CI: 95% 1.6-3.3, p<0.0001). After adjusting for age, gender, smoking status, ILD severity, the association of PPFE with survival, FVC and DLco decline was confirmed. Conclusions We confirm an association between oesophageal dysmotility and respiratory symptoms in Ssc-ILD. Furthermore, oesophageal measures are independent predictors of ILD-SSc decline. PPFE is an independent predictor of survival and functional worsening in IPF. Further studies in different ethnic groups and other diffuse fibrosing lung diseases are needed.