IPF patients are limited by mechanical and not pulmonary-vascular factors \u2013 results of a derivation-validation cohort study

Benjamin D Fox,Baruch Vainshelboim,Barak Pertzov,Irit Terner,Shimon Itzhakian,Yael Shostak,Mordechai R Kramer

doi:10.1186/s12890-019-1015-3

Abstract

BackgroundDuring cardiopulmonary exercise testing (CPET), Idiopathic Pulmonary Fibrosis (IPF) patients do not reach their direct maximum voluntary ventilation (MVV) and have deranged gas exchange. Their exercise limitation is therefore attributed to a pulmonary vascular mechanism.MethodsWe studied two cohorts (derivation and validation) of IPF patients with lung function testing and CPET. Maximal ventilation at exercise (VEpeak) was compared to direct MVV by Bland-Altman analysis.ResultsIn the derivation cohort (n = 101), direct MVV over-estimated VEpeak by a factor of 1.51, driven by respiratory rate during MVV that was 1.99 times higher at rest as compared to VEpeak at exercise. The formula (FEV1 × 20.1) + 15.4 was shown to predict VEpeak (r2 = 0.56) in the derivation cohort. In the validation cohort of 78 patients, VEpeak was within a factor of 1.27 (6.8 l/min) of predicted according to the novel formula. According to the novel prediction formula the majority of patients (58%) in the entire cohort have VEpeak within 85% of their predicted MVV, which would indicate a mechanical respiratory limitation to exercise.ConclusionEstimation of direct MVV performed at rest leads to significant over-estimation of the breathing reserve in IPF patients. This may lead to over-diagnosis of pulmonary vascular limitation in these patients. Expected maximal ventilation at exercise may be accurately predicted indirectly by an IPF-specific formula.

Highlights

During cardiopulmonary exercise testing (CPET), Idiopathic Pulmonary Fibrosis (IPF) patients do not reach their direct maximum voluntary ventilation (MVV) and have deranged gas exchange
The aim of the present study was to (a) evaluate whether direct MVV systematically overestimates the Ventilation at peak exertion (VEpeak) reached by IPF patients and (b) to derive and validate an IPF-specific indirect MVV formula for CPET based on resting lung function measurements
We showed that the traditional threshold values for setting the mechanical respiratory limit derived from resting measurements significantly overestimate the level of ventilation that IPF patients can reach during peak exertion

Summary

Introduction

During cardiopulmonary exercise testing (CPET), Idiopathic Pulmonary Fibrosis (IPF) patients do not reach their direct maximum voluntary ventilation (MVV) and have deranged gas exchange. Their exercise limitation is attributed to a pulmonary vascular mechanism. The indirect FEV1 × 35 formula has not been validated in IPF patients The implication of this is that IPF patients, since they do not reach the predicted respiratory mechanical limit but have derangements in gas exchange, according to the diagnostic logic of CPET interpretation, they have a pulmonary vascular limitation [3, 10]. Given that many patients did not have PH at rest or at exercise yet still had significant exercise limitation, it strongly suggests that other factors may play a role

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