Balakrishnan B; Cleveland Clinic, Cleveland, Ohio, USA,
Marakini A; Detloff L; Mahalwar G; Lane JE; Paul D; Tonelli AR

Respiration. 105(7):715-726, 2026.

Introduction: Pulmonary vascular abnormalities coexist with interstitial
lung disease (ILD), leading to a spectrum of physiologic impairments. We
hypothesized that ILD patients with exercise intolerance have a
heterogenous hemodynamic profile when assessed by invasive cardiopulmonary
exercise testing (iCPET).

METHODS: From January 2018 to December 2023, we prospectively performed
iCPET for several conditions. The primary outcome of the study was to
assess the hemodynamic phenotypes both at rest and during exercise of ILD
patients with exercise intolerance, which cannot be fully explained by the
severity of ILD.

RESULTS: Of the 43 ILD patients included in the study, 10 (23%) had no
pulmonary hypertension (PH), 16 (37%) had no PH with pulmonary vascular
resistance (PVR) >2 WU, 7 (16%) had precapillary PH, 7 (16%) had
postcapillary or combined pre- and postcapillary PH, and 3 (7%) had
unclassified PH. Four (9%) patients had exercise PH. Forced vital
capacity, diffusion capacity for carbon monoxide, peak oxygen consumption,
and resting partial pressure of oxygen (PaO2) were significantly lower
across the no PH to precapillary PH spectrum. Peak exercise PaO2 decreased
(97 +/- 25, 73 +/- 15, and 62 +/- 10 mm Hg, p = 0.001) while mPAP/CO slope
(1.9 +/- 1.1, 3.1 +/- 2.1, and 5.1 +/- 2.7, p = 0.009) and PAWP/CO slope
(0.9 +/- 0.7, 0.9 +/- 0.7, and 3.0 +/- 3.0, p = 0.007) increased from no
PH, to no PH with high PVR, to precapillary PH. No associations were noted
for gender, presence of fibrotic ILD and scleroderma, and mPAP/CO >3 WU
across this spectrum.

CONCLUSION: Patients with ILD and exercise intolerance have several
hemodynamic phenotypes with parameters that reveal worse exercise
performance from no PH to no PH with elevated PVR to precapillary PH