Multiple breath washout: A new and promising lung function test for patients with idiopathic pulmonary fibrosis

Background and objective Idiopathic pulmonary fibrosis (IPF) is a devastating progressive lung disease affecting the parenchyma. Nitrogen multiple‐breath washout (N2‐MBW) is a lung function test that measures ventilation inhomogeneity, a biomarker of small airway disease. We assessed clinical properties of N2‐MBW in IPF. Methods In this prospective cohort pilot study, 25 IPF patients and 25 healthy controls were assessed at baseline and 10 patients at median 6.2 months later. Outcomes included the lung clearance index (LCI) from N2‐MBW, forced vital capacity (FVC) from spirometry, diffusion capacity of the lungs for carbon monoxide (DLCO), bronchiectasis score from computed tomography scans, the Gender–Age–Physiology (GAP score for IPF) stage and death or lung transplantation (LTx). Study end points were feasibility, repeatability, discriminative capacity and correlation with disease severity and structural lung damage. Results All patients were able to perform N2‐MBW. LCI was repeatable and reproducible. Median (interquartile range (IQR)) LCI in IPF was 11.6 (10.1–13.8) in IPF versus 7.3 (6.9–8.4) in controls (P < 0.0001). LCI correlated with DLCO corrected for haemoglobin (corrDLCO; r = −0.49, P = 0.016), bronchiectasis score (r = 0.45, P = 0.024) and the GAP stage (r = 0.59, P = 0.002), but not with FVC. FVC was not related to bronchiectasis. During follow‐up, six patients died and one received LTx. LCI correlated with the latter compound outcome: hazard ratio (95% CI) was 2.43 (1.26; 4.69) per one LCI SD from the patient population. Conclusion N2‐MBW is a feasible, reliable and valid lung function test in IPF. LCI correlates with diffusion impairment, structural airway damage and clinical disease severity. LCI is a promising surveillance tool in IPF that may predict mortality. In this pilot study, we demonstrate that nitrogen‐multiple breath washout (N2‐MBW) is a feasible, sensitive and reproducible lung function test in patients with idiopathic pulmonary fibrosis. The N2‐MBW‐derived lung clearance index correlates with clinical disease severity, structural airway pathology and mortality. See related Editorial