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Zone of z-scores uncertainty in pulmonary function interpretation: A proof-of-concept study from CO and NO lung
Giovanni Barisione1, Sanja Stanojevic2, Vito Brusasco3
1Struttura Semplice Fisiopatologia Respiratoria, Clinica Malattie Respiratorie e Allergologia, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genova, Italy.
Background:
The probabilistic interpretation of unusually low lung diffusing capacity (DL) has been recently standardized but the impact of different reactive gases, reference equations and structural abnormalities on definition of lower limits of normal (LLN) is not well established.
Methods And Results:
To assess the uncertainty zone of LLN (z-scores) interpretation in computed tomography (CT)-determined interstitial pulmonary fibrosis (IPF) and pulmonary emphysema (PE), we have measured the single-breath DL for carbon monoxide (DLCO) and nitric oxide (DLNO) in 120 adults, 66 of them with IPF and the other 54 with PE. 41 asymptomatic, never-smokers, served as a control group. Z-scores derived from Global Lung Function Initiative (GLI) for standard (11-s breath-hold time) DLCO and non-specific (ERS) or sex- and device-specific (Munkholm et al.) reference equations for DLNO (6-s breath-hold time) analyzed. DLCOz-scores from GLI and DLNOz-scores from any reference equations showed high sensitivity and specificity for both IPF and PE, with DLCO showing the highest diagnostic accuracy for PE and DLNO from Munkholm et al. for IPF. However, the best thresholds separating IPF and PE from control subjects were widely different and ranging from ∼14th percentile (-1.100 z-score) for DLCO GLI to ∼3rd percentile (-1.885 z-score) for DLNO ERS. The z-scores of DLCO GLI showed the strongest negative correlation with PE (r = -0.710, P < 0.0001) and DLNO ERS with IPF (r = -0.754, P < 0.0001) but in females z-scores from ERS were not significantly correlated with extent of IPF.
Conclusions:
DLCO and DLNO thresholds separating subjects with IPF or PE from healthy controls may differ substantially from standard LLN of -1.645 and -1.960 z-scores. For DLCO it may be due to inhomogeneous impairment of blood-to-air barrier whereas for DLNO different devices and reference equations seem to play a major role. Clinical trial registered with https://register.
Clinicaltrials:
gov/prs/beta/records (ClinicalTrials.gov Identifier: NCT07091838).
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