Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias

J Appl Physiol (1985). 2016 May 1;120(9):1029-38. doi: 10.1152/japplphysiol.00964.2015. Epub 2016 Feb 18.


Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a nonnegligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO.

Trial registration: NCT02596841.

Keywords: alveolar membrane diffusive conductance; computed tomography; nonspecific interstitial pneumonia; pulmonary capillary volume; usual interstitial pneumonia.

MeSH terms

  • Aged
  • Biomarkers / metabolism*
  • Carbon Monoxide / metabolism
  • Female
  • Humans
  • Idiopathic Interstitial Pneumonias / metabolism*
  • Idiopathic Interstitial Pneumonias / physiopathology*
  • Lung
  • Male
  • Nitric Oxide / metabolism*
  • Pulmonary Diffusing Capacity / physiology*
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / physiopathology*
  • Retrospective Studies
  • Tomography, X-Ray Computed / methods


  • Biomarkers
  • Nitric Oxide
  • Carbon Monoxide

Associated data