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JOURNAL ARTICLE
REVIEW
Rationale underlying the measurement of fractional exhaled nitric oxide in systemic sclerosis patients.
Clinical and Experimental Rheumatology 2019 July
Systemic sclerosis (SSc) is an autoimmune disease characterised by tissue fibrosis leading to vascular injury. Nitric oxide (NO) has been implicated in the pathogenesis of autoimmune diseases. A deficiency in basal NO production by the constitutive endothelial isoform of nitric oxide synthase may promote vasoconstriction and vascular wall thickening. In January 2017, we searched the PubMed/Medline, Cochrane Library and Enbase/Medline databases for studies analysing physio-pathological correlations with lung fractional exhaled NO (FeNO) production. This review describes the rationale underlying possible applications of FeNO measurements in the management of SSc. Measuring NO levels at multiple expiratory flow rates makes it possible to distinguish airway NO production and distal airway/alveolar NO concentration (ANOC), and there is increasing evidence indicating that it may be useful in many non-respiratory conditions. FeNO levels are increased in SSc patients with fibrosing lung disease, whereas those with pulmonary hypertension have relatively low FeNO levels, thus suggesting that NO plays an important role in regulating pulmonary vascular resistance in SSc. However, a number of studies have shown increased ANOC in SSc patients without increased FeNO levels. The relationship between lung diffusing capacity for carbon monoxide and ANOC may be related to increased alveolar membrane thickness impeding NO diffusion or alveolar inflammation in SSc lung disease. The findings concerning the usefulness of FeNO measurements in SSc patients are discordant, but the available papers suggest that ANOC is a more accurate indicator of progressive lung dysfunction and an increase in ANOC could assess the extent of interstitial lung disease non-invasively.
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