Acinar effect of inhaled steroids evidenced by exhaled nitric oxide

Abstract

The effects of inhaled corticosteroids (ICSs) on distal lung inflammation, as assessed by alveolar nitric oxide concentration (C(A)NO), are a matter of debate. Recently, a theoretic study suggested that acinar airway obstruction that is relieved by ICS treatment and associated with a decrease in fraction of exhaled nitric oxide (FeNO) concentration might, paradoxically, increase C(A)NO. This increase could be a hallmark effect of ICSs at the acinar level. In the light of this new hypothesis, we studied changes in C(A)NO and FeNO after administration of ICSs. C(A)NO and FeNO were measured before and after ICS treatment of 38 steroid-naive patients with uncontrolled asthma who showed clinical improvement after ICS therapy. The average FeNO decreased from 78.3 to 28.9 ppb (P< .001); C(A)NO decreased from 7.7 to 4.3 ppb (P= .009). In 14 subjects (low-slope group), slope(= ΔC(A)NO/ΔFeNO) values (Δ=post-ICS- pre-ICS value) were less than the 95% normal CI (average ΔFeNO= -32.7 ppb and average ΔC(A)NO= +2.9 ppb). In this group, baseline C(A)NO was abnormally low when FeNO was taken into account. In 11 subjects (the high-slope group), the slope was above the normal interval (average ΔFeNO= -42.5 ppb and average ΔC(A)NO= -14.7 ppb). Opposite patterns (one that was predicted) can indicate peripheral actions of ICSs; this difference might account for conflicting data reported from studies using C(A)NO to determine the peripheral action of ICSs. We show that a low C(A)NO does not preclude distal inflammation.