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.
- [show abstract] [hide abstract]
ABSTRACT: We have previously shown that allergen inhalation by asthmatics is associated with increases in bone marrow eosinophil/basophil colony-forming cells (Eo/B-CFU), and increases in CD34(+) hemopoietic progenitors expressing the alpha-subunit of the IL-5 receptor (IL-5Ralpha). This study investigated the effect of inhaled corticosteroid on baseline numbers and allergen-induced increases in these parameters. Nine subjects with mild, stable asthma inhaled budesonide (400 microgram/d) for 8 d in a placebo-controlled, double-blind, randomized crossover study. On Day 7, subjects inhaled allergen, with bone marrow sampling before and 24 h after challenge. Budesonide inhalation significantly attenuated the allergen-induced early and late asthmatic responses, degree of increase in sputum and blood eosinophils, as well as the baseline numbers of total bone marrow CD34(+) cells (p < 0.05), CD34(+)IL-3Ralpha+ cells (p < 0.01) and IL-5-responsive Eo/B-CFU (p < 0.05). Allergen inhalation significantly increased Eo/B-CFU grown in the presence of IL-3, GM-CSF, or IL-5 alone (p < 0.05) and in combination (p < 0.01), as well as the number of CD34(+)IL-5Ralpha+ cells (p < 0.01). However, these increases in Eo/B-CFU and CD34(+)IL-5Ralpha+ cells were not affected by budesonide treatment. These data demonstrate that short-term inhaled budesonide treatment has a systemic effect in inhibiting the turnover of a subpopulation of bone-marrow-derived progenitors, but that inhalation of allergen overcomes this inhibitory effect.American Journal of Respiratory and Critical Care Medicine 05/1999; 159(5 Pt 1):1457-63. · 11.04 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: We investigated acinar airway involvement in 20 patients with stable asthma, using the phase III slope analysis of the multiple breath N2 washout previously applied in a group of patients with COPD (Am. J. Respir. Crit. Care Med. 1998;157:1573-1577). This technique quantifies severity of conductive and acinar components of ventilation maldistribution separately, through indices S(cond) and S(acin), which increase when respective ventilation inhomogeneities increase. We also investigated the effect of salbutamol inhalation on S(cond) and S(acin) in patients with asthma and compared it with that obtained in patients with COPD. Baseline measurements in the patients with asthma show that (1) acinar ventilation inhomogeneity was indeed abnormal in patients with asthma (S(acin) = 0.195 +/- 0.026 L-1) despite the normal diffusing capacity in this group; S(acin) values were intermediate between those obtained in unaffected individuals and patients with COPD, and that (2) conductive ventilation inhomogeneity was abnormal in the patients with asthma (S(cond) = 0.076 +/- 0.006 L-1) but similar to that obtained in the patients with COPD. Measurements after salbutamol inhalations showed significant changes in S(cond) and S(acin) only in the patients with asthma (p < 0.001). This study primarily demonstrated significant, but partially reversible, acinar airway impairment in patients with asthma, as compared with the more severe baseline acinar airway impairment in patients with COPD, which was not reversible after salbutamol inhalation.American Journal of Respiratory and Critical Care Medicine 05/1999; 159(5 Pt 1):1545-50. · 11.04 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The 7-item Asthma Control Questionnaire (ACQ) has been validated to measure the goals of asthma management as defined by international guidelines (minimisation of day- and night-time symptoms, activity limitation, beta(2)-agonist use and bronchoconstriction). Responses are given on a 7-point scale and the overall score is the mean of the responses (0=totally controlled, 6=severely uncontrolled). The aim of this analysis was to determine the cut-point on the ACQ that best differentiates between 'well-controlled' and 'not well-controlled' for (a) clinical practice (low risk of missing 'not well-controlled') and (b) clinical trials (low risk of including 'well-controlled'). All 1323 patients who provided data sets at week 12 in the Gaining Optimal Asthma Control (GOAL) clinical trial were included in the analysis. The gold standard for 'well-controlled' was a composite based on the GINA/NIH guidelines and derived from data collected in the clinical trial diaries and clinic records. The analysis showed that the crossover point between 'well-controlled' and 'not well-controlled' is close to 1.00 on the ACQ. However, to be confident that a patient has well-controlled asthma, the optimal cut-point is 0.75 (negative predictive value=0.85). To be confident that the patient has inadequately controlled asthma, the optimal cut-point is 1.50 (positive predictive value=0.88). In conclusion, knowledge of these cut-points will enhance practising clinicians ability to identify patients whose asthma requires additional treatment, enable investigators to enroll poorly controlled patients into studies and for both clinicians and investigators to evaluate whether treatment goals are being achieved.Respiratory Medicine 05/2006; 100(4):616-21. · 2.59 Impact Factor