Mj. Lanz et al., The effect of low-dose inhaled fluticasone propionate on exhaled nitric oxide in asthmatic patients and comparison with oral zafirlukast, ANN ALLER A, 87(4), 2001, pp. 283-288
Background: Exhaled nitric oxide (ENO) is a noninvasive marker of ongoing i
nflammation in asthmatic patients. Comparison between inhaled and oral anti
inflammatory medications in reduction of ENO in asthmatic patients has not
been performed.
Objective: We measured changes in ENO, spirometry, need for rescue medicati
on quality of life (QOL), and diary scores (DS) after inhaled and oral anti
inflammatory therapy in adults with moderate asthma.
Methods: A randomized, double-blind, placebo-controlled, crossover design w
ith 4-week washout periods was used. A plateau level of ENO, measured in pa
rts per billion (ppb), was obtained by chemiluminescence with a Sievers 280
NOA as per American Thoracic Society recommendations. Eighteen asthmatic ad
ults (15 Hispanic, with a percentage predicted forced expiratory volume in
I second (FEV1%) of 50% to 85%) on bronchodilators (beta (2)) only were stu
died. Subjects used fluticasone propionate (FP) metered-does inhaler (44 mu
g), two puffs twice daily, and matching placebo (PB) for 4 weeks. Eight of
the asthmatic patients (7 Hispanic, FEV1% 50% to 85%) on bronchodilators on
ly then received blinded zafirlukast (ZK) 20 mg and matching PB twice daily
for 4 weeks.
Results: Low-dose inhaled FP resulted in significant improvements in ENO, s
pirometry, QOL, DS, and beta (2) use. A significant difference in mean ENO
was found (P < 0.01) before and after FP from 34 <plus/minus> 7 ppb to 13 /- 3 ppb. A significant improvement was found (P < 0.05) with FEV1% from 75
<plus/minus> 3 to 85 +/- 3 with FP treatment. The other measured parameter
s, percentage predicted of peak expiratory flow rate, beta (2) need, DS, an
d QOL measurements, were improved with low-dose FP treatment, No significan
t reduction was found in ENO with oral ZK for 4 weeks. After oral ZK washou
t and the second extension arm of placebo, ENO significantly increased back
to 47 +/- 14 ppb (P < 0.05), but spirometry measures did not worsen. Signi
ficant improvements were found with DS and <beta>(2) use with oral ZK thera
py.
Conclusions: These results reveal ENO is reduced with only low-dose inhaled
Fl? in asthmatic patients not on anti-inflammatory medication. In the smal
ler extension study, ENO was reduced with FP and not with oral ZK treatment
, and ENO levels increased back to near prestudy levels after ZK washout an
d the second extension arm of placebo. As a marker of inflammation, ENO lev
els reveal an improvement with anti-inflammatory medication and worsening w
hen it is discontinued.