PT  - JOURNAL ARTICLE
AU  - J. Cohen
AU  - D.S. Postma
AU  - W.R. Douma
AU  - J.M. Vonk
AU  - A.H. De Boer
AU  - N.H.T. ten Hacken
TI  - Particle size matters: diagnostics and treatment of small airways involvement in asthma
AID  - 10.1183/09031936.00204109
DP  - 2011 Mar 01
TA  - European Respiratory Journal
PG  - 532--540
VI  - 37
IP  - 3
4099  - http://erj.ersjournals.com/content/37/3/532.short
4100  - http://erj.ersjournals.com/content/37/3/532.full
SO  - Eur Respir J2011 Mar 01; 37
AB  - Small airways are an important site of inflammation and obstruction in asthma, which contributes to the severity of airway hyperresponsiveness (AHR) that is usually measured by nebulisation of large-particle stimuli. We investigated whether small and large particle sizes of aerosolised adenosine monophospate (AMP) provoke similar severity of AHR. Additionally, effects of the small-particle inhaled corticosteroid (ICS) ciclesonide and large-particle ICS fluticasone on AHR to large- and small-particle size AMP were assessed. After a 4-week run-in period using open-label fluticasone (100 μg b.i.d.), 37 mild-to-moderate asthmatics underwent provocations with standard-size (3.7 μm), large-particle (9.9 μm) and small-particle (1.06 μm) AMP. Subjects received 4-week ciclesonide (160 μg s.i.d.) or fluticasone (100 μg b.i.d.) treatment (double-blind and double-dummy) followed by large- and small-particle AMP provocation. Small-particle AMP induced a 20% decrease in forced expiratory volume in 1 s (FEV1) at a significantly higher dose than large-particle AMP. Ciclesonide and fluticasone had comparable effects on AMP provocations. Not all subjects reached the provocative concentration causing a 20% fall in FEV1 (PC20) at the highest AMP dose. In those who did, ciclesonide improved small-particle AMP PC20 by 1.74 doubling doses (DD) (p = 0.03), whereas fluticasone did not. Conversely, fluticasone improved large-particle AMP PC20 significantly (1.32 DD; p = 0.03), whereas ciclesonide did not. Small-particle AMP provocation appears to be a promising tool to assess changes in small airway inflammation. Future adjustments are necessary taking into account the very small particle size used, with large exhaled fractions. In asthmatics reaching a PC20 with small- and large-particle AMP provocations, ciclesonide improves hyperresponsiveness to small particle size AMP, and fluticasone to large particle size. This warrants further research to target provocations and treatment to specific airway sizes.