Bronchial challenge test in asthmatics sensitized to mites: Role of particle size in bronchial response

Although major house dust mite allergen (Der p 1) is carried mainly on large particles (>10 mu m), standard bronchial challenge tests (BCT) use nebulizers that deliver smaller particles (sizes from 1 to 5 mu m) and may therefore not reflect actual domestic exposure. The objective of this study was to evaluate the influence of particle size of Dermatophagoides pteronyssinus extract on bronchial response. Specific BCT were performed with different mass median aerodynamic diameters (MMAD): 1.1, 5.6, and 9.7 mu m. Each of the 19 mite-sensitized patients underwent mite BCT three times, once with each nebulizer. 11-5 levels were assessed in induced sputum and blood samples. The PD20 for Der p 1 differed substantially with particle size, with less Der p 1 (11.2 ng) needed to produce a PD20 with the largest particles (9.7 Am), compared to 18.1 ng for the 5.6 Am particles and 142.5 ng for the 1.1 mu m particles (p < 0.0001). Large particles also induced an early phase response significantly more often than small particles (100% vs. 63%). Although the late phase reaction (LPR) frequency was similar with all three particle sizes, lower mean oral corticosteroid doses were needed to treat LPR with the largest particles (23 mg), compared to the smaller particles, with 34 mg for the 5.6 mu m particles and 51 mg for the 1.1 mu m. The 1.1 mu m particles produced a significantly greater increase in IL-5 concentrations in sputum and blood compared to the larger particles. Large particles clearly play a role in the immediate bronchial response in asthmatics sensitized to mites and, therefore, should be included in pharmacological studies in humans.