Effect of inhaled dust mite allergen on regional particle deposition and mucociliary clearance in allergic asthmatics

Abstract

Background: Acute exacerbations in allergic asthmatics may lead to impaired ability to clear mucus from the airways, a key factor in asthma morbidity.

Objective: The purpose of this study was to determine the effect of inhaled house dust mite challenge on the regional deposition of inhaled particles and mucociliary clearance (MCC) in allergic asthmatics.

Methods: We used gamma scintigraphy (inhalation of (99m) Tc -sulphur colloid particles) to measure the regional particle deposition and MCC in allergic asthmatics (n=12) 4 h following an inhaled dust mite allergen challenge (Dermatophagoides farinae extract; PD(max) =fall in forced expiratory volume in 1 s of 10%) for comparison with baseline non-challenge measures.

Results: In responders (n=9 PD(max) dose), lung function returned to pre-challenge values by 3 h but was significantly decreased at 6 and 24 h in three of the responders (i.e. late-phase response) and induced sputum eosinophils were increased at 24 h post-challenge (P<0.05). Responders showed enhanced bronchial airway deposition of inhaled particles (P<0.05) and slowed clearance from the central lung zone (P<0.01) at 4 h post-challenge compared with the baseline (no allergen challenge) that was predicted by the PD(max) allergen concentration (r=-0.70, P<0.05). The decline in lung function at 24 h post-challenge correlated with reduced MCC from the central lung zone (r=-0.78, P<0.02) and PD(max) . Non-responders (n=3) showed no change in lung function, regional deposition or MCC post-challenge vs. baseline.

Conclusions and clinical relevance: These data suggest that regional deposition and clearance of inhaled particles may be sensitive for detecting mild airway obstruction associated with early- and late-phase allergen-induced effects on mucus secretions. The study was listed on clinicaltrials.gov (NCT00448851).

© 2011 Blackwell Publishing Ltd.

Figures

Figure 1

Schematic of study design showing order and timing of procedures for baseline and allergen challenge study days. *Post challenge spirometry on the challenge day was performed at 10 min, 20 min, 30 min, 1 hr, 90 min, 2 hr, 3 hr, and 6 hr post end of challenge.

Figure 2

Central (C) vs. Peripheral (P) deposition and clearance. Schematic (left) illustrating C and P regions based on outline of Xenon Equilibrium image (center). A deposition image from the same individual is shown on right.

Figure 3

FEV1 as % of initial saline dose as a function of allergen dose in the 9 patients who had at least a 10% drop associated with the challenge. Each symbol represents data from one patient. Those patients who had a late phase response (LPR), i.e. a > 10% fall in FEV1 from pre-challenge at 6 and 24 hours post challenge, are indicated with dashed lines.

Figure 4

Baseline vs. post challenge. (C/P = 1.08 vs. 1.72 and Skew = 1.27 vs. 1.56 respectively).

Figure 5

Whole lung tracheobronchial (TB) retention vs. time for responders, baseline vs. 4 hours post challenge.

Figure 6

a. Central (C) lung TB retention vs. time (for the C region of figure 2) for responders, baseline vs. 4 hours post challenge. b. Central (C) lung TB retention vs. time (bottom) for LPR and nLPR at baseline vs. 4 hours post challenge. 2) c. Central (C) lung TB retention vs. time for non-responders, baseline vs. 4 hours post challenge.

Figure 6

a. Central (C) lung TB retention vs. time (for the C region of figure 2) for responders, baseline vs. 4 hours post challenge. b. Central (C) lung TB retention vs. time (bottom) for LPR and nLPR at baseline vs. 4 hours post challenge. 2) c. Central (C) lung TB retention vs. time for non-responders, baseline vs. 4 hours post challenge.

Figure 6

a. Central (C) lung TB retention vs. time (for the C region of figure 2) for responders, baseline vs. 4 hours post challenge. b. Central (C) lung TB retention vs. time (bottom) for LPR and nLPR at baseline vs. 4 hours post challenge. 2) c. Central (C) lung TB retention vs. time for non-responders, baseline vs. 4 hours post challenge.