Safety of and Cellular Response to Segmental Bronchoprovocation in Allergic Asthma

<div><h3>Rationale</h3><p>Despite its incorporation into research studies, the safety aspects of segmental allergen bronchoprovocation and differences in cellular response among different allergens have received limited consideration.</p> <h3>Methods</h3><p>We performed 87 segmental challenges in 77 allergic asthma subjects. Allergen dose was based on each subject’s response to whole lung allergen challenge. Bronchoalveolar lavage was performed at 0 and 48 hours. Safety indicators included spirometry, oxygen saturation, heart rate, and symptoms.</p> <h3>Results</h3><p>Among subjects challenged with ragweed, cat dander, or house dust mite, there were no differences in safety indicators. Subjects demonstrated a modest oxygen desaturation and tachycardia during the procedure that returned to normal prior to discharge. We observed a modest reduction in forced vital capacity and forced expiratory volume in one second following bronchoscopy. The most common symptoms following the procedure were cough, sore throat and fatigue. Total bronchoalveolar lavage fluid cell numbers increased from 13±4 to 106±108×10⁴ per milliliter and eosinophils increased from 1±2 to 44±20 percent, with no significant differences among the three allergens.</p> <h3>Conclusions</h3><p>In mild allergic asthma, segmental allergen bronchoprovocation, using individualized doses of aeroallergens, was safe and yielded similar cellular responses.</p> </div

Comparison of oxygen saturation and heart rate on D0 and 48 hours after SBP-AG (D2).

<p>On D0, oxygen saturation and heart rate were monitored immediately before initiation of bronchoscopy, during BAL, during SBP-AG, immediately after the procedure, and at discharge. On D2, hemodynamic monitoring was done immediately before bronchoscopy, during BAL, immediately after the procedure, and at discharge. Bars represent median with 25 and 75^th percentiles for subjects challenged with RW (white), HDM (gray), CAT (black). Whisker lines represent 10 and 90^th percentiles. *p<0.05 compared to value for respective allergen group immediately before procedure. NS indicates there were no significant differences among allergen groups for the indicated time point.</p

Comparison of BAL on D0 and 48 hours after SBP-AG (D2).

<p>Data reflect cells as a percentage of total cells for subjects challenged with RW (white), HDM (gray), or CAT (black) allergen. Bars represent median with 25 and 75^th percentiles. Whisker lines represent 10 and 90^th percentile. *p<0.05 for D2 compared to D0 for respective allergen group. NS indicates there were no significant differences among allergen groups for the indicated cell type.</p

Comparison of FEV₁, FVC, and FEV₁/FVC on D0 and 48 hours after SBP-AG (D2) pre-BAL and immediately after BAL.

<p>Data are from subjects challenged with RW (white), HDM (gray), or CAT (black) allergen. Bars represent median with 25 and 75^th percentiles for challenged subjects. Whisker lines represent 10 and 90^th percentiles. *p<0.05 for D2 pre-BAL compared to D0 pre-BAL for respective allergen group, ^†p<0.05 for D0 post-BAL compared to D0 pre-BAL for respective allergen group. NS indicates there were no significant differences among allergen groups for the indicated time point.</p

Baseline subject characteristics.

<p>Baseline subject characteristics.</p

Symptoms during and after bronchoscopy.

1<p>Data reflect the percent of subjects for each of the three administered allergens. Symptoms not available for 1 RW, 4 HDM, and 1 CAT procedures 12 h post bronchoscopy; and 2 RW, 2 HDM, and 5 CAT procedures 24 h post bronchoscopy.</p><p>(Percentage of subjects reporting each symptom among RW [n = 25], HDM [n = 32] or CAT [n = 30])^1.</p