Aerosol Generation During Methacholine Challenge Testing: Clinical Implications During the COVID-19 Pandemic

Abstract

Rationale: Methacholine challenge testing (MCT) is a common bronchoprovocation technique to assess airway hyperresponsiveness. Current ATS/ERS MCT technical standards recommend a one-minute tidal breathing protocol with a doubling or quadrupling dosing strategy to standardize dosing and delivery. A variety of delivery devices are commonly used in laboratory testing, all of which generate substantial particle volumes that present significant infection control concerns given the ongoing COVID-19 pandemic. We compared small particle generation with two different nebulizer devices and a dosimeter, each with and without a viral filter. Methods: In order to optimize signal-to-noise ratio and to detect ultrafine particle generation in ambient air, the study was performed in a highly controlled, nearly particle-free, sealed room representing a small simulated procedure area (74 x 36 x 36 inches). Two devices continuously sampled the ambient air during the procedure, detecting ultrafine (P-Trak, 0.02 - 1 μ m) and a broader range (Fluke, 0.3, 0.5, 1.0, 2.0, 5.0, and 10 μ m) of particles respectively. Five healthy participants performed simulated MCT using nebulized saline after one-minute of unmasked tidal breathing, including five, one-minute tidal breathing periods, each of which was followed by three simulated FVC maneuvers through a commercially available viral filter (Vyaire Microguard II). Each subject then repeated the same simulated MCT with a HEPA quality filter attached to the exhalation port to minimize expelled particle volume. Testing was performed using the Hudson Micromist, PARI LC Plus, and Koko dosimeter. Results: Mean ultrafine particle generation is demonstrated in Figure 1. Unmasked tidal breathing generated 3.1±1.7 ultrafine particles per cubic centimeter (p/cc). Unfiltered Koko dosimeter generated 5358±2853 p/cc;addition of a viral filter decreased particle generation to 635±301 p/cc (p<0.0001). Unfiltered PARI LC Plus generated 20540±3257 p/cc;addition of a viral filter decreased particle generation to 3153±1201 (p<0.0001). Unfiltered Hudson Micromist generated 52140±13772 p/cc;addition of a viral filter decreased particle generation to 5345±985 p/cc (p<0.0001). Similar reductions in particles <1 μ m were observed with viral filters using the Fluke device. Conclusions: MCT was associated with substantial production of small particles, with a predominance of ultrafine particles (0.02-1 μ m). Addition of a viral filter led to significant reductions in small particle generation with all devices used but there were significant differences between delivery systems, representing potentially important infection control considerations. Testing with additional participants and nebulizer devices is ongoing, in addition to experimental measurement of the impact of a viral filter on methacholine dose delivery.