Scanlon, Paul D.

Abstract Background Single breath diffusing capacity of the lung for carbon monoxide (DLCO) remains the most widely used test to assess pulmonary gas exchange. GLI DLCO reference equations are based on a larger, more diverse dataset and offer age-specific and internally consistent reference values. However, their impact on interpretation in a real-world population remains uncertain. Research Question Describe the direction and magnitude of DLCO interpretation changes resulting from our multicenter PFT laboratory transition from Miller to GLI reference equations. Study Design and Methods In this multicenter cross-sectional study, we reanalyzed 88,060 DLCO measurements in a large pulmonary function laboratory database performed between 2016 and 2022 using GLI and Miller reference equations, stratified by self-reported race and ethnicity. Baseline patient characteristics and lung function measurements were summarized with continuous characteristics as median (IQR) and categorical variables as n (%). Kruskal-Wallis test was used to evaluate the difference between GLI and Miller DLCO % predicted difference between races, and two-by-two and four-by-four tables were generated to summarize the proportion of concordance and discordance of GLI to Miller severity levels. A repeated measures multivariable logistic regression was used to evaluate discordance between GLI and Miller severity and patient characteristics (age, sex, race, and BMI). Results We included 63,357 individuals with 88,060 PFT visits; 91.6% (58,076) identified as Caucasian, 5.2% (3,262) as Black, 1.4 % (895) as Asian, and 1.8% (1,113) as mixed/other race. Fifty-one percent were female with an median age of 64 years (range: 5- 85). 7.4% (6509) of DLCO results were discordant, with 0.5% (n = 439) abnormal by GLI only, and 6.9% (n = 6070) abnormal by Miller only. Compared to the Miller, GLI interpretations were associated with a greater shift toward normal interpretations. Younger age, lower BMI, female sex, and being of NE Asian, SE Asian, or Other/mixed race compared to Caucasian were associated with higher odds of discordance in DLCO severity/normal classification. Interpretation The use of GLI reference equations substantially alters the interpretation of DLCO results, shifting a meaningful subset of patients from abnormal to normal classification. While GLI reference equations offer more comprehensive, population-based approach, it is crucial to place these interpretations within the context of the patient presentation until further investigations more clearly define the clinical implications of these transitions. This abstract is funded by: none

Abstract Rationale Global Lung Function Initiative (GLI) Global spirometry reference equations were recently derived to offer a “race-neutral” interpretation option. The impact of transitioning from the race-specific GLI-2012 to the GLI Global reference equations is unknown. Objectives Describe the direction and magnitude of changes in predicted lung function measurements in a population of diverse race and ethnicity using GLI Global in place of GLI-2012 reference equations. Methods In this multicenter cross-sectional study using a large pulmonary function laboratory database, 109,447 spirometry tests were reanalyzed using GLI Global reference equations and compared with the existing GLI-2012 standard, stratified by self-reported race and ethnicity. Measurements and Main Results Mean FEV1 and FVC percent predicted increased in the White and Northeast Asian groups and decreased in the Black, Southeast Asian, and mixed/other race groups. The prevalence of obstruction increased by 9.7% in the White group, and prevalences of possible restriction increased by 51.1% and 37.1% in the Black and Southeast Asian groups, respectively. Using GLI Global in a population with equal representation of all five race and ethnicity groups altered the interpretation category for 10.2% of spirometry tests. Subjects who self-identified as Black were the only group with a relative increase in the frequency of abnormal spirometry test results (32.9%). Conclusions The use of GLI Global reference equations will significantly impact spirometry interpretation. Although GLI Global offers an innovative approach to transition from race-specific reference equations, it is important to recognize the continued need to place these data within an appropriate clinical context.

BACKGROUND: Methacholine challenge testing (MCT) is a common bronchoprovocation technique used to assess airway hyper-responsiveness. We previously demonstrated that the addition of a viral filter to the nebulizer exhalation limb substantially reduced expelled particles during MCT. Our aim was to evaluate whether this modification affects the delivered dose of methacholine. METHODS: A mechanical ventilator was connected to a lung simulator with breathing frequency 15 breaths/min, tidal volume 500 mL, inspiratory-expiratory ratio 1:1, with a sinusoidal waveform. We compared methacholine dose delivery using the Hudson Micro Mist or AeroEclipse II BAN nebulizers powered by either a dry gas source or a compressor system. A filter placed in line between the nebulizer and test lung was weighed before and after 1 min of nebulized methacholine delivery. Mean inhaled mass was measured with and without a viral filter on the exhalation limb. Dose delivery was calculated by multiplying the mean inhaled mass by the respirable fraction (particles < 5 μm) and inhalation time. Unpaired t test was used to compare methacholine dose delivery with and without viral filter placement. RESULTS: The addition of a viral filter did not significantly affect methacholine dose delivery across all devices tested. Using a 50-psi dry gas source, dose delivered with or without a viral filter did not differ with the Hudson (422.3 μg vs 282.0 μg, P = .11) or the AeroEclipse nebulizer (563.0 μg vs 657.6 μg, P = .59). Using the compressor, dose delivered with and without a viral filter did not differ with the Hudson (974.0 μg vs 868.0 μg, P = .03) or the AeroEclipse nebulizer (818.0 μg vs 628.5 μg, P = .42). CONCLUSIONS: The addition of a viral filter to the nebulizer exhalation limb did not affect methacholine dose during bronchoprovocation testing. Routine use of a viral filter should be considered to improve pulmonary function technician safety and infection control measures during the ongoing COVID-19 pandemic.

BACKGROUND: Methacholine bronchoprovocation or challenge testing (MCT) is commonly performed to assess airway hyper-responsiveness in the setting of suspected asthma. Nebulization is an aerosol-generating procedure, but little is known about the risks of MCT in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. We aimed to quantify and characterize aerosol generation during MCT by using different delivery methods and to assess the impact of adding a viral filter. METHODS: Seven healthy subjects performed simulated MCT in a near particle-free laboratory space with 4 different nebulizers and with a dosimeter. Two devices continuously sampled the ambient air during the procedure, which detected ultrafine particles, from 0.02–1 μm, and particles of sizes 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm, respectively. Particle generation was compared among all the devices, with and without viral filter placement. RESULTS: Ultrafine-particle generation during simulated MCT was significant across all the devices. Ultrafine-particle (0.02–1 μm) concentrations decreased 77%–91% with the addition of a viral filter and varied significantly between unfiltered (P < .001) and filtered devices (P < .001). Ultrafine-particle generation was lowest when using the dosimeter with filtered Hudson nebulizer (1,258 ± 1,644 particle/mL). Ultrafine-particle concentrations with the filtered nebulizer devices using a compressor were higher than particle concentrations detected when using the dosimeter: Monaghan (3,472 ± 1,794 particles/mL), PARI (4,403 ± 2,948), Hudson (6,320 ± 1,787) and AirLife (9,523 ± 5,098). CONCLUSIONS: The high particle concentrations generated during MCT pose significant infection control concerns during the COVID-19 pandemic. Particle generation during MCT was significantly reduced by using breath-actuated delivery and a viral filter, which offers an effective mitigation strategy.