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BACKGROUND: The guidelines to conduct and interpret conventional pulmonary function (PFT) tests are frequently reviewed and updated. However, the quality assurance and quality control (QA/QC) guidelines for respiratory oscillometry testing remain limited. QA/QC guidelines are essential for oscillometry to be used as a diagnostic pulmonary function test (PFT) in a clinical setting. METHODS: We developed a QA/QC protocol shortly after oscillometry was introduced in our laboratory as part of a clinical study. The first clinical study began after the research personnel completed 3 h of combined didactic and hands-on training and establishment of a standard operating protocol (SOP) for oscillometry testing. All oscillometry tests were conducted using the initial SOP protocol from October 17, 2017, to April 6, 2018. At this time, the first QA/QC audit took place, followed by revisions to the SOP, the addition of a QA/QC checklist, and the development of a 12-h training program. A second audit of oscillometry tests was conducted from April 9, 2018, to June 30, 2019. Both audits were completed by a registered cardiopulmonary technologist from the Toronto General Pulmonary Function Lab. RESULTS: The first audit evaluated 197 paired oscillometry-PFT tests and found 10 tests (5.08%) to be invalid, with a coefficient of variation > 15%. The second audit examined 1,930 paired oscillometry-PFT tests; only 3 tests (0.16%) were unacceptable, with a coefficient of variation > 15%. Improvement in QA/QC was significantly better compared to the first audit (P < .001). CONCLUSIONS: Although oscillometry requires minimal subject cooperation, application of the principles that govern the conduct and application of a PFT are important for ensuring that oscillometry testing is performed according to acceptability and reproducibility. Specifically, the inclusion of a SOP, a proper training program, a QA/QC checklist, and regular audits with feedback are vital to ensure that oscillometry is conducted accurately and precisely.

Purpose: The CYP3A5*1 polymorphism, predominant in African Americans (AAs), and drug interactions with CYP3A inhibitors/inducers significantly impact tacrolimus metabolism. Minimal data evaluating tacrolimus dose requirements (TDRs) in lung transplant recipients (LTRs) on concurrent strong CYP3A inhibitors exists. We sought to assess the effect of race on TDRs and transplantation outcomes in a cohort of LTRs initiated on a fixed tacrolimus dose and antifungal prophylaxis with a systemic azole after transplant. Methods: All adult LTRs transplanted from 1/2015-10/2019 initiated on an equivalent tacrolimus dose posttransplant per institutional protocol were included and stratified by race. TDRs, tacrolimus levels, systemic azole use, biopsy proven acute rejection (BPAR), patient survival, and graft survival for the first year posttransplant were evaluated. Results: 68 LTRs were included (10 AA, 58 non-AA); the majority were on a systemic azole at 1 (90.8%) and 3 (90.3%) months posttransplant. TDRs were significantly higher in AAs at the first therapeutic level, discharge, and months 1, 3, 12 posttransplant (Figure 1); tacrolimus levels and time within therapeutic range (55% AA vs 40.5% non-AA, p=0.13) were similar. AAs had a similar time to first therapeutic level (11.2 days AA vs 7.8 days non-AA, p=0.10) and number of dose adjustments to achieve this level (4 vs 2.6, p=0.08). The majority of LTRs did not achieve a therapeutic tacrolimus level prior to discharge (80% AA vs 69% non-AA, p=0.48). No differences in BPAR (20% AA vs 25.9% non-AA, p=0.69), patient survival (100% AA vs 86.2% non-AA, p=0.21), or graft survival (100% for both) within 12 months posttransplant were observed. Conclusion: While AA LTRs had significantly higher TDRs to maintain similar trough levels compared to non-AAs, this did not influence transplantation outcomes. Further research is needed to determine the optimal dosing strategy in LTRs immediately posttransplant.

Resting muscle sympathetic nerve activity (MSNA) displays high inter‐individual variability, yet the neural characteristics of those with high vs. low MSNA and resultant cardiovascular consequences are largely unclear. The purpose of this study was to examine blood pressure (BP) variability at rest and during exercise in individuals with high vs. low resting MSNA, and to characterize differences in resting sympathetic and cardiac baroreflex sensitivity (cBRS), in order to understand the accompanying neural characteristics and cardiovascular consequences of different levels of vasoconstrictor outflow. We retrospectively analyzed MSNA (microneurography) and continuous BP (Finometer) obtained at rest and during 2 minutes of static handgrip exercise at 30% maximal voluntary contraction from 60 young healthy men (n=30) and women (n=30). Within each sex, data was split into tertiles based on resting MSNA burst frequency and a comparative analysis was performed on the highest vs. lowest MSNA groups. BP variability was calculated as the beat‐to‐beat standard deviation. Spontaneous sympathetic baroreflex sensitivity (sBRS) was calculated using a weighted linear regression between diastolic blood pressure (DBP) and MSNA burst incidence. Threshold values (T50) were obtained by calculating the resting DBP associated with 50% of the MSNA bursts. cBRS was determined using the sequence technique. As expected, resting MSNA burst frequency was different between high and low groups (30±4 vs. 14±6 bursts/min [mean±SD], p<0.01), however, baseline anthropometrics, BP, heart rate, and cBRS sensitivity were not different (all, p>0.05). Resting DBP variability was lower in the high group (4±1 vs. 5±2 mmHg, p=0.05). sBRS was higher in the high group (−5.4±1.9 vs. −4.6±1.6 bursts/100 heartbeats/mmHg, p<0.01), and was correlated with resting MSNA (r=−0.46, p<0.01). T50 did not differ between the groups (60 vs. 55 mmHg, p>0.05), however, the prevailing mean DBP was above the T50 DBP to a lower extent in the high group (mean DBP – T50 DBP: 10±3 vs. 18±7 mmHg, p<0.01), and this value was negatively correlated with resting MSNA burst incidence (r=−0.76, p<0.01). During static handgrip exercise, BP and heart rate increased similarly in both groups (all, p>0.05), yet the increase in MSNA burst frequency was smaller in the high group (Δ 4±7 vs 10±6 bursts/min, p<0.01); similar results were obtained using MSNA burst incidence and total MSNA (both p<0.01). The change in burst frequency was unrelated to resting sBRS (r=0.23, p>0.05). Systolic BP variability was lower in the high group during exercise (7±3 vs 10±5 mmHg, p<0.05), but DBP variability was not different. In conclusion, differences in resting MSNA are unrelated to resting and exercising BP, but are likely associated with inter‐individual differences in the degree of BP variability and arterial baroreflex‐mediated suppression of MSNA. Further, baseline MSNA was found to influence the magnitude of the change during static handgrip exercise, though the hemodynamic consequences of these differences, and mechanisms responsible warrant further research.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant; Canada Foundation for InnovationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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