Kelley, Eli F.

ABSTRACT Introduction Measurement of the work of breathing (Wb) during exercise provides useful insights into the energetics and mechanics of the respiratory muscles across a wide range of minute ventilations. The methods and analytical procedures used to calculate the Wb during exercise have yet to be critically appraised in the literature. Purpose The aim of this systematic review was to evaluate the quality of methods used to measure the Wb during exercise in the available literature. Methods We conducted an extensive search of three databases for studies that measured the Wb during exercise in adult humans. Data were extracted on participant characteristics, flow/volume and pressure devices, esophageal pressure (P oes ) catheters, and methods of Wb analysis. Results A total of 120 articles were included. Flow/volume sensors used were primarily pneumotachographs ( n = 85, 70.8%), whereas the most common pressure transducer was of the variable reluctance type ( n = 63, 52.5%). Esophageal pressure was frequently obtained via balloon-tipped catheters ( n = 114, 95.0%). Few studies mentioned calibration, frequency responses, and dynamic compensation of their measurement devices. The most popular method of measuring the Wb was pressure–volume integration ( n = 51, 42.5%), followed by the modified Campbell ( n = 28, 23.3%) and Dean & Visscher diagrams ( n = 26, 21.7%). Over one-third of studies did not report the methods used to process their pressure–volume data, and the majority (60.8%) of studies used the incorrect Wb units and/or failed to discuss the limitations of their Wb measurements. Conclusions The findings of this systematic review highlight the need for the development of a standardized approach for measuring Wb, which is informative, practical, and accessible for future researchers.

The purpose of this study was to determine whether the longitudinal progression of decline in left ventricular ejection fraction (LVEF) in Duchenne muscular dystrophy (DMD) patients is moderated by ADRB1 genotype and whether the efficacy of ß-blocker therapy is influenced by genotype status. About 147 DMD patients (6-34 years.) were analyzed with a focus on β 1 adrenergic receptor (ADRB1) genotype variants. Patients were grouped by ADRB1 genotype resulting in Gly389 patients and Arg389 patients. A generalized additive mixed effects model was used to examine differences in the nonlinear trend of LVEF across patient ages between genotype groups and for ß-blocker use. Both genotype groups displayed a progressive decline in LVEF starting around the mean age of ambulation loss (~12 years). However, there was no difference between genotype groups in the progression of decline in LVEF. There was a significant effect of ß-blocker use on longitudinal LVEF, wherein patients on ß-blockers had systematically lower LVEF when compared to patients not on ß-blockers. However, the effect of ß-blocker therapy on LVEF was not affected by ADRB1 genotype. The current study did not demonstrate an influence of patient ADRB1 genotype on longitudinal LVEF in our cohort. Despite previous literature suggesting a positive influence of ß-blocker use on cardiac function in DMD patients and of an ADRB1 genotypic difference in responsiveness to ß-blocker use, we did not observe this in our cohort. Interestingly, our cohort did not demonstrate a positive influence of ß-blocker use on LVEF measures.

Duchenne muscular dystrophy (DMD) is an inheritable disease that presents itself in diminished respiratory function and is the main contributor to mortality in these patients. The main respiratory concerns in DMD are reduced diaphragmatic function, reduced mucocilliary clearance, increased muscle proteolysis, and increased inflammation. The Gly16 variant of the β 2 ‐adrenergic receptor (ADRB2) has been identified as providing a protective effect for respiratory weakness. The aim of this study was to identify the influence of ADRB2 genotype on the age of use for nocturnal ventilatory assistance in DMD. Data from CINRG‐DNHS including 175 DMD patients (ages 3–25 years) with up to 9.7 years follow‐up were analyzed focusing on ADRB2 functional variants. We performed Cox proportional hazard and Kaplan‐Meier time to event analyses for the age of nocturnal ventilation use. There were no differences between genotype groups in age, height, weight, corticosteroid use, number of ambulatory patients, or age of loss of ambulation. The genotype groups differed significantly in the age at which nocturnal ventilation use was prescribed with the Gly16 demonstrating a 2.77‐fold increased risk of using nocturnal ventilation at any given age. These data suggest that genetic variations in the ADRB2 gene may influence the age of nocturnal ventilation use in DMD. Specifically, the Gly16 polymorphism of the ADRB2 may have a deleterious effect on age of nocturnal ventilation use in DMD. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Background : Research suggests the beta‐1 adrenergic receptor (ADRB1) has been shown to play a functional role in cardiomyocyte function and accounts for up to 80% of the cardiac tissue adrenergic receptors with ADRB1 stimulation increasing cardiac rate, contractility, and work. Multiple polymorphisms of the ADRB1 have been identified such as the Gly49 polymorphism that includes at least one glycine (Gly) for serine (Ser) at amino acid 49 resulting in either homozygous for Gly (Gly49Gly) or heterozygous for Gly (Gly49Ser) polymorphisms. The Gly49 polymorphism has been shown to have decreased receptor density, decreased cAMP accumulation, and a dampening influence on the cardiostimulant effect during norepinephrine infusion. Heart failure patients with this polymorphism (Gly49) have also been shown to have improved cardiac function and decreased mortality risk, but if there is an effect in healthy subjects is less clear. This suggests the Gly49 polymorphism may have cardioprotective effects similar to that of a beta‐blocker. Purpose The purpose of this study was to determine the effects of the Gly/Ser polymorphism at position 49 of the ADRB1on the cardiovascular response to exercise in healthy subjects. Methods We performed genotyping of the ADRB1 (amino acid 49) and high‐intensity, steady‐state exercise on 71 healthy subjects (Ser49Ser = 52, Gly49Ser = 19). Results There were no differences between genotype groups in age, height, weight, BMI, or watts achieved (age = 28.9 ± 5.6yrs., 30.6 ± 6.4yrs., height = 173.6 ± 9.9cm, 174 ± 7.5cm, weight = 74.4 ± 13.3kg, 71.9 ± 13.5kg, BMI = 24.6 ± 3.5, 23.6 ± 3.3, and watts = 223.8 ± 76.8, 205 ± 49.4, for Ser49Ser and Gly49Ser respectively). Additionally, there were no differences for genotype groups for cardiac output (CO), systolic blood pressure (BP sys ), or diastolic blood pressure (BP dias ) at rest, peak exercise, or in change from rest to peak exercise. The genotype groups differed significantly in heart rate (HR max ) at peak exercise and cardiac index at rest (CI) (HR max = 184.2 ± 9.5bpm, 190.7 ± 10.6bpm, CI = 0.063 ± 0.014, 0.071 ± 0.013, for Ser49Ser and Gly49Ser respectively). There was a trend towards significance (p = 0.058) for the change in stroke volume from rest to peak exercise (ΔSV) (0.016 ± 0.018L, 0.0076 ± 0.012L, for Ser49Ser and Gly49Ser respectively). Conclusion : These data suggest genetic variations of the ADRB1 may influence cardiovascular responses to exercise in healthy subjects. Support or Funding Information NIH grants: HL108962‐06 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

The purpose of this report was to 1) detail the construction of a low-cost device that provides a “reference” flow waveform for pneumotachograph (PNT) calibration, i.e., the “syringe potentiometer” (SP), and to compare the 2) accuracy and 3) practical performance of “calibration curves” obtained with the SP device to other more established methods of PNT calibration, i.e., the weighted averaging (WA) and polynomial least-squares (PolyLS) methods. Volume and flow waveforms obtained via the SP device were validated against a motion capture system and were deemed accurate surrogates of actual syringe volume and flows. The SP device was used to construct a calibration curve of a PNT by dividing the flow waveform of the SP by the analog output of the PNT amplifier. A total of 187 inspiratory and 187 expiratory strokes were collected. When the entire data set of expiratory strokes was used, the SP, WA, and PolyLS methods together demonstrated acceptable volume and flow errors as per American Thoracic Society/European Respiratory Society recommendations (less than ±3.5% and less than ±5.0% errors, respectively). The “practical” performance of each method was assessed with a nested subsampling procedure, whereby volume and flow errors were evaluated as the number of strokes was increased (in blocks of 5 strokes). To this end, the SP method demonstrated practical performance superior to that of the WA and PolyLS approaches, whereby acceptable volume and flow errors were achieved after only 5 calibration strokes; the WA and PolyLS methods required 15 and 20 strokes, respectively, to achieve the same level of volume and flow accuracy.NEW & NOTEWORTHY This report describes the construction and validation of a low-cost device for the purposes of pneumotachograph (PNT) calibration: the “syringe potentiometer” (SP). Calibration of a PNT with the SP device yielded acceptable volume and flow errors (<3.5% and 5%, respectively) across a wide range of flows (<0.5 to 15 L/s). The SP device offered superior “practical performance” over other established PNT calibration methods, whereby acceptable volume and flow errors were achieved after only five calibration strokes.