Citations

Cardiopulmonary exercise testing (CPET) using a spectrum of different approaches demonstrates usefulness for objectively assessing patient disease severity in clinical and research settings. Still, an absence of trained specialists and/or improper data interpretation techniques can pose major limitations to the effective use of CPET for the clinical classification of patients. This study aimed to test an automated disease likelihood scoring algorithm system based on cardiopulmonary responses during a simplified step‐test protocol. For patients with heart failure (HF), pulmonary hypertension (PAH), obstructive lung disease (OLD), or restrictive lung disease (RLD), we compared patient scores stratified into one of four “silos” generated from our novel algorithm system against patient evaluations provided by expert clinicians. Patients with HF (n = 12), PAH (n = 9), OLD (n = 16), or RLD (n = 10) performed baseline pulmonary function testing followed by submaximal step‐testing. Breath‐by‐breath measures of ventilation and gas exchange, in addition to oxygen saturation and heart rate were collected continuously throughout testing. The algorithm demonstrated close alignment with patient assessments provided by clinical specialists: HF (r = 0.89, P < 0.01); PAH (r = 0.88, P < 0.01); OLD (r = 0.70, P < 0.01); and RLD (r = 0.88, P < 0.01). Furthermore, the algorithm was capable of differentiating major disease from other disease pathologies. Thus, in a clinically relevant manner, these data suggest this simplified automated disease algorithm scoring system used during step‐testing to identify the likelihood that patients have HF, PAH, OLD, or RLD closely correlates with patient assessments conducted by trained clinicians.

The United Kingdom‐Primary Biliary Cholangitis (UK‐PBC) risk scores are a set of prognostic models that estimate the risk of end‐stage liver disease in patients with PBC at 5‐, 10‐ and 15‐year intervals. They have not been externally validated outside the United Kingdom. In this retrospective, external validation study, data were abstracted from outpatient charts and discrimination and calibration of the UK‐PBC risk scores were assessed. A total of 464 patients with PBC treated with ursodeoxycholic acid were included. The median diagnosis age was 52.4 years, and 88% were female patients. The cumulative incidence of events was 6%, 9%, and 15% at 5, 10, and 15 years, respectively. Concordance (c‐statistic) was 0.88, 0.85, and 0.84 using the 5‐, 10‐ and 15‐year risk scores, respectively, which was slightly lower than values observed in the United Kingdom validation cohort. Using the 5‐year risk score, more events were observed than predicted (25 versus 16.8; P = 0.046); using the 10‐year risk score, there was no difference between the observed and predicted number of events (35 versus 44.9; P = 0.14); conversely, using the 15‐year risk score, fewer events were observed than predicted (46 versus 67.5; P = 0.009). Limiting evaluation by the 15‐year UK‐PBC risk score to those with >10 years of follow‐up demonstrated no difference between observed and predicted events. Using the 5‐year risk score, patients within the highest quartile had statistically significant worse event‐free survival compared to the rest of the cohort: 82% versus 98% at 5 years, 73% versus 97% at 10 years, and 58% versus 93% at 15 years. Conclusion: In patients assessed at a North American tertiary medical center, the UK‐PBC risk score had excellent discrimination and was reasonably calibrated both in the short and long term. (Hepatology Communications 2018;2:676‐682)

It is unknown whether the greater total work of breathing (WOB) with aging is due to greater elastic and/or resistive WOB. We hypothesized that older compared with younger adults would exhibit a greater total WOB at matched ventilations (V̇e) during graded exercise, secondary to greater inspiratory resistive and elastic as well as expiratory resistive WOB. Older (OA: 60 ± 8 yr; n = 9) and younger (YA: 38 ± 7 yr; n = 9) adults performed an incremental cycling test to volitional fatigue. Esophageal pressure, inspiratory (IRV) and expiratory reserve volumes (ERV), expiratory flow limitation (EFL), and ventilatory variables were measured at matched V̇e (i.e., 25, 50, and 75 l/min) during exercise. The inspiratory resistive and elastic as well as expiratory resistive WOB were quantified using the Otis method. At V̇e of 75 l/min, older adults had greater %EFL and larger tidal volumes to inspiratory capacity but smaller relative IRV ( P ≤ 0.03) than younger adults. Older compared with younger adults had greater total WOB at V̇Eof 50 and 75 l/min (OA: 90 ± 43 vs. YA: 49 ± 21 J/min; P < 0.04 for both). At V̇e of 75 l/min, older adults had greater inspiratory elastic and resistive WOB (OA: 44 ± 27 vs. YA: 24 ± 22 and OA: 23 ± 15 vs. YA: 11 ± 3 J/min, respectively, P < 0.03 for both) and expiratory resistive WOB (OA: 23 ± 19 vs. YA: 14 ± 9 J/min, P = 0.02) than younger adults. These data demonstrate that aging-induced pulmonary alterations result in greater inspiratory elastic and resistive as well as expiratory resistive WOB, which may have implications for the integrated response during exercise.NEW & NOTEWORTHY Aging-induced changes to the pulmonary system result in increased work of breathing (WOB) during exercise. However, it is not known whether this higher WOB with aging is due to differences in elastic and/or resistive WOB. Herein, we demonstrate that older adults exhibited greater inspiratory elastic and resistive as well as expiratory resistive WOB during exercise.

AbstractAimIn contrast to knowledge that heart failure (HF) patients demonstrate peak exercise uncoupling across ventilation, gas exchange and cardiac haemodynamics, whether this dyssynchrony follows that at the exercise on‐transition is unclear. This study tested whether exercise on‐transition temporal lag for ventilation relative to gas exchange and oxygen pulse (O2pulse) couples with effects from abnormal pulmonary gaseous oxygen store (O2store) contributions to O2 to interdependently precipitate persistently elevated ventilatory demand and low oxidative metabolic capacity in HF.MethodsBeat‐to‐beat HR and breath‐to‐breath ventilation and gas exchange were continuously acquired in HF (N = 9, ejection fraction = 30 ± 9%) and matched controls (N = 10) during square‐wave ergometry at 60% O2peak (46 ± 14 vs 125 ± 54‐W, P < .001). Temporal responses across E, O2 and O2pulse were assessed for the exercise on‐transition using single exponential model Phase II on‐kinetic time constants (τ = time to reach 63% steady‐state rise). Breath‐to‐breath gas fractions and respiratory flows were used to determine O2stores.ResultsHF vs controls: τ for E (137 ± 93 vs 74 ± 40‐seconds, P = .03), O2 (60 ± 40 vs 23 ± 5‐seconds, P = .03) and O2pulse (28 ± 18 vs 23 ± 15‐seconds, P = .59). Within HF, τ for E differed from O2pulse (P < .02), but not O2. Exercise E rise (workload indexed) differed in HF vs controls (545 ± 139 vs 309 ± 88‐mL min−1 W−1, P < .001). Exercise on‐transition O2store depletion in HF exceeded controls, generally persisting to end‐exercise.ConclusionThese data suggest HF demonstrated exercise on‐transition O2store depletion (high O2store contribution to O2) coupled with dyssynchronous E, O2 and O2pulse kinetics—not attributable to prolonged cardiac haemodynamics. Persistent high ventilatory demand and low oxidative metabolic capacity in HF may be precipitated by physiological uncoupling occurring within the exercise on‐transition.