The Coupling of Peripheral Blood Pressure and Ventilatory Responses during Exercise in Young Adults with Cystic Fibrosis

Abstract

PurposeCystic fibrosis (CF) is commonly recognized as a pulmonary disease associated with reduced airway function. Another primary symptom of CF is low exercise capacity where ventilation and gas-exchange are exacerbated. However, an independent link between pathophysiology of the pulmonary system and abnormal ventilatory and gas-exchange responses during cardiopulmonary exercise testing (CPET) has not been established in CF. Complicating this understanding, accumulating evidence suggests CF demonstrate abnormal peripheral vascular function; although, the clinical implications are unclear. We hypothesized that compared to controls, relative to total work performed (WorkTOT), CF would demonstrate increased ventilation accompanied by augmented systolic blood pressure (SBP) during CPET.Methods16 CF and 23 controls (age: 23±4 vs. 27±4 years, P = 0.11; FEV1%predicted: 73±14 vs. 96±5, P<0.01) participated in CPET. Breath-by-breath oxygen uptake (), ventilation (), and carbon dioxide output () were measured continuously during incremental 3-min stage step-wise cycle ergometry CPET. SBP was measured via manual sphygmomanometry. Linear regression was used to calculate slope from rest to peak-exercise.ResultsCompared to controls, CF performed less WorkTOT during CPET (90±19 vs. 43±14 kJ, respectively, P<0.01). With WorkTOT as a covariate, peak (62±8 vs. 90±4 L/min, P = 0.76), (1.8±0.3 vs. 2.7±0.1 L/min, P = 0.40), and SBP (144±13 vs. 152±6 mmHg, P = 0.88) were similar between CF and controls, respectively; whereas CF demonstrated increased slope (38±4 vs. 28±2, P = 0.02) but lower peak versus controls (22±5 vs. 33±4 mL/kg/min, P<0.01). There were modest-to-moderate correlations between peak SBP with (r = 0.30), (r = 0.70), and (r = 0.62) in CF.ConclusionsThese data suggest that relative to WorkTOT, young adults with mild-to-moderate severity CF demonstrate augmented slope accompanied by increased SBP during CPET. Although the underlying mechanisms remain unclear, the coupling of ventilatory inefficiency with increased blood pressure suggest important contributions from peripheral pathophysiology to low exercise capacity in CF.

Ventilation efficiency to exercise in patients with cystic fibrosis

“…Bongers et al also reported a normal ΔV′E/ΔV′CO 2 slope of 27.1 ± 2.9 in 22 adolescents with CF and an FEV 1 of 79±17%, while the V′E over work rate ratio was elevated. Van Iterson et al examined the ΔV′E/ΔV′CO 2 slope in 16 young adults with CF and an FEV 1 of 73 ± 14%predicted in comparison to healthy controls. In their study, patients with CF had higher ΔV′E/ΔV′CO 2 slopes (38 ± 4) than healthy controls (28 ± 2).…”

“…Despite the growing evidence for the value of the V′E over V′CO 2 ‐relationship in the clinical assessment of people with various diseases, few studies, addressed its role in CF . Van Iterson et al, after testing 16 patients with CF, recently noted that ΔV′E/ΔVC′O 2 slope was increased in contrast to healthy controls but they conclude that “underlying mechanisms remain unclear.”…”

Does partitioning the subcomponents of the ventilatory equivalent for carbon dioxide slope provide evidence that ventilatory efficiency is retained in cystic fibrosis?

“…This is a key omission because contrary to their CPET interpretations and discussion, it is recognized the V̇ E /V̇CO 2 slope and reported thresholds for adults are not translational to adolescent populations and vice‐versa, ventilatory efficiency inversely relates with adult age, and cardiopulmonary disease exacerbates effects of aging on ventilatory inefficiency . The message that ventilatory efficiency is retained in CF based on an interpretation that V̇ E /V̇CO 2 slope does not differ between percent predicted forced expiratory volume in 1‐sec (FEV 1 ) severity, percent predicted V̇O 2peak , and are overall lower than those (of adults) observed elsewhere is not rigorously supported by their data.…”

“…Clinicians and physiologists interested in cardiopulmonary exercise testing (CPET) and ventilatory efficiency appreciate adolescent physiological responses to exercise are not directly translational to the adult, and vice‐versa . It follows that while Kampouras et al provides plentiful discussion involving comparisons between their CPET data and those of our group (Van Iterson et al) reported in adult CF, they missed a critical opportunity to dissect the body of evidence so as to underscore why they consider it is reasonable to compare studies of adults with those of adolescents, particularly in CF. This is a key omission because contrary to their CPET interpretations and discussion, it is recognized the V̇ E /V̇CO 2 slope and reported thresholds for adults are not translational to adolescent populations and vice‐versa, ventilatory efficiency inversely relates with adult age, and cardiopulmonary disease exacerbates effects of aging on ventilatory inefficiency .…”

“…These authors should be given credit for an outstanding job of highlighting there is clinical value in understanding the integrative physiological mechanisms and origins from which the slope for the ventilatory equivalent for carbon dioxide (V̇ E /V̇CO 2 ) measurement relates with ventilatory efficiency. The authors propose a thought‐provoking mechanistic association aimed at explaining why individuals with CF do not demonstrate abnormal ventilatory efficiency when others have suggested otherwise. Compensatory high respiratory frequency (f B ) coupled with increased physiological dead space (V D ) ventilation is a key mechanism which the authors claim help individuals with CF “retain” ventilatory efficiency .…”