Babu AS, Arena , Morris NR.

Adv Exp Med Biol. 2017;1000:153-172. doi: 10.1007/978-981-10-4304-8_10.

Pulmonary hypertension (PH) is a chronic, debilitating condition which gravely
affects exercise tolerance and quality of life. Though most therapies focus
purely on medical intervention, there is a growing body of evidence to suggest
the role and benefits of exercise training. This chapter discusses the various
physiological basis for exercise intolerance observed in PH and highlights the
rationale for exercise training. Recent evidence related to exercise training is
summarized and potential pathways to suggest adaptations to exercise training are
put forward. While keeping the paper applicable to clinicians, details on
evaluating exercise intolerance, prescribing exercise and setting up
rehabilitation centers for PH are discussed.

Nielsen MKF;Christensen JF; Frandsen TL; Thorsteinsson T; Andersen LB; Christensen KB; Nersting J; Faber M; Schmiegelow K; Larsen HB;

Pediatric Blood & Cancer [Pediatr Blood Cancer] 2018 May 09, pp. e27100. Date of Electronic Publication: 2018 May 09.

Background: The physical function of children with cancer is reduced during treatment, which can compromise the quality of life and increase the risk of chronic medical conditions. The study, “REhabilitation, including Social and Physical activity and Education in Children and Teenagers with cancer” (Clinicaltrials.gov: NCT01772862) examines the efficacy of multimodal rehabilitation strategies introduced at cancer diagnosis. This article addresses the feasibility of and obstacles to testing physical function in children with cancer.
Methods: The intervention group comprised 46 males and 29 females aged 6-18 years (mean ± SD: 11.3 ± 3.1 years) diagnosed with cancer from January 2013 to April 2016. Testing at diagnosis and after 3 months included timed-up-and-go, sit-to-stand, flamingo balance, handgrip strength, and the bicycle ergometer cardiopulmonary exercise test (CPET).
Results: Of the 75 children, 92% completed a minimum of one test; two children declined testing and four were later included. Completion was low for CPET (38/150, 25%) but was high for handgrip strength (122/150, 81%). Tumor location, treatment-related side effects, and proximity to chemotherapy administration were primary obstacles for testing physical function. Children with extracranial solid tumors and central nervous system tumors completed significantly fewer tests than those with leukemia and lymphoma. Children with leukemia demonstrated reduced lower extremity function, that is, 24% reduction at 3 months testing in timed-up-and-go (P = 0.005) and sit-to-stand (P = 0.002), in contrast with no reductions observed in the other diagnostic groups.
Conclusion: Children with cancer are generally motivated to participate in physical function tests. Future studies should address diagnosis specific obstacles and design testing modalities that facilitate physical function tests in this target group.

Durrand JW; Wagstaff K; Kasim A; Cawthorn L; Danjoux GR; Kothmann E

Anaesthesia [Anaesthesia], ISSN: 1365-2044, 2018 May 04

Arm-crank ergometry may be useful in patients unable to pedal, for instance due to peripheral arterial disease. Twenty participants with small abdominal aortic aneurysm undertook two serial arm-crank tests and then a pedal test, four of whom had indeterminate anaerobic thresholds, precluding analysis. The mean (SD) peak arm and leg oxygen consumptions in 16 participants were 13.71 (2.62) ml.kg-1 .min-1 and 16.82 (4.44) ml.kg-1 .min-1 , with mean (SD) individual differences of 3.11 (2.48) ml.kg-1 .min-1 , p = 0.0001. The respective values at the anaerobic thresholds were 7.83 (1.58) ml O2 .kg-1 .min-1 and 10.09 (3.15) ml O2 .kg-1 .min-1 , with mean (SD) individual differences of 2.26 (2.34) ml O2 .kg-1 .min-1 , p = 0.0001. The correlation coefficients (95%CI) for peak oxygen consumption and anaerobic threshold were 0.88 (0.62-1.0) and 0.70 (0.32-1.0). There were no significant differences in serial arm-crank tests, with intracluster correlations (95%CI) of 0.87 (0.86-0.88) and 0.65 (0.61-0.69) for peak oxygen consumption and anaerobic threshold, respectively.

Karenovics W, Licker M, Ellenberger C, Christodoulou M, Diaper J,
Bhatia C, Robert J, Bridevaux PO, Triponez F

Eur J Cardiothorac Surg. 2017 Jul 1;52(1):47-54. doi: 10.1093/ejcts/ezx030

OBJECTIVES: Poor aerobic fitness is a potential modifiable risk factor for
long-term survival and quality of life in patients with lung cancer. This
randomized trial evaluates the impact of adding rehabilitation (Rehab) with
high-intensity interval training (HIIT) before lung cancer surgery to enhance
cardiorespiratory fitness and improve long-term postoperative outcome.
METHODS: Patients with operable lung cancer were randomly assigned to usual care
(UC, n  = 77) or to intervention group (Rehab, n  = 74) that entailed HIIT that
was implemented only preoperatively. Cardiopulmonary exercise testing (CPET) and
pulmonary functional tests (PFTs) including forced vital capacity (FVC), forced
expiratory volume (FEV 1 ) and carbon monoxide transfer factor (KCO) were
performed before and 1 year after surgery.
RESULTS: During the preoperative waiting time (median 25 days), Rehab patients
participated to a median of 8 HIIT sessions (interquartile [IQ] 25-75%, 7-10). At
1 year follow-up, 91% UC patients and 93% Rehab patients were still alive ( P
= 0.506). Pulmonary functional changes were non-significant and comparable in
both groups (FEV 1 mean -7.5%, 95% CI, -3.6 to -12.9 and in KCO mean 5.8% 95% CI
0.8-11.8) Compared with preoperative CPET results, both groups demonstrated
similar reduction in peak oxygen uptake (mean -12.2% 95% CI -4.8 to -18.2) and in
peak work rate (mean -11.1% 95% CI -4.2 to -17.4).
CONCLUSIONS: Short-term preoperative rehabilitation with HIIT does not improve
pulmonary function and aerobic capacity measured at 1 year after lung cancer
resection.

Vignati C, Cattadori G

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S48-S52. doi:
10.1513/AnnalsATS.201611-852FR.

Cardiac output is a key parameter in the assessment of cardiac function, and its
measurement is fundamental to the diagnosis, treatment, and prognostic evaluation
of all heart diseases. Until recently, cardiac output determination during
exercise had been only possible through invasive methods, which were not
practical in the clinical setting. Because [Formula: see text]o2 is cardiac
output times arteriovenous content difference, evaluation of cardiac output is
usually included in its measurement. Because of the difficulty of directly
measuring peak exercise cardiac output, indirect surrogate parameters have been
proposed, but with only modest clinical usefulness. Direct measurement of cardiac
output can now be made by several noninvasive techniques, such as rebreathing
inert gases, impedance cardiology, thoracic bioreactance, estimated continuous
cardiac output technology, and transthoracic echocardiography coupled to
cardiopulmonary exercise testing, which allow more definitive results and better
understanding of the underlying physiopathology.

Agostoni P, Corrà U, Emdin M

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S116-S122. doi:
10.1513/AnnalsATS.201701-003FR.

Periodic breathing during incremental cardiopulmonary exercise testing is a
regularly recurring waxing and waning of tidal volume due to oscillations in
central respiratory drive. Periodic breathing is a sign of respiratory control
system instability, which may occur at rest or during exercise. The possible
mechanisms responsible for exertional periodic breathing might be related to any
instability of the ventilatory regulation caused by: (1) increased circulatory
delay (i.e., circulation time from the lung to the brain and chemoreceptors due
to reduced cardiac index leading to delay in information transfer), (2) increase
in controller gain (i.e., increased central and peripheral chemoreceptor
sensitivity to arterial partial pressure of oxygen and of carbon dioxide), or (3)
reduction in system damping (i.e., baroreflex impairment). Periodic breathing
during exercise is observed in several cardiovascular disease populations, but it
is a particularly frequent phenomenon in heart failure due to systolic
dysfunction. The detection of exertional periodic breathing is linked to outcome
and heralds worse prognosis in heart failure, independently of the criteria
adopted for its definition. In small heart failure cohorts, exertional periodic
breathing has been abolished with several dedicated interventions, but results
have not yet been confirmed. Accordingly, further studies are needed to define
the role of visceral feedbacks in determining periodic breathing during exercise
as well as to look for specific tools for preventing/treating its occurrence in
heart failure.

Mezzani A

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S3-S11. doi:
10.1513/AnnalsATS.201612-997FR

Cardiopulmonary exercise testing adds measurement of ventilation and volume of
oxygen uptake and exhaled carbon dioxide to routine physiological and performance
parameters obtainable from conventional exercise testing, furnishing an
all-around vision of the systems involved in both oxygen transport from air to
mitochondria and its use during exercise. Peculiarities of cardiopulmonary
exercise testing methodology are the use of ramp protocols and calibration
procedures for flow meters and gas analyzers. Among the several parameters
provided by this technique, peak oxygen uptake, first and second ventilatory
thresholds, respiratory exchange ratio, oxygen pulse, slope of ventilation
divided by exhaled carbon dioxide relationship, exercise oscillatory ventilation,
circulatory power, and partial pressure of end-tidal carbon dioxide are among the
most relevant in the clinical setting. The choice of parameters to be considered
will depend on the indication to cardiopulmonary exercise testing in the
individual subject or patient, namely, exercise tolerance assessment, prognostic
stratification, training prescription, treatment efficacy evaluation, diagnosis
of causes of unexplained exercise tolerance reduction, or exercise
(patho)physiology evaluation for research purposes. Overall, cardiopulmonary
exercise testing is a methodology now widely available and supported by sound
scientific evidence. Despite this, its potential still remains largely underused.
Strong efforts and future investigations are needed to address these issues and
further promote the use of cardiopulmonary exercise testing in the clinical and
research setting.

Older PO, Levett DZH

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S74-S83. doi:
10.1513/AnnalsATS.201610-780FR

The surgical patient population is increasingly elderly and comorbid and poses
challenges to perioperative physicians. Accurate preoperative risk stratification
is important to direct perioperative care. Reduced aerobic fitness is associated
with increased postoperative morbidity and mortality. Cardiopulmonary exercise
testing is an integrated and dynamic test that gives an objective measure of
aerobic fitness or functional capacity and identifies the cause of exercise
intolerance. Cardiopulmonary exercise testing provides an individualized estimate
of patient risk that can be used to predict postoperative morbidity and
mortality. This technology can therefore be used to inform collaborative
decision-making and patient consent, to triage the patient to an appropriate
perioperative care environment, to diagnose unexpected comorbidity, to optimize
medical comorbidities preoperatively, and to direct individualized preoperative
exercise programs. Functional capacity, evaluated as the anaerobic threshold and
peak oxygen uptake ([Formula: see text]o2peak) predicts postoperative morbidity
and mortality in the majority of surgical cohort studies. The ventilatory
equivalents for carbon dioxide (an index of gas exchange efficiency), is
predictive of surgical outcome in some cohorts. Prospective cohort studies are
needed to improve the precision of risk estimates for different patient groups
and to clarify the best combination of variables to predict outcome. Early data
suggest that preoperative exercise training improves fitness, reduces the
debilitating effects of neoadjuvant chemotherapy, and may improve clinical
outcomes. Further research is required to identify the most effective type of
training and the minimum duration required for a positive effect.

Dumitrescu D, Rosenkranz S.

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S12-S21. doi:
10.1513/AnnalsATS.201612-955FR

Cardiopulmonary exercise testing is a well-known, valuable tool in the clinical
evaluation of patients with different causes of exercise limitation and
unexplained dyspnea. A wealth of data is generated by each individual test. This
may be challenging regarding a comprehensive and reliable interpretation of an
exercise study in a timely manner. An optimized graphical display of exercise
data may substantially help to improve the efficacy and reliability of the
interpretation process. However, there are limited and heterogeneous
recommendations on standardized graphical display in current exercise testing
guidelines. To date, a widely used three-by-three array of specifically arranged
graphical panels known as the “nine-panel plot” is probably the most common
method of plotting exercise gas exchange data in a standardized way. Furthermore,
optimized scaling of the plots, the use of colors and style elements, as well as
suitable averaging methods have to be considered to achieve a high level of
quality and reproducibility of the results. Specific plots of key parameters may
allow a fast and reliable visual determination of important diagnostic and
prognostic markers in cardiac and pulmonary diseases.

Riley MS, Nicholls DP, Cooper CB

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S129-S139. doi:
10.1513/AnnalsATS.201701-014FR

Skeletal muscle requires a large increase in its ATP production to meet the
energy needs of exercise. Normally, most of this increase in ATP is supplied by
the aerobic process of oxidative phosphorylation. The main defects in muscle
metabolism that interfere with production of ATP are (1) disorders of
glycogenolysis and glycolysis, which prevent both carbohydrate entering the
tricarboxylic acid cycle and the production of lactic acid; (2) mitochondrial
myopathies where the defect is usually within the electron transport chain,
reducing the rate of oxidative phosphorylation; and (3) disorders of lipid
metabolism. Gas exchange measurements derived from exhaled gas analysis during
cardiopulmonary exercise testing can identify defects in muscle metabolism
because [Formula: see text]o2 and [Formula: see text]co2 are abnormal at the
level of the muscle. Cardiopulmonary exercise testing may thus suggest a likely
diagnosis and guide additional investigation. Defects in glycogenolysis and
glycolysis are identified by a low peak [Formula: see text]o2 and absence of
excess [Formula: see text]co2 from buffering of lactic acid by bicarbonate.
Defects in the electron transport chain also result in low peak [Formula: see
text]o2, but because there is an overreliance on anaerobic processes, lactic acid
accumulation and excess carbon dioxide from buffering occur early during
exercise. Defects in lipid metabolism result in only minor abnormalities during
cardiopulmonary exercise testing. In defects of glycogenolysis and glycolysis and
in mitochondrial myopathies, other features may include an exaggerated
cardiovascular response to exercise, a low oxygen-pulse, and excessive ammonia
release.