Category Archives: Publications

Poor Work Efficiency is Associated with Poor Exercise Capacity and Health-Related Quality of Life in Patients with Chronic Obstructive Pulmonary Disease.

Yang SH; Yang MC; Wu YK; Wu CW; Hsieh PC; Kuo CY; Tzeng IS; Lan CC;

International journal of chronic obstructive pulmonary disease [Int J Chron Obstruct Pulmon Dis] 2021 Feb 10; Vol. 16, pp. 245-256. Date of Electronic Publication: 2021 Feb 10 (Print Publication: 2021).

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive disease with deteriorating cardiopulmonary function that decreases the health-related quality of life (HRQL) and exercise capacity. Patients with COPD often have cardiovascular and muscular problems that hinder oxygen uptake by peripheral tissues, resulting in poor oxygen consumption efficiency. It is important to develop new physiological parameters to evaluate oxygen consumption efficiency during activities and to evaluate its association with exercise capacity and HRQL. Work efficiency (WE) measures oxygen consumption efficiency during exercise. We hypothesize that patients with poor WE should have exercise intolerance and poor HRQL. Therefore, we aimed to evaluate the association between WE and exercise capacity, HRQL and other cardiopulmonary parameters.
Patients and Methods: Seventy-eight patients with COPD were evaluated with spirometry, cardiopulmonary exercise testing, and assessment of dyspnea score and HRQL (using the St. George’s Respiratory Questionnaire [SGRQ]). Cardiopulmonary exercise testing was performed using a cycle ergometer with an incremental protocol and exhaled breath analysis to assess oxygen consumption. WE was defined as the relationship between oxygen consumption and workload.
Results: There were 31 patients with normal WE (group I) and 47 patients (group II) with poor WE. Patients with poor WE had lower exercise capacity (maximal oxygen consumption, group I vs II as 1050±53 vs 845 ±34 mL/min, p=0.0011), poorer HRQL (SGRQ score 41.1±3.0 vs 55±2.2, p=0.0002), higher exertional dyspnea score (5.1±0.2 vs 6.1±0.2, p= 0.0034) and early anaerobic metabolism during exercise (anaerobic threshold, 672±27 vs 583 ±18 mL/min, p=0.0052).
Conclusion: WE is associated with exercise capacity and HRQL. Here, patients with poor WE also had exercise intolerance, poorer HRQL, and more exertional dyspnea.

Role of confirmed and potential predictors of an unfavorable outcome in heart failure in everyday clinical practice.

Chuda A; Banach M; Maciejewski M; Bielecka-Dabrowa A;

Irish journal of medical science [Ir J Med Sci] 2021 Feb 17. Date of Electronic Publication: 2021 Feb 17.

Heart failure (HF) is the only cardiovascular disease with an ever increasing incidence. HF, through reduced functional capacity, frequent exacerbations of disease, and repeated hospitalizations, results in poorer quality of life, decreased work productivity, and significantly increased costs of the public health system. The main challenge in the treatment of HF is the availability of reliable prognostic models that would allow patients and doctors to develop realistic expectations about the prognosis and to choose the appropriate therapy and monitoring method. At this moment, there is a lack of universal parameters or scales on the basis of which we could easily capture the moment of deterioration of HF patients’ condition. Hence, it is crucial to identify such factors which at the same time will be widely available, cheap, and easy to use. We can find many studies showing different predictors of unfavorable outcome in HF patients: thorough assessment with echocardiography imaging, exercise testing (e.g., 6-min walk test, cardiopulmonary exercise testing), and biomarkers (e.g., N-terminal pro-brain type natriuretic peptide, high-sensitivity troponin T, galectin-3, high-sensitivity C-reactive protein). Some of them are very promising, but more research is needed to create a specific panel on the basis of which we will be able to assess HF patients. At this moment despite identification of many markers of adverse outcomes, clinical decision-making in HF is still predominantly based on a few basic parameters, such as the presence of HF symptoms (NYHA class), left ventricular ejection fraction, and QRS complex duration and morphology.

ERS International Congress 2020 Virtual: highlights from the Allied Respiratory Professionals Assembly.

Smith E; Thomas M; Calik-Kutukcu E; Torres-Sánchez I; Granados-Santiago M; Quijano-Campos JC; Sylvester K; Burtin C; Sajnic A; DBrandt J; Cruz J;

ERJ open research [ERJ Open Res] 2021 Feb 08; Vol. 7 (1). Date of Electronic Publication: 2021 Feb 08 (Print Publication: 2021).

This article provides an overview of outstanding sessions that were (co)organised by the Allied Respiratory Professionals Assembly during the European Respiratory Society International Congress 2020, which this year assumed a virtual format. The content of the sessions was mainly targeted at allied respiratory professionals, including respiratory function technologists and scientists, physiotherapists, and nurses. Short take-home messages related to spirometry and exercise testing are provided, highlighting the importance of quality control. The need for quality improvement in sleep interventions is underlined as it may enhance patient outcomes and the working capacity of healthcare services. The promising role of digital health in chronic disease management is discussed, with emphasis on the value of end-user participation in the development of these technologies. Evidence on the effectiveness of airway clearance techniques in chronic respiratory conditions is provided along with the rationale for its use and challenges to be addressed in future research. The importance of assessing, preventing and reversing frailty in respiratory patients is discussed, with a clear focus on exercise-based interventions. Research on the impact of disease-specific fear and anxiety on patient outcomes draws attention to the need for early assessment and intervention. Finally, advances in nursing care related to treatment adherence, self-management and patients’ perspectives in asthma and chronic obstructive pulmonary disease are provided, highlighting the need for patient engagement and shared decision making. This highlights article provides readers with valuable insight into the latest scientific data and emerging areas affecting clinical practice of allied respiratory professionals.

A prospective cohort study evaluating screening and assessment of six modifiable risk factors in HPB cancer patients and compliance to recommended prehabilitation interventions.

van Wijk L; van der Snee L; Buis CI; Hentzen JEKR; Haveman ME; Klaase JM;

Perioperative medicine (London, England) [Perioper Med (Lond)] 2021 Feb 17; Vol. 10 (1), pp. 5. Date of Electronic Publication: 2021 Feb 17.

Introduction: Despite improvements in perioperative care, major abdominal surgery continues to be associated with significant perioperative morbidity. Accurate preoperative risk stratification and optimisation (prehabilitation) are necessary to reduce perioperative morbidity. This study evaluated the screening and assessment of modifiable risk factors amendable for prehabilitation interventions and measured the patient compliance rate with recommended interventions.
Method: Between May 2019 and January 2020, patients referred to our hospital for HPB surgery were screened and assessed on six modifiable preoperative risk factors. The risk factors and screening tools used, with cutoff values, included (i) low physical fitness (a 6-min walk test < 82% of patient’s calculated norm and/or patient’s activity level not meeting the global recommendations on physical activity for health). Patients who were unfit based on the screening were assessed with a cardiopulmonary exercise test (anaerobic threshold ≤ 11 mL/kg/min); (ii) malnutrition (patient-generated subjective global assessment ≥ 4); (iii) iron-deficiency anaemia (haemoglobin < 12 g/dL for women, < 13 g/dL for men and transferrin saturation ≤ 20%); (iv) frailty (Groningen frailty indicator/Robinson frailty score ≥ 4); (v) substance use (smoking and alcohol use of > 5 units per week) and (vi) low psychological resilience (Hospital Anxiety and Depression Scale ≥ 8). Patients had a consultation with the surgeon on the same day as their screening. High-risk patients were referred for necessary interventions.
Results: One hundred consecutive patients were screened at our prehabilitation outpatient clinic. The prevalence of high-risk patients per risk factor was 64% for low physical fitness, 42% for malnutrition, 32% for anaemia (in 47% due to iron deficiency), 22% for frailty, 12% for smoking, 18% for alcohol use and 21% for low psychological resilience. Of the 77 patients who were eventually scheduled for surgery, 53 (68.8%) needed at least one intervention, of whom 28 (52.8%) complied with 100% of the necessary interventions. The median (IQR) number of interventions needed in the 77 patients was 1.0 (0-2).
Conclusion: It is feasible to screen and assess all patients referred for HPB cancer surgery for six modifiable risk factors. Most of the patients had at least one risk factor that could be optimised. However, compliance with the suggested interventions remains challenging.

Quantifying the relationship and contribution of mitochondrial respiration to systemic exercise limitation in heart failure.

Knuiman P; Straw S; Gierula J; Koshy A; Roberts LD; Witte KK; Ferguson C; Bowen TS;

ESC heart failure [ESC Heart Fail] 2021 Feb 20. Date of Electronic Publication: 2021 Feb 20.

Aims: Heart failure with reduced ejection fraction (HFrEF) induces skeletal muscle mitochondrial abnormalities that contribute to exercise limitation; however, specific mitochondrial therapeutic targets remain poorly established. This study quantified the relationship and contribution of distinct mitochondrial respiratory states to prognostic whole-body measures of exercise limitation in HFrEF.
Methods and Results: Male patients with HFrEF (n = 22) were prospectively enrolled and underwent ramp-incremental cycle ergometry cardiopulmonary exercise testing to determine exercise variables including peak pulmonary oxygen uptake (V̇O 2peak ), lactate threshold (V̇O 2LT ), the ventilatory equivalent for carbon dioxide (V̇ E /V̇CO 2LT ), peak circulatory power (CircP peak ), and peak oxygen pulse. Pectoralis major was biopsied for assessment of in situ mitochondrial respiration. All mitochondrial states including complexes I, II, and IV and electron transport system (ETS) capacity correlated with V̇O 2peak (r = 0.40-0.64; P < 0.05), V̇O 2LT (r = 0.52-0.72; P < 0.05), and CircP peak (r = 0.42-0.60; P < 0.05). Multiple regression analysis revealed that combining age, haemoglobin, and left ventricular ejection fraction with ETS capacity could explain 52% of the variability in V̇O 2peak and 80% of the variability in V̇O 2LT , respectively, with ETS capacity (P = 0.04) and complex I (P = 0.01) the only significant contributors in the model.
Conclusions: Mitochondrial respiratory states from skeletal muscle biopsies of patients with HFrEF were independently correlated to established non-invasive prognostic cycle ergometry cardiopulmonary exercise testing indices including V̇O 2peak , V̇O 2LT , and CircP peak . When combined with baseline patient characteristics, over 50% of the variability in V̇O 2peak could be explained by the mitochondrial ETS capacity. These data provide optimized mitochondrial targets that may attenuate exercise limitations in HFrEF.

Reference values for cardiopulmonary exercise testing in healthy subjects – an updated systematic review,

T. Takken, C.F. Mylius, D. Paap, W. Broeders, H.J. Hulzebos, M. Van Brussel & B.C. Bongers

Expert Review of Cardiovascular Therapy,
DOI: 10.1080/14779072.2019.1627874

Introduction: Reference values for cardiopulmonary exercise testing (CPET) parameters provide the
comparative basis for answering important questions concerning the normalcy of exercise responses in
patients, and significantly impacts the clinical decision-making process.
Areas covered: The aim of this study was to provide an updated systematic review of the literature on
reference values for CPET parameters in healthy subjects across the life span.
A systematic search in MEDLINE, Embase, and PEDro databases were performed for articles describing
reference values for CPET published between March 2014 and February 2019.
Expert opinion: Compared to the review published in 2014, more data have been published in the last
five years compared to the 35 years before. However, there is still a lot of progress to be made. Quality
can be further improved by performing a power analysis, a good quality assurance of equipment and
methodologies, and by validating the developed reference equation in an independent (sub)sample.
Methodological quality of future studies can be further improved by measuring and reporting the level
of physical activity, by reporting values for different racial groups within a cohort as well as by the
exclusion of smokers in the sample studied. Normal reference ranges should be well defined in
consensus statements.

Cardiopulmonary exercise testing and cardiopulmonary morbidity in patients undergoing major head and neck surgery
Cardiopulmonary exercise testing (CPET) is used as a risk stratification tool for patients undergoing major surgery. In this study, we investigated the role of CPET in predicting day five cardiopulmonary morbidity in patients undergoing head and neck surgery. This observational cohort study included 230 adults. We recorded preoperative CPET variables and day five postoperative cardiopulmonary morbidity. Full data from 187 patients were analysed; 43 patients either had incomplete data sets or declined surgery/CPET. One hundred and nineteen patients (63.6%) developed cardiopulmonary morbidity at day five. Increased preoperative heart rate and duration of surgery were independently associated with day five cardiopulmonary morbidity. Those with such morbidity also had lower peak V̇O2 11.4 (IQR 8.4-18.0) vs 16.0 (IQR 14.0-19.7), P<0.0001 and V̇O2 at AT 10.6 (IQR 9.1-13.1) vs 11.5 (IQR 10.5-13.0), p=0.03. Logistic regression model containing peak V̇O2 and duration of surgery demonstrated that increased peak V̇O2 was associated with a reduction in the likelihood of cardiopulmonary complications OR 0.92(95%CI 0.87 to 0.96), p=0.001. The area under the receiver operating characteristic curve for this model was 0.75(95%CI 0.68 to 0.82), p<0.0001, 64% sensitivity, 81% specificity. CPET can help to predict day five cardiopulmonary morbidity in the patients undergoing head and neck surgery. A model containing peak V̇O2 allowed identification of those with such complications.

Reference values for cardiopulmonary exercise testing in healthy adults: A systematic review

Papp D; Takken T;

December 2014. Expert Review of Cardiovascular Therapy 12(12):1439-53

Reference values (RV) for cardiopulmonary exercise testing (CPET) provide the comparative basis for answering important questions concerning the normality of exercise response in patients and significantly impacts the clinical decision-making process. The aim of this study is to systematically review the literature on RV for CPET in healthy adults. A secondary aim is to make appropriate recommendations for the practical use of RV for CPET. Systematic searches of MEDLINE, EMBASE and PEDro databases up to March 2014 were performed. In the last 30 years, 35 studies with CPET RV were published. There is no single set of ideal RV; characteristics of each population are too diverse to pool the data in a single equation. Therefore, each exercise laboratory must select appropriate sets of RV that best reflect the characteristics of the population/patient tested, and equipment and methodology utilized.

New Data-based Cutoffs for Maximal Exercise Criteria across the Lifespan


Med. Sci. Sports Exerc., Vol. 52, No. 9, pp. 1915–1923, 2020.

Purpose: To determine age-dependent cutoff values for secondary exhaustion criteria for a general population free
of exercise limiting chronic conditions; to describe the percentage of participants reaching commonly used exhaustion criteria during a cardiopulmonary exercise test (CPET); and to analyze their oxygen uptake at the respective criteria to quantify the impact of a given criterion on the respective oxygen uptake (V˙O2) values.
Methods: Data from the COmPLETE-Health Study were analyzed involving participants from 20 to 91 yr of age. All underwent a CPET to maximal voluntary exertion using a cycle ergometer. To determine new exhaustion criteria, based on maximal respiratory exchange ratio (RERmax) and age-predicted maximal HR (APMHR), one-sided lower tolerance intervals for the tests confirmingV˙O2 plateau status were calculated using a confidence level of 95% and a coverage of 90%.
Results: A total of 274 men and 252 women participated in the study. Participants were nearly equally distributed across age decades from20 to >80 yr. A V˙O2 plateauwas present in 32%. There were only minor differences in secondary exhaustion criteria between participants exhibiting a V˙O2 plateau and participants not showing a V˙O2 plateau. New exhaustion criteria according to the tolerance intervals for the age group of 20 to 39 yr were: RERmax ≥ 1.13, APMHR210 − age ≥ 96%, and APMHR208 × 0.7 age ≥ 93%; for the age group of 40 to 59 yr: RERmax ≥ 1.10, APMHR210 − age ≥ 99%, and APMHR208 × 0.7 age ≥ 92%; and, for the age group of 60 to 69 yr: RERmax ≥ 1.06, APMHR210 − age ≥ 99%, and APMHR208 × 0.7 age ≥ 89%.
Conclusions: The proposed cutoff values for secondary criteria reduce the risk of underestimating V˙02max. Lower values would increase false-positive results, assuming participants are exhausted although, in fact, they are not.

Breath acetone change during aerobic exercise is moderated by cardiorespiratory fitness

Karsten Königstein, Sebastian Abegg, Andrea N Schorn, Ines C Weber, Nina Derron,
Andreas Krebs, Philipp A Gerber, Arno Schmidt-Trucksass and Andreas T Güntner

J. Breath Res. 15 (2021) 016006

Exhaled breath acetone (BrAce) was investigated during and after submaximal aerobic exercise as a
volatile biomarker for metabolic responsiveness in high and lower-fit individuals in a prospective
cohort pilot-study. Twenty healthy adults (19–39 years) with different levels of cardiorespiratory
fitness (VO2peak), determined by spiroergometry, were recruited. BrAce was repeatedly measured
by proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) during 40–55 min
submaximal cycling exercise and a post-exercise period of 180 min. Activity of ketone and fat
metabolism during and after exercise were assessed by indirect calorimetric calculation of fat
oxidation rate and by measurement of venous β-hydroxybutyrate (βHB). Maximum BrAce ratios
were significantly higher during exercise in the high-fit individuals compared to the lower-fit group
(t-test; p = 0.03). Multivariate regression showed 0.4% (95%-CI = −0.2%–0.9%, p = 0.155)
higher BrAce change during exercise for every ml kg−1 min−1 higher VO2peak. Differences of BrAce
ratios during exercise were similar to fat oxidation rate changes, but without association to
respiratory minute volume. Furthermore, the high-fit group showed higher maximum BrAce
increase rates (46% h−1) in the late post-exercise phase compared to the lower-fit group
(29% h−1). As a result, high-fit young, healthy individuals have a higher increase in BrAce
concentrations related to submaximal exercise than lower-fit subjects, indicating a stronger
exercise-related activation of fat metabolism.