Exercise Intolerance in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is associated with symptoms of dyspnea and fatigue, which contribute to exercise limitation. The origins and significance of dyspnea and fatigue in PAH are not completely understood. This has created uncertainly among healthcare professionals regarding acceptable levels of these symptoms, on exertion, for patients with PAH. Dysfunction of the right ventricle (RV) contributes to functional limitation and mortality in PAH; however, the role of the RV in eliciting dyspnea and fatigue has not been thoroughly examined. This paper explores the contribution of the RV and systemic and peripheral abnormalities to exercise limitation and symptoms in PAH. Further, it explores the relationship between exercise abnormalities and symptoms, the utility of the cardiopulmonary exercise test in identifying RV dysfunction, and offers suggestions for further research

Defining the appropriate waiting time between multiple-breath nitrogen washout measurements

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Australian perspective regarding recommendations for physical activity and exercise rehabilitation in pulmonary arterial hypertension

Aim: To determine the opinion of health care professionals within Australia, regarding acceptable levels of exertion and symptoms, and referral for exercise rehabilitation in patients with pulmonary arterial hypertension (PAH). Method: In 2010, 76 health care professionals at a specialist pulmonary hypertension meeting in Australia were surveyed using a self-administered questionnaire. The questionnaire included case studies of patients with PAH in World Health Organization (WHO) functional classes II–IV. For each case study, respondents were asked to report their opinion regarding the acceptable level of exertion and symptoms during daily activities, and whether they would refer the patient for exercise rehabilitation. Three additional questions asked about advice in relation to four specific physical activities. Results: The response rate was 70% (n = 53). Overall, 58% of respondents recommended patients undertake daily activities 'as tolerated'. There was no consensus regarding acceptable levels of breathlessness or fatigue, but the majority of respondents considered patients should have no chest pain (73%) and no more than mild light-headedness (92%) during daily activities. Overall, 63% of respondents would have referred patients for exercise rehabilitation. There was little difference in opinion regarding the acceptable level of exertion or symptoms, or referral for exercise rehabilitation, according to functional class. However, the patients' functional class did influence the advice given regarding the specific physical activities. Conclusion: In 2010, there were inconsistencies between individual health care professionals within Australia regarding appropriate levels of physical exertion and acceptable symptoms during daily activities. Almost two-thirds of the respondents reported they would refer patients for exercise rehabilitation

A genome-wide association study of outcome from traumatic brain injury

Background Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.& nbsp;Methods We performed the first genome-and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.& nbsp;Findings The estimated heritability of TBI outcome was 0.26. GWAS revealed no genetic variants with genome-wide significance (p < 5 x 10(-8)), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10(-5)). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5.24 x 10(-4)).& nbsp;Interpretation While multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.& nbsp;Copyright (C)& nbsp;2022 Published by Elsevier B.V.Peer reviewe

Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension

BACKGROUND: The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and the Medical Outcomes Study Short Form 36 (SF-36) are widely used to assess patient-reported outcome in individuals with pulmonary hypertension (PH). The aim of the study was to compare the psychometric properties of the two measures. METHODS: Participants were recruited from specialist PH centres in Australia and New Zealand. Participants completed the CAMPHOR and SF-36 at two time points two weeks apart. The SF-36 is a generic health status questionnaire consisting of 36 items split into 8 sections. The CAMPHOR is a PH-specific measure consisting of 3 scales; symptoms, activity limitations and needs-based QoL. The questionnaires were assessed for distributional properties (floor and ceiling effects), internal consistency (Cronbach's alpha), test-retest reliability and construct validity (scores by World Health Organisation functional classification). RESULTS: The sample comprised 65 participants (mean (SD) age = 57.2 (14.5) years; n(%) male = 14 (21.5%)). Most of the patients were in WHO class 2 (27.7%) and 3 (61.5%). High ceiling effects were observed for the SF-36 bodily pain, social functioning and role emotional domains. Test-retest reliability was poor for six of the eight SF-36 domains, indicating high levels of random measurement error. Three of the SF-36 domains did not distinguish between WHO classes. In contrast, all CAMPHOR scales exhibited good distributional properties, test retest reliability and distinguished between WHO functional classes. CONCLUSIONS: The CAMPHOR exhibited superior psychometric properties, compared with the SF-36, in the assessment of PH patient-reported outcome

Short term effects of exercise training on exercise capacity and quality of life in patients with pulmonary arterial hypertension: protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Advances in the understanding and management of pulmonary arterial hypertension have enabled earlier diagnosis and improved prognosis. However, despite best available therapy, symptoms of exertional dyspnoea and fatigue are commonly reported and result in a reduced capacity to perform daily activities and impaired quality of life. Exercise training has demonstrated efficacy in individuals with other respiratory and cardiovascular diseases. Historically, however, exercise training has not been utilised as a form of therapy in pulmonary arterial hypertension due to the perceived risk of sudden cardiac death and the theoretical possibility that exercise would lead to worsening pulmonary vascular haemodynamics and deterioration in right heart function. Now, with the advances in pharmaceutical management, determining the safety and benefits of exercise training in this population has become more relevant. Only three studies of supervised exercise training in pulmonary arterial hypertension have been published. These studies demonstrated improvements in exercise capacity and quality of life, in the absence of adverse events or clinical deterioration. However, these studies have not utilised an outpatient-based, whole body exercise training program, the most common format for exercise programs within Australia. It is uncertain whether this form of training is beneficial and capable of producing sustained benefits in exercise capacity and quality of life in this population.</p> <p>Design/Methods</p> <p>This randomised controlled trial will determine whether a 12 week, outpatient-based, supervised, whole body exercise training program, followed by a home-based exercise program, is safe and improves exercise capacity and quality of life in individuals with pulmonary arterial hypertension. This study aims to recruit 34 subjects who will be randomly allocated to the exercise group (supervised exercise training 3 times a week for 12 weeks, followed by 3 sessions per week of home exercise for 12 weeks) or the control group (usual medical care). Subjects will be assessed at baseline, 12 weeks and 24 weeks.</p> <p>Discussion</p> <p>This study will determine whether outpatient-based, whole body exercise training is beneficial and safe in individuals with pulmonary arterial hypertension. Additionally, this study will contribute to clinical practice guidelines for this patient population.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000502235.aspx">ACTRN12609000502235</a></p

A comparison of the acute haemodynamic response to aerobic and resistance exercise in subjects with exercise-induced pulmonary arterial hypertension

Background: Exercise-induced pulmonary arterial hypertension (EIPAH) is associated with reduced exercise capacity and abnormal central haemodynamic responses to maximal aerobic exercise. Aerobic and resistance exercise training are commonly employed to treat reduced exercise capacity; however, the haemodynamic response to aerobic and resistance exercise, at training intensities, in subjects with EIPAH is unknown. Methods: Fourteen subjects (11 with scleroderma, 12 females) with EIPAH underwent cardiopulmonary exercise testing on a cycle ergometer, a one-repetition maximum (1RM) strength test and resistance exercise at 40% and 60% of maximum on a bilateral leg press machine. All tests were performed with a pulmonary artery catheter in situ. Haemodynamic and symptomatic responses to aerobic and resistance exercise, performed at 40% of peak oxygen consumption and 40% of 1RM, and at 60% of peak oxygen consumption and 60% of 1RM, were compared. For maximal exercise, the highest haemodynamic responses recorded during the cycling and 1RM tests were compared.Results: There were no differences in haemodynamic or symptomatic responses between the two modalities of submaximal exercise. At maximal exercise, all haemodynamic and symptomatic responses were lower during resistance compared with aerobic exercise (p < 0.05). Conclusions: At the intensities studied, lower-limb resistance exercise was well tolerated and was mostly associated with similar or lower haemodynamic responses compared with aerobic exercise, in subjects with EIPAH

Validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for the Australian and New Zealand population

Background and objective: Individuals with pulmonary arterial hypertension (PAH) experience severely impaired quality of life. A disease-specific patient reported outcome measure for PAH (the Cambridge Pulmonary Hypertension Outcome Review—CAMPHOR) has recently been developed and validated in the UK, USA and Canada. It has demonstrated reliability and validity in PAH populations in these countries. The aim of this study was to assess the reliability and validity of the CAMPHOR in an Australian and New Zealand (NZ) PAH population. Methods: Semistructured interviews were conducted with a cohort of 15 PAH patients (aged 68.9 ± 10.0 years; 11 women) to determine the relevance of the CAMPHOR and ensure the terminology and language used was understandable and appropriate for our PAH population. The test–retest reliability, internal consistency and construct validity of the CAMPHOR were then examined in an Australian and NZ PAH population (n = 61, aged 56.9 ± 14.5 years; 48 women). Results: Data from the patient interviews confirmed that the CAMPHOR is appropriate for use in our PAH population. The three CAMPHOR scales (symptoms, activity limitations and quality of life) had excellent test–retest reliability (correlation coefficients (rs) = 0.86–0.94, P \u3c 0.01) and internal consistency (Cronbach\u27s alpha coefficients = 0.89–0.92). The CAMPHOR also demonstrated the ability to distinguish between individuals with PAH who differed according to World Health Organisation functional class. Conclusions: We have shown the CAMPHOR to be valid and reliable in an Australian and NZ PAH population and recommend its use in clinical practice