Exercise training for people following curative intent treatment for non-small cell lung cancer: a randomized controlled trial.

OBJECTIVE: In people following curative intent treatment for non-small cell lung cancer, to investigate the effects of supervised exercise training on exercise capacity, physical activity and sedentary behavior, peripheral muscle force, health-related quality of life, fatigue, feelings of anxiety and depression, and lung function. METHOD: This pilot randomized controlled trial included participants 6-10 weeks after lobectomy for non-small cell lung cancer or, for those who required adjuvant chemotherapy, 4-8 weeks after their last cycle. Participants were randomized to either 8 weeks of supervised exercise training (exercise group) or 8 weeks of usual care (control group). Prior to and following the intervention period, both groups completed measurements of exercise capacity, physical activity and sedentary behavior, quadriceps and handgrip force, HRQoL, fatigue, feelings of anxiety and depression, and lung function. Intention-to-treat analysis was undertaken. RESULTS: Seventeen participants (mean age 67, SD=9 years; 12 females) were included. Nine and eight participants were randomized to the exercise and control groups, respectively. Four participants (44%) adhered to exercise training. Compared with any change seen in the control group, those in the exercise group demonstrated greater gains in the peak rate of oxygen consumption (mean difference, 95% confidence interval for between-group difference: 0.19 [0.04-0.33]Lmin-1) and 6-minute walk distance (52 [12-93]m). No other between-group differences were demonstrated. CONCLUSIONS: In people following curative intent treatment for non-small cell lung cancer, 8 weeks of supervised exercise training improved exercise capacity, measured by both laboratory- and field-based exercise tests. These results suggest that this clinical population may benefit from attending exercise training programs.

Comparison of the six-minute walk test with a cycle-based cardiopulmonary exercise test in people following curative intent treatment for non-small cell lung cancer.

This study is aimed to (i) compare both the magnitude of impairment in exercise capacity and exercise responses measured during the six-minute walk test (6MWT) and the cardiopulmonary exercise test (CPET) and (ii) investigate the effect of test repetition on six-minute walk distance (6MWD) in people following curative intent treatment for non-small cell lung cancer (NSCLC). Twenty participants (67 ± 10 years; 14 females), 6-10 weeks following lobectomy, underwent a CPET and two 6MWTs. Peak exercise responses, dyspnoea and leg fatigue, as well as heart rate (HR) and oxygen saturation (SpO2) during the 6MWT, were compared to those during the CPET. Compared with exercise capacity when expressed as peak rate of oxygen consumption (%pred) measured during the CPET, exercise capacity when expressed as 6MWD (%pred) was less impaired (81 ± 10 vs. 63 ± 15 %pred; p < 0.001). Compared with the CPET, the 6MWT elicited lower peak HR (119 ± 15 vs. 128 ± 18 beats minute(-1); p = 0.02), lower SpO2 (93 ± 2 vs. 95 ± 3%; p < 0.05), less dyspnoea (3.1 ± 1.6 vs. 6.9 ± 2.6; p < 0.01) and less leg fatigue (2.0 ± 1.9 vs. 6.8 ± 2.4; p < 0.01). The 6MWD increased 19 ± 19 metre (4 ± 4%) with test repetition (p < 0.001). In people following curative intent treatment for NSCLC, the 6MWT appears to elicit sub-maximal exercise responses when compared with the CPET. There is a significant effect of test repetition on 6MWD.

Impairments after curative intent treatment for non-small cell lung cancer: a comparison with age and gender-matched healthy controls.

BACKGROUND: The aim of this study was to compare measures of exercise capacity, health-related quality of life (HRQoL), muscle force, lung function and feelings of anxiety and depression in people after curative intent treatment for NSCLC with age and gender-matched healthy controls. METHODS: This cross-sectional study included 23 participants (68 ± 10yr; 16 females), 6-10 weeks after lobectomy for NSCLC or, for those who received adjuvant chemotherapy, 4-8 weeks after their last cycle. The study also included 20 age and gender-matched healthy controls (69 ± 5yr; 13 females). All participants underwent measurements of exercise capacity (cycle-ergometry test [CPET] and 6-min walk test [6MWT]), HRQoL (Short-Form 36 general health survey [SF-36]), handgrip force, quadriceps torque, lung function and feelings of anxiety and depression. RESULTS: When compared with data collected in healthy controls, those in the NSCLC group demonstrated impairments in the peak rate of oxygen consumption (15 ± 3 versus 24 ± 7 ml kg(-1)·min(-1); p < 0.001) and maximum work rate (75 ± 25 versus 127 ± 51Watts; p < 0.001) measured during the CPET, and 6-min walk distance (494 ± 77 versus 649 ± 61 m; p < 0.001). Similarly, impairments were demonstrated in all domains of the SF-36 (p < 0.01 for all), isometric handgrip force (28 ± 7 versus 34 ± 10 kg; p = 0.02), and all measures of lung function (p ≤ 0.001 for all). A higher score for depression was also seen (3.0 ± 2.5 versus 1.5 ± 1.6; p = 0.03). There was no difference between the groups in isometric quadriceps torque or feelings of anxiety. CONCLUSIONS: After curative intent treatment for NSCLC, compared to healthy controls, impairments were demonstrated in laboratory and field-based measures of exercise capacity, HRQoL, isometric handgrip force and lung function. Although people after curative intent treatment for NSCLC reported greater feelings of depression, these levels were below those considered clinically relevant. These findings suggest that people after curative intent treatment for NSCLC may benefit from rehabilitative strategies to optimise exercise capacity and HRQoL.

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.

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.

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.

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 (r(s))=0.86-0.94, P<0.01) and internal consistency (Cronbach's 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.

Effects of high-intensity inspiratory muscle training following a near-fatal gunshot wound.

BACKGROUND AND PURPOSE: Severe injuries sustained during combat may classify individuals as undeployable for active service. It is imperative that every effort is made to optimize physical function following such injuries. CASE DESCRIPTION: A 38-year-old man sustained a gunshot wound during armed combat. The bullet entered via the left axilla and exited from the right side of the abdomen, resulting in severe thoracic and abdominal injuries. Five months later, he continued to describe severe dyspnea on exertion. During a cardiopulmonary exercise test on a cycle ergometer, he achieved a maximum rate of oxygen uptake of 2,898 mL·min(-1) (114% predicted) and maximum power of 230 W (114% predicted). His maximum forced inspiratory flow was 5.95 L·s(-1), and inspiratory reserve volume at test end was ∼80 mL. The test was terminated by the patient due to dyspnea that was too severe to tolerate. Video fluoroscopy demonstrated impaired right hemidiaphragm function. The main goals of therapy were to reduce dyspnea on exertion and to enable return to full work duties. A program of high-intensity, interval-based threshold inspiratory muscle training (IMT) was undertaken. OUTCOMES: An average of 5 sessions of IMT were completed each week for 10 weeks. During a repeat cardiopulmonary exercise test, the patient achieved a similar power and maximum rate of oxygen uptake. His maximum forced inspiratory flow increased by 48% to 8.83 L·s(-1), and he was limited by leg fatigue. DISCUSSION: High-intensity IMT was safe and well tolerated. It was associated with improvements in maximum forced inspiratory flow and changed the locus of symptom limitation during high-intensity exercise from dyspnea to leg fatigue.

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.

BACKGROUND: 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. DESIGN/METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000502235.

Implications of exercise-induced pulmonary arterial hypertension.

PURPOSE: To characterize the hemodynamic and ventilatory responses to exercise in a group of patients with unexplained dyspnea, increased risk for pulmonary arterial hypertension (PAH), and an elevated mean pulmonary artery pressure (mPAP; >30 mm Hg) on exercise. METHODS: A total of 37 symptomatic patients at risk of PAH and 20 healthy controls underwent a cardiopulmonary exercise test and were assessed for quality of life (QOL). Patients had a pulmonary artery catheter in situ during the exercise test. RESULTS: Seventeen subjects had exercise-induced PAH (EIPAH), which we defined as mPAP ≤ 25 mm Hg at rest, and mPAP > 30 mm Hg and pulmonary artery wedge pressure <20 mm Hg on exercise. These subjects had reduced peak exercise cardiac output (72% ± 19% predicted). Further, compared with matched controls, subjects with EIPAH had reduced peak oxygen consumption (1.2 ± 0.4 vs 1.7 ± 0.5 L · min, P < 0.05), an elevated ventilatory equivalent for carbon dioxide (41.0 ± 7.3 vs 31.0 ± 2.9, P < 0.05) and reduced end-tidal carbon dioxide tension (32.6 ± 3.6 vs 39.4 ± 2.7 mm Hg, P < 0.05) at the anaerobic threshold. These exercise abnormalities were associated with impaired QOL (P < 0.05). CONCLUSIONS: Elevated pulmonary artery pressure on exercise can be associated with hemodynamic and ventilatory abnormalities typical of PAH, along with impaired exercise capacity and reduced QOL.

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.

Recent consumption of a large meal does not affect measurements of lung function.

BACKGROUND AND OBJECTIVE: It is currently recommended that patients avoid large meals prior to their lung function tests. The aim of this study is to determine whether this recommendation is necessary in clinical practice. METHODS: A randomized controlled cross-over trial was conducted. Subjects performed lung function tests (spirometry, measurement of lung volumes and gas transfer) prior to, directly following and 2 h after consuming a large breakfast. On the control arm, subjects performed the same lung function tests while fasting for the duration of the morning. The study subjects comprised 12 healthy subjects, 10 COPD patients and 10 patients with interstitial lung disease. RESULTS: There were no significant differences between measurements on the meal and control days for FEV(1), FVC, TLC or DL(CO). There were no significant changes with time in any of these parameters over the course of either the meal or control morning. CONCLUSIONS: Common measures of lung function are not affected by the prior consumption of a large meal and it is unnecessary to advise patients to avoid a large meal prior to lung function assessment.

Continuous positive airway pressure titration for obstructive sleep apnoea: automatic versus manual titration.

BACKGROUND AND AIMS: Manual laboratory continuous positive airway pressure (CPAP) titration for obstructive sleep apnoea (OSA) is costly, time intensive and delays access to treatment. Automatic positive airway pressure (APAP) titration has the potential to reduce cost and improve access to treatment. The aim of this study was to assess the clinical efficacy and costs of APAP titration compared with manual titration in moderate-severe OSA. METHODS: Patients with moderate-severe OSA (apnoea/hypopnoea index >15 and Epworth Sleepiness Score > or = 8) who were free of co-morbidities that could impair APAP titration were eligible. 249 participants were randomised to manual titration, home APAP or laboratory APAP titration to determine a fixed pressure for CPAP. Clinical and direct cost outcomes were assessed after 4 weeks of treatment. RESULTS: Average nightly CPAP use, subjective sleepiness, SF36 quality of life, Trails A and B cognitive function and polysomnographic outcomes were similar among the per-protocol groups. Non-hypertensive patients had a lower resting heart rate (and greater reduction in heart rate) at 4 weeks after laboratory APAP titration compared with home APAP titration. Costs per patient were highest in manual (AU$817.84), followed by laboratory (AU$647.56) and home (AU$132.09) APAP titration. An intention-to-treat analysis confirmed the effectiveness of APAP titration compared with manual titration in the standard clinical setting. CONCLUSIONS: Among patients with moderate-severe OSA without serious co-morbidities, outcomes at 1 month indicate that APAP titration is more cost-effective than manual laboratory titration to determine an appropriate pressure for CPAP for long-term use; with the largest savings occurring in the home APAP patients.