Pulmonary Function and Lung Fibrosis up to 12 Years After Breast Cancer Radiotherapy.

PURPOSE: Breast cancer (BC) treatment may affect pulmonary function, but evidence of long-term pulmonary toxicity is scarce. This study aimed to evaluate pulmonary function, radiation fibrosis (RF), and patient-reported dyspnea up to 12 years after different BC treatment modalities. METHODS AND MATERIALS: Two hundred fifty patients with BC referred to postoperative radiotherapy (RT) were included in this study. High-resolution computed tomography, pulmonary function tests (PFTs), clinical examinations, and patient-reported dyspnea were assessed before RT and at 3, 6, and 12 months and up to 12 years after RT. RESULTS: Vital capacity (VC), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusion capacity of the lungs for carbon monoxide (DLCO) declined at 3 months after RT and remained low at long-term follow-up except for DLCO, which increased up to 12 years after RT. VC, FEV1, and FVC changes differed between patients treated with and without chemotherapy, and FEV1 differed between patients treated with locoregional and local RT. An early decline in VC, FEV1, and FVC predicted a late decline in PFT values up to 12 years after RT (P = .020, P = .004, and P = .020, respectively). RF, mainly grade 1, was observed in 91% of patients at long-term follow-up. Few patients reported severe dyspnea at long-term follow-up, and there was no statistically significant association with concurrent RF or decline in PFT values from baseline. CONCLUSIONS: Chemotherapy and locoregional RT affected performance in PFTs up to 12 years after RT. Reduction in VC, FVC, and FEV1 3 months after RT predicted a decline in PFT values at long-term follow-up. However, a late decline in PFT values was not associated with long-term RF or patient-reported dyspnea.

Identification of exercise-regulated genes in mice exposed to cigarette smoke.

Cigarette smoke (CS) is the major risk factor for COPD and is linked to cardiopulmonary dysfunction. Exercise training as part of pulmonary rehabilitation is recommended for all COPD patients. It has several physiological benefits, but the mechanisms involved remain poorly defined. Here, we employed transcriptomic profiling and examined lung endothelium to investigate novel interactions between exercise and CS on cardiopulmonary alterations. Mice were exposed to 20 weeks of CS, CS + 6 weeks of high-intensity interval training on a treadmill, or control. Lung and cardiac (left and right ventricle) tissue were harvested and RNA-sequencing was performed and validated with RT-qPCR. Immunohistochemistry assessed pulmonary arteriolar changes. Transcriptome analysis between groups revealed 37 significantly regulated genes in the lung, 21 genes in the left ventricle, and 43 genes in the right ventricle (likelihood-ratio test). Validated genes that showed interaction between exercise and CS included angiotensinogen (p = 0.002) and resistin-like alpha (p = 0.019) in left ventricle, with prostacyclin synthetase different in pulmonary arterioles (p = 0.004). Transcriptomic profiling revealed changes in pulmonary and cardiac tissue following exposure to CS, with exercise training exerting rescue effects. Exercise-regulated genes included angiotensinogen and resistin-like alpha, however, it remains unclear if these represent potential candidate genes or biomarkers that could play a role during pulmonary rehabilitation.

Exercise and obstructive sleep apnoea: a 24-week follow-up study.

Objective: Report on long-term follow-up results in the apnoea hypopnea index (AHI) and self-reported daytime sleepiness in participants with moderate to severe obstructive sleep apnoea at 12 weeks after completion of a high-intensity exercise training or control intervention. Methods: Twenty-six participants with obstructive sleep apnoea (body mass index (BMI) 37 (36-39) kg/m, age 52 (49-55) years, apnoea-hypopnoea index 40.5 (31.3-50.2) events/hour), randomised to either 12 weeks of supervised high-intensity interval training (HIIT) (4×4 min of treadmill running or walking at 90%-95% of maximal heart rate) or no intervention (control), underwent a sleep evaluation follow-up 24 weeks after intervention initiation. Respiratory measures during sleep were registered at baseline, 12 weeks (postintervention) and 24 weeks (long-term follow-up). Results: At the 24-week follow-up, there were no statistically significant differences between the groups in the AHI (HIIT 30.7 (17.2-44.1) and control 38.7 (22.8-54.5) events/hour), Epworth score (HIIT 7.0 (4.7-9.3) and control 5.5 (3.9-7.0)), mean oxygen saturation (HIIT 93.2 (92.5-93.9) and control 92.0 (91.1-92.8)) or oxygen desaturation events (HIIT 32.9 (20.4-45.4) and control 44.3 (27.3-61.3) n/hour). BMI remained unchanged from the baseline in both groups. In the HIIT group, only two participants reported having continued with HIIT at 24 weeks. Conclusion: The effect of 12 weeks of supervised high-intensity exercise training on AHI and self-reported daytime sleepiness was lost at the 24-week follow-up.

Effect of continuous positive airway pressure therapy on recurrence of atrial fibrillation after pulmonary vein isolation in patients with obstructive sleep apnea: A randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Whether treatment with continuous positive airway pressure (CPAP) reduces AF recurrence after catheter ablation with pulmonary vein isolation (PVI) is unknown. OBJECTIVE: The purpose of this study was to assess the effect of CPAP treatment on the recurrence and burden of AF after PVI in patients with OSA. METHODS: We randomized patients with paroxysmal AF and an apnea-hypopnea index (AHI) ≥15 events/hour to treatment with CPAP or standard care. Heart rhythm was monitored by an implantable loop recorder. AF recurrence after PVI was defined as any episode of AF lasting >2 minutes after a 3-month blanking period. RESULTS: PVI was performed in 83 patients. Thirty-seven patients were randomized to CPAP treatment and 46 patients to standard care. The AHI was reduced from 26.7 ± 14 events/hour to 1.7 ± 1.3 events/hour at follow-up in the CPAP group (P = .001). A total of 57% of patients in both the CPAP group and the standard care group had at least 1 episode of AF 3-12 months after PVI (P for difference = 1). AF burden after ablation was reduced in both groups, with no between-group difference (P = .69). CONCLUSION: In patients with paroxysmal AF and OSA, treatment with CPAP did not further reduce the risk of AF recurrence after ablation. PVI considerably reduced the burden of AF in OSA patients, without any difference between groups.

Effect of 5 years of exercise training on the cardiovascular risk profile of older adults: the Generation 100 randomized trial.

AIMS: The aim of this study was to compare the effects of 5 years of supervised exercise training (ExComb), and the differential effects of subgroups of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), with control on the cardiovascular risk profile in older adults. METHODS AND RESULTS: Older adults aged 70-77 years from Trondheim, Norway (n = 1567, 50% women), able to safely perform exercise training were randomized to 5 years of two weekly sessions of HIIT [∼90% of peak heart rate (HR), n = 400] or MICT (∼70% of peak HR, n = 387), together forming ExComb (n = 787), or control (instructed to follow physical activity recommendations, n = 780). The main outcome was a continuous cardiovascular risk score (CCR), individual cardiovascular risk factors, and peak oxygen uptake (VO2peak). CCR was not significantly lower [-0.19, 99% confidence interval (CI) -0.46 to 0.07] and VO2peak was not significantly higher (0.39 mL/kg/min, 99% CI -0.22 to 1.00) for ExComb vs. control. HIIT showed higher VO2peak (0.76 mL/kg/min, 99% CI 0.02-1.51), but not lower CCR (-0.32, 99% CI -0.64 to 0.01) vs. control. MICT did not show significant differences compared to control or HIIT. Individual risk factors mostly did not show significant between-group differences, with some exceptions for HIIT being better than control. There was no significant effect modification by sex. The number of cardiovascular events was similar across groups. The healthy and fit study sample, and contamination and cross-over between intervention groups, challenged the possibility of detecting between-group differences. CONCLUSIONS: Five years of supervised exercise training in older adults had little effect on cardiovascular risk profile and did not reduce cardiovascular events. REGISTRATION: ClinicalTrials.gov: NCT01666340.

High-intensity interval training and pulmonary hemodynamics in COPD with hypoxemia.

BACKGROUND: Exercise is recommended for all patients with COPD. Evidence for its benefit is considerably weaker in the more severe stages of the disease. The aim of this study was to investigate whether high-intensity interval training could improve exercise capacity, pulmonary hemodynamics and cardiac function in patients with severe COPD and hypoxemia. METHODS: Stable patients with COPD GOLD stage III or IV and hypoxemia were included. They underwent extensive cardiopulmonary testing including right heart catheterization, lung function tests, echocardiography and 6-minute walk test before and after completion of 10 weeks of high-intensity interval training performed with supplemental oxygen. Primary endpoint was change in pulmonary artery pressure measured by right heart catheterization. RESULTS: Ten patients with very severe airflow obstruction, mean FEV1 28.7% predicted and mean FEV1/VC 0.39 completed the exercise programme. Pulmonary artery pressure remained unchanged following the intervention (26,3 mmHg vs. 25,8 mmHg at baseline, p 0.673). Six-minute walk distance improved by a mean of44.8 m (p 0.010), which is also clinically significant. We found marginally improved left ventricular ejection fraction on echocardiography (54.6% vs 59.5%, p 0.046). CONCLUSION: High-intensity interval training significantly improved exercise capacity while pulmonary hemodynamics remained unchanged. The improvement may therefore be due to mechanisms other than altered pulmonary artery pressure. The increase in ejection fraction is of uncertain clinical significance. The low number of patients precludes firm conclusions.

Lung function and peak oxygen uptake in chronic obstructive pulmonary disease phenotypes with and without emphysema.

Previous studies of associations of forced expiratory lung volume in one second (FEV1) with peak oxygen uptake (VO2peak) in chronic obstructive pulmonary disease (COPD) have not taken sex, age and height related variance of dynamic lung volumes into account. Nor have such demographic spread of spirometric measures been considered in studies comparing VO2peak between COPD phenotypes characterized by degree of emphysema. We aimed to assess the association of FEV1Z-score with VO2peak in COPD (n = 186) and investigate whether this association differs between emphysema (E-COPD) and non-emphysema (NE-COPD) phenotypes. Corresponding assessments using standardized percent predicted FEV1 (ppFEV1) were performed for comparison. Additionally, phenotype related differences in VO2peak were compared using FEV1Z-score and ppFEV1 as alternative expressions of FEV1. E-COPD and NE-COPD were defined by transfer factor of the lung for carbon monoxide below and above lower limits of normal (LLN), respectively. The associations were assessed in linear regression models. One unit reduction in FEV1Z-score was associated with 1.9 (95% CI 1.4, 2.5) ml/kg/min lower VO2peak. In stratified analyses, corresponding estimates were 2.2 (95% CI 1.4, 2.9) and 1.2 (95% CI 0.2, 2.2) ml/kg/min lower VO2peak in E-COPD and NE-COPD, respectively. The association did not differ statistically by COPD phenotype (p-value for interaction = 0.153). Similar estimates were obtained in analyses using standardized ppFEV1. Compared to NE-COPD, VO2peak was 2.2 (95% CI 0.8, 3.6) and 2.1 (95% CI 0.8, 3.5) ml/kg/min lower in E-COPD when adjusted for FEV1Z-score and ppFEV1, respectively. In COPD, FEV1Z-score is positively associated with VO2peak. This association was stronger in E-COPD but did not differ statistically by phenotype. Both the association of FEV1 with VO2peak and the difference in VO2peak comparing COPD phenotypes seems independent of sex, age and height related variance in FEV1. Mechanisms leading to reduction in FEV1 may contribute to lower VO2peak in E-COPD.

Effect of Continuous Positive Airway Pressure on Arrhythmia in Atrial Fibrillation and Sleep Apnea: A Randomized Controlled Trial.

Rationale: Sleep apnea (SA) is highly prevalent in patients with atrial fibrillation (AF), and both conditions are associated with adverse cardiovascular outcomes.Objectives: To determine the effect of continuous positive airway pressure (CPAP) on AF burden.Methods: This open-label, parallel-group, randomized controlled trial included patients with paroxysmal AF and moderate to severe SA (apnea-hypopnea index ⩾15). A computerized system randomized eligible patients (1:1) to 5 months' treatment with CPAP plus usual care (CPAP, n = 55) or usual care alone (control, n = 54). The outcome assessment was blinded. The planned primary outcome was the difference between CPAP treatment and control groups in change of AF burden (percentage of time in AF) as measured by implantable loop recorder.Measurements and Main Results: A total of 579 patients with paroxysmal AF had respiratory polygraphy, of whom 244 (42%) had moderate to severe SA. Of these, 158 (65%) participated in the CPAP run-in period, of whom 39 (25%) patients did not tolerate the treatment. A total of 108 patients were available for the primary analysis. The mean time in AF decreased from 5.6% at baseline to 4.1% during the last 3 months of CPAP intervention and from 5.0% to 4.3% in the control group. The adjusted between-group difference at follow-up was -0.63 (95% confidence interval, -2.55 to 1.30) percentage points (P = 0.52). Seven serious adverse events (13%) occurred in the CPAP group, and two (4%) occurred in the control group.Conclusions: In patients with paroxysmal AF and SA, treatment with CPAP did not result in a statistically significant reduction in the burden of AF.Clinical trial registered with www.clinicaltrials.gov (NCT02727192).

Comparing manual and automatic scoring of sleep monitoring data from portable polygraphy.

We used sleep monitoring data from a study that investigated the prevalence, characteristics, risk factors and type of sleep apnea (SA) in 579 patients with paroxysmal atrial fibrillation. Most patients were screened for two nights, resulting in 1,043 sleep recordings that each contained data from one night. SA was diagnosed using the Nox T3 portable sleep monitor. An experienced sleep specialist scored the recordings manually using Noxturnal software. A total of 157 women (27%) and 422 men (73%) were examined; 477 (82.7%) had an apnea-hypopnea index (AHI) ≥ 5/hr, whereas moderate to severe SA (AHI ≥ 15/hr) was diagnosed in 243 patients (42.1%). The AHI derived from automatic and manual scoring showed a good agreement (Pearson's r coefficient of 0.96). The median difference in AHI was very small (i.e., 0.72 [mean difference, 1.06]), but was statistically significant (p < .0001). Automatic scoring classified sleep recordings with more than 90% accuracy into SA categories of mild (AHI ≥ 5/hr), moderate (AHI ≥ 15/hr) and severe (AHI ≥ 30/hr). We found a minor (11%-21%) mis-estimation of the number of recordings right above and below the boundary separating mild and moderate SA. The accuracy of automatic scoring differed from recording to recording, especially regarding the sensitivity of detecting disrupted breathing events. We found low to moderate agreement for the duration of disrupted breathing events (r = .53), for which the automatic scoring led to a statistically significant overestimation by 5.22 s (p < .0001).

Effect of exercise training for five years on all cause mortality in older adults-the Generation 100 study: randomised controlled trial.

OBJECTIVE: To evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years). DESIGN: Randomised controlled trial. SETTING: General population of older adults in Trondheim, Norway. PARTICIPANTS: 1567 of 6966 individuals born between 1936 and 1942. INTERVENTION: Participants were randomised to two sessions weekly of high intensity interval training at about 90% of peak heart rate (HIIT, n=400), moderate intensity continuous training at about 70% of peak heart rate (MICT, n=387), or to follow the national guidelines for physical activity (n=780; control group); all for five years. MAIN OUTCOME MEASURE: All cause mortality. An exploratory hypothesis was that HIIT lowers mortality more than MICT. RESULTS: Mean age of the 1567 participants (790 women) was 72.8 (SD 2.1) years. Overall, 87.5% of participants reported to have overall good health, with 80% reporting medium or high physical activity levels at baseline. All cause mortality did not differ between the control group and combined MICT and HIIT group. When MICT and HIIT were analysed separately, with the control group as reference (observed mortality of 4.7%), an absolute risk reduction of 1.7 percentage points was observed after HIIT (hazard ratio 0.63, 95% confidence interval 0.33 to 1.20) and an absolute increased risk of 1.2 percentage points after MICT (1.24, 0.73 to 2.10). When HIIT was compared with MICT as reference group an absolute risk reduction of 2.9 percentage points was observed (0.51, 0.25 to 1.02) for all cause mortality. Control participants chose to perform more of their physical activity as HIIT than the physical activity undertaken by participants in the MICT group. This meant that the controls achieved an exercise dose at an intensity between the MICT and HIIT groups. CONCLUSION: This study suggests that combined MICT and HIIT has no effect on all cause mortality compared with recommended physical activity levels. However, we observed a lower all cause mortality trend after HIIT compared with controls and MICT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.

The association between normal lung function and peak oxygen uptake in patients with exercise intolerance and coronary artery disease.

In coronary artery disease (CAD), exercise intolerance with reduced oxygen uptake at peak exercise (VO2peak) is assumed to primarily reflect cardiovascular limitation. However, oxygen transport and utilization depends on an integrated organ response, to which the normal pulmonary system may influence overall capacity. This study aimed to investigate the associations between normal values of lung function measures and VO2peak in patients with exercise intolerance and CAD. We hypothesized that forced expiratory lung volume in one second (FEV1), transfer factor of the lung for carbon monoxide (TLCO) and TLCO/alveolar volume (TLCO/VA) above lower limits of normal (LLN) are associated with VO2peak in these patients. We assessed patients with established CAD (n = 93; 21 women) referred for evaluation due to exercise intolerance from primary care to a private specialist clinic in Norway. Lung function tests and cardiopulmonary exercise testing (CPET) were performed. Z-scores of FEV1, FEV1/forced vital capacity (FVC), TLCO and TLCO/VA were calculated using the Global Lung Function Initiative (GLI) software and LLN was defined as the fifth percentile (z = -1.645). Non-obstructive patients, defined by both FEV1 and FEV1/FVC above LLN, were assessed. The associations of FEV1Z-score, TLCOZ-score and TLCO/VAZ-score above LLN with VO2peak were investigated using linear regression models. Mean VO2peak ± standard deviation (SD) was 23.8 ± 6.4 ml/kg/min in men and 19.7 ± 4.4 ml/kg/min in women. On average, one SD increase in FEV1, TLCO and TLCO/VA were associated with 1.4 (95% CI 0.2, 2.6), 2.6 (95% CI 1.2, 4.0) and 1.3 (95% CI 0.2, 2.5) ml/kg/min higher VO2peak, respectively. In non-obstructive patients with exercise intolerance and CAD, FEV1, TLCO and TLCO/VA above LLN are positively associated with VO2peak. This may imply a clinically significant influence of normal lung function on exercise capacity in these patients.

Expiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight: a meta-analysis of individual participant data.

BACKGROUND: Maximal expiratory airflow peaks early in the third decade of life, then gradually declines with age. The pattern of airflow through adulthood for individuals born very preterm (at <32 weeks' gestation) or with very low birthweight (<1501 g) is unknown. We aimed to compare maximal expiratory airflow in these individuals during late adolescence and early adulthood with that of control individuals born with normal birthweight (>2499 g) or at term. METHODS: We did a meta-analysis of individual participant data from cohort studies, mostly from the pre-surfactant era. Studies were identified through the Adults born Preterm International Collaboration and by searching PubMed and Embase (search date May 25, 2016). Studies were eligible if they reported on expiratory flow rates beyond 16 years of age in individuals born very preterm or with very low birthweight, as well as controls born at term or with normal birthweight. Studies with highly selected cohorts (eg, only participants with bronchopulmonary dysplasia) or in which few participants were born very preterm or with very low birthweight were excluded. De-identified individual participant data from each cohort were provided by the holders of the original data to a central site, where all the data were pooled into one data file. Any data inconsistencies were resolved by discussion with the individual sites concerned. Individual participant data on expiratory flow variables (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, and forced expiratory flow at 25-75% of FVC [FEF25-75%]) were converted to Z scores and analysed with use of generalised linear mixed models in a one-step approach. FINDINGS: Of the 381 studies identified, 11 studies, comprising a total of 935 participants born very preterm or with very low birthweight and 722 controls, were eligible and included in the analysis. Mean age at testing was 21 years (SD 3·4; range 16-33). Mean Z scores were close to zero (as expected) in the control group, but were reduced in the very preterm or very low birthweight group for FEV1 (-0·06 [SD 1·03] vs -0·81 [1·33], mean difference -0·78 [95% CI -0·96 to -0·61], p<0·0001), FVC (-0·15 [0·98] vs -0·38 [1·18], -0·25 [-0·40 to -0·10], p=0·0012), FEV1/FVC ratio (0·14 [1·10] vs -0·64 [1·35], -0·74 [-0·85 to -0·64], p<0·0001), and FEF25-75% (-0·04 [1·10] vs -0·95 [1·47], -0·88 [-1·12 to -0·65], p<0·0001). Similar patterns were observed when we compared the proportions of individuals with values below the fifth percentile. INTERPRETATION: Individuals born very preterm or with very low birthweight are at risk of not reaching their full airway growth potential in adolescence and early adulthood, suggesting an increased risk of chronic obstructive pulmonary disease in later adulthood. FUNDING: National Health and Medical Research Council (Australia), University of Bergen, Western Norway Regional Authority, National Institute for Health Research (UK), Stichting Astmabestrijding, St Olav's Hospital's Research Fund, Academy of Finland, European Commission, National Institute of Child Health and Human Development (USA), Victorian Government's Operational Infrastructure Support Program.

The association between dynamic lung volume and peak oxygen uptake in a healthy general population: the HUNT study.

BACKGROUND: Although dynamic lung volume is not considered a limiting factor of peak oxygen uptake (VO2peak) in healthy subjects, an association between forced expiratory lung volume in one second (FEV1) and VO2peak has been reported in a healthy population aged 69 - 77 years. We hypothesized that a corresponding association could be found in a healthy general population including young and middle-aged subjects. METHODS: In a population-based study in Norway, we investigated the association between FEV1 above the lower limit of normal (LLN) and VO2peak using linear regression and assessed the ventilatory reserve (VR) in healthy subjects aged 20 - 79 years (n = 741). RESULTS: On average, one standard deviation (SD) increase in FEV1 was associated with 1.2 ml/kg/min (95% CI 0.7 - 1.6) higher VO2peak. The association did not differ statistically by sex (p-value for interaction = 0.16) and was similar (0.9 ml/kg/min, 95% CI 0.2 - 1.5) in a sensitivity analysis including only never-smokers (n = 376). In subjects below and above 45 years of age, corresponding estimates were 1.2 ml/kg/min (95% CI 0.5 - 1.8) and 1.2 ml/kg/min (95% CI 0.5 - 1.9), respectively. Preserved VR (≥ 20%) was observed in 66.6% of men and 86.4% of women. CONCLUSIONS: Normal dynamic lung volume, defined as FEV1 above LLN, was positively associated with VO2peak in both men and women, in never-smokers and in subjects below and above 45 years of age. The majority of subjects had preserved VR, and the results suggest that FEV1 within normal limits may influence VO2peak in healthy subjects even when no ventilatory limitation to exercise is evident.

Comparison of procalcitonin, C-reactive protein, white blood cell count and clinical status in diagnosing pneumonia in patients hospitalized with acute exacerbations of COPD: A prospective observational study.

Lower respiratory tract infection is the most common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of the present study was to compare the accuracy of procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC) as single diagnostic tests and in combination with clinical signs and symptoms to diagnose pneumonia in patients hospitalized with AECOPD. This was a prospective, single centre observational study. Patients with spirometry-confirmed COPD who were hospitalized due to AECOPD were consecutively recruited at the hospital's Emergency Unit. Pneumonia was defined as a new pulmonary infiltrate on chest X-ray. The values of PCT, CRP and WBC were determined at admission. Receiver operating characteristic (ROC) curve analysis was used to study the accuracy of various diagnostic tests. Of the 113 included patients, 35 (31%) had pneumonia at admission. Area under the ROC curve (AUC) for PCT, CRP and WBC as a single test to distinguish between patients with and without pneumonia was 0.67 (95% CI 0.55-0.79), 0.73 (95% CI 0.63-0.84) and 0.67 (95% CI 0.55-0.79), respectively ( p = 0.42 for the test of difference). The AUC for a model of clinical signs and symptoms was 0.84 (95% CI 0.76-0.92). When biomarkers were added to the clinical model, the AUCs of the combined models were not significantly different from that of the clinical model alone ( p = 0.54). PCT had about the same accuracy as CRP and WBC in predicting pneumonia in patients hospitalized with AECOPD both as a single test and in combination with clinical signs and symptoms.

The Prevalence and Symptom Profile of Asthma-COPD Overlap: The HUNT Study.

The concept of asthma and COPD as separate conditions has been questioned, and the term asthma-COPD overlap syndrome has been introduced. We assessed the prevalence, symptoms, and lifestyle factors of asthma-COPD overlap (ACO) in a large Norwegian population-based study. From 2006 to 2008, a total of 50,777 residents of Nord-Trøndelag participated in the Nord-Trøndelag Health Study, Norway. They completed questionnaires regarding respiratory symptoms, disease status, and medication use. We estimated the prevalence and 95% confidence intervals of ACO. Additionally, spirometry was used to estimate the prevalence of ACO in a subgroup. The prevalence of self-reported ACO was 1.9%, and in age groups <40, 40-60 and ≥60 years it was 0.7%, 1.4%, and 3.2%, respectively. Among those reporting COPD, the proportion of ACO was 0.56. In the spirometry subgroup when ACO was defined as doctor diagnosed asthma ever and FEV1/FVC < 0.70, the prevalence of ACO was 2.0%. All respiratory symptoms, separately or in combination, as well as medication use were reported most frequently in those with ACO compared to the other groups. Strikingly, we observed a two-fold higher proportion of allergic rhinitis in ACO compared to COPD only. In this Norwegian population, the prevalence of self-reported ACO was 1.9%, and the corresponding proportion of ACO among those with COPD was 0.56. Participants with ACO generally had the highest proportions of respiratory symptoms compared to asthma or COPD.

Treatment of sleep apnea in patients with paroxysmal atrial fibrillation: design and rationale of a randomized controlled trial.

RATIONALE: Atrial fibrillation is associated with increased mortality as well as morbidity. There is strong evidence for an association between atrial fibrillation and sleep apnea. It is not known whether treatment of sleep apnea with continuous positive airway pressure (CPAP) will reduce the burden of atrial fibrillation. OBJECTIVE: The Treatment of Sleep Apnea in Patients with Paroxysmal Atrial Fibrillation study will investigate the effects of CPAP in patients with paroxysmal atrial fibrillation and sleep apnea. DESIGN: The trial has a dual center, randomized, controlled, open-label, parallel design. METHODS: Two centers will enroll a total of 100 patients with both paroxysmal atrial fibrillation and sleep apnea (apnea-hypopnea index [AHI] ≥ 15 events/h) who are scheduled for catheter ablation. Patients will be randomized in a 1:1 ratio to CPAP or control group (50 patients in each arm). The effects of CPAP treatment on atrial fibrillation will be determined using an implanted loop recorder (Reveal LINQ™, Medtronic) that detects all arrhythmia episodes. The primary endpoint is a reduction of the total burden of atrial fibrillation in the intervention group, after 5 months' follow-up (preablation). Reduction in the arrhythmia recurrence rate after ablation is the main secondary endpoint. All patients will be followed up for 12 months after ablation. CONCLUSION: This study is the first randomized controlled trial that will provide data on the effects of CPAP therapy in patients with paroxysmal atrial fibrillation and sleep apnea. The results are expected to improve our understanding of the interaction between paroxysmal atrial fibrillation and sleep apnea. ClinicalTrials.gov Identifier. NCT02727192.

Cardiorespiratory Reference Data in Older Adults: The Generation 100 Study.

PURPOSE: Cardiorespiratory fitness (CRF) is regarded a clinical vital sign, and accurate reference values for all age groups are essential. Little data exist on CRF and cardiorespiratory function in older adults. The aim of this study was to provide normative values for CRF and cardiorespiratory function in older adults, including people with history of cardiovascular diseases (CVD). METHODS: In total, 1537 (769 women) participants age 70 to 77 yr underwent clinical examinations and cardiopulmonary exercise tests. Peak oxygen uptake (V˙O2peak), ventilation (V˙Epeak), expiration of carbon dioxide (VV˙CO2peak), breathing frequency (BFpeak), tidal volume (VTpeak), oxygen pulse (O2 pulsepeak), ventilatory efficiency (EqV˙O2peak and EqV˙CO2peak), and 1-min HR recovery were assessed. RESULTS: Men compared with women had higher V˙O2peak (31.3 ± 6.7 vs 26.2 ± 5.0 mL·min·kg), BFpeak (41.8 ± 8.0 vs 39.7 ± 7.1 breaths per minute), VTpeak (2.3 ± 0.5 vs 1.6 ± 0.3), O2 pulsepeak (16.4 ± 3.2 vs 11.3 ± 2.0), V˙CO2peak (2.9 ± 0.2 and 1.9 ± 0.1 L·min), V˙Epeak (96.2 ± 21.7 vs 61.1 ± 21.6 L·min), EqV˙O2peak (38.0 ± 6.9 vs 35.1 ± 5.6), and EqV˙CO2peak (33.5 ± 5.7 vs 31.9 ± 4.5). Women and men with CVD had lower V˙O2peak (14% and 19%), peak HR (5% and 6%), V˙Epeak (8% and 10%), VTpeak (7% and 4%), and lower EqV˙CO2peak (4% and 6%) compared with their healthy counterparts, respectively. Compared with healthy women and men, 1-min HR recovery was 12% and 16% lower for women and men with CVD. CONCLUSIONS: This study represents the largest reference material on directly measured CRF and cardiorespiratory function in older men and women, with and without CVD. This novel information will help researchers and clinicians to interpret data form cardiopulmonary testing in older adults.

Lung function parameters improve prediction of VO2peak in an elderly population: The Generation 100 study.

Peak oxygen uptake (VO2peak) is an indicator of cardiovascular health and a useful tool for risk stratification. Direct measurement of VO2peak is resource-demanding and may be contraindicated. There exist several non-exercise models to estimate VO2peak that utilize easily obtainable health parameters, but none of them includes lung function measures or hemoglobin concentrations. We aimed to test whether addition of these parameters could improve prediction of VO2peak compared to an established model that includes age, waist circumference, self-reported physical activity and resting heart rate. We included 1431 subjects aged 69-77 years that completed a laboratory test of VO2peak, spirometry, and a gas diffusion test. Prediction models for VO2peak were developed with multiple linear regression, and goodness of fit was evaluated. Forced expiratory volume in one second (FEV1), diffusing capacity of the lung for carbon monoxide and blood hemoglobin concentration significantly improved the ability of the established model to predict VO2peak. The explained variance of the model increased from 31% to 48% for men and from 32% to 38% for women (p<0.001). FEV1, diffusing capacity of the lungs for carbon monoxide and hemoglobin concentration substantially improved the accuracy of VO2peak prediction when added to an established model in an elderly population.

Does an Integrated Care Intervention for COPD Patients Have Long-Term Effects on Quality of Life and Patient Activation? A Prospective, Open, Controlled Single-Center Intervention Study.

BACKGROUND: Implementation of the COPD-Home integrated disease management (IDM) intervention at discharge after hospitalizations for acute exacerbations of COPD (AECOPD) led to reduced hospital utilization during the following 24 months compared to the year prior to study start. AIMS: To analyze the impact of the COPD-Home IDM intervention on health related quality of life, symptoms of anxiety and depression, and the degree of patient activation during 24 months of follow-up and to assess the association between these outcomes. METHODS: A single center, prospective, open, controlled clinical study. Changes in The St. George Respiratory Questionnaire (SGRQ), the Hospital anxiety (HADS-A) and depression (HADS-D) and the patient activation measure (PAM) scores were compared between the patients in the integrated care group (ICG) and the usual care group (UCG) 6, 12 and 24 months after enrolment. RESULTS: The questionnaire response rate was 80-96%. There were no statistically significant differences in the change of the SGRQ scores between the groups during follow up. After 12 months of follow-up there was a trend towards a reduction in the mean HADS-A score in the ICG compared to the UCG. The HADS-D scores remained stable in the ICG compared with an increasing trend in the UCG. Clinically significant difference in the PAM score was achieved only in the ICG, 6.7 (CI95% 0.7 to 7.5) compared to 3.6 (CI95% -1.4 to 8.6) in the UCG. In a logistic regression model a higher HADS-D score and current smoking significantly increased the odds for a low PAM score. CONCLUSION: The COPD-Home IDM intervention did not result in any statistically significant changes in mean SGRQ, HADS-A, HADS- D or PAM scores during the 24 months of follow-up. TRIAL REGISTRATION: The ID number for the study in the Clinical.Trials.gov registration system is 17417. ClinicalTrials.gov Identifier: NCT 00702078.

Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice.

PURPOSE: Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease and emphysema. However, evidence on the extrapulmonary effects of smoke exposure that precede lung impairments remains unclear at present, as are data on nonpharmacological treatments such as exercise training. METHODS: Three groups of mice, including control (n = 10), smoking (n = 10), and smoking with 6 wk of high-intensity interval treadmill running (n = 11), were exposed to 20 wk of fresh air or whole-body cigarette smoke. Exercise capacity (peak oxygen uptake) and lung destruction (histology) were subsequently measured, whereas the heart, peripheral endothelium (aorta), and respiratory (diaphragm) and limb (extensor digitorum longus and soleus) skeletal muscles were assessed for in vivo and in vitro function, in situ mitochondrial respiration, and molecular alterations. RESULTS: Smoking reduced body weight by 26% (P < 0.05) without overt airway destruction (P > 0.05). Smoking impaired exercise capacity by 15% while inducing right ventricular dysfunction by ~20%, endothelial dysfunction by ~20%, and diaphragm muscle weakness by ~15% (all P < 0.05), but these were either attenuated or reversed by exercise training (P < 0.05). Compared with controls, smoking mice had normal limb muscle and mitochondrial function (cardiac and skeletal muscle fibers); however, diaphragm measures of oxidative stress and protein degradation were increased by 111% and 65%, respectively (P < 0.05), but these were attenuated by exercise training (P < 0.05). CONCLUSIONS: Prolonged cigarette smoking reduced exercise capacity concomitant with functional impairments to the heart, peripheral endothelium, and respiratory muscle that preceded the development of overt emphysema. However, high-intensity exercise training was able to reverse these smoke-induced extrapulmonary impairments.