Serum Matrix Metalloproteinase-7, Respiratory Symptoms, and Mortality in Community-Dwelling Adults. MESA (Multi-Ethnic Study of Atherosclerosis).

RATIONALE: Matrix metalloproteinase-7 (MMP-7) has been implicated in interstitial lung disease pathobiology and proposed as a diagnostic and prognostic biomarker of idiopathic pulmonary fibrosis. OBJECTIVES: To test associations between serum MMP-7 and lung function, respiratory symptoms, interstitial lung abnormalities (ILA), and all-cause mortality in community-dwelling adults sampled without regard to respiratory symptoms or disease. METHODS: We measured serum MMP-7 in 1,227 participants in MESA (Multi-Ethnic Study of Atherosclerosis) at baseline. The 5-year outcome data were available for spirometry (n = 697), cough (n = 722), and dyspnea (n = 1,050). The 10-year outcome data were available for ILA (n = 561) and mortality (n = 1,227). We used linear, logistic, and Cox regression to control for potential confounders. MEASUREMENTS AND MAIN RESULTS: The mean (±SD) serum MMP-7 level was 4.3 (±2.5) ng/ml (range, 1.2-24.1 ng/ml). In adjusted models, each natural log unit increment in serum MMP-7 was associated with a 3.7% absolute decrement in FVC% (95% confidence interval [CI] = 0.9-6.6%), a 1.6-fold increased odds of exertional dyspnea (95% CI = 1.3-1.9), a 1.5-fold increased odds of ILAs (95% CI = 1.1-2.1), and a 2.2-fold increased all-cause mortality rate (95% CI = 1.9-2.5). The associations with ILA and mortality tended to be stronger among never-smokers (P values for interaction 0.06 and 0.01, respectively). CONCLUSIONS: Serum MMP-7 levels may be a quantitative biomarker of subclinical extracellular matrix remodeling in the lungs of community-dwelling adults, which may facilitate investigation of subclinical interstitial lung disease.

High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study.

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3-11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8-13.0), lower forced vital capacity (FVC) (mean adjusted difference -82 mL, 95% CI -119--44), lower 6-min walk distance (mean adjusted difference -40 m, 95% CI -1--80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43-2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39-1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.

Analysis of Skeletal Muscle Torque Capacity and Circulating Ceramides in Patients with Advanced Heart Failure.

BACKGROUND: Heart failure (HF)-related exercise intolerance is thought to be perpetuated by peripheral skeletal muscle functional, structural, and metabolic abnormalities. We analyzed specific dynamics of muscle contraction in patients with HF compared with healthy, sedentary controls. METHODS: Isometric and isokinetic muscle parameters were measured in the dominant upper and lower limbs of 45 HF patients and 15 healthy age-matched controls. Measurements included peak torque normalized to body weight, work normalized to body weight, power, time to peak torque, and acceleration and deceleration to maximum strength times. Body morphometry (dual energy X-ray absorptiometry scan) and circulating fatty acids and ceramides (lipodomics) were analyzed in a subset of subjects (18 HF and 9 controls). RESULTS: Extension and flexion time-to-peak torque was longer in the lower limbs of HF patients. Furthermore, acceleration and deceleration times in the lower limbs were also prolonged in HF subjects. HF subjects had increased adiposity and decreased lean muscle mass compared with controls. Decreased circulating unsaturated fatty acids and increased ceramides were found in subjects with HF. CONCLUSIONS: Delayed torque development suggests skeletal muscle impairments that may reflect abnormal neuromuscular functional coupling. These impairments may be further compounded by increased adiposity and inflammation associated with increased ceramides.

Impact of pulmonary hypertension on exercise performance in patients with interstitial lung disease undergoing evaluation for lung transplantation.

BACKGROUND AND OBJECTIVE: Pulmonary hypertension (PH) is a known complication in patients with interstitial lung disease (ILD). Cardiopulmonary exercise testing (CPET) is an essential tool for the assessment of patients with cardiac and pulmonary diseases due to its prognostic and therapeutic implications. Few studies have evaluated the relationship between CPET response and mean pulmonary artery pressures (mPAP) in ILD. The purpose of the present study was to determine and compare the potential correlations between CPET, 6-min walk test (6MWT), pulmonary function testing (PFT) and PH in patients with ILD being evaluated for lung transplantation. METHODS: The present study reviewed patients with ILD who received lung transplantations and had CPETs within 2 years before transplantation, right heart catheterizations, PFTs and 6MWTs within 4 months of CPET. RESULTS: A total of 72 patients with ILD were analysed; 36% had PH. There were significant correlations between mPAP and CPET parameters in patients with PH; but mPAP had no impact on percent of predicted diffusion capacity of the lung for carbon monoxide or 6-min walk distance (6MWD). CPET parameters were able to detect differences between levels of severity of PH through the use of the ratio of minute ventilation to rate of carbon dioxide production (VE/VCO2) and the partial pressure of end-tidal carbon dioxide. CONCLUSIONS: This is the first study that analyses 6MWD, PFT and CPET in patients with ILD awaiting lung transplantation with and without PH. The present study demonstrates the significant impact of PH on exercise capacity and performance in patients with ILD awaiting lung transplantation.

Comparing cardiopulmonary exercise testing in severe COPD patients with and without pulmonary hypertension.

PURPOSE: To determine; (i) the effect of PH on exercise capacity, gas exchange and oxygen pulse; (ii) the variables that correlate with mean pulmonary artery pressure (mPAP) in severe COPD patients. METHODS: We reviewed 98 severe COPD patients who had pulmonary function, right heart catheterisation, and cardiopulmonary exercise testing (CPET) performed within six months of each other. PH was defined by a resting mPAP > 25 mmHg. COPD patients with and without PH were compared using the independent samples t-test and Mann-Whitney U test. Pearson correlation coefficients were used to assess the relationship between continuous variables. RESULTS: PH was present in 32% of patients and the majority of PH was mild (mPAP, 25-35 mmHg). Peak workload, oxygen uptake and oxygen pulse on CPET were significantly lower in the PH group. Mean PAP was found to inversely correlate with peak oxygen uptake, with a tendency towards lower six-minute walk distance. No difference between two groups was seen in any of the gas exchange variables. CONCLUSION: In severe COPD, there is a relatively high percentage of PH which causes a decrease in exercise capacity and oxygen pulse without significantly altered ventilation as measured by CPET. Lower than expected exercise performance without a change in pulmonary function may indicate a need for evaluation for possible PH.

Distinguishing pulmonary hypertension in interstitial lung disease by ventilation and perfusion defects measured by cardiopulmonary exercise testing.

BACKGROUND: Pulmonary hypertension (PH) is common in interstitial lung disease (ILD). Since cardiopulmonary exercise testing (CPET) is useful in understanding the pathophysiology of respiratory disorders and can distinguish between ventilation and perfusion (V/Q) defects, it may have a role in the detection of PH in ILD. We evaluated whether CPET can detect PH through analysis of V/Q defects in ILD. OBJECTIVES: We aimed to use CPET to determine if there are changes in the ventilation and the activity pattern of mixed-expired carbon dioxide pressure (PECO2) and end-tidal carbon dioxide pressure (PetCO2) in ILD patients with and without PH. METHODS: A retrospective chart review was done of all patients who received lung transplants at the Columbia University Medical Center between 2000 and 2011 with the diagnosis of ILD. CPETs were performed during the 2 years prior to transplantation; right heart catheterizations and pulmonary function tests were performed within 4 months of CPET. RESULTS: The ILD patients with PH demonstrated significantly lower PetCO2 and PECO2 during certain levels of exercise with a distinctive activity pattern for PECO2/PetCO2. CONCLUSIONS: Evaluation of V/Q defects through the PECO2 and PetCO2 patterns on CPET in ILD patients can distinguish between patients with and without PH.

Exercise capacity and ventilatory response during exercise in COPD patients with and without ß blockade.

BACKGROUND: Although ß blockade (BB) in patients with chronic obstructive pulmonary disease (COPD) does not show signs of worsening pulmonary function or respiratory symptoms, the effects on cardiopulmonary exercise testing (CPET) remain unclear. The aim of this study was to determine whether BB affects exercise capacity, gas exchange, and hemodynamic responses in patients with COPD. METHODS: Twenty-four COPD subjects on BB were matched to 24 COPD subjects without BB according to age, gender, body mass index, and severity of COPD. All subjects underwent resting pulmonary function and symptom-limited CPET. RESULTS: Comparing COPD patients with and without BB revealed that percent peak oxygen consumption and VE/VCO2 nadir were not significantly different (45 ± 16 vs. 51 ± 23 %, p = 0.30, and 35.1 ± 8.5 vs. 36.2 ± 11.6 %, p = 0.69). Systolic blood pressure and heart rate at peak exercise were significantly decreased in COPD patients with BB (168 ± 16 vs. 185 ± 20 mmHg, and 109 ± 16 vs. 122 ± 14 bpm, respectively, p < 0.05). CONCLUSION: Exercise capacity and gas exchange remain unaffected in patients with COPD in the presence of BB, although heart rate and blood pressure are lower. These findings imply that BB does not adversely affect functional capacity in patients with COPD.

Selective serotonin reuptake inhibitors and lung function in the multi-ethnic study of atherosclerosis lung study.

OBJECTIVE: Depression in patients with Chronic Obstructive Pulmonary Disease (COPD) has been shown to be chronic and potentially increase the burden of symptoms. Selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory and serotonergic effects that may improve lung function. We hypothesized that participants taking SSRIs have better lung function than those not taking SSRIs. The dataset was the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. Use of SSRIs was assessed by medication inventory; spirometry was conducted following standard guidelines; dyspnea ratings were self-reported. RESULTS: Contrary to our hypothesis, FEV1 was lower, and odds of dyspnea were higher among participants taking SSRIs as compared with those not taking an antidepressant; these differences persisted even with control for potential confounders including depressive symptoms. We found no evidence of a beneficial association between SSRI use and lung function or dyspnea in a large US-based cohort.

Symptoms of anxiety and depression and use of anxiolytic-hypnotics and antidepressants in current and former smokers with and without COPD - A cross sectional analysis of the COPDGene cohort.

OBJECTIVES: To compare the frequency of anxiety/depressive symptoms and use of anxiolytic-hypnotics/antidepressants in smokers with and without COPD and to identify characteristics associated with having unmedicated symptoms. METHODS: Cross-sectional analysis of ambulatory, current/former smokers ≥10 pack years enrolled in the COPDGene study. We measured anxiety/depressive symptoms using the Hospital Anxiety and Depression Scale (subscales ≥8), recorded anxiolytic-hypnotic/antidepressant use, and defined unmedicated symptoms as elevated anxiety/depressive symptoms and not on medications. Regression analysis identified characteristics associated with having unmedicated symptoms. KEY RESULTS: Of 5331 current/former smokers (45% with and 55% without COPD), 1332 (25.0%) had anxiety/depressive symptoms. Anxiety symptoms were similar in frequency in smokers with and without COPD (19.7% overall), while depressive symptoms were most frequent in severe-very severe COPD at 20.7% (13.1% overall). In the entire cohort, 1135 (21.2%) were on medications. Anxiolytic-hypnotic use was highest in severe-very severe COPD (range 7.6%-12.0%), while antidepressant use showed no significant variation in smokers with and without COPD (range 14.7%-17.1%). Overall, 881 (66% of those with symptoms) had unmedicated symptoms, which was associated with African American race (adjusted OR 2.95, 95% CI 2.25-3.87), male gender (adjusted OR 1.93, 95% CI 1.57-2.36), no health insurance (adjusted OR 2.38, 95% CI 1.30-4.35), severe-very severe COPD (adjusted OR 1.48, 95% CI 1.04-2.11), and higher respiratory symptoms/exacerbation history (adjusted OR 2.21, 95% CI 1.62-3.02). CONCLUSIONS: Significant unmet mental health care needs exist in current and former smokers with and without COPD. One in five have unmedicated symptoms, identified by key demographic and clinical characteristics. PRIMARY FUNDING SOURCE: National Institutes of Health and The COPD Foundation.

The Impact of Hypomania on Aerobic Capacity and Cardiopulmonary Functioning-A Case Report.

Background: Hypomanic episodes are characterized by increased goal-directed behavior and psychomotor agitation. While the affective, cognitive, and behavioral manifestations of such episodes are well-documented, their physiological influence on aerobic capacity and cardiopulmonary functioning are unknown. Methods: We describe a case report of an individual with schizophrenia who experienced a hypomanic episode while serving as a control participant (wait list) in a single-blind, randomized clinical trial examining the impact of aerobic exercise (AE) on neurocognition in people schizophrenia. As part of the trial, participants completed two scheduled clinical assessments and cardiopulmonary exercise tests (VO2max) at baseline and 12 weeks later at end of study. All participants received standard psychiatric care during the trial. Following a baseline assessment in which he displayed no evidence of mood lability, the subject returned on Week-12 for his scheduled follow-up assessment displaying symptoms of hypomania. He was able to complete the follow-up assessment, as well as third assessment 2 weeks later (Week-14) when his hypomanic symptoms ebbed. Results: While not engaging in AE, the subject's aerobic capacity, as indexed by VO2max, increased by 33% from baseline to Week-12. In comparison, participants engaged in the aerobic exercise training increased their aerobic capacity on average by 18%. In contrast, participants in the control group displayed a small decline (-0.5%) in their VO2max scores. Moreover, the subject's aerobic capacity increased even further by Week-14 (49% increase from baseline), despite the ebbing of his hypomania symptoms at that time. These changes were accompanied by increases in markers of aerobic fitness including peak heart rate, respiratory exchange rate, peak minute ventilation, watts, and peak systolic blood pressure. Resting systolic and diastolic blood pressure, and peak diastolic blood pressure remained unchanged. Conclusions: Our findings suggest that hypomania produce substantial increase in aerobic capacity and that such elevations may remain sustained following the ebbing of hypomanic symptoms. Such elevations may be attributed to increased mobility and goal-directed behavior associated with hypomania, as individuals in hypomanic states may ambulate more frequently, for longer duration, and/or at higher intensity. Our results provide a first and unique view into the impact of hypomania on aerobic capacity and cardiopulmonary functioning.

Cardiopulmonary exercise factors predict survival in patients with advanced interstitial lung disease referred for lung transplantation.

BACKGROUND: The purpose of this work was to determine if parameters assessed during Cardiopulmonary Exercise Testing (CPET) while using supplemental oxygen can independently predict one-year transplant-free survival in patients with Interstitial Lung Disease (ILD) referred for lung transplant evaluation. METHODS: We performed a chart review of patients with ILD who completed CPET with 30% FiO2 and gathered spirometry, pulmonary hemodynamic, six-minute walk, and CPET data. The primary end-point was death or lung transplantation within one-year of CPET. RESULTS: The final data set included 192 patients. 79 patients died/underwent transplant, 113 survived transplant-free. Multivariable Cox regression revealed peak workload % predicted, nadir CPET SpO2, and FVC% predicted as independent predictors of one-year transplant-free survival. Of the independent predictors of survival, receiver operating characteristics analysis revealed peak workload %predicted cutoff of 35% to be highly discriminatory, more so than nadir CPET SpO2 or FVC % predicted in identifying patients at risk for one-year mortality or transplant (peak workload % predicted < 35% HR = 4.71, 95% CI = 2.64-8.38 and area under the curve (AUC) = 0.740, nadir CPET SpO2 < 86% HR = 2.27, 95%CI = 1.41-3.68, AUC = 0.645, FVC %predicted <45% HR = 1.82, 95% CI = 1.15-2.87, AUC = 0.624). CONCLUSION: Peak workload % predicted, nadir CPET SpO2, and FVC% predicted in ILD patients referred for lung transplant evaluation are independently predictive of one-year mortality or need for transplant.

Frailty and maximal exercise capacity in adult lung transplant candidates.

BACKGROUND: Frail lung transplant candidates are more likely to be delisted or die without receiving a transplant. Further knowledge of what frailty represents in this population will assist in developing interventions to prevent frailty from developing. We set out to determine whether frail lung transplant candidates have reduced exercise capacity independent of disease severity and diagnosis. METHODS: Sixty-eight adult lung transplant candidates underwent cardiopulmonary exercise testing (CPET) and a frailty assessment (Fried's Frailty Phenotype (FFP)). Primary outcomes were peak workload and peak aerobic capacity (V˙O2). We used linear regression to adjust for age, gender, diagnosis, and lung allocation score (LAS). RESULTS: The mean ± SD age was 57 ± 11 years, 51% were women, 57% had interstitial lung disease, 32% had chronic obstructive pulmonary disease, 11% had cystic fibrosis, and the mean LAS was 40.2 (range 19.2-94.5). In adjusted models, peak workload decreased by 10 W (95% CI 4.7 to 14.6) and peak V˙O2 decreased by 1.8 mL/kg/min (95% CI 0.6 to 2.9) per 1 unit increment in FFP score. After adjustment, exercise tolerance was 38 W lower (95% CI 18.4 to 58.1) and peak V˙O2 was 8.5 mL/kg/min lower (95% CI 3.3 to 13.7) among frail participants compared to non-frail participants. Frailty accounted for 16% of the variance (R2) of watts and 19% of the variance of V˙O2 in adjusted models. CONCLUSION: Frailty contributes to reduced exercise capacity among lung transplant candidates independent of disease severity.

Lung function, percent emphysema, and QT duration: The Multi-Ethnic Study of Atherosclerosis (MESA) lung study.

BACKGROUND: The QT interval on electrocardiogram (ECG) reflects ventricular repolarization; a prolonged QT interval is associated with increased mortality risk. Prior studies suggest an association between chronic obstructive pulmonary disease (COPD) and prolonged QT interval. However, these studies were small and often enrolled hospital-based samples. We tested the hypotheses that lower lung function and increased percent emphysema on computed tomography (CT) are associated with a prolonged QT interval in a general population sample and additionally in those with COPD. METHODS: As part of the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, we assessed spirometry, full-lung CT scans, and ECGs in participants aged 45-84 years. The QT on ECGs was corrected for heart rate (QTc) using the Framingham formula. QTc values = 460 msec in women and ≥450 msec in men were considered abnormal (prolonged QTC). Multivariate regression models were used to examine the cross-sectional association between pulmonary measures and QTC. RESULTS: The mean age of the sample of 2585 participants was 69 years, and 47% were men. There was an inverse association between FEV1%, FVC%, FEV1/FVC%, emphysema, QTc duration and prolonged QTc. Gender was a significant interaction term, even among never smokers. Having severe COPD was also associated with QTc prolongation. CONCLUSIONS: Our analysis revealed a significant association between lower lung function and longer QTc in men but not in women in a population-based sample. Our findings suggest the possibility of gender differences in the risk of QTc-associated arrhythmias in a population-based sample.

Primary graft dysfunction: Long-term physical function outcomes among lung transplant recipients.

BACKGROUND: Adults with primary graft dysfunction (PGD) after lung transplantation are at increased risk for pulmonary and functional impairment. No prior studies have described the long-term (within 1.5 years of transplant) cardiopulmonary exercise testing (CPET) results in adults with grade 3 PGD. The objective of this study was to compare the functional outcomes of lung transplant patients with and without grade 3 PGD via CPET and six-minute talk tests (6MWD). METHODS: 243 adults underwent lung transplantation between 2003 and 2010, 128 (53%) of whom underwent CPET and 6MWD within 12-18 months of transplantation. The primary measure of exposure was grade 3 PGD at 72 h, however grade 3 PGD within 72 h was also assessed. In addition, the impact of potential confounding variables was explored. RESULTS: Approximately one-third (32%) of the 243 patients experienced grade 3 PGD within 72 h; among these, 15 (6%) had grade 3 PGD at the 72 h time point. There were no differences in CPET or 6MWD between those with and without grade 3 PGD at 72 h despite a longer length of hospital stay and lower pulmonary function. Similar results were seen for patients with and without grade 3 PGD within 72 h, with the exception of a lower heart rate on CPET. CONCLUSIONS: Participants with grade 3 PGD are able to achieve functional outcomes comparable to those without PGD.

Use of Active-Play Video Games to Enhance Aerobic Fitness in Schizophrenia: Feasibility, Safety, and Adherence.

OBJECTIVE: Active-play video games have been used to enhance aerobic fitness in various clinical populations, but their use among individuals with schizophrenia has been limited. METHODS: Feasibility, acceptability, safety, and adherence data were obtained for use of aerobic exercise (AE) equipment by 16 individuals with schizophrenia during a 12-week AE program consisting of three one-hour exercise sessions per week. Equipment included exercise video games for Xbox 360 with Kinect motion sensing devices and traditional exercise equipment. RESULTS: Most participants (81%) completed the training, attending an average of 79% of sessions. The proportion of time spent playing Xbox (39%) exceeded time spent on any other type of equipment. When using Xbox, participants played 2.24±1.59 games per session and reported high acceptability and enjoyment ratings, with no adverse events. CONCLUSIONS: Measures of feasibility, acceptability, adherence, and safety support the integration of active-play video games into AE training for people with schizophrenia.

A Retrospective Review of Unintended Effects After Single-Event Multi-Level Chemoneurolysis With Botulinum Toxin-A and Phenol in Children With Cerebral Palsy.

BACKGROUND: Single-event multi-level chemoneurolysis (SEMLC) is a single-session procedure that treats various limbs of patients with spasticity at multiple levels with chemoneurolytic agents. Phenol is used in combination with botulinum toxin A (BTX-A) to enable spastic muscles to be treated without overdosing with BTX-A. OBJECTIVE: To review unintended effects (UEs) of SEMLC for children with spastic cerebral palsy (CP). DESIGN: Retrospective chart review. SETTING: Pediatric rehabilitation outpatient clinic at an academic medical center. PARTICIPANTS: The study included 98 children with CP who underwent SEMLC on at least one occasion. INTERVENTIONS: SEMLC. MAIN OUTCOME MEASURES: UEs, the goal achievement for each SEMLC session, and the Gross Motor Function Classification System (GMFCS-ER). RESULTS: A total of 98 subjects and 146 SEMLC procedures were reviewed. Patients had a mean age of 7.56 years (standard deviation, 4.28); 57% were male; and 14 had hemiplegia, 22 had diplegia, 8 had triplegia, and 54 had quadriplegia. Most SEMLCs (72%) were performed with a combination of BTX-A and 5% phenol in a session. UEs were reported for 31/146 (21%) of SEMLC sessions, with 16 of 31 UEs being temporary weakness. The overall incidence of UEs of the group that received combined agent treatment was not different from the group that received BTX-A only (P = .267). Transient pain occurred in 7 of 105 patients who were treated with the combined agents BTX-A and phenol. Dysesthesia did not develop in any of the patients. The type of CP, GMFCS level, number of muscles injected, and doses of medications were not correlated with the incidence of UEs. CONCLUSIONS: SEMLC using combined BTX-A and phenol is a safe procedure for children with spastic CP. It could be a treatment option for patients with diffuse spasticity, because combining agents allowed more muscles to be treated without enduring or serious UEs. Patient and family education is essential to prepare them for the occurrence of common UEs, such as temporary weakness and pain.

Effect of lung transplantation on heart rate response to exercise.

OBJECTIVES: To evaluate if patients have a change in percent of predicted heart rate reserve used at peak exercise (%HRR) after lung transplantation, even at matching workloads. BACKGROUND: Lung disease of obstructive, restrictive, and mixed types may be associated with an autonomic imbalance. Lung transplantation may improve the effects of pulmonary disease on cardiac function. However, the effect of lung transplantation on heart rate responses during exercise has not been investigated in detail. METHODS: Retrospective review of patients who underwent lung transplantation. Pre and post transplant cardiopulmonary exercise tests were reviewed. RESULTS: The %HRR significantly improved by a median of 37% (p < 0.001) following lung transplantation. When matching workloads were analyzed, the %HRR also decreased from a median of 36% to 24% (p < 0.001). CONCLUSIONS: Corresponding to an increase in peak exercise capacity, percentage of heart rate reserve used improves significantly after lung transplantation, even at matching workloads, indicating a likely improvement in autonomic modulation.

Ventilatory efficiency before and after lung volume reduction surgery.

BACKGROUND: Lung volume reduction surgery (LVRS) has been shown to improve the clearance of carbon dioxide and minute ventilation (V̇E) in select patients with COPD. One variable often assessed in COPD is ventilatory efficiency (V̇E/V̇CO2 ). METHODS: We compared 55 LVRS subjects with 25 controls from the National Emphysema Treatment Trial. V̇E/V̇CO2 was calculated from cardiopulmonary exercise testing at baseline and 6-months. We sought to assess V̇E/V̇CO2 changes with LVRS compared with controls who only received standard medical care. RESULTS: At 6 months, the LVRS group significantly increased peak V̇O2 , work load, V̇E, V̇CO2 , and tidal volume while lowering peak and lowest V̇E/V̇CO2 (improved ventilatory efficiency) and end-tidal carbon dioxide pressure. The control group did not display these changes. The changes were greatest in the LVRS subjects who improved their exercise capacity after surgery (> 10 W). CONCLUSIONS: The changes were greatest in the LVRS subjects who showed the most functional improvement, indicating an association of improved ventilation with improved functional outcome.

Quantification of Improvements in Static and Dynamic Ventilatory Measures Following Lung Volume Reduction Surgery for Severe COPD.

Rationale: This study quantitatively measured the effects of lung volume reduction surgery (LVRS) on spirometry, static and dynamic lung and chest wall volume subdivision mechanics, and cardiopulmonary exercise measures. Methods: Patients with severe COPD (mean FEV1 = 23 ± 6% predicted) undergoing LVRS evaluation were recruited. Spirometry, plethysmography and exercise capacity were obtained within 6 months pre-LVRS and again within 12 months post- LVRS. Ventilatory mechanics were quantified using stationary optoelectronic plethysmography (OEP) during spontaneous tidal breathing and during maximum voluntary ventilation (MVV). Statistical significance was set at P< 0.05. Results:Ten consecutive patients met criteria for LVRS (5 females, 5 males, age: 62±6yrs). Post -LVRS (mean follow up 7 months ± 2 months), the group showed significant improvements in dyspnea scores (pre 4±1 versus post 2 ± 2), peak exercise workload (pre 37± 21 watts versus post 50 ± 27watts ), heart rate (pre 109±19 beats per minutes [bpm] versus post 118±19 bpm), duty cycle (pre 30.8 ± 3.8% versus post 38.0 ± 5.7%), and spirometric measurements (forced expiratory volume in 1 second [FEV1] pre 23 ± 6% versus post 32 ± 13%, total lung capacity / residual lung volume pre 50 ± 8 versus 50 ± 11) . Six to 12 month changes in OEP measurements were observed in an increased percent contribution of the abdomen compartment during tidal breathing (41.2±6.2% versus 44.3±8.9%, P=0.03) and in percent contribution of the pulmonary ribcage compartment during MVV (34.5±10.3 versus 44.9±11.1%, P=0.02). Significant improvements in dynamic hyperinflation during MVV occurred, demonstrated by decreases rather than increases in end expiratory volume (EEV) in the pulmonary ribcage (pre 207.0 ± 288.2 ml versus post -85.0 ± 255.9 ml) and abdominal ribcage compartments (pre 229.1 ± 182.4 ml versus post -17.0 ± 136.2 ml) during the maneuver. Conclusions: Post-LVRS, patients with severe COPD demonstrate significant favorable changes in ventilatory mechanics, during tidal and maximal voluntary breathing. Future work is necessary to determine if these findings are clinically relevant, and extend to other environments such as exercise.

Left and Right Ventricular Functional Dynamics Determined by Echocardiograms Before and After Lung Transplantation.

Impaired cardiac function is considered a contraindication for lung transplantation (LT). Because right ventricular (RV) function is expected to improve after LT, poor left ventricular (LV) function is often the determinant for LT eligibility. However, the changes in cardiac function before and after LT have not yet been elucidated. Therefore, we reviewed echocardiograms obtained from 67 recipients before and after LT. In a subset of 49 patients, both RV and LV longitudinal strains based on 2-dimensional speckle tracking echocardiography were analyzed. The cardiopulmonary exercise tests were also reviewed. All patients showed significant improvements in their exercise capacity after LT. RV echo parameters improved in all patients after LT (RV fractional area change: 36.7 ± 5.6% to 41.5 ± 2.7%, RV strain: -15.5 ± 2.9% to -18.0 ± 2.1%, RV E/E': 8.4 ± 1.8 to 7.7 ± 1.8; all p <0.05). Overall, the left ventricular ejection fraction (LVEF) did not change (58.7 ± 6.0% to 57.5 ± 9.7%, p = 0.385); however, 20 patients (30%) showed >10% decrease in LVEF after LT (61.5 ± 6.1% to 47.3 ± 4.2%, p <0.001) and an increase in LV E/E' (11.8 ± 1.8 to 12.9 ± 2.2, p = 0.049). Multivariate logistic regression analysis revealed that pre-LT LV E/E' was associated with decrease in LVEF after LT (odds ratio 1.381, 95% confidence interval 1.010 to 1.947, p = 0.043). Furthermore, patients with strain data showed that lower pre-LT LV strain was independently associated with LVEF decrease after LT (odds ratio 1.293, 95% confidence interval 1.088 to 1.614, p = 0.002). Although RV function improves after LT, LV systolic and diastolic functions deteriorate in a sizable proportion of patients. Impaired LV diastolic function before transplant appears to increase the risk of LVEF deterioration after LT.