Anxiety is associated with diminished exercise performance and quality of life in severe emphysema: a cross-sectional study.

BACKGROUND: Anxiety in patients with chronic obstructive pulmonary disease (COPD) is associated with self-reported disability. The purpose of this study is to determine whether there is an association between anxiety and functional measures, quality of life and dyspnea. METHODS: Data from 1828 patients with moderate to severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), collected prior to rehabilitation and randomization, were used in linear regression models to test the association between anxiety symptoms, measured by the Spielberger State Trait Anxiety Inventory (STAI) and: (a) six-minute walk distance test (6 MWD), (b) cycle ergometry peak workload, (c) St. Georges Respiratory Questionnaire (SRGQ), and (d) UCSD Shortness of Breath Questionnaire (SOBQ), after controlling for potential confounders including age, gender, FEV1 (% predicted), DLCO (% predicted), and the Beck Depression Inventory (BDI). RESULTS: Anxiety was significantly associated with worse functional capacity [6 MWD (B = -0.944, p < .001), ergometry peak workload (B = -.087, p = .04)], quality of life (B = .172, p < .001) and shortness of breath (B = .180, p < .001). Regression coefficients show that a 10 point increase in anxiety score is associated with a mean decrease in 6 MWD of 9 meters, a 1 Watt decrease in peak exercise workload, and an increase of almost 2 points on both the SGRQ and SOBQ. CONCLUSION: In clinically stable patients with moderate to severe emphysema, anxiety is associated with worse exercise performance, quality of life and shortness of breath, after accounting for the influence of demographic and physiologic factors known to affect these outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000606.

Integrating health status and survival data: the palliative effect of lung volume reduction surgery.

RATIONALE: In studies that address health-related quality of life (QoL) and survival, subjects who die are usually censored from QoL assessments. This practice tends to inflate the apparent benefits of interventions with a high risk of mortality. Assessing a composite QoL-death outcome is a potential solution to this problem. OBJECTIVES: To determine the effect of lung volume reduction surgery (LVRS) on a composite endpoint consisting of the occurrence of death or a clinically meaningful decline in QoL defined as an increase of at least eight points in the St. George's Respiratory Questionnaire total score from the National Emphysema Treatment Trial. METHODS: In patients with chronic obstructive pulmonary disease and emphysema randomized to receive medical treatment (n = 610) or LVRS (n = 608), we analyzed the survival to the composite endpoint, the hazard functions and constructed prediction models of the slope of QoL decline. MEASUREMENTS AND MAIN RESULTS: The time to the composite endpoint was longer in the LVRS group (2 years) than the medical treatment group (1 year) (P < 0.0001). It was even longer in the subsets of patients undergoing LVRS without a high risk for perioperative death and with upper-lobe-predominant emphysema. The hazard for the composite event significantly favored the LVRS group, although it was most significant in patients with predominantly upper-lobe emphysema. The beneficial impact of LVRS on QoL decline was most significant during the 2 years after LVRS. CONCLUSIONS: LVRS has a significant effect on the composite QoL-survival endpoint tested, indicating its meaningful palliative role, particularly in patients with upper-lobe-predominant emphysema.

Changes in arterial oxygenation and self-reported oxygen use after lung volume reduction surgery.

RATIONALE: Lung volume reduction surgery (LVRS) is inconsistently reported to improve arterial oxygenation in patients with chronic obstructive pulmonary disease. OBJECTIVES: We studied the effects of surgery on oxygenation in a large cohort and identified predictors of postoperative oxygenation improvement. METHODS: We evaluated oxygenation in 1,078 subjects with chronic obstructive pulmonary disease enrolled in the National Emphysema Treatment Trial after LVRS compared with medical control subjects, including arterial blood gases, use of supplemental oxygen during treadmill walking, and self-reported use of oxygen during rest, exertion, and sleep. MEASUREMENTS AND MAIN RESULTS: Pa(O(2)) breathing room air was equal in medical and surgical subjects at baseline (64.8 vs. 65.0 mm Hg, P = not significant), but lower in medical subjects at 6 months (63.6 vs. 70.0 mm Hg, P < 0.001), 12 months (63.9 vs. 68.7 mm Hg, P < 0.001), and 24 months (62.4 vs. 68.0 mm Hg, P < 0.001). Fewer medical subjects required oxygen for treadmill walking at baseline compared with surgical subjects (46 vs. 53%, P = 0.02). However, more medical subjects required oxygen for this activity at 6 months (49 vs. 33%, P < 0.001), 12 months (50 vs. 36%, P < 0.001), and 24 months (52 vs. 42%, P = 0.02). Self-reported oxygen use was greater in medical than in surgical subjects at 6, 12, and 24 months. Multivariate modeling of preoperative characteristics showed baseline oxygenation status was the best predictor of postoperative oxygenation. CONCLUSIONS: LVRS increases Pa(O(2)), and decreases treadmill and self-reported use of oxygen for up to 24 months post-procedure. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Longitudinal change in the BODE index predicts mortality in severe emphysema.

RATIONALE: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. OBJECTIVES: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. METHODS: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. MEASUREMENTS AND MAIN RESULTS: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components. CONCLUSIONS: The mBODE demonstrates short- and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Continuous oxygen use in nonhypoxemic emphysema patients identifies a high-risk subset of patients: retrospective analysis of the National Emphysema Treatment Trial.

BACKGROUND: Continuous oxygen therapy is not recommended for emphysema patients who are not hypoxemic at rest, although it is often prescribed. Little is known regarding the clinical characteristics and survival of nonhypoxemic emphysema patients using continuous oxygen. Analysis of data from the National Emphysema Treatment Trial (NETT) offers insight into this population. METHODS: We analyzed demographic and clinical characteristics of 1,215 participants of NETT, stratifying by resting PaO(2) and reported oxygen use. Eight-year survival was evaluated in individuals randomized to medical therapy. RESULTS: At enrollment, 33.8% (n = 260) of participants nonhypoxemic at rest reported continuous oxygen use. When compared to nonhypoxemic individuals not using oxygen (n = 226), those using continuous oxygen had worse dyspnea, lower quality of life, more frequent exercise desaturation, and higher case-fatality rate. After adjusting for age, body mass index, and FEV(1) percentage of predicted, the presence of exercise desaturation accounted for the differential mortality seen between these groups. CONCLUSIONS: In the NETT, the use of continuous oxygen in resting nonhypoxemic emphysema patients was associated with worse disease severity and survival. The differential survival observed could nearly all be accounted for by the higher prevalence of exercise desaturation in those using continuous oxygen, suggesting that it is not a harmful effect of oxygen therapy contributing to mortality. It remains unclear whether continuous oxygen therapy improves survival in normoxic patients with exercise desaturation.

Sex, depression, and risk of hospitalization and mortality in chronic obstructive pulmonary disease.

BACKGROUND: We sought to determine whether depressive or anxiety symptoms are associated with chronic obstructive pulmonary disease (COPD) hospitalization or mortality. These data were collected as part of the National Emphysema Treatment Trial (NETT), a randomized controlled trial of lung volume reduction surgery vs continued medical treatment conducted at 17 clinics across the United States between January 29, 1998, and July 31, 2002. METHODS: Prospective cohort study among participants in the NETT with emphysema and severe airflow limitation who were randomized to medical therapy. Primary outcomes were 1- and 3-year mortality, as well as COPD or respiratory-related hospitalization or emergency department visit during the 1-year follow-up period. Of 610 patients randomized to medical therapy, complete data on hospitalization and mortality were available for 3 years of follow-up for 603 patients (98.9%). RESULTS: Depressive symptoms were assessed using the Beck Depression Inventory (BDI) questionnaire, and anxiety was assessed using the State-Trait Anxiety Inventory. Among 610 subjects, 40.8% had at least mild to moderate depressive symptoms. Patients in the highest quintile of BDI score (BDI score, >or=15) had an increased risk of respiratory hospitalization in unadjusted analysis compared with patients in the lowest quintile (BDI score, < 5) (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.30-3.93). After adjustment for disease severity, this relationship was no longer statistically significant. The adjusted risk of 3-year mortality was increased among those in the highest quintile of BDI score (OR, 2.74; 95% CI, 1.42-5.29) compared with those in the lowest quintile. Anxiety was not associated with hospitalization or mortality in this population. CONCLUSIONS: Depressive symptoms are common in patients with severe COPD and are treated in few subjects. Depressive symptoms are associated with increased risk for 3-year mortality but not 1-year mortality or hospitalization.

Primary pulmonary arterial hypertension: a look back.

For the first half of the twentieth century, the published reports on primary pulmonary hypertension (PPH) were confined to clinical pathological correlations. In the 1950s the physiological aspects began to be reported followed by epidemiologic studies triggered by an epidemic of PPH due to the ingestion of an appetite suppressant, aminorex fumarate. The epidemic prompted a series of meetings of the World Health Organization, which led, in turn, to the creation of the U.S. Registry of Primary Pulmonary Hypertension, standardization of nomenclature, and an etiologic classification of all types of pulmonary hypertension.

The effects of pulmonary rehabilitation in the national emphysema treatment trial.

STUDY OBJECTIVES: Pulmonary rehabilitation is an established treatment in patients with chronic lung disease but is not widely utilized. Most trials have been conducted in single centers. The National Emphysema Treatment Trial (NETT) provided an opportunity to evaluate pulmonary rehabilitation in a large cohort of patients who were treated in centers throughout the United States. DESIGN: Prospective observational study of cohort prior to randomization in a multicenter clinical trial. SETTING: University-based clinical centers and community-based satellite pulmonary rehabilitation programs. PATIENTS AND INTERVENTION: A total of 1,218 patients with severe emphysema underwent pulmonary rehabilitation before and after randomization to lung volume reduction surgery (LVRS) or continued medical management. Rehabilitation was conducted at 17 NETT centers supplemented by 539 satellite centers. MEASUREMENTS AND RESULTS: Lung function, exercise tolerance, dyspnea, and quality of life were evaluated at regular intervals. Significant (p < 0.001) improvements were observed consistently in exercise (cycle ergometry, 3.1 W; 6-min walk test distance, 76 feet), dyspnea (University of California, San Diego Shortness of Breath Questionnaire score, -3.2; Borg breathlessness score: breathing cycle, -0.8; 6-min walk, -0.5) and quality of life (St. George Respiratory Questionnaire score, -3.5; Quality of Well-Being Scale score, +0.035; Medical Outcomes Study 36-item short form score: physical health summary, +1.3; mental health summary, + 2.0). Patients who had not undergone prior rehabilitation improved more than those who had. In multivariate models, only prior rehabilitation status predicted changes after rehabilitation. In 20% of patients, exercise level changed sufficiently after rehabilitation to alter the NETT subgroup predictive of outcome. Overall, changes after rehabilitation did not predict differential mortality or improvement in exercise (primary outcomes) by treatment group. CONCLUSIONS: The NETT experience demonstrates the effectiveness of pulmonary rehabilitation in patients with severe emphysema who were treated in a national cross-section of programs. Pulmonary rehabilitation plays an important role in preparing and selecting patients for surgical interventions such as LVRS.

Effect of lung volume reduction surgery on resting pulmonary hemodynamics in severe emphysema.

RATIONALE: To determine the effect of medical treatment versus lung volume reduction surgery (LVRS) on pulmonary hemodynamics. METHODS: Three clinical centers of the National Emphysema Treatment Trial (NETT) screened patients for additional inclusion into a cardiovascular (CV) substudy. Demographics were determined, and lung function testing, six-minute-walk distance, and maximum cardiopulmonary exercise testing were done at baseline and 6 months after medical therapy or LVRS. CV substudy patients underwent right heart catheterization at rest prerandomization (baseline) and 6 months after treatment. MEASUREMENTS AND MAIN RESULTS: A total of 110 of the 163 patients evaluated for the CV substudy were randomized in NETT (53 were ineligible), 54 to medical treatment and 56 to LVRS. Fifty-five of these patients had both baseline and repeat right heart catheterization 6 months postrandomization. Baseline demographics and lung function data revealed CV substudy patients to be similar to the remaining 1,163 randomized NETT patients in terms of age, sex, FEV(1), residual volume, diffusion capacity of carbon monoxide, Pa(O(2)), Pa(CO(2)), and six-minute-walk distance. CV substudy patients had moderate pulmonary hypertension at rest (Ppa, 24.8 +/- 4.9 mm Hg); baseline hemodynamic measurements were similar across groups. Changes from baseline pressures to 6 months post-treatment were similar across treatment groups, except for a smaller change in pulmonary capillary wedge pressure at end-expiration post-LVRS compared with medical treatment (-1.8 vs. 3.5 mm Hg, p = 0.04). CONCLUSIONS: In comparison to medical therapy, LVRS was not associated with an increase in pulmonary artery pressures.

Sex differences in severe pulmonary emphysema.

RATIONALE: Limited data on sex differences in advanced COPD are available. OBJECTIVES: To compare male and female emphysema patients with severe disease. METHODS: One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. MEASUREMENTS AND MAIN RESULTS: Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower body mass index (BMI), shorter smoking history, less severe airflow obstruction, lower Dl(co) and arterial Po(2), higher arterial Pco(2), shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV(1)% predicted, age, number of pack-years, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. CONCLUSIONS: In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.

Long-term follow-up of patients receiving lung-volume-reduction surgery versus medical therapy for severe emphysema by the National Emphysema Treatment Trial Research Group.

BACKGROUND: The National Emphysema Treatment Trial defined subgroups of patients with severe emphysema in whom lung-volume-reduction surgery (LVRS) improved survival and function at 2 years. Two additional years of follow-up provide valuable information regarding durability. METHODS: A total of 1218 patients with severe emphysema were randomized to receive LVRS or medical treatment. We present updated analyses (4.3 versus 2.4 years median follow-up), including 40% more patients with functional measures 2 years after randomization. RESULTS: The intention-to-treat analysis of 1218 randomized patients demonstrates an overall survival advantage for LVRS, with a 5-year risk ratio (RR) for death of 0.86 (p = 0.02). Improvement was more likely in the LVRS than in the medical group for maximal exercise through 3 years and for health-related quality of life (St. George's Respiratory Questionnaire [SGRQ]) through 4 years. Updated comparisons of survival and functional improvement were consistent with initial results for four clinical subgroups of non-high-risk patients defined by upper-lobe predominance and exercise capacity. After LVRS, the upper-lobe patients with low exercise capacity demonstrated improved survival (5-year RR, 0.67; p = 0.003), exercise throughout 3 years (p < 0.001), and symptoms (SGRQ) through 5 years (p < 0.001 years 1 to 3, p = 0.01 year 5). Upper-lobe-predominant and high-exercise-capacity LVRS patients obtained no survival advantage but were likely to improve exercise capacity (p < 0.01 years 1 to 3) and SGRQ (p < 0.01 years 1 to 4). CONCLUSIONS: Effects of LVRS are durable, and it can be recommended for upper-lobe-predominant emphysema patients with low exercise capacity and should be considered for palliation in patients with upper-lobe emphysema and high exercise capacity.