Computed tomographic-based quantification of emphysema and correlation to pulmonary function and mechanics.

Computed tomographic based indices of emphysematous lung destruction may highlight differences in disease pathogenesis and further enable the classification of subjects with Chronic Obstructive Pulmonary Disease. While there are multiple techniques that can be utilized for such radiographic analysis, there is very little published information comparing the performance of these methods in a clinical case series. Our objective was to examine several quantitative and semi-quantitative methods for the assessment of the burden of emphysema apparent on computed tomographic scans and compare their ability to predict lung mechanics and function. Automated densitometric analysis was performed on 1094 computed tomographic scans collected upon enrollment into the National Emphysema Treatment Trial. Trained radiologists performed an additional visual grading of emphysema on high resolution CT scans. Full pulmonary function test results were available for correlation, with a subset of subjects having additional measurements of lung static recoil. There was a wide range of emphysematous lung destruction apparent on the CT scans and univariate correlations to measures of lung function were of modest strength. No single method of CT scan analysis clearly outperformed the rest of the group. Quantification of the burden of emphysematous lung destruction apparent on CT scan is a weak predictor of lung function and mechanics in severe COPD with no uniformly superior method found to perform this analysis. The CT based quantification of emphysema may augment pulmonary function testing in the characterization of COPD by providing complementary phenotypic information.

The effect of lung volume reduction surgery on chronic obstructive pulmonary disease exacerbations.

RATIONALE: Lung volume reduction surgery (LVRS) has been demonstrated to provide a functional and mortality benefit to a select group of subjects with chronic obstructive pulmonary disease (COPD). The effect of LVRS on COPD exacerbations has not been as extensively studied, and whether improvement in postoperative lung function alters the risk of disease exacerbations is not known. OBJECTIVES: To examine the effect, and mechanism of potential benefit, of LVRS on COPD exacerbations by comparing the medical and surgical cohorts of the National Emphysema Treatment Trial (NETT). METHODS: A COPD exacerbation was defined using Centers for Medicare and Medicaid Services data and International Classification of Diseases, Ninth Revision, discharge diagnosis. MEASUREMENTS AND MAIN RESULTS: There was no difference in exacerbation rate or time to first exacerbation between the medical and surgical cohorts during the year before study randomization (P = 0.58 and 0.85, respectively). Postrandomization, the surgical cohort experienced an approximate 30% reduction in exacerbation frequency (P = 0.0005). This effect was greatest in those subjects with the largest postoperative improvement in FEV(1) (P = 0.04) when controlling for changes in other spirometric measures of lung function, lung capacities, and room air arterial blood gas tensions. Finally, LVRS increased the time to first exacerbation in both those subjects with and those without a prior history of exacerbations (P = 0.0002 and P < 0.0001, respectively). CONCLUSIONS: LVRS reduces the frequency of COPD exacerbations and increases the time to first exacerbation. One explanation for this benefit may be the postoperative improvement in lung function.

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.

Predictors of mortality in patients with emphysema and severe airflow obstruction.

PURPOSE: Limited data exist describing risk factors for mortality in patients having predominantly emphysema. SUBJECTS AND METHODS: A total of 609 patients with severe emphysema (ages 40-83 yr; 64.2% male) randomized to the medical therapy arm of the National Emphysema Treatment Trial formed the study group. Cox proportional hazards regression analysis was used to investigate risk factors for all-cause mortality. Risk factors examined included demographics, body mass index, physiologic data, quality of life, dyspnea, oxygen utilization, hemoglobin, smoking history, quantitative emphysema markers on computed tomography, and a modification of a recently described multifunctional index (modified BODE). RESULTS: Overall, high mortality was seen in this cohort (12.7 deaths per 100 person-years; 292 total deaths). In multivariate analyses, increasing age (p=0.001), oxygen utilization (p=0.04), lower total lung capacity % predicted (p=0.05), higher residual volume % predicted (p=0.04), lower maximal cardiopulmonary exercise testing workload (p=0.002), greater proportion of emphysema in the lower lung zone versus the upper lung zone (p=0.005), and lower upper-to-lower-lung perfusion ratio (p=0.007), and modified BODE (p=0.02) were predictive of mortality. FEV1 was a significant predictor of mortality in univariate analysis (p=0.005), but not in multivariate analysis (p=0.21). CONCLUSION: Although patients with advanced emphysema experience significant mortality, subgroups based on age, oxygen utilization, physiologic measures, exercise capacity, and emphysema distribution identify those at increased risk of death.

Measurement of health-related quality of life in the national emphysema treatment trial.

PURPOSES: To evaluate two generic and two disease-specific measures of health-related quality of life (QOL) using prerandomization data from the National Emphysema Treatment Trial (NETT). METHOD: The analyses used data collected from the 1,218 subjects who were randomized in the NETT. Patients completed evaluations before and after completion of the prerandomization phase of the NETT pulmonary rehabilitation program. Using data obtained prior to participation in the rehabilitation program, QOL measures were evaluated against physiologic and functional criteria using correlational analysis. The physiologic criteria included estimates of emphysema severity based on FEV(1) and measures of Pao(2) obtained with the subject at rest and breathing room air. Functional measures included the 6-min walk distance (6MWD), maximum work, and hospitalizations in the prior 3 months. RESULTS: Correlation coefficients between QOL measures ranged from -0.31 to 0.70. In comparison to normative samples, scores on general QOL measures were low, suggesting that the NETT participants were quite ill. All QOL measures were modestly but significantly correlated with FEV(1), maximum work, and 6MWD. Patients who had stayed overnight in a hospital in the prior 3 months reported lower QOL on average than those who had not been hospitalized. There were significant improvements for all QOL measures following the rehabilitation program, and improvements in QOL were correlated with improvements in 6MWD. COMMENT: The disease-specific and general QOL measures used in the NETT were correlated. Analyses suggested that these measures improved significantly following the rehabilitation phase of the NETT.

Safety and efficacy of median sternotomy versus video-assisted thoracic surgery for lung volume reduction surgery.

BACKGROUND: The National Emphysema Treatment Trial, a randomized trial comparing lung volume reduction surgery with medical therapy for severe emphysema, included randomized and nonrandomized comparisons of the median sternotomy and video-assisted thoracoscopic approaches for lung volume reduction surgery. METHODS: Lung volume reduction surgery was performed by median sternotomy only at 8 centers and video-assisted thoracoscopy only at 3 centers; 6 centers randomized the approach to lung volume reduction surgery. Mortality, morbidity, functional status, and costs were assessed. RESULTS: In the nonrandomized comparison, 359 patients received lung volume reduction surgery by median sternotomy, and 152 patients received lung volume reduction surgery by video-assisted thoracoscopy. The 90-day mortality was 5.9% for median sternotomy and 4.6% for video-assisted thoracoscopy (P =.67). Overall mortality was 0.08 deaths per person-year for median sternotomy and 0.10 deaths per person-year for video-assisted thoracoscopy (video-assisted thoracoscopy-median sternotomy risk ratio, 1.18; P =.42). Complication rates were low and not statistically different for the 2 approaches. The median hospital length of stay was longer for median sternotomy than for video-assisted thoracoscopy (10 vs 9 days; P =.01). By 30 days after surgery, 70.5% of median sternotomy patients and 80.9% of video-assisted thoracoscopy patients were living independently (P =.02). Functional outcomes were similar for median sternotomy and video-assisted thoracoscopy at 12 and 24 months. Costs for the operation and the associated hospital stay and costs in the 6 months after surgery were both less for video-assisted thoracoscopy than for median sternotomy (P <.01 in both cases). Similar results were noted for the randomized comparison. CONCLUSIONS: Morbidity and mortality were comparable after lung volume reduction surgery by video-assisted thoracoscopy or median sternotomy, as were functional results. The video-assisted thoracoscopic approach to lung volume reduction surgery allowed earlier recovery at a lower cost than median sternotomy.

Which strategies facilitate improvement in quality of care for elderly hospitalized pneumonia patients?

BACKGROUND: A retrospective cohort study was conducted to elucidate which hospital-based quality improvement (QI) strategies are most effective in facilitating improvement in care for patients with community-acquired pneumonia. METHODS: In 1999 telephone interviews were conducted with 29 acute care hospitals in Connecticut regarding their use of QI strategies for 1,234 patients at baseline and 1,081 patients at follow-up. RESULTS: Hospital-based QI strategies were grouped into two domains of implementation approach (epidemiologic and social influence). Hospitals scoring a 4 in either the epidemiologic or social influence approach (versus a score of < or = 3) experienced a greater-than-average increase in percentage of patients with blood culture collection within 24 hours of hospital presentation. Hospitals applying all four social influence QI strategies showed a greater-than-average increase in delivery of antibiotics within 8 hours of patients' hospital arrival when compared with all the other hospitals combined. DISCUSSION: The finding that an increased proportion of patients receiving antibiotics within 8 hours and blood cultures within 24 hours of hospital arrival when the greatest numbers of hospital-based QI strategies were implemented in suggestive of a possible "dose effect" of QI.

Superiority of 10% air-10% blood-saline mixture for measuring the velocity of tricuspid regurgitation in patients with severe emphysema.

BACKGROUND: Severe emphysema frequently is associated with elevated pulmonary artery systolic pressure. However, it is often difficult to obtain adequate tricuspid regurgitation (TR) signals for measurement of pulmonary artery systolic pressure in patients with severe emphysema. PURPOSE: This study was conducted to evaluate the usefulness of air-blood-saline mixture in measuring TR velocity in severe emphysema. METHODS: We studied 82 patients with severe emphysema (67.7 +/- 9.2 years, 57 males) who had no or mild TR on color Doppler. Contrast echocardiography studies were performed with agitated 10% air-90% saline and 10% air-10% blood-80% saline mixtures. Tracing quality and peak velocity were assessed on baseline continuous wave signals and contrast continuous wave signals with the 2 mixtures. RESULTS: With the injection of an air-saline mixture, the quality of TR tracing improved in 45 patients (P <.0001) and a higher peak TR velocity was obtained (2.46 +/- 0.37 m/s vs 2.95 +/- 0.40 m/s, P <.0001) compared with baseline echocardiography. Compared with air-saline mixture, the air-blood-saline mixture further enhanced TR tracing quality in 17 patients (P <.0001) and the peak TR velocity increased to 3.13 +/- 0.42 m/s (P <.0001). CONCLUSIONS: In patients with severe emphysema, an air-blood-saline mixture improves the quantifiable TR signals for more accurate estimation of pulmonary artery systolic pressure, even when there is minimal valve TR.

Single-breath diffusing capacity of the lung for carbon monoxide: a predictor of PaO2, maximum work rate, and walking distance in patients with emphysema.

OBJECTIVE: The National Emphysema Treatment Trial (NETT) is a randomized, multicenter, clinical trial comparing two different methods of lung volume reduction surgery plus medical therapy to medical treatment alone in patients with advanced emphysema. The purpose of this article was to use the data obtained from the NETT to assess the ability of the single-breath diffusing capacity of the lung for carbon monoxide (DLCO) to predict the need for supplemental oxygen during rest and exercise, as well as overall exercise capacity. METHODS: One thousand seventy-one patients with a mean (+/- SD) FEV(1) of 0.76 +/- 0.24 L were studied. RESULTS: The mean DLCO was 8.0 +/- 3.1 mL/min/mm Hg (28 +/- 10% of predicted). The mean resting PaO(2) was 64 +/- 10 mm Hg. There was a positive association between DLCO and both resting PaO(2) and the requirement for oxygen during a walk at 1 mile per hour (mph). The odds of requiring supplemental oxygen while walking at 1 mph was nine times greater in patients with a DLCO of < or = 20% of predicted than for patients with a DLCO of > 35% of predicted, after adjusting for age and gender. Eighty four percent of individuals with a DLCO of < or = 20% required supplemental oxygen with low levels of exercise compared to 38% of those with a DLCO of > 35%. CONCLUSION: Our results demonstrated that patients with reduced DLCO, particularly when < or = 20% of predicted, are more likely to have reduced PaO(2) at rest and are more likely to require supplemental oxygen with low levels of activity. Thus, DLCO is useful in evaluating whether supplemental oxygen is required for exercise.

Airflow limitation and breathing strategy in congestive heart failure patients during exercise.

BACKGROUND: Congestive heart failure (CHF) patients experience dyspnea on exertion and therefore have decreased exercise tolerance. OBJECTIVE: This study explores the hypothesis that stable New York Heart Association (NYHA) class III CHF patients without a history of pulmonary disease exhibit airflow limitation with increasing exercise. METHODS: We characterized flow limitations and breathing reserves at baseline, during exercise before anaerobic threshold (pre-AT), and after anaerobic threshold (post-AT) in CHF patients and normal subjects. Data were collected in the form of maximal flow volume loops and subsequent tidal flow volume loops at baseline and during exercise. Expiratory flow limitation was expressed as percent of tidal volume that corresponded with overlap of the tidal flow volume loops and maximal flow volume loops during expiration. The area directly between the maximum flow volume loops and the tidal flow volume loops during the expiratory phase is expressed as expiratory flow volume reserve (EFVR). RESULTS: CHF patients experienced expiratory flow limitation during exercise (pre-AT and post-AT) that was significantly increased compared to baseline and to normal subjects at similar exercise levels (CHF, baseline 8.5 +/- 7, pre-AT 37 +/- 10, post-AT 38 +/- 8%, n = 9, p < 0.05). Both CHF patients and normal subjects increased EFVR during exercise, but only the normal subjects increased EFVR to a significantly different value at post-AT exercise levels (normal subjects, 9.5 +/- 2, 11 +/- 2, 32 +/- 4%, n = 7, p < 0.05). Both CHF patients and normal subjects increased end inspiratory lung volume (EILV) during exercise, but only the normal subjects significantly increased EILV at post-AT exercise levels (normal subjects, 49 +/- 4, 55 +/- 5, 76 +/- 4%, p < 0.05). Inspiratory capacity (IC)/forced vital capacity (FVC) ratios were increased in CHF patients compared to normal subjects. However, IC/FVC values did not change during exercise in either group. CONCLUSIONS: CHF patients cannot utilize their full respiratory capacity during exercise secondary to expiratory flow limitation and an inability to increase EILV and EFVR.

Six-minute walk distance in chronic obstructive pulmonary disease: reproducibility and effect of walking course layout and length.

The 6-minute walk test is used in clinical practice and clinical trials of lung diseases; however, it is not clear whether replicate tests need to be performed to assess performance. Furthermore, little is known about the impact of walking course layout on test performance. We conducted 6-minute walks on 761 patients with severe emphysema (mean +/- SD FEV1% predicted = 26.3 +/- 7.2) who were participants in the National Emphysema Treatment Trial. Four hundred seventy participants had repeated walks on a separate day. The second test was improved by an average of 7.0 +/- 15.2% (66.1 +/- 146 feet, p < 0.0001, by paired t test), with an intraclass correlation coefficient of 0.88 between days. The course layout had an effect on the distance walked. Participants tested on continuous (circular or oval) courses had a 92.2-foot longer walking distance than those tested on straight (out and back) courses. Course length had no significant effect on walking distance. The training effect found in these patients with severe emphysema is less than in previous reports of patients with chronic obstructive pulmonary disease. Furthermore, the layout of the track may influence the 6-minute walk performance.

Grading the severity of obstruction in the presence of a restrictive ventilatory defect.

STUDY OBJECTIVES: No recommendation currently exists for grading the severity of airway obstruction in the presence of additional restriction. The grading of airway obstruction is currently based on the FEV(1) (American Thoracic Society [ATS] recommendations), while prior recommendations by the Intermountain Thoracic Society (ITS) graded the severity of obstruction based on the FEV(1)/FVC ratio. The objective was to compare the grading of airway obstruction using the percent predicted FEV(1) (ATS) with a confidence interval-based system (ITS), with particular focus on pulmonary functions in patients having both airway obstructions and restrictions. DESIGN: Retrospective analysis. SETTING: Tertiary medical center. PATIENTS: A retrospective analysis of 21,499 patient pulmonary function tests (PFTs) was performed. The predicted values of Crapo and coworkers were used. MEASUREMENTS AND RESULTS: The distribution of the severity of the obstruction was compared using the ATS and ITS methods for PFTs with normal, increased, or decreased total lung capacity (TLC). Analysis was performed using the chi(2) method. Of the 21,499 PFTs that were analyzed, TLC was measured in 28% (5,962 PFTs). In this cohort, 44% (2,619 PFTs) gave evidence of obstruction. Of these, 147 PFTs demonstrated additional restriction. While the ATS criteria graded 133 of these PFTs (90%) as being severe, the ITS criteria graded only 4 PFTs (3%) as severe (the severity distribution between the methods was significantly different [p < 0.01]). CONCLUSIONS: In view of the possible overestimation of the severity of obstruction in PFTs with concurrent restriction using the percentage of predicted FEV(1) values, consideration should be given to grading the severity of obstruction on the basis of the FEV(1)/FVC ratio in this specific subset of PFTs.