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Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

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 FEV1 (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. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

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.

Article-at-a-Glance 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 ≤ 3) experienced a greater-than-average increase in percentage of patients with blood culture collection within 24hours of hospital presentation. Hospitals applying all four social influence QI strategies showed a greater-than-average increase in delivery of antibiotics within 8hours of patients' hospital arrival when compared with all the other hospitals combined. Discussion The finding that an increased proportion of patients receiving antibiotics within 8hours and blood cultures within 24hours of hospital arrival when the greatest numbers of hospital-based QI strategies were implemented is suggestive of a possible "dose effect" of QI.

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.This study was conducted to evaluate the usefulness of air-blood-saline mixture in measuring TR velocity in severe emphysema.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.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).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.

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) FEV1 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 PaO2 was 64 10 mm Hg. There was a positive association between DLCO and both resting PaO2 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 35% of predicted, after adjusting for age and gender. Eighty four percent of individuals with a DLCO of 35%. Conclusion: Our results demonstrated that patients with reduced DLCO, particularly when < 20% of predicted, are more likely to have reduced PaO2 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. (CHEST 2003; 123:1394 –1400)

With modern medical technology, it is now possible to sustain life for prolonged periods in critically ill patients, even when there is no reasonable hope of improvement or achieving the goals of therapy. Such futile and medically inappropriate interventions may violate both the ethical and medical precepts generally accepted by patients, families, and physicians. In this study, we sought to determine who was primarily responsible for such interventions, the nature of their motivation, and the role of a timely bioethical consultation. In a retrospective review, we identified 100 patients of 331 bioethical consultations who had futile or medically inappropriate therapy. The average age of patients was 73.5 6 32 years (mean 6 2 SD) with 57% being male. Fifty-seven percent of the patients were admitted to the hospital with a degenerative disorder, 21% with an inflammatory disorder, and 16% with a neoplastic disorder. The family was responsible for futile treatment in 62% of cases, the physician in 37% of cases, and a conservator in one case. Unreasonable expectation for improvement was the most common underlying factor. Family dissent was involved in 7 of 62 cases motivated by family, but never when physicians were primarily responsible. Liability issues motivated physicians in 12 of 37 cases where they were responsible but in only 1 of 62 cases when the family was (x 2 5 degrees of freedom 5 26.7, p < 0.001). When the bioethics consultation resulted in cessation of the therapy, patients died in a median of 2 days as opposed to 16 days if therapy continued (p < 0.001). (CHEST 2001; 119:1944 ‐1947)

Background: We studied patients of a hospitalist teaching service and patients receiving routine private care (control subjects). We sought to evaluate whether inpatients cared for by an academic hospitalist service had lower lengths of stay and resource utilization rates. Methods: Using monthly hospital census data, 477 hospitalist cases and 1,160 control cases were selected by explicit criteria from the Medicaid population of a large, university-affiliated, community medical center between July 1, 1996, and June 30, 1997. Outcomes in hospitalist faculty patients were compared to those of control patients under the care of private providers. Results: Median length of stay was 4 days for control subjects and 3 days for the hospitalist service (p 65 years old showed statistically significant reductions in both length of stay (p 65 years old, especially in the control group (p 5 0.001). No significant differences in mortality, 30-day readmissions, or interfacility transfers were observed. Conclusions: Patients cared for by an academic hospitalist service that includes actively participating medical residents appear to have lower lengths of stay, total costs, and consultation rates than patients receiving routine private care. The reductions are largely observed among patients > 65 years old. (CHEST 2001; 119:580 ‐589)

Background: Gastric mucosal ischemia develops in critically ill patients in a number of clinical settings due to diversion of blood flow from the splanchnic bed to more vital organs, and can be detected by the measurement of gastric intramucosal pH (pHi). Study Objective: We hypothesized that similar changes would occur during obstructive sleep apnea (OSA) due to increased respiratory work during the periods of apnea. Methods: Gastric Pco2, pHi and arterial blood gases were measured during 3 conditions in 8 patients with severe OSA: at baseline awake, while asleep with ≧30 obstructive apneas or hypopneas per hour, and asleep after elimination of apneas with continuous positive airway pressure (CPAP). Results: Significant changes between the baseline and apnea conditions were detected using ANOVA for repeated measures for gastric PCO2, 40.2 ± 5.3 vs. 85.4 ± 34.0 (p < 0.001), pHi, 7.41 ± 0.06 vs. 7.11 ± 0.17 (p CO2 difference (DCO2), –2.3 ± 5.5 vs. 44.3 ± 36.21 (p < 0.006). Nasal CPAP returned all measures back to baseline values. Conclusions: Gastric tissue hypoxia develops in patients with severe OSA and may be a marker of disease severity. Treatment of OSA with CPAP eliminates the regional tissue hypoxia.

The objective of this study was to assess the utility of forced inspiratory vital capacity (FIVC) to identify bronchodilator reversibility (BDR) for patients with obstructive lung disease (OLD) in relation to customary BDR criteria as defined by the American Thoracic Society (ATS). Concurrent data analysis was used in an academic medical center setting. Two hundred patients with OLD (including chronic obstructive lung disease and asthma) undergoing testing at the Pulmonary Function Laboratory at Cedars-Sinai Medical Center from January 1995 to December 1996 were identified. These 200 patients were categorized into four grades of obstruction by ATS-defined forced expiratory volume in 1 sec (FEV1) criteria (severe, moderately severe, moderate, and mild). Each of these groups was further subdivided into equal subgroups according to the presence (+) or absence (-) of BDR. Inspiratory flow-volume loops and FIVC were analyzed for each of these subgroups. Of the patients exhibiting BDR on the forced expiratory maneuver (FEM), FIVC correctly identified 53% of the cases. For patients not exhibiting BDR on FEM, FIVC identified an additional 12 cases. In 72% of cases, the maximal FIVC was not obtained from the maximal FEM flow-volume loop. FIVC inspection of the data (which were already available from standard spirometric testing) identified a subgroup of OLD patients with BDR not appreciated by FEV1 or FVC criteria, which may respond to bronchodilator therapy. The maximal FIVC value should be obtained by manual inspection to identify the best inspiratory flow-volume loop.

Objective We attempted to identify clinical practice guideline and pathway articles in the area of pulmonary medicine published in peer-reviewed journals since 1974. Design Review. Data sources MEDLINE, the Cochrane Database, Best Evidence, and Abstracts of Clinical Care Guidelines from January 1974 to December 1998. Study selection All articles contained relevant search terms for pulmonary topics and were included irrespective of setting (primary or specialty, inpatient or outpatient). Controlled and uncontrolled trials as well as observational studies and consensus opinion/statements were all identified. The articles were stratified by design as well as by pulmonary topic. Data extraction Limited data on study type, study focus, year of publication, and results of study were abstracted. Results Our criteria yielded 271 articles, including 115 consensus statements and expert opinion guidelines; 30 controlled studies, meta-analyses, or systematic reviews; and 126 uncontrolled trials and observational studies. Of these, 82 articles (30.3%) related to asthma, 46 articles (17.0%) related to COPD, and 36 articles (13.3%) related to pneumonia. In addition, we tracked the increasing publication of all guideline-related pulmonary articles; randomized, controlled trials (RCTs); systematic reviews; and consensus statements by year for the past 25 years. Conclusion Pulmonary guidelines are increasingly published in peer-reviewed journals, but few are tested clinically in RCTs. There is continued reliance on consensus statements and expert opinion. Pulmonary guideline publications have continued to dramatically increase in number and in importance since 1974, both on the local level and internationally.

To examine the frequency of bronchoscopy performance in a large tertiary medical center over a period of 8 years.Retrospective data analysis.Academic medical center.Using a computerized database of all bronchoscopies performed between 1991 and 1997, we analyzed trends in (1) the total number of bronchoscopies; and (2) the numbers of bronchoscopies performed for patients on the basis of the postbronchoscopic diagnosis in the following three main disease groups: AIDS, interstitial lung disease (ILD), and lung cancer. We measured the following outcomes in the patients of high-volume and low-volume bronchoscopists: procedure length (time to perform procedure), nondiagnostic rate, and repeat-bronchoscopy rate. In addition, we compared total admissions, outpatient visits, and insurance status of the patients during the same period.In total, 5,580 bronchoscopies were performed. A 17% decline in the number of procedures was noted between 1991 and 1997 (from 943 to 783, respectively; p0.05). The number of AIDS-related bronchoscopies fell from 235 (25% of 943) to 96 (12% of 783), a 59% decline during this period (p0.05). There was a corresponding 76% decrease in the number of bronchoscopies associated with a diagnosis of Pneumocystis carinii pneumonia (PCP; p0.05). During the same period, no similar decrease was noted in the number of bronchoscopies associated with a diagnosis of ILD or lung cancer. Moreover, no significant differences were noted in the procedure length, nondiagnostic rate, or repeat-bronchoscopy rate between high-volume and low-volume bronchoscopists. Although there was no significant change in the number of total admissions between 1991 and 1997, there was a 48% increase in the number of managed-care patients and a 25.4% increase in the number of Medicaid health insurance program for California patients between 1991 and 1997.We noted a significant decline in the number of bronchoscopies performed between 1991 and 1997. The significant reduction in the number of AIDS-associated bronchoscopies accounted for 87% of the decline. Other possible factors include the introduction of a management pathway for the empiric treatment of PCP in 1996, a reduction in the number of pulmonary admissions, an increase in the number of managed care patients, and a reduction in the remuneration for the performance of bronchoscopy.

1. With the advent of single-photon emission computerized tomography, controversy has arisen with regard to the significance of gravitational influences on regional pulmonary perfusion (Q̊r) in the supine versus prone postures. We investigated the dorsal—ventral distributions of Q̊r in prone (n = 5) and supine (n = 5) normal subjects, as assessed by single-photon emission computerized tomography after intravenous injection of technetium-99m-labelled macroaggregated albumin at end-tidal expiration. Reconstructed serial (one pixel thickness) coronal sections were traced on a computer screen, to yield the encompassed radioactive counts and number of pixels per each image. Coronal section data (expressed as mean radioactive counts/pixel) were expressed in a ‘profile’ and normalized to the maximum coronal section of each lung (%maximum). 2. Coefficients of variation and linear regression slopes for the prone versus supine profiles for left and right lungs were not statistically different (unpaired Student's t-test). The coronal section with maximum Q̊r was identified in the more dependent lung regions and, hence, affected by gravity. 3. We conclude that, in contrast to previous canine models, which have suggested postural differences in dorsal-ventral perfusion gradients, in normal man gravity primarily determines the non-dependent to dependent distribution of Q̊r. We speculate that interspecies differences in physiology may be teleological and related to the different perfusion demands of the quadruped compared with upright man.

BACKGROUND: The hypothesis that gastric intramural pH (pHi) is predictive of outcome in haemodynamically stable, mechanically ventilated patients was tested in 25 patients on assisted mechanical ventilation for respiratory failure. METHODS: Simultaneous samples of arterial blood and gastric juice were obtained from patients on assist control, synchronised intermittent and pressure control ventilation during the first 48 hours of mechanical ventilation. Gastric pHi was calculated from the equation: pHi= 6.1 + log HCO3/(gastric PCO2 X 0.03). The outcome was survival or death due to respiratory or circulatory failure within 45 days of admission. RESULTS: Gastric pHi proved to be a better predictor of outcome than all presently utilised parameters. Although all patients included in this study were haemodynamically stable and were similar for all laboratory indices, the only variable capable of accurately predicting outcome was gastric pHi. Patients with a normal arterial pH but a gastric intramural pH of less than 7.25 had an observed mortality of 66%. Standard severity of illness scores grossly underestimated mortality rates. The sensitivity and specificity of a gastric pHi value of less than 7.25 in predicting death were 86% and 83%, respectively. A receiver operator curve for all variables exaggerates the superiority of gastric pHi as a predictor of outcome. CONCLUSION: Low gastric pHi, a marker of gastrointestinal ischaemia, may occur in the presence of normal haemodynamics and may be used to predict severity of illness and mortality accurately.

1. Single-photon emission computerized tomography in both an intact canine model and man has demonstrated an aspect of pulmonary perfusion to be independent of gravitational forces. 2. Using technetium 99 m-labelled macroaggregated albumin single-photon emission computerized tomographic imaging, we investigated normal human subjects (n = 5), stable unilateral lung transplant recipients (n = 6) and transplant recipients with chronic allograft dysfunction related to obliterative bronchiolitis (n = 5). 3. In coronal isogravitational sections, a 1 × 1 × N pixel strip (medial to lateral) was constructed through the ‘core’ pixel of maximal radioactive counts. The counts were measured for the ‘core’ pixel and at two mid-points (medial and lateral) between the core pixel and the lung edges. Coefficients of variation were computed for each isogravitational strip and compared between groups. Fractional whole-lung perfusion was determined for left versus right lungs of normal subjects and allograft versus native lungs of transplant recipients. 4. Using these indices, ‘isogravitational heterogeneity’ (i.e. increased ‘core’ versus peripheral perfusion) was observed in allografts and native diseased lungs after unilateral transplantation. Despite significantly increased fractional whole-lung perfusion directed to the allografts (84.8% ± 3.0% and 75.8% + 12.1% for stable unilateral lung transplant recipients and patients with obliterative bronchiolitis respectively) compared with normal lungs (50.2% ± 1.2% and 49.8% ± 1.2% for left and right respectively), ‘isogravitational flow heterogeneity’ (i.e. increased ‘core’ versus peripheral perfusion) was preserved after transplantation. 5. These findings suggest that ‘isogravitational heterogeneity’ was maintained despite increased unilateral pulmonary perfusion and the presumed increase in pulmonary capillary recruitment and/or distension.

Aspergillus fumigatus hyphae is often found in the lung tissue of patients with bronchocentric granulomatosis (BCG). This organism is believed to be one agent responsible for inciting the hypersensitivity response and subsequent development of the characteristic pathology that defines BCG. The definitive etiology of this disease, however, remains conjectural. Corticosteroids represent the mainstay of therapy. The fungi recovered from patients with BCG are considered noninvasive; thus, the risk of fungal invasion secondary to steroid-induced immunosuppression is believed to be negligible. However, we report a case of spinal aspergillus abscess that developed in a patient with BCG subsequent to steroid therapy. This case also highlights the necessity for aggressive medical and neurosurgical intervention to avert the development of neurological sequelae.

Abnormalities of oxygen use occur in obstructive sleep apnea, as do impaired cerebral perfusion and alterations of cerebral function. In this case study, the authors quantitated the local cerebral glucose metabolic rate in two patients with obstructive sleep apnea (one with and one without oxygen supply dependency) and assessed cerebral glucose use by increasing oxygen delivery through passive leg elevation. Obstructive sleep apnea was confirmed by visual analysis of nocturnal pulse oximetry traces in two patients and its severity assessed from the respiratory disturbance index and minimum oxygen saturation. Awake local cerebral glucose metabolic rate (microM/min/100 g) was determined by positron-emission tomography using [18F]-2-Fluoro-2-Deoxy-D-Glucose at baseline and on the following day during passive leg elevation. Conditions otherwise were unchanged. The patient with global oxygen supply dependency exhibited a significant increase in the local cerebral glucose metabolic rate. In contrast, the patient without global supply dependency had no change in the local cerebral glucose metabolic rate. These case studies demonstrate the first evidence of improvement in regional metabolic consumption in response to increased oxygen delivery and in the presence of global oxygen supply dependency.

We present a 64-year-old man with New York Heart Association (NYHA) Class III chronic congestive heart failure (CHF) who was examined for an alteration in cerebral cortex regional oxygen utilization as reflected by changes in local cerebral metabolic rates for glucose (LCMRglu). LCMRglu was determined by positron emission tomography at baseline and while oxygen delivery (DO2) was optimized during dobutamine infusion. Baseline DO2 was 8.31 mL/min/kg and cardiac output (CO) was 3.4 L/min, whereas oxygen consumption (VO2) measured by respired gas analysis was 3.64 mL/min/kg. At optimal dobutamine effect (7.5 μg/kg/min), DO2 increased to 16.8 mL/min/kg, CO to 7.2 L/min, and VO2MEAS was 3.67 mL/min/kg. Mean percentage Increase in cortical gray matter LCMRglu was 99.4 ± 11.7% (mean ± SD) and was statistically significant ( p < 0.001; Student's paired t-test). Our results demonstrate that the cerebral glucose utilization and therefore oxygen consumption increased parallel with Increases in DO2. This phenomenon is contrary to the conventional concept that cerebral perfusion is strictly autoregulated and that substrate utilization is independent of oxygen delivery.

A reduced exercise tolerance, maximum oxygen uptake (VO2max), and anaerobic threshold have been reported after lung transplantation (LT). We prospectively assessed the hemodynamic responses to incremental cycle ergometry before and after LT in eight recipients. All recipients underwent a 6-week formal exercise training program. The VO2max increased after versus before LT (13.4 +/- 0.8 vs 9.2 +/- 0.8 ml/min/kg) (p < 0.01). No transition thresholds by analysis of arterial standard bicarbonate were discerned before LT, while the thresholds after LT were abnormally low (VO2 = 9.4 +/- 0.6 ml/min/kg or 35 +/- 3 percent of predicted maximum VO2). An early rise in arterial lactate was similarly observed after LT. Maximum stroke volume index increased in six of seven patients after versus before LT (51 +/- 4 vs 37 +/- 2 ml/beat/m2) (p < 0.05). Three patients demonstrated an increased mean pulmonary arterial pressure at rest, while pressures during exercise were elevated in six. Pulmonary vascular resistance was mildly elevated after LT but decreased appropriately during incremental exercise and was associated with normal cardiac output responses. We conclude that pulmonary vascular abnormalities occurred during hemodynamic exercise testing in the majority of LT recipients; however, exercise limitation was primarily attributed to cardiovascular limitation or to deconditioning in five of the recipients. In the remaining three, the exercise study was considered to be submaximal by virtue of low peak heart rates. A persistent state of deconditioning may have important implications with respect to exercise training regimens after LT.

We compared the intraobserver and interobserver agreement of blood (BCT) and gas exchange (GET) methods for determination of the anaerobic threshold (AT) in patients with COPD. In addition, we determined the sensitivity and specificity of the gas exchange methods for determination of the AT. Two noninvasive methods, the V-slope (VS) and the ventilatory equivalents method (VEM) were compared with two blood sampling methods, the log standard HCO 3 (SB) vs log V ˙ O 2 (SBT) and base excess (BE) vs V ˙ O 2 (BET). Twenty-nine patients with COPD (FEV 1

Study Settings and Interventions Sixty individuals complaining of dyspnea on exertion, but with normal spirometry and lung volumes and normal chest roentgenograms were reviewed for this study. These individuals were selected from a large group of outpatients (552 individuals over a seven-year period) who were referred to our laboratory for exercise testing to determine the cause of their exertional dyspnea. They were grouped according to the single-breath diffusing capacity, with those less than 70 percent of predicted in the low DCO group (group 1) and those greater than 70 percent of predicted in the normal DCO group (group 2). Both study groups underwent an incremental exercise test. Results Twenty-three individuals had a DCO less than 70 percent of predicted. During exercise, seven of these (30 percent) had an abnormal PaO 2 and five had an abnormal P(A-a)O 2 . Thirty-seven people had a normal DCO. Thirty-six of these (97 percent) had a normal PaO 2 and P(A-a)O 2 during exercise. Overall, eight individuals had an abnormal PaO 2 or P(A-a)O 2 during exercise; seven of these had an abnormally low DCO at rest. Conclusions Based on this selected group of a subpopulation, we conclude that the DCO is an important determinant of the diagnostic approach to a patient with dyspnea who is otherwise normal. If all pulmonary functions, including DCO are normal, an exercise study will fail to reveal abnormal PaO 2 or P(A-a)O 2 in 97 percent of the cases. However, a low DCO has a poor predictive value with respect to abnormal gas exchange during exercise. Therefore, when investigating exertional dyspnea, based on this selected subpopulation, if the spirometry, lung volumes, and DCO are normal, one may forego additional invasive gas exchange evaluation. However, an abnormal DCO warrants further physiologic testing.

The purpose of our study was to evaluate the reproducibility of a Borg rating of dyspnea in patients with COPD. We examined nine patients with COPD who performed a SST on four separate days within a ten-day period. The patients walked on a treadmill for 6 min. At the end of each minute, patients matched a Borg rating to the intensity of their breathlessness. We measured the HR, VE, VO2, VT and f at the end of each minute. While the mean VO2, VE, HR, VT and f stabilized after one or two attempts, the Borg ratings decreased with successive tests. We conclude that the Borg scale for measuring breathlessness shows progressive decreases with repetition whereas VO2, VE, HR, VT and f stabilize after one or two practice attempts. This suggests that desensitization to dyspnea may play a role in the improvement of patients after exercise.

The purpose of this study was to determine if endogenous levels of carboxyhemoglobin (COHb) are elevated in patients intubated for respiratory failure, and, if so, whether these levels are predictive of in-hospital mortality, as was suggested previously. An arterial blood gas was drawn within 24 hours of admission and no sooner than 6 hours after intubation, in patients admitted to our respiratory intensive care unit (RICU) or medical intensive care unit (MICU) for respiratory failure. An IL682 co-oximeter was used to measure COHb levels. Apache II severity scoring was completed upon admission to the hospital. Patients were then followed prospectively until either end point of death or extubation and discharge were reached. Both smokers and nonsmokers were included in the study. Of the 13 patients in the study, there were 4 survivors to extubation and discharge home and 9 deaths. None of the patients had elevated COHb levels. The average level of COHb was less in the nonsurvivors (1.29%) than in the survivors (1.85%, NS). A statistically significant correlation was not noted between COHb level and either Apache II score or outcome. Apache II levels correlated well with outcome. There was a 100% mortality rate in all patients with scores ≥15. In patients intubated for respiratory failure and protected from environmental sources of CO, endogenous production of CO is not elevated. COHb levels therefore have no prognostic value in patients with RF.

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.

In order to assess the long-term clinical benefits of palliative Nd:YAG laser photoresection, we studied 69 patients with obstructing exophytic tracheobronchial lesions treated with this modality between Oct 25, 1984 and May 8, 1989. In 55 patients, there was greater than 75 percent restoration of the luminal caliber ("successful"), and this group was compared to 14 patients in whom the lumen was not restored ("unsuccessful"). Stratifying for squamous cell carcinoma (squamous) alone vs other lung histologic cell types (non-squamous) demonstrated a significant survival benefit for "successful" squamous vs "unsuccessful" squamous and for "successful" squamous vs "successful" nonsquamous (p less than 0.05). The prolongation in survival was unrelated to patients' age, baseline Karnofsky performance indices, technical aspects of photoresection, and other modes of therapy (ie, radiation or chemotherapy or both). Although only six of 24 of the "successfully" photoresected patients with squamous cell carcinoma survived for one year, only one patient with inoperable mucoepidermoid carcinoma in the nonsquamous group survived beyond ten months. Karnofsky indices improved in both "successful" (p less than 0.001) and "unsuccessful" (p less than 0.05) photoresection groups. Improvement in the latter group may be attributed to either a salutary effect of the bronchoscopic procedure or variability in patients' level of functioning. We conclude that a subset of patients with advanced stages of squamous cell carcinoma and airway obstruction due to exophytic tumor may derive substantial benefit in both functional status and survival after Nd:YAG laser photoresection. In addition, unsuccessful restoration of the airway is a grave prognostic sign leading to limited survival.

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) evalu- ated 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 se- verity 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 youngerandexhibited a lowerbody massindex(BMI),shorter smoking history, less severe airflow obstruction, lower DLCO and arterial PO2, higher arterial PCO2, shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV1% 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. What This Study Adds to the Field In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with dispropor- tionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.

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.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.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 (p0.001), and symptoms (SGRQ) through 5 years (p0.001 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 (p0.01 years 1 to 3) and SGRQ (p0.01 years 1 to 4).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.

Comprising 1 to 4% of all tumors and 7 to 15% of malignant neoplasms of the major salivary glands, acinic cell carcinoma (ACC) rarely occurs in the respiratory tract. There has been only one case of ACC of the trachea previously reported in the medical literature. A second case of ACC of the trachea associated with upper airway obstruction and its management by Nd: YAG laser and surgical resection is reported.

Purpose: 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 Pa o 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.

BackgroundThe 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.MethodsLung 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.ResultsIn 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.ConclusionsMorbidity 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.

We present a 42-year-old woman with status asthmaticus who required mechanical ventilation and a combination of maneuvers, including barbiturate coma, general anesthesia, high-dose steroids, bronchoscopic pulmonary toilet, and helium-oxygen ventilation, resulting in successful extubation and eventual hospital discharge. This case report illustrates the possible role of combination therapy in the management of severe asthma exacerbation.

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.One thousand seventy-one patients with a mean (+/- SD) FEV(1) of 0.76 +/- 0.24 L were studied.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 ofor = 20% of predicted than for patients with a DLCO of35% of predicted, after adjusting for age and gender. Eighty four percent of individuals with a DLCO ofor = 20% required supplemental oxygen with low levels of exercise compared to 38% of those with a DLCO of35%.Our results demonstrated that patients with reduced DLCO, particularly whenor = 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.

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.

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 χ 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 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.

Comprehensive exercise testing offers an opportunity to study the cellular, cardiovascular, and ventilatory systems’ responses simultaneously under controlled conditions (1).

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.

In 1990, it was estimated that approximately 1% of all US health-care costs (approximately $6.2 billion) were spent on asthma-related health expenses. Of this, hospitalization charges alone exceeded $2.6 billion. Practice guidelines and clinical pathways are being developed to standardize the management of acute asthma with the aim of improving care and safely reducing health-care costs. In this report, we evaluate the impact of an asthma pathway developed and instituted at a large community-based teaching hospital. This pathway was evidence based and was developed by a multidisciplinary group.The study was conducted during a 6-month period in 1995, while a similar period in 1994 was used as a historical control period. Data collected included patient demographics, hospital admission and discharge peak expiratory flow rates, pulse oximetry measurements, length of stay, conversion from hand-held nebulizer to metered-dose inhaler, use of corticosteroids within 24 h of hospitalization, and conversion of i.v. steroids to oral steroids.A total of 42 patients were enrolled during the study period. Of these, 19 were placed on the pathway, while 23 were not treated according to the pathway. There were 38 patients in the 1994 historical control period. For 1995, there was no significant difference between the pathway and nonpathway groups with regard to the length of stay (4.4+/-3.3 vs 3.2+/-2.3 days; p0.05), hospital discharge peak expiratory flow rates (324 vs 286 L/min; p0.05), or use of steroids (100% vs 91%; p0.05). However, a significant increase in conversion from hand-held nebulizer to metered-dose inhaler was noted in the pathway group (68% vs 34%; p0.05). The data from 1994 compared to 1995 pathway were similar in that there was no difference in the length of stay (3.4+/-2.1 vs 4.4+/-3.3 days; p0.05) and/or use of steroids (92% vs 100%; p0.05), while a significant increase in hand-held nebulizer to metered-dose inhaler conversion was observed for the 1995 pathway group (68% vs 26%; p=0.002).We conclude that although the asthma pathway did not significantly reduce length of stay, it was associated with a significant increase in hand-held nebulizer to metered-dose inhaler conversion, resulting in a substantial cost savings of $288,000/year.

The objectives of this study were to examine the reported accuracy of cooximetry in determination of methemoglobin levels, to report the apparent discrepant values of “measured” methemoglobin and carboxyhe-moglobin, and to discuss the effect that methemoglobinemia has on pulse oximetry readings. Secondly, relative oxygen saturations measured by pulse oximetry and calculated from arterial blood gas samples were compared. A retrospective analysis was performed in an academic medical center with two patients who were diagnosed with acute methemoglobinemia after taking sulfa-containing medications. Serial pulse oximetry, arterial blood gas, and cooximeter analysis were performed for two patients. Cooximetry was performed using an IL-482 oximeter, arterial blood gas analysis was performed using a BLE 1400 oximeter, and pulse oximetry was performed using Ohmeda Biox 3740, Hewlett Packard SP02, or Marquette SP02 models. Methemoglobin levels ranged from 6% to 48%, however, summation of methemoglobin and oxyhemoglobin were as high as 120%. As a result, negative values of carboxyhemoglobin were recorded by the cooximeter, generating a total sum of 100%. Comparison of pulse oximetry and arterial blood gas oxygen saturation (measured and calculated values, respectively) revealed significant discrepancies; methemoglobin was > 9%, whereas oxygen saturation uniformly was lower with pulse oximetry. Therefore, we recommend that when methemoglobin levels exceed 10%, cooximetry be used as a screen for methemoglobinemia and that serial cooximeter measurements be used to guide therapy and reliance on noninvasive pulse oximetry.

There is widespread interest in the evaluation of clinical strategies that safely reduce health-care costs. Elimination of inappropriate chest physiotherapy may represent one of those strategies.An academic community hospital.One-hundred one patients receiving chest physiotherapy were prospectively randomized to continue their chest physiotherapy or to inform their physicians that the order for the chest physiotherapy may have been inappropriate.Patients who were randomized to have their chest physiotherapy discontinued received 45% fewer chest physiotherapy treatments than control patients (p0.01). There was no increase in the mortality rate or length of hospital stay associated with the reduction in chest physiotherapy in carefully selected patients. The estimated cost savings would be $319,000, which is 50 times greater than the cost associated with the intervention.Chest physiotherapy is frequently provided to patients for inappropriate indications. Reducing chest physiotherapy for these patients may significantly reduce respiratory therapy costs without increasing length of stay or mortality rates.

Pneumocystis carinii organisms have been shown to persist throughout therapy in the majority of patients with Pneumocystis carinii pneumonia (PCP). This study evaluated the relationship between persistence of organisms and recurrence of disease, and the effect of chemoprophylaxis on bronchoalveolar lavage specimens. Seven patients receiving PCP chemoprophylaxis underwent serial bronchoalveolar lavage (BAL) examinations at 1, 4, and 7 mo after recovery from a first episode of PCP. Specimens were examined for persistent organisms with Gomori's methenamine silver stain and immunofluorescent antibody staining. There were no persistent organisms 1 mo after completion of antimicrobial treatment in six of the seven patients. The one patient with persistent organisms demonstrated clearance of organisms by 4 mo and had no recurrence of PCP. One patient had a recurrence of PCP at 4 mo, after a negative 1-mo BAL. We conclude that a positive BAL result by silver stain or immunofluorescent antibody staining more than a month after ending treatment may indicate clinical recurrence of PCP and not just persistence of nonpathologic cysts. These findings suggest that recurrences of PCP are more likely due to new infection than to relapse of prior disease.

Atovaquone is a new hydroxynapthoquinone antiprotozoal agent active against Pneumocystis carinii in vitro and in animal models. The authors report an experience using atovaquone to treat 25 patients with mild to moderate P. carinii pneumonia. Eligible patients were treated for 21 days with 750 mg of atovaquone orally three times daily. Prednisone was added when the P(A-a)O2 gradient was between 35-45 mm Hg. Patients were treated under three treatment protocols. Patients in Group 1 participated in one of two randomized comparative drug trials, designed for patients with and without sulfonamide intolerance. Six of seven patients successfully completed treatment, and one patient discontinued treatment because of an adverse reaction (> 5 times baseline increase in transaminase level). Patients in Group 2 were treated with atovaquone for mild to moderate P. carinii pneumonia under a treatment Investigational New Drug protocol because of prior sulfonamide reactions. Fifteen of these 18 patients successfully completed treatment; one died from other complications during treatment and two discontinued treatment for adverse reactions (> 5 times baseline increase in transaminase levels, and a diffuse rash). Serum transaminase levels returned to normal at the end of treatment in all patients with elevated levels. All patients demonstrated clinical resolution of their pneumonia and improvement of pretreatment hypoxemia (Group 1: pretreatment PaO2 = 82 +/- 14 mm Hg, posttreatment PaO2 = 92 +/- 9 mm Hg). Overall, 21 (84%) of 25 patients successfully finished therapy without significant adverse reactions. Atovaquone appears to be an effective and well-tolerated oral treatment for mild to moderate P. carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Granular cell myoblastoma is an uncommon benign tumor that causes pulmonary complications due to obstruction of the airways. We report the first case of bronchial obstruction due to granular cell tumor treated with Nd:YAG laser. The Nd:YAG laser appears to be an effective new tool for relieving obstruction and, in some cases, preventing recurrence, and can be delivered with the use of a flexible bronchoscope.

Cardiopulmonary exercise testing has previously demonstrated a reduced maximum oxygen uptake and anaerobic threshold, as well as abnormal wasted ventilation fraction and gas exchange after unilateral lung transplantation. To further explain the mechanisms of these abnormalities, we assessed the regional distribution of pulmonary blood flow and ventilation at rest and during steady-state exercise in nine recipients of unilateral lung transplants. Krypton-81 (81mKr) aerosol and technetium-99m (99mTc) were utilized to assess lung ventilation (V) and perfusion (Q), respectively. The digitalized images were trisected to analyze apical, mid-, and basilar lung perfusion and ventilation in both the transplanted and native lung, both at rest and steady-state upright exercise. Results were compared with previously reported data obtained in normal subjects in our laboratory using the identical technique. At rest, 75 +/- 13 percent of perfusion was directed to the transplanted lung; however, the corresponding fractional ventilation was only 67 +/- 14 percent. During exercise, there was no significant change in fractional perfusion or ventilation. Resting apical perfusion in the transplanted lung was higher than normal in four patients and comparable to normal in five patients. In contrast to the augmentation of apical perfusion observed in normal subjects during upright exercise, none of our patients increased the regional perfusion to the apices during exercise in either transplanted or native lungs. These unexpected responses suggest either more maximal allograft apical recruitment at rest due to the increased allograft perfusion or an abnormality in the apical pulmonary vasculature after transplantation. Furthermore, the relative mismatch in ventilation and perfusion in transplanted and native lungs suggests regions of high V/Q in the native, and low V/Q in the transplanted lung. This mismatch is most pronounced in recipients of single lung transplants for pulmonary vascular disease.

We studied the acute hemodynamic effects of increasing nasal continuous positive airway pressure (CPAP) in 13 patients with acute decompensation of congestive heart failure. Heart rate, respiratory rate, pulmonary capillary wedge pressure, right atrial pressure, systemic blood pressure, and thermodilution cardiac outputs were measured at baseline, during, and after application of nasal CPAP at increasing pressures of 5, 10, and 15 cm H2O. Cardiac index, stroke volume, and oxygen delivery were calculated. Based on a significant change in cardiac output greater than or equal to 400 ml, seven patients were classified as responders, whereas six patients were considered to be nonresponders. In responders, significant increases were noted in cardiac index (2.5 +/- 0.7 to 2.9 +/- 0.9 L/min/m2), stroke volume (49 +/- 15 to 57 +/- 16 ml), and oxygen delivery (10.3 +/- 5.1 to 12.3 +/- 6.0 ml/min/kg) without a change in pulmonary capillary wedge pressure. In contrast, the nonresponders showed no significant change in any of the hemodynamic parameters. Improvement in cardiac output could not be predicted by any of the baseline hemodynamic or clinical variables, nor was it related to random variations since all variables returned to baseline after cessation of CPAP. Increase in stroke volume without a change in pulmonary capillary wedge pressure (preload) suggests either improved inotropic function of the left ventricle or reduced left ventricular afterload with CPAP. Thus, CPAP may offer a new noninvasive adjunct to improving left ventricular function and augmenting cardiac performance in a subset of patients with congestive heart failure.

The diffusing capacity of the lung for carbon monoxide (DL) is affected by changes in alveolar partial pressure of oxygen (PAO2), hemoglobin concentration (Hb), and carboxyhemoglobin concentration (COHb). A number of investigators have derived empiric adjustment equations to account for changes in these variables. We evaluated an adjustment of DL for changes in COHb and PAO2 using a single equation derived from Roughton and Forster's original definitions (J. Appl. Physiol., 1957). Unadjusted DL values declined significantly with rising COHb (-0.938%/percent COHb increase, P less than 0.0001) and rising PAO2 (-0.343%/mm Hg PAO2 increase, P less than 0.0001). Adjusted measured DL using the derived equation showed no significant change with changing COHb and PAO2 levels and provides an acceptable method for adjustment of DL for the effects of varying COHb and PAO2 levels from the standard conditions of COHb% = 0, and PAO2 = 110 mm Hg. Since a similar equation has previously been used to adjust for changes in DL due to anemia, we propose to use a single equation which is theoretically derived and empirically verified to adjust DL measurements for changes in COHb, PAO2 and hemoglobin.

Mucoid impaction of tracheobronchial tree is a common condition which may complicate tracheostomy. Here we describe a case of a 72-year-old man, status after tracheostomy, who presented to the hospital with an acute upper airways obstruction and respiratory arrest due to a tracheal cast. The cast was successfully dislodged by the Nd-Yag laser.

Objective: Our objective was to study the effects of extreme obesity on pulmonary function tests and the effects of smoking on these variables in a population group larger than has previously been reported. Design: Retrospective data analysis. Setting: Academic medical center. Patients: Forty-three patients with extreme obesity [ratio of weight in kilograms to height in centimeters greater than 0.9 (W/H)] who underwent pulmonary function testing at Cedars-Sinai on an out-patient or in-patient basis during the period of 1979 to 1997. Measurements and Results: Patients underwent standard pulmonary function testing. The patients were divided into 2 groups based on the W/H ratio: group A (0.9-0.99) and group B (greater than 1.0). Chart review was performed to identify pertinent historyl co-morbidities. The independent effects of smoking between each group's patients were assessed. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), expiratory reserve volume (ERV), functional residual capacity (FRC), maximum voluntary ventilation (MVV), and forced expiratory flow during midexpiratory phase (FEF 25–75% ) were significantly reduced in both groups. Single-breath diffusing capacity for carbon monoxide (OLCO) and the volume of gas into which the single-breath of carbon monoxide and helium was diluted were not elevated. Smoking did not account for the results in group A but did seem to partially explain the decrease in FVC, FEV1, and FEF 25–75% in group B. Conclusions: Extreme obesity is associated with a reduction in ERV, FVC, FEV1, FRC, FEF 25–75% , and MVV. However, contrary to prior reports, OLCO is not elevated. These effects are only partially explained by smoking.