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Background: The hypothesis that ventilation of emphysematous lungs would be enhanced by communication with the parenchyma through holes in the pleural surface was tested. Methods: Fresh human lungs were obtained from patients with emphysema undergoing lung transplantation. Control human lungs were obtained from organ donors whose lungs, for technical reasons, were not considered suitable for implantation. Lungs were ventilated through the bronchial tree or transpleurally via a small hole communicating with the underlying parenchyma over which a flanged silicone tube had been cemented to the surface of the lung (spiracle). Measurements included flow-volume-time curves during passive deflation via each pathway; volume of trapped gas recovered from lungs via spiracles when no additional gas was obtainable passively from the airways; and magnetic resonance imaging assessment of spatial distribution of hyperpolarised helium ( 3 He) administered through either the airways or spiracles. Results: In emphysematous lungs, passively expelled volumes at 20 s were 94% greater through spiracles than via the airways. Following passive deflation from the airways, an average of 1.07 litres of trapped gas volume was recoverable via spiracles. Regions were ventilated by spiracles that were less well ventilated via bronchi. Conclusions: Because of the extensive collateral ventilation present in emphysematous lungs, direct communication with the lung parenchyma through non-anatomical pathways has the potential to improve the mechanics of breathing and hence ventilation.

The development of laser-polarized helium-3 (3He) technology (1,2) now allows for imaging of the gas spaces of human and animal lungs (3,4). Typical absolute polarizations of 30%–50% are approximately 100,000 times that available at thermal equilibrium in typical imaging fields of 1.5 T, with a corresponding increase in signal to noise (S/N) for a given quantity of gas. Many of the early applications of hyperpolarized 3He magnetic resonance (MR) imaging used ventilation images (or spin-density images) (3,4), which show the spatial distribution of the 3He after inhalation of a bolus followed by breathhold. In small animals with continuous breathing of 3He, exquisitely resolved microimages have been reported (5). In recent years, the effort of our group at Washington University has focused on MR determinations of the changes in airways at the acinar level (airways lined with alveoli) using 3He diffusion MR. The following describes the approaches we have taken and presents some of the results at our institution and is not intended as a review of the field (for more comprehensive reviews, see references 3 and 4).

Objectives: Though numerous studies have demonstrated the short-term efficacy of lung volume reduction surgery (LVRS) in select patients with emphysema, the longer-term follow-up studies are just being reported. The primary objectives of this study were to assess long-term health-related quality of life, satisfaction, physiologic status, and survival of patients following LVRS. Design: We used a prospective cohort study design to assess the first 200 patients undergoing bilateral LVRS (from 1993 to 1998), with follow-up through the year 2000. Each patient served as his own control, initially receiving optimal medical management including exercise rehabilitation before undergoing surgery. Preoperative postrehabilitation data were used as the baseline for comparisons with postoperative data. The primary end points were the effects of LVRS on dyspnea (modified Medical Research Council dyspnea sale), general health-related quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]), patient satisfaction, and survival. The secondary end points were the effects of LVRS on pulmonary function, exercise capacity, and supplemental oxygen requirements. Setting: A tertiary care urban university-based referral center. Patients: Eligibility requirements for LVRS included disabling dyspnea due to marked airflow obstruction, thoracic hyperinflation, and heterogeneously distributed emphysema that provided target areas for resection. Patients were assessed at 6 months, 3 years, and 5 years after surgery. Interventions: Preoperative pulmonary rehabilitation and bilateral stapling LVRS. Measurements and results: The 200 patients accrued 735 person-years (mean ± SD, 3.7 ± 1.6 years; median, 4.0 years) of follow-up. Over the three follow-up periods, an average of > 90% of evaluable patients completed testing. Six months, 3 years, and 5 years after surgery, dyspnea scores were improved in 81%, 52%, and 40% of patients, respectively. Dyspnea scores were the same or improved in 96% (6 months), 82% (3 years), and 74% (5 years) of patients. Improvements in SF-36 physical functioning were demonstrated in 93% (6 months), 78% (3 years), and 69% (5 years) of patients. Good-to-excellent satisfaction with the outcomes was reported by 96% (6 months), 89% (3 years), and 77% (5 years) of patients. The FEV 1 was improved in 92% (6 months), 72% (3 years), and 58% (5 years) of patients. Changes in dyspnea and general health-related quality-of-life scores, and patient satisfaction scores were all significantly correlated with changes in FEV 1 . Following surgery, the median length of hospital stay in survivors was 9 days. The 90-day postoperative mortality was 4.5%. Annual Kaplan-Meier survival through 5 years after surgery was 93%, 88%, 83%, 74%, and 63%, respectively. During follow-up, 15 patients underwent subsequent lung transplantation. Conclusions: In stringently selected patients, LVRS resulted in substantial beneficial effects over and above those achieved with optimized medical therapy. The duration of improvement was at least 5 years in the majority of survivors.

To evaluate the repeatability of quantitative computed tomographic (CT) indexes of emphysema and the effect of spirometric gating of lung volume during CT in candidates for lung volume reduction surgery (LVRS).Initial and same-day repeat routine inspiratory spiral chest CT studies were performed in 29 LVRS candidates (group 1, routine study vs repeat study). In a separate cohort of 29 LVRS candidates, spiral chest CT studies were performed both without and with spirometric gating by using a spirometer to trigger scanning at 90% of vital capacity (group 2, spirometric gating study). In each study, Pearson and intraclass correlation coefficients were calculated to determine the agreement between multiple pairs of whole-lung quantitative CT indexes of emphysema, and mean values were compared with two-tailed paired t tests.Pearson and intraclass correlation coefficients were high for all quantitative CT indexes (allor = 0.92). No significant differences were found between mean values of quantitative CT indexes in group 1. Variation in quantitative CT results was small but more prominent in group 2 than in group 1. The variation in quantitative CT results was primarily related to differences in lung volume (r(2) as great as 0.83).Repeatability of quantitative CT test results in LVRS candidates is high and unlikely to improve by using spirometric gating.

Eponyms are a time-honoured tradition in medicine as well as the sciences. Some fields of medicine, such as rheumatology and neurology, are particularly fond of them and the term “eponymophilia” has been coined to describe their affinity 1. Those who like their eponyms argue that their use adds flavour to our daily practice and that they are universally understood. They also claim that, as they are everywhere anyway, change would be impractical 2. During the last decade or so, the use of eponyms has become the subject of intense controversy. In 2003, Panush et al. 3 reported on the biography of Hans Reiter, after whom a form of reactive arthritis was named despite the fact that others had described the condition well before him. Apart from being an outspoken lecturer in favour of “racial hygiene”, Reiter served on the advisory board to Hitler's physician, Karl Brandt, who headed the infamous “euthanasia” programme. This systematic killing of patients with mental and other illnesses developed the killing mechanism utilised in the genocide of the Jews, and the Roma and Sinti people. Brandt was executed for this and other crimes in 1948. Moreover, Reiter, as Chief of the Reich Health Service, approved not only the sterilisation programmes but also the deliberate infection of concentration camp inmates with rickettsia. The report by Panush et al. 3 led many physicians, particularly in the USA and Germany, to abandon the use of the eponym in favour of a more descriptive name 4. Panush's work also led to the formal retraction, in 2007, of the initial publication that coined this particular eponym 5. It is probably fair to say that there is no coherent approach to these issues within the rheumatology community. Some have disdained its use, whereas others continue the use of …

Objectives: We used whole-lung quantitative CT analysis (QCT)—an objective method of evaluating emphysema severity and distribution based on measurement of lung density—to determine whether subjective selection criteria for lung volume reduction surgery are applied consistently and to model the patient selection process, and assessed the relationship of the model to postoperative outcome. Design: Logistic regression analysis using QCT indexes of emphysema and preoperative physiologic test results as the independent variables, and the decision to operate as the dependent variable. Setting: University hospital. Patients: Seventy patients selected for bilateral lung volume reduction surgery and 32 otherwise operable patients excluded from surgery based on subjective assessment of emphysema morphology on chest radiography, CT, and perfusion scintigraphy. Intervention: Bilateral lung volume reduction surgery in the selected group. Measurements and results: Emphysema in patients selected for surgery was more severe overall and in the upper lungs by multiple QCT indexes (p < 0.01, unpaired two-tailed t test). Physiologic abnormalities were slightly more severe in selected patients (p < 0.05, unpaired two-tailed t test). The range of many QCT and physiologic values overlapped considerably between the selected and excluded groups. The percent severe emphysema (

Hyperpolarized (3)He gas MRI was used to form maps of the effective diffusivity of gas in human lungs. Images of diffusion as well as spin density are presented from a study of 11 healthy volunteers and 5 patients with severe emphysema. The effective rate of diffusion, D(e), of the gas is reduced by the alveolar walls; tissue destruction in emphysema is hypothesized to result in larger D(e). Indeed, the mean value of D(e) in the emphysematous lungs is found here to be about 2.5 times that of healthy lungs, although still smaller than the unrestricted diffusivity of (3)He in free air. Histograms of D(e) values across coronal slices are presented. The results are discussed in terms of spatial variations, variations among individuals, healthy and diseased, and variations due to changes in lung volume. Magn Reson Med 44:174-179, 2000.

We applied the rapid imaging capability of echo planar MR pulse sequences and hyperpolarized 3 He ventilation imaging to observe the dynamic distribution of gas in the lungs during breathing. Findings in five normal volunteers (age 19-53 years) and four patients with severe smoking-related emphysema (age 56-71 years) were compared. All studies were performed on a 1.5 T whole body scanner using a 30 cm Helmholtz surface coil and 0.5 l of 20-40% polarized 3 He mixed with 1-2 l nitrogen. Our echo planar imaging pulse sequence allowed acquisition of each image in 0.04 s, with a pixel size of 7 mm 2 (TR = 40.5 ms, TE = 12.1 ms, flip angle = 22 °, echo train length = 32, matrix = 32 64, field of view = 225 450 mm, slice thickness = 10 mm). Imaging was performed in the transaxial plane repeatedly at 3, 10 or 20 evenly spaced levels, immediately before and during breathing of the gas mixture. In normal subjects during the first breath, 3 He appeared throughout each slice first in the mid lungs, then in the lower lungs, then in the upper lungs, with slightly greater signal in the dependent posterior regions. In patients with emphysema, sequential filling of different lung regions was seen during the first breath, with delayed filling of other regions observed during rebreathing and room air washout. We conclude that subsecond dynamic 3 He MR ventilation imaging can reveal normal and abnormal ventilation phenomena not seen with conventional scintigraphic methods, and offers another approach to the study of ventilation physiology and pathophysiology. Copyright © 2000 John Wiley & Sons, Ltd.

To compare quantitative computed tomographic (CT) and preoperative physiologic values in emphysema with outcome after lung-volume reduction surgery.In 46 patients, emphysema was quantified by measuring lung attenuation on preoperative CT scans. Quantitative CT and preoperative physiologic values and postoperative outcomes (1-second forced expiratory volume, PaO2, and 6-minute walk distance) were compared.Moderately strong correlations were found between several quantitative CT and preoperative physiologic values (magnitude of r = .29-.58, P.05) and several quantitative CT and outcome measures (magnitude of r = .31-.47, P.05). With stratification, postoperative outcome was better with mean lung attenuation greater than -900 HU; 75% or greater of upper lung below -900 HU (emphysema index); greater than 25% of lung below -960 HU (severe emphysema index); ratio of upper- and lower-lung emphysema indexes 1.5 or greater; volume of normally attenuated lung (-850 to -701 HU) greater than 1 L; and full width at half maximum of attenuation-frequency distribution 80 HU or less. Differences in outcome measures between groups stratified with quantitative CT values were often two- to threefold; patients with greater numbers of favorable quantitative CT values had better outcome. Correlations between preoperative physiologic measures and outcome were few.In emphysema, quantitative CT values correlate with outcome. Quantitative assessment of emphysema in candidates for lung-volume reduction surgery is potentially useful.

Between January 1993 and February 1996, we performed 150 bilateral lung volume reduction procedures for patients with severe emphysema. Patients were selected on the basis of severe dyspnea, increased lung capacity, and a pattern of emphysema that included regions of severe destruction, hyperinflation, and poor perfusion. Twenty percent to 30% of the volume of each lung was excised with the use of a linear stapler and bovine pericardial strips attached to buttress the staple line. Patients were between 36 and 77 years old, with an average 1-second forced expiratory volume of 25% of predicted, total lung capacity of 142% of predicted, and residual volume of 283% of predicted. Ninety-three percent of patients required supplemental oxygen, continuously or with exertion. All patients but one were extubated at the end of the procedure. The 90-day mortality was 4%. Hospital stay progressively decreased with experience, and for the last 50 patients the median hospital stay was 7 days. Prolonged air leakage was the major complication. Results at 6 months show a 51% increase in the 1-second forced expiratory volume and a 28% reduction in the residual volume. The Pao 2 increased by an average of 8 mm Hg, and 70% of the patients who had previously required continuous supplemental oxygen no longer had this requirement. The improvements in measured pulmonary function were paralleled by a significant reduction in dyspnea and an improvement in the quality of life. Reevaluation at 1 year and 2 years after operation showed the benefit to be well maintained. We conclude that lung volume reduction offers benefits not achievable by any means other than lung transplantation for highly selected patients with severe emphysema. (J THORAC CARDIOVASC SURG 1996;112:1319-30)

To quantitatively characterize early emphysematous changes in the lung microstructure of current and former smokers with noninvasive helium 3 ((3)He) lung morphometry and to compare these results with the clinical standards, pulmonary function testing (PFT) and low-dose computed tomography (CT).This study was approved by the local institutional review board, and all subjects provided informed consent. Thirty current and former smokers, each with a minimum 30-pack-year smoking history and mild or no abnormalities at PFT, underwent (3)He lung morphometry. This technique is based on diffusion MR imaging with hyperpolarized (3)He gas and yields quantitative localized in vivo measurements of acinar airway geometric parameters, such as airway radii, alveolar depth, and number of alveoli per unit lung volume. These measurements enable calculation of standard morphometric characteristics, such as mean linear intercept and surface-to-volume ratio.Noninvasive (3)He lung morphometry was used to detect alterations in acinar structure in smokers with normal PFT findings. When compared with smokers with the largest forced expiratory volume in 1 second (FEV(1)) to forced vital capacity (FVC) ratio, those with chronic obstructive pulmonary disease had significantly reduced alveolar depth (0.07 mm vs 0.13 mm) and enlarged acinar ducts (0.36 mm vs 0.3 mm). The mean alveolar geometry measurements in the healthiest subjects were in excellent quantitative agreement with literature values obtained by using invasive techniques (acinar duct radius, 0.3 mm; alveolar depth, 0.14 mm at 1 L above functional residual capacity). (3)He lung morphometry depicted greater abnormalities than did PFT and CT. No adverse events were associated with inhalation of (3)He gas.(3)He lung morphometry yields valuable noninvasive insight into early emphysematous changes in alveolar geometry with increased sensitivity compared with conventional techniques.

The purpose of this study was to assess the accuracy of emphysema measurements obtained from systematic samples of evenly spaced CT images compared with measurements obtained from the entire scan.Evenly spaced transverse sections from the CT studies of 136 heavy smokers who underwent screening for lung cancer in the National Lung Screening Trial and of 112 subjects who underwent imaging before lung volume reduction surgery were sampled retrospectively. The samples were acquired both by selection of specific numbers of evenly spaced images and by selection of images at specific distance intervals. The percentage of lung pixels with attenuation below specific thresholds was used as an emphysema index. The image sample error was determined as the difference in emphysema index between the image samples and the entire scan.The largest absolute image sample errors in the National Lung Screening Trial cohort with image sample sizes of five, 10, and 20 were 2.2, 0.8, and 0.5 index percentage points, respectively, at 1-mm section thickness (-960 HU threshold), and 2.6, 1.1, and 0.5 index percentage points at 5-mm section thickness (-930 HU threshold). The largest errors in the lung volume reduction surgery cohort for image sample sizes of five and 10 were 5.6 and 2.3 index percentage points at 8- to 10-mm section thickness (-900 HU threshold). Image sample errors were equivalent for the two sampling methods.Systematic sampling resulted in very small errors in emphysema quantification and may be useful for decreasing radiation exposure in clinical research studies of emphysema.

To evaluate the safety of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging.Local institutional review board approval and informed consent were obtained. Physiologic monitoring data were obtained before, during, and after hyperpolarized (3)He MR imaging in 100 consecutive subjects (57 men, 43 women; mean age, 52 years +/- 14 [standard deviation]). The subjects inhaled 1-3 L of a gas mixture containing 300-500 mL (3)He and 0-2700 mL N(2) and held their breath for up to 15 seconds during MR imaging. Heart rate and rhythm and oxygen saturation of hemoglobin as measured by pulse oximetry (Spo(2)) were monitored continuously throughout each study. The effects of (3)He MR imaging on vital signs and Spo(2) and the relationship between pulmonary function, number of doses, and clinical classification (healthy volunteers, patients with asthma, heavy smokers, patients undergoing lung volume reduction surgery for severe emphysema, and patients with lung cancer) and the lowest observed Spo(2) were assessed. Any subjective symptoms were noted.Except for a small postimaging decrease in mean heart rate (from 78 beats per minute +/- 13 to 73 beats per minute +/- 11, P.001), there was no effect on vital signs. A mean transient decrease in Spo(2) of 4% +/- 3 was observed during the first minute after gas inhalation (P.001) in 77 subjects who inhaled a dose of 1 L for 10 seconds or less, reaching a nadir of less than 90% at least once in 20 subjects and of less than 85% in four subjects. There was no correlation between the lowest Spo(2) and pulmonary function parameters other than baseline Spo(2) (r = 0.36, P = .001). The lowest mean Spo(2) varied by 1% between the first and second and second and third doses (P.001) and was unrelated to clinical classification (P = .40). Minor subjective symptoms were noted by 10 subjects. No serious adverse events occurred.Hyperpolarized (3)He MR imaging can be safely performed in healthy subjects, heavy smokers, and those with severe obstructive airflow limitation, although unpredictable transient desaturation suggests that potential subjects should be carefully screened for comorbidities.

As a result of technological progress and a better understanding of respiratory disease processes, new modes of mechanical ventilation for the critically ill patient have been developed. These new methods may offer specific advantages over traditional techniques by avoiding or reducing complications commonly associated with positive pressure ventilation. A thorough understanding of anticipated benefits and potential problems is carefully considered for each mode of mechanical ventilation. Several alternate approaches to ventilatory assistance are discussed. Clinical applications of nursing care are also discussed

MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema.We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8.Techniques for purging and imaging excised lungs are discussed.

Ethics plays an important, formative role in medical education, stimulating the transformation of a physiologist-scientist into a compassionate and competent clinician. Our clinical ethics program challenges students to observe and recognize inherent value conflicts and understand how such issues must be resolved in their day-to-day work. Advances in biomedical research that hold potential to enhance human health and treat disease are provoking controversial questions of current practices in medical ethics and spawning new, unprecedented ethical dilemmas.

Objective: Numerous reports have confirmed the early benefits of lung volume reduction surgery for selected patients with emphysema. This report documents the long-term survival and functional results after lung volume reduction surgery. Methods: Between January 1993 and June 2000, a total of 250 consecutive patients underwent bilateral lung volume reduction surgery through median sternotomy at our institution. All patients had disabling dyspnea, thoracic hyperinflation, and a heterogeneous pattern of emphysema with suitable target areas for resection. Preoperative pulmonary rehabilitation was required and post-rehabilitation data were used as the baseline for data analysis. Follow-up ranged from 1.8 to 9.1 years (median 4.4 years). Results: Prolonged air leaks (>7 days) were the most common complication (45.2%, n=113). Reexploration rates for air leak and bleeding were 3.2% (n = 8) and 1.2% (n = 3), respectively. Eighteen patients (7.2%) required reintubation and mechanical ventilation. The in-hospital mortality in this series was 4.8% (n = 12). The median length of hospitalization was 9 days (range 4-168 days). Kaplan-Meier survivals after lung volume reduction surgery were 93.6%, 84.4%, and 67.7% at 1, 3, and 5 years, respectively. Eighteen patients (7.2%) have subsequently undergone lung transplantation after a median interval of 4.3 years (range 2.1-6.4 years). Spirometric values, lung volumes, and gas exchange parameters improved after surgery. The forced expiratory volume in 1 second and the residual volume showed statistically significant improvements between preoperative values and each time point of follow-up. Health-related quality of life showed significant postoperative improvement and with time correlated well with the improvement in forced expiratory volume in 1 second. Conclusions: Lung volume reduction surgery produces significant functional improvement for selected patients with emphysema. For most of these patients, benefits appear to last at least 5 years. J Thorac Cardiovasc Surg 2003;125:513-25

The study of lung emphysema dates back to the beginning of the 17th century. Nevertheless, a number of important questions remain unanswered because a quantitative localized characterization of emphysema requires knowledge of lung structure at the alveolar level in the intact living lung. This information is not available from traditional imaging modalities and pulmonary function tests. Herein, we report the first in vivo measurements of lung geometrical parameters at the alveolar level obtained with 3 He diffusion MRI in healthy human subjects and patients with severe emphysema. We also provide the first experimental data demonstrating that 3 He gas diffusivity in the acinus of human lung is highly anisotropic. A theory of anisotropic diffusion is presented. Our results clearly demonstrate substantial differences between healthy and emphysematous lung at the acinar level and may provide new insights into emphysema progression. The technique offers promise as a clinical tool for early diagnosis of emphysema.

Hyperpolarized (3)He gas MRI was used to form maps of the effective diffusivity of gas in human lungs. Images of diffusion as well as spin density are presented from a study of 11 healthy volunteers and 5 patients with severe emphysema. The effective rate of diffusion, D(e), of the gas is reduced by the alveolar walls; tissue destruction in emphysema is hypothesized to result in larger D(e). Indeed, the mean value of D(e) in the emphysematous lungs is found here to be about 2.5 times that of healthy lungs, although still smaller than the unrestricted diffusivity of (3)He in free air. Histograms of D(e) values across coronal slices are presented. The results are discussed in terms of spatial variations, variations among individuals, healthy and diseased, and variations due to changes in lung volume. Magn Reson Med 44:174-179, 2000.

We applied the rapid imaging capability of echo planar MR pulse sequences and hyperpolarized (3)He ventilation imaging to observe the dynamic distribution of gas in the lungs during breathing. Findings in five normal volunteers (age 19-53 years) and four patients with severe smoking-related emphysema (age 56-71 years) were compared. All studies were performed on a 1.5 T whole body scanner using a 30 cm Helmholtz surface coil and 0.5 l of 20-40% polarized (3)He mixed with 1-2 l nitrogen. Our echo planar imaging pulse sequence allowed acquisition of each image in 0.04 s, with a pixel size of 7 mm(2) (TR = 40.5 ms, TE = 12.1 ms, flip angle = 22 degrees, echo train length = 32, matrix = 32 x 64, field of view = 225 x 450 mm, slice thickness = 10 mm). Imaging was performed in the transaxial plane repeatedly at 3, 10 or 20 evenly spaced levels, immediately before and during breathing of the gas mixture. In normal subjects during the first breath, (3)He appeared throughout each slice first in the mid lungs, then in the lower lungs, then in the upper lungs, with slightly greater signal in the dependent posterior regions. In patients with emphysema, sequential filling of different lung regions was seen during the first breath, with delayed filling of other regions observed during rebreathing and room air washout. We conclude that subsecond dynamic (3)He MR ventilation imaging can reveal normal and abnormal ventilation phenomena not seen with conventional scintigraphic methods, and offers another approach to the study of ventilation physiology and pathophysiology.

We used whole-lung quantitative CT analysis (QCT)-an objective method of evaluating emphysema severity and distribution based on measurement of lung density-to determine whether subjective selection criteria for lung volume reduction surgery are applied consistently and to model the patient selection process, and assessed the relationship of the model to postoperative outcome.Logistic regression analysis using QCT indexes of emphysema and preoperative physiologic test results as the independent variables, and the decision to operate as the dependent variable.University hospital.Seventy patients selected for bilateral lung volume reduction surgery and 32 otherwise operable patients excluded from surgery based on subjective assessment of emphysema morphology on chest radiography, CT, and perfusion scintigraphy.Bilateral lung volume reduction surgery in the selected group.Emphysema in patients selected for surgery was more severe overall and in the upper lungs by multiple QCT indexes (p0.01, unpaired two-tailed t test). Physiologic abnormalities were slightly more severe in selected patients (p0.05, unpaired two-tailed t test). The range of many QCT and physiologic values overlapped considerably between the selected and excluded groups. The percent severe emphysema (- 960 Hounsfield units [HU]), upper/lower lung emphysema ratio (- 900 HU threshold), and residual volume were the key variables in the model predicting selection decisions (model r(2) = 0.48; p0.0001). The model correctly predicted selection decisions in 87% of all cases, 91% of the selected group, and 78% of the excluded group. Surgical patients with a higher model-derived probability of selection had greater postoperative improvement in FEV(1) and 6-min walk distance.Radiologic selection criteria are applied consistently to the majority of patients. QCT features are strongly associated with selection decisions, are related to outcome, and may help improve consistency and confidence in patient selection.

Background. Lung volume reduction operation shows promise in relieving symptoms and improving function in highly selected patients with emphysema. Withdrawal of Medicare funding for patients selected for operation by standard criteria created a matched control group with which to compare lung volume reduction recipients. Methods. A retrospective study was done comparing 22 volume reduction candidates denied operation with 65 contemporaneous and comparable volume reduction recipients. Baseline physiologic characteristics were compared and longitudinal measures of pulmonary function were followed up for 24 months. Results. Patients denied operation were similar to volume reduction recipients in all baseline measurements. Patients denied operation experienced a progressive worsening of their function, whereas volume reduction patients experienced sustained improvements. Absolute survival to date is 82% for the surgical group and 64% for the medical group. Conclusions. The improvement seen in volume reduction patients cannot be attributed to the effects of patient selection or preoperative and postoperative rehabilitation.

To identify preoperative pulmonary perfusion scintigraphic findings that might be associated with clinical outcomes after lung volume reduction surgery.Preoperative perfusion scintigrams in 103 patients (56 men, 47 women; age range, 41-76 years; mean age, 61 years +/- 9) were reviewed and graded for emphysematous heterogeneity (from isolated areas to diffuse distribution), extent of maximally perfused lung, and lobar predominance (upper-lobe vs lower-lobe asymmetry). These findings were correlated with clinical outcome on the basis of pulmonary function, arterial blood gas levels, and exercise test results before and 6 months after surgery.Among the 96 patients who survived surgery, there was an average improvement of 47% in the forced expiratory volume in 1 second (FEV1), of 20% in arterial oxygen tension, and of 20% in the 6-minute walking distance. Scintigraphic markers correlated best with FEV1 improvement. The strongest scintigraphic predictor of increase in FEV1 was upper-lobe predominance (r = .38, P.001), which was followed by heterogeneity (r = .31, P = .002). The seven patients who died had a significantly lower percentage of maximally perfused lung than the survivors (25% vs 34%, P = .004).Perfusion scintigraphy can provide modest prognostic information in patients who undergo evaluation for lung volume reduction surgery.

The efficacy of lung volume reduction surgery has been demonstrated by improvements in functional status, dyspnea, pulmonary function, alveolar gas exchange, and exercise tolerance. However, surgery has a significant morbidity, mortality, and cost. Surgical outcome is dependent on the clinical, anatomical, and physiological features of the patients and their emphysema. Therefore, the patient evaluation process and the preoperative optimization of medical therapy are crucial for success. Through understanding mechanisms for improvement have added insight to the selection process, patient selection needs further clarification.

▪ Abstract Volume reduction surgery is based on the removal of volume-occupying but nonfunctioning emphysematous lung, which is thought to improve pulmonary elastic recoil. The reduction in thoracic volume may also improve thoracic cage and inspiratory muscle function. In addition, dyspnea is lessened, exercise tolerance is increased, and measured pulmonary function is improved. Alveolar gas exchange may also be improved. Selection criteria include marked airway obstruction secondary to emphysema, marked hyperinflation of the chest wall, and regional heterogeneity in the distribution of the emphysema. The best results are obtained with a bilateral procedure utilizing stapling resection. The two surgical approaches are median sternotomy and video-assisted thoracic surgery.

There has been dramatic resurgence of interest in surgical treatment of emphysema, particularly "lung volume reduction" procedures. Recent studies have demonstrated improvements in pulmonary function, lung mechanics, exercise tolerance, and quality of life in selected patients following volume reduction procedures. However, considerable uncertainty remains regarding overall benefit, optimal patient selection, operative techniques, and duration of response. This summarizes current approaches to lung volume reduction surgery, available clinical outcome information, selection criteria, and physiologic mechanisms of response, and discusses the potential role for surgical volume reduction in treatment of emphysema. Recent data appear to support the efficacy of bilateral staple lung volume reduction surgery in patients with severe symptomatic heterogeneously distributed emphysema. Further studies will be needed to determine relative value of different operative techniques and benefit in patients with other clinical presentations.

Lung-reduction surgery (LVRS) for patients disabled by emphysema is based on a concept proposed by Brantigan ' 40 years ago that dyspnoea in emphysemic patients might be improved by a reduction in the size of the hyperinflated lung. This proposal has proved to be essentially correct. LVRS, or the resection of functionless areas of the lung, improves dyspnoea by restoration of elastic recoil, which in turn stabilises intraparenchymal airways; by restoration to normal of the position of the diaphragm and rib cage, which improves respiratory mechanics and muscle function; by a decrease in dynamic hyperinflation and intrinsic positive end-expiratory [ pressure; and by a reduction in respiratory drive. When LVRS was introduced it was recognised to be a palliative procedure applicable to a small Cordova12 minority of patients with DanieF emphysema. The duration Date16 Kotlof-P s of benefit following LVRS McKenna 1° was uncertain in view of Miller11 the natural history of Snell~3 progressive deterioration of severe emphysema. Furthermore, the impact on survival could not be anticipated, given the risk of major pulmonary surgery in this group of patients. Now, 5 years after we reported our initial experience with LVRS for patients disabled hy emphysema, ~ some perspective can be cast on the role and value of the procedure. Of the original 20 patients, one has died from hepatic cancer. In the remaining 19, the initial benefit achieved has gradually declined but, on objective and subjective criteria, most of them continue to be better than they were pre-operatively. Reference Year n Surgery Mean increase in FEV1

In Reply. —Dr Carlen's letter quite correctly discusses the indications for isoniazid prophylaxis in close contacts of children with tuberculosis whose initial tuberculin tests are negative. The article to which he is referring was discussing the interpretation of tuberculin testing in elderly patients and not the indications for isoniazid prophylaxis, especially in children. I certainly agree that children, particularly infants, should receive isoniazid prophylaxis if they are close contacts of patients with tuberculosis, regardless of their initial tuberculin test results. Although one could argue this point for adults, it seems reasonable to begin isoniazid prophylaxis initially and repeat the tuberculin test in 4 to 6 weeks and judge continuation of treatment at that point.

The shape and position of the oxyhemoglobin dissociation curve contribute to efficient transport of oxygen from the lungs to the tissues. In the past several years, factors affecting the position of the oxyhemoglobin dissociation curve in many disease states have been studied, and the important role of 2,3-diphosphoglycerate (2,3-DPG) in mediating alterations in the affinity of blood for oxygen has been repeatedly confirmed. At present, the effects of blood pH and blood oxygenation on levels of 2,3-DPG and on the oxygen affinity of blood are well established; on the other hand, precise prediction of the position of the oxyhemoglobin dissociation curve in complex disease states is not yet possible.

Over a 6 year period, three cases of pulmonary carcinoma in young men with severe bullous lung disease were seen at Washington University Medical Center. The patients did not have a long cigarette-smoking exposure. It would seem that patients with severe bullous lung disease are at a higher risk for the development of pulmonary neoplasm than the general population. Physicians should be aware of this association to expedite diagnosis and therapy.

Isoniazid therapy has been proved an effective means of preventing overt clinical tuberculosis in persons with positive tuberculin skin tests, persons who are close contacts of active cases, and persons with inactive tuberculosis that were never treated. The administration of isoniazid in standard dosage for one year in these situations will help greatly to reduce tuberculosis as a community health problem in the future. Studies in recent years, however, point to hepatic dysfunction as a complication of isoniazid therapy in up to 10% of patients. In a few patients, liver disease as a complication of this therapy has been fatal. The likelihood of this complication increases with age. Accordingly, isoniazid chemoprophylaxis should be undertaken with the understanding that the patient has to be followed up closely, especially for evidence of liver disease during the course of therapy. This potentially serious side effect suggests that isoniazid chemoprophylaxis should be used primarily with patients in high risk groups.

Hypoxemia is a frequent occurrence in patients with severe hepatic disease. Multiple mechanisms have been implicated in the production of such hypoxemia. The case of a 35-year-old man with cyanosis, clubbing, and cirrhosis is presented. Physiologic data from this patient revealed normal pulmonary function, except for a low diffusing capacity and a 28 percent shunt while the patient was breathing 100 percent oxygen. A perfusion scan with radioactive 99m technetium-labelled macroaggregated albumin revealed 67 percent of the labelled macroaggregated albumin in the systemic circulation. Postmortem examination demonstrated normal pulmonary parenchyma, markedly dilated intraparenchymal capillaries and arterioles, subpleural angiomata, and cirrhosis. No anatomic arteriovenous connections were demonstrated before or after death. We conclude that the arterial hypoxemia of some patients with hepatic cirrhosis results from dilated gas-exchanging blood vessels. These widened vessels prevent end pulmonary capillary oxygen tension from reaching equilibrium with alveolar gas, perhaps because of the widened distance for diffusion.

Objectives A report from the National Emphysema Treatment Trial indicated that lung volume reduction candidates with a forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of 20% or less of predicted value were at high risk for mortality and were unlikely to benefit from surgical intervention. This article examines the applicability of the National Emphysema Treatment Trial findings to our own patients. Methods We reviewed 280 patients who underwent bilateral lung volume reduction surgery at our institution between January 1993 and December 2001. All patients met our selection criteria, including heterogeneous distribution of emphysema. Of these 280 patients, 20 patients had both a preoperative forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of less than or equal to 20% of the predicted normal values, thus meeting one National Emphysema Treatment Trial criterion for high risk. Outcomes of the 20 patients were assessed through 5 years after the operation. The survival of the 20 patient cohort was compared with that of the 260 patients not meeting the National Emphysema Treatment Trial high-risk criterion. Results Ninety-day operative mortality included 1 (5%) patient. In all patients the forced expiratory volume in 1 second increased from 0.46 L (17%) to 0.78 L (32%), a 73% change; the diffusing capacity of carbon monoxide increased from 16% to 27%, a 70% improvement; residual volume decreased from 6.33 L (305%) to 4.26 L (205%), a 33% improvement; and room air arterial partial pressure of oxygen increased from 55 mm Hg to 64 mm Hg. Kaplan-Meier 5-year survivals did not differ between the high-risk and non–high-risk groups. Conclusions Patients with a forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of 20% or less of predicted value might experience improvements in lung function, exercise tolerance, and quality of life with acceptable morbidity and mortality after lung volume reduction surgery.

Objective: Between January 1993 and May 1998, we performed 200 consecutive bilateral lung volume reduction operations. After initial assessment, 99 of these patients were eligible for lung volume reduction and potentially eligible for immediate or eventual lung transplantation on the basis of age and absence of contraindications. All chose to proceed with lung volume reduction surgery. The outcomes of these 99 patients are reviewed to assess the consequences of proceeding with lung volume reduction surgery on patients potentially eligible for lung transplantation. Methods: A retrospective study was performed with the use of a prospectively assembled computer database. Results: The 61 men and 38 women were 55 ± 7 years old at evaluation for lung volume reduction. Mean values for first second expired volume, total lung capacity, and residual volume were 24% ± 8%, 141% ± 19%, and 294% ± 54% predicted. There were 4 operative deaths and 17 late deaths. Two-year and 5-year survival after evaluation for lung volume reduction are 92% and 75%. The 32 patients who have been listed for transplantation after lung volume reduction include 15 who have undergone transplantation, 14 who remain on the list, and 3 who have been removed from the list. All 15 transplant recipients survived transplantation and 3 have subsequently died of rejection or late infection. The 12 living recipients have a median post-transplantation follow-up of 1.7 years. The age at transplantation was 58 ± 5 years with transplantation occurring 3.8 ± 1.1 years after lung volume reduction. Sixteen of 99 patients underwent lower lobe volume reduction with an increased rate of listing (63%, P =.008) and transplantation (38%, P =.003) compared with patients undergoing upper lobe volume reduction. Patients listed for transplantation were younger, more impaired, and experienced less benefit from lung volume reduction than patients not yet listed for transplantation. Conclusions: The preliminary use of lung volume reduction in patients potentially suitable for transplantation does not appear to jeopardize the chances for subsequent successful transplantation. J Thorac Cardiovasc Surg 2001;122:10-7

Accurate determination of the resting energy expenditure (REE) for patients in intensive care units has assumed increasing importance as the adverse effects of underfeeding or overfeeding have become clearer. As a result, indirect calorimetry is frequently used to determine the REE. This technique, however, is neither universally available nor inexpensive. Furthermore, it requires meticulous measurements of gas exchange and technical expertise. Because of this, we have developed a method to determine REE for those patients in intensive care units who have thermodilution pulmonary artery catheters in place. This method requires determining the oxygen consumption from data obtained from such a catheter. The REE is then calculated by multiplying the determined oxygen consumption by the caloric value for oxygen (4.86 kcal/L at a nonprotein respiratory quotient of 0.85). We made 20 simultaneous measurements of REE, comparing our method with indirect calorimetry in 19 patients. There was excellent agreement between both methods (r = 0.90; p less than 0.0001). Therefore, for those patients in intensive care units who require thermodilution pulmonary artery catheters, this method will allow accurate determination of REE and thus caloric requirements, without the need for indirect calorimetry using measurements of gas exchange.