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Improvement in pulmonary function and elastic recoil after lung-reduction surgery for diffuse emphysema.

BACKGROUND: Pulmonary function may improve after surgical resection of the most severely affected lung tissue (lung-reduction surgery) in patients with diffuse emphysema. The basic mechanisms responsible for the improvement, however, are not known. METHODS: We studied 20 patients with diffuse emphysema before and at least three months after either a unilateral or a bilateral lung-reduction procedure. Clinical benefit was assessed by measurement of the six-minute walking distance and the transitional-dyspnea index, which is a subjective rating of the change from base line in functional impairment and the threshold for effort- and task- dependent dyspnea. Pressure-volume relations in the lungs were measured with static expiratory esophageal-balloon techniques, and right ventricular systolic function was assessed by echocardiography. RESULTS: The patients had significant improvement in the transitional-dyspnea index after surgery (P<0.001). The mean (+/-SD) coefficient of retraction, an indicator of elastic recoil of the lung, improved (from 1.3+/-0.6 cm of water per liter before surgery to 1.8+/-0.8 after, P<0.001). Sixteen patients with increased elastic recoil had a greater increase in the distance walked in six minutes than the other four patients, in whom recoil did not increase (P=0.02). The improved lung recoil led to disproportionate decreases in residual volume as compared with total lung capacity (16 percent vs. 6 percent), but the decreases in both values were significant (P<0.001). Forced expiratory volume in one second increased (from 0.87+/-0.36 to 1.11+/-0.45 liters, P<0.001). End-expiratory esophageal pressure also decreased (P=0.002). These improvements in lung mechanics led to a decrease in arterial partial pressure of carbon dioxide form 42+/-6 to 38+/-5 mm Hg (P=0.006). Furthermore, the fractional change in right ventricular area, an indicator of systolic function, increased from 0.33+/-0.11 to 0.38+/-0.010 (P=0.02). CONCLUSIONS: Lung-reduction surgery can produce increases in the elastic recoil of the lung in patients with diffuse emphysema, leading to short-term improvement in dyspnea and exercise tolerance.

Adult↗

Effect of lung-volume-reduction surgery in patients with severe emphysema.

BACKGROUND: Although many patients with severe emphysema have undergone lung-volume-reduction surgery, the benefits are uncertain. We conducted a randomized, controlled trial of the surgery in patients with emphysema. Patients with isolated bullae were excluded because such patients are known to improve after bullectomy. METHODS: Potentially eligible patients were given intensive medical treatment and completed a smoking-cessation program and a six-week outpatient rehabilitation program before random assignment to surgery or continued medical treatment. After 15 patients had been randomized, the entry criteria were modified to exclude patients with a carbon monoxide gas-transfer value less than 30 percent of the predicted value or a shuttle-walking distance of less than 150 m, because of the deaths of 5 such patients (3 treated surgically and 2 treated medically). RESULTS: Of the 174 subjects who were initially assessed, 24 were randomly assigned to continued medical treatment and 24 to surgery. At base line in both groups, the median forced expiratory volume in one second (FEV1) was 0.75 liter, and the median shuttle-walking distance was 215 m. Five patients in the surgical group (21 percent) and three patients in the medical group (12 percent) died (P=0.43). After six months, the median FEV1 had increased by 70 ml in the surgical group and decreased by 80 ml in the medical group (P=0.02). The median shuttle-walking distance increased by 50 m in the surgical group and decreased by 20 m in the medical group (P=0.02). There were similar changes on a quality-of-life scale and similar changes at 12 months of follow-up. Five of the 19 surviving patients in the surgical group had no benefit from the treatment. CONCLUSIONS: In selected patients with severe emphysema, lung-volume-reduction surgery can improve FEV1, walking distance, and quality of life. Whether it reduces mortality is uncertain.

Adrenergic beta-Agonists↗

Superiority of end-to-end versus telescoped bronchial anastomosis in single lung transplantation for pulmonary emphysema.

OBJECTIVE: To assess the influence of surgical technique (telescoped versus end-to-end anastomosis) on the incidence of bronchial anastomotic complications in patients who underwent single lung transplantation for pulmonary emphysema. METHODS: Seventy-six adult recipients of single lung transplants for pulmonary emphysema were evaluated for the presence of 3 types of major bronchial anastomotic complications: ischemia, dehiscence, and severe stenosis. Surgical technique, clinical course, and mortality were reviewed retrospectively. RESULTS: The 3 major complications were observed in 11 (34%; ischemia), 8 (25%; dehiscence), and 11 (34%; severe stenosis) of 32 telescoped bronchial anastomoses. In contrast, ischemia, dehiscence, and severe stenosis occurred in only 4 (9%), 1 (2%), and 2 (5%) of 44 end-to-end anastomoses (P =.0087, P =.0034, and P =.0012, respectively). The relative risk of ischemia, dehiscence, and severe stenosis in telescoped anastomoses was 2.1, 2.5, and 2.5, respectively, compared with end-to-end anastomoses. Five (13%) telescoped anastomoses required stent placement as compared with only 2 (5%) end-to-end anastomoses (P =.1244). Early postoperative pneumonia was more common in the telescoped anastomosis group (56%) than in the end-to-end group (32%; P =.0380). There was a trend toward shorter survival in the telescoped anastomosis group (mean survival 1045 +/- 145 days) as compared with the end-to-end group (mean survival 1289 +/- 156 days), but these differences did not achieve statistical significance (P =.2410). CONCLUSIONS: In patients who underwent single lung transplantation for pulmonary emphysema, telescoped anastomoses were associated with a higher incidence of bronchial anastomotic complications than end-to-end anastomoses.

Adult↗

Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema.

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.

Aged↗

Direct interactions between nitrous oxide and exogenous pulmonary surfactant in vitro.

During inhalation anesthesia, lung alveolar and Clara cells are exposed directly to volatile anesthetic. Porcine-derived natural lung surfactant (Curosurf) was used for in vitro measurements of surface activity under exposure to N2O mixed with air at concentration used in prolonged anesthesia. The study suggests that prolonged use of N2O may be associated with increased value of the minimum surface tension and reduction of surface tension-bubble radius hysteresis obtained in the pulsating bubble surfactometer used in the experiments. These phenomena indicate the physicochemical inactivation of surfactant.

Animals↗

Airway inflammation in cadmium-exposed rats is associated with pulmonary oxidative stress and emphysema.

The aim of this study was to test the hypothesis that pulmonary inflammation and emphysema induced by cadmium (Cd) inhalation are associated with pulmonary oxidative stress. Two groups of Sprague Dawley rats were used: one vehicle-exposed group undergoing inhalation of NaCl (0.9%, n = 24) and one Cd-exposed group undergoing inhalation of CdCl(2) (0.1%, n = 24). The animals in the vehicle-and Cd-exposed groups were divided into 4 subgroups (n = 6 per group), which underwent either a single exposure (D2) of 1H or repeated exposures 3 times/week for 1H for a period of 3 weeks (3W), 5 weeks (5W) or 5 weeks followed by 2 weeks without exposure (5W + 2). At sacrifice, the left lung was fixed for histomorphometric analysis (median inter-wall distance, MIWD), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. Cytological analysis of BALF was performed and BALF was analysed for oxidant markers 8-iso-PGF(2a), uric acid (UA), reduced (AA) and oxidised ascorbic acid (DHA) and reduced (GSH) and oxidised glutathione (GSSG). Cd-exposure induced a significant increase of BALF macrophages and neutrophils. 8-iso-PGF(2a), UA, GSH and GSSG were significantly increased at D2. At 5W and 5W + 2, AA and GSH were significantly lower in Cd-exposed rats, indicating antioxidant depletion. MIWD significantly increased in all repeatedly Cd-exposed groups, suggesting development of pulmonary emphysema. 8-iso-PGF(2a) and UA were positively correlated with macrophage and neutrophil counts. GSH, GSSG and 8-iso-PGF(2a) were negatively correlated with MIWD, indicating that Cd-induced emphysema could be associated with pulmonary oxidative stress.

Animals↗

Buttressing staple lines with bovine pericardium in lung resection for bullous emphysema.

The utility of buttressing an endoscopic mechanical stapler with strips of bovine pericardium in resection of pulmonary bullous areas was evaluated by comparing the duration of air leakage in two randomized patient groups, one with and one without buttressing. The duration of air leakage was not related to bulla size in either group but showed a linear relation with the radiologic emphysema score in both groups (p < 0.001) and was shorter when the stapler had been fitted with bovine pericardium, but significantly reduced (p = 0.019) only in patients with a high emphysema score. The duration of air leakage was thus related to emphysema score, and in patients with high scores was shortened by application of bovine pericardium to the stapler.

Adult↗

Respiratory function responses of animals and man to oxidant gases and to pulmonary emphysema.

Data on the respiratory functional responses of animals and humans to inhaled oxidant gases and to pulmonary emphysema were reviewed and compared. Comparisons included responses to short-term inhalation of ozone, nitrogen dioxide, and oxygen and the functional manifestations of chronic emphysema. The comparisons illustrated that animals and humans have qualitatively similar functional responses to the irritant, bronchoconstrictive, and sensitizing effects of acutely inhaled ozone and nitrogen dioxide. Animals and humans responded similarly to the inflammatory and edematous effects of inhaled oxygen. Similar changes in maximal expiratory flow-volume curves, pressure-volume curves, lung volumes, and alveolar-capillary gas exchange occurred in animals and humans with emphysema. These results suggest that similar respiratory functional changes occur in both animals and humans when similar morphological changes result from lung injury. This observation lends confidence to the use of laboratory animals in studies to predict the effects of long-term exposure of humans to inhaled oxidant gases.

Aged↗

An inhaled matrix metalloprotease inhibitor prevents cigarette smoke-induced emphysema in the mouse.

Inadequately regulated proteolytic activity is responsible for the chronic lung tissue degeneration and irreversible loss of pulmonary function that define emphysema. In this study, we show that an inhaled broad-spectrum matrix metalloprotease inhibitor, ilomastat, can provide protection against the development of emphysema in cigarette smoke-treated mice. Control animals were exposed to daily cigarette smoke for 6 months. As has been reported previously, cigarette smoke was seen to increase significantly the recruitment of macrophages into the lungs of these animals, leading to concomitant alveolar airspace enlargement and emphysema. In animals treated daily with nebulized ilomastat for 6 months, lung macrophage levels were greatly reduced, and neutrophil accumulation was also inhibited. Corresponding reductions in airspace enlargement of up to 96% were observed. These striking observations suggest that delivery of ilomastat directly into the lungs of smoke-treated mice can not only inhibit lung tissue damage mediated by metalloproteases, but may also reduce that component of tissue degeneration mediated by excess neutrophil-derived products. Our data also suggest that the matrix metalloprotease inhibitors may represent a class of drugs that, when delivered by inhalation, could be used practically to treat cigarette smoking-related chronic obstructive pulmonary disease by modifying the course of the disease.

Administration, Inhalation↗

Lung volume reduction surgery (LVRS) for emphysema: initial experience at the University Hospital Gasthuisberg. Leuven LVRS Group.

Emphysema is a disabling disease, for which there is no curative therapy available today. Lung transplantation offers a valuable option for a very selected number of patients, however, due to the enormous organ shortage, only few patients can be offered such a therapy. Recently there has been important resurgence of interest in lung volume reduction surgery and as a consequence, we have embarked in such a program since may 1997. We have now performed unilateral lung volume reduction surgery in 29 emphysema patients (25 on the right and 4 on the left side). Twenty-four patients were already discharged home. There has been no perioperative mortality. The mean hospital stay was 19.8 +/- 11.4 days (range, 8-47 d). Twenty patients of whom we already have follow-up data during 6 months (m) form the further basis of this report. Six weeks after the procedure the FEV1 increased from 0.82 +/- 0.28 L (28 +/- 8%) to 1.05 +/- 0.39 L, a mean increase of 28%. There was a further increase of the FEV1 to a maximum of 1.06 +/- 0.42 L at 6 m, a mean maximum increase of 29% (p = 0.0046, ANOVA). Similarly, the FVC increased from 2.80 +/- 1.10 L to 3.15 +/- 1.00 L, a mean increase of 12.5%. A further increase was also obtained at 6 m and was 19.6% (3.35 +/- 1.05 L, p = 0.014, ANOVA). The maximum decrease in RV was obtained at 3 m (from 5.91 +/- 1.37 L to 4.37 +/- 0.85 L (p = 0.0001, ANOVA), a mean decrease of 26%. The maximum TLC decrease was demonstrated at 3 m (from 8.71 +/- 1.71 L to 7.60 +/- 1.56 L (p = 0.002, ANOVA), a mean decrease of 12.8%. Afterwards there was again a gradual raise of the TLC. The six minute walking distance increased from 231 +/- 31 m to 272 +/- 34 m (p = NS) after pulmonary rehabilitation and to 416 +/- 77 m at 3 m and 415 +/- 18 m at 6 m (p = 0.0002, ANOVA) after the operation. The quality of life (measured with a standardized questionnaire, the Nottingham Health Profile) improved significantly in several domains (e.g. mobility, pain, energy, emotions and social) at 3 m postoperatively. There was one late death (at 6 m) due to an unknown cause. The actuarial survival rate was therefore 100% at 3 m and 95% at 12 m. In conclusion, unilateral thoracoscopic lung volume reduction surgery is a new and safe treatment modality for patients suffering from severe end-stage emphysema. The objective and subjective improvement is marked and the mortality is very low. Rigid selection criteria are, however, necessary to be able to guarantee an optimal result.

Actuarial Analysis↗

Application of electrical impedance tomography in diagnosis of emphysema--a clinical study.

In this paper, electrical impedance tomography (EIT) ventilation images from a group of 12 patients (11 patients with emphysema and one patient with only chronic obstructive pulmonary disease (COPD) (chronic bronchitis) and a group of 15 normal subjects were acquired using a Sheffield mark 1 EIT system, at the levels of second, fourth and sixth intercostal spaces. Patients were diagnosed based on CT scans of the thorax, pulmonary function tests and posteroanterior x-ray graphs. One of the patients with emphysema has also a malignant lung tumour. Ventilation-related conductivity changes at total lung capacity (TLC) relative to residual volume were measured quantitatively in EIT images. These quantitative values demonstrate marked differences compared to those values obtained from the EIT images of 15 normal subjects. The EIT images of the patients were also compared with the CT images. In addition to the visual examination of the EIT images a statistical confidence test is applied to compare the images of the patients with the images of the normal subjects. Prior to statistical analysis all images are normalized with TLC to minimize the effect of mismatch between the TLC of different subjects. A normal mean image is created by averaging the normalized images from the normal subjects, at each intercostal space level. Than a 95% confidence interval is defined for each normal mean image. For each image of the patients, a confidence test image, which represents the deviations from the 95% confidence interval of the normal mean image, is created. The regions with emphysematous bulla and parencyhma are detectable in the confidence test images as regions of positive and negative deviations from the confidence interval of the normal mean, respectively. In the test images, it is possible to differentiate emphysematous parenchyma from emphysematous bulla, tumour structure, and COPD. However, the emphysematous bulla, the tumour structure, and COPD result in the same type of defect in the test images and are therefore indistinguishable from each other. In some case, off-plane contributions in the EIT images may result in underestimation of the defects. EIT may be a useful screening device in detecting emphysema rather than a diagnostic tool.

Adult↗

Opposing effects of emphysema, hay fever, and select genetic variants on lung cancer risk.

The authors compared histories of nonmalignant respiratory diseases (asthma, bronchitis, emphysema, hay fever, and pneumonia) in 1,553 lung cancer patients and 1,375 healthy controls enrolled in a Texas case-control study from 1995 to 2003. They incorporated data on two biologically relevant polymorphic genes, matrix metalloproteinase-1 and myeloperoxidase. Emphysema was associated with a statistically significant increased lung cancer risk (odds ratio (OR) = 2.87, 95% confidence interval (CI): 2.20, 3.76), while hay fever had a significant protective effect (OR = 0.58, 95% CI: 0.48, 0.70). Odds ratios were consistent after exclusion of respiratory disease diagnoses made up to 10 years before interview. There was little association between other respiratory diseases and lung cancer risk. Among carriers of "protective" genotypes, emphysema was associated with a 1.7-fold increased risk (95% CI: 0.84, 3.50), as compared with the substantially higher risk for persons possessing one (OR = 4.98, 95% CI: 2.94, 8.44) or two (OR = 4.23, 95% CI: 1.84, 9.73) "adverse" genotypes. For hay fever, significantly decreased risks were evident with one (OR = 0.32, 95% CI: 0.21, 0.50) or two (OR = 0.35, 95% CI: 0.19, 0.66) protective genotypes as compared with none (OR = 0.69, 95% CI: 0.30, 1.59). The biologic role of respiratory disease in lung cancer is unclear. Further study may yield new insights for identification of susceptible subgroups.

Asthma↗

Titanium dioxide nanoparticles induce emphysema-like lung injury in mice.

Titanium dioxide nanoparticles (nanoTiO2) have been widely used as a photocatalyst in air and water cleaning. However, these nanoparticles inhalation can induce pulmonary toxicity and its mechanism is not fully understood. In this study we investigated the pulmonary toxicity of nanoTiO2 and its molecular pathogenesis. The adult male ICR mice were exposed to intratracheal single dose of 0.1 or 0.5 mg nanoTiO2 (19-21 nm) and lung tissues were collected at 3rd day, 1st wk, and 2nd wk for morphometric, microarray gene expression, and pathway analyses. NanoTiO2 can induce pulmonary emphysema, macrophages accumulation, extensive disruption of alveolar septa, type II pneumocyte hyperplasia, and epithelial cell apoptosis. NanoTiO2 induced differential expression of hundreds of genes include activation of pathways involved in cell cycle, apoptosis, chemokines, and complement cascades. In particular, nanoTiO2 up-regulates placenta growth factor (PlGF) and other chemokines (CXCL1, CXCL5, and CCL3) expressions that may cause pulmonary emphysema and alveolar epithelial cell apoptosis. Cultured human THP-1 cell-derived macrophages treated with nanoTiO2 in vitro also resulted in up-regulations of PlGF, CXCL1, CXCL5, and CCL3. These results indicated that nanoTiO2 can induce severe pulmonary emphysema, which may be caused by activation of PlGF and related inflammatory pathways.

Animals↗

Pulmonary emphysema: current concepts of pathogenesis.

Pulmonary emphysema is a major public health problem and is primarily a disease of smokers. The pathogenesis of emphysema in smokers is likely to be multifactorial and may involve protease-antiprotease imbalance, abnormal host response to injury, the inactivation of antiproteases by oxidants, and direct damage of lung tissue by pulmonary phagocytes. The data regarding current concepts of pathogenesis of emphysema in smokers are reviewed in this article.

Blood Proteins↗

Reduction pneumonoplasty for emphysema. Early results.

OBJECTIVE: The authors determined the role of Nd:YAG laser reduction pneumonoplasty for selected patients with diffuse emphysema. SUMMARY BACKGROUND DATA: The study is based on the concepts introduced 30 years ago by Brantigan regarding the value of lung reduction surgery in patients with emphysema. The authors used minimally invasive techniques with the hopes of providing appropriate clinical results with the least surgical morbidity. METHODS: Fifty-five patients with advanced symptomatic emphysema were treated with unilateral Nd:YAG laser reduction pneumonoplasty to achieve lung volume reduction. RESULTS: Patients experienced significant improvement in exercise capacity and relief of breathlessness. This correlated with improvement in objective measures of pulmonary function and with reduction in lung volume by radiographic and spirometric measures. Significant associated hospital morbidity and a 5.5% mortality were associated. CONCLUSIONS: These encouraging results with treatment of only one lung will be built on with both sequential lung and simultaneous, bilateral lung treatment protocols.

Humans↗

Pulmonary interstitial emphysema in the adult respiratory distress syndrome.

Chest x-rays of 15 patients with the adult respiratory distress syndrome (ARDS) were evaluated retrospectively for the presence of pulmonary interstitial emphysema (PIE). PIE was radiographically detected in 13 (88%) patients, 10 (77%) of whom also had pneumothorax. In five of these, pneumothorax occurred within the first 12 h after interstitial emphysema appeared. Pneumomediastinum was less common and occurred in five (39%) patients. The appearance of PIE and its complications, i.e., pneumothorax and pneumomediastinum, occurred over a wide range of mean airway pressures and positive end-expiratory pressures; there was no direct relationship between barotrauma and mean airway pressure or positive end-expiratory pressure. In 12 of the 13 patients all manifestations of barotrauma occurred at or above a peak airway pressure of 40 cm H2O, indicating a threshold level of peak airway pressure which would place the ARDS patient at high risk for developing pulmonary barotrauma. Time on the respirator at peak airway pressures above 40 cm H2O, clinical severity of ARDS, and associated pulmonary pathology (emphysema, bacterial pneumonia) appear to play a role in developing barotrauma.

Adolescent↗

Assessment of the progression of emphysema by quantitative analysis of spirometrically gated computed tomography images.

RATIONALE AND OBJECTIVES: The authors assessed the progression of pulmonary emphysema by means of quantitative analysis of computed tomography images. METHODS: Twenty-three patients suffering from emphysema due to an alpha 1-antitrypsin deficiency, aged 45 +/- 7 years and exsmokers, were scanned twice with a 1-year time interval. At 90% of the vital lung capacity, slices with a thickness of 1.5 mm were acquired at the level of the carina and 5 cm above the carina; slices with a thickness of 1 cm were acquired 5 cm below the carina. The entire lung was scanned spirally at a respiratory status, corresponding with 75% of the total lung capacity at baseline. The mean lung densities (MLD) were calculated in an objective manner with new analytic software featuring automated detection of the lung contours. RESULTS: Mean lung densities decreased by 14.2 +/- 12.0 Hounsfield units (HU; P < 0.001) above the carina, by 18.1 +/- 14.4 HU (P < 0.001) at the carina level, by 23.6 +/- 15.0 HU (P < 0.001) below the carina, and by 12.8 +/- 22.2 HU (P < 0.01) for the entire lung. The decrease in MLD was most obvious in the lower lung lobes. For the same patient group, the annual decrease in the forced expiratory volume (FEV1) and the carbon monoxide-diffusion were 120 +/- 190 mL (P < 0.01) and 10 +/- 70 mmol/kg/minute ( P < 0.2), respectively. No significant correlation was found between the decrease in MLD and the decrease in FEV1. CONCLUSIONS: Progression of emphysema can be assessed in an objective manner based on the mean lung density (MLD), measured from computed tomography volume scans as well as from single-slice scans. Mean lung density has proved to be more sensitive than FEV1 and carbon monoxide-diffusion.

Adult↗

On defining microcardia: application in pulmonary emphysema.

Pulmonary emphysema was the disease entity from which we derived a definition for microcardia in males. After the fourth decade, a cardiothoracic ratio of 38% or less is considered to represent a small heart. Among male Veterans Hospital patients between the ages of 41 and 83, the probability of an individual without emphysema having a cardiothoracic ratio of 38% or less was under 1%. Microcardia, even as an isolated sign, should make one suspect strongly the presence of subclinical emphysema and to consider instituting a prophylactic regimen. Hearts should be measured to judge not only increased size but decreased size in both patient and examinee groups.

Adult↗