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Rapidly progressive emphysema developed in a 59 year old smoker after exposure to cadmium fumes in a factory. Very high levels of cadmium in air sampled at the workplace and in the patient's blood, urine, and lung tissue confirmed massive exposure. These data strongly suggest an association between the patient's cadmium exposure and the development of emphysema.
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.
PURPOSE: To quantitatively evaluate hyperpolarized helium 3 ((3)He) diffusion magnetic resonance (MR) images of the lung in patients with emphysema and to determine whether apparent diffusion coefficients (ADCs) measured with MR imaging correlate with spirometric indexes. MATERIALS AND METHODS: Hyperpolarized (3)He diffusion MR imaging was performed in 16 healthy volunteers and 11 patients. Coronal diffusion-sensitized MR images were obtained during suspended respiration after inhalation of laser-polarized (3)He gas, and images of the ADC were calculated. Spirometry was performed immediately before imaging. The mean and SD of the ADCs were compared between subject groups and were correlated with spirometric indexes. RESULTS: ADC images were homogeneous in volunteers, but demonstrated regional variations in patients. The mean and SD of the ADCs for patients were significantly larger (P <.002) than those for volunteers. The mean ADCs for all subjects correlated with the percentage of predicted forced expiratory volume in 1 second, or FEV(1), (r = -0.797, P <.001) and the ratio of FEV(1) to forced vital capacity, or FVC, (r = -0.930, P <.001). ADC images in patients demonstrated a significant increase (P <.001) in the ADCs in the upper regions compared with the lower regions of the lung. CONCLUSION: Hyperpolarized (3)He diffusion MR imaging demonstrated potential for use in evaluating the global and regional severity of emphysema.
Through the use of diffusion-weighted 3He MR imaging, Fain et al in this issue of Radiology demonstrated the potential for detection of early emphysema in the lungs of healthy smokers. The technique possibly could become an important tool for understanding the pulmonary processes that occur with emphysema, for implementing treatment before clinical symptoms occur, and for monitoring the effect of treatment.
Persistent foci of tension pulmonary interstitial emphysema (TPIE) may represent a clinically significant threat to the neonate with bronchopulmonary dysplasia. A 5-year experience with 21 cases of TPIE is reported. These patients were treated with lateral decubitus positioning (LDP). The emphysematous side was placed down approximately 70% of the time for an average of slightly over 3 days. Progress was followed by serial chest radiographs. The overall success rate of LDP was 90%. Respiratory status either improved or remained stable in all responding neonates, and no proved complications were observed. The authors recommend lateral decubitus positioning as the initial treatment of choice in managing neonatal tension pulmonary emphysema.
A rare pulmonary manifestation of the acquired immunodeficiency syndrome or intravenous (IV) drug abuse is upper lobe cystic disease--pneumatoceles in Pneumocystis carinii pneumonia (PCP) and bullous emphysema in IV drug abuse. Because these disorders overlap, the radiographic findings in 56 patients were compared. During a 12-month period, 16 patients less than 40 years of age were found to have bullous emphysema; the 10 who were IV drug abusers constituted group 1. In the same time period, 40 patients with PCP were encountered; the eight (20%) who had or developed pneumatoceles constituted group 2. In both groups, the conventional radiographic manifestations of upper lobe cystic disease were similar. Eight patients underwent computed tomography of the chest. In five patients with bullous disease, the distribution of the bullous lesions was peripheral, with sparing of the central portions of the lungs. In contrast, PCP pneumatoceles in three patients were dispersed throughout the lung parenchyma.
PURPOSE: The authors present their experience with previously unsuspected carcinoma of the lung detected at preoperative computed tomography (CT) in patients with severe pulmonary emphysema who were scheduled to undergo lung volume reduction surgery. MATERIALS AND METHODS: Preoperative chest CT was performed in 148 patients (84 men, 64 women; mean age, 65 years +/- 8 [standard deviation]) with advanced pulmonary emphysema before lung volume reduction surgery. At surgery, an attempt was made to excise any pulmonary nodule considered suspicious for carcinoma at CT. RESULTS: Eighteen pulmonary nodules suspicious for lung cancer were found at CT in 17 (11%) of the 148 patients. Sixteen of these 148 nodules were resected at lung volume reduction surgery. Nine non-small cell carcinomas (adenocarcinoma, n = 4, including three with bronchioloalveolar differentiation; poorly differentiated, n = 3; squamous cell carcinoma, n = 2) were found in eight (5%) patients. Eight of the cancers were stage I, and one was unstaged surgically. Maximum diameters of the cancers ranged between 1.0 and 3.8 cm (median, 1.6 cm). The seven (5%) other resected nodules were all benign. CONCLUSION: A 5% rate of stage I primary lung cancer in patients selected for lung volume reduction surgery suggests that performance of chest CT in candidates for lung volume reduction surgery is appropriate not only to identify patterns of pulmonary parenchymal destruction but also to search for stage I lung cancer.
PURPOSE: 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). MATERIALS AND METHODS: 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. RESULTS: Pearson and intraclass correlation coefficients were high for all quantitative CT indexes (all > or = 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). CONCLUSION: Repeatability of quantitative CT test results in LVRS candidates is high and unlikely to improve by using spirometric gating.
alpha 1-Antitrypsin (alpha 1-AT) is the major endogenous inhibitor of neutrophil elastase. Individuals with alpha 1-AT deficiency are susceptible to premature development of emphysema. Thus a greater understanding of this serine proteinase inhibitor (serpin) has been a major objective of research on the pathogenesis of emphysema. In this article, we review recent literature on the alpha 1-AT gene and its relationship to other members of the serpin supergene family, particularly as it pertains to the function of alpha 1-AT. We also discuss the current literature on biosynthesis of alpha 1-AT and how its synthesis may be tightly regulated by the net balance of neutrophil elastase and alpha 1-AT at sites of inflammation/tissue injury. The net functional activity of alpha 1-AT in complex biological fluids is also affected by interaction with other enzymes, inhibitors, matrix proteins, and endogenous oxidants. Finally, we discuss the pathogenesis, clinical manifestations, and treatment of injury to the lung associated with deficiency variants of the alpha 1-AT gene.
To correlate lung structure and function in an animal model of emphysema, 17 dog lungs were treated with intrabronchial instillation of papain (range of concentration 0.5-5%); the contralateral lungs served as controls. The lungs were inflated to the volume at a transpulmonary pressure (PL) of 25 cmH2O (V25), and static pressure-volume and maximal expiratory flow-volume curves were obtained. Eight pairs of lungs were processed for histology at a PL of 5 cmH2O, and eight pairs of lungs were processed at a PL of 25 cmH2O. Significant loss of elastic recoil was found in the papain-treated lungs, between 30 and 90% predicted V25 (P less than 0.02). However, there was no correlation between the mean linear intercept corrected to predicted lung volume (indicative of alveolar destruction) and loss of elastic recoil. There was a significant reduction of maximal flow (Vmax) between 20 and 90% predicted V25. However, the reduction in Vmax was commensurate with the reduction of elastic recoil, since there was no significant change in resistance of the upstream segment between 30 and 70% predicted V25. Airway morphometry demonstrated no significant differences in small airway dimensions between control and emphysema-treated lungs. In both control and papain-treated lungs, small airway dimensions changed relatively more than lung volume a PL of 25 and 5 cmH2O.
In vitro contractile properties of the diaphragm were measured in four groups of inbred adult hamsters (greater than 40wk), randomly divided into sedentary control (SC), exercise control (EC), sedentary emphysematous (SE), and exercise emphysematous (EE) groups. Emphysema was induced by a single endotracheal instillation of elastase. Exercise consisted of running 1 h/day, 7 days/wk for 20 wk. Functional residual capacity (FRC), measured by means of a pressure box, was approximately 2.5 times greater in both emphysematous groups compared with control groups. Small diaphragmatic bundles were then isolated and subjected to in vitro analysis of isometric contractile properties. No differences were observed among the four groups in time to peak tension, half-relaxation time, and shape of the force-frequency curve. The diaphragmatic length-tension curve of emphysematous animals was displaced toward the left; maximal tetanic tension was similar in all groups, while optimal length (Lo), defined as the length at which maximal twitch tension occurred, was significantly shorter in both emphysematous groups. The Lo was negatively correlated with the FRC. Exercise tended to increase the in vitro endurance of the diaphragm bundles in control animals only. Diaphragms from both emphysematous groups, however, did show the greatest resistance to fatigue. It is concluded that 1) daily running for 1 h does not influence the diaphragmatic contractile properties in the hamster, but fatigue was reduced; 2) the load of chronic emphysema decreased the hamster's diaphragm fatiguability; and 3) the diaphragms of emphysematous hamsters chronically adapt by decreasing diaphragmatic length in proportion to the degree of hyperinflation and thus probably continue to operate at an Lo.
A large body of circumstantial evidence has accumulated in the last 20 yr, suggesting that alveolar effacement in pulmonary emphysema is due to unrestrained proteolytic (elastolytic) activity in lung connective tissue. Even though this hypothesis still requires rigorous proof, newer information is rapidly developing that links the protease-pathogenesis model to the primary environmental risk factor associated with the disease, namely cigarette smoking. A triad of chemical and cellular effects produced by cigarette smoke have been suggested as factors contributing to altered elastin metabolism and eventual development of emphysema in smokers. The present article reviews some of these observations, seeks to place them within the overall framework of the protease model, and attempts to raise questions for future study.
In five patients with hypoxic chronic bronchitis and emphysema we measured ear O2 saturation (SaO2), chest movement, oronasal airflow, arterial and mixed venous gas tensions, and cardiac output during nine hypoxemic episodes (HE; SaO2 falls greater than 10%) in rapid-eye-movement (REM) sleep and during preceding periods of stable oxygenation in non-REM sleep. All nine HE occurred with recurrent short episodes of reduced chest movement, none with sleep apnea. The arterial PO2 (PaO2) fell by 6.0 +/- 1.9 (SD) Torr during the HE (P less than 0.01), but mean arterial PCO2 (PaCO2) rose by only 1.4 +/- 2.4 Torr (P greater than 0.4). The arteriovenous O2 content difference fell by 0.64 +/- 0.43 ml/100 ml of blood during the HE (P less than 0.05), but there was no significant change in cardiac output. Changes observed in PaO2 and PaCO2 during HE were similar to those in four normal subjects during 90 s of voluntary hypoventilation, when PaO2 fell by 12.3 +/- 5.6 Torr (P less than 0.05), but mean PaCO2 rose by only 2.8 +/- 2.1 Torr (P greater than 0.4). We suggest that the transient hypoxemia which occurs during REM sleep in patients with chronic bronchitis and emphysema could be explained by hypoventilation during REM sleep but that the importance of changes in distribution of ventilation-perfusion ratios cannot be assessed by presently available techniques.
Motivated by the introduction of single-lung transplantation into clinical practice, we compared the static mechanical properties of the respiratory system in six supine dogs before (at baseline) with those after the induction of unilateral emphysema. Relaxation volume (Vrel), total lung capacity (TLC), and static compliance of the emphysematous lung increased to 214 +/- 68, 186 +/- 39, and 253 +/- 95% (SD) of baseline, respectively. Vrel of the nonemphysematous lung fell to 81 +/- 28% of baseline, with no significant change in TLC of the nonemphysematous lung or its pressure-volume relationship, indicating that unilateral hyperinflation does not cause dropout of contralateral lung units. After unilateral emphysema, the chest wall shifted to a higher unstressed or neutral volume (when pleural pressure equals atmospheric pressure) in three of six animals, minimizing the anticipated decrease in lung recoil pressure at the higher respiratory system Vrel. The pattern of relative lung emptying in the intact dog and in the excised lungs was similar during stepwise deflations from TLC, suggesting that mean pleural pressure of the hemithoraces is equal. We conclude that in the dog the static volume distribution between emphysematous and nonemphysematous lungs is determined only by differences in lung recoil and compliance.
Changes in pulmonary hemodynamics and vascular reactivity in emphysematous hamsters were studied in an isolated lung preparation perfused at constant flow with blood and 3% dextran. Hamsters were treated with intratracheal porcine pancreatic elastase at 70 days of age, and experimental studies were conducted at 1, 3, and 8 mo after treatment. Baseline pulmonary arterial pressure in elastase-treated lungs was increased compared with saline-treated control lungs 1 mo after treatment, but this increase did not progress at 3 and 8 mo. Increases in pulmonary arterial pressure in elastase-treated lungs were temporally correlated with the morphological development of emphysema and right ventricular hypertrophy; both of these were evident at 1 mo after treatment and showed little change thereafter. Pressor responses to hypoxia and angiotensin II were not different between elastase-treated and control lungs at 1 and 3 mo. At 8 mo, however, pressor responses in emphysematous lungs to 0% O2 (but not to angiotensin II) were significantly increased. This was the result of a lack of the normal age-related fall in the hypoxic pressor response. Our results suggest that the right ventricular hypertrophy found in these emphysematous animals results from a chronically increased pulmonary vascular resistance. Furthermore, increases in pulmonary vascular resistance in the early development of emphysema are likely a result of the loss of vascular beds and supporting connective tissue.
Occupational exposure to some types of mineral particles has been shown to be associated with the development of emphysema, but the mechanism of this process is unknown. Because many mineral particles are known to catalyze the formation of active oxygen species in aqueous solution, we hypothesized that mineral particles could oxidatively inactive antiproteinases, leading to an imbalance between protease and antiprotease activities, events similar to those believed to occur with cigarette smoke. To test this hypothesis, human alpha 1-antiproteinase (alpha 1-AP) was incubated with suspensions of freshly ground or aged quartz, and antiproteolytic activity was determined by using porcine pancreatic elastase. Increasing concentrations of quartz were associated with increasing losses of antiproteolytic activity; this effect could be prevented by catalase. Freshly ground quartz was more active than aged quartz. Western blot analysis for alpha 1-AP showed abnormal banding, suggesting that porcine pancreatic elastase-alpha 1-AP complex formation was impaired by silica exposure. Chemical assay of aqueous quartz suspensions demonstrated production of hydrogen peroxide; incubation of alpha 1-AP with hydrogen peroxide caused a dose-dependent loss of antiproteolytic activity, and this also could be prevented by catalase. We conclude that, at least in vitro, quartz can inactivate alpha 1-AP through a hydrogen peroxide-mediated mechanism and that oxidative loss of antiproteinase activity could play a role in mineral dust-induced emphysema.
The deposition and dispersion of inhaled aerosol boluses were investigated as markers of lung injury in three dogs before and after emphysema was induced by papain exposure. After the experiments, lung damage was assessed histologically. Four unexposed dogs were used as controls. Effective air space diameter (EAD) was determined from aerosol deposition during a 5-s breath hold. Nonuniform ventilation was assessed from the spreading of the expired bolus, quantified as a coefficient of dispersion (CD), and from expired bolus skewness (SK). Experiments were done with a range of bolus penetrations and ventilatory flow rates. After papain exposure, EAD measured with the most penetrating boluses increased an average of 89% (P < 0.0001); CD and SK measured with boluses of medium penetration and a flow rate of 0.5 l/s increased an average of 24% (P < 0.02) and 98% (P < 0.002), respectively. The effects of lung injury on CD and SK increased with flow rate. Lung injury was confirmed by changes in lung mechanics and by histology. EAD measured with deeply penetrating boluses correlated significantly with the mean chord length measured morphometrically (P < 0.05). No correlation was found with more shallow boluses. The results indicate that EAD, CD, and SK are sensitive markers of lung injury in experimental emphysema and that EAD is a specific marker of increased air space size.
Loading of skeletal muscles is associated with increased generation of oxidants, which in turn may impair muscle contractility. We investigated whether the load on the hamster diaphragm imposed by pulmonary emphysema induces oxidative stress, as indicated by glutathione oxidation, and whether the degree of glutathione oxidation is correlated with contractility of the diaphragm. In addition, the effect of 12 wk of treadmill exercise training on contractility and glutathione content in the normal (NH) and emphysematous hamster (EH) diaphragm was investigated. Training started 6 mo after elastase instillation. After the training period, glutathione content and in vitro contractility of the diaphragm were determined. Twitch force and maximal tetanic force were significantly reduced (by approximately 30 and approximately 15%, respectively) in EH compared with NH. In sedentary hamsters, the GSSG-to-GSH ratio was significantly elevated in the EH compared with the NH diaphragm. A significant inverse correlation was found between GSSG-to-GSH ratio and twitch force in the diaphragm (P < 0. 01). Training improved maximal tetanic force and reduced fatigability of the EH diaphragm but did not alter its glutathione content. In conclusion, 1) emphysema induces oxidative stress in the diaphragm, 2) training improves the contractile properties of the EH diaphragm, and 3) this improvement is not accompanied by changes in glutathione redox status.