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PubMed2005

Effects of exercise training on papain-induced pulmonary emphysema in Wistar rats.

The purpose of the present study was to evaluate the role of exercise training on the development of papain-induced emphysema in rats. Our hypothesis was that the increase in pulmonary tissue stretching associated with exercise could increase the severity of a protease-induced emphysema. Wistar rats were randomly assigned to four groups (n = 10 for each group) that received, respectively, intratracheal infusion of papain (6 mg in 1 ml of 0.9% NaCl) or vehicle and were submitted or not to a protocol of exercise on a treadmill. Rats exercised at 13.3 m/min, 6 days/wk, for 9 wk (increasing exercise time, from 10 to 35 min). We measured respiratory system elastance and resistance, the size and weight of the heart, and pulmonary mean linear intercept (Lm). After 9 wk of exercise training, there were no differences in respiratory system resistance and elastance values among the four experimental groups. Volume of the heart was significantly greater in rats submitted to exercise training (P = 0.007) compared with sedentary rats due to increases in volumes of both right and left cardiac chambers. Lm was significantly greater in rats that received papain compared with saline-infused rats (P = 0.025). Surprisingly, this was true, even though there was no significant decrease in elastance, possibly due to connective tissue remodeling. However, Lm was significantly greater in papain + exercise rats compared with rats that received papain and were not submitted to exercise. We conclude that exercise training can increase alveolar damage induced by papain infusion.

Airway Resistance↗
PubMed2005

Quantitative characterization of airspace enlargement in emphysema.

The mean linear intercept (L(m)) can be used to estimate the surface area for gas exchange in the lung. However, in recent years, it is most commonly used as an index for characterizing the enlargement of airspaces in emphysema and the associated severity of structural destruction in the lung. Specifically, an increase in L(m) is thought to result from an increase in airspace sizes. In this paper, we examined how accurately L(m) measures the linear dimensions of airspaces from histological sections and a variety of computer-generated test images. To this end, we developed an automated method for measuring linear intercepts from digitized images of tissue sections and calculate L(m) as their mean. We examined how the shape of airspaces and the variability of their sizes influence L(m) as well as the distribution of linear intercepts. We found that, for a relatively homogeneous enlargement of airspaces, L(m) was a reliable index for detecting emphysema. However, in the presence of spatial heterogeneities with a large variability of airspace sizes, L(m) did not significantly increase and sometimes even decreased compared with its value in normal tissue. We also developed an automated method for measuring the area and computed an equivalent diameter of each individual airspace that is independent of shape. Finally, we introduced new indexes based on the moments of diameter that we found to be more reliable than L(m) to characterize airspace enlargement in the presence of heterogeneities.

Algorithms↗
PubMed2003

Cortical bone dynamics, strength, and densitometry after induction of emphysema in hamsters.

Recent evidence suggests that patients suffering from chronic obstructive pulmonary disease are also at an increased risk of developing osteoporosis. The pathophysiological mechanism(s) linking these progressive diseases is unknown. The goal of this investigation was to determine whether there were alterations in bone mineral density and content, cortical bone structure and strength, and indexes of bone formation and resorption in the elastase-induced emphysematous hamster. At 3 wk after induction of emphysema, the femoral bone mineral content was 8% less (P = 0.026) and the femoral fracture strength was 6% less (P = 0.032) in the emphysematous hamster than in controls. The cortical area was 8.4% less (P = 0.013) and the periosteal mineral appositional rate was 27% less (P = 0.05) than in controls. Additionally, the endocortical eroded surface in the emphysematous group was about twice that in the control group (P = 0.003). Differences in some indexes of bone formation and resorption, paralleled by differences in bone structure and strength, were observed 3 wk after induction of emphysema. These differences in skeletal metabolism and strength may help explain some of the skeletal changes associated with chronic obstructive pulmonary disease in humans.

Animals↗
PubMedDate not supplied

Lung volume reduction for emphysema and the Canadian Lung Volume Reduction Surgery (CLVR) Project.

OBJECTIVE: To review the literature on the surgical treatment of emphysema and to present preliminary results from a pilot study of lung volume reduction (LVR) surgery. DESIGN: Case series of consecutive patients referred for LVR surgery. Outcomes were quality of life, pulmonary function and exercise capacity. SETTING: Two university-affiliated hospitals in Ontario. POPULATION STUDIED: Patients between the ages of 40 and 75 years with emphysema who had severe airflow limitation, hyperinflation of the lungs and impaired quality of life. INTERVENTION: Bilateral reductions with multiple wedge resections of the lung using a linear stapling device with bovine pericardial buttressing were completed via a median sternotomy. MAIN RESULTS: Of 50 patients referred, 24 underwent LVR surgery. Mean age of the cohort was 63 years. Operative 30-day or in hospital mortality was 8%. Two other patients (8%) died from respiratory failure after LVR within the first year. Postoperative complications included prolonged air leaks (six of 24), tracheobronchitis (five of 24), mechanical ventilation (four of 24) and pneumonia (three of 24). Mean length of stay was 18 days (median 12 days). At one year, there was a sustained decrease in total lung capacity from 133% to 123% predicted. There were improvements in forced expiratory volume in 1 s, from 22% of predicted preoperatively to 32% postoperatively, and in 6 min walk performance, from 345 to 381 m. Improvements were also noted in the quality of life assessments. CONCLUSIONS: Preliminary results suggest that LVR surgery is feasible and may improve the patient's quality of life, pulmonary function and exercise capacity. A randomized clinical trial comparing LVR plus the best medical management with the best medical management alone is currently underway to determine the effectiveness of LVR.

Adult↗
PubMed2005

[Lung transplantation for emphysema: retrospective study of 65 patients].

BACKGROUND AND OBJECTIVE: Our goal was to analyze the incidence of perioperative complications in patients with pulmonary emphysema who underwent lung transplantation and to identify variables associated with the incidence of morbidity and mortality during the immediate postoperative period. PATIENTS AND METHOD: We undertook a retrospective study of 65 pulmonary emphysema patients who received lung transplants from 1994 through 2002 with the aim of determining the most common intra- and early postoperative complications in the ICU. An univariate analysis was carried out in order to identify variables associated with the incidence of mortality and postoperative complications. Those variables showing statistical significance underwent a multivariate analysis, by means of a pattern of logistic regression, in order to calculate the odds ratio and confidence interval. RESULTS: Seventeen patients received single-lung transplants (SLT) and 48 patients received sequential double-lung transplants (DLT). Intraoperative complications appeared more frequently in the DLT group. Most frequent complications during surgery were reperfusion syndrome (44.6%) and pulmonary hypertension (16.9%). The intraoperative survival was 100%. Fifty-five patients had some type of postoperative complication. Commonest postoperative complications were infection (56.9%) and primary graft failure (36.6%). In the early postoperative period the mortality rate was 16.9%. Main cause of death in the ICU was sepsis (54.5%). A time of mechanical ventilation > 48 hours and postoperative hemorrhage were the variables with a higher predictive value for mortality in the early postoperative period. CONCLUSIONS: Patients with SLT had a lower rate of perioperative complications and a higher survival during their stay in the ICU. Time of mechanical ventilation > 48 hours and postoperative hemorrhage were the variables that best predicted death in the early postoperative period following lung transplantation. Despite our experience, however, perioperative mortality in lung transplantation remains high up to this day.

Female↗
PubMed1997

Morphologic and histochemical evaluation of muscle in patients with chronic pulmonary emphysema manifesting generalized emaciation.

Twelve severely emaciated patients with emphysema and 4 control patients with mild emaciation were studied. Arterial blood gas analysis, pulmonary function tests, and muscle biopsy were performed. According to the percentage of ideal body weight (%IBW), patients were divided into two groups of 6 patients each; one with %IBW values greater than 70.0 (group 1) and the other with %IBW values less than 70.0 (group 2), and 4 control patients with emphysema whose %IBW values were greater than 85.5. %FEV1.0, PaO2 and Hugh-Jones scores in group 2 patients were consistent with significantly greater deterioration as compared with those in group 1 patients and controls. In the muscle fibers of 11 patients and 4 controls, nicotinamide and adenosine dinucleotide tetrazolium reductase activity was studded with spots. Nemalin rods were detected in 3 specimens in group 2 and in 1 specimen each in both group 1 and controls. These changes probably result from chronic hypoxemia. Fiber type grouping accompanied by type II dominant fiber atrophy was demonstrated in 5 patients of group 2, whereas type II fiber atrophy was shown in 2 specimens from patients of group 1. Diameters of both types I and II fibers in group 2 were smaller than those in group 1 and controls. Significant correlations were observed between fiber diameters and %IBW, %FEV1.0 and %IBW, and PaO2 and %IBW. Neurogenic and disuse muscular atrophy due to both hypoxic axonal disorder and disuse is likely to be the cause of the emaciation, and a 'vicious circle' between muscular atrophy, respiratory function and hypoxemia probably exists in group 2. Since mild or moderate emaciation was observed in controls and group 1 in spite of the lack of fiber atrophy, involvement of fat and connective tissue should also be taken into consideration to determine the cause of emaciation.

Aged↗
PubMed1976

The pathogenesis of pulmonary emphysema (II).

The most important primary cause of generalized pulmonary emphysema is in all probability the loss of mechanical stability of the connective tissue framework in the lung parenchyma. The complexity of the interrelations and interdependencies between the fibres and the ground substance, leads to the mapping out of a more detailed outline of the vulnerable parts in a similar framework. It is concluded that the junctions especially constitute weak spots. Glycosaminoglycans, glycoproteins and proteoglycans particularly hold a key position as cementing substances. The importance of female sex hormones in the metabolism of the ground substance is indicated. A survey is given of the possible threats to a similar system. An attempt is made to disentangle the multitude of possible pathogenetic pathways which lead to emphysematous disintegration. Perspectives of future emphysema research are discussed on the basis of these considerations. Preventive, protective, and reconstructive measures are proposed.

Ascorbic Acid↗
PubMed1978

Emphysema with minor airway obstruction and abnormal tests of small airway disease.

In 9 patients complaining primarily of exertional dyspnea, the diagnosis of early emphysema was made on the basis of a decrease of the elastic recoil of the lung and of the single breath diffusing capacity, in the presence of only minor airway obstruction as estimated from the routine pulmonary function tests. Closing volume, the alveolar plateau, dynamic compliance and maximal flow at 50% of the vital capacity were markedly abnormal; the maximal flow-static recoil pressure relationships suggest, however, that none of the patients suffered from small airway disease. We conclude that one should systematically consider early emphysema in the differential diagnosis of small airway disease.

Adult↗
PubMed1981

Role of chemosensitivity during exercise in normal subjects and patients with pulmonary emphysema.

In 11 normal subjects (mean age = 22.8 years) and 8 patients with pulmonary emphysema (mean age = 70.4 years), the role of chemosensitivity in determining ventilation, cardiac output, lactic acid, and cyclic AMP and GMP was evaluated quantitatively during 150 or 30 W exercise and simulated exercise. Simulated exercise was done while the subjects took a rest by regulating arterial blood gases at exercise levels in patients and at PaO2 = 65 mm Hg and PaCO2 = 48 mm Hg in normal subjects. In normal subjects, the role of arterial blood gases in determining exercise ventilation, cardiac output, cyclic AMP and GMP are large, while those contributed much less to lactic acid. In patients, PaO2 contributed only half of the exercise ventilation. It accounted for a negligibly small portion of exercise cardiac output, lactic acid, and cyclic GMP. These results indicate, by deduction, that either augmentation of chemosensitivity, pH, or humoral factors is responsible for about half of the changes of exercise ventilation in patients with pulmonary emphysema. These factors seem to influence cardiac output, lactic acid, and cyclic AMP and GMP more strongly than PaO2 alone in exercising patients.

Adult↗
PubMed1986

Comparison of the cell content of lung lavage fluid with the presence of emphysema and peripheral airways inflammation in resected lungs.

This study was designed to investigate the relationship between the cellular components of lung lavage fluid and the presence of airways disease and emphysema in resected lung specimens, primarily from current and ex-smokers. Since standard bronchopulmonary lavage cannot be performed on these specimens, an intrapulmonary lavage technique was developed and compared to the results of bronchoalveolar lavage performed prior to surgery on the lung or lobe opposite to the one resected. The specimen lavage produced inflammatory cell differential counts similar to those obtained by bronchopulmonary lavage, and studies on postmortem lungs showed that the fluid washed alveoli, respiratory and membranous bronchioles, and small cartilaginous bronchi. The results show that the variation in peripheral airways inflammation and extent of lung destruction by emphysema did not correlate with the variation in cell content observed in the lavage fluid. Similarly, the differential counts performed in the lavage fluid did not correlate with the smoking habits of the patient. We conclude that the changes in cell content of the lavage fluid do not reflect the extent or severity of the inflammatory disease and lung destruction present in the lungs of this group of patients.

Body Fluids↗
PubMed1988

Effects of elastase-induced emphysema on histochemical properties of guinea pig diaphragm.

We studied the changes of histochemical properties of diaphragm in guinea pigs with elastase-induced emphysema. Using myofibrillar ATPase staining, three types of diaphragmatic muscle fibers were classified as slow-twitch, oxidative (SO), fast-twitch, oxidative, glycolytic (FOG), and fast-twitch, glycolytic (FG). Capillaries adjacent to individual fibers were also demonstrated by ATPase reaction. After 24 weeks of tracheal instillation of elastase, both the size and number of SO and FOG fibers were increased, thereby indicating the increase in relative areas occupied by these oxidative fibers in the diaphragm (p less than 0.01 in each case). Moreover, these changes were accompanied by the increased capillary density (p less than 0.01). These results suggest that chronic respiratory load with emphysema may establish the diaphragm more resistant to fatigue by increasing oxidative capacity of the diaphragmatic muscle fibers.

Animals↗
PubMed1993

Pulmonary emphysema followed by pulmonary fibrosis of undetermined cause.

Idiopathic pulmonary fibrosis (IPF) and pulmonary emphysema (PE) have distinct clinical and pathological characteristics, and have been considered to be separate disorders. However, recent animal experiments have suggested that, with regard to their pathogenesis, the diseases have some features in common. However, there are no clinical data supporting this hypothesis. We report here 9 patients (all male, 67 +/- 2 years, mean +/- SE) who had PE followed by IPF. They were found among 152 PE patients who came to Tohoku University Hospital during the past 15 years (1976-1991). All patients were male and heavy smokers and 2 patients also had prostate cancer and gastric cancer, respectively. Three patients were alive during this study and had been diagnosed as having IPF and PE by the combination of transbronchial biopsy, selective alveolobronchogram, CT examination and lung function tests. The diagnosis of IPF and PE in the other patients was based on the pathological findings of autopsied lungs in addition to clinical findings. All patients showed PE mainly in the upper lobes and IPF in the lower lobes. In all patients, in addition to all known causes of pulmonary fibrosis, the possibilities that chronic or recurrent infections in PE induced pulmonary fibrosis and that IPF produced emphysematous changes were carefully excluded by medical records and pathological findings. It is not clear whether the occurrence of emphysema and pulmonary fibrosis in these cases is coincidental, or whether the two diseases are linked by a common pathogenetic pathway.

Aged↗
PubMed1995

Influence of sleep on respiratory function in emphysema.

To assess the influence of sleep on respiratory function, five patients with chronic obstructive pulmonary disease (COPD) with laboratory evidence of emphysema were monitored during sleep in a horizontal body plethysmograph. Neither lung volume nor lower airway resistance (Rla) changed in association with sleep. Upper airway resistance (Rua) increased during sleep and was highest during rapid eye movement (REM) sleep (Rua = 5.9 +/- 1.1, 9.6 +/- 2.1, 11.2 +/- 1.5, and 15.6 +/- 4.1 cm H2O/L/s during wakefulness, Stages 2, 3-4, and REM, respectively, p < 0.05). Tidal volume (VT) decreased during sleep, resulting in a sleep-associated decrement in minute ventilation (VI = 8.69 +/- 0.46, 7.64 +/- 0.65, 7.08 +/- 0.70, and 5.62 +/- 0.47 L during wakefulness, Stages 2, 3-4, and REM, respectively, p < 0.05). Respiratory neuromuscular output was also reduced during sleep (esophageal occlusion pressure [P0.1] = 2.69 +/- 0.39, 2.02 +/- 0.27, 1.90 +/- 0.27, and 1.63 +/- 0.25 cm H2O during wakefulness, Stages 2, 3-4, and REM, respectively, p = 0.005). We conclude that in patients with emphysema (1) sleep does not alter lung volume or increase lower airway resistance, (2) sleep is associated with a decrease in VT and VI, and (3) sleep is associated with an increase in Rua and a reduction in P0.1 that may contribute to the sleep-associated decrease in VI.

Adult↗
PubMed1995

Comparison of computed density and macroscopic morphometry in pulmonary emphysema.

High-resolution computed tomography (HRCT) scans were obtained at 1 cm intervals in 63 subjects referred for surgical resection of a cancer or for transplantation to find out whether the relative area of lung occupied by attenuation values lower than a threshold would be a measurement of macroscopic emphysema. Using a semiautomatic procedure, the relative areas occupied by attenuation values lower than eight thresholds ranging from -900 to -970 HU were calculated on the set of scans obtained through the lobe or the lung to be resected. The extent of emphysema was quantified by a computer-assisted method on horizontal paper-mounted lung sections obtained every 1 to 2 cm. The only level for which no statistically significant difference was found between the HRCT and the morphometric data was -950 HU. To determine the number of scans sufficient for an accurate quantification, we recalculated the relative area occupied by attenuation values lower than -950 HU on progressively fewer numbers of scans and investigated the departure from the results obtained with 1 cm intervals. Because of wide variations in this departure from patient to patient, a standard cannot be recommended as the optimal distance between scans.

Adult↗
PubMed1996

Mineral dusts cause elastin and collagen breakdown in the rat lung: a potential mechanism of dust-induced emphysema.

It is now accepted that workers with exposure to mineral dusts can develop airflow obstruction. The basis of this process is uncertain, but carefully performed morphologic studies suggest that coal, silica, and perhaps other dusts may produce emphysema in humans. To investigate the mechanisms involved in this process, we administered crystalline silica (quartz) or titanium dioxide (rutile) to rats in a single intratracheal instillation. At varying times after instillation, the animals' lungs were lavaged, the lavageate from one lung was dried and hydrolyzed, and the amounts of desmosine (DES),as a measure of elastin breakdown, and hydroxyproline (HP), as a measure of collagen breakdown, were determined. The lavageate from the other lung was counted for inflammatory cells. Both silica and titanium dioxide caused a dose-dependent increase in DES and HP 24 h after instillation. When an equivalent dose (30 mg) of silica or rutile was administered and animals were sacrificed at various times up to 21 d, a sustained increase in lavage DES and HP was seen in the silica-treated animals, and this was accompanied by a sustained increase in polymorphonuclear leukocytes (PMN); in contrast, both lavage PMN and lavage DES/HP rapidly peaked and then declined in the titanium dioxide-treated animals. Numbers of macrophages remained elevated over the 21-d period of sacrifice with both types of treatment. These data show for the first time that mineral dusts can cause connective-tissue breakdown in the lung, with the release of matrix components into the alveolar spaces. The amount of connective-tissue breakdown appears to parallel the number of PMN but not the number of macrophages in the alveolar spaces, suggesting that PMN-derived proteolytic enzymes are responsible for the breakdown. This process probably plays a role in dust-induced emphysema.

Animals↗
PubMed1996

Health-care technology assessment of surgical procedures: the case of reduction pneumoplasty for emphysema.

End-stage chronic obstructive pulmonary disease (COPD) is frequent in the practice of pulmonology. The recent report that reduction pneumoplasty results in lung function improvement in a high proportion of patients with emphysema has raised the question of how effectively the medical profession assesses the efficacy of new surgical procedures. Unlike drugs and devices, the introduction of new surgical procedures is not regulated. Technique changes rapidly for a period of time after new procedures are introduced. Peer review is done mainly by quality-improvement activities in the surgeon's hospital and by publication in peer-reviewed journals. Randomized clinical trials (RCT) are procedurally and ethically difficult to do and few have been done for new surgical procedures. Some trials have been problematic. For example, a controlled cooperative trial of radial keratotomy resulted in unsuccessful antitrust suits brought by physicians and patients alleging that third-party payers would not reimburse them for surgery. RCTs that have been done have tended to be reported long after the procedure has been incorporated into surgical practice. A RCT of reduction pneumoplasty would be impossible at this time because of rapid flux in surgical techniques. There might also be ethical problems because of the substantial improvement in lung function of many patients in the existing case series, a level of improvement seen with no other treatment than lung transplantation. It is proposed that a prospective, cooperative, consecutive-case, observational study (registry) of reduction pneumoplasty for emphysema could greatly speed the acquisition of information about the efficacy of this new procedure.

Humans↗
PubMed1997

Theoretical basis for improvement following reduction pneumoplasty in emphysema.

Reduction pneumoplasty may improve flow rates, comfort, and exercise tolerance in severe emphysema. The basis for improvement has not been systematically addressed. The major disability of emphysema stems from impairment of maximal expiratory flow-volume performance of the lung (MEFV). This requires the chest wall to operate at high volumes, which in turn severely compromises inspiratory muscle function. Clinical benefit, then, requires that MEFV performance improve so that the operating lung volume is reduced. This study presents theory and illustrative calculations. Removing nonventilating lung (e.g., bullae) simply displaces the MEFV curve down the volume axis. Removing ventilating parenchyma reduces both volume and maximal expiratory flow at iso-lung recoil pressure, and shortens the curve on the volume axis. The critical beneficial effect in both cases is reduction of the volume for a given limiting flow, VL (Vmax). Removing a given fraction of lung from the ventilating compartment is nearly as effective as removing it from the nonventilating compartment. Lowering of operating volumes benefits the strength, efficiency, endurance, and reserve of the inspiratory muscles and thus extends the metabolic scope of the emphysematous patient.

Humans↗