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PubMed2002

Urinary desmosine excretion is inversely correlated with the extent of emphysema in patients with chronic obstructive pulmonary disease.

An enhanced proteolysis of lung interstitium is key event in the pathogenesis of emphysema, a major constituent of chronic obstructive pulmonary disease. To assess whether urinary desmosine and/or hydroxyproline may be used as a marker of lung destruction we studied urinary excretions of these products in 20 patients with chronic obstructive pulmonary disease and in 19 appropriate controls in 24h urine collection samples. For desmosine measurements, we developed a new indirect competitive enzyme-linked immunosorbent assay. The extent of emphysema was measured in high resolution computed tomography (CT) scans, by considering lung area with CT numbers <-950 Hounsfield units (HU). Urinary desmosine excretion was significantly higher in patients with chronic obstructive pulmonary disease than in controls (294+/-121 microg versus 183+/-93 microg, P=0.003), and was unrelated with both age and smoking habits. In patients with no evidence or only mild emphysema, desmosine excretion values were significantly higher (P=0.006) than those of patients with moderate to severe emphysema. In patients with chronic obstructive pulmonary disease, urinary hydroxyproline excretion was positively correlated with urinary desmosine excretion but on the average, it was not different from that of controls. These data indicate that urinary desmosine is a sensitive biological marker of lung elastin catabolism. The relatively low levels of urinary desmosine observed in patients with severe emphysema may be accounted for a decrease in elastin catabolism due to reduced lung elastin mass. Urinary desmosine may be used to identify subjects at risk of developing emphysema and to assess the efficacy of therapeutic interventions.

Adult↗
PubMed1999

Subcutaneous tissue emphysema of the hand secondary to noninfectious etiology: a report of two cases.

Subcutaneous emphysema of the hand can be benign and noninfectious in origin. Emphysema from gas-forming organisms is associated with systemic symptoms, whereas benign subcutaneous emphysema is not. High-pressure pneumatic tool injuries are a well-known cause of subcutaneous emphysema. Minor wounds in the web space skin may result in a transport of air across the defect, acting like a ball valve mechanism to trap and then force the air into the subcutaneous tissue, as illustrated by 1 of our patients. In the second patient, use of a high-vibration tool without apparent breach of skin was associated with extensive subcutaneous emphysema. The benign nature of the emphysema was revealed by a lack of local pain and inflammation in the presence of extensive crepitus and a lack of systemic symptoms. A noninfectious cause should always be considered. This may prevent unnecessary surgical intervention, which occurred in 1 of the 2 cases presented here.

Adult↗
PubMed1980

[Intrapulmonary interstitial emphysema in ventilatorsy supported infants (author's transl)].

Development of intrapulmonary interstitial emphysema together with other forms of extraalveolar air collections following alveolar rupture was investigated retrospectively in 46 term and preterm newborn infants with respect to gestational age severity of pulmonary disease and mode of ventilatory assistance. Intrapulmonary interstitial emphysema was found in 31 of these 46 infants (67%). Development depended on the severity of pulmonary disease, mode of ventilatory assistance and level of inspiratory pressure. Intrapulmonary interstitial emphysema was found at an average age of 1 day (1-6 days) in 2 out of 23 infants (9%) during unassisted spontaneous breathing, in 8 out of 24 infants (33%) during CPAP and in 21 out of 26 infants (81%) during controlled ventilation. 18 out of these 31 infants (58%) additionally developed other forms of extraalveolar air collections but only in 9 from these interstitial emphysema has been found prior to other forms of extraalveolar air. Mortality rate of infants with intrapulmonary interstitial emphysema alone (10 out of 13; 77%) and infants who additionally developed other forms of extraalveolar air collections (16 out of 18; 89%) did not differ significantly. Development of intrapulmonary interstitial emphysema even in he absence of other forms of extraalveolar air collections has therefore to be judged as a severe complication in infants undergoing different forms of ventilatory assistance.

Humans↗
PubMed2003

Different proliferative capacity of lung fibroblasts obtained from control subjects and patients with emphysema.

To characterize the possible role of a dysregulated proliferative capacity of pulmonary fibroblasts in insufficient tissue repair in lungs from patients with pulmonary emphysema, the authors undertook in vitro proliferative studies with pulmonary fibroblasts obtained from lung tissue of patients with emphysema. A comparison was made with fibroblasts from control subjects. The authors determined the in vitro proliferative capacity of fibroblasts at basal culture conditions and after modulation with interleukin-1beta, interferon-gamma, transforming growth factor-beta(1), and basic fibroblast growth factor. Proliferative capacity was determined by measurement of 5-bromo-2-deoxyuridine (BrdU) incorporation. BrdU incorporation by fibroblast cultures from both groups was very similar. Fibroblast cultures from control subjects, however, incorporated more BrdU after incubation with interleukin-1beta than cultures from patients with emphysema (P<.05). On the other hand, transforming growth factor-beta(1) decreased incorporation of BrdU stronger in fibroblast cultures from control subjects than from patients with emphysema (P<.05). Thus, the proliferative capacity of fibroblast cultures isolated from lung tissue of patients with pulmonary emphysema is different from that of control subjects. Although the difference is small, it may be an essential contribution to the development of pulmonary emphysema that only occurs after repeated smoke-induced injury over many years of an individual's life.

Adolescent↗
PubMed2002

Visual grading of emphysema severity in candidates for lung volume reduction surgery. Comparison between HRCT, spiral CT and "density-masked" images.

PURPOSE: To investigate which of three types of CT imaging yielded the best results in estimating the degree of emphysema in patients undergoing evaluation for lung volume reduction surgery (LVRS), whether there was any difference in this regard between the cranial and caudal part of the lung, and whether the degree of emphysema had an impact on the estimation. MATERIAL AND METHODS: Four radiologists visually classified different degrees of emphysema on three different types of CT images into four groups. The degree of emphysema was calculated by a computer. The three types of images were as follows: HRCT images (2-mm slice thickness); spiral CT images (10-mm slice thickness); and density-masked images (spiral CT images printed with pixels below -960 HU, depicted in white). RESULTS: The conventionally presented images from HRCT and spiral CT yielded the same results (60% respective 62% correct classifications) in assessing the degree of emphysema irrespective of localisation. Significantly improved results were obtained when the spiral CT images were presented as density-masked images (74%). CONCLUSION: There was no difference between HRCT and spiral CT in assessing the degree of emphysema in candidates for LVRS. Improvement can be achieved by the use of density-masked images.

Absorptiometry, Photon↗
PubMed2002

Emphysema in heavy smokers with normal chest radiography. Detection and quantification by HCRT.

PURPOSE: To determine the severity and extent of emphysema in heavy smokers by high-resolution CT (HRCT) and to correlate the findings with spirometric tests (STs) and symptomatology. MATERIAL AND METHODS: Fifty adult smokers with a mean age of 53 years with a smoking history of more than 30 pack years and normal chest radiographs underwent HRCT of the chest and ST (FEV1, FEV1/FVC, PEFR). Among these, 22 had symptoms of pulmonary disease and 28 were asymptomatic. Quantification of emphysema was done using a density mask program and the visual scoring method. The results were correlated with ST and symptomatology. RESULTS: 58% (29 out of 50) of the subjects had significant emphysema on HRCT. Eleven out of 15 with normal ST showed emphysema on HRCT while 2 with airflow obstruction on ST showed normal CT scores. 14% (4 out of 28) asymptomatic subjects had severe emphysema compared to 64% of symptomatic subjects. Emphysematous changes were predominantly seen in upper lung zones in 48% of the patients while in 52% it was distributed equally in both upper and lower zones. The number of pack years of smoking showed a positive correlation with CT scores. The correlation between HRCT scores and ST was statistically significant. CONCLUSION: A significant number of asymptomatic and clinically undiagnosed smokers tend to have significant emphysema. HRCT helps in early detection of disease and thus helps implementation of preventive measures.

Adult↗
PubMed2004

Volume adjustment of lung density by computed tomography scans in patients with emphysema.

PURPOSE: To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema. MATERIAL AND METHODS: Fifty patients with emphysema underwent 3 CT scans at 2-week intervals. The scans were analyzed with a software package that detected the lung in contiguous images and subsequently generated a histogram of the pixel attenuation values. The total lung volume (TLV), lung weight, percentile density (PD), and relative area of emphysema (RA) were calculated from this histogram. RA and PD are commonly applied measures of pulmonary emphysema derived from CT scans. These parameters are markedly influenced by changes in the level of inspiration. The variability of lung density due to within-subject variation in TLV was explored by plotting TLV against PD and RA. RESULTS: The coefficients for volume adjustment for PD were relatively stable over a wide range from the 10th to the 80th percentile, whereas for RA the coefficients showed large variability especially in the lower range, which is the most relevant for quantitation of pulmonary emphysema. CONCLUSION: Volume adjustment is mandatory in repeated CT densitometry and is more robust for PD than for RA. Therefore, PD seems more suitable for monitoring the progression of emphysema.

Absorptiometry, Photon↗
PubMed2004

Stochastic simulation of alveolar particle deposition in lungs affected by different types of emphysema.

In the present study, disease-specific stochastic models were developed for the computation of particle deposition in lungs affected by COPD, emphysema, or both, distinguishing between four types of pulmonary emphysema-centriacinar, paraseptal, panacinar, and bullous. To simulate COPD, airway calibers of the tracheobronchial tree were randomly reduced between 20% and 50% in each airway. For the study of pure COPD ("blue bloaters"), alveolated airway dimensions of the healthy lung were used, while for the simulation of emphysema without COPD ("pink puffers"), normal conductive airway diameters were assumed. Deposition calculations in diseased lungs were carried out by assuming (a) identical inspiration and expiration times (no breath-hold time) and (b) a continuous increase of the functional residual capacity (from 3,300 to 5,000 mL), accompanied by a simultaneous drop of the tidal volume (from 1,000 to 500 mL). Independent of particle size, total alveolar deposition in emphysematous lungs was significantly decreased relative to normal lungs. In particular, the deposition maximum at large particle sizes, which is a characteristic for healthy subjects, completely disappeared. Among the various emphysema models, deposition was smallest in lungs with bullous emphysema due to strongly enhanced settling and diffusion distances within the alveolar structures. A change of the lung volume caused a further decrease in particle deposition. Alveolar deposition in "blue bloaters" and "pink puffers" was very similar to the deposition in patients suffering from COPD and emphysema. Alveolar deposition per acinar airway generation was also strongly reduced in diseased lungs compared to normal lungs. Besides this reduction, deposition patterns became more uniform throughout the alveolar region.

Aerosols↗
PubMed1999

Cigarette smoke exposure produces more evidence of emphysema in B6C3F1 mice than in F344 rats.

Cigarette smoke (CS) causes pulmonary emphysema in humans, but results of previous studies on CS-exposed laboratory animals have been equivocal and have not clearly demonstrated progression of the disease. In this study, morphometry and histopathology were used to assess emphysema in the lungs of B6C3F1 mice and Fischer-344 rats. The animals were exposed, whole-body, to CS at a concentration of 250 mg total particulate matter/m3 for 6 h/day, 5 days/week, for either 7 or 13 months. Morphometry included measurements of parenchymal air space enlargement (alveolar septa mean linear intercept [Lm], volume density of alveolar air space [VVair]), and tissue loss (volume density of alveolar septa [VVspt]). In addition, centriacinar intra-alveolar inflammatory cells were counted to assess species differences in the type of inflammatory response associated with CS exposure. In mice, many of the morphometric parameters indicating emphysema differed significantly between CS-exposed and control animals. In CS-exposed rats, only some of the parameters differed significantly from control values. The Lm in both CS-exposed mice and rats was increased at 7 and 13 months, indicating an enlargement of parenchymal air spaces, but the VVair was increased significantly only in CS-exposed mice. The VVspt was decreased at both time points in mice, but not in rats, indicating damage to the structural integrity of parenchyma. Morphologic evidence of tissue destruction in the mice included alveoli that were irregular in size and shape and alveoli with multiple foci of septal discontinuities and isolated septal fragments. Morphometric differences in the mice at 13 months were greater than at 7 months, suggesting a progression of the disease. Inflammatory lesions within the lungs of mice contained significantly more neutrophils than those lesions in rats. These results suggest that B6C3F1 mice are more susceptible than F344-rats to the induction of emphysema by this CS exposure regimen and that in mice the emphysema may be progressive. Furthermore, the type of inflammatory response may be a determining factor for species differences in susceptibility to emphysema induction by CS exposure.

Animals↗
PubMed1992

High-resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusing capacity.

To determine the prevalence of "nonobstructive" (impairment of gas transfer) emphysema in a select population of smokers with dyspnea, a retrospective study of patients with emphysema evident at high-resolution computed tomography (HRCT) was undertaken. Four hundred seventy HRCT studies were reviewed. In 47 cases, centrilobular emphysema was the dominant or sole parenchymal abnormality. Concomitant chest radiographs were available in 41 of these cases; 16 of the 41 lacked radiographic findings of emphysema. Among these 16 patients, pulmonary function testing revealed 10 to have normal flow rates (ratio of forced expiratory volume in 1 second to forced vital capacity and forced expiratory volume in 1 second greater than 80% predicted) and impaired gas transfer (single-breath carbon monoxide diffusing capacity [DLCOSB] less than 80% predicted). With the exclusion of one patient with congestive heart failure from the group of 10, the severity of emphysema at HRCT correlated inversely with DLCOSB (r = -.643). These results indicate that HRCT allows detection of emphysema in symptomatic patients when chest radiographs and pulmonary function tests are nondiagnostic.

Female↗
PubMed1994

Left ventricular systolic performance is depressed in chronic pulmonary emphysema in dogs.

The effect of chronic right ventricular (RV) pressure overload on left ventricular (LV) systolic function in chronic obstructive lung disease is unclear. To examine LV systolic performance in pulmonary emphysema, a chronic canine model was developed in which pulmonary artery pressure could be elevated to a level found in human disease. Severe emphysema was produced by the repeated instillations of the enzyme papain into the lung. Sonomicrometry was used to assess LV dimensions along the septal-lateral, apex-base, and anterior-posterior orthogonal axes of the LV. With the animal conscious, measurements of LV systolic function were obtained over a wide range of LV circumferential end-ejection stresses at baseline and after 1 yr of emphysema (post-1-yr study). In the emphysema group (n = 5), the results showed that at the post-1-yr study, measurements of LV ejection fraction, mean velocity of circumferential shortening, and rate of anterior-posterior dimensional shortening were reduced compared with those obtained at the baseline study. In the emphysema group, end-systolic volume was increased for a given end-systolic pressure or stress at the post-1-yr study compared with baseline values, while fractional shortening measured along the three axes was decreased. There were no similar changes in systolic parameters in control groups. We conclude that chronic RV pressure overload may cause an impairment in LV systolic performance in chronic emphysema.

Analysis of Variance↗
PubMed2004

Defect of hepatocyte growth factor production by fibroblasts in human pulmonary emphysema.

Pulmonary emphysema results from an excessive degradation of lung parenchyma associated with a failure of alveolar repair. Secretion by pulmonary fibroblasts of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) is crucial to an effective epithelial repair after lung injury. We hypothesized that abnormal HGF or KGF secretion by pulmonary fibroblasts could play a role in the development of emphysema. We measured in vitro production of HGF and KGF by human fibroblasts cultured from emphysematous and normal lung samples. HGF and KGF production was quantified at basal state and after stimulation. Intracellular content of HGF was lower in emphysema (1.52 pg/mug, range of 0.15-7.40 pg/mug) than in control fibroblasts (14.16 pg/mug, range of 2.50-47.62 pg/mug; P = 0.047). HGF production by emphysema fibroblasts (19.3 pg/mug protein, range of 10.4-39.2 pg/mug) was lower than that of controls at baseline (57.5 pg/mug, range of 20.4-116 pg/mug; P = 0.019) and after stimulation with interleukin-1beta or prostaglandin E(2). Neither retinoic acids (all-trans and 9-cis) nor N-acetylcysteine could reverse this abnormality. KGF production by emphysema fibroblasts (5.3 pg/mug, range of 2.2-9.3 pg/mug) was similar to that of controls at baseline (2.6 pg/mug, range of 1-6.1 pg/mug; P = 0.14) but could not be stimulated with interleukin-1beta. A decreased secretion of HGF by pulmonary fibroblasts could contribute to the insufficient alveolar repair in pulmonary emphysema.

Acetylcysteine↗
PubMed2006

Elastin protein levels are a vital modifier affecting normal lung development and susceptibility to emphysema.

Cigarette smoking is the strongest risk factor for emphysema. However, sensitivity to cigarette smoke-induced emphysema is highly variable, and numerous genetic and environmental factors are thought to mitigate lung response to injury. We report that the quantity of functional elastin in the lung is an important modifier of both lung development and response to injury. In mice with low levels of elastin, lung development is adversely affected, and mice manifest with congenital emphysema. Animals with intermediate elastin levels exhibit normal alveolar structure but develop worse emphysema than normal mice following cigarette smoke exposure. Mechanical testing demonstrates that lungs with low levels of elastin experience greater tissue strains for any given tissue stress compared with wild-type lungs, implying that force-mediated propagation of lung injury through alveolar wall failure may worsen the emphysema after an initial enzymatic insult. Our findings suggest that quantitative deficiencies in elastin predispose to smoke-induce emphysema in animal models and suggest that humans with altered levels of functional elastin could have relatively normal lung function while being more susceptible to smoke-induced lung injury.

Animals↗
PubMed1980

Pressure-volume characteristics of excised human lungs: effects of sex, age, and emphysema.

Static deflationary pressure-volume curves were obtained in 28 emphysema-free (18 male and 10 female) and 39 emphysematous excised human lungs inflated to a maximum transpulmonary pressure (Pl) of 30 cmH2O. In emphysema-free lungs, the lung volumes at Pl 30 cmH2O (V30) were significantly related to body length in males and were significantly larger than predicated total lung capacity in vivo. However, corrected for stature (V30/body length), there was no significant age correlation. In both males and females, highly significant correlations between the PL at 50--90% V30 and age were obtained. There were no significant differences in these regressions between males and females. The emphysematous lungs were divided into three groups with increasing emphysema grades. Progressive decreases in the PL at 50--90% V30 and increases in the V30 were seen in the groups with increasing degrees of emphysema. Significant changes occurred in these measurements even in group 2 with mild emphysema, suggesting that the lesions of emphysema are not directly responsible for these changes.

Adolescent↗
PubMed1998

Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity.

Skeletal muscle oxidative enzyme capacity is impaired in patients suffering from emphysema and chronic obstructive pulmonary disease. This effect may result as a consequence of the physiological derangements because of the emphysema condition or, alternatively, as a consequence of the reduced physical activity level in these patients. To explore this issue, citrate synthase (CS) activity was measured in selected hindlimb muscles and the diaphragm of Syrian Golden hamsters 6 mo after intratracheal instillation of either saline (Con, n = 7) or elastase [emphysema (Emp); 25 units/100 g body weight, n = 8]. Activity level was monitored, and no difference between groups was found. Excised lung volume increased with emphysema (Con, 1.5 +/- 0.3 g; Emp, 3.0 +/- 0.3 g, P < 0.002). Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 +/- 2.0; Emp, 39.2 +/- 0.8 micromol . min-1 . g wet wt-1, P < 0.05) and vastus lateralis (Con, 48.5 +/- 1.5; Emp, 44.9 +/- 0.8 micromol . min-1 . g wet wt-1, P < 0.05) but not in the plantaris (Con, 47.4 +/- 3.9; Emp, 48.0 +/- 2.1 micromol . min-1 . g wet wt-1, P < 0.05) muscle. In contrast, CS activity increased in the costal (Con, 61.1 +/- 1.8; Emp, 65.1 +/- 1.5 micromol . min-1 . g wet wt-1, P < 0.05) and crural (Con, 58.5 +/- 2.0; Emp, 65.7 +/- 2.2 micromol . min-1 . g wet wt-1, P < 0.05) regions of the diaphragm. These data indicate that emphysema per se can induce decrements in the oxidative capacity of certain nonventilatory skeletal muscles that may contribute to exercise limitations in the emphysematous patient.

Animals↗
PubMed1978

Evaluation of the distribution of air and blood in emphysema patients using radioisotopic tracers.

Continuous recording of the respiratory cycle with the simultaneous or sequential radionucleic exploration (gamma camera) of ventilation (133Xe) and perfusion (MAT-99) was performed to determine the V/Q index in regional areas (Polaroid photography, mini-computer, memory visualization system, Benson incremental tracer, etc.) from the level of 1,024 points. An average ratio per sector was calculated and only three median sectors were retained. The wash-in and wash-out curves were traced by computer, and the calculation of the average T 1/2 for the different compartments of each median sector (apex--middle and base) was done in about 22 observations: in 18 diffuse emphysema, 11 of which were associated with giant cystic emphysema (spirometric, plethysmographic and radiographic data), T 1/2 values were greater than those of normal subjects (compartments C1 and C2) in diffuse emphysema and can become indefinable in zones of cystic emphysema. The values of the index V/Q approach the normal in diffuse emphysema with a tendency toward equalization of the ratios from the apex to the base. Extremely large divergence is observed in the elevated V/Q ratios in cystic emphysema.

Adult↗
PubMed1994

Scanning electronmicroscopic morphometry of emphysema in humans.

We quantitated the holes in alveolar walls in 11 nonemphysematous lungs and in 11 lungs with mild emphysema, all of which were removed at surgery. We found that in the nonemphysematous lungs, 94.1% of the holes were smaller than 10 microns in diameter and only 0.2% were larger than 20 microns. In the lung parenchyma distant from emphysema, both the maximum diameter of the holes and the diameter of alveoli increased. In the parenchyma between emphysema, the areas of alveolar walls represented by holes also increased, as did the average hole area and number of holes per alveolus. We found that alveolar holes in the regions between emphysema correlated better with pulmonary function tests than did those in regions distant from emphysema. The maximum diameter of holes and the number of holes per alveolus correlated with functional residual capacity, residual volume, closing capacity expressed as a proportion of total lung capacity (CC/TLC), and static recoil pressure of the lung at TLC. Emphysema correlated with CC/TLC and with the transpulmonary pressure at 90% TLC. Bronchiolar lesions were not related to pulmonary function tests. Our data provide support for the hypothesis that the tissue surrounding emphysematous lesions contributes to loss of recoil.

Functional Residual Capacity↗
PubMed1995

Oxygen cost of breathing in patients with emphysema or chronic bronchitis in acute respiratory failure.

This study compared the oxygen cost of breathing (VO2 resp) in 19 patients with severe chronic obstructive pulmonary disease intubated for acute respiratory failure. Ten patients showed radiologic (X-ray and/or computed tomographic scan) evidence of emphysema. The remaining ones were considered as having chronic bronchitis. Measurements were made just before extubation. Despite similar expiratory airflow obstruction, patients with emphysema exhibited significantly higher VO2 resp than patients with chronic bronchitis (109 +/- 61 versus 42 +/- 26 ml/min/m2, respectively; p < 0.006). Moreover, emphysema was associated with nutritional depletion assessed through decreases in body mass index (emphysema: 17.9 +/- 3.5 kg/m2; chronic bronchitis: 28.8 +/- 8.2 kg/m2; p < 0.005). This seemed to affect somatic stores (significant decreases in arm muscular circumference and triceps skin-fold thickness, whereas visceral stores were preserved (no decreases in serum albumin, serum prealbumin, and retinol binding protein). Malnutrition appeared to be the consequence of a hypermetabolic state of the respiratory muscles, with a significant negative correlation between VO2 resp and body mass index, arm muscular circumference, and triceps skinfold thickness (p < 0.05). Total oxygen consumption normalized for body surface was similar in the two groups. Thus, in emphysematous patients, the oxygen available for tissues other than respiratory muscles was significantly reduced (emphysema: 124 +/- 51 ml/min/m2; chronic bronchitis: 207 +/- 78 ml/min/m2; p < 0.02). This could explain nutritional differences observed between patients with emphysema and those with chronic bronchitis.

Acute Disease↗