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PubMed1996

Changes in lung volume and volume of emphysema after unilateral lung reduction surgery: analysis with CT lung densitometry.

PURPOSE: To evaluate changes in volume of the lungs and volume of emphysema after unilateral lung reduction surgery (ULRS) by using computed tomographic (CT) lung densitometry. MATERIALS AND METHODS: Twenty-eight patients underwent CT before and 3 months after ULRS. With use of a density mask software program and a three-dimensional graphics workstation, CT scans were analyzed to define the volume of the lungs and the volume of emphysema. Pre- and postoperative mean CT numbers were determined. RESULTS: After ULRS, the surgically reduced lung volume decreased 22%, and the intact opposite lung volume increased 4%. Emphysema in the surgically reduced lung decreased 14% and was unchanged in the intact opposite lung. Mean CT numbers in the surgically reduced lung increased 26 HU but were unchanged in the intact opposite lung. CONCLUSION: The effects of ULRS on each lung can be evaluated by using CT lung densitometry and a three-dimensional graphics workstation. ULRS reduces emphysema and lung volume in the surgically reduced lung without statistically significant worsening of contralateral emphysema at 3 months.

Adult↗
PubMed2003

Progressive adult-onset emphysema in transgenic mice expressing human MMP-1 in the lung.

Mice with lung-specific expression of human matrix metalloproteinase-1 (MMP-1) develop emphysematous changes similar to those seen in smoking-induced emphysema in humans. Morphometric analyses of three transgenic lines [homozygous colony (Col) 34, Col 50, and Col 64] with varying temporal expression of MMP-1 were undertaken to determine the validity of this animal as a model of adult-onset emphysema. Line 50 mice, which have early expression of MMP-1 (14 days postconception), exhibited morphometric changes by 5 days of age. In contrast, homozygous line 34 and 64 with delayed expression (birth and 2 wk of age) were normal up until 4 wk of age when progressive changes in their mean linear intercept were first noted. In contrast, heterozygous mice from line 34 with lower transgene expression did not develop emphysema until 1 yr of age. The changes in mean linear intercept coincided with an increase in lung compliance. Emphysema in these mice was associated with decreased immunostaining for type III collagen within the alveolar septa. This study provides evidence that MMP-1 induces progressive adult-onset emphysema by the selective degradation of type III collagen within the alveolar wall.

Acute Disease↗
PubMed2005

Tomato juice prevents senescence-accelerated mouse P1 strain from developing emphysema induced by chronic exposure to tobacco smoke.

The senescence-accelerated mouse (SAM) is a naturally occurring animal model for accelerated aging after normal development and maturation. SAMP1 strain was reported to show age-related structural and functional changes in lung and to be a murine model of senile lung. We postulated that aging of lung is an important intrinsic process for development of emphysema and even in a short period of tobacco smoke exposure may be able to generate emphysema. At age 12 wk, SAMP1 inhaled air or 1.5% tobacco smoke (total particulate matter 23.9 mg/m3) through the nose for 30 min/day, 5 days/wk, and for 8 wk. The mean linear intercepts (MLI) and destructive index (DI) of lung were significantly increased [air vs. smoke (means+/-SE); MLI, 68.76+/-0.69 vs. 75.34+/-1.70 microm, P<0.05 and DI, 8.61+/-0.38 vs. 16.18+/-1.54%, P<0.05], whereas no significant changes were observed in SAMR1, control mice that show normal aging. In contrast, smoke-induced emphysema was completely prevented by concomitant ingestion of lycopene given as tomato juice [MLI: smoke with/without lycopene (mean+/-SE), 62.87+/-0.8 vs. 66.90+/-1.33 microm, P<0.05]. Smoke exposure increased apoptosis and active caspase-3 of airway and alveolar septal cells and reduced VEGF in lung tissues, but tomato juice ingestion significantly reduced apoptosis and increased tissue VEGF level. We conclude that SAMP1 is a useful model for tobacco smoke-induced emphysema and a valuable tool to explore both pathophysiological mechanisms and the effect of therapeutic intervention on smoke-induced emphysema.

Aging↗
PubMed1995

Smoke-induced emphysema in guinea pigs is associated with morphometric evidence of collagen breakdown and repair.

We have previously shown that chronic cigarette smoke exposure produces emphysema and airflow obstruction in the guinea pig. To further examine the changes in the connective tissue matrix associated with emphysema in this model, we used ultrastructural morphometry to determine the volume proportions of collagen and elastin in the alveolar walls of animals exposed to smoke or air (control) for 1, 3, 6, and 12 mo. After 1 mo of smoke exposure, there was a statistically significant (P < 0.001) decrease in the volume proportion of collagen in the smoke-exposed animals, whereas by 6 and 12 mo of smoke exposure, the proportion of collagen had significantly (P < 0.02, P < 0.03, respectively) increased. The volume proportion of elastin was increased in the smoke-exposed animals at the 12-mo time period. While our results do not exclude reorganization of elastin within the alveolar wall, we conclude that, in this model, cigarette smoke-induced emphysema appears to be associated with collagen breakdown and repair. We suggest that the currently accepted proteolysis-antiproteolysis theory is too narrow in its focus on elastin destruction as the major contributor to emphysema and should be broadened to the concept that smoke-induced emphysema reflects breakdown and resynthesis (possibly overproduction in the form of scarring) of a variety of connective tissue proteins in addition to elastin.

Animals↗
PubMed1976

Exercise stress and enzyme-induced emphysema.

Rats were exposed to an aerosol of 10% papain for 8 h found in pilot studies to produce marked emphysema. One week after exposure some animals were forced to exercise in a motor-driven activity wheel 2 h daily for 4 wk, while others remained at rest. Another group of rats which served as the control were exposed to saline under the same conditions and divided into exercise and rest groups. Elastic recoil pressure (Pst) of lung was measured from static deflation pressure-volume curves with air and saline. Pst measured in air-filled lungs was not significantly different between the emphysema-rest and emphysema-exercise groups. When inflated with saline the Pst was significantly reduced in the emphysema-exercise compared to the emphysema-rest group at high and mid (100, 80, 60%) lung volumes. Pst in air- and saline-filled lungs was not significantly different between the control-rest and control-exercise groups. We therefore conclude that mechanical stress resulting from physical exercise decreased Pst of lung tissue in emphysematous rats.

Animals↗
PubMed1998

Effects of emphysema on diaphragm blood flow during exercise.

Chronic hyperinflation of the lung in emphysema displaces the diaphragm caudally, thereby placing it in a mechanically disadvantageous position and contributing to the increased work of breathing. We tested the hypothesis that total and regional diaphragm blood flows are increased in emphysema, presumably reflecting an increased diaphragm energetic demand. Male Syrian Golden hamsters were randomly divided into emphysema (E; intratracheal elastase 25 units/100 g body wt) and control (C; saline) groups, and experiments were performed 16-20 wk later. The regional distribution of blood flow within the diaphragm was determined by using radiolabeled microspheres in hamsters at rest and during treadmill exercise (walking at 20 feet/min, 20% grade). Consistent with pronounced emphysema, lung volume per unit body weight was greater in E hamsters (C, 59.3 +/- 1.8; E, 84.5 +/- 5.0 ml/kg; P < 0.001) and arterial PO2 was lower both at rest (C, 74 +/- 3; E, 59 +/- 2 Torr; P < 0.001) and during exercise (C, 93 +/- 3; E, 69 +/- 4 Torr; P < 0.001). At rest, total diaphragm blood flow was not different between C and E hamsters (C, 47 +/- 4; E, 38 +/- 4 ml . min-1 . 100 g-1; P = 0.18). In both C and E hamsters, blood flow at rest was lower in the ventral costal region of the diaphragm than in the dorsal and medial costal regions and the crural diaphragm. During exercise in both C and E hamsters, blood flows increased more in the dorsal and medial costal regions and in the crural diaphragm than in the ventral costal region. Total diaphragm blood flow was greater in E hamsters during exercise (C, 58 +/- 7; E, 90 +/- 14 ml . min-1 . 100 g-1; P = 0.03), as a consequence of significantly higher blood flows in the medial and ventral costal regions and crural diaphragm. In addition, exercise-induced increases in intercostal (P < 0.005) and abdominal (P < 0.05) muscle blood flows were greater in E hamsters. The finding that diaphragm blood flow was greater in E hamsters during exercise supports the contention that emphysema increases the energetic requirements of the diaphragm.

Animals↗
PubMed2001

Volume displaced by diaphragm motion in emphysema.

To examine the effect of hyperinflation on the volume displaced by diaphragm motion (DeltaVdi), we compared nine subjects with emphysema and severe hyperinflation [residual volume (RV)/total lung capacity (TLC) 0.65 +/- 0.08; mean +/- SD] with 10 healthy controls. Posteroanterior and lateral chest X rays at RV, functional residual capacity, one-half inspiratory capacity, and TLC were used to measure the length of diaphragm apposed to ribcage (Lap), cross-sectional area of the pulmonary ribcage, DeltaVdi, and volume beneath the lung-apposed dome of the diaphragm. Emphysema subjects, relative to controls, had increased Lap at comparable lung volumes (4.3 vs. 1.0 cm near predicted TLC, 95% confidence interval 3.4-5.2 vs. 0-2.1), pulmonary rib cage cross-sectional area (emphysema/controls 1.22 +/- 0.03, P < 0.001 at functional residual capacity), and DeltaVdi/DeltaLap (0.25 vs. 0.14 liters/cm, P < 0.05). During a vital capacity inspiration, relative to controls, DeltaVdi was normal in five (1.94 +/- 0.51 liters) and decreased in four (0.51 +/- 0.40 liters) emphysema subjects, and volume beneath the dome did not increase in emphysema (0 +/- 0.36 vs. 0.82 +/- 0.80 liters, P < 0.05). We conclude that DeltaVdi can be normal in emphysema because 1) hyperinflation is shared between ribcage and diaphragm, preserving Lap, and 2) the diaphragm remains flat during inspiration.

Abdomen↗
PubMed2006

Evaluation of emphysema severity and progression in a rabbit model: comparison of hyperpolarized 3He and 129Xe diffusion MRI with lung morphometry.

The apparent diffusion coefficients (ADCs) of hyperpolarized (3)He and (129)Xe gases were measured in the lungs of rabbits with elastase-induced emphysema and correlated against the mean chord length from lung histology. In vivo measurements were performed at baseline and 2, 4, 6, and 8 wk after instillation of elastase (mild and moderate emphysema groups) or saline (control group). ADCs were determined from acquisitions that used two b values. To investigate the effect of b value on the results, b-value pairs of 0 and 1.6 s/cm(2) and 0 and 4.0 s/cm(2) were used for (3)He, and b-value pairs of 0 and 5.0 s/cm(2) and 0 and 10.0 s/cm(2) were used for (129)Xe. At 8 wk after instillation, the rabbits were euthanized, and the lungs were analyzed histologically and morphometrically. ADCs for the rabbits in the control group did not change significantly from baseline to week 8, whereas ADCs for the rabbits in the emphysema groups increased significantly (P < 0.05) for all gas and b-value combinations except (129)Xe with the b-value pair of 0 and 5.0 s/cm(2). The largest percent change in mean ADC from baseline to week 8 (15.3%) occurred with (3)He and the b-value pair of 0 and 1.6 s/cm(2) for rabbits in the moderate emphysema group. ADCs (all b values) were strongly correlated (r = 0.62-0.80, P < 0.001) with mean chord lengths from histology. These results further support the ability of diffusion-weighted MRI with hyperpolarized gases to detect regional and global structural changes of emphysema within the lung.

Animals↗
PubMed2005

Single-breath test in lateral decubitus reflects function of single lungs grafted for emphysema.

The slope of alveolar plateau for nitrogen derived from the single-breath test is useful to assess the function of bilateral lung grafts, but this technique is not applicable to patients with single-lung grafts due to the confounding influence of the native lung. We tested the hypothesis that the nitrogen slope measured in lateral decubitus with the graft in nondependent position may primarily reflect the distribution of ventilation in this lung. Fifteen patients with single-lung transplantation for emphysema, 10 healthy controls, and 7 patients with advanced emphysema performed single-breath washouts in right and left lateral decubitus; nitrogen slope was measured between 75 and 100% of expired volume. In 10 transplant recipients, the volume of each lung was measured in the two postures by computerized tomography. Nitrogen slope was unaffected by posture in normal controls and emphysema patients. On the other hand, nitrogen slope in transplant recipients was invariably smaller, with the graft in nondependent vs. in dependent position. Values of nitrogen slope with the graft in nondependent position were similar to those obtained in normal controls but significantly smaller than those obtained in emphysema patients. Computerized tomography studies in this position indicated that the volume expired below functional residual capacity was exclusively contributed by the graft. We conclude that, in patients with single-lung transplantation for emphysema, 1) measuring nitrogen slope in lateral decubitus allows to distinguish between the graft and the native lung, and 2) nitrogen slope obtained with the graft in nondependent position reflects ventilation distribution in this lung.

Breath Tests↗
PubMedDate not supplied

Revisiting "respiratory function in emphysema in relation to prognosis".

BACKGROUND: The 1956 paper by DV Bates, JMS Knott and RV Christie, "Respiratory function in emphysema in relation to prognosis" Quart J Med 1956;97:137-157 is largely reprinted with a commentary by the first author, Dr David Bates. Although the pathology of emphysema was well recognized at the time, the clinical diagnosis and assessment of its severity were known to be imprecise; physiological measurements assessing and following the clinical course had not been established. The study aimed to follow systematically a group of patients, selected by clinical criteria using standardized clinical and physiological techniques, over four years and correlate physiological and clinical changes in relation to prognosis and eventually to postmortem findings. Fifty-nine patients were recruited to an emphysema clinic at St Bartholomew's Hospital, London, England. Inclusion criteria were dyspnea without other causes and no cor pulmonale present. Patients' symptoms were assessed by a standardized questionnaire, and measurements were taken of lung volumes, maximal ventilatory volume, carbon monoxide diffusing capacity at rest, exercise and oxygen saturation by oximetry. During the four years of the study, 17 patients died (actuarial expected - four) and 13 presented with signs of pulmonary heart failure. All postmortem examinations (n=9) showed advanced emphysema. A seasonal variation in dyspnea was established (the period included the infamous 1952 London smog). Four patients improved, and the remainder were unchanged or deteriorated. Close relationships were shown between dyspnea and function results, particularly for the diffusing capacity of lungs for carbon monoxide (DLCO). A comparison among a group of patients with chronic bronchitis without dyspnea showed that the DLCO discriminated between them. A loss of the normal increase in DLCO during exercise was shown in emphysema. IMPORTANCE: The study showed the value of standardized clinical and physiological techniques in following chronic obstructive pulmonary disease patients, and of separating the effects of airflow obstruction from impaired gas exchange function. Impaired gas exchange was shown to be important in influencing prognosis.

History, 20th Century↗
PubMedDate not supplied

Bullae, bronchiectasis and nutritional emphysema in severe anorexia nervosa.

STUDY OBJECTIVES: Pulmonary complications of anorexia nervosa are rarely documented. The case of a patient with anorexia nervosa and pulmonary disease is presented, a new quantitative computed tomography (CT) method for the detection of emphysema is employed, the literature is reviewed and the concept of 'nutritional' emphysema is discussed. RESULTS: The case of a 34-year-old, nonsmoking woman with long-standing severe anorexia nervosa who was evaluated for cough and progressive shortness of breath is reported. Pulmonary function testing showed a predominant restrictive pattern with a marked reduction in carbon monoxide transfer and respiratory muscle strength, and an elevated residual volume. Imaging revealed bullae and bronchiectasis, and quantitative analysis of the CT scan was consistent with mild, generalized emphysema. Bronchial washings grew Pseudomonas aeruginosa. Known causes for bronchiectasis were excluded. A literature review disclosed few reported noninfectious pulmonary complications of anorexia nervosa. CONCLUSIONS: To the authors' knowledge, this is the first report of bullae and bronchiectasis in a patient with anorexia nervosa, and the CT analysis was consistent with mild emphysema. Malnutrition has been associated with emphysematous changes in animals and may be the primary insult in the development of emphysema, bullae and bronchiectasis in the present patient.

Adult↗
PubMed1979

Dco at various breath-holding times: comparison in patients with chronic bronchial asthma and emphysema.

Measurement of Dco is known to be dependent upon functional inhomogeneities. Because different types of inhomogeneities are operative in patients with bronchial asthma and patients with emphysema, different changes of Dco with increasing breath-holding time, tA, are to be expected. We studied the change of Dco with increasing breath-holding time in healthy subjects, patients with asthma bronchiale and patients with emphysema. In the patients the severity of airway obstruction was about the same. The following results were obtained: (a) in healthy subjects and in the asthmatics Dco decreased with tA, in a similar manner, approaching a value (ml . min-1 . Terror-1) of 34.7 and 31.6 at 10 sec, respectively, and (b) in patients with emphysema Dco increased with tA, yielding negative values at small tA: 1.5 sec-23.4; 10 sec: 11.7. From these results we suggest that in healthy subjects and in patients with bronchial asthma parallel inhomogeneities influence the course of Dco. In emphysema the time couse of Dco is best explained with a faster intrapulmonary mixing of He compared to CO. This behavior indicates that in emphysema low Dco values can be mainly attributed to large diffusional resistances (stratification) within the lungs.

Adult↗
PubMed1993

Altered left ventricular chamber stiffness and isovolumic relaxation in dogs with chronic pulmonary hypertension caused by emphysema.

BACKGROUND: In chronic obstructive lung disease, a right to left ventricular septal shift that occurs as a consequence of right ventricular pressure overload is the usual mechanism given to explain a decrease in left ventricular (LV) diastolic performance. The purpose of the present study was to examine the extent to which this mechanism could account for a decrease in LV diastolic function in a canine model in which pulmonary artery pressure was elevated to a level found in human disease. METHODS AND RESULTS: Severe emphysema was produced in dogs by repeated instillations of the enzyme papain into the lung. To assess LV diastolic function, we used sonomicrometry, in which three pairs of subendocardial crystal transducers were implanted along the three orthogonal axes of the LV. LV end-diastolic dimensions and pressure-strain relations along the three axes, as well as the time constant of LV isovolumic relaxation (T), were measured before (baseline) and after 1 year of emphysema (post-1-year study). The results showed that after 1 year of pulmonary hypertension, LV pressure-strain relations were decreased along the septal-lateral and anterior-posterior axes, but a right to left ventricular septal shift was not detected. The relation of average midwall circumferential stress to midwall circumferential strain was used to describe the intrinsic compliance of the LV. The results showed that myocardial stiffness increased in emphysema but that chamber volume was not reduced. At the post-1-year study, T was abnormally increased in the emphysema group in response to augmented preload and afterload compared with preemphysema measurements. CONCLUSIONS: We conclude that mechanisms other than ventricular interdependence may be operative in leading to altered LV diastolic filling in chronic emphysema.

Analysis of Variance↗
PubMed1994

Neutrophil formyl-peptide receptors. Relationship to peptide-induced responses and emphysema.

A reproducible assay was established to assess the number of formyl-peptide receptors expressed on the surface of human polymorphonuclear leukocytes (PMN). Using this assay the number of receptors was shown to demonstrate wide within- and between-subject variability. However, the receptor numbers were related to the chemotactic response (r = 0.572) and degranulation response (r = 0.512) to the peptide formyl-methionyl-leucyl-phenylalanine. Subsequent studies showed increased receptor numbers on PMN from patients with emphysema (median, 459 x 10(3)/cell; range, 207 to 1,080) as compared with age-matched control subjects (median, 288; range, 168 to 519; p < 0.02), which may explain the increased chemotactic response of the PMN to formyl peptides. This difference was not observed in patients with bronchiectasis, suggesting that the increased receptor number is a feature of emphysema. Furthermore, the increase was largely a feature of smokers with emphysema (median, 463; range, 362 to 1,080), whereas age-matched smokers without emphysema had lower numbers of receptors (p < 0.001; median, 332; range, 243 to 411). This observation suggests a mechanism that may explain the susceptibility of some smokers to the development of emphysema.

Adult↗
PubMed1994

Apocynin improves the efficacy of secretory leukocyte protease inhibitor in experimental emphysema.

Secretory leukocyte protease inhibitor (SLPI) is a potent proteinase inhibitor produced in the lung. Stimulated neutrophils at sites of inflammation can inactivate SLPI by myeloperoxidase-mediated oxidation of the methionine residue in the active site of SLPI. Apocynin is a selective inhibitor of NADPH oxidase and may therefore protect SLPI against neutrophil-mediated oxidative inactivation. The aim of the present study was to determine the effect of apocynin on the efficacy of SLPI in preventing experimental emphysema. To investigate the effect of apocynin on emphysema without SLPI treatment, three groups of eight hamsters each received drinking water containing apocynin at concentrations of 2, 20, and 200 micrograms/ml, respectively. Emphysema was induced in these hamsters by intratracheal instillations of 500 micrograms of lipopolysaccharide (LPS) twice a week for 4 wk. In hamsters that received 200 micrograms/ml apocynin, the development of emphysema was reduced by 26.2% (p = 0.01). Other apocynin concentrations had no effect. The experiment was repeated, with SLPI added to the treatment. Of a total of six groups of hamsters, four groups (three with apocynin and one with solvent) received twice-weekly doses of a mixture of 500 micrograms of LPS and 1 mg SLPI in 200 microliters saline in the trachea for 4 wk. In addition, each LPS instillation was followed 24 and 48 h later by an instillation containing 1 mg of SLPI. Apocynin (20 and 200 micrograms/ml) improved the protective effect of SLPI from 37 to 64% and 79%, respectively (p < 0.01). We conclude that oral administration of apocynin can improve the efficacy of SLPI in preventing LPS-induced emphysema.

Acetophenones↗
PubMed1995

Radiologic evaluation of emphysema in patients with chronic obstructive pulmonary disease. Chest radiography versus high resolution computed tomography.

To objectively reappraise the role of the chest radiograph (CXR) in the clinical assessment of emphysema, we compared a standardized reading of CXR with both a visual scoring and a quantitative analysis of high resolution computed tomography (HRCT) of the chest in 46 consecutive patients with chronic obstructive pulmonary disease (COPD) and fixed expiratory airflow limitation. CXR were scored for signs of overinflation and pulmonary vascular deficiency by three independent observers. HRCT scans were independently scored for extent of emphysema and for both severity and extent of emphysema. In 28 of 46 patients, inspiratory and expiratory HRCT scans were analyzed quantitatively by measuring the mean CT number in Hounsfield Units (HU) and the percentage of lung area with CT numbers < -900 HU. Quantitative CT data were compared with reference values obtained in seven normal nonsmokers. The CXR score of emphysema showed a highly significant interobserver reproducibility and correlated linearly (p < 0.001) with HRCT visual scores and quantitative data from both inspiratory and expiratory CT scan. CXR score correlated with functional indices of airflow obstruction, overinflation, and impaired lung diffusing capacity in a way comparable to that obtained by using qualitative and quantitative CT data. Patients with no signs of emphysema on CXR had mean expiratory CT numbers within normal range and a fraction of lung area with CT numbers < -900 HU on expiratory scan not exceeding 15% of total cross-sectional area. The latter value was consistently greater than 15% in patients with CXR score > 0.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1996

Lack of a relationship of elastin peptide level to emphysema assessed by CT scans.

Clinical reports suggest that peptide (EP) concentration may be used as a subclinical marker of pulmonary emphysema. This hypothesis was tested in a clinical study by comparing EP concentration in male emphysematous patients with the level in two control groups, and by exploring the relation of elastin peptide level to high-resolution computed tomography (HRCT) scan emphysema score among emphysematous patients. Serum EP level was determined among male emphysematous patients with at least 20% of emphysema (n = 27) and in two populations of male workers, drawn from epidemiologic studies (227 coal miners and 310 policemen). No difference in elastin peptide concentration was observed between emphysematous patients and control subjects (mean +/- SD = 2.39 +/- 1.18 micrograms/ml in patients versus 2.55 +/- 1.34 micrograms/ml in policemen and 2.59 +/- 1.20 micrograms/ml in coal miners). The correlation of elastin peptide concentration with percentage of pulmonary emphysema was negative and of borderline significance (r = -0.36; p = 0.06). These results cast doubts on the usefulness of elastin peptide level as a predictive marker of pulmonary emphysema.

Adult↗
PubMed2001

Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema.

Emphysema due to cigarette smoking is characterized by a loss of alveolar structures. We hypothesize that the disappearance of alveoli involves apoptosis of septal endothelial cells and a decreased expression of lung vascular endothelial growth factor (VEGF) and its receptor 2 (VEGF R2). By terminal transferase dUTP nick end labeling (TUNEL) in combination with immunohistochemistry, we found that the number of TUNEL+ septal epithelial and endothelial cells/lung tissue nucleic acid (microg) was increased in the alveolar septa of emphysema lungs (14.2 +/- 2.0/microg, n = 6) when compared with normal lungs (6.8 +/- 1.3/microg, n = 7) (p < 0.01) and with primary pulmonary hypertensive lungs (2.3 +/- 0.8/microg, n = 5) (p < 0.001). The cell death events were not significantly different between healthy nonsmoker (7.4 +/- 1.9/microg) and smoker (5.7 +/- 0.7/microg) control subjects. The TUNEL results were confirmed by single-stranded DNA and active caspase-3 immunohistochemistry, and by DNA ligation assay. Emphysema lungs (n = 12) had increased levels of oligonucleosomal-length DNA fragmentation when compared with normal lungs (n = 11). VEGF, VEGF R2 protein, and mRNA expression were significantly reduced in emphysema. We propose that epithelial and endothelial alveolar septal death due to a decrease of endothelial cell maintenance factors may be part of the pathogenesis of emphysema.

Adolescent↗