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PubMed1999

Diffusing capacity limitations of the extent of lung volume reduction surgery in an animal model of emphysema.

OBJECTIVE: The purpose of this study was to investigate in an elastase-induced emphysema rabbit model the effects of increasing resection volumes during lung volume reduction surgery on pulmonary compliance, forced expiratory air flow, and diffusing capacity to assess factors limiting optimal resection. METHODS: Emphysema was induced in 68 New Zealand White rabbits with 15,000 units of aerosolized elastase. Static respiratory system compliance, forced expiratory flow, and single-breath diffusing capacity were measured before the induction of emphysema, after the induction of emphysema, and 1 week after a bilateral upper and middle lobe lung volume reduction operation. RESULTS: Static respiratory system compliance with 60 mL insufflation above functional residual capacity increased with emphysema induction and then decreased progressively with resection of larger volumes of lung tissue (P =.001 by analysis of variance). Expiratory flow improved after lung resection in the rabbits with large resection volumes. In contrast, diffusing capacity tended to deteriorate with larger resection volumes (P =. 18). CONCLUSION: Improvements in respiratory system compliance and forced expiratory flow after lung volume reduction operations may account for the improvements seen clinically. Declines in diffusing capacity with extensive lung reduction may limit the clinical benefits associated with greater tissue resection volumes. Future investigations with animal models may reveal other physiologic parameters that may further guide optimal lung volume reduction procedures.

Animals↗
PubMed2002

CT of emphysema.

This article focuses on three main topics: (1) the importance of emphysema as a serious respiratory disease, (2) qualitative assessment of emphysema using CT, and (3) the emerging importance of quantitative CT in the evaluation of patients with emphysema for surgery and drug therapy. CT also can identify the major anatomic subtypes of emphysema. CT is critical in the assessment of patients with the potential for lung volume reduction surgery. CT may well be superior to pulmonary function tests in the longitudinal assessment of current and proposed drug therapies for the treatment of emphysema.

Administration, Inhalation↗
PubMed1999

Radiologic evaluation of emphysema for lung volume reduction surgery.

Lung volume reduction surgery has created an opportunity for the advanced imaging of emphysema. Patients with CT or perfusion scintigraphy demonstrating an upper- or lower-lobe-predominant pattern of emphysema have better patient outcomes after LVRS than patients with emphysema diffusely or homogeneously distributed throughout the lungs. Some patients with diffuse or homogeneous emphysema may demonstrate improvement in function or dyspnea after surgery, but the magnitude of the improvement seen is less than in patients with heterogeneous emphysema, and the duration of benefit is not known. An ongoing, multicenter National Heart, Lung, and Blood Institute (NHLBI)/Health Care Financing Association (HCFA) sponsored trial of LVRS aims to determine whether LVRS together with maximal medical therapy and pulmonary rehabilitation improves patient outcomes compared with maximal medical therapy and pulmonary rehabilitation alone. This study will address the duration of clinical benefit and the cost-effectiveness of LVRS.

Diagnostic Imaging↗
PubMed1988

Airway inflammatory cells in upper and lower lobes in lungs of patients with and without emphysema.

Tissue destruction seen in emphysema is thought to be due to the proteolytic enzymes released by inflammatory cells. Since centriacinar emphysema is worse in upper lobes, it has been suggested that inflammation should be more marked in the upper lobes. To ascertain whether the inflammatory cell population in the walls and lumens of airways is similar in the upper and lower lobes and whether this distribution is altered by the presence of emphysema, we examined the number and types of airway inflammatory cells in 10 surgical pneumonectomy specimens. We found that there was no difference between the upper and lower lobes in the numbers and types of inflammatory cells in the airway walls and lumens. This was true whether or not emphysema was present. We conclude that, in this cross-sectional study, the presence of emphysema in the upper lobes of lung is not associated with an increased number of acute inflammatory cells.

Aged↗
PubMed1997

[Value and limits of selective bronchial obstruction in neonatal unilateral interstitial emphysema].

BACKGROUND: Two methods of selective ventilation have been used for treating severe localized pulmonary emphysema in the neonates: controlateral selective intubation and selective bronchial obstruction. CASE REPORTS: Three neonates with acute respiratory distress required respiratory support that was complicated by development of severe localized pulmonary interstitial emphysema of the right lobe (two cases) and the middle lobe (one case). Selective bronchial obstruction with a Swann Ganz catheter SF was tentatively made: in one case, improvement was moderate and transitory, requiring middle lobectomy. The localized emphysema disappeared within 3 days in the two other cases but a localized emphysema appeared in the controlateral lung in one of them, requiring left inferior lobectomy because the ineffectiveness of selective intubation or selective obstruction. CONCLUSION: Selective bronchial obstruction may fail but this easy and well tolerated method should be tried in severe localized emphysema, specially in those patients who cannot be ventilated with high-frequency oscillation.

Bronchi↗
PubMed1996

Pulmonary function of patients with spontaneous pneumothorax in relation to the extent of emphysema-like changes.

The aim of the present study was to analyse pulmonary function parameters of patients with spontaneous pneumothorax (SP) in relation to the extent of emphysema-like changes (ELCs). Pulmonary function tests were performed in 85 patients with unilateral SP, 6 weeks after video-assisted thoracoscopy (VAT). In 63 patients, thoracic computer tomography (CT) was obtained. An ELCs score, based on findings of CT and VAT, was used to quantify ELCs, ranging from 0 (expressing no ELCs) to 3 (expressing extensive ELCs). Emphysema-like changes were detected during VAT in 74% of patients, of which 70% were considered larger than 2 cm. An ELCs score > or = 2 was found in 27 patients. Clinical characteristics of the patients grouped according to thoracoscopical findings and ELCs score did not differ, except for age. Patients with large ELCs were significantly older than patients without ELCs or small ELCs (P = 0.0009). In patients with large ELCs and ELCs score > or = 2, increased mean percentages of predicted total lung capacity and decreased diffusing capacity (KCO) were found. None of the patients exhibited all pulmonary function criteria of emphysema, in contrast to 43% of the patients with an ELCs score > or = 2. KCO was the only pulmonary function parameter which was decreased in smokers, especially in patients with large ELCs or ELCs score > or = 2. Static lung compliance (Cstat) was the only pulmonary function parameter which was increased in patients with recurrent SP. The authors concluded that KCO is related to smoking behaviour and ELCs in patients with SP. Cstat is the only parameter which is increased in patients with recurrent SP. The discrepancy between pulmonary function and macroscopical parenchymal changes could be explained by the fact that not all patients with SP are old enough at presentation to show all signs of emphysema with pulmonary function testing. On the other hand, it might be possible that ELCs in SP cause different pulmonary function abnormalities than in centriacinar or panacinar emphysema.

Adult↗
PubMed1998

Intermediate alpha 1-antitrypsin deficiency PiSZ: a risk factor for pulmonary emphysema?

It is well documented that the severe hereditary disorder alpha 1-antitrypsin deficiency (alpha 1ATD) PiZZ is a strong risk factor for emphysema, especially among smokers, but the role of intermediate alpha 1ATD PiMZ and PiSZ in the development of emphysema remains uncertain. In this study, we have evaluated mortality and lung function of 94 persons with intermediate alpha 1ATD PiSZ of whom 66 were non-index cases, i.e. persons ascertained through family studies. The index cases and the non-index cases were similar with respect to sex, age and follow-up time, but differed in smoking habits and FEV1. Among the smokers there was no significant difference in pack-years between index cases and non-index cases. The overall Standardized Mortality Ratio (SMR) was 1.6 (95% confidence intervals (CI): 0.8-2.7). For the index cases the SMR was 4.3 (95% CI: 1.9-8.5) and for the non-index cases it was 0.8 (95% CI: 0.3-1.8). In the index group six patients died of pulmonary emphysema, one of pulmonary fibrosis, and one of colon cancer. In the non-index group two died of pulmonary emphysema, two of pneumonia, and one of cerebral haemorrhage. The mean initial FEV1% predicted among the index cases was 59% compared with 94% among the non-index cases. Based on the analysis of the non-index cases it is concluded that only a small fraction of persons with the PiSZ phenotype are at increased risk of developing pulmonary emphysema, and at an older age than persons with the PiZ phenotype.

Adult↗
PubMed1999

Acute native lung hyperinflation is not associated with poor outcomes after single lung transplant for emphysema.

BACKGROUND: Single-lung transplantation for emphysema may be complicated by acute native lung hyperinflation (ANLH) with hemodynamic and ventilatory compromise. Some groups advocate the routine use of independent lung ventilation, double-lung transplant, or right-lung transplant with or without contralateral lung volume reduction surgery in high-risk patients. The goal of this study was to determine the incidence of ANLH and identify its potential predictors. METHODS: We reviewed 51 consecutive single-lung transplants for emphysema. Symptomatic ANLH was defined as mediastinal shift and diaphragmatic flattening on chest x-ray with hemodynamic or respiratory failure requiring cardiopressor agents or independent lung ventilation. Preoperative and postoperative physiologic and hemodynamic data were analyzed from both recipients and donors. RESULTS: Sixteen patients developed radiographic ANLH; 8 were symptomatic, 2 severely so. We could not identify high-risk patients before transplant by pulmonary function tests, predicted donor total lung capacity (TLC)/actual recipient TLC ratio, pulmonary artery pressures, or the side transplanted. There was a trend toward an increased incidence of symptomatic ANLH in patients with bullous emphysema on chest computed tomography, but this was accounted for primarily by patients with alpha1-antitrypsin deficiency (4/13 vs 4/38 with chronic obstructive pulmonary disease, P = 0.10). No patient required cardiopulmonary bypass or inhaled nitric oxide intraoperatively. Patients with acute native lung hyperinflation did not have increased reperfusion edema as measured by chest x-ray score or PaO2/F(I)O2 ratio. Compared to patients without ANLH, symptomatic patients had longer ventilator times (64.9+/-14.6 hours vs 40.4+/-3.9, P = 0.02, ANOVA) and longer lengths of stay (19.3+/-2.1 days vs 13.7+/-1.3, P = 0.07), but 30-day survival was 100%. Two symptomatic patients required independent lung ventilation or inhaled nitric oxide; the others were managed with decreased minute ventilation, early extubation, and cardiopressor agents. No patient required early lung volume reduction surgery or retransplantation. Acute native lung hyperinflation had no effect on FEV1 or 6-minute walk results at 1 year; survival at 1, 2, or 3 years; or the rate of acute rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. CONCLUSION: Acute native lung hyperinflation is common radiographically but is rarely clinically severe. Although there was a trend toward an increase in symptomatic ANLH in patients with bullous emphysema, a high-risk group could not be identified preoperatively. Our results do not support the routine use of bilateral lung transplant, the exclusive use of right single-lung transplant, simultaneous lung volume reduction surgery, or independent lung ventilation for patients with emphysema. Management strategies should be employed that limit overdistension of the native lung and lead to early extubation.

Acute Disease↗
PubMed2000

Gene polymorphism for microsomal epoxide hydrolase and susceptibility to emphysema in a Japanese population.

Recently, it was reported that gene polymorphism for microsomal epoxide hydrolase (mEPHX), an enzyme involved in the first-pass metabolism of epoxide intermediates, was associated with susceptibility to emphysema. This association was examined in a Japanese population, performing polymerase chain reaction (PCR)-based direct sequencing and restriction fragment length polymorphism assays for variant forms of mEPHX. The subjects consisted of 79 smokers with moderate to severe emphysema diagnosed by lung computed tomography scans, 58 smokers without emphysema, with a comparable smoking history, and 114 consecutive subjects who undertook annual health checkups. The allele frequency of exon 3 Tyr113 to His113, which was reported to confer slow mEPHX activity, was substantially higher in the population control group compared with that of the Caucasian control subjects in a previous study. However, neither the genotype distribution of exon 3, nor that of exon 4 His139 to Arg139, was significantly different between the two groups of smokers. These data indicate that the gene polymorphism for mEPHX is not associated with susceptibility to emphysema in the Japanese population. The discrepancy between the two studies may be explained either by racial difference or by the selection bias of subjects in the previous study, which examined those who had only mild to moderate emphysema with lung cancer or those who were clinically diagnosed as having chronic obstructive pulmonary disease.

Disease Susceptibility↗
PubMed2005

Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice.

Alveolar cell apoptosis is involved in the pathogenesis of emphysema, a prevalent disease primarily caused by cigarette smoking. We report that ceramide, a second messenger lipid, is a crucial mediator of alveolar destruction in emphysema. Inhibition of enzymes controlling de novo ceramide synthesis prevented alveolar cell apoptosis, oxidative stress and emphysema caused by blockade of the vascular endothelial growth factor (VEGF) receptors in both rats and mice. Emphysema was reproduced with intratracheal instillation of ceramide in naive mice. Excessive ceramide triggers a feed-forward mechanism mediated by activation of secretory acid sphingomyelinase, as suggested by experiments with neutralizing ceramide antibody in mice and with acid sphingomyelinase-deficient fibroblasts. Concomitant augmentation of signaling initiated by a prosurvival metabolite, sphingosine-1-phosphate, prevented lung apoptosis, implying that a balance between ceramide and sphingosine-1-phosphate is required for maintenance of alveolar septal integrity. Finally, increased lung ceramides in individuals with smoking-induced emphysema suggests that ceramide upregulation may be a crucial pathogenic element and a promising target in this disease that currently lacks effective therapies.

Acyltransferases↗
PubMed2004

Regional ventilation and distribution of emphysema - a quantitative comparison.

The distribution of ventilation and emphysema throughout the lung was compared in 20 emphysematous patients who were candidates for lung volume reduction surgery. Ventilation distribution among 1.6-cm-high stripe regions was obtained in supine position by planar gamma camera scintigraphy after inhalation of technegas. Results from nine healthy subjects provided normal stripe count rates. Patient count rates were expressed as the difference from predicted normal stripe count rate (DeltaSVI). Thus, DeltaSVI is a relative index of abnormal ventilation. Emphysema was assessed quantitatively by a density mask method on corresponding slices of high resolution computed tomography (HRCT). The results show that in the majority of patients, there is a highly significant relationship between the degree of stripe hypoventilation and the amount of distribution of emphysema, but in some patients no such relationship is found. We speculate that the distribution of airway obstruction not necessarily follows the distribution of emphysema, which could explain the lack of concordance between ventilation and emphysema distribution in some patients. We conclude that ventilation scintigraphy contains complementary information to lung HRCT.

Adult↗
PubMed1986

Selective bronchial intubation in infants with lobar emphysema: indications, complications, and long-term outcome.

Thirteen infants underwent selective intubation of a mainstem bronchus (SBI) for lobar emphysema of varying etiologies. Seven infants had pulmonary interstitial emphysema (PIE) with lobar hyperinflation secondary to hyaline membrane disease and mechanical ventilation. Six of these improved with SBI and five maintained permanent resolution upon cessation of SBI. Two infants with localized areas of emphysema who were subsequently shown to have histologic evidence of bronchopulmonary dysplasia had unsuccessful SBI. SBI was also unsuccessful in permanently resolving congenital lobar emphysema although temporary collapse of the affected lobe occurred during SBI. Complications including hypoxia, bradycardia, right upper lobe atelectasis, pneumonia, and additional air leaks occurred during SBI in six cases. Follow-up xenon ventilation scans in four infants in whom SBI was successful revealed normal ventilation of the previously diseased lobes. SBI can be a useful alternative to surgical excision of the affected lobe in patients with localized lobar hyperinflation secondary to PIE. SBI is generally unsuccessful in permanently correcting congenital lobar emphysema, nor should it be used when chronic diffuse parenchymal damage is present.

Bronchi↗
PubMed1995

Lobar emphysema and atelectasis syndrome, a nosological unity.

Shrinking and atelectatic pulmonary processes--atelectasis syndrome--and lobar emphysema show morphological similarities: congenital malformations of the bronchial structure, external compression of the bronchi as well as inflammatory processes. Ventilation mechanics determine whether in the described processes an atelectasis or an emphysema manifests itself clinically. Usually, one finds over-expansions in connection with atelectasis syndrome and atelectases together with lobar emphysema. Both processes can be reversible, if we are not dealing with bronchial malformations. Longer lasting processes as well as acute, life threatening forms require operation. The belief that atelectasis syndrome and lobar emphysema constitute a nosological unity is illustrated by our cases of 9 patients with atelectasis syndrome and 16 patients with lobar emphysema.

Bronchi↗
PubMed2003

Superiority of 10% air-10% blood-saline mixture for measuring the velocity of tricuspid regurgitation in patients with severe emphysema.

BACKGROUND: Severe emphysema frequently is associated with elevated pulmonary artery systolic pressure. However, it is often difficult to obtain adequate tricuspid regurgitation (TR) signals for measurement of pulmonary artery systolic pressure in patients with severe emphysema. PURPOSE: This study was conducted to evaluate the usefulness of air-blood-saline mixture in measuring TR velocity in severe emphysema. METHODS: We studied 82 patients with severe emphysema (67.7 +/- 9.2 years, 57 males) who had no or mild TR on color Doppler. Contrast echocardiography studies were performed with agitated 10% air-90% saline and 10% air-10% blood-80% saline mixtures. Tracing quality and peak velocity were assessed on baseline continuous wave signals and contrast continuous wave signals with the 2 mixtures. RESULTS: With the injection of an air-saline mixture, the quality of TR tracing improved in 45 patients (P <.0001) and a higher peak TR velocity was obtained (2.46 +/- 0.37 m/s vs 2.95 +/- 0.40 m/s, P <.0001) compared with baseline echocardiography. Compared with air-saline mixture, the air-blood-saline mixture further enhanced TR tracing quality in 17 patients (P <.0001) and the peak TR velocity increased to 3.13 +/- 0.42 m/s (P <.0001). CONCLUSIONS: In patients with severe emphysema, an air-blood-saline mixture improves the quantifiable TR signals for more accurate estimation of pulmonary artery systolic pressure, even when there is minimal valve TR.

Aged↗
PubMedDate not supplied

Structural emphysema does not correlate with lung compliance: lessons from the mouse smoking model.

The murine smoke-induced model produces histologic emphysema. The authors sought to assess whether the structural emphysema that occurred correlated with the development of compliance changes. The study exposed 2 strains of mice (CBA/J/J x C57BL/6J and A/J) to chronic cigarette smoke. Lung compliance and morphometry were measured. The smoking model generated significant emphysema in A/J mice in the absence of changes in compliance, lung matrix, or apoptosis. Importantly, there was no correlation between the emphysema measured by lung morphometry and pulmonary compliance. This lack of correlation suggests that the mechanisms involved in anatomic emphysema may be distinct from those that cause the loss of elastic recoil.

Animals↗
PubMed2004

Short-term reproducibility of computed tomography-based lung density measurements in alpha-1 antitrypsin deficiency and smokers with emphysema.

PURPOSE: To study the short-term reproducibility of lung density measurements by multi-slice computed tomography (CT) using three different radiation doses and three reconstruction algorithms. MATERIAL AND METHODS: Twenty-five patients with smoker's emphysema and 25 patients with alpha1-antitrypsin deficiency underwent 3 scans at 2-week intervals. Low-dose protocol was applied, and images were reconstructed with bone, detail, and soft algorithms. Total lung volume (TLV), 15th percentile density (PD-15), and relative area at -910 Hounsfield units (RA-910) were obtained from the images using Pulmo-CMS software. Reproducibility of PD-15 and RA-910 and the influence of radiation dose, reconstruction algorithm, and type of emphysema were then analysed. RESULTS: The overall coefficient of variation of volume adjusted PD-15 for all combinations of radiation dose and reconstruction algorithm was 3.7%. The overall standard deviation of volume-adjusted RA-910 was 1.7% (corresponding to a coefficient of variation of 6.8%). Radiation dose, reconstruction algorithm, and type of emphysema had no significant influence on the reproducibility of PD-15 and RA-910. However, bone algorithm and very low radiation dose result in overestimation of the extent of emphysema. CONCLUSION: Lung density measurement by CT is a sensitive marker for quantitating both subtypes of emphysema. A CT-protocol with radiation dose down to 16 mAs and soft or detail reconstruction algorithm is recommended.

Absorptiometry, Photon↗
PubMed2006

Quantitative assessment of regional emphysema distribution in patients with chronic obstructive pulmonary disease (COPD).

PURPOSE: To compare objective and subjective assessment of the distribution of emphysema in unselected patients with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: 167 patients were computed tomography (CT) scanned, and the relative area (RA-910) of emphysema in each CT slice was plotted against table position. The craniocaudal distribution was calculated as the slope of the regression line, and grouped as upper-lung-zone predominance (ULP), lower-lung-zone predominance (LLP), or mild/homogeneous distribution (MHE). CT scans were also classified as ULP, LLP, and MHE based on visual assessment of three high-resolution CT (HRCT) slices, and the leading pattern of emphysema was classified as centrilobular (CLE), paraseptal (PSE), panlobular (PLE), or no emphysema (NE). RESULTS: By objective classification, scans were divided into almost equal numbers of ULP, LLP, and MHE, whereas visual evaluation classified more scans as ULP (P<0.001) and very few as LLP (P<0.0001). In patients with CLE, 49% had ULP by objective classification, whereas LLP was the commonest leading pattern in PSE, PLE, and NE. CONCLUSION: We found significant discrepancies between the objective and subjective distributions of emphysema in various morphological patterns, which may be of clinical importance in, for instance, lung-volume-reduction surgery.

Aged↗
PubMed2002

Effects of concurrent ozone exposure on the pathogenesis of cigarette smoke-induced emphysema in B6C3F1 mice.

Episodic elevation of air pollutants may exacerbate respiratory distress associated with chronic obstructive pulmonary disease (COPD), yet few experiments have been performed to determine how continuously polluted atmospheres may contribute to the etiology of COPD, in general and pulmonary emphysema in particular. This study describes the effects of concurrent exposure to ozone (O(3)) in the pathogenesis of cigarette smoke (CS)-induced emphysema in the mouse. Female B6C3F1 mice were whole-body exposed either to filtered air (FA) or to mainstream CS at a concentration of 250 mg total particulate material/m(3) for 6 h/day, 5 days/wk for 15 or 32 wk. Concurrently, mice were exposed either to FA or to O(3) at 0.3 ppm for 8 h/night, 5 nights/wk for the same time periods. At necropsy, mouse lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cell numbers, total protein, lactate dehydrogenase (LDH) and alkaline phosphatase (AP) activities, superoxide production by isolated alveolar macrophages, glutathione content, inflammatory cytokines, and proteolytic activity. Other lungs were inflated at constant pressure for 6 h with formalin for fixation, routine histopathology, and stereology. After 32 wk of exposure, CS with or without concurrent O(3) exposure produced stereologic evidence of emphysema as previously described. Concurrent O(3) exposure did not worsen any of these parameters, nor did O(3) by itself cause stereologic changes that were consistent with emphysema. The O(3) exposure caused only slight elevations of BALF macrophages, while CS exposure caused marked increases in the numbers of both BALF macrophages and neutrophils. Neutrophils in the BALF in response to CS exposure were also more numerous at 32 wk than at 15 wk. Exposure to CS caused an increase in BALF total protein, LDH, AP, and interleukin (IL)-1beta. After 32 wk, CS exposure was associated with decreased superoxide production from isolated alveolar macrophages. The CS exposure elevated BALF total glutathione primarily at 15 wk. Overall, O(3) had little effect on endpoints that were significantly affected by CS exposure. We conclude that concurrent O(3) exposure has no effect on the induction of emphysema by CS in this animal model.

Animals↗