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Radiology is the basic factor in diagnosis of emphysema. Further differentiation is possible by assessment of the concomitant cardio-vascular changes. By these means, the type of emphysema (accompanying emphysema in chronic bronchitis, or primary emphysema) can be established.
Subcutaneous emphysema of the hand can be related to non-infectious causes and most commonly high-pressure injection injuries. Surgical emphysema of the hand is rare. We report a case of surgical emphysema of the dorsum of the hand following the excision of a dorsal wrist ganglion when the inserted suction drain did not work properly, accompanied by the inadvertent compression of the patient's body. Conservative management was adequate; oedema and emphysema subsided in several days.
The core fucosylation (alpha1,6-fucosylation) of glycoproteins is widely distributed in mammalian tissues, and is altered under pathological conditions. To investigate physiological functions of the core fucose, we generated alpha1,6-fucosyltransferase (Fut8)-null mice and found that disruption of Fut8 induces severe growth retardation and death during postnatal development. Histopathological analysis revealed that Fut8(-/-) mice showed emphysema-like changes in the lung, verified by a physiological compliance analysis. Biochemical studies indicated that lungs from Fut8(-/-) mice exhibit a marked overexpression of matrix metalloproteinases (MMPs), such as MMP-12 and MMP-13, highly associated with lung-destructive phenotypes, and a down-regulation of extracellular matrix (ECM) proteins such as elastin, as well as retarded alveolar epithelia cell differentiation. These changes should be consistent with a deficiency in TGF-beta1 signaling, a pleiotropic factor that controls ECM homeostasis by down-regulating MMP expression and inducing ECM protein components. In fact, Fut8(-/-) mice have a marked dysregulation of TGF-beta1 receptor activation and signaling, as assessed by TGF-beta1 binding assays and Smad2 phosphorylation analysis. We also show that these TGF-beta1 receptor defects found in Fut8(-/-) cells can be rescued by reintroducing Fut8 into Fut8(-/-) cells. Furthermore, exogenous TGF-beta1 potentially rescued emphysema-like phenotype and concomitantly reduced MMP expression in Fut8(-/-) lung. We propose that the lack of core fucosylation of TGF-beta1 receptors is crucial for a developmental and progressive/destructive emphysema, suggesting that perturbation of this function could underlie certain cases of human emphysema.
Emphysema is a pulmonary disease characterized by alveolar wall destruction, resulting in enlargement of gas exchange spaces without fibrosis. This condition is a part of chronic obstructive pulmonary disease (COPD), which causes 3.5% of deaths worldwide [Anonymous (1990) World Health Stat. Q. Special, 1-51] and contributes greatly to the global burden of disease [Murray, C. J. & Lopez, A. D. (1996) Science 274, 740-743]. Alveolar regeneration has been shown in animal models and could have potential for clinical treatment of early-stage emphysema. However, current techniques for detection of emphysema are not sensitive at the initial stages. Early-stage human panacinar emphysema is modeled in elastase-treated animals. Here, we provide an in vivo imaging method for differentiating normal and emphysematous rat lungs by measuring the apparent diffusion coefficient (ADC) of hyperpolarized (3)He by using magnetic resonance imaging. These data show that the ADC is significantly larger in elastase-treated rats, indicating alveolar expansion. Whereas these rats were clinically asymptomatic, conventional histology confirmed presence of injury. Our results indicate that measurement of the hyperpolarized (3)He ADC can be a valuable research tool and has potential application in the clinical setting.
Review of 2895 consecutive autopsies from 1962 to 1980 inclusive showed no significant differences in the prevalence of emphysema or other chronic lung disease between 282 active and retired employees of a cotton textile mill and the nontextile population. There was no statistical evidence that exposure to cotton dust, even after many years, produced emphysema, interstitial fibrosis, or cor pulmonale. The prevalence of emphysema in the series was highest in white males (22.0%), followed closely by black males (18.3%). In white females it was 7.5%, in black females, 5.5%. The prevalence in subjects under age 50 yr was 4.5%; in the age group 60-64 yr, 14.6%; and in subjects 65 yr of age and older, 21.9%. A significant increase in the prevalence of emphysema occurred between the 1962 to 1969 period and the 1970 to 1980 period.
A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by nose-only inhalation exposure would be a more efficient means of targeting damaged lung tissue. Emphysema was induced in male Fischer 344 rats by intratracheal instillation of pancreatic elastase (0.5 IU/g body weight). Four weeks after elastase instillation, animals were treated once daily, 4 days/week, for 3 weeks by exposing them nose-only to aerosolized ATRA (target concentration-time of 3000 or 15,000 mg-min/m3) or by injecting them intraperitoneally with ATRA in cottonseed oil (0.5 or 2.5 mg/kg). Based on estimates of particle deposition in the respiratory tract, inhalation doses were chosen to be consistent with injected doses. Lungs were fixed by inflation with formalin (constant pressure for 6 hours followed by >48 hours of immersion) and were embedded in paraffin. Sections were evaluated by histopathology and stereology. Inhalation exposure to ATRA at both aerosol concentrations caused significant elevations of ATRA in the lung, whereas only the high-dose injection treatment was associated with an elevation of lung ATRA. The mean ATRA concentration from lungs of rats in the high-dose inhalation exposure groups as measured by liquid chromatography--mass spectrometry was approximately 12-fold greater than that of high-dose injection-treated rats. Elastase instillation caused increased lung volumes, irregular alveolar air space enlargement, and fragmentation and attenuation of alveolar septa. Neither inhaled nor injected ATRA reduced the enlarged lung volumes associated with this emphysema model. Stereology demonstrated that alveolar air space enlargement in ATRA-treated rats was similar to that in sham-treated emphysematous animals. Thus, while inhalation treatment caused greater levels of the drug in lung tissue in comparison to that of injection-treated animals, treatment with ATRA by either route of administration did not cause a reversal of lung tissue damage in this model of elastase-induced emphysema.
PURPOSE: To assess serial CT as a measure of the progress of emphysema in patients with severe alpha 1-antitrypsin deficiency (phenotype PiZ). MATERIAL AND METHODS: In a randomized placebo-controlled study of alpha 1-antitrypsin augmentation therapy, 22 patients with moderate emphysema were followed for 2-4 years with an annual lung CT. The images were analysed by means of semiautomatic lung detection, and the degree of emphysema was quantitated by the density-mask and the percentile methods. The influence of lung volume was standardised by a regression model. RESULTS: A highly significant decline in Hounsfield units (HU) was found in low-density areas, corresponding to a mean (SE) annual loss of lung tissue of 2.1 (0.4) g/l lung volume. Analysis of a single slice at 5 cm below the level of the carina gave comparable results: 2.4 (0.4) g/l. CONCLUSION: Serial CT is a sensitive measure of the progress of emphysema in patients with severe alpha 1-antitrypsin deficiency.
In alpha 1-antitrypsin deficiency in humans, inadequately regulated activity of serine protease activity is responsible for the chronic lung tissue degeneration and irreversible loss of pulmonary function seen in those individuals with emphysema. Typically, disease symptoms in this patient population are exacerbated by cigarette smoke. Here we show that inhaled recombinant alpha 1-antitrypsin (rAAT) can provide significant protection against the development of emphysema in cigarette smoke-treated mice. As has been reported previously, cigarette smoke was seen to increase significantly the recruitment of neutrophils and macrophages into the lungs of these animals, leading to concomitant alveolar airspace enlargement and emphysema. In smoking animals treated for 6 months with inhaled rAAT, effects on lavage levels of neutrophils and macrophages were only moderate when compared with untreated animals. Furthermore, neutralizing antibodies to rAAT were generated in all rAAT-treated animals. Despite this, however, reductions in airspace enlargement of up to 73% were observed. These findings demonstrate that delivery of rAAT directly to the lungs of smoke-treated mice can inhibit lung tissue damage mediated by proteases, suggesting that rAAT inhalation therapy might represent a practical approach towards treating emphysema in humans, by modifying the course of the disease.
Chronic inflammation containing CD8(+) lymphocytes, neutrophils, and macrophages, and pulmonary emphysema coexist in lungs from patients with chronic obstructive pulmonary disease. Although this inflammatory response is believed to cause the remodeling that is seen in these tissues, the mechanism(s) by which inflammation causes emphysema have not been defined. Here we demonstrate that interferon gamma (IFN-gamma), a prominent product of CD8(+) cells, causes emphysema with alveolar enlargement, enhanced lung volumes, enhanced pulmonary compliance, and macrophage- and neutrophil-rich inflammation when inducibly targeted, in a transgenic fashion, to the adult murine lung. Prominent protease and antiprotease alterations were also noted in these mice. They included the induction and activation of matrix metalloproteinase (MMP)-12 and cathepsins B, H, D, S, and L, the elaboration of MMP-9, and the selective inhibition of secretory leukocyte proteinase inhibitor. IFN-gamma causes emphysema and alterations in pulmonary protease/antiprotease balance when expressed in pulmonary tissues.
BACKGROUND: Studies of the accuracy of partial rebreathing measurements of pulmonary blood flow (PBF) in patients with abnormal lungs have not fully explained the sources of error. METHODS: We used computer models of emphysema and pulmonary embolism incorporating both ventilation-perfusion (V/Q) and ventilation-volume (V/V) heterogeneity to investigate systematic errors in partial rebreathing PBF measurements. We studied (i) errors produced under usual conditions, (ii) effects of recirculation, (iii) effects of alveolar-proximal airway and alveolar-capillary PCO2 and VCO2 differences, (iv) effects of alveolar V/Q inhomogeneity and (v) effects of rebreathing time. RESULTS: In the pulmonary embolism model the systematic error is only acceptable (<10%) when the simulated PBF is low (2-3 litre min(-1)). In the emphysema model PBF is underestimated by more than 20% at all cardiac outputs studied. Four sources of systematic errors were found. (i) Alveolar-proximal airway PCO2 gradients and flux differences between the proximal airway and alveolar compartments contribute most to the systematic error. (ii) V/Q inhomogeneity causes PCO2 gradients between the alveolar compartments and pulmonary capillary blood, and between pulmonary capillary compartments. (iii) Rebreathing times are inadequate in the presence of V/V mismatch. (iv) The apparent effect of venous blood recirculation is small in emphysema but significant in pulmonary embolism. CONCLUSIONS: We conclude that PBF cannot be measured accurately by partial rebreathing in lungs with emphysema or embolism. Systematic errors are caused mainly by errors in end-tidal PCO2 values.
OBJECTIVES: The objective of this study is to evaluate the mild physiologic changes of elastase-induced pulmonary emphysema in the pig by radionuclide scintigraphy and to correlate these findings with high-resolution computed tomography (HRCT) and histologic examination. METHODS: Eight 7- to 12-week-old Yorkshire pigs were studied. Perfusion and ventilation studies were performed in six pigs at 1- or 2-week intervals after elastase instillation. HRCT was simultaneously performed for correlation with radionuclide scintigraphy. For the perfusion scans, technetium 99m (99mTc) macroaggregated albumin (MAA) was used, and both planar and single-photon emission CT (SPECT) images were obtained. Ventilation studies were performed with xenon-133 gas with dynamic sequential imaging. RESULTS: Histopathologic findings demonstrated dilatation and destruction of the alveoli and were similar to those previously reported by the authors. The SPECT perfusion images showed significantly impaired perfusion of the involved segment of the lung, corresponding to the region where elastase was instilled. The planar xenon-133 ventilation scintigraphy did not show abnormal air trapping. The mild emphysema induced with elastase manifested as decreased and impaired perfusion with no detectable ventilation abnormalities. The sensitivity of SPECT perfusion studies for the detection of the mild changes of elastase-induced pulmonary emphysema were higher than that of HRCT. CONCLUSIONS: The perfusion studies reflect functional or physiologic changes in contrast to structural changes seen on HRCT. This pig model was valuable to study the scintigraphic manifestation of elastase-induced pulmonary emphysema.
RATIONALE AND OBJECTIVES: Multislice computed tomography (MSCT) of the lungs provides a new opportunity for longitudinal assessment of lung densities because of shorter scan duration. The aim of the present study was to assess the intraindividual variation of lung densities measured by MSCT of patients with emphysema. METHODS: Ten patients with emphysema participated in a study in which MSCT was obtained on two occasions, approximately 2 weeks apart. Scanning parameters were 140 kV, 20 mAs, 4 x 2.5-mm collimation, and effective slice thickness of 2.5 mm. Lung density was measured as the 15th percentile point and the relative area below -910 Hounsfield units (HU) by using Pulmo-LKEB software. RESULTS: The mean difference of the 15th percentile point was -1.29 +/- 3.2 HU, and that for the relative area below the -910-HU parameter was -1.02% +/- 3.09%. Intraclass coefficients of variation were 0.96 (0.86-0.99) and 0.94 (0.8-0.98), respectively (95% confidence interval). CONCLUSIONS: Lung density parameters of emphysema derived by MSCT provide an opportunity for analysis of the treatment effects of new drugs on the progression of emphysema.
A case of postlaparoscopic subcutaneous emphysema developed along cutaneous striae was reported. A 35-year-old male patient with marked cutaneous striae underwent hand-assisted laparoscopic proctocolectomy for steroid-dependent ulcerative colitis. After an uneventful surgery, he developed subcutaneous emphysema, which was noted along the cutaneous striae in the bilateral thigh. The localization of emphysema suggested that Pfannensteil mini-laparotomy for hand access was most responsible for the development of subcutaneous emphysema.
Orbital emphysema is a rare condition in the absence of trauma or sinus disease. We report two cases of orbital emphysema caused by sneezing. The patients presented with sudden unilateral eyelid swelling after sneezing. Otorhinolaryngologic and ophthalmic examinations were accompanied by computed tomography (CT). Patient examination disclosed crepitant eyelid swelling, ptosis, and mild unilateral exophthalmos. CT demonstrated areas of emphysema in the orbit. One patient had history of past trauma. The other patient had a history of nasal surgery and concurrent chronic sinusitis. Sneezing may cause orbital emphysema in patients with a history of old periorbital trauma or surgery.
A 19-year-old man sustained a blowout fracture to the left orbital floor. Subcutaneous emphysema developed after a protracted sneezing episode. Some signs of respiratory distress ensued, and the patient was emergently intubated. He underwent surgical repair of the fracture and then had further extension of the subcutaneous emphysema. The left nasal cavity was packed and the emphysema slowly resolved. Clinically significant subcutaneous emphysema is an uncommon complication of orbital blowout fracture. Informing the patient to avoid excessive nose-blowing and to avoid occluding the nose while sneezing may prevent this complication.
HIV-seropositive individuals are at an increased risk for an accelerated form of emphysema. The purpose of this study was to determine the distribution of HIV-1 RNA in lung tissues and correlate this with the histologic findings and expression of matrix metalloproteases (MMPs). Reverse transcriptase (RT) in situ PCR analysis was performed on 11 AIDS lung autopsy specimens which showed varying degrees of emphysematous changes. In each lung, HIV-1 RNA was detected. In areas of histologically normal lung, very rare HIV-1-infected cells were evident. In contrast, many HIV-1-infected cells were noted in areas of emphysema. HIV-1 gag RNA was evident primarily in macrophages; infected pneumocytes were also seen. Similarly, MMP mRNA and protein, primarily MMP-9, localized to the areas of emphysema. Colabeling experiments documented that MMP expression was found primarily in cells that were HIV-1 negative and adjacent to HIV-1-infected macrophages. These results suggest that AIDS-related emphysema may be due, in part, to direct infection by HIV-1 of, primarily, alveolar macrophages, and concomitant up-regulation of MMP expression in the neighboring, noninfected cells.
OBJECTIVES: The objectives of this study were to investigate whether computed tomography (CT) densitometry can be applied consistently in different centers; and to evaluate the reproducibility of densitometric quantification of emphysema by assessment of different sources of variation, ie, intersite, interscan and inter- and intraobserver variability, in comparison with intersubject variability. MATERIALS AND METHODS: In 5 different hospitals, 119 patients with emphysema were scanned using standardized protocols. In each site, an observer performed a quantitative densitometric analysis (including blood recalibration) on the corresponding patient group (n=23-25) and one observer analyzed the entire group of 119 patients. After several months, the latter observer analyzed all data for a second time. Subsequently, different sources of variation were assessed by variance component analysis with and without volume correction of the data. RESULTS: Inter- and intraobserver variability marginally contributes to the total variability (<0.001%). The interscan variability was 0.02% of the total variation after application of volume correction. The intersite variability was 48% as a result of one deviating CT scanner. Air recalibration normalized deviating air densities in CT scanners. Within sites, the intersubject variability ranged between 93% and 99% based on the analysis of 2 subsequent CT scans of the patients. CONCLUSIONS: Almost all variability in the density measurement of emphysema originates from differences between scanners and from differences in severity of emphysema between patients. Lung densitometry with multislice CT scanners is a highly reproducible measurement, especially if corrected for lung volume, because this reduces interscan variability.
Computed tomography (CT) has become the new reference standard for quantification of emphysema. The most popular measure of emphysema derived from CT is the pixel index (PI), which expresses the fraction of the lung volume with abnormally low intensity values. As PI is calculated from a single, fixed threshold on intensity, this measure is strongly influenced by noise. This effect shows up clearly when comparing the PI score of a high-dose scan to the PI score of a low-dose (i.e., noisy) scan of the same subject. In this paper, the noise variance (NOVA) filter is presented: a general framework for (iterative) nonlinear filtering, which uses an estimate of the spatially dependent noise variance in an image. The NOVA filter iteratively estimates the local image noise and filters the image. For the specific purpose of emphysema quantification of low-dose CT images, a dedicated, noniterative NOVA filter is constructed by using prior knowledge of the data to obtain a good estimate of the spatially dependent noise in an image. The performance of the NOVA filter is assessed by comparing characteristics of pairs of high-dose and low-dose scans. The compared characteristics are the PI scores for different thresholds and the size distributions of emphysema bullae. After filtering, the PI scores of high-dose and low-dose images agree to within 2%-3% points. The reproducibility of the high-dose bullae size distribution is also strongly improved. NOVA filtering of a CT image of typically 400 x 512 x 512 voxels takes only a couple of minutes which makes it suitable for routine use in clinical practice.