Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Emphysema”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1994

Orbital emphysema: case reports and review of the literature.

OBJECTIVE: This study was designed to describe the usual clinical findings of orbital emphysema as well as unusual and infrequent but important causes of this condition. DESIGN: We present seven detailed cases of orbital emphysema and review the pertinent English-language literature published since 1900. MATERIAL AND METHODS: Characterization of the seven patients with orbital emphysema illustrates the various causes and clinical findings of the disorder. Additionally, we review 78 previously published cases of orbital emphysema to determine the treatment and prognosis of this condition. RESULTS: Trauma is the most frequent cause of orbital emphysema; however, orbital emphysema also may occur spontaneously or as a complication of pulmonary barotrauma, infection, and operation. In most cases, orbital emphysema resolves spontaneously without compromising ocular function. If excessive amounts of air accumulate within the orbit, however, complications such as occlusion of the central retinal artery or compressive optic neuropathy may lead to loss of vision if not recognized promptly and treated. CONCLUSION: In most cases, orbital emphysema is an incidental, benign finding that resolves with time. Careful observation is the only treatment necessary unless an orbital fracture involves an infected sinus, in which case prophylactic orally administered antibiotics may be prescribed.

Adolescent↗
PubMed2002

Bullectomy is comparable to lung volume reduction in patients with end-stage emphysema.

OBJECTIVES: Emphysema is one of the most prevalent disabling diseases, not modified by current medical treatment and physical rehabilitation. Lung transplantation is an effective clinical option in end-stage emphysema but it is available only for a limited number of patients. Bullectomy and lung volume reduction represent other surgical options to improve symptoms and exercise tolerance in selected patients. Both procedures allow the removal of the area of emphysematous lung resulting in improvement in chest wall mechanics, ventilation/perfusion ratio and re-expansion and better function of the residual lung. There is some evidence that in patients with end-stage emphysema bullectomy and lung volume reduction work in the same manner and yield similar functional results. METHODS: We compared and analyzed retrospectively two groups of patients with end-stage emphysema who underwent bullectomy or lung volume reduction. Over the last 5 years 20 patients with end-stage emphysema presenting with bullae underwent thoracoscopic bullectomy (Group I). During the same period of time 18 patients with end-stage non-bullous emphysema underwent thoracoscopic unilateral lung volume reduction. Pre-operative baseline respiratory function data, peri-operative data, and functional results recorded at 6 and 12 months were compared and analyzed. RESULTS: Both groups were homogeneous in terms of age, degree of respiratory derangement and severity of emphysema. Complication rate and peri-operative data were similar in the two groups. Improvement in symptoms, respiratory function and exercise tolerance was comparable. CONCLUSIONS: Our experience supports the hypothesis that the physiopathological basis of respiratory improvement after bullectomy and lung volume reduction surgery in patients with end-stage emphysema is the same, although the exact mechanism remains incompletely understood.

Aged↗
PubMed2000

End-tidal oxygraphy during pre-oxygenation in patients with severe diffuse emphysema.

We hypothetised that the rate of pre-oxygenation could be altered by the increase in lung volume and airflow obstruction observed in emphysema. End-tidal oxygen concentration was monitored, using a paramagnetic oxygen analyser, during 10-min pre-oxygenation (tidal breathing of 100% oxygen) in 10 normal patients and in 10 patients with severe diffuse emphysema documented by computerised tomography. Emphysema was characterised by an important increase in functional residual capacity of the lungs [190 (23)% of predicted values] and a decrease in expiratory flow. The increase in end-tidal oxygen concentration was slower in the emphysema group than in the control group (p = 0.0024). After 3 and 5 min of pre-oxygenation, the end-tidal fractional oxygen concentration was significantly lower in the emphysema group than the control group [mean (SD); value at 3 min: emphysema: 0.83 (0.06) vs. control: 0.91 (0.02), p = 0.0005]. Individual values of end-tidal oxygen concentration measured after 3, 5 and 10 min of pre-oxygenation were negatively correlated with functional residual capacity in the emphysema group, whereas no such correlation was found in the control group. These results suggest that pre-oxygenation should be monitored in patients with diffuse emphysema to ensure that adequate pre-oxygenation is achieved.

Adult↗
PubMed2005

Patterns of changes in arterial PO2 during one-lung ventilation: a comparison between patients with severe pulmonary emphysema and patients with preserved lung function.

OBJECTIVES: One-lung ventilation (OLV) during thoracoscopic surgery is associated with a significant decline in arterial PO(2) in patients with severe pulmonary emphysema and patients with preserved lung function. The authors hypothesized that patterns of arterial PO(2) changes are different in these 2 patient groups. DESIGN: Prospective nonrandomized study. SETTING: University hospital. PARTICIPANTS: Twenty-five patients undergoing thoracoscopic interventions: 16 with severe pulmonary emphysema and 9 patients without emphysema. INTERVENTIONS: Continuous arterial blood gas measurement (PaO(2), PaCO(2), pHa) during OLV of the left lung in left lateral position using the Paratrend 7 blood gas monitoring system (PT7; Pfizer Hospital Products Group, High Wycombe, UK). MAIN RESULTS: The decrease of PaO(2) was delayed in patients with severe emphysema. Steady state (defined as DeltaPaO(2) <7.5 mmHg/min) was reached after 18 +/- 4 minutes compared with 11 +/- 3 minutes (mean +/- standard deviation) in patients with normal lung function (p = 0.0002). PaO(2) values at steady state were comparable (p = 0.49); the pattern of changes in PaO(2) for the first 15 minutes of left-sided OLV was significantly different between the groups (p = 0.0004). The difference of predicted versus measured PaO(2) at steady state was -48 +/- 160 mmHg for patients with emphysema and -51 +/- 60 mmHg for patients with normal lung function (p = 0.019). CONCLUSION: During OLV, oxygenation is better preserved for a longer period of time in patients with severe pulmonary emphysema as compared with patients with normal lung function. In contrast to patients without emphysema, prediction of oxygenation during OLV for the individual patient with emphysema is unreliable because of large interindividual differences.

Adolescent↗
PubMed2000

Direct medical costs of chronic obstructive pulmonary disease: chronic bronchitis and emphysema.

In this study we aimed to estimate direct medical costs of Chronic Obstructive Pulmonary Disease (COPD) by disease type; chronic bronchitis and emphysema. This study estimates direct costs in 1996 dollars using a prevalence approach and both aggregate and microcosting. A societal perspective is taken using prevalence, and multiple national, state and local data sources are used to estimate health-care utilization and costs. Chronic bronchitis and emphysema together account for $14.5 billion in annual direct costs. Inpatient costs are greater than outpatient and emergency costs ($8.3 vs. $7.8 billion) and hospital and medication costs account for most resources spent. The high prevalence of chronic bronchitis accounts for its larger total costs ($11.7 billion) compared with emphysema ($2.8 billion). Emphysema, which is more severe, has higher costs per prevalent case ($1341 vs. $816). Hospital stays account for the highest costs, $6.0 billion for chronic bronchitis and $1.9 billion for emphysema. The hospitalization rate, length of stay and average cost per prevalent case are higher for emphysema than for chronic bronchitis. Medication costs are the second highest cost category ($4.4 billion for chronic bronchitis, $0.693 billion for emphysema). The high hospitalization and low home care costs (0.2% of total) suggest underuse of home care and room to shift from acute to preventive care. More attention to healthcare management of chronic bronchitis and emphysema is suggested, and improving inhaler and anti-smoking compliance might be important targets.

Ambulatory Care↗
PubMed2002

Relationship between lung function, ventilation-perfusion inequality and extent of emphysema as assessed by high-resolution computed tomography.

UNLABELLED: The development of the high-resolution computed tomography (HRCT) has improved the ability to detect and quantify emphysema in various groups of patients with chronic airflow obstruction (COPD). Significant correlations have previously been found between indices of air flow obstruction, hyperinflation, reduced diffusing capacity for carbon monoxide (DLCO), and the extent of emphysema (emph.%) assessed by HRCT. However, the relationship between emph.% and ventilation-perfusion (V(A)/Q) inequality in COPD is unknown. Twenty COPD patients with a mean forced expiratory volume in 1 s (FEV1) of 38.2 (+/- 15.5)% in percent of predicted value (%P), a mean PaO2 value of 9.6 (+/- 1.3) kPa, and a mean diffusing capacity of 43.6 (+/- 23.0)%P, were subjected to measurements by the multiple elimination inert gas technique (MIGET). The extent of emphysema was determined by HRCT at both full inspiration, emph.I(%) and at full expiration, emph.E(%), with a cut-off limit of -910 Hounsfield Units (HU) using the "Density Mask" method. The ventilation directed towards high V(A)/Q areas was 73 (+/- 10.2)% and the mean ventilation (V-mean) was elevated about three times compared to normal. The mean emph.(I)% and emph.(E) was 45.6 (+/- 16.9) and 32.7 (+/- 190)%, respectively. Significant correlations were shown between the emphysema extent and several lung function parameters, but no correlation was found between the emphysema extent and the V(A)/Q relationships or the blood gas values. Reduced DLCO%P correlated with less high V(A)/Q ventilation (r=0.73, P < 0.05) for the subgroup of COPD patients with DLCO(%P) less than 50% (n=12). CONCLUSIONS: In COPD patients, suffering from moderate to severe emphysema without severe blood gas impairment, no correlation was shown between the extent of emphysema, as assessed by HRCT, and the severity of ventilation-perfusion inequality. A substantial collateral ventilation in severe emphysema may be a mechanism that prevents a deterioration in V(A)/Q relationships and in blood gas levels.

Aged↗
PubMed2004

[Fully automatic detection and quantification of emphysema on thin section MD-CT of the chest by a new and dedicated software].

PURPOSE: Introduction of a novel software tool (YACTA -- yet another CT analyzer) for detection and quantification of pulmonary emphysema in thin-slice chest MDCT data sets. MATERIALS AND METHODS: Consisting of grey-level threshold-based algorithms (e. g., region-growing), expert rules and morphological image postprocessing YACTA segments the tracheobronchial tree prior to the detection and quantification of pulmonary emphysema. In addition to general parameters, such as the mean lung density (MLD) and the emphysema index (EI -- also described as pixel index PI), the previously described bullae index (BI) is transformed into a three-dimensional parameter for a morphological description of emphysema. A first evaluation of chest MDCT data sets of 11 patients was performed as well as a comparison of MLD, lung volume (LV), emphysema volume (EV) and PI calculated with two established commercial tools of Siemens Medical Solutions (Volume and Pulmo). Furthermore, the BI was calculated with YACTA. RESULTS: YACTA processed the image data without manual interaction and demonstrated more user-comfort than Volume and Pulmo software, which require manual correction especially for lung segmentation at the hilar regions to separate central airways from lung parenchyma. MLD, LV, and EV values calculated with YACTA were systematically higher (Pulmo: + 50 HU/+ 597 ml/+ 159 ml; Volume: + 32 HU/+ 110 ml/+ 155 ml). Different segmentation algorithms are responsible for this: YACTA includes areas not assessed by mere threshold-based techniques. Constantly lowered LV values of Pulmo are caused by a missing dilatation algorithm. The error correction as a special feature of YACTA results in increased emphysema volumes and indices. The segmentation of the tracheobronchial tree lowers the part of airways falsely classified as emphysema. CONCLUSION: The new developed software shows higher user comfort as established by semi-automated tools. RESULTS: of LV, EV, MLD and PI are comparable or moderately different. Automatic calculation of a BI is possible, providing information about bullous morphology of pulmonary emphysema. Further studies are necessary to correlate data with clinical or pathological parameters.

Adult↗
PubMed2000

Animal models of emphysema and their relevance to studies of particle-induced disease.

Emphysema is a pulmonary disease that may be exacerbated by inhaled particles. Over the years, many animal models of emphysema have been developed that may be useful in studying the effects of inhaled particles on humans with emphysema. Models have been described in many species, and many approaches have been described for inducing emphysema. Emphysema in humans is a parenchymal component of chronic obstructive pulmonary disease and frequently coexists in a complex with disease of the airways such as bronchitis. Animal models of emphysema usually recapitulate only one or a few aspects of this complex disease. Thus, the emphysema model must be selected carefully in order to answer specific questions about the interactive effects of particles and emphysema.

Air Pollutants↗
PubMed2003

Can aerosol-derived airway morphometry detect early, asymptomatical lung emphysema?

The aerosol-derived airway morphometry technique (ADAM) can be used to assess non-invasively peripheral airspace dimensions. It has been shown that this technique can identify permanent peripheral airspace enlargement in patients with lung emphysema, but it is yet unknown if early stages of emphysema can be detected. In this study, 89 aluminum welders were investigated. Although all (except two subjects) showed normal spirometry, in 29% of the subjects visual signs of early emphysema were observed with high-resolution computed tomography (HRCT) in a previous study. Using the ADAM technique, 28% of the subjects showed increased peripheral airspace dimensions. However, both groups with positive findings overlapped only in about half of the cases. Peripheral airspace dimensions correlated significantly with the mean lung density calculated from the HRCT scans, and lung density was significantly decreased in the group with increased airspace dimensions. The poor overlap of the positive findings observed with both techniques can be explained if it is considered that the visual HRCT technique and ADAM focus on different aspects of emphysematous changes in the lungs. Whereas visual HRCT is a powerful tool to identify focal changes in lung density but cannot detect mild homogeneous emphysema, ADAM delivers a measure for homogeneously distributed emphysema but cannot detect focal emphysema or regions with emphysema which are badly ventilated. Since ADAM is easy to perform, non-invasive, and can be repeatedly applied to human subjects without radiological concerns, this technique might become a useful tool for the detection and monitoring of lung emphysema in occupational medicine, epidemiology, and pharmaceutics.

Adult↗
PubMedDate not supplied

Multi-detector CT of the chest: influence of dose onto quantitative evaluation of severe emphysema: a simulation study.

PURPOSE: Quantitative evaluation of the lung parenchyma might be impaired or unreliable by use of reduced-dose CT protocols. Aim of the study was to define the threshold where reduced dose has significant impact on quantitative emphysema parameters. MATERIALS AND METHODS: Thirty patients with severe centrilobular emphysema underwent multidetector computed tomography (120 kV, 150 mAs). Original CT raw data were simulated using 10 mAs settings (10-100 SIMmAs). Quantitative analysis provided lung volume, emphysema volume, emphysema index, mean lung density, and 4 emphysema volume classes. Simulated low-dose results were compared with original acquisition. RESULTS: Emphysema index showed no clinical relevant variation down to 30 SIMmAs. The large emphysema volume class was significantly different below 50 SIMmAs. The intermediate and small classes showed an overproportional variation below 50 SIMmAs. CONCLUSIONS: Dose reduction down to 30 SIMmAs is possible for clinical routine. Settings below 50 SIMmAs significantly alter the in-detailed 3-dimensional emphysema quantification.

Adult↗
PubMed1986

CT in the qualitative assessment of emphysema.

To assess the ability of CT to demonstrate the different types of emphysema, the CT appearance was compared with the corresponding barium-impregnated pathologic specimens cut in the transverse plane, in four patients with emphysema. The CT appearance was also compared with the chest radiographs of two patients with irregular emphysema associated with progressive massive fibrosis. The parenchymal destruction visualized on CT in the patients with mild and moderate centriacinar emphysema was distinctly different from that seen in the patient with panacinar emphysema in appearance and distribution. Paraseptal and irregular emphysema were also well demonstrated using CT. Window widths between 800 and 1,500 were found to demonstrate the parenchymal changes most accurately. We conclude that CT can help to identify the presence of emphysema and to distinguish radiologic characteristics of the different types of emphysema.

Humans↗
PubMed2005

Proteases and emphysema.

PURPOSE OF REVIEW: The protease-antiprotease theory of emphysema is widely accepted, but exactly which cells/proteases play a role continues to be a controversial subject. RECENT FINDINGS: Reports in humans show increased metalloproteinase activity in emphysema, but the exact role of metalloproteinases remains unclear. In laboratory animals, neutrophils turn out to be crucial, and neutrophil influx correlates well with measurements of matrix destruction. Neutrophil influx is linked to metalloproteinase activity, and in mice MMP12-induced release of tumor necrosis factor-alpha drives neutrophil infiltration. Serine elastase inhibitors, knockout of neutrophil elastase, and interference with tumor necrosis factor-alpha signaling all provide significant protection against smoke-induced emphysema, but metalloproteinase inhibitors may yield greater protection. In genetically modified mice, emphysema can be produced by overexpression of mediators such as tumor necrosis factor-alpha, interferon-gamma, or interleukin-13, and these models show evidence of metalloproteinase, cysteine protease, and serine protease attack with complicated relationships among these mediators. Collagen breakdown also appears to be important in the genesis of emphysema. Pro-apoptotic agents produce emphysema as well, possibly via an elastolytic pathway. SUMMARY: The idea that a single protease or a single type of inflammatory cell is responsible for human emphysema is unlikely to be true; rather, there are complex interactions among proteases, and between proteases and other mediators. The problem at this time is attempting to sort out the numerous candidate effector agents and to determine which of the animal models are relevant to human disease, since there may be considerable discrepancies in the types of proteases and their roles between laboratory animals and humans. There is now good evidence from animal models that antiproteolytic therapy can be of benefit in ameliorating cigarette smoke-induced emphysema.

Animals↗
PubMed2006

Association between markers of emphysema and more severe chronic obstructive pulmonary disease.

BACKGROUND: The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate whether COPD patients, with or without emphysema quantitatively confirmed by high resolution computed tomography (HRCT), have different COPD severity as assessed by the BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and inspiratory capacity to total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. METHODS: Twenty six outpatients with COPD and eight healthy non-smokers were examined. Each subject underwent HRCT scanning, pulmonary function tests, cell counts, and measurements of neutrophil elastase, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. RESULTS: Patients with HRCT confirmed emphysema had a higher BODE index and lower IC/TLC ratio than subjects without HRCT confirmed emphysema and controls. Forced expiratory volume in 1 second (FEV(1)), FEV(1)/forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP-9, and the MMP-9/TIMP-1 ratio in sputum were higher in patients with emphysema. In COPD patients the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). CONCLUSIONS: These results suggest that COPD associated with HRCT confirmed emphysema is characterised by more severe lung function impairment, more intense airway inflammation and, possibly, more serious systemic dysfunction than COPD not associated with HRCT confirmed emphysema.

Aged↗
PubMed1982

Annual decline of lung function in pulmonary emphysema: influence of radiological distribution.

Fifty-six male patients with pulmonary emphysema and normal serum alpha 1-antitrypsin were followed for a minimum period of three years (range 3-13 yr) to observe the effects of the radiological distribution of emphysema on the annual rate of change of lung function indices. The subjects were placed in three categories--upper zone (UZ), lower zone (LZ), and generalised (G). The influence of smoking was taken into account with subjects in each radiographic category being divided into ex-smokers (group EX-S) and continuing smokers (group S). The rate of decline of FEV1, VC, TCO, and KCO was greater in group S than EX-S in all three x-ray categories. In group S, FEV1, VC, TCO, and KCO declined significantly faster in UZ emphysema than in G emphysema. In group EX-S, FEV1, TCO, and PaO2 declined significantly faster in UZ than G emphysema but VC remained unaltered. KCO and PaCO2 did not change significantly in any radiographic category in either group S or EX-S. Patients with G and LZ emphysema underwent very similar physiological changes over the course of time. Those with UZ emphysema, however, complained of exertional dyspnoea at an earlier age; a number of their lung function indices deteriorated at a faster rate than in patients from the other two categories, suggesting that UZ emphysema is a different disease entity.

Adult↗
PubMed1999

Pulmonary emphysema: subjective visual grading versus objective quantification with macroscopic morphometry and thin-section CT densitometry.

PURPOSE: To compare subjective visual grading of pulmonary emphysema with macroscopic morphometry and computed tomographic (CT) densitometry. MATERIALS AND METHODS: In 62 consecutive patients who underwent thinsection CT before surgical lung resection, emphysema was objectively quantified with computer-assisted macroscopic morphometry and CT densitometry. The percentage of lung macroscopically occupied by emphysema was compared with the percentage occupied on CT scans by pixels with attenuation values lower than a predefined threshold (CT densitometry). Three readers with varying degrees of expertise subjectively graded emphysema with visual assessment at two reading sessions. Data from objective quantification and subjective grading were analyzed with correlation coefficients, and interobserver and intraobserver agreement were calculated. RESULTS: Subjective grading of emphysema showed less agreement with the macroscopic reference standard results (r = 0.439-0.505; P < .05) than with objective CT densitometric results (r = 0.555-0.623; P < .001). The 95% CIs for the intercepts of the linear regression lines were suggestive of systematic subjective overestimation of emphysema by all three readers. Interobserver agreement was moderate (kappa = 0.431-0.589). Intraobserver agreement was good to excellent (kappa = 0.738-0.936). The expertise of individual readers did not substantially influence results. CONCLUSION: Systematic overestimation and moderate interobserver agreement may compromise subjective visual grading of emphysema, which suggests that subjective visual grading should be supplemented with objective methods to achieve precise, reader-independent quantification of emphysema.

Absorptiometry, Photon↗
PubMed1997

Respiratory impedances and acinar gas transfer in a canine model for emphysema.

We examined how the changes in the acini caused by emphysema affected gas transfer out of the acinus (Taci) and lung and chest wall mechanical properties. Measurements were taken from five dogs before and 3 mo after induction of severe bilateral emphysema by exposure to papain aerosol (170-350 mg/dose) for 4 consecutive wk. With the dogs anesthetized, paralyzed, and mechanically ventilated at 0.2 Hz and 20 ml/kg, we measured Taci by the rate of washout of 133Xe from an area of the lung with occluded blood flow. Measurements were repeated at positive end-expiratory pressures (PEEP) of 10, 5, 15, 0, and 20 cmH2O. We also measured dynamic elastances and resistances of the lungs (EL and RL, respectively) and chest wall at the different PEEP and during sinusoidal forcing in the normal range of breathing frequency and tidal volume. After final measurements, tissue sections from five randomly selected areas of the lung each showed indications of emphysema. Taci during emphysema was similar to that in control dogs. EL decreased by approximately 50% during emphysema (P < 0.05) but did not change its dependence on frequency or tidal volume. RL did not change (P > 0.05) at the lowest frequency studied (0.2 Hz), but in some dogs it increased compared with control at the higher frequencies. Chest wall properties were not changed by emphysema (P > 0.05). We suggest that although large changes in acinar structure and EL occur during uncomplicated bilateral emphysema, secondary complications must be present to cause several of the characteristic dysfunctions seen in patients with emphysema.

Aerosols↗
PubMed1990

Emphysema in silicosis. A comparison of smokers with nonsmokers using pulmonary function testing and computed tomography.

The presence of emphysema in silicosis is believed to be secondary to the development of progressive massive fibrosis (PMF). However, it is difficult to separate out other causative factors, particularly cigarette smoking. In order to attempt to distinguish these factors, we examined 30 patients with silicosis by means of pulmonary function testing and computed tomography (CT) scans of the chest. Eighteen of these patients were either exsmokers or current smokers, and 12 of them were nonsmokers. The CT scans were read independently by two observers on two separate occasions. Silicosis was graded on a 5-point scale from 0 to 4; emphysema was graded as a percentage of lung involved. Percent emphysema was associated with level of pulmonary function (FEV1, FVC, and DLCO) independent of its association with either cigarette smoking or silicosis grade (p less than 0.01). Silicosis grade was associated with DLCO (p less than 0.05) independent of its association with either cigarette smoking or percent emphysema, but was not associated with level of FEV1 or FVC. In the group without PMF (silicosis Grade 0, 1, or 2), smokers had worse emphysema than nonsmokers (p less than 0.01); there was no such difference among the patients with PMF (silicosis Grade 3 or 4). Only one of the nonsmoking subjects with silicosis but without PMF had any emphysema detected on CT. Our data suggest that silicosis, in the absence of PMF, does not cause significant emphysema, and that it is primarily the degree of emphysema rather than the degree of silicosis that determines the level of pulmonary function.

Adult↗
PubMed1994

Pitfalls in antiprotease therapy of emphysema.

Many individuals with emphysema are unable to stop smoking despite the best efforts of specialists in smoking cessation. Because emphysema is a slowly progressive disease, it is rational to attempt to develop drugs for it. The hope is that drug therapy will slow the rate of decline of lung function, thereby delaying the onset of disability and prolonging life. The major emphasis in drug development has been on antiproteases having the ability to inhibit neutrophil elastase. There are a number of potential pitfalls in the development of such drugs. Although there is gathering evidence that elastin degradation is a part of the development of human emphysema, it is evident from studies in experimental emphysema that protease-antiprotease imbalance is not the only pathogenetic mechanism that gives rise to emphysema. There is strong evidence that human centrilobular and panacinar emphysema are different in pathogenesis. Indeed, airspace enlargement may be considered one of the stereotyped ways that the lung heals after a variety of injuries. There is accumulating evidence that macrophages as well as neutrophils may participate in elastolysis; antiproteases designed to inhibit neutrophil elastase may not inhibit the metalloproteases produced by macrophages. Some antiproteases may serve to transport elastase into the interstitium of the lung and actually increase the risk of emphysema. A process study of antiprotease therapy, using a measure of alteration of elastase burden of the lungs and urinary elastin peptides and desmosine measurements as markers of elastin degradation is now feasible. An outcome study of antiprotease therapy of emphysema should not be undertaken unless there is evidence from a process study that an antiprotease has biochemical efficacy and no unacceptable side effects.

Animals↗