A Combined Pulmonary Function and Emphysema Score Prognostic Index for Staging in Chronic Obstructive Pulmonary Disease

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality. Lung computed tomography parameters, individually or as part of a composite index, may provide more prognostic information than pulmonary function tests alone.

Aim

To investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach.

Material-Methods

Predictors of mortality were assessed in COPD outpatients whose lung computed tomography, spirometry, lung volumes and gas transfer data were collected prospectively in a clinical database. Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used.

Results

169 patients were included (59.8% male, 61.1 years old; Forced Expiratory Volume in 1 second % predicted: 40.5±19.2). 20.1% died; mean survival was 115.4 months. Age (HR = 1.098, 95% Cl = 1.04–1.252) and emphysema score (HR = 1.034, 95% CI = 1.007–1.07) were the only independent predictors of mortality. Pulmonary artery dimensions were not associated with survival. An emphysema score of 55% was chosen as the optimal threshold and 30% and 65% as suboptimals. Where emphysema score was between 30% and 65% (intermediate risk) the optimal lung volume threshold, a functional residual capacity of 210% predicted, was applied. This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk (Functional Residual Capacity ≥210% predicted) or low risk (Functional Residual Capacity <210% predicted). This approach was more discriminatory for survival (HR = 3.123; 95% CI = 1.094–10.412) than either individual component alone.

Conclusion

Although to an extent limited by the small sample size, this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD, than other individual predictors alone.     

The Surgical Treatment of Pulmonary Emphysema

Emphysema may be focal or multifocal. In either type an area of disease may enlarge and reduce the function of adjacent lung.Thirty patients who required treatment for emphysema and its complications are described. Fifteen patients with focal emphysema that did not constitute a space-occupying lesion required operation because of recurrent pneumothorax or infection in the affected area. The results were excellent. Ten patients with focal emphysema and progressive “space occupation” complained of moderate but increasing dyspnea. Removal of the enlarging lesion resulted in marked improvement. Five patients with multifocal emphysema and progressive space occupation in one focal area suffered from severe dyspnea and poor general health. The space-occupying lesion was removed by lobectomy. The results, measured by pulmonary function tests and subjective improvement, were rewarding in most cases. No patient with multifocal emphysema but without a space-occupying lesion under-went operation.     

Pulmonary Emphysema and α1-Antitrypsin Deficiency

Of 72 patients with radiological evidence of pulmonary emphysema, emphysema occurred either alone or in association with bronchitis in 61, and 8 of these (13%) were found to have α₁-antitrypsin deficiency. The main features of this condition are: exertional dyspnoea of relatively early onset (generally between 30 and 45 years of age), severely impaired FEV₁ and T_LCO, and radiological emphysema predominantly affecting the lower zones of the lungs. It is probable that any patient with all the above abnormalities has α₁-antitrypsin deficiency. There is evidence to suggest that cigarette smoking may hasten the onset of this type of emphysema.     

Observations on the Classification and Distribution of Pulmonary Emphysema in Canada

General principles of epidemiology are reviewed, using as an example the chronic non-specific respiratory diseases in Canada. Lack of agreement in definition and classification seriously hampers the use of governmental statistics to study the epidemiology of these diseases. Though Canada is experiencing a mid-century epidemic of deaths from emphysema, evidence is presented which suggests that provincial variation in this death rate is artificial and is likely apparent because physicians do not categorize deaths from this and related diseases in any similar fashion. Three-year-average age-standardized death rates by provincial areas for emphysema with or without bronchitis, asthma, chronic bronchitis and bronchiectasis are presented in evidence that provincial variation is largely obliterated when all chronic non-specific respiratory diseases are considered as a single nosological unit. Advantages and disadvantages of a recent clinical classification of these diseases are reviewed, and it is concluded that such a classification has a great deal to offer epidemiologists or clinicians studying the cause and natural history of these diseases.     

Stratified Pulmonary Blood Flow: Some Consequences in Emphysema and Pulmonary Embolism

Both ventilation and blood flow in the secondary lobule of the lung are stratified; each unit of lung tissue in the proximal portion of the lobule receives up to four times the blood flow of units in the peripheral portion. Questions of the limiting role of gas diffusion within the small airways become virtually irrelevant in the face of this stratification of function.The central portion of the lobule, with its high ventilation, blood flow, and gas exchange, is very vulnerable; small lesions at this site will produce disproportionately large disturbances of gas exchange and of pulmonary vascular resistance. This may well account for some of the phenomena of conditions such as centrilobular emphysema and pulmonary microembolism.     

Experimental Emphysema—Histologic Changes and Alterations in Pulmonary Circulation

Detailed study of the pathogenesis of bullous emphysema has been hampered by lack of a suitable animal model of this disease. Prolonged exposure of rats and dogs to elevated partial pressures of oxygen produced a chronic obstructive disease in the lungs of these animals which anatomically resembles bullous emphysema in man. The disease was characterized by extensive bullae formation, alveolar septal destruction, airway obstruction and pronounced circulatory changes. It is suggested that this condition in laboratory animals may serve as a model for the study of pulmonary obstructive disease.     

Pulmonary Emphysema in Cystic Fibrosis Detected by Densitometry on Chest Multidetector Computed Tomography

Background

Histopathological studies on lung specimens from patients with cystic fibrosis (CF) and recent results from a mouse model indicate that emphysema may contribute to CF lung disease. However, little is known about the relevance of emphysema in patients with CF. In the present study, we used computationally generated density masks based on multidetector computed tomography (MDCT) of the chest for non-invasive characterization and quantification of emphysema in CF.

Methods

Volumetric MDCT scans were acquired in parallel to pulmonary function testing in 41 patients with CF (median age 20.1 years; range 7-66 years) and 21 non-CF controls (median age 30.4 years; range 4-68 years), and subjected to dedicated software. The lung was segmented, low attenuation volumes below a threshold of -950 Hounsfield units were assigned to emphysema volume (EV), and the emphysema index was computed (EI). Results were correlated with forced expiratory volume in 1 s percent predicted (FEV1%), residual volume (RV), and RV/total lung capacity (RV/TLC).

Results

We show that EV was increased in CF (457±530 ml) compared to non-CF controls (78±90 ml) (P<0.01). EI was also increased in CF (7.7±7.5%) compared to the control group (1.2±1.4%) (P<0.05). EI correlated inversely with FEV1% (r_s=-0.66), and directly with RV (r_s=0.69) and RV/TLC (r_s=0.47) in patients with CF (P<0.007), but not in non-CF controls. Emphysema in CF was detected from early adolescence (~13 years) and increased with age (r_s=0.67, P<0.001).

Conclusions

Our results indicate that early onset emphysema detected by densitometry on chest MDCT is a characteristic pathology that contributes to airflow limitation and may serve as a novel endpoint for monitoring lung disease in CF.