Attilio D. Renzetti

The veterans administration cooperative study of pulmonary function: III. Mortality in relation to respiratory function in chronic obstructive pulmonary disease

Abstract A cooperative study of life expectancy in chronic obstructive pulmonary disease (COPD) has been conducted in fifteen Veterans Administration Hospitals that had previously contributed to the study of pulmonary function in normal men [9,10]. Between October 1957 and July 1960, 487 men were selected for study on the basis of characteristic clinical manifestations of COPD and the presence of residual volume: total lung capacity (RV:TLC) ratio of 35 per cent or greater, together with a total lung capacity (TLC) larger than 80 per cent of their predicted normal value. Upon entrance into the study, clinical information was obtained for each patient and all were studied by those pulmonary function tests previously standardized among the participating hospitals. These consisted of measurements of lung volume, maximal expiratory air flow rates and maximal voluntary ventilation. In addition, arterial blood-gas contents were measured by conventional methods. At four years after entrance into the study, the mortality rate for this group of patients was 53 per cent. An excellent correlation was found between life expectancy and the degree of physiologic disturbance at the time of first study. This was true for disturbances in ventilatory function as well as alterations in gas exchange. In addition, the previously reported unfavorable influence upon prognosis of an episode of right heart failure from cor pulmonale was confirmed. In contrast to previous studies, a correlation of the vital capacity, residual volume and residual volume to total lung capacity ratio and a lack of correlation of polycythemia with survival was found. Finally, it was observed that patients with COPD who reside at moderately elevated altitudes have a significantly higher mortality rate than those who live at sea level. This difference probably results from the higher incidence of cor pulmonale among the patients residing at high altitude.

Clinical and physiologic features of some types of pulmonary diseases with impairment of alveolar-capillary diffusion: The syndrome of “alveolar-capillary block”

Abstract 1.1. Twelve additional cases with various diffuse diseases of the lungs characterized physiologically principally by interference with the diffusion of oxygen across the alveolar-capillary septum have been studied. 2.2. The patients in this group included two with pulmonary granulomatosis following exposure to beryllium; one with pulmonary granulomatosis of the Boecks sarcoid type; one with pulmonary granulomatosis of undetermined etiology, in which the granulomatous lesion contained unusually large numbers of foreign body-type giant cells and bi-refractile crystals; one patient with scleroderma; three patients with pulmonary fibrosis of unknown etiology (in one case after exposure to beryllium, in two cases associated with granulomas in other organs), and four cases in which a diagnosis could not be made. 3.3. The pattern of pulmonary dysfunction consisted of (1) reduced lung volumes, (2) maintenance of a large maximum breathing capacity, (3) hyperventilation at rest and during exercise, (4) normal or nearly normal arterial oxygen saturation at rest but a marked reduction of the arterial oxygen saturation after exercise, (5) normal alveolar oxygen tension, (6) a reduced oxygen diffusing capacity and (7) pulmonary artery hypertension. 4.4. In some severe cases the dead space-like ventilation and the venous admixture-like perfusion was increased. These findings have been interpreted as an indication of the inhomogeneous nature of the pathologic process. 5.5. The clinical findings have been analyzed in the light of the physiologic data and the evolutionary trends, both clinical and physiologic, have been described. 6.6. Because the major pathologic changes are localized in the alveolar capillary septa and because the major physiologic defect is a reduction of the permeability of the alveolar capillary membrane for oxygen, the name alveolar-capillary block has been tentatively offered to describe this syndrome.

Comparison of the anticholinergic bronchodilator ipratropium bromide with metaproterenol in chronic obstructive pulmonary disease: A 90-day multi-center study

The short- and long-term efficacy and safety of an inhaled quaternary ammonium anticholinergic agent, ipratropium bromide, and a beta agonist aerosol, metaproterenol, were compared in 261 nonatopic patients with chronic obstructive pulmonary disease (COPD). The study was a randomized, double-blind, 90-day, parallel-group trial. On three test days-one, 45, and 90-mean peak responses for forced expiratory volume in one second and forced vital capacity and mean area under the time-response curve were higher for ipratropium than for metaproterenol. Clinical improvement was noted in both treatment groups, especially during the first treatment month, with persistence of improvement throughout the remainder of the study. Side effects were relatively infrequent and generally mild; tremor, a complication of beta agonists, was not reported by any subject receiving ipratropium. These results support the effectiveness and safety of long-term treatment with inhaled ipratropium in COPD.

CLINICAL AND PHYSIOLOGICAL ASPECTS OF A CASE OF OBESITY, POLYCYTHEMIA AND ALVEOLAR HYPOVENTILATION

The occurrence of arterial hypoxia with poly-cythemia usually results from some known type of pulmonary disease or from an abnormal communication between the right and left sides of the circulation. Although arterial oxygen unsatura-tion has been observed in patients with polycy-themia vera (1-4), it is usually of only mild degree. Recently, Newman, Feltman, and Devlin (5) found polycythemia and a severe degree of arterial hypoxia in two patients who did not have evidence of any previously described form of lung disease. These authors postulated that polycy-themia vera by its effects on the lung or on the respiratory center could give rise to oxygen un-saturation of arterial blood. They also suggested that in some patients polycythemia is secondary to respiratory center disease of undetermined etiology. It is the purpose of the present report to present the clinical and physiological findings in an obese young man with polycythemia and arterial oxygen unsaturation. CLINICAL REPORT C. D., a thirty-year old white man was admitted to the hospital on January 8, 1954 complaining of shortness of breath and ankle swelling. He had weighed more than 200 pounds for at least 13 years. In 1942 he worked as a furnace feeder in an aluminum plant for six months. He first noted a non-productive cough in 1950 and since then had experienced an increased frequency of respiratory infections. In March, 1952, an elevated hemato-crit was observed, and by October, 1952 he had to stop work because of dyspnea and ankle edema. In the six months before entering the hospital these symptoms increased , and he developed orthopnea. Physical examination revealed an alert, cyanotic, slightly orthopneic man who weighed 290 pounds and was 67 inches in height. A few rales were heard at the right posterior lung base. The heart was in gallop rhythm, and the pulmonic second sound was accentuated. Mild edema of the abdominal wall and marked edema of the lower extremities was present. The significant laboratory findings were as follows: red blood cells 6.77 million per cu. mm.; hemoglobin 20 gm. per cent; hematocrit 69 per cent; white blood cells 6,000 per cu. mm. with a normal differential count and normal cellular morphology; platelets 150,000 per cu. mm. The bone marrow showed hyperplasia of the erythroid series, and reticulocytes were 1 per cent of the red blood cells. The blood uric acid was 9.6 mg. per cent. The urinary 17-ketosteroid excretion was 8 mg. …

Predictors of survival in subjects with chronic airflow limitation

In a study of chronic airflow limitation, we followed 140 subjects living in Utah at altitudes of 1,300 to 1,500 meters for seven to 13 years. Twelve-year survival probabilities were determined and compared with an age- and sex-matched Utah population. The lowest 12-year survival probability was 0.40 for those patients with a forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of less than or equal to 0.40, indicating that there is much variability in survival. Other indicators of a lower survival probability (and increased death risk ratio) were an FEV1 percent predicted less than or equal to 50, an FEV1 less than or equal to 1.5 liters, male gender, partial pressure of oxygen (PO2) [exercise] less than or equal to 50 mm Hg, partial pressure of carbon dioxide (PCO2) [rest] greater than 39 mm Hg, PCO2 (exercise) greater than 39 mm Hg, FVC percent predicted less than or equal to 80, PO2 (rest) less than or equal to 55 mm Hg, and a carbon monoxide diffusing capacity (DLCO) percent predicted less than or equal to 80. Current smokers had a poorer survival probability than the reference population and an increased death risk when compared with the nonsmokers in the study. Pack/years of smoking also affected survival. Other variables associated with reduced survival were a diagnosis of chronic bronchitis combined with emphysema, more rapid annual declines in the FEV1 and/or FVC, low alpha 1-antitrypsin levels, a 20 percent improvement in FEV1 following the use of a bronchodilator aerosol, and a lower socioeconomic class. Differences between these findings and those noted in other studies are in the main due to differences in the characteristics (such as age, diagnosis, and extent of disease) of the patients in the study populations. The findings have relevance in estimating a patients prognosis and for developing guidelines for disability determination purposes.

Variables Associated with Changes in Spirometry in Patients with Obstructive Lung Diseases

One hundred fifty subjects were enrolled in a long-term study of obstructive lung diseases; 84 of these were subjected to five or more spirometric studies over a period of two or more years. Stepdown regression analysis was performed to determine the association between many different variables and the annual rates of change in the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). The following associations were noted to be significant (p less than 0.03); more favorable rates of change of the FVC and FEV1 were associated with a higher alpha1-antitrypsin level and older age. Less favorable changes were associated with more years of cigarette smoking, more airway reactivity and more frequent lower respiratory tract illnesses.

Roentgenologic, physiologic and structural estimations of the total lung capacity in normal and emphysematous subjects☆

Abstract The results of a previously described roentgenologic method for estimating total lung capacity are compared to those obtained using a conventional closed circuit helium method and the body plethysmograph method in twenty normal subjects and twenty patients with chronic pulmonary emphysema. In normal subjects, no significant difference was found in the total lung capacity among the three methods. In the emphysematous patients, the values for total lung capacity obtained by the roentgenographic and plethysmographic methods were the same but were significantly greater than those obtained by the helium dilution method and the predicted normal value. In sixty-six deceased subjects the total lung capacity, as determined with the roentgenographic method, correctly predicted the absence of emphysema in nineteen and showed a good correlation with the severity of anatomic emphysema in the remaining forty-seven. It is concluded that the roentgenologic method of estimating total lung capacity described by Barnhard et al. [19] is as accurate in normal and emphysematous subjects as the best physiological methods currently in use. Because it can be carried out simply, rapidly and inexpensively, it is recommended for office and hospital use and in large scale screening studies for pulmonary emphysema.

Pathologic patterns of chronic obstructive pulmonary disease in patients with normal and deficient levels of alpha1 antitrypsin

Abstract Twenty-nine patients with chronic obstructive pulmonary disease (COPD), selected on the basis of their alpha 1 antitrypsin (AAT) phenotype or trypsin inhibitory capacity (TIC), were studied by clinical and physiologic methods. Six were homozygous, 10 were heterozygous and 13 were normal with respect to their AAT levels. Spirometry, lung volume and diffusing capacity measurements indicated that the extent of pulmonary disease was greater in the patients with homozygous AAT deficiency as compared to the other groups. Quantitative measurements of regional ventilation and perfusion were made using xenon 133 and the results were evaluated by statistical technics. Two different methods of discriminant analysis of the regional ventilation and perfusion data clearly showed the three groups of patients to be significantly different from each other. Since the heterozygous AAT deficient patients had a pattern of disease which distinguished them from patients with both severely deficient and normal AAT levels, it is concluded that heterozygosity for AAT is an important factor in the development of COPD.

Regional ventilation and perfusion in silicosis and in the alveolar-capillary block syndrome

Eleyen patients selected on the basis of bilateral, diffuse linear and/or nodular densities in their chest roentgenograms were studied by a battery of pulmonary function tests, including quantitative measurements of regional ventilation and perfusion with radioactive xenon (Xe 133 ). Two groups were separated according to the presence of arterial oxygen unsaturation following a one minute standard step test. Group A, without arterial oxygen unsaturation following exercise, consisted of six patients with minimal nodular uncomplicated silicosis. Group B, with arterial oxygen unsaturation following exercise, consisted of four patients with diffuse interstitial pneumonitis and one with silicosis which was also nodular and uncomplicated but with larger and more extensive involvement than those in group A. The patients in group B demonstrated the physiologic characteristics associted with the alveolar-capillary block syndrome. Regional ventilation measurements in both groups A and B were not significantly different from those in a control group of eleven normal subjects. Regional perfusion was also found to be normal in group A so that the normally decreasing ventilation-perfusion ratios from apex to base of the lungs was maintained. However, the evenly distributed perfusion in group B resulted in more uniform ventilation-perfusion ratios from upper to lower lung zones. This finding is interpreted as support for the concept that the arterial oxygen unsaturation after exercise demonstrated by patients with the alveolar capillary-block syndrome results from the reduced diffusing capacity of the lung rather than from an imbalance between alveolar ventilation and perfusion.