Adelbert H. Bigler

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.

Simple fecal tests of absorption. A prospective study and critique.

A prospective study in which the value of four stool screening tests of malabsorption was assessed demonstrated that the Sudan stain for fat, with or without heat and acid, microscopic search for meat fibers and radiotriolein excretion, but not the gelatin film tests, was accurate in 69–79% of studies. Accuracy was lowest in mild steatorrhea and because of this, screening tests were least helpful in patients in whom these tests might have realized their greatest potential value for clinical diagnosis. With high meat intake, stool meal fibers proved as good as, or better than, the other methods for testing for nonspecific malabsorption. The gelatin film test, stool meat fibers and the differential results of the Sudan test before and after heat and acid were of no specific value in distinguishing patients with pancreatic insufficiency from those with other causes of malabsorption; their use for this purpose should be abandoned.

Hypocapnia and measurement of airflow resistance and dynamic compliance as functions of respiratory frequency

Measurements of lung mechanical behaviour as a function of respiratory frequency may be associated with significantly increased ventilation at high breathing rates. It follows that these measurements may be influenced by hypocapnia which has been shown to increase airflow resistance and to decrease dynamic compliance. To examine this possibility we continuously monitored the end-tidal CO2 tension during the determination of pulmonary resistance and dynamic compliance as functions of frequency and we compared measurements obtained by the standard method and by a technique designed to prevent the development of hypocapnia at high breathing rates. We studied 11 patients with chronic obstructive pulmonary disease and also two smokers with normal spirometry and resistance. Although conventional measurements at frequencies higher than 40-45 breaths/min were associated with a significant decrease in end-tidal CO2, no systematic differences were found between the values of pulmonary resistance and dynamic compliance obtained by the two techniques. Our data indicate that the development of hypocapnia at high breathing rates does not significantly affect measurements of resistance and compliance as functions of frequency, at least when the duration of each period of hyperventilation is limited to the minimum necessary for a single determination, which was less than 30 seconds in the present study. A comparison of our results with previously published data suggests that the time factor may be critical with respect to the possible effects of hypocapnia on these measurements.

Pulmonary Resistance and Dynamic Compliance as Functions of Respiratory Frequency

The behavior of pulmonary resistance (RL) and that of dynamic compliance (Cdyn) as functions of respiratory frequency (f) were compared in normal subjects and in patients with chronic obstructive pulmonary disease (COPD). Although both RL and Cdyn varied with f in most COPD patients and in some normal subjects, Cdyn appeared to be more sensitive than RL to variations of frequency; no significant changes in RL could be demonstrated in subjects in whom Cdyn was frequency dependent. The degree of frequency dependence of Cdyn was correlated with the severity of respiratory impairment (as quantified by conventional pulmonary function tests); in contrast, RL was not detectably frequency dependent in some subjects with advanced COPD. Compared with Cdyn, RL was more commonly nonlinearly related to respiratory frequency, often increasing at high breathing rates. Our results indicate that changes in RL with frequency are less predictable and more difficult to detect than the corresponding changes in Cdyn.