This clinical study was undertaken to compare the diffusion capacity of the lungs in man at rest measured by three different methods utilizing carbon monoxide (DCO) and by direct calculation from two-level alveolar-arterial oxygen "gradients" (DO2); to establish normal values for the DCO methods; and to assess their clinical diagnostic value in patients with diffusion impairment. Thirty-three patients with alveolar-capillary block syndrome were selected on the basis of (1) diffuse, finely dispersed pulmonary lesions, (2) normal ventilatory function or dyspnea out of proportion to measured ventilatory impairment, (3) diminished diffusion capacity demonstrated by at least two methods, and (4) absence of physiologic evidence of obstructive emphysema. Diagnoses of beryllium disease, sarcoidosis, chronic interstitial pneumonitis, silicosis, miliary tuberculosis, scleroderma and eosinophilic granuloma were made by lung or other tissue biopsy, on epidemiologic grounds or by bacteriologic study in twenty-four patients, and on clinical grounds alone in nine. Thirteen normal volunteers were studied as controls by the same methods to establish normal values for the DCO. Conventional tests consisted of ventilatory function studies including lung volumes, breathing capacities, pulmonary mixing and spirometry; and respiratory studies including determination of arterial and alveolar O2 tensions, arterial O2 saturation, CO2 tension, CO2 content and pH all during ambient air and lowoxygen breathing. Diffusion studies included calculation of the DO2 from the data obtained, determination of DCO by the steady state and single breath methods, and calculation of the fraction of carbon monoxide removed (FCO). The steady state DCO was 19.5 ± 3.2 cc./ min./mm. Hg for normal subjects and for the patients averaged 7.0 cc. (range of 2.5 to 13.1); there was no overlap between the two groups. The normal single breath DCO was 30.2 ± 4.6 cc./min./mm. Hg with a mean for the patients of 16.8 (range 4.7 to 28.1) and some overlap. The FCO was more than 50 per cent in all but one normal subject (mean 62 ± 9) and less than 50 per cent in all but one patient (mean 31, range 13 to 50). In eighteen patients the mean DO2 of 9.1 cc./min./mm. Hg compared well with the mean steady state DCO of 7.9 cc./ min./mm. Hg (corrected × 1.23 for the greater diffusibility of oxgyen) and there was good individual correlation (r = +0.67, P < 0.01). During exercise requiring about four times basal oxygen uptake the increase in the mean steady state DCO from 20 to 31 cc./min./mm. Hg in 11 normal subjects was about the same as the rise from 7.5 cc. to 15 cc. in twenty-one patients; all those who were able to exercise were also able to increase their DCO And the discrimination of the test was no better during exercise than at rest. The theoretic, technical and clinical problems in application of the DCO methods were discussed. Both DCO methods were much more easily performed than the direct DO2 method but only the steady state technic resulted in comparable values. Further simplifications of the steady state method may be possible particularly in patients without obstructive emphysema. The single breath test may prove useful for screening studies and, if low, is indicative of impaired diffusion. If it is normal the diagnosis of alveolarcapillary block cannot be ruled out by present standards. An increasing number of patients are seen with dyspnea or disability out of proportion to the measured mechanical defects of ventilation. The diagnostic and medico-legal importance of diffusion capacity measurements under these circumstances was stressed.
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