Intravenous administration of alpha-1-proteinase inhibitor in patients of PiZ and PiM phenotype. Preliminary report.

Nine patients with moderate pulmonary emphysema, six of PiZ phenotype and three of PiM phenotype, have received a single intravenous infusion of alpha-1-proteinase inhibitor (human) (A1PI), in a dose of 60 mg/kg over a 30-minute period. They also received a tracer dose (300 microCi) of 131I-labeled A1PI. No active or passive immunization against hepatitis was given. No acute toxicity was observed. Compared with baseline data, significant elevations of serum A1PI (measured both antigenically and as anti-elastase activity) occurred, with a serum half-life approximating 110 hours. Bronchoalveolar lavage fluid, obtained 48 hours after infusion, reflected a significant increase in A1PI concentration versus baseline bronchoalveolar lavage fluid values. Serial gamma camera images of the lungs confirmed persistence of enhanced lung radioactivity for several days. Urinary desmosine excretion did not change following A1PI infusion. During the period of follow-up thus far, no patient has had chronic toxicity, results of liver function tests have been stable, and there has been no development of hepatitis B antigen or antibodies to hepatitis B surface or core antigens.

Determining changes in airway caliber in asthma: the role of submaximal expiratory flow rates.

Sixteen patients with suspected reversible airway obstruction who had previously demonstrated an increase in specific airway conductance after isoproterenol, but who had not demonstrated an increase in forced expiratory flow were studied using a measurement of submaximal flow. Flow during tidal breathing (VTV) was measured spirometrically, and VTV increased in all 16 patients from a value of 0.61 L/sec before isoproterenol to 0.80 L/sec after isoproterenol. In addition, each of these 16 patients experienced a significant increase in vital capacity and a significant decompression of functional residual capacity after isoproterenol. If plethysmography is not available, the measurement of VTV may provide evidence of bronchodilatation. The mechanism responsible for the dichotomy between maximal and submaximal flow is the compression of airways by high positive pleural pressure which is present during maximal, but not submaximal maneuvers.

Determination of bronchodilation in the clinical pulmonary function laboratory. Role of changes in static lung volumes.

Improved airway resistance following bronchodilator inhalation is not always accompanied by improvement in forced expiratory flow. We studied 241 patients with airways obstruction to learn whether changes in static lung volumes (vital capacity and function residual capacity measured by body plethysmography [FRCB]) would reveal bronchodilation not demonstrated by expiratory flow rates (the ratio of forced vital capacity at one second to the total forced vital capacity [FEV1/FVC]), and the forced expiratory flow for the midportion of the forced vital capacity (FEF25--75%). A significant fall in Raw occurred in 129 patients, 46 of whom had a significant increase in vital capacity (mean of + 465 ml +/- 43, P less than 0.001) and a fall in FRCB (mean of -763 ml +/- 78 P less than 0.001) with no change in FEV1/FVC% of FEF25--75%. We interpret these data to indicate that improvement in static lung volumes can reflect bronchodilation in the absence of improved expiratory flow.

Multiorgan scans for staging lung cancer. Correlation with clinical evaluation.

One hundred consecutive patients with findings suggestive of resectable bronchogenic carcinoma were studied prospectively to determine if routine liver, brain, and bone scans (multiorgan scans) detected metastases which were not suggested by a history, physical examination, and serum chemistries. Multiorgan scans were compared with clinical evaluations in 52 patients found to have operable bronchogenic carcinoma. There was a discordance between scans and clinical evaluations in 25/153 scans (16 per cent). Two of the 22 negative scans in patients with abnormal clinical findings were false negative. Sixteen of the 17 positive scans in patients with normal clinical findings were false positive. One of the 131 scans done in patients with no evidence of metastases on clinical evaluation was true positive. These data indicate that the routine use of multiorgan scans in the initial staging of potentially resectable bronchogenic carcinoma is not justified.

Preoperative identification and evaluation of the patient with lung disease.

Preoperative pulmonary function evaluation begins with the bedside, clinical identification of the presence of significant lung disease. Once a patient is so identified, preoperative pulmonary-function studies are indicated. The optimal screening studies for most patients are spirometry and arterial blood gas analysis. Patients who are identified as having marginal function by screening techniques should be studied further by more specialized studies, including radioisotopic evaluation of regional lung function. If a patient is identified as an operative candidate, but one who has increased risk of postoperative morbidity, prophylactic measures should be instituted to reduce postoperative complications. The essence of such measures is increased care preoperatively, intraoperatively, and postoperatively. The use of preoperative evaluation of pulmonary function presents a different magnitude of problem in defining the risk of morbidity in contrast to that of mortality. Available data provide a firm basis for the identification of the patient at increased risk of morbidity. After 23 years and dozens of spirometric studies involving thousands of patients, it is apparent that there is no spirometric number, percentage, or category that will absolutely separate the operable from the inoperable patient. There are estimates of risk--guidelines, to be sure--but no absolutes. The patient whose lung function would have been considered to prohibit lung resection in the 1950s has been successfully operated on in the 1980s. In dealing with the risk of mortality, the physician should always bear in mind that, although statistics apply to groups, they often do not apply to individual patients.

The effect of short-term oxygen supplementation on oxygen hemoglobin affinity in patients with chronic obstructive pulmonary disease.

In 12 hypoxemic patients with chronic obstructive pulmonary disease, the partial pressure of oxygen at which hemoglobin is 50% saturated (P50) and levels of 2,3-diphosphoglycerate (2,3-DPG) were determined under 3 study conditions: (1) while breathing room air, (2) during oxygen supplementation for 72 h sufficient to increase PaO2 above 70 mmHg, and (3) at 72 h after the period of oxygen supplementation. The data showed that in the control period in hypoxemic (PaO2, 52 +/- 6 mmHg), mildly hypercapnic (PaCO2, 47 +/- 6 mmHg) patients with a borderline elevation of pH (7.42 +/- 0.03), there was an increase in P50 (28.6 +/- 1.6 versus a normal value of 26.5 +/- 1; p less than 0.005), and a concomitant increase in 2,3-DPG (19.02 +/- 1.77 mg/g Hb versus a normal value of 13.52 +/- 1.27; p less than 0.005). Nine patients received oxygen for 24 h, and 5 received oxygen for 72 h. In these 5 patients, oxygen supplementation resulted in a shift in P50 to a normal value of 26.7 +/- 1.8 (this value was different from the patients' level while breathing room air and not different from that of the normoxemic control subjects) and a decrease in 2,3-DPG toward but not to a normal value (16.34 +/- 1.92; p less than 0.01). This shift in P50 to the left could be related to the decrease in 2,3-DPG. Accordingly, in patients with COPD who are treated with supplemental oxygen, the net effect on oxygen transport would be a function of the changes produced in PaO2 versus those in hemoglobin-oxygen affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo dimensional response of airways of different size to transpulmonary pressure.

We studied four supine dogs that were anesthetized with pentobarbital, intubated, and ventilated with a piston pump. The dimensional response of central (CAW) (greater than 2 mm diam) and peripheral airways (PAW) (smaller than 2 mm diam) to changes in transpulmonary pressure (Ptp) was determined by progressive increments in tidal volume (VT). A specially designed electronics relay circuit permitted this relationship to be obtained for points of no flow during tidal volume breathing: i.e., preinspiration (FRC); end inspiration (FRC + VT). The airways were dusted with powdered tantalum. Six airway divisions were identified: four CAW: trachea, main stem, lobar, segmental; and two PAW: subsegmental, and lobular. AP and lateral roentgenograms were obtained by standard technics and primary magnification (mag factor 2). Airway diameters were plotted as a function of transpulmonary pressure between 3 and 26 cmH2O with the diameter at total lung capacity expressed as 100%. The data show that: 1) there is significant distensibility above 5 cmH2O for all airways from the trachea to the lobular airways; 2) that the pressure-diameter plot is a linear plot for each airway from 3 to 26 cmH2O with R values between 0.846 and 0.957; 3) the peripheral lobular airways are more distensible than the central airways (P smaller than 0.05). We attribute the difference in distensibility of the peripheral lobular airways to their lack of cartilaginous support, and their decreased muscular support when compared to the CAW.

Effect of aerosolized isoproterenol on resting myogenic tone in normals.

The effects of aerosolized isoproterenol on expiratory (exp) and inspiratory (insp) conductance (Gaw), maximal exp and insp flow (VEmax and VImax), and static elastic recoil pressure (Pst) were measured in 12 normals. Both exp and insp Gaw increased throughout the vital capacity (37% at 50% VC; P less than 0.01). VEmax increased only at 50% VC (9%; P less than 0.01). VImax and Pst did not change. Accordingly, a dichotomy existed between the Gaw and Vmax changes during both exp and insp. We do not attribute this dichotomy to loss of driving pressure or to volume-time-dependent behavior of airway tone. We interpret the increased exp and insp Gaw to indicate isoproterenol deposition within and bronchodilatation of larger central airways (trachea, main stem, lobar, segmental). Since insp Gaw increased and VImax did not, we conclude that the caliber of these central airways is not the exclusive deteminant of VImax, that the caliber of some more distal airways (subsegmental and beyond) did not change, and that these airways are important determinants of VImax. We conclude that non-uniform distribution of isoproterenol could account for the Gaw-Vmax dichotomy during inspiration, and that such non-uniform distribution coupled with resultant increased compliance and compressibility of the downstream segment could account for the Faw-Vmax dichotomy during expiration.

Hypoxemia during apnea in normal subjects: mechanisms and impact of lung volume.

Seven normal awake males were studied to define the mechanisms and impact of lung volume on the hypoxemia occurring during apnea. During repeated 30-s voluntary breath holding, these subjects were studied at different lung volumes, during various respiratory maneuvers, and in the sitting and supine body positions. Analysis of expired gases and arterial O2 saturation during these repeated breath holdings yielded the following conclusions. Apnea of 30-s duration at low lung volumes is accompanied by severe arterial O2 desaturation in normal awake subjects. Initial lung volume is the most important determinant of hypoxemia during apnea. The hypoxemia of apnea at most lung volumes can be explained by simple alveolar hypoventilation in a uniform lung. The lung does not behave as a single-compartment model at lung volumes at which dependent airways are susceptible to closure.