Alpha 1 antitrypsinin the livers of patients with emphysema.

Parenchymal liver cells from emphysema patients with an inherited deficiency of alpha(1)-antitrypsin contain globules of glycoprotein that bind fluorescent antibody to alpha(1)-antitrypsin. The globules can be seen after hematoxylin and eosinstaining or on electron microscopy, but are more readily demonstrated by PAS stain of amylase-treated liver sections. It appears that an inappropriately large amount of alpha(1)-antitrypsin is found in the liver even when there is a deficiency in the serum. Genetic variants of the normal antitrypsin molecule may be unable to leave their site of synthesis in the liver cell because of some molecular aberration.

Aging of the lungs: speculation on the role of oxidants and proteases.

In most regards, aging of the human lungs mimics the development of emphysema. Various lines of evidence suggest that oxidants and proteases play an important role in the pathogenesis of emphysema. The disease seems to arise through a complex interplay of genetic and environmental factors. This paper explores the possibility that normal aging of the lungs, as it has been defined by various cross-sectional and longitudinal studies, is part of a pathological continuum ending with frank emphysema. It is not clear if these are "normal" aging effects or the result of the accumulation of disease.

A simplified method for measuring helium closing volume.

A simple method for delivering a constant volume of helium for the measurement of airway closing volume is described. Using a standard fiveway valve and PVC plastic irrigation pipe, a device was constructed which permits the delivery of a uniform volume of helium and avoids the troublesome valve change during inspiration. Results obtained when using this device were comparable to those with the use of conventional bag to contain the helium.

A new pendant storage oxygen-conserving nasal cannula.

With increasing interest in reducing the cost of oxygen therapy, we recently designed an oxygen-conserving cannula. It reduces the oxygen supply flow necessary to achieve adequate oxygen saturation, but because it requires the use of a reservoir situated under the nose, some patients find it obtrusive. We therefore designed a similar system but displaced the reservoir away from the face and onto the anterior chest wall where it could be hidden from view by the patient's clothing. We evaluated this pendant conserving nasal cannula (PNC) in seven hypoxemic patients with chronic obstructive pulmonary disease. We compared oxygen saturations achieved using the PNC vs the standard steady flow nasal cannula (SNC) at 0.5 through 4 L/min. The mean improvement in oxygen saturation using the PNC vs the SNC was 3.3 percent at 0.5 L/min, 4.3 percent at 1 L/min and 3.1 percent at 2 L/min. These differences were statistically significant (p less than 0.001). The saturation achieved by the PNC at 0.5 L/min was equivalent to that achieved by the SNC at 1.8 L/min. We conclude that the PNC provides effective oxygen delivery to patients at supply flows substantially less than the SNC. The device is aesthetically acceptable to patients and its widespread use in patients requiring chronic oxygen therapy could bring about significant financial savings.

Reversibility of airways injury over a 12-month period following smoking cessation.

In this investigation, we examined changes in exfoliated tracheobronchial cells in sputum in 46 individuals (mean age = 49.2 years; mean packyears = 48.7) who discontinued smoking and 37 individuals (mean age = 54.9 years; mean packyears = 65.2) who continued to smoke over a 12-month period after participation in the St. Helena Hospital and Health Center one-week residential smoking cessation program. Before the beginning of the smoking cessation program, those who went on to quit were not different from those who did not quit with respect to baseline cytomorphology ratings. In those individuals with a minimum of three follow-up tests, results indicated significant reductions from precessation levels in macrophages, pigmented macrophages, and neutrophils after adjustment for differences in age, packyears, and pulmonary function (FEV1/FVC). Over the course of follow-up, quitters, in comparison with nonquitters, also had significantly lower mean levels of columnar cells, mucus, mucous spirals, and metaplasia. These results indicate a consistent effect of smoking cessation on cytomorphology and demonstrate that on cessation, some of the measured elements promptly return toward a more normal pattern.

Bolus technique for assessing distribution of inspired gas during tidal breathing.

The washout of an insoluble tracer from the lung may be represented by a model with two ventilatory compartments representing poorly and better-ventilated regions. Using boli of a second insoluble gas delivered at a given point during inspirations of a multibreath washout test, the proportions of labeled inspired ventilation reaching the poorly and well-ventilated regions may be determined by analyzing the kinetics of the exhaled tracer. We studied eight normal subjects breathing through large-bore solenoid valves controlled to maintain tidal volume at 600 or 900 ml. Boli consisting of 15 ml of 80% He-20% O2 were delivered over 75 ms; this labeled approximately 125 ml of inspired gas. Boli were delivered after 50 ml had been inspired to mark early inspiration and after 300 ml had been inspired to mark midinspiration. Using 900-ml tidal breaths, late inspiration was marked by boli delivered at 600 ml. Subjects were studied in the seated and the supine positions. In both positions, significantly more of the early breath went to the poorly ventilated compartment. Several possible physiological mechanisms, singly or in combination, could account for these observations, but differences in dead space path length are most likely involved.

Familial temperature sensitive alpha 1 protease inhibitor (M1Anaheim).

An alpha 1 protease inhibitor which is sensitive to increased temperatures and which migrates in the same position as the normal M1 phenotype, has been identified. The sensitivity of the trypsin inhibitory capacity is an inherited characteristic, which is enhanced by acid conditions, as well as conditions during isoelectric focusing. Loss of the serum trypsin inhibitory capacity is not parallel to that of the serum elastase capacity, suggesting that the inhibitory sites for these proteases are oriented differently within the alpha 1 protease inhibitor molecule.

Relationship of cytomorphology to spirometric findings in cigarette smokers.

The objective of the study was to determine the relationship between sputum cytomorphology and pulmonary function. A cross-sectional correlation analysis of results from pulmonary function testing and eight cytomorphologic indices of inflammation and metaplasia was conducted in 143 smokers registered in a residential smoking-cessation program. Stepwise multiple regression analysis revealed that after adjusting for age and smoking history, lower levels of pulmonary function were related significantly to higher levels of macrophage pigmentation, neutrophils and metaplasia. Higher levels of macrophages were associated with higher levels of pulmonary function. The overall regression coefficient, 0.35, was highly significant (F[5,136] = 14.84, P = .0001). Categorical analyses revealed that smokers with high counts of neutrophils, macrophage pigmentation, columnar cells, spirals and metaplasia were two to three times more likely to have abnormal pulmonary function than were those with low counts. From these results we conclude that elevations in certain cytologic indices are associated with abnormal lung function. These findings may reflect the pathophysiology of obstructive lung disease. Longitudinal studies are required to determine whether cytomorphologic parameters can identify individuals at risk for functional deterioration at a stage amenable to intervention.

The respiratory disease questionnaire: use of a self-administered version.

A re-designed and simplified respiratory disease questionnaire was self-completed by 245 coke oven workers who previously were interviewed using the Standardized Medical Research Council/National Heart and Lung Institute form. The self-completion survey yielded significantly greater numbers of positive responses to various questions; nearly twice as many men were classified as having chronic bronchitis based on responses to the self-administered questionnaire. The severity of symptoms correlated with various factors such as the worker's smoking history; family history of lung disease, and job history. We suggest that, when compared with an interview using the British Medical Research Council/National Heart and Lung Institute respiratory disease questionnaire, a simplified, self-completion form may serve as a less expensive, more sensitive, and equally uniform and selective epidemiological tool. Self-completion forms deserve the attention and study previously afforded the interview process.

A study on the lung function in alpha 1-antitrypsin-deficient (PiMZ) patients.

Laurel and Eriksson published the first report indicating that alpha 1-antitrypsin deficiency predisposed patients to the development of Chronic Obstructive Pulmonary Disease (COPD). For the purpose of early detection, disturbances of pulmonary function in alpha 1-antitrypsin mild deficiency cases (PiMZ) were compared with those of normal cases (PiMM) in caucasian Americans. The marked results are as follows. 1) Parameters of flow-volume curves were more disturbed in PiMZ cases than in PiMM cases. 2) Volumes of isoflow are specially different between PiMZ and PiMM cases. 3) Mechanical properties, like lung work of breathing, were larger in PiMZ cases than in PiMM cases.