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 patient's 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.

Bronchocentric granulomatosis associated with rheumatoid arthritis.

A 49-year-old woman with biopsy-proved bronchocentric granulomatosis (BCG) had repeated exacerbations of seronegative rheumatoid arthritis and vasculitis of the skin concurrent with BCG. To our knowledge, there have been no prior reports of this form of systemic involvement in BCG. While its pathogenesis remains obscure, this case, along with another recent report of eye involvement, suggests that BCG is part of a widespread immunologic response and is not a distinct entity.

Bronchodilator effects of nebulized fenoterol: a comparison with isoproterenol.

In an attempt to find the optimal single therapeutic dose of fenoterol inhalant solution administered by compressor-powered nebulization, bronchodilator and side effects of five different doses of fenoterol (0.5, 1.0, 1.5, 2.0, and 2.5 mg) and of placebo were compared with those of the recommended therapeutic dose delivered from a metered dose canister in 16 patients with reversible airway obstruction. The fenoterol (except for the metered dose) and the placebo were given in a double-blind, cross-over manner. In comparison with placebo, all doses of fenoterol produced a significant increase in average values of FEV1, FEF25-75%, FVC, and SGaw and decrease in FRC for five to eight hours. There was a trend for the bronchodilator action to become greater and more prolonged with increasing doses of fenoterol. Compared with 0.4 mg given from a metered dose canister, 0.5 mg of fenoterol delivered by compressor powered nebulization was equally effective in bronchodilator potency. Dose-by-dose comparison with isoproterenol indicates that fenoterol is a more potent and longer lasting bronchodilator and has no significant effect on heart rate and blood pressures. The most common side effects were shakiness or tremor of hands which appeared to be dose-related in terms of incidence and intensity. The results of the present study suggest that 0.5 to 1.0 mg of fenoterol is a suitable single therapeutic dose when administered by compressor-powered nebulization.

Antinuclear antibodies in Utah coal miners.

Antinuclear antibodies (ANA) were detected using a mouse kidney substrate in 69 of 238 (29 percent) underground Utah coal miners at a titer of 1:16. At titers of 1:4 and higher, 52 percent were positive. The majority had a speckled pattern and were not directed against any previously characterized antigens. Fifteen of 28 with high titer ANA had reduced complement. The ANA was more apt to be present in those with coal workers' pneumoconiosis (CWP), and as ANA titer increased, the percentage with CWP increased. The ANA increased with both age and coal mine dust exposure. It is hypothesized that ANA and CWP both result from long-term dust exposure, but that there is insufficient evidence to implicate ANA in the pathogenesis of CWP.

Cardiac output and mixed venous oxygen content measurements by a tracer bolus method: theory.

We present a bolus method of inert-gas delivery to the lungs that facilitates application of multiple inert gases and the multiple inert-gas-exchange technique (MIGET) model to noninvasive measurements of cardiac output (CO) and central mixed venous oxygen content Reduction in recirculation error is made possible by 1) replacement of sinusoidal input functions with impulse inputs and 2) replacement of steady-state analyses with transient analyses. Recirculation error reduction increases the inert-gas selection to include common gases without unusually high (and difficult to find) tissue-to-blood partition coefficients for maximizing the systemic filtering efficiency. This paper also presents a practical method for determining the recirculation contributions to inert expired profiles in animals and determining their specific contributions to errors in the calculations of CO and from simulations applied to published ventilation-perfusion ratio (V/Q) profiles. Recirculation errors from common gases were found to be reducible to the order of 5% or less for both CO and whereas simulation studies indicate that measurement bias contributions from recirculation, V/Q mismatch, and the V/Q extraction process can be limited to 15% for subjects with severe V/Q mismatch and high inspired oxygen fraction levels. These studies demonstrate a decreasing influence of V/Q mismatch on parameter extraction bias as the number of inert gases are increased. However, the influence of measurement uncertainty on parameter extraction error limits improvement to six gases.

Chronic diffuse interstitial fibrosis of the lung in uranium miners.

Many uranium miners have been disabled by and died of pulmonary fibrosis that was not recognized as an occupational disease. A review of animal studies, complications from whole body irradiation, pulmonary function, and mortality studies of uranium miners led us to suspect radiation-induced chronic diffuse interstitial fibrosis in miners who had inhaled excessive radon progeny. A selected group of uranium miners (22) with severe respiratory disease (but no rounded nodules in chest films) were studied. Lung tissue from five disclosed severe diffuse interstitial fibrosis, with "honeycomb lung" in all. Some also had small anthrasilicotic nodules and birefringent crystals. Although quartz crystals probably contributed, we concluded that the predominant injurious agent in these cases was alpha particles from radon progeny. This disease, after a long latent period, usually results in pulmonary hypertension, shortness of breath, and death by cardiopulmonary failure.

Chronic eosinophilic pneumonia: a report of four cases and a review of the literature.

The clinical and radiological findings of four patients with chronic eosinophilic pneumonia are presented. This brings the total number of cases in the English literature to 27. A comparison of all 27 patients is given. The syndrome can readily be distinguished from other eosinophilic pneumonias. After appropriate evaluation, a therapeutic trial can often be initiated with corticosteroids without the necessity for histologic confirmation of the diagnosis.

Functional and metabolic activity of granulocytes from patients with adult respiratory distress syndrome. Evidence for activated neutrophils in the pulmonary circulation.

Although it has been proposed that the circulating granulocyte (PMN) is an effector cell that causes pulmonary vascular injury in the adult respiratory distress syndrome (ARDS), the functional status of PMNs from patients with this disorder has not been previously defined. In the present study we found that PMNs in samples of pulmonary artery blood from patients with ARDS are in a functionally and metabolically activated state. The mean chemotactic index of PMNs from ARDS patients was 172 +/- 22 SEM compared with a mean chemotactic index of 79 +/- 8 of PMNs from normal subjects (p = 0.0001), a 227 +/- 24% increase over the control value. Respiratory burst activity of PMNs, as assessed by the chemiluminescence response (CL), was 151 +/- 12% of control (mean peak CL of PMNs from patients with ARDS, 166 +/- 31 cpm X 10(3); mean peak CL of normal PMNs, 105 +/- 16 cpm X 10(3); p = 0.04), suggesting that granulocytes from patients with ARDS are likely to generate increased quantities of active oxygen metabolites when stimulated. The chemotactic and chemiluminescence responses of PMNs from patients with ARDS were much greater than those of critically ill patients without ARDS, were enhanced in the absence of concurrent bacterial infection, and did not appear to be blunted by recent administration of glucocorticoids. The PMNs from patients with ARDS had increased ratios of intracellular cyclic GMP to cyclic AMP (165 +/- 5% of control, p = 0.0002), which may be related to the enhanced metabolic activity. Release of superoxide anion, a potential mediator of endothelial injury, was increased over that of control by PMNs from 4 of 8 patients with ARDS (mean, 205 +/- 71% of normal). The results suggest that the circulating PMN is in an activated state in patients with ARDS and may be more likely to release active oxygen species and other inflammatory mediators when perturbed, potentially contributing to pulmonary vascular injury and alveolitis.

Mechanical and gas-distribution behavior of a collateral ventilation model.

We extended the theoretical analysis of Otis et al. (J. Appl. Physiol. 8: 427-443, 1956) to study the effects of collateral ventilation on lung mechanics and gas distribution. Equations were developed to express the effective compliance, the effective resistance, and the distribution of airflow and tidal volume in a two-compartment model incorporating a collateral communication. The analysis of the model showed that, in general, collateral ventilation tends to attenuate the degree of frequency dependence of compliance and resistance, the magnitude of this effect being dependent on the mechanical properties of the model, including collateral resistance. The influence of collateral ventilation is important when the model simulates the mechanical characteristics of the emphysematous lung (marked time-constant inequality with regionally high airway resistance, and relatively low collateral resistance). Under these conditions, a large fraction of the tidal volume of the high airway resistance lung compartment is contributed by the collateral communication. The effects of collateral ventilation on the mechanical behavior of the model are negligible when collateral resistance largely exceeds airway resistance (simulating experimental findings in normal lungs). The present theoretical data suggest that the use of equations based on a model incorporating collateral ventilation is justified, at least in predicting the mechanical and gas-distribution behavior of the lung in emphysema.