Edward H. Chester

Bronchospastic responses to aerosolized metabisulfite in asthmatic subjects: Potential mechanisms and clinical implications

Eight asthmatic patients with a history suggestive of sulfite sensitivity were studied, six of whom had a positive oral challenge to doses from 10 mg to 50 mg. All eight patients had aerosol metabisulfite challenge; six positive tests were observed at doses of 0.5 mg/ml and 5.0 mg/ml. Aerosolizing solutions of metabisulfite at 5.0 mg/ml generated significant amounts of free sulfur dioxide. Implications of these findings are discussed.

Phthalic anhydride asthma.

A patient with occupational asthma caused by phthalic anhydride is described. Inhalation challenges under laboratory control produced immediate and delayed asthmatic responses. Repeat exposure to phthalic anhydride after treatment with cromolyn sodium showed inhibition of the late but not the early bronchoconstrictive, asthmatic response.

Pulmonary gas transport characterization by a dynamic model

Abstract A mathematical model is developed which describes and predicts pulmonary transport of N2 and CO. The model is structured as a system of five well-mixed compartments, four of which have variable volumes, arranged in parallel and series. For this structure, the unsteady, mass-balance equations are derived and the effect of parameters investigated. The model may be used to simulate experiments of nitrogen washout and carbon monoxide uptake with normal subjects and those with chronic obstructive lung disease (COLD). With each subject, these experiments are conducted at several levels of tidal volume and frequency under controlled conditions. When all experiments of a subject are simulated, a set of parameter values is obtained that characterizes the volume and distensibility distributions in airways and alveoli and the CO mass transport across the pulmonary membrane. The model has been applied to analyze the differences between normal subjects and those with COLD. The parameters yield quantitative information about abnormal transport which is caused by greater volume inhomogeneities, more distensible airways, and apparently less effective surface area of the membrane. Finally, model and experimental studies show how the effective ventilation of a subject with COLD having a large FRC is improved by increasing Vt/Frc.

A proposed standardized method for bronchoprovocation tests in toluene diisocyanate-induced asthma

Exposure to vapors of toluene diisocyanate (TDI), a chemical widely used in the plastics and rubber industry, can cause respiratory disease at low concentrations and can be a nonspecific respiratory irritant at high concentrations.‘. 2 While these clinical patterns have been known for some time, laboratory diagnosis has been a challenge because of several problems, including lack of methods for performing quantitative studies of the effect of inhaling precise TDI concentrations. For this to be possible, a delivery system must produce adjustable, stable concentrations of TDI that can be monitored accurately throughout the time of exposure to TDI fumes. Three major problems are encountered in the implementation of a suitable delivery system. First, TDI is an extremely volatile liquid at room temperature which readily produces a dense vapor (vapor density = 6.0; air = 1). Thus, exposed TDI liquid can create vapors of high concentration which vary with location, room size, and room ventilation characteristics. Second, TDI vapor readily adsorbs onto the surface of most materials, except glass and Teflon,” so that efficient transport of TDI test gases is difficult. Third, the present commercially available instruments for the continuous measurement of TDI concentration have an overall response time of 18 min. Therefore, unless the delivery system is stable throughout test procedures, it is impossible to determine the actual concentration of TDI the subject is inhaling because one is always measuring 18 min behind the event. Previous methods of controlling inhaled dosages of TDI for challenge-response studies have been based on reproducing a given environmental situation. Pepys et al.” had their subjects tested in a closed room, in which a polyurethane varnish containing

Influence of breathing rate on airway resistance and compliance measurements.

Abstract Airway resistance is commonly measured in a total body plethysmograph. However, measurements during naturally assumed breathing at frequencies below 2 breaths/sec are known to be a problem due to the presence of plethysmograph artefact. Specifically, breathing by the subject within the closed plethysmograph chamber produces undesired warming and wetting of chamber air and this in turn increases chamber pressure. In the present paper, a fundamental frequency method of analysis is used over a range of frequencies above and below 2 breaths/sec to extract values of airway resistance from data corrupted by artefact. Resistance values by this method were examined in seven normals and 17 subjects with obstructive lung disease. Within the limits of measurement accuracy, groups of normals and abnormais showed constant mean values of effective airway resistance over a range from 0.15 to 3.2 breaths/sec. A plethysmograph artefact occurred in response to changes in lung volume and appeared as a compliance-like effect on plethysmograph pressure. Compliance parameters, associated with the artefact, were nearly constant below 1.2 breaths/sec, and the means were the same for normals and abnormais. Above 1.2 breaths/sec the compliance parameter for normals tended to increase while that for abnormais decreased. These results suggest that if compliance measurements are derived from plethysmograph data both lung mechanical parameters and artefacts will contribute to computed values.

Bronchodilating effect of terbutaline aerosol

We compared the efficacy of terbutaline with that of metaproterenol, isoproterenol, and placebo aerosols in 16 asthmatic patients. Terbutaline, metaproterenol, and isoproterenol produced equivalent improvements in flow rates. At 5 hr, the effect of terbutaline on tests of small airways, FEF25%–75% and FEF50%, was greater (p < 0.05) than that of metaproterenol and isoproterenol. Terbutaline produced no significant change of heart rate or blood pressure.

Mass-Balance Model of Pulmonary Oxygen Transport

A dynamic lumped-parameter model for pulmonary gas transport has been developed to characterize the lung and predict the effect of various parameter changes. The gas side of the lung is modeled as a series and parallel arrangement of five perfectly mixed, variable-volume compartments that correspond roughly to airway and alveolar regions. The blood side of the lung is modeled as a series of perfectly mixed, constant-volume compartments that represent the pulmonary capillary bed. From nonsteady mass balances, equations are derived which yield the time course of concentration for each compartment. Model simulations indicate that the oxygen-hemoglobin reaction does not reach equilibrium in the pulmonary capillaries, an assumption commonly made in analyses of pulmonary oxygen transport. Simulations also show the extent to which breathing amplitude and rate can affect the oxygen level in the blood leaving the lung. A comparison of simulations for a normal state and chronic obstructive lung disease (COLD) with identical input conditions demonstrates that the oxygen level in the blood leaving the lung is much lower in COLD. Also, the simulations are compared with experimental findings.

Ventilation inhomogeneity: Alveolar mechanics and gas distribution

The effects of regional lung differences in alveolar mechanics on the transpulmonary pressure-volume (Ptp-V) relationship and the single-breath washout (SBW) of nitrogen were investigated by mathematical modeling and postmorten human lung experiments. Regional nonuniformity in alveolar collapse and re-opening were associated with differences in gravitational stress or elasticity. Model simulations predict that neither type of regional nonuniformity qualitatively affects the shape of the Ptp-V curve, but does affect the terminal (or small-volume) portion of the SBW. Comparisons of characteristics of the Ptp-V and SBW curves indicate that regional nonuniformity in alveolar collapse is an important mechanism associated with ventilation inhomogeneity.