Seasonal variation of airway function in allergic rhinitis.

We set out to examine seasonal variation in airway bronchoconstriction in patients with seasonal allergic rhinitis. Airway conductance and response to methacholine challenge were measured during pollen season, as well as in winter when pollen exposure was not present. Airway conductance and spirometry were performed on 17 subjects during allergy season and in winter. In eight of these subjects the measurements were repeated in the successive allergy season. Methacholine bronchoprovocation was performed on 17 of the subjects in winter and in eight subjects in allergy season. We found airway constriction in both allergy seasons as evidenced by specific airway conductance (SGaw) of 0.188 +/- 0.06 and 0.203 +/- 0.03. In contrast, SGaw during winter was 0.27 +/- 0.11. When winter and summer seasons were compared, both summer SGaw values were significantly lower than winter SGaw, p less than 0.01 and p less than 0.05, respectively. Mean airway sensitivity to methacholine during allergy season was 16.1 breath units and not different than out of season 11.7 breath units; p = NS. The reactivity to methacholine (slope of the dose-response curve) and spirometry (FVC, FEV1, FEV1/FVC) in and out of allergy season were likewise not different. The data indicate that patients with allergic rhinitis have unique physiologic behavior separating them from patients with asthma or normal subjects. They develop seasonal bronchoconstriction unassociated with clinical bronchospasm, but this seasonal bronchoconstriction does not potentiate their sensitivity to methacholine. However, they have increased airway sensitivity to methacholine, and this feature distinguishes them from normal subjects.

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.

Computation of respiratory impedance from forced sinusoidal oscillations during breathing.

Computation of impedances from forced oscillation data during breathing can yield results which reflect not only changes in respiratory mechanics, but artifacts related to the signal analysis. A method has been developed, employing sinusoidal forcing, to determine intra-breath variations of respiratory impedance. The measured pressure and flow waveforms are each the sum of a slowly varying constituent associated with breathing, and a high-frequency oscillatory constituent, whose amplitude and phase vary with time. The signal constituents were separated with a moving-average filter. Characteristic amplitudes and phases of the oscillatory constituents over a short time interval (window) were determined by correlating the constituents with sine waves of the same frequency. Continuous estimates of the time-varying impedance were obtained by moving the window over the data. Two procedures were developed to examine the accuracy of impedances computed with this technique: (1) the analysis of fixed-amplitude sinusoids superimposed on a breathing pattern; and (2) the analysis of a known, time-varying impedance. The effects of forcing frequency, window size, breathing frequency, and the position within the respiratory cycle on the computed impedances were examined. For quiet breathing, the technique can yield impedances which are accurate to within 5% in magnitude, and 5 degrees in phase angle at all instants within the breath. An efficient algorithm was developed for implementing the technique on a computer.

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.

Comparison of the respiratory responses to external resistive loading and bronchoconstriction.

The effects of resistive loads applied at the mouth were compared to the effects of bronchospasm on ventilation, respiratory muscle force (occlusion pressure), and respiratory sensations in 6 normal and 11 asthmatic subjects breathing 100% O2. External resistive loads ranging from 0.65 to 13.33 cm H2O/liter per s were applied during both inspiration and expiration. Bronchospasm was induced by inhalation of aerosolized methacholine. Bronchospasm increased ventilation, inspiratory airflow, respiratory rate, and lowered PACO2. External resistive loading, on the other hand, reduced respiratory rate and inspiratory flow, but left ventilation and PACO2 unaltered. FRC increased to a greater extent with bronchospasm than external flow resistive loads. With both bronchospasm and external loading, occlusion pressure increased in proportion to the rise in resistance to airflow. However, the change in occlusion pressure produced by a given change in resistance and the absolute level of occlusion pressure at comparable levels of airway resistance were greater during bronchospasm than during external loading. These differences in occlusion pressure responses to the two forms of obstruction were not explained by differences in chemical drive or respiratory muscle mechanical advantage. Although the subjects' perception of the effort involved in breathing was heightened during both forms of obstruction to airflow, at any given level of resistance the sense of effort was greater with bronchospasm than external loading. Inputs from mechanoreceptors in the lungs (e.g., irritant receptors) and/or greater stimulation of chest wall mechanoreceptors as a result of increases in lung elastance may explain the differing responses elicited by the two forms of resistive loading.

Adverse effect of propranolol on airway function in nonasthmatic chronic obstructive lung disease.

Bronchomotor tone is, in part, under beta-adrenergic control, and beta-adrenergic agonists are commonly used in the therapy for chronic obstructive pulmonary disease (COPD). Beta-adrenergic blockade with propranolol is contraindicated in asthmatic patients, yet little is known of its effect in patients with COPD. We studied 13 patients with COPD in a random-entry, double-blind crossover comparison of oral propranolol, 40 mg, and oral placebo on separate day. Pulmonary function worsened after administration of propranolol. Significant differences were present between the drugs' effect on heart rate, airway resistance, specific resistance, and flow rates at one hour, and persisting through four hours (p less than 0.01). Propranolol may have a deleterious effect on pulmonary function in nonasthmatic COPD. We conclude that when propranolol is to be used in patients with COPD, the short- and long-term effects on airway should be measured sequentially.

Ventilation inhomogeneity using multibreath nitrogen washout: comparison of moment ratios and other indexes.

In this study we compared a variety of indexes of ventilation inhomogeneity based on multibreath nitrogen washout of the lungs. We studied 40 subjects in 5 clinical groups: 6 normal subjects, 5 "normal" smokers, 6 subjects with asthma, 13 with diffuse interstitial lung disease (DILD), and 10 with chronic obstructive pulmonary disease (COPD). We found that a moment ratio (micron 1/micron 0), which is a mean dilution number (or number of volume turnovers), is superior to other indexes studied with respect to minimal intrasubject variability and maximal diagnostic sensitivity. Even minimal ventilation inhomogeneity could be detected in "normal" smokers, as evidenced by the difference in micron 1/micron 0 values from those found in normal nonsmokers. As a group, asthmatics showed mild ventilation inhomogeneity, with greater variation depending on their functional status at the time of testing. Subjects with DILD tended to have moderate ventilation inhomogeneity, which appeared to increase with age. As expected, the greatest ventilation inhomogeneity occurred in COPD.

Aerosol bronchodilator therapy: a comparison of the effects of bronkometer with isoetharine, isoproterenol and phenylephrine.

The bronchodilator action and cardiovascular toxicity of aerosols of (1) isoetharine, (2) isoetharine in combination with phenylephrine, (3) isoproterenol, and (4) phenylephrine were compared in a group of severe stable ambulatory asthmatics. All preparations except phenylephrine produced reduction in specific airway resistance and increased flow rates which peaked at 15 minutes. The action of isoproterenol and the two isoetharine preparations peaked at 15 minutes while the peak effect of isoetharine and isoetharine in combination with phenylephrine continued for 60 minutes. The difference between isoproterenol and isoetharine alone or in combination with phenylephrine was not statistically significant. None of the drugs produced any cardiovascular side effects. The authors conclude that isoetharine, though less potent than isoproterenol on a weight-for-weight basis, is an effective and safe bronchodilator. Addition of phenylephrine to isoetharine does not potentiate or prolong the action of the latter.

Vectorcardiographic detection of early hemodynamic abnormalities in chronic obstructive pulmonary disease.

The ability of the vectorcardiogram to detect mild circulatory abnormalities in patients with chronic obstructive pulmonary disease (COPD) is unclear. Therefore, vectorcardiographic changes were correlated with hemodynamic measurements made at rest and during supine exercise in 32 patients with COPD and no clinical or electrocardiographic evidence of right ventricular hypertrophy. Twelve patients had normal hemodynamic data (group 1), nine had abnormal hemodynamic data only during exercise (group 2), and 11 had abnormal hemodynamic data at rest and during exercise (group 3). The extent of rightward terminal QRS forces noted on the vectorcardiogram was significantly less in group 1 (5.5 +/- 8.7 percent) than in either group 2 (19.0 +/- 10.7 percent) or group 3 (17.8 +/- 14.8 percent). Sixty-five percent (13) of the 20 patients with hemodynamic abnormalities had rightward terminal QRS forces of 15 percent or more, whereas only 8 percent (one) of the 12 patients with normal hemodynamic data had such forces of 15 percent or more. The mean of the rightward terminal QRS forces in 27 age-matched normal subjects was 5.0 +/- 5.4 percent, and only one subject had forces of 15 percent or more. We conclude that hemodynamic abnormalities are frequent in patients with COPD and no clinical evidence of right ventricular hypertrophy and that the vectorcardiogram provides an indirect method of detecting these abnormalities.

Real-time moment analysis of pulmonary nitrogen washout.

A real-time moment analysis was applied to multibreath nitrogen-washout dynamics of the lung. Because the analysis accounts for breathing pattern variations, subjects could perform the washout with spontaneous breathing. The real-time digital processing of the nitrogen and flow signals incorporates filtering, delay compensation, and corrections for the effects of gas composition and temperature changes. In our study, moment analysis of the multibreath washout was evaluated for 37 subjects: 6 normal nonsmokers, 4 "normal" smokers, 6 asthmatics, 12 with diffuse interstitial disease, and 9 with chronic obstructive pulmonary disease. Moments were computed from end-tidal and breath-averaged nitrogen fractions. The ratio of 1st-to-0th moments was found to yield distinctions among subjects with different degrees of ventilation inhomogeneity, even between normal nonsmokers and "normal" smokers. With minimal computational facilities, this moment analysis not only provides a sensitive index of ventilatory dysfunction, but also a cost-effective tool.

Dysfunction of small airways following pulmonary injury due to nitrogen dioxide.

Serial physiologic studies were performed to characterize both the immediate and delayed effects of a single occupational exposure to nitrogen dioxide in a nonsmoker. During the initial acute stage of pulmonary edema, the abnormal static pressure-volume curve and decreased static compliance corresponded to a reduction in pulmonary volume. During the delayed acute stage, elastic recoil and properties of resistance to flow were normal, but dynamic compliance was reduced and dependent on respiratory frequency, and oxygen transport was abnormal during exercise, which is consistent with dysfunction of the small airways.

A calibrated delivery system for inhalation challenge of toluene di-isocyanate vapor.

The vapor of TDI, a chemical commonly used in the plastics industry, may be associated with pulmonary symptoms at various concentrations. Because of the high volatility and adsorptivity of TDI, it has been difficult to deliver known, dilute concentrations of TDI to test subjects in inhalation challenge studies. A delivery system has been developed which can be calibrated to deliver an air-TDI mixture having a given flow rate and TDI concentration. The delivered gas stream is produced by diluting a gas stream having a low flow rate and a fixed concentration of TDI with a high-flow-rate stream of TDI-free air. A TDI detector continuously monitors the concentration of the resultant mixture, which is delivered to the subject by means of a face mask. For dilute mixtures, the output concentration is proportional to the ratio of the input flow rates; the proportionality factor depends on temperature and the geometry of the system. The flows for the described system could be regulated to produce concentrations in the range 0.0 to 0.08 ppm which remain stable to within +/- 10%.

A comparison of the prevalence of sensitization to Aspergillus antigens among asthmatics in Cleveland and London.

A survey of the frequency of sensitization to Aspergillus antigens was conducted in a group of asthmatics in Cleveland and compared with a group of asthmatics in London, using common antigens for testing purposes. The two groups were comparable except for earlier onset, longer duration of asthma, and a larger number of males in the London group. Twenty-eight per cent of the asthmatics from Cleveland and 23% from London had immediate skin reactivity to Aspergillus. Seven and one-half percent from the Cleveland group and 10.5% of the London group had Aspergillus precipitins in the serum. Aspergillus skin test reactivity was related to the severity of airways obstruction (p less than 0.01) but was not influenced by other factors. We conclude that sensitization to Aspergillus antigens occur with equal frequency in both the United States and the United Kingdom.

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 less than 0.05) than that of metaproterenol and isoproterenol. Terbutaline produced no significant change of heart rate or blood pressure.

On respirable organic antigens, mattresses and some idiopathic lung diseases.

In surveying the environment of workers in a mattress factory thermophilic actinomycetes as well as phycomycetes and aspergillus species were isolated readily from work room dust, finished bat, sissal and the interior of baled linters. Those persons working with cotton products were shown to have a heavy, daily exposure to organisms known to be implicated in the pathogenesis of hypersensitivity pneumonitis. The authors suggest that further study of the inhaled antigens to which cotton workers are exposed is indicated before discarding immunologic mechanisms to explain the development of byssinosis and other pulmonary disorders to which such workers are subject.