Measurements Of Specific Airway Conductance Research Articles

The duration of bronchodilation of salmeterol and salbutamol as measured by specific airway conductance in healthy subjects

According to the duration of bronchodilation, beta-2-agonists are divided into short and long acting bronchodilators. The bronchodilatory effect of available long acting beta-2-agonists (LABAs) beyond 12 h is not sufficiently studied. In order to evaluate the bronchodilatory effects of LABA in subjects without airway obstruction, the measurement of specific airway conductance (sGaw) with whole body plethysmography has been demonstrated to be a sensitive method. We aimed to determine the bronchodilatory effects of single doses of salmeterol 25, 50 and 200 μg and salbutamol 200 μg in healthy subjects ( n = 16) over a 24 h period in a randomized, double-blind, triple-dummy, placebo-controlled cross-over-study. At the 12-h endpoint, all three doses of salmeterol significantly increased sGaw compared with placebo. At the 24-h endpoint, there was a significant increase in sGaw with salmeterol 200 μg, while with 25 and 50 μg salmeterol the sGaw increase failed to reach statistical significance. There was no statistically significant increase in sGaw with salbutamol 200 μg at either the 12-h or 24-h endpoints. For weighted means, all three salmeterol doses showed statistically significant increase in sGaw compared with placebo over 0–12, 12–24 and 0–24 h periods, while for salbutamol 200 μg a significant increase in sGaw was recorded only over 0–12 h period. We conclude that sGaw measurement is a suitable method for recording the bronchodilatory effect of beta-2-agonists in healthy subjects. Using this method we could demonstrate that salmeterol 200 μg provides significant increase in specific airway conductance up to 24 h after a single dose.

Methacholine‐induced lung function changes measured with infant body plethysmography

Several techniques have been applied to measure airway responsiveness (AR) in infants, but there are limited data on lung function changes measured by body plethysmography during induced bronchoconstriction. The aim of this study was to compare changes in maximum forced expiratory flow measured at functional residual capacity (V'(maxFRC)) by rapid thoracoabdominal compression (RTC) technique with plethysmographic measurements of specific airway conductance (sG(aw) ), and to investigate whether changes in functional residual capacity (FRC) occur during methacholine-induced bronchoconstriction in infants. We examined 94 infants with recurrent airway symptoms using methacholine airway challenge test including RTC and plethysmographic measurements. A significant association between changes in V'(maxFRC) and sG(aw) (r = 0.30; P = 0.004) was observed, but after adjustments with baseline variability the changes in V'(maxFRC) were greater and showed a closer association with changes in oxygen saturation. At the point of maximal airway obstruction, there was a poor agreement between V'(maxFRC) and sG(aw) to indicate a significant methacholine-induced bronchoconstriction. Airway challenge was also associated with a significant increase in FRC (P < 0.001), with decreasing V'(maxFRC). We conclude that in infants undergoing airway challenge with methacholine, plethysmographic measurements of sG(aw) correlate with the changes in V(maxFRC), but the agreement is poor and the methods cannot be used interchangeably. V(maxFRC) is also more sensitive to detect airway obstruction than sG(aw). However, methacholine-induced bronchoconstriction was associated with significant increases in FRC, which may affect the validity of V(maxFRC) measurements during the test.

Influence of respiratory frequency in measurement of specific airway conductance during non-panting breathing

In order to investigate the influence of respiratory frequency in the measurement of specific airway conductance (sGaw) during non-panting breathing, we examined specific airway conductance using a body plethysmograph (BX-82, Minato) in 20 stable pulmonary emphysema patients and 19 normal control subjects. Our body plethysmograph device can measure sGaw automatically without panting by making various corrections using a 16-bit microcomputer. We measured sGaw first at a flow of 0.5 L/sec during both inspiratory and expiratory ventilatory phases, then the respiratory frequency was changed from 0.5 to 1.0, 1.5 and 2.0 Hz. In normal control subjects sGaw, tidal volume and mouth flow significantly changed by increasing respiratory frequency, and there was a significant correlation between sGaw and mouth flow. In pulmonary emphysema patients, tidal volume decreased significantly by increasing respiratory frequency, and there was a significant correlation between sGaw and tidal volume, but sGaw and mouth flow did not change significantly by increasing respiratory frequency. These results suggest that specific airway conductance is influenced by respiratory frequency, possibly due to the change in tidal volume and mouth flow. It is necessary to standardize respiratory frequencies and mouth flows in the measurement of specific airway conductance during non-panting breathing.

Airway hyperreactivity test by measurement of specific airway conductance during quiet breathing

In asthmatic patients, the threshold for specific airway conductance during quiet breathing (sGawqt) in the airway hypersensitivity test was determined using our newly developed pressure corrected flow type body plethysmograph and compared with that measured by means of respiratory resistance (Grs) Astograph in relation to the following parameters: 1) Dmin, an index of airway sensitivity (accumulated methacholine concentration at the time of onset of linear decrease in the dose-response curve), 2) SsGawqt and SGrs, indicators of airway sensitivity (slope when the value begins to decrease) and 3) PD35 (accumulated methacholine concentration when the valve has decreased to 35% of the initial value). Although no significantly difference was observed in SsGawqt and SGrs, significantly lower values of Dmin and PD35, indexes of airway sensitivity, were obtained with sGawqt method as compared to Astograph. These findings may indicate that the airway hypersensitivity test using our body plethysmography technique can be performed using a smaller amount of inhaled methacholine with less patient burden as compared to Astograph.

Time course of the protective effect of inhaled heparin on exercise-induced asthma.

We have previously shown that heparin attenuates allergic bronchoconstriction in sheep, inhibits anti-IgE mediated histamine release in isolated mast cells, and prevents the bronchoconstrictor response in subjects with exercise-induced asthma (EIA). The purpose of the present study was to determine the pharmacokinetics of anti-asthmatic activity of inhaled heparin in EIA and compare it with cromolyn sodium, a mast cell stabilizing agent with established efficacy in EIA. Nine subjects with a history of EIA were studied on 10 different experiment days. After obtaining baseline pulmonary functions on day 1, subjects performed a standardized exercise challenge to document the presence of EIA. While monitoring minute ventilation and heart rate, exercise challenge was performed on a treadmill with increasing workload, until 85% of predicted maximum heart rate was achieved. The subjects then continued the exercise at that workload for 10 min. EIA was assessed by measurements of specific airway conductance (SGaw) before and after exercise. On experiment days 2-10, the exercise challenge was performed after the subjects inhaled 4 ml of either heparin (20,000 u/ml), cromolyn (20 mg), or placebo solutions with increasing pretreatment intervals of 15 min, 1 h, 3 h, or 6 h in a single-blind, randomized fashion. Maximum decreases in SGaw (mean +/- SE) at 3 to 5 min after exercise on control (39 +/- 2.1%) and placebo (37 +/- 2.6%) days were reproducible. Heparin and cromolyn had no effect on baseline SGaw but attenuated the EIA in a time-dependent fashion. Heparin inhibited the bronchoconstrictor responses to exercise by 58%, 78%, and 67% (p < 0.05) when nebulized 15 min, 1 h and 3 h, respectively, before exercise; cromolyn attenuated the responses by 37%, 46%, and 41%, respectively, (p < 0.05). Although heparin offered greater protection than cromolyn (at 1 to 3 h), both agents were ineffective when administered 6 h before exercise. These data demonstrate that inhaled heparin prevents EIA for up to 3 h and is more effective than cromolyn.

Effects of nitrous acid exposure on human mucous membranes.

Nitrous acid (HONO) is formed both indirectly from the reaction of nitrogen dioxide (NO2) with water on indoor surfaces, and directly during combustion. This gaseous pollutant may be a previously unrecognized causal factor in assessments of nitrogen oxide exposure effects. The present study is the first attempt to evaluate exposure effects of HONO on the human airways and the mucous membranes of the eyes and nose. Fifteen healthy adult nonsmokers were exposed for 3.5 h in a double-blind, balanced protocol to clean air, 77, and 395 ppb HONO. Each exposure was preceded by a 1-h baseline measurement period, and exposures were separated by 1 wk. There was a 10-min exercise period during exposure. Effects measurements included assessment of bronchial reactivity, measurement of specific airway conductance, spirometry, acoustic rhinometry, nasal lavage, tear-fluid cytology, a CO2 eye-provocation test, evaluation of eye redness, and subjective sensations. Effects of HONO exposure on the eyes were found as exposure-related changes in tear-fluid cytology. In particular, the number of squamous cells increased by 20, 67, and 80% following exposure to clean air, 77, and 395 ppb HONO, respectively (p = 0.004). Possible indications of exposure effects on sensitivity to CO2 eye provocation and on specific airway conductance were also measured. For specific airway conductance there was an approximate 10% decrease in conductance following exercise in association with HONO exposure, compared with a 2% decrease with clean air (p = 0.038).

Effect of an inhaled histamine H3‐receptor agonist on airway responses to sodium metabisulphite in asthma.

Histamine H3-receptor agonists inhibit excitatory neuro-transmission in human and guinea-pig airways. Since neural bronchoconstriction may be important in asthma we have studied the effect of a specific H3-receptor agonist R-alpha-methylhistamine (alpha MeHA) on bronchoconstriction induced by the inhaled irritant sodium metabisulphite (MBS) in six mild asthmatic subjects in a randomised double-blind crossover study. Subjects received either alpha MeHA, 10 mg (as a chloride salt) or matched placebo (P) and were then challenged with doubling concentrations of MBS (0.3-80 mg ml-1) nebulised from a dosimeter at 5 min intervals with measurement of specific airway conductance (sGaw) and FEV1 at 2 and 4 min respectively after each inhalation. There was no effect of alpha MeHA on baseline airway calibre and the log concentrations of MBS required to lower sGaw by 50% (log PC50) and FEV1 by 20% (log PC20) were not significantly different after alpha MeHA when compared with placebo, suggesting that selective stimulation of airway H3-receptors does not inhibit MBS-induced bronchoconstriction.

Measurement of specific airway conductance in guinea pigs: A noninvasive method

A constant volume plethysmographic technique has been developed to measure specific airway conductance (sGaw) in unanesthetized spontaneously breathing guinea pigs. The technique utilizes a specially designed animal restraining device and mask piece. sGaw is measured at end-expiration and does not require knowledge of thoracic gas volume. Control values are within the range reported previously for this species. The method is noninvasive with minimum stress to the animals. Exposure of guinea pigs to an aerosol of cotton dust extract produces similar qualitative changes (a fall) in sGaw to those observed in human volunteers exposed to the same aerosol. The method is proposed as a suitable model for the study of byssinosis (the occupational lung disease associated with chronic exposure to cotton dust). The technique may also be applied to the acute and chronic study of the airway response to other airborne pharmacological and toxicological agents.

An electronic processor for use with a whole body plethysmograph to determine specific airways conductance

The panting manoeuvre traces produced by a whole body plethysmograph during the measurement of specific airways conductance (sGaw) are traditionally analysed by hand. Since this technique is tedious and time consuming it is prone to error, as well as suffering from considerable inter-observer variability. We describe a new inexpensive analogue electronic processor which rapidly produces readouts of sGaw and overcomes many of the problems associated with hand analysis. The system takes as its inputs the mouth flow and plethysmograph volume outputs from a pressure-corrected flow-displacement whole body plethysmograph, but it could be adapted for use with other types of plethysmograph. Since the processor is intended mainly for use during serial measurements of sGaw it does not carry out an unnecessary correction for flowmeter resistance. Using an electronic simulator of sGaw signals the output of the processor was found to be linear to better than 2% of full scale and to be insensitive to drift on the volume signal. The system has been comprehensively evaluated using signals from both normal subjects and patients. The processor output was found to agree well with the results of hand analysis, an agreement which was comparable with that obtained from computer based systems. For the normal subjects the equal value line adequately described the relationship between the processor and hand estimates of sGaw. However, for patients the slope of the best fit line was 18% less than unity but the correlation coefficient was high: 0.95. Reproducibility was found to be better than 3%. The coefficient of variation of sGaw determinations was less using the processor than using hand analysis, with the respective mean values for normals being 10.2% and 12.9% and for patients 8.8% and 13.2%. This processor is easy to use and gives reliable and repeatable results, which are available immediately after the end of a panting manoeuvre.

A new adaptable computerized system for the measurement of specific airways conductance

We have developed an automated system for the measurement of specific airways conductance ( SG aw) which differs in several aspects from other reported automated systems. In seven subjects this system was used to measure baseline SG aw and the provocation concentration (PC) of histamine producing a 35% fall in SG aw. The results produced were compared with those obtained by manual analysis using both one limb and two limbs of the inspiratory part of the flow/box pressure curve. Using the automated system, baseline SG aw and PC 35 SG aw results were similar to those obtained by the two limbs method of manual analysis, but the analysis time was considerably reduced. A single measurement of SG aw was obtained within 2–3 seconds. Both the automated and two limbs manual methods of analysis were more reproducible than the one limb method of manual analysis.

Effect of prior bronchoconstriction on the airway response to histamine in normal subjects.

We have examined the effect of prior bronchoconstriction on the bronchial responsiveness to inhaled histamine in nine normal subjects. The airway response to increasing concentrations of histamine aerosol was assessed by measurement of specific airways conductance (sGaw) in a body plethysmograph. The threshold provocative dose of histamine needed to cause a 35% fall in starting sGaw (PD35) and the steepest slope of the response were measured from cumulative log dose response curves. Histamine challenges were performed in duplicate after premedication with 0.9% sodium chloride (control) or methacholine aerosol on separate days. The mean starting sGaw did not change significantly after inhalation of 0.9% sodium chloride but methacholine caused a mean reduction in sGaw of 42%. Mean control PD35 values did not differ significantly from mean PD35 values after methacholine. The mean steepest slope of the response after methacoline was 47% lower than the mean control value. There was a significant linear relationship between starting sGaw and the steepest slope for the control and for the methacholine premedicated challenges. The reduction in slope after methacholine was accounted for by the fall in starting sGaw. Because histamine PD35 was not altered by prior bronchoconstriction, it is concluded that the bronchial hyperresponsiveness of asthmatic subjects to non-specific bronchoconstrictor stimuli is unlikely to be a direct consequence of their low starting airway calibre.

Effects of ascorbic acid and indomethacin on the airways of healthy male subjects with and without induced bronchoconstriction

We have investigated the effects of ascorbic acid (1.0 gm orally) and indomethacin (50 mg orally) on airway tone in the basal state in six healthy nonsmoking male adults. Airway tone was assessed from measurements of specific airway conductance and flow rates interpolated from partial expiratory flow-volume curves by means of whole-body plethysmography and spirometry, respectively. Neither ascorbic acid nor indomethacin alone produced a significant change in basal tone. However, both the duration and intensity of the bronchoconstriction induced by methacholine aerosol (10 mg/ml for 30 sec) were significantly reduced by prior administration of ascorbic acid. This ameliorating action of ascorbic acid was blocked by ingestion of indomethacin. The results suggest that ascorbic acid exerts its effects by altering the production of a bronchodilator prostaglandin.

Inhalation of terbutaline spray through an extended mouthpiece: effect on central and peripheral airways.

In a cross-over experiment, 16 adult asthmatics slowly inhaled, at functional residual capacity, cumulative doses of terbutaline spray with and without extension of the mouthpiece of the aerosol canister by a cylindrical tube (length 10.0 cm, diameter 3.2 cm). No difference was found between the two modes of treatment with regard to the bronchodilator response assessed by measurement of specific airway conductance, registration of expiratory flow-volume curves and determination of helium response. The results suggest that the use of an extension tube may not promote a more extensive nor a more peripheral deposition in the bronchial tree of a properly inhaled pressurized aerosol drug.

Alpha1 Antitrypsin Levels in Sarcoidosis: Relationship to Disease Activity

Alpha1 antitrypsin levels measured by the trypsin inhibitory capacity method were increased in a group of 23 patients with active sarcoidosis not under treatment when compared with a group of 17 patients, with inactive sarcoidosis, or age and sex matched healthy controls. Twelve of these patients and two of the control subjects were also studied by the radial immunodiffusion method and cellulose acetate serum electrophoresis methods for measuring a1 antitrypsin. Obstruction of larger airways was present in 10 of 40 sarcoidosis patients, while the remainder had either a restrictive or normal pattern. In eight patients, measurement of diffusing capacity and a closer assessment for airways obstruction was obtained with measurements of specific airway conductance, thoracic gas volumes, and static and dynamic lung compliance at several respiratory frequencies. Disease of smaller airways was present in six patients as determined by frequency dependence of their dynamic lung compliance. Since three were nonsmokers, airways obstruction was thought to be due to mechanical effects of granulomas. a1 antitrypsin levels may be another useful determinant of disease activity and may be used to supplement other clinical and laboratory indices of activity. Alpha1 antitrypsin levels measured by the trypsin inhibitory capacity method were increased in a group of 23 patients with active sarcoidosis not under treatment when compared with a group of 17 patients, with inactive sarcoidosis, or age and sex matched healthy controls. Twelve of these patients and two of the control subjects were also studied by the radial immunodiffusion method and cellulose acetate serum electrophoresis methods for measuring a1 antitrypsin. Obstruction of larger airways was present in 10 of 40 sarcoidosis patients, while the remainder had either a restrictive or normal pattern. In eight patients, measurement of diffusing capacity and a closer assessment for airways obstruction was obtained with measurements of specific airway conductance, thoracic gas volumes, and static and dynamic lung compliance at several respiratory frequencies. Disease of smaller airways was present in six patients as determined by frequency dependence of their dynamic lung compliance. Since three were nonsmokers, airways obstruction was thought to be due to mechanical effects of granulomas. a1 antitrypsin levels may be another useful determinant of disease activity and may be used to supplement other clinical and laboratory indices of activity.

Comparison of Cardiorespiratory Effects of Isoprenaline and Salbutamol in Patients with Bronchial Asthma

The effects of isoprenaline and salbutamol administered orally, by inhalation, or by intravenous infusion were compared in 13 asthmatic patients. Bronchodilator activity was assessed by serial measurement of specific airways conductance (SGaw). Log-dose response curves were obtained for both drugs and showed them to be equipotent as bronchodilators. Cardiovascular effects were variable, but in general, isopenaline caused greater rise in pulse rate and a greater change in blood pressure than the same dose of salbutamol.Cardiorespiratory measurements during continuous intravenous infusion of increasing doses of both drugs suggested a greater effect of isoprenaline than the same dose of salbutamol on metabolic rate, pulmonary ventilation, pulmonary gas exchange, cardiac output, and heart rate. The effect of salbutamol on the heart rate was about 10 times less than that of isoprenaline but lasted longer.