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Biomedical subjects

I Danta

Publications and source records attributed to I Danta.

18 recordsLinked to original sources
PubMed2003

Comparative bronchial vasoconstrictive efficacy of inhaled glucocorticosteroids.

The vasoconstrictive efficacies of glucocorticosteroids (GS) are usually compared by the McKenzie skin-blanching test and taken as an index of relative potency. The rationale for the present study was to transpose the McKenzie test to the airway and to compare the airway vascular effects of three inhaled GS: beclomethasone dipropionate (BDP), fluticasone propionate (FP) and budesonide (BUD), in healthy subjects and patients with mild stable asthma. A soluble, inert gas-uptake method was used to measure airway blood flow (Qaw). Baseline mean+/-SD Qaw normalised for anatomical dead space was 53.1+/-1.4 microL x min(-1) x mL(-1) in healthy subjects (n=10) and 67.8+/-3 microL x min(-1) x mL(-1) in asthmatics (n=10). All GS caused a transient decrease in Qaw. The magnitude of the vasoconstriction was greater in asthmatics. The relative vasoconstrictive effect of BDP, FP and BUD was 1, 1.9, and 2.7, respectively, in asthmatics and 1, 3.3 and 3.0, respectively, in healthy subjects, as assessed by the dose required to decrease Qaw by 20%, from the baseline, 30-min postdrug inhalation. Therefore, measuring airway blood flow may be a useful, site-specific parameter to assess the tissue bioavailability and vasoconstrictive efficacy of inhaled glucocorticosteroids.

Administration, Inhalation↗
PubMed2000

Effect of an inhaled glucocorticosteroid on airway mucosal blood flow in mild asthma.

We determined airway mucosal blood flow (Qaw) and FEV (1) before and after inhaled albuterol in 19 glucocorticosteroid (GS)-naive patients with mild intermittent asthma, and assessed the effects of a 2-wk course of fluticasone propionate (FP; 440 microg daily) on these parameters. Twelve healthy nonsmokers served as controls. Baseline Qaw was 55.5 +/- 0.7 microl/min/ml (mean +/- SE) in the asthmatic subjects and 44.2 +/- 0.7 microl/min/ml in the controls; the respective FEV(1) values were 2.8 +/- 0.2 L and 3.4 +/- 0.2 L (p < 0.01 for both parameters). Albuterol increased Qaw by 27 +/- 3% in the control subjects (p < 0.01) but had no effect on Qaw in the asthmatic subjects; it increased FEV (1) by 7 +/- 1% and 6 +/- 1% in the two groups, respectively. Qaw decreased to 49.2 +/- 0.8 microl/min/ml (p < 0.05 versus baseline), and the Qaw responsiveness to albuterol was restored ( +21 +/- 2%; p < 0.05) in the asthmatic subjects after FP. Eleven asthmatic subjects stopped using FP at this time; 2 wk later, their Qaw returned to baseline (55.2 +/- 0.9 microl/min/ml) and they lost the Qaw responsiveness to albuterol. Mean ( +/- SE) FEV(1) and FEV(1) responsiveness to albuterol were not affected by FP. The GS-sensitive increase in Qaw and its hyporesponsiveness to albuterol in asthmatic subjects may be consequences of airway inflammation.

Administration, Inhalation↗
PubMed2000

Transient effect of inhaled fluticasone on airway mucosal blood flow in subjects with and without asthma.

Topically applied glucocorticosteroids (GS) have been shown to cause local vasoconstriction in normal skin and this phenomenon is commonly used to assess the potency of topical GS (McKenzie skin blanching test). The purpose of the present study was to determine if an inhaled GS, fluticasone propionate (FP), similarly leads to vasoconstriction in the airway mucosa and if subjects with and without asthma have differential vascular responsiveness to GS. In 10 nonsmokers with stable asthma and 10 nonasthmatic nonsmokers, airway mucosal blood flow (Qaw) expressed per milliliter of anatomical dead space and the forced expiratory volume in 1 s (FEV (1)) were determined before and serially after inhalation of FP (88 to 1,760 microg) or placebo. Baseline mean (+/- SE) Qaw was 55.1 +/- 1.0 and 44.2 +/- 1.1 microl x min(-1) x ml(-1) in subjects with and without asthma, respectively (p < 0.001). The corresponding mean FEV(1) values were 2.34 +/- 0.13 and 3.22 +/- 0.12 L (p < 0.001). FP at 880 microg but not placebo produced a transient decrease in mean Qaw with a nadir at 30 min and return toward baseline at 90 min post-inhalation; the maximum mean decrease was 37% in subjects with asthma and 21% in unaffected subjects (p < 0.01); 880 microg of FP was the lowest effective dose. FEV(1) did not change after FP administration in either group. These results demonstrate a transient vasoconstrictive action of inhaled FP in the airway mucosa, with a greater vascular responsiveness in subjects with asthma than in unaffected subjects. The measurement of Qaw may provide a more relevant means of assessing the potency of inhaled GS than the McKenzie skin blanching test. In addition, our observation suggests that inhaled GS have potentially beneficial effects in asthma that is not related to their antiinflammatory action.

Administration, Inhalation↗
PubMed1999

Prevention of exercise-induced bronchoconstriction by inhaled low-molecular-weight heparin.

Because many biological actions of heparin including the antiallergic activity are molecular weight dependent, we hypothesized that low-molecular-weight heparin (LMWH) may have greater potency in attenuating exercise-induced bronchoconstriction (EIB). Therefore, in the present investigation we studied the effects of inhaled LMWH, enoxaparin, and unfractionated heparin on EIB in subjects with asthma. Thirteen asthmatic subjects performed a standardized exercise challenge on a treadmill to document the presence of EIB. The workload was increased until 85% of predicted maximal heart rate was achieved, and the exercise was sustained at that workload for 10 min. EIB was assessed by measuring FEV(1) before and immediately after the exercise. On five different experiment days the subjects were pretreated with 4 ml of aerosolized heparin (80,000 units = 7.5 mg/kg), placebo, or 3 different doses of enoxaparin (0.5 mg/kg, 1 mg/kg, 2 mg/kg) in a double-blind, randomized, crossover design, and exercise challenge was performed 45 min later. Bronchial provocation with methacholine was also performed in five subjects on two additional days after pretreatment with either placebo or inhaled enoxaparin (2 mg/kg), and venous blood was obtained for analysis of plasma antifactor Xa. Postexercise, the maximal decreases in FEV(1) (mean +/- SE) were 30 +/- 4% and 29 +/- 5% on control and placebo days. The exercise-induced decreases in FEV(1) were inhibited by 31% with heparin (DeltaFEV(1) = 20 +/- 4%); and by 28%, 38%, and 48% by enoxaparin at doses of 0.5 mg/kg (DeltaFEV(1) = 21 +/- 5%), 1 mg/kg (DeltaFEV(1) = 18 +/- 5%), and 2 mg/kg (DeltaFEV(1) = 15 +/- 3%), respectively (p < 0.05). The inhibitory effect of 0.5 mg/kg dose of enoxaparin was comparable to heparin (7.5 mg/kg), whereas 2 mg/ kg dose of enoxaparin was the most potent. Inhaled enoxaparin failed to modify the bronchoconstrictor response to methacholine, and did not change the plasma antifactor Xa activity. These data demonstrate that inhaled enoxaparin prevents EIB in a dose-dependent manner; and its antiasthmatic activity is independent of its effect on plasma antifactor Xa activity.

Administration, Inhalation↗
PubMed1998

Airway mucosal blood flow in bronchial asthma.

As an inflammatory airway disease, asthma is expected to be associated with an increase in airway blood flow. We therefore compared airway mucosal blood flow (Qaw) among normal subjects (n = 11) and patients with stable asthma receiving (n = 13) or not receiving (n = 10) long-term inhaled glucocorticosteroid (GS) therapy. Qaw was calculated from the uptake of dimethyl ether in the anatomic dead space minus the most proximal 50 ml (DS), and expressed as blood flow per ml DS. Mean (+/- SE) Qaw was 38.5 +/- 5. 3 microl . min-1 . ml-1 in normals, 68.2 +/- 7.9 microl . min-1 . ml-1 in GS-naive asthmatics (p < 0.01), and 55.4 +/- 5.3 microl . min-1 . ml-1 in GS-treated asthmatics (p < 0.05). Ten minutes after administration of 180 microg albuterol by metered dose inhaler, mean Qaw increased by 83 +/- 26% in normal subjects (p < 0.01), but did not change significantly in GS-naive (+5 +/- 8%) or GS-treated (+32 +/- 15%) asthmatics. These results demonstrate that Qaw is increased in stable asthmatics and resistant to further increase by a standard inhaled dose of a beta-adrenergic agonist.

Adolescent↗
PubMed1996

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.

Administration, Inhalation↗
PubMed1996

Metaproterenol responsiveness after methacholine- and histamine-induced bronchoconstriction.

We investigated whether the bronchodilator response to a beta-adrenergic agonist is influenced by the mechanism of induced bronchoconstriction. Normal subjects and asymptomatic asthmatics inhaled a dry aerosol (mass median aerodynamic diameter, 1.5 microns) with increasing concentrations of methacholine or histamine to produce a 35% decrease in specific airway conductance (SGaw), followed by a single inhalation of a metaproterenol aerosol. By studying normal subjects and asthmatics, we were able to compare metaproterenol responsiveness after widely divergent doses of the bronchoprovocative agents but the same degree of bronchoconstriction. Airway deposition of methacholine, histamine, and metaproterenol was measured using a quinine fluorescence technique. Mean baseline SGaw, metaproterenol responsiveness, and metaproterenol mass deposited were similar in normal subjects and asthmatics. Likewise, mean SGaw after completion of methacholine and histamine challenge, and the subsequently deposited metaproterenol mass were similar in the two groups. After methacholine challenge (mean +/- SD provocative drug mass causing a 35% decrease in SGaw, PM35: 8.94 +/- 5.96 mumol in normal subject and 0.30 +/- 0.29 mumol in asthmatics), metaproterenol increased mean SGaw by 89 +/- 33% in normal subjects and by 190 +/- 55% in asthmatics (p < 0.05, two-way analysis of variance). After histamine challenge (PM35, 2.92 +/- 2.49 mumol in normal subjects and 0.17 +/- 0.29 mumol in asthmatics), metaproterenol increased mean SGaw by 111 +/- 38% in normal subjects and 113 +/- 69% in asthmatics (p = not significant). Thus, for the same degree of bronchoconstriction, metaproterenol responsiveness was influenced by the dose of methacholine but not the dose of histamine. The differential metaproterenol response could be related to a functional antagonism between muscarinic and beta-adrenergic agonists.

Adrenergic beta-Agonists↗
PubMed1993

Preventing bronchoconstriction in exercise-induced asthma with inhaled heparin.

BACKGROUND: We have previously reported that inhaled heparin prevents allergic bronchoconstriction in sheep and inhibits the anti-IgE-mediated release of histamine from mast cells in vitro. Since the release of such mediators has been implicated in exercise-induced asthma, we investigated whether inhaled heparin could also attenuate the bronchoconstrictor response in this disease. METHODS: On five days we studied 12 subjects with a history of exercise-induced asthma. On day 1 they underwent a standardized exercise challenge on a treadmill to document the presence of exercise-induced asthma. Minute ventilation was estimated with a calibrated respiratory inductive plethysmograph. The workload was increased until the heart rate reached 85 percent of the predicted maximal value, and was sustained for 10 minutes. The magnitude of bronchoconstriction was assessed by measuring specific airway conductance before and after the exercise. On day 2 the partial-thromboplastin time was measured in plasma obtained before and after the subjects inhaled a nebulized solution of heparin (1000 U per kilogram of body weight). On days 3 through 5 the subjects were pretreated with 4 ml of inhaled heparin (1000 U per kilogram), cromolyn sodium (20 mg), or placebo according to a single-blind, randomized, crossover design and underwent exercise challenge 45 minutes later. To exclude the possibility that heparin had any direct effect on airway smooth muscle, bronchial provocation with histamine was induced in five subjects on two further days after pretreatment with either heparin or placebo. RESULTS: Inhaled heparin and cromolyn sodium had no effect on specific airway conductance at base line, but did attenuate the exercise-induced decreases in this variable: the mean (+/- SE) maximal decrease five minutes after exercise was 9 +/- 5 percent after pretreatment with heparin, as compared with 22 +/- 5 percent after pretreatment with cromolyn and 35 +/- 2 percent after pretreatment with placebo. Heparin did not change the partial-thromboplastin time and did not modify the bronchoconstrictor response to histamine. CONCLUSIONS: Inhaled heparin prevents exercise-induced asthma without influencing histamine-induced bronchoconstriction. This non-anticoagulant action of heparin is more likely to be related to a modulation of mediator release than to a direct effect on smooth muscle.

Administration, Inhalation↗
PubMed1992

Modification of histamine- and methacholine-induced bronchoconstriction by calcium antagonist gallopamil in asthmatics.

We studied the comparative modification of histamine- and methacholine-induced bronchoconstriction by a calcium antagonist, gallopamil, in 8 subjects with bronchial asthma. Dose-response curves to aerosolized methacholine or histamine were performed, without and following pretreatment with inhaled gallopamil (10 mg), on 6 different experiment days to determine the cumulative provocative dose (PD50) of each agonist in breath units which caused a 50% decrease in specific airway conductance (SGaw). Baseline values of SGaw were similar on different experiment days and gallopamil had no significant effect on SGaw. PD50 values for histamine on control and placebo days were 6.8 +/- 2.8 and 5.2 +/- 2.8 breath units (mean +/- SE), respectively. Pretreatment with gallopamil increased histamine PD50 to 19.8 +/- 7.5 breath units, which was significantly greater than on control and placebo days (p < 0.01). PD50 values for methacholine on control and placebo days were 9.5 +/- 5.6 and 8.8 +/- 5.8 breath units, respectively. Gallopamil pretreatment had no significant effect on methacholine-induced bronchoconstriction; methacholine PD50 increased to 13.4 +/- 5.5 breath units (p = NS). The mean dose ratio (ratio of PD50 for the agonist in the presence and absence of gallopamil) for histamine was 6.9, which was 3.7-fold higher than the dose ratio of 1.9 methacholine in the same subjects. These data suggest that gallopamil causes greater inhibition of histamine- versus methacholine-induced bronchoconstriction. This suggests that calcium influx in airway smooth muscle through voltage-dependent channels primarily occurs in response to histamine and not to methacholine.

Adult↗
PubMed1989

Relationship between deposition of and responsiveness to inhaled methacholine in normal and asymptomatic subjects.

The purpose of this study was to determine if the intersubject variability in airway responsiveness to methacholine is a function of the methacholine mass deposited in the airways and if methacholine hyperresponsiveness in asymptomatic subjects with asthma is related to increased methacholine deposition. Ten normal and 10 age-matched asymptomatic subjects with asthma inhaled, with a standardized single breath maneuver, a dry aerosol (mass median aerodynamic diameter, 1.5 micron; geometric SD, 2.1) generated from solutions of methacholine at concentrations ranging from 0.078 mg/ml to 80 mg/ml in buffered saline, mixed with a fixed concentration of the fluorescent tracer quinine. The mass of methacholine deposited was calculated from the fluorescence of the inspired and expired aerosol trapped on an absolute filter before inspiration and during expiration. Specific airway conductance (SGaw) was measured before and after the inhalation of increasing concentration of methacholine, and the provocative deposited mass corresponding to a 35% decrease in SGaw was calculated. Baseline aerosol deposition (quinine-labeled buffered saline) ranged from 63% to 94% and was similar in normal subjects (mean 85%) and asymptomatic subjects with asthma (mean 84%). There was a correlation between the decrease in SGaw and methacholine mass deposited at first dose in the normal subjects (p less than 0.001) but not in asymptomatic subjects with asthma. Mean provocative methacholine mass corresponding to a 35% decrease in SGaw was 86 micrograms (range 2 to 157 micrograms) in asymptomatic subjects with asthma and 1361 micrograms (range 157 to 3434 micrograms) in normal subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1988

Inhibition of antigen-induced bronchoconstriction by a new calcium antagonist, gallopamil: comparison with cromolyn sodium.

We have previously demonstrated partial attenuation of antigen-induced bronchoconstriction by aerosolized verapamil (Chest 1985;88:176-80). In the present investigation, we studied the effect of a new calcium antagonist, gallopamil, on allergic bronchial reactivity and compared it to that of cromolyn sodium. Nine asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma were studied on 4 different days, without and after pretreatments with aerosolized placebo, gallopamil (10 mg), or cromolyn sodium (20 mg) solution, in a single-blind, randomized, crossover design. Bronchial reactivity was measured as the cumulative provocative dose of ragweed antigen in breath units (PD35) that caused a 35% decrease in specific airway conductance (SGaw). Baseline SGaw was comparable on control, placebo-, gallopamil- and cromolyn sodium-treatment days. The airway deposition dose of gallopamil and cromolyn sodium was calculated at 1.05 mg and 2.1 mg, respectively. Neither cromolyn sodium nor gallopamil had a significant effect on mean SGaw. Mean +/- PD35 on control and placebo-treatment days was 0.54 +/- 0.95 and 0.23 +/- 0.17 breath units, respectively. Aerosolized gallopamil and cromolyn sodium increased the mean PD35 to 56 +/- 41 and 24 +/- 35 breath units, respectively (p less than 0.05). Gallopamil completely inhibited the antigen-induced bronchoconstriction in six (67%) subjects, whereas cromolyn sodium was totally effective in two of the nine (22%) subjects. These results demonstrate that aerosolized gallopamil inhibits allergic bronchial reactivity with efficacy comparable or better than cromolyn sodium.

Adult↗
PubMed1988

Effect of cold air exposure and exercise on nonspecific bronchial reactivity.

Exercise and eucapnic hyperventilation with cold air can produce bronchoconstriction in asthmatic subjects, but their enhancement of nonspecific bronchial reactivity remains unclear. We studied the effect of submaximal exercise and cold air exposure on bronchial reactivity to methacholine in a normal control group (n = 10) and in subjects with bronchial asthma (n = 17). Bronchial provocation testing was performed to determine the provoking dose (PD35) of methacholine that caused a 35 percent decrease in specific airway conductance (Gaw/VL) in the two groups. Each subject was studied on three different occasions to determine the PD35 to methacholine on a control day, after ten minutes of submaximal exercise, and after a 30-minute exposure to cold air. Methacholine challenge was performed after the Gaw/VL had returned to the baseline values. In the normal group, neither cold air exposure nor exercise challenge had any significant effect on baseline Gaw/VL, whereas in the asthmatic group, both stimuli caused 20 percent and 15 percent decreases in Gaw/VL, respectively (p less than .05). Mean +/- SD control PD35 was 6.1 +/- 11.6 breath units in the asthmatic group, which decreased to 2.2 +/- 2.8 after exercise and 3.0 +/- 5.0 breath units after cold air exposure (p less than .05). In the normal group, control PD35 was 73 +/- 32 breath units, which was not different from PD35 values of 64 +/- 75 and 52 +/- 64 breath units after exercise and cold air exposure, respectively (p = NS). These data suggest that submaximal exercise and cold air exposure enhance nonspecific bronchial reactivity in asthmatic but not in normal subjects.

Adult↗
PubMed1985

Prolonged bronchial obstruction after a single antigen challenge in ragweed asthma.

Some patients with allergic asthma exhibit late-phase responses to inhalation challenge with specific antigen. However, the duration of these responses is difficult to determine because of diurnal variations in airway function, a common phenomenon in patients with asthma. We therefore examined the pattern and duration of pulmonary function in six asymptomatic patients with a history of ragweed asthma and a documented late-phase response after specific and nonspecific bronchial challenge and compared them to responses after control challenge with normal saline. On 3 different days, specific airway conductance (SGaw) and gas distribution by the single breath nitrogen test were measured before (9:00 A.M.) and hourly for 24 hours after inhalation challenge with either normal saline, ragweed extract, or histamine at concentrations sufficient to decrease SGaw immediately by 35% or more. The fluctuations in SGaw after saline and histamine were considerable but failed to follow a typical diurnal or biphasic pattern. There was no difference in mean SGaw between the histamine and saline challenges from 1 to 24 hours after inhalation. In contrast, ragweed challenge produced a typical late-phase response followed by partial recovery of mean SGaw. However, mean SGaw remained subsequently lower than after saline challenge throughout the remaining observation period with fluctuations about this lower level. Gas distribution demonstrated marked intra- and intersubject variations and was therefore not different among the three challenges at any time of measurement. These observations suggest that a single specific but not nonspecific bronchial challenge causes prolonged airflow obstruction in subjects with allergic asthma that lasts 24 hours or longer, independent of variations in baseline airway function.

Airway Obstruction↗
PubMed1985

Comparative modification of antigen-induced bronchoconstriction by the calcium antagonists, nifedipine and verapamil.

We compared the effects of the two calcium antagonists, nifedipine and verapamil, on baseline airway function and antigen-induced bronchoconstriction in asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma. Twelve subjects received a single oral dose of 20 mg of nifedipine or 160 mg of verapamil before inhalation with ragweed antigen. Mean specific airway conductance, a measurement of airway obstruction, was not affected by either agent; nifedipine caused bronchodilatation in two subjects, and verapamil was followed by slight bronchoconstriction in another subject. Nifedipine partially or completely blocked the antigen-induced bronchoconstriction in 67 percent (8/12) of the subjects (p less than 0.05). Two of the subjects who were protected by nifedipine were also protected by pretreatment with verapamil, while this drug was without effect in the others. This study demonstrates that both nifedipine and verapamil in a single oral dose may attenuate antigen-induced bronchoconstriction in some subjects with allergic bronchial asthma and that nifedipine may be more effective than verapamil.

Adult↗
PubMed1985

Comparative effects of oral and inhaled verapamil on antigen-induced bronchoconstriction.

We investigated the comparative effects of oral and inhaled verapamil on specific airway conductance (SGaw) and allergic bronchial reactivity. Ten asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma were studied on four different days, without and with pre-treatments by oral (160 mg) or inhaled (20 mg) verapamil. Bronchial reactivity was measured as the cumulative provocative dose of ragweed antigen which caused a 35 percent decrease in SGaw, ie PD35. The amount of inhaled verapamil actually deposited in the tracheobronchial tree was estimated to be 0.56 mg. Mean SGaw was not affected by either mode of administration; mean SGaw (SE) was 0.13(.02) and 0.12(.02) L/sec-1 before and .14(.02) and 0.12(.02) L/sec-1 after oral and inhaled verapamil, respectively. Mean (SE) PD35 was reproducible on two control days, ie 0.9(.4) and 0.8(.4) breath units, respectively. Inhaled verapamil increased mean PD35 to 18.8 (10.8) breath units (p less than 0.02), while oral verapamil had no significant effect on mean PD35. This study demonstrates that route of administration of calcium antagonist verapamil is an important factor in protection against antigen-induced bronchoconstriction. Inhalation of verapamil appears to be more effective than oral administration.

Administration, Oral↗
PubMed1984

Mechanism of bronchoconstrictive effects of aerosolized buffered saline in asthmatics.

Bronchoconstriction, measured by spirometry and body plethysmography, has been reported with deep breaths of air and of aerosolized buffered saline (ABS) (0.5% sodium chloride and phosphate buffer), in some stable asthmatics. To investigate the mechanisms of this phenomenon, we measured airway resistance (Raw) and functional residual capacity (FRC) in ten asthmatics after deep breaths of ABS, tidal breaths of ABS, tidal breaths of unbuffered normal saline (0.9% sodium chloride) and tidal breaths of 0.5% sodium chloride (ABS without phosphate) on different days. Raw and FRC increased with deep breaths and tidal breaths of ABS in all asthmatics, but not with tidal breaths of normal saline and unbuffered 0.5% sodium chloride. Thus the phosphate buffer rather than the hypoosmolarity of aerosolized buffered saline causes bronchoconstriction in asthmatics.

Adult↗
PubMed1982

Response to bronchodilator drug administration by a new reservoir aerosol delivery system and a review of other auxiliary delivery systems.

Response to bronchodilator aerosols delivered by metered dose inhalers (MDI) depends in part upon the amount of drug depositing on the airways. Ideally, the MDI should be actuated during a slow deep inhalation followed by a breathholding pause, an impossible maneuver for many patients. We developed a new reservoir aerosol delivery system (RADS) consisting of a 700-ml collapsible bag in which aerosol could be injected. The mouthpiece-canister was filtered with a reed that vibrated at inspiratory flows greater than 0.3 L/s to produce a noise. Patients were instructed to keep inhalation silent while breathing from RADS. One puff of metaproterenol (650 microgram) administered via RADS (with one breath rebreathed) was compared with one puff of metaproterenol (650 micrograms) from usual MDI using serial measurements of body plethysmography and spirometry. Respiratory inductive plethysmography measured the point of MDI actuation, volume of inhalation, inspiratory flow, and breathholding pause. Ten patients with chronic airflow limitation caused by asthma or chronic bronchitis were given typed instructions on MDI usage and trained shortly before the study. Metaproterenol via RADS produced significantly greater maximal increase in SGaw (195 +/- 52% SE) compared with metaproterenol via conventional MDI (101 +/- 24%, p less than 0.003). Bronchodilator response in 4 patients unable to coordinate actuation of the MDI with inspiration was significantly less than in 6 patients with good MDI technique (p less than 0.005). The mean flow rates were 0.54 +/- 0.16 L/s during inhalation of metaproterenol compared with 0.19 +/- 0.02 L/s and 0.24 +/- 0.03 L/s during the first and second inhalations, respectively, using RADS. This reservoir aerosol delivery system, which was well accepted by the patients, promotes more effective bronchodilation than the conventional metered dose inhaler.

Adult↗