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PubMed1992

Bronchoconstriction in helminthic infection.

In order to determine whether infection by helminthic parasites can be associated with a state of bronchoconstriction, we evaluated the response to the inhalation of a bronchodilator before and after long-term anthelmintic treatment of children in a urban slum of Caracas, Venezuela. In untreated children, a direct association was found between the degree of helminthic infection and the increase in peak expiratory flow rates caused by the bronchodilator. The elimination of the infections was accompanied by a significant decrease in response to the bronchodilator. These results indicate that helminthic infection could contribute to the development of asthmatic conditions in areas where these parasites are endemic.

Albuterol↗
PubMed1994

Effect of pilocarpine on propranolol-induced bronchoconstriction in asthma.

To investigate whether increased release of acetylcholine may be involved in propranolol-induced bronchoconstriction (PIB), the inhibitory effect of pilocarpine (Pilo), an agonist of M2-muscarinic receptors that in 11 stable asthmatic subjects. The bronchial responsiveness to Pilo was also measured in terms of Dmin, defined as the cumulative dose at the point where respiratory resistance (Rrs) began to increase. In PIB, the maximum increase in Rrs (Rrs max) after stopping inhalation for 1 min was measured. Atropine reversed PIB. After pilocarpine pretreatment at a dose equal to Dmin, Rrs max divided by baseline Rrs decreased significantly from 206.6 +/- 61.1 to 163.0 +/- 42.6% (mean +/- SD) (p = 0.001). The ratio of PIB (Rrs max/baseline Rrs) with Pilo to PIB without Pilo correlated inversely according to the pretreatment dose (Dmin) of Pilo (p < 0.05). These results suggest increased release of acetylcholine in PIB and that M2-muscarinic receptors are at least in part functioning in stable asthmatic airways.

Acetylcholine↗
PubMed1995

Improvement in VA/Q distributions during inhalation of nitric oxide in pigs with methacholine-induced bronchoconstriction.

Effects of nitric oxide (NO) and aerosolized terbutaline inhalation on ventilation-perfusion (VA/Q) distributions were determined during methacholine-induced bronchoconstriction in nine mechanically ventilated pigs. Animals inhaled, in random order, zero, 20, and 80 parts per million (ppm) of NO or aerosolized terbutaline. Inhalation of either 20 ppm NO or terbutaline produced similar reduction in pulmonary resistance and increase in lung compliance. Bronchodilation was most pronounced during inhalation of 80 ppm NO. NO inhalation increased PaO2 from 65 +/- 4 to 90 +/- 5 (20 ppm NO) and 104 +/- 6 mm Hg (80 ppm NO) (p < 0.05), and oxygen delivery (DO2) from 484 +/- 49 to 565 +/- 25 (20 ppm NO) and 619 +/- 43 ml/kg/min (80 ppm NO) (p < 0.05) compared with control. Aerosolized terbutaline did not increase PaO2 and DO2. NO inhalation accounted for a decrease in blood flow to shunt units (20 ppm NO: 14 +/- 1%, 80 ppm NO: 19 +/- 2%; p < 0.05) and an increase in the perfusion of normal VA/Q units (20 ppm NO: 12 +/- 1%, 80 ppm NO: 18 +/- 1%; p < 0.05). Perfusion of shunt and normal VA/Q units was similar in the absence of NO inhalation with and without aerosolized terbutaline. Pulmonary vascular resistance decreased from 510 +/- 55 to 332 +/- 22 dyn.s/cm5 with 20 ppm NO (p < 0.05) and to 329 +/- 41 dyn.s/cm5 with 80 ppm NO (p < 0.05) but did not change with terbutaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

U46619-induced bronchoconstriction in asthmatic subjects is mediated by acetylcholine release.

Thromboxane A2 (TxA2) has been implicated in the pathogenesis of airway hyperresponsiveness. U46619 is a chemical that mimics the effects of TxA2. Both TxA2 and U46619 have been demonstrated to act presynaptically to enhance the release of acetylcholine from cholinergic nerves in canine airway smooth muscle. The purpose of this study was to determine whether the bronchoconstriction caused by inhaled U46619 in asthmatic subjects is caused by acetylcholine release. Airway responsiveness to inhaled methacholine and U46619 was measured in eight subjects with mild stable asthma and expressed as the provocation concentration causing a 20% fall in FEV1 (PC20). Subjects were studied on 4 d, each separated by 3 days. On each study day, subjects inhaled a cholinergic antagonist ipratropium bromide (80 micrograms), or placebo, and 1 h later, increasing doubling doses of methacholine or U46619 were inhaled, and a PC20 value was obtained. The mean methacholine PC20 on the placebo day was 1.42 mg/ml (%SEM, 1.47) and after treatment with ipratropium bromide this increased to 127.33 mg/ml (%SEM, 1.29) (p = 0.0001), a mean 89.4-fold (%SEM, 1.19) increase. The mean U46619 PC20 on the placebo day was 2.09 micrograms/ml (%SEM, 1.56) and after treatment with ipratropium bromide this increased to 47.54 micrograms/ml (%SEM, 1.43) (p = 0.0001), a mean 22.8-fold (%SEM, 1.36) increase. The ability of ipratropium bromide to attenuate responsiveness to the noncholinergic mediator histamine was also investigated in six subjects. The mean increase in histamine PC20 was a 3.09-fold (%SEM, 1.17) increase, significantly less than the increase seen for both methacholine and U46619 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Effect of inhaled atrial natriuretic peptide and a neutral endopeptidase inhibitor on histamine-induced bronchoconstriction.

The reduced ability of inhaled compared with intravenous atrial natriuretic peptide (ANP) to modify bronchial reactivity and tone may be due to degradation of the peptide by neutral endopeptidase (NEP) within the airways. To test this hypothesis, we have examined the effect of thiorphan, an NEP inhibitor, on the protection afforded by inhaled ANP against histamine-induced bronchoconstriction in 10 mildly asthmatic patients. Pretreatment with ANP alone attenuated the bronchoconstrictor response to histamine with a mean (SEM) maximum percent fall in FEV1 after histamine of 15.9 (2.9) (p < 0.05) compared with 24 (2.9) after placebo and 24 (4) after pretreatment with thiorphan alone. Prior inhalation of thiorphan greatly enhanced the ANP effect: the mean maximum percent fall after this combination was 5.1 (2.3) (p < 0.01, compared with ANP alone). Our results suggest that airway NEP is important in modulating the effect of inhaled ANP. It may be possible to exploit the guanylyl cyclase pathway, by which ANP acts, in the treatment of asthma by the administration of ANP analogues stable to neutral endopeptidase.

Administration, Inhalation↗
PubMed1995

Inhaled indomethacin prevents bronchoconstrictive response to distilled water but not to histamine in children with asthma.

We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory drug (NSAID), against bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with asthma. Ten children with asthma (eight males and two females, with a mean +/- SEM age of 10.7 +/- 0.7 yr), who had a decrease in FEV1 of at least 20% after UNDW inhalation, were enrolled in this study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body-surface area) or placebo (0.9% saline) according to a single-blind, randomized, crossover design, and underwent a UNDW challenge test 15 min after the pretreatment. Furthermore, to study the possibility that indomethacin has a direct effect on airway smooth muscle, bronchial provocation with histamine was performed in seven subjects on two further days after pretreatment with indomethacin or placebo. Inhaled indomethacin had no effect on baseline pulmonary function, but did prevent the UNDW-induced decline in FEV1 (p < 0.01). Inhaled indomethacin did not modify the bronchoconstrictor response to histamine, indicating that a direct effect of this agent on airway smooth muscle is unlikely. The inhibition of local prostaglandin synthesis in the airways may be involved in the effect of indomethacin.

Administration, Inhalation↗
PubMed1995

Effect of 5-lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma.

To investigate the contribution of leukotrienes (LTs) to inflammation and bronchoconstriction in nocturnal asthma, we performed a randomized trial in 12 asthmatic patients and 6 normal control subjects. This study involved pulmonary function testing, methacholine challenge, bronchoscopy for cell counts, LT and thromboxane (TX) levels in bronchoalveolar lavage (BAL) fluid, and collection of urine for LTs at 4:00 P.M. and 4:00 A.M. At 4:00 P.M. BAL fluid LTB4 and sulfidopeptide LT levels in asthmatic and control subjects were not statistically different. At 4:00 A.M. alone, LTB4 and cysteinyl LT levels increased to become significantly greater in asthmatic than in control subjects, LTB4 levels correlating significantly (r = -0.66, p < 0.0001) with nocturnal fall in FEV1. Nocturnal asthmatic urinary LTE4 levels were also significantly higher than those of control subjects. The 4:00 A.M. testing was repeated during treatment with a 5-lipoxygenase inhibitor, zileuton. In asthmatic subjects, zileuton decreased BAL fluid LTB4 (p = 0.01) and urinary LTE4 (p = 0.01) while showing a trend for improving nocturnal FEV1 (p = 0.086). These decreases in LTB4 levels and improvement in FVE1 were associated with significant reductions in 4 A.M. BAL fluid and blood eosinophil percentages on zileuton compared with placebo administration. These findings demonstrate the importance of LTs in both the inflammation and the physiology of nocturnal asthma.

Adolescent↗
PubMed1996

Prolonged effect of tiotropium bromide on methacholine-induced bronchoconstriction in asthma.

Inhaled anticholinergic drugs are effective in the treatment of chronic obstructive pulmonary diseases (COPD), of acute asthma, and of some patients with nocturnal asthma. Tiotropium bromide (tiotropium) is a novel anticholinergic agent with a long duration of action and kinetic selectivity for M1- and M3-subtypes of muscarinic receptors. We investigated the duration of protection of a single dose of inhaled tiotropium against methacholine-induced bronchoconstriction in 12 male atopic asthmatic volunteers in a double-blind, placebo-controlled study. On four separate occasions 8 to 24 d apart, methacholine PC20 was measured serially for up to 48 h after placebo and after three doses of tiotropium (10, 40, and 80 microg). Each dose of tiotropium produced mild bronchodilatation as measured by an increase in FEV1 of between 5.5 and 11.1% from baseline, that was sustained for 24 h. There was significant dose-dependent protection against methacholine challenge at 2 h of 5.0 +/- 1.1, 7.1 +/- 0.5, and 7.9 +/- 0.7 (mean +/- SEM) doubling doses after 10, 40, and 80 microg respectively, and this persisted for 48 h. There were no adverse effects reported at any dose. The prolonged bronchodilator response and protection against methacholine challenge suggest that tiotropium may be useful in the treatment of COPD and nocturnal asthma and that once-daily dosing may be sufficient.

Adult↗
PubMed1997

Effect of inhaled indomethacin on exercise-induced bronchoconstriction in children with asthma.

We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory drug (NSAID), on exercise-induced bronchoconstriction (EIB) in children with asthma. Nine asthmatic children (7 boys, 2 girls, with a mean +/- SEM age of 11.0 +/- 0.8 yr) with a history of EIB participated in this study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body surface area [BSA]) or placebo (0.9% saline) according to a double-blind, randomized, crossover design, and underwent an exercise challenge test 15 min after the pretreatment. Inhaled indomethacin significantly attenuated EIB. The mean maximal percent decrease in FEV1 following exercise was 36.1 +/- 5.7% after placebo and 18.0 +/- 4.6% after indomethacin pretreatment (p = 0.0310). Indomethacin also significantly reduced the mean maximal decrease in arterial oxygen saturation after exercise (p = 0.0378). The inhibition of local prostaglandin synthesis and/or ion transport in the airways may be a mechanism involved in the protective potency of inhaled indomethacin.

Administration, Inhalation↗
PubMed1999

Protection against methacholine bronchoconstriction to assess relative potency of inhaled beta2-agonist.

The purposes of this study were to estimate the relative dose potency (RP) of two formulations of salbutamol pressurized metered-dose inhalers (Proventil-HFA and Ventolin-CFC MDIs) to protect against methacholine bronchoconstriction, to validate this method and provide recommendations. The protective effects of 100-, 200-, and 400-micrograms doses of Proventil-HFA were compared with the same doses of Ventolin-CFC in 18 adult asthmatics (mean FEV1, 92% predicted; mean baseline PC20 methacholine, 1.8 mg/ml), in a dose-level blind, balanced, eight-period, crossover, placebo-controlled study. The log-transformed PC20 values after each dose of the drugs were compared by repeated-measures analysis of variance (ANOVA). A significant dose-effect was present (p < 0.0001). Using the Finney assay, the RP of Proventil-HFA compared with Ventolin-CFC was 1.08 (90% CI, 0.81-1.46) (80% power). This was also estimated using a nonlinear Emax model to validate the Finney method. The most precise estimate of RP was obtained with the comparison between 100- and 200-micrograms doses (RP, 1.00; 90% CI, 0.77-1.31). There were no adverse events resulting from the drugs or methacholine. We conclude that Proventil-HFA salbutamol is bioequivalent to Ventolin-CFC salbutamol. Bronchoprotection to methacholine is a valid method of demonstrating bioequivalence. By this method, 100- and 200-micrograms doses of salbutamol inhalations from an MDI will suffice.

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↗
PubMed1999

Chest wall hyperinflation during acute bronchoconstriction in asthma.

The mechanics of the chest wall was studied in seven asthmatic patients before and during histamine-induced bronchoconstriction (B). The volume of the chest wall (VCW) was calculated by three-dimensional tracking of 89 chest wall markers. Pleural (Ppl) and gastric (Pga) pressures were simultaneously recorded. VCW was modeled as the sum of the volumes of the pulmonary-apposed rib cage (VRC,p), diaphragm-apposed rib cage (VRC,a), and abdomen (VAB). During B, hyperinflation was due to the increase in end-expiratory volume of the rib cage (0.63 +/- 0.09 L, p < 0.01), whereas change in VAB was inconsistent (0.09 +/- 0.07 L, NS) because of phasic recruitment of abdominal muscles during expiration. Changes in end-expiratory VRC,p and VRC,a were along the rib cage relaxation configuration, indicating that both compartments shared proportionally the hyperinflation. VRC,p-Ppl plot during B was displaced leftward of the relaxation curve, suggesting persistent activity of rib cage inspiratory muscles throughout expiration. Changes in end-expiratory VCW during B did not relate to changes in FEV(1) or time and volume components of the breathing cycle. We concluded that during B in asthmatic patients: (1) rib cage accounts largely for the volume of hyperinflation, whereas abdominal muscle recruitment during expiration limits the increase in VAB; (2) hyperinflation is influenced by sustained postinspiratory activity of the inspiratory muscles; (3) this pattern of respiratory muscle recruitment seems to minimize volume distortion of the rib cage at end-expiration and to preserve diaphragm length despite hyperinflation.

Abdominal Muscles↗
PubMed2000

Heparin inhibits eicosanoid metabolism and hyperventilation-induced bronchoconstriction in dogs.

Inhalation of heparin, an anticoagulant, attenuates exercise- induced asthma (EIA) in human subjects. The purpose of this study was to determine if heparin inhibits hyperventilation-induced bronchoconstriction (HIB) in a canine model of EIA, and if its mode of action involves the inhibition of eicosanoid mediator production and release. We used a wedged bronchoscope technique to measure baseline peripheral airway resistance (Rp). We then performed either a 2-min or 5-min dry air challenge (DAC) by temporarily increasing from 200 to 2,000 ml/min the flow of 5% CO(2) in air used to ventilate a wedged sublobar segment. We compared HIB before and 60 min after aerosol treatment with either bacteriostatic water (BW) or heparin. We found that (1) heparin had no effect on baseline Rp, (2) BW did not alter the response to DAC, and (3) heparin reduced HIB by approximately 50-60%. On the basis of bronchoalveolar lavage fluid (BALF) cell analysis, heparin and BW caused acute infiltration of macrophages and eosinophils, and heparin increased the number of erythrocytes recovered immediately after DAC. Despite these acute inflammatory effects initiated prior to DAC, BALF mediator analyses revealed that pretreatment with heparin either attenuated or abolished hyperventilation-induced leukotriene, prostaglandin, and thromboxane release. Thus, our data provide direct evidence that inhaled heparin inhibits eicosanoid mediator production and release caused by hyperventilation with dry air, and significantly attenuates HIB.

Administration, Inhalation↗
PubMed2000

Symptom perception during acute bronchoconstriction.

The hypothesis underlying the present study was that some of the variability in symptom intensity seen during acute bronchoconstriction may result from varying intensities of several stimuli yielding several sensations that can be identified by specific descriptive expressions (symptoms). A total of 232 subjects inhaled methacholine in doubling concentrations to a 20% decrease in FEV(1), or 64 mg/ml. The study identified the prevalence of dyspnea, nonspecific discomfort associated with the act of breathing, and 10 specific symptom expressions. Each symptom intensity was rated in Borg scale units. The contribution of the specific symptoms to the intensity of dyspnea is illustrated in the following equation (r = 0. 84): Dyspnea = 0.44 + 0.19 Difficult breathing + 0.41 Chest tightness + 0.20 Breathlessness + 0.14 Labored breathing + 0.11 Chest pain. Dyspnea was more intense with broncho-constriction, baseline pulmonary impairment, weight, and sex (being female). Dyspnea was less intense with age (being older) and as airway responsiveness to methacholine increased (p < 0.05 for all factors). Chest tightness and chest pain were at polar extremes on the discrimination scale, i.e., easily discriminated; chest tightness, difficult and labored breathing were not easily discriminated.

Adult↗
PubMed2000

A computed tomographic scan assessment of endotracheal suctioning-induced bronchoconstriction in ventilated sheep.

This study was directed at assessing changes in bronchial cross-sectional surface areas (BCSA) and in respiratory resistance induced by endotracheal suctioning in nine anesthetized sheep. Cardiorespiratory parameters (Swan-Ganz catheter), respiratory resistance (inspiratory occlusion technique), BCSA, and lung aeration (computed tomography) were studied at baseline, during endotracheal suctioning, and after 20 consecutive hyperinflations. Measurements performed initially at an inspired oxygen fraction (FI(O(2))) of 0.3 were repeated at an FI(O(2)) of 1.0. At an FI(O(2)) of 0.3, endotracheal suctioning resulted in atelectasis, a reduction in BCSA of 29 +/- 23% (mean +/- SD), a decrease in arterial oxygen saturation from 95 +/- 3% to 87 +/- 12% (p = 0.02), an increase in venous admixture from 19 +/- 10% to 31 +/- 19% (p = 0. 006), and an increase in lung tissue resistance (DR(rs)) (p = 0. 0003). At an FI(O(2)) of 1.0, despite an extension of atelectasis and an increase in pulmonary shunt from 19 +/- 5% to 36 +/- 2% (p < 0.0001), arterial O(2) desaturation was prevented and BCSA decreased by only 7 +/- 32%. A recruitment maneuver after endotracheal suctioning entirely reversed the suctioning-induced increase in DR(rs) and atelectasis. In three lidocaine-pretreated sheep, the endotracheal suctioning-induced reduction of BCSA was entirely prevented. These data suggest that the endotracheal suctioning-induced decrease in BCSA is related to atelectasis and bronchoconstriction. Both effects can be reversed by hyperoxygenation maneuver before suctioning in combination with recruitment maneuver after suctioning.

Airway Resistance↗
PubMed1990

Endogenous opioids modulate the increase in ventilatory output and dyspnea during severe acute bronchoconstriction.

The aim of this study was to evaluate whether endogenous opioids are involved in the regulation of breathing pattern and respiratory drive during bronchoconstriction induced by methacholine (MCh). We studied six male asymptomatic asthmatics 18 to 35 yr of age. In a preliminary study we determined the concentration of MCh causing a 60% fall in FEV1 (PC60 FEV1). On two subsequent days, we measured breathing pattern, dyspnea sensation (Borg scale), mouth occlusion pressure (P0.1), and FEV1 before and 10 min after an intravenous injection of either naloxone (0.1 mg/kg) or saline according to a randomized double-blind crossover design. A MCh concentration equal to the PC60 FEV1 was then inhaled, and measurements were repeated 5 min later. Neither placebo nor naloxone affected baseline breathing pattern, P0.1, and FEV1. Naloxone pretreatment did not influence airway response to MCh; the mean percent fall in FEV1 was 65.9 +/- 1.3 and 64.7 +/- 1.2% (mean +/- 1 SE) on the placebo day and the naloxone day, respectively. After MCh inhalation no significant changes in VE, VT, and breathing frequency occurred when patients received placebo. However, P0.1 increased from 1.48 +/- 0.17 to 3.43 +/- 0.70 cm H2O (p less than 0.05), and VT/TI fell from 0.66 +/- 0.08 to 0.52 +/- 0.04 L/s (p less than 0.05). Naloxone pretreatment resulted in an increase in breathing frequency (from 18.2 +/- 1.7 to 22.8 +/- 2.6 breaths/min; p less than 0.05) and VT/TI (from 0.58 +/- 0.06 to 0.74 +/- 0.05 L/s; p less than 0.05) after MCh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Effect of inhaled furosemide and bumetanide on adenosine 5'-monophosphate- and sodium metabisulfite-induced bronchoconstriction in asthmatic subjects.

Inhaled furosemide, a high ceiling diuretic, inhibits bronchoconstrictor responses to sodium metabisulfite (MBS) and other indirect challenges by unknown mechanisms. Furosemide acts by inhibition of Na+/Cl- transport in renal tubules and may exert similar effects on asthmatic airways. To evaluate this hypothesis we compared the effects of nebulized furosemide with those of bumetanide, another high ceiling diuretic that inhibits Na+/Cl- transport, on bronchial challenge with adenosine 5'-monophosphate (AMP) and MBS in 16 asthmatic subjects. We also studied the effects of furosemide on histamine-induced bronchoconstriction in seven of these subjects. Nine subjects inhaled furosemide (30 mg) or placebo (P) 30 min before challenge with nebulized AMP (0.39 to 400 mg/ml). Seven returned for similar study with histamine (0.125 to 32 mg/ml). In another study, seven subjects inhaled bumetanide (2 mg) or P 5 and 30 min before AMP and MBS (0.3 to 80 mg/ml) challenge. The provocative concentration causing a 20% fall in FEV1 (logPC20) was calculated by linear interpolation of log dose-response curves. Furosemide (F) significantly attenuated responses to AMP: mean +/- SEM logPC20, 1.59 +/- 0.24 (geometric mean PC20 [GM], 39.0 mg/ml) after F and 0.98 +/- 0.29 (GM, 9.5 mg/ml) after P (p less than 0.01), but it did not alter responsiveness to histamine: logPC20, 0.09 +/- 0.17 (GM 1.2 mg/ml) after F and 0.09 +/- 0.20 (GM, 1.2 mg/ml) after P.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate↗
PubMed1992

Terbutaline acts at multiple sites to inhibit bronchoconstriction induced by dry air in canine peripheral airways.

We examined the effect of the beta 2-agonist terbutaline on dry airflow-induced bronchoconstriction (AIB) in the canine lung periphery. Using a wedged bronchoscope technique, collateral resistance (Rcs) and airway wall temperature (Taw) were measured before and after a 2-min exposure to dry air. When sublobar segments were challenged with dry air, Taw fell during challenge (p less than 0.001), and Rcs increased 5 min postchallenge (p less than 0.01). Pretreatment with terbutaline (100 micrograms/kg) reduced the fall induced by dry-air challenge in Taw by 37% and the subsequent rise in Rcs by 87%. Terbutaline significantly reduced the concentrations of thromboxane B2 (TxB2) and prostaglandin D2 (PGD2), and decreased the concentration of epithelial cells recovered in bronchoalveolar lavage fluid 5 min postchallenge. In addition, terbutaline attenuated histamine- and PGD2-induced constriction. Finally, peripheral lung sensitivity (as assessed by delta Rcs/delta Taw) to challenge after treatment with terbutaline was significantly less than that calculated for untreated control animals (p less than 0.05). These data are consistent with the idea that terbutaline attenuates AIB by (1) facilitating replacement of water lost during exposure to dry air, (2) inhibiting mediator production and release from osmosensitive cells, and (3) reducing smooth muscle responsiveness.

Airway Resistance↗