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Biomedical subjects

K F Chung

Publications and source records attributed to K F Chung.

At least 217 records · Page 12Linked to original sources
PubMed1995

Regular formoterol treatment in mild asthma. Effect on bronchial responsiveness during and after treatment.

Regular beta 2-adrenoceptor agonist therapy may lead to a rebound increase in bronchial responsiveness on discontinuation of therapy and a reduction in bronchoprotective effects. Formoterol, a long-acting beta 2-agonist, is effective in single doses in the prevention of methacholine-induced bronchoconstriction. In a double-blind, placebo-controlled cross-over study, we examined the effect of an inhaled long-acting beta 2-adrenoceptor agonist, formoterol (24 micrograms twice a day) for 2 wk on airway function and responsiveness in 17 subjects with mild asthma (mean age, 26.3 +/- 1.4 yr) who were not taking inhaled glucocorticosteroids. FEV1 and the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) were measured at 36, 60, and 108 h and at 2 wk after the last dose of regular treatment. In addition, PC20 was measured 12 h after the first and the last dose of formoterol and placebo. PC20 values at 36, 60, and 108 h and at 2 wk after formoterol treatment cessation were not significantly different from those after placebo. Mean FEV1 was 3.44 +/- 0.18 L after placebo compared with 3.79 +/- 0.20 L after formoterol (p < 0.001) 12 h after the first dose, and mean PC20 was 0.53 (GSEM 1.4) mg/ml after placebo compared with 2.0 (GSEM 1.4) mg/ml after formoterol (p < 0.001). After 2 wk of regular treatment, mean FEV1 at 12 h after the final dose of formoterol fell to 3.51 +/- 0.23 L compared with 3.41 +/- 0.18 L after the final dose of placebo (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1995

Effect of acute and chronic inhaled furosemide on bronchial hyperresponsiveness in mild asthma.

We determined whether chronic administration of furosemide aerosol would be beneficial for the treatment of asthma. First, we showed that furosemide aerosol delivered from a metered-dose inhaler (10 and 20 mg) significantly protected against sodium metabisulfite (MBS) challenge by 0.6 and 1.3 doubling dilutions respectively in 12 volunteers with mild asthma. In a double-blind cross-over study, we examined the effect of furosemide aerosol from a twice more efficient metered-dose inhaler (10 mg four times per day) inhaled over 4 wk versus placebo in 12 other asthmatic subjects. There was no significant effect of furosemide on bronchial responsiveness to methacholine or MBS. Treatment with furosemide over 1 mo did not improve bronchial hyperresponsiveness in subjects with mild asthma.

Administration, Inhalation↗
PubMed1995

Leukotriene receptor antagonists and biosynthesis inhibitors: potential breakthrough in asthma therapy.

Cysteinyl leukotrienes are potent bronchoconstrictors, inducers of airway microvascular leakage and oedema, and of mucus secretion, in addition to causing an eosinophilic airway infiltration. Increased urinary excretion of the cysteinyl leukotriene E4 (LTE4) has been demonstrated following allergen challenge and during acute asthma attacks. Strategies for inhibition of cysteinyl leukotriene effects include antagonism of cysteinyl leukotriene receptors and inhibition of 5-lipoxygenase activity. In experimental challenge studies in asthmatic patients, these compounds can inhibit bronchoconstriction in response to exercise, aspirin and allergen. Results from clinical studies using receptor antagonists, such as ICI 204,219 and MK-571, and synthesis inhibitors, such as zileuton, demonstrate beneficial effects, with improvement in symptoms and forced expiratory volume in one second (FEV1), and a reduction in the use of beta 2-adrenergic relief medication. Further studies are needed to clarify the exact mechanisms by which these compounds provide beneficial effects. Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of asthma.

Anti-Asthmatic Agents↗
PubMed1995

T-cells subsets and activation in bronchial mucosa of sensitized Brown-Norway rats after single allergen exposure.

We have investigated the relationship between changes in T-cell activation in the bronchial mucosa, airway responsiveness and eosinophilic inflammation in sensitized Brown-Norway rats exposed to ovalbumin (OVA). Rats sensitized intraperitoneally with OVA and exposed to OVA aerosol 21 days later showed an enhanced increase in lung resistance (RNL) to acetylcholine (P < 0.05), and a significant increase in the number of eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BAL) (P < 0.05), compared with sensitized but saline-exposed controls. There was a significant increase in cells expressing the T-cell activation marker CD25 (P < 0.05) and the numbers of CD8+ T cells (P < 0.05), but not in the numbers of CD2+ and CD4+ cells. Eosinophil counts in airway submucosal tissue, as assessed by staining with BMK-13; a monoclonal antibody that binds to eosinophil major basic protein (MBP), were increased in rats receiving sensitization and exposure to OVA compared with naive controls (P < 0.002). There were significant positive correlations between the increase in RL to acetylcholine and the numbers of CD25+ (r = 0.92, P < 0.001), CD4+ (r = 0.77, P < 0.05), CD8+ (r = 0.71, P < 0.05) and MBP+ (r = 0.72, P < 0.03) cells in the OVA-sensitized and exposed group, but not in saline-exposed or naive animals. The number of MBP+ cells also correlated with CD25 expression (r = 0.71, P < 0.05). We conclude that airway hyper-responsiveness and inflammatory cell infiltration caused by OVA exposure of sensitized animals is associated with the presence of activated T cells in the airway mucosa. CD8+ T cells may play a role in the regulation of events leading to eosinophil inflammation and airway hyper-responsiveness.

Allergens↗
PubMed1995

Airway hyperresponsiveness, elevation of serum-specific IgE and activation of T cells following allergen exposure in sensitized Brown-Norway rats.

T lymphocytes may play a regulatory role in the development of allergic airway hyperresponsiveness (AHR). We have studied the relationship between airway responsiveness and a number of immunological changes in Brown-Norway rats sensitized intraperitoneally and repeatedly exposed to ovalbumin (OVA) aerosol. Acetylcholine provocation concentration (PC)150 (the concentration of acetylcholine causing a 150% increase of base-line lung resistance) was measured and peripheral blood and bronchoalveolar lavage (BAL) cells were collected 18-24hr after the final exposure. Total and OVA-specific IgE in serum was measured by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells were analysed by flow cytometry after labelling with monoclonal antibodies against CD2 (pan T-cell marker), CD4, CD8 (T-cell subsets) or CD25 (interleukin-2 receptor). There were significant differences in PC150 (P < 0.05) and in OVA-specific IgE levels in serum (P < 0.002); CD4+ T cells expressed a significantly increased level of CD25 immunoreactivity in BAL, but not in peripheral blood, of rats sensitized and exposed to OVA, compared with saline-exposed controls (P < 0.02). There was a significant correlation between CD25 expression and BAL eosinophil numbers (r = 0.74, P < 0.001), PC150 (r = 0.63, P < 0.003) and OVA-specific IgE (r = 0.77, P < 0.001). These data suggest that activated T cells may be involved in the regulation of allergen-induced AHR in a relevant animal model of allergic asthma.

Allergens↗
PubMed1995

Bradykinin receptor subtypes in rat lung: effect of interleukin-1 beta.

We have characterized bradykinin (BK) receptors in the rat lung and studied the effect of recombinant human interleukin-1 beta (IL-1 beta) on BK receptors in vitro and in vivo. In lung membranes, saturation studies with [3]BK revealed a single class of specific and saturable binding sites. The BK B1 antagonist des-Arg9[Leu8]-BK was less effective in displacing [3H]BK binding sites from lung membranes. In contrast, the selective BK B2 antagonists, Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK) and NPC 567 (D-Arg-[Hyp3,D-Phe7]-BK) fully inhibited the binding of [3H]BK to lung membranes with Ki values of 96.7 +/- 17.8 pM and 9.0 +/- 2.5 nM, respectively. Intratracheal administration of 500 U of IL-1 beta induced airway hyper-responsiveness to inhaled BK and neutrophilia in bronchoalveolar lavage fluid 18 to 24 hr later. Compared to naive or saline-treated animals, IL-1 beta had no effect on [3H]BK binding characteristics at 4, 12 or 24 hr after IL-1 beta administration. Twenty-four hours after IL-1 beta instillation, there was no change in the affinity of the selective BK B1 or B2 antagonists when compared to control animals. In vivo, the selective BK B2 receptor antagonists, NPC 567 (3 mumol kg-1 i.v.) and Hoe 140 (100 nmol kg-1 i.v.), inhibited BK-induced increase in lung resistance, whereas the selective BK B1 antagonist, des-Arg9[Leu8]-BK (10 mumol kg-1 i.v.), was without effect. These data suggest that the action of BK in the rat lung is dependent mainly on the activation of the BK B2 receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of a bradykinin receptor antagonist, HOE 140, against bradykinin- and vagal stimulation-induced airway responses in the guinea-pig.

We have investigated the effect of inhaled HOE 140, a novel bradykinin B2 receptor antagonist, against bradykinin- and vagal stimulation-induced airway microvascular leakage and bronchoconstriction in anesthetized guinea-pigs. Lung resistance was measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. Bradykinin was given by inhalation (1 mM, 45 breaths) and bilateral vagus nerves were stimulated electrically during a 5-min period (3 and 10 Hz, 5 V, pulse width of 5 ms), both of which caused a significant increase in lung resistance and leakage of dye in the airway. HOE 140 (20 and 200 microM, 60 breaths) completely abolished both the airway effects induced by bradykinin, whereas even the higher dose of HOE 140 had no effect against those induced by electrical vagal stimulation. In conclusion, airway microvascular leakage and bronchoconstriction induced by inhaled bradykinin are mediated by activation of bradykinin B2 receptors in the guinea-pig. In contrast, mechanisms via bradykinin B2 receptors do not play an important role in the acute airway responses induced by vagal stimulation.

Administration, Inhalation↗
PubMed1994

Effect of interleukin-1 beta on airway hyperresponsiveness and inflammation in sensitized and nonsensitized Brown-Norway rats.

Airway responsiveness (AR) to inhaled acetylcholine and bradykinin and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred male Brown-Norway rats actively sensitized to ovalbumin and later given 500 U interleukin-1 beta (IL-1 beta) intratracheally. We examined animals 14 to 21 days after initial sensitization at 18 to 24 hours after the intratracheal administration of IL-1 beta. We evaluated AR to acetylcholine as -log PC200, which is -log10 transformation of provocative concentration of acetylcholine producing 200% increase in lung resistance, and to bradykinin as percent increase in lung resistance. BALF was examined as an index of inflammatory changes within the lung. Although there was no significant difference in baseline lung resistance, nonsensitized and sensitized animals that were given IL-1 beta demonstrated a significant increase of AR to bradykinin at 18 to 24 hours and a significant increase of neutrophil counts in BALF, which was already observed by 4 to 6 hours. There was a significant correlation between AR to bradykinin and neutrophil counts in BALF in all animals (r = 0.644; p < 0.0005). We conclude that intratracheal administration of IL-1 beta induces the inflammatory changes, which are characterized by an increase in neutrophil counts in BALF, and increased AR to bradykinin, and that active sensitization per se does not potentiate the effect of IL-1 beta on AR to acetylcholine or bradykinin or on airway inflammation.

Acetylcholine↗
PubMed1994

Effect of sodium metabisulphite on bronchial blood flow in conscious sheep: pharmacological modulation.

1. Sodium metabisulphite (MBS) can induce bronchoconstriction in patients with asthma. We investigated the effects of MBS aerosol on bronchial blood velocity (Vbr) and pulmonary resistance in intubated conscious sheep. 2. Bronchial blood velocity was measured by implanting a 20 MHz ultrasonic Doppler flow probe on the common bronchial branch of the bronchoesophageal artery. 3. Inhaled MBS induced a dose-dependent, transient increase in Vbr lasting for a few minutes without any changes in aortic and pulmonary artery pressures. There was some tachyphylaxis of the Vbr response to successive inhalations of MBS. 4. The cholinoceptor antagonist, ipratropium bromide and the H1 and H2 histamine antagonists, chlorpheniramine and cimetidine, had no significant effect on MBS-induced increase on Vbr. The loop diuretic, frusemide, and the anti-inflammatory drug, nedocromil sodium, which both inhibit MBS-induced bronchoconstriction in patients with asthma, were also without effect. 5. We conclude that MBS induces bronchial vasodilatation in conscious sheep, and that this effect is not dependent on the release of histamine or other mediators, or an activation of cholinergic pathways.

Administration, Inhalation↗
PubMed1994

Effect of acetazolamide and amiloride against sodium metabisulphite-induced bronchoconstriction in mild asthma.

BACKGROUND: Inhaled frusemide but not bumetanide, another loop diuretic, reduces bronchial responsiveness to sodium metabisulphite (MBS). To investigate whether the effect of frusemide could be mediated through mechanisms other than Na+/K+/Cl- cotransporter inhibition, the effects of amiloride--an inhibitor of sodium channels in the airway epithelium--and of acetazolamide--a specific inhibitor of carbonic anhydrase--against MBS challenge were studied. METHODS: In two separate randomised double blind placebo controlled studies, 10 subjects with mild asthma attended on four separate occasions to inhale 7.5 mg amiloride or matched placebo, and 500 mg acetazolamide or placebo, immediately before MBS challenge. The concentration of MBS required to cause a 20% fall in baseline FEV1 (PC20) was measured. RESULTS: Amiloride and acetazolamide had no effect on baseline FEV1. Amiloride had no effect against MBS challenge, but acetazolamide increased -log PC20 from a mean (SE) of 0.75 (0.09) to 0.98 (0.06) representing a 0.77 (0.24) doubling dose increase. CONCLUSIONS: These results suggest that carbonic anhydrase activity in the airways, but not sodium flux, modulates bronchial responsiveness to MBS challenge. The action of frusemide is not likely to involve inhibition of carbonic anhydrase activity.

Acetazolamide↗
PubMed1994

Inhibition of sodium metabisulphite induced bronchoconstriction by frusemide in asthma: role of cyclooxygenase products.

BACKGROUND: Inhaled frusemide inhibits airway responses to sodium metabisulphite and other indirect bronchial challenges in asthma by undetermined mechanisms which may relate to its ability to stimulate prostaglandin release. Inhalation of sodium metabisulphite provokes indirect bronchoconstriction, possibly by activating sensory nerves. To investigate the role of cyclooxygenase products in the airway actions of frusemide and sodium metabisulphite, the effects of a potent cyclooxygenase inhibitor, flurbiprofen, alone and in combination with frusemide were investigated against airway responsiveness to sodium metabisulphite. METHODS: In a double blind double placebo controlled study, 12 mild asthmatic subjects attended on four occasions to undergo three inhalation challenges with sodium metabisulphite. A baseline challenge was performed one hour before oral intake of flurbiprofen 200 mg or matched placebo, and two hours before inhalation of frusemide 40 mg or matched placebo. A second challenge was performed immediately after inhalation of frusemide (two hours after flurbiprofen) with a further challenge three hours later. The log concentration provoking a 20% fall in FEV1 (log PC20) was used to assess airway responsiveness to sodium metabisulphite. RESULTS: Frusemide caused an immediate 1.9 doubling dose protection and a lesser 0.7 doubling dose protection at three hours. This protection was enhanced by flurbiprofen at both time points to 2.7 (early) and 1.9 (late) doubling doses. In addition, flurbiprofen alone significantly reduced airway responsiveness to sodium metabisulphite by 1.1 doubling doses at both two and five hours. CONCLUSIONS: The generation of bronchoprotective prostaglandins is unlikely to underlie the inhibitory action of frusemide against airway responsiveness to sodium metabisulphite. Endogenous contractile prostaglandins within the airways may be involved in the bronchoconstrictor response to sodium metabisulphite.

Adult↗
PubMed1994

Tumor necrosis factor-induced interleukin-8 expression in cultured human airway epithelial cells.

The effects of tumor necrosis factor-alpha (TNF-alpha) on interleukin-8 (IL-8) expression and generation were examined in primary cultured human airway epithelial cells (HAEC) and a human lung epithelial cell line (A549). TNF-alpha increased IL-8 mRNA and protein expression in HAEC in a concentration- and time-dependent manner and these effects were inhibited by dexamethasone (1 microM). There was no change in the stability of IL-8 mRNA, and a nuclear run-on assay confirmed that TNF-alpha increased IL-8 gene transcription. TNF-alpha-induced IL-8 mRNA expression showed a biphasic response in HAEC, with an early increase at 2 h followed by a sustained increase from 8 h, which was abolished by the addition of cycloheximide, suggesting that the synthesis of another protein was involved. A549 cells also increased IL-8 secretion and mRNA after incubation of TNF-alpha, with inhibition by dexamethasone. However, A549 cells showed only an early single peak. A549 cells showed a 250-fold increase in the generation of IL-8 immunoreactivity, whereas primary cultured HAEC showed only a threefold increase, suggesting that HAEC and A549 cells may respond to TNF-alpha in different ways. The sustained increase in IL-8 secretion due to an increase in gene transcription in response to TNF-alpha may be an important amplification step in inflammatory diseases of the airways.

Bronchi↗
PubMed1994

Role of cyclooxygenase and 5-lipoxygenase metabolites, platelet-activating factor and 5-hydroxytryptamine in allergen-induced airway responses in the brown Norway rat.

We determined the effects of selective inhibition of arachidonic acid metabolism via the cyclooxygenase and 5'-lipoxygenase pathways using flurbiprofen and BWA4C, respectively, of 5-hydroxytryptamine (5-HT) using methysergide and of platelet-activating factor (PAF) using WEB 2086 on the airway responses to ovalbumin (OA) aerosol in OA-sensitized Brown Norway rats. Twenty-one days after intraperitoneal injection of OA, rats were exposed to a 1% OA or saline aerosol. Only methysergide (10 mg/kg i.p.; 3 doses over 24 h) provided significant protection of the immediate response to OA. The increase in airway responsiveness to acetylcholine after OA exposure was not significantly altered by methysergide, flurbiprofen (10 mg/kg i.p.), BWA4C (50 mg/kg i.p.) and WEB 2086 (50 mg/kg i.p.) all given over 24 h prior to OA challenge. In addition, there was no effect on the increased recovery of eosinophils and lymphocytes in bronchoalveolar lavage fluid at 24 h. We conclude that 5-HT is an important mediator of the acute response to OA, but that 5-HT, lipoxygenase and cyclooxygenase products and PAF are unlikely to be involved in OA-induced airway hyperresponsiveness and inflammation in the Brown Norway rat.

Allergens↗
PubMed1994

Contribution of intercellular-adhesion molecule-1 in allergen-induced airway hyperresponsiveness and inflammation in sensitised brown-Norway rats.

We investigated the potential role of intercellular-adhesion molecule-1 (ICAM-1) in allergen-induced bronchial hyperresponsiveness (BHR) and inflammation in sensitised Brown-Norway rats. Rats were sensitised with ovalbumin (OA) intraperitoneally and 21 days later they were either exposed to 0.9% NaCl or 1% OA aerosol for 15 min. Rats exposed to OA aerosol were pretreated either with ICAM-1 antibody (3 mg/kg i.p. and i.v., 45 min prior to OA exposure) or with the diluent for the antibody. Eighteen to twenty-four hours after OA or 0.9% NaCl exposure, rats were anaesthetised, tracheostomised and mechanically ventilated, and airway responsiveness to acetylcholine (ACh) aerosol was measured as the provocative concentration of ACh needed to increase pulmorary resistance by 100% (PC100). Mean -log PC100 was increased in rats exposed to OA but pretreated with diluent (2.75 +/- 0.06) compared to rats treated with ICAM-1 antibody (2.51 +/- 0.08; < 0.05). However, only the former group showed significantly higher mean -log PC100 compared to the sensitised group exposed to 0.9% NaCl alone (2.22 +/- 0.12; p < 0.01). There was a significant increase in eosinophil and lymphocyte counts in bronchoalveolar lavage fluid at 24 h in rats pretreated with diluent compared to saline exposed rats. However, in ICAM-1 antibody-pretreated rats, eosinophil and lymphocyte counts were significantly different from diluent-treated ones. We conclude that ICAM-1 antibody inhibits BHR without reducing the influx of inflammatory cells.

Allergens↗
PubMed1994

Involvement of tachykinin receptors (NK1 and NK2) in sodium metabisulfite-induced airway effects.

We have investigated the effects of CP-96,345 and SR-48968, new nonpeptide (neurokinin) NK1 and NK2 receptor antagonists, respectively, against bronchoconstriction and airway microvascular leakage induced by inhaled sodium metabisulfite (MBS) in anesthetized guinea pigs. Lung resistance (RL) was measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. MBS (80 mM, 30 breaths) caused a significant increase in RL and leakage of dye at all airway levels. CP-96,345 (2 mg/kg, intravenous) but not SR-48968 (1.5 mg/kg, intravenous) significantly inhibited the leakage of dye at all airway levels except for trachea. Each antagonist inhibited significantly the maximal increase in RL. The combination had a significant additive effect against the bronchoconstriction, when compared with SR-48968 alone, and significantly inhibited the leakage of dye at the same airway levels as CP-96,345. We conclude that bronchoconstriction induced by inhaled MBS is, at least partly, mediated by activation of both NK1 and NK2 receptors, and the airway microvascular leakage by NK1 receptor stimulation alone.

Administration, Inhalation↗
PubMed1994

Effects of prolonged repeated exposure to ovalbumin in sensitized brown Norway rats.

The effects of chronic exposure to ovalbumin (OA) aerosol were studied in Brown Norway rats following intraperitoneal injections with OA and AI(OH)3 and exposure to OA or saline aerosols, once or every third day for 3 to 8 wk. Measurements of airway responsiveness to acetylcholine (ACh) aerosol at 18 to 24 h after allergen exposure showed a significant increase in -logPC150, the concentration of ACh needed to cause a 150% increase in baseline lung resistance, in animals single-exposed or chronic OA-exposed for 3 wk, compared with saline-exposed control animals. The group receiving 8 wk of OA exposure demonstrated no difference from the control animals with -logPC150 lower than that of the two previous groups (p < 0.001). In all three groups, BAL fluid showed a significant increase in neutrophils, but a significant increase in eosinophils (p < 0.01) was only observed in the single-exposed group when compared with saline-exposed control animals. In the 8-wk exposed rats, there was a higher recovery of macrophages and lymphocytes (p < 0.01) compared with control animals and the other two groups. AHR, present after single or 3-wk repeated exposure, disappears by 8 wk of continuous allergen exposure. Both the enhancement and suppression of AHR may be linked to OA-induced immune and inflammatory mechanisms.

Acetylcholine↗
PubMed1994

Inhibitory effect of UK,74505, a potent and specific oral platelet activating factor (PAF) receptor antagonist, on airway and systemic responses to inhaled PAF in humans.

Inhaled PAF provokes bronchoconstriction, causes peripheral blood neutropenia with rebound neutrophilia, and generates urinary production of the bronchoconstrictor eicosanoids, thromboxane (TX)A2, and the cysteinyl leukotrienes. We examined the effects of an oral PAF antagonist UK,74505 on each of these responses to a single 36 micrograms dose of inhaled PAF. In a double-blind randomized placebo-controlled crossover study, 12 normal male subjects inhaled PAF on two consecutive days, 3 and 24 h after intake of two doses of UK,74505 25 mg and 100 mg, or matched placebo (P). After P, inhalation of PAF provoked bronchoconstriction, measured at regular time points for 60 min as a change in sGaw from baseline and computed as area under the curve (AUC), induced a neutropenia at 5 min and rebound neutrophilia at 2 h, and stimulated production of urinary eicosanoids. Bronchoconstriction was maximal at 5 min but had receded at 1 h; (AUC mean [95% Cl]; 20.0 [13.2, 26.8] at 3 h; 11.0 [5.3, 16.6] at 24 h) and was completely abolished by both doses of UK,74505 at 3 h and by the higher 100 mg dose at 24 h. PAF-induced neutropenia and rebound neutrophilia were abolished by both doses of drug; neutropenia at 5 min (expressed as mean [95% Cl] change from baseline; -2.5 x 10(9)/L [-2.9, -2.1] after P; -0.3 [-0.7, 0.1] after 25 mg; 0.1 [-0.3, 0.4] after 100 mg), neutrophilia at 2 h (2.0 [-1.3, 2.6] after P; -0.2 [-0.8, 0.5] after 25 mg; -0.1 [-0.8, 0.5] after 100 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗