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Biomedical subjects

I Aziz

Publications and source records attributed to I Aziz.

At least 19 recordsLinked to original sources
PubMed2005

Investigation and management of chronic cough using a probability-based algorithm.

Chronic cough is a common and distressing symptom. A novel algorithm has been developed for the management of chronic cough, in which an assessment of clinical probability of disease determines the need to proceed to investigation. In this study, the performance of this algorithm in clinical practice was prospectively evaluated. A total of 131 consecutively referred patients (86 females) whose principal presenting symptom was a cough of duration >8 weeks were studied. Their age (median (range)) was 60 (16-88) yrs and cough duration 5.9 (0.2-65) yrs. A cause of cough was established in 93% of cases. The most frequent diagnoses were asthma (24% of cases), gastro-oesophageal disease (22%), post-viral cough (8%), bronchiectasis (8%) and interstitial lung disease (8%). Primary pulmonary disease was significantly more likely in patients with a productive cough and in patients with an abnormal chest radiograph. Only a small proportion (<8%) of patients had multiple causes of cough. The probability of treatment started on the basis of a high clinical suspicion of either asthma, gastro-oesophageal disease or rhinitis being successful was 74%. Overall, 26% of the patients were managed successfully without the need for any form of investigation other than chest radiography and spirometry. Use of the algorithm resulted in identification of the cause of cough and successful treatment in the large majority of cases. It is concluded that this protocol has the potential to improve management by providing a structured approach, reducing the number of investigations performed, and minimising unnecessary delays in treatment.

Adolescent↗
PubMed2003

Abnormal oesophageal motility in patients with chronic cough.

BACKGROUND: Although gastro-oesophageal reflux is a recognised cause of chronic cough, the role of oesophageal dysmotility is unknown. The aim of this study was to determine the prevalence of abnormal oesophageal motility in a selected group of patients with chronic cough. METHODS: Oesophageal manometry and 24 hour pH monitoring were performed in 43 patients with chronic cough, 34 of whom had symptoms suggestive of gastro-oesophageal reflux. Comparative manometric measurements were made in 21 healthy subjects. RESULTS: Nine patients with chronic cough had normal manometry and 24 hour pH. Of the remaining 34 patients, 11 (32%) had abnormal manometry alone, five (15%) had abnormal 24 hour pH monitoring alone, and in 18 (53%) both tests were abnormal. Only one patient in the control group had manometric abnormalities. CONCLUSIONS: These results point to a previously unrecognised high prevalence of abnormal oesophageal manometry in patients presenting with chronic cough. Oesophageal dysmotility may therefore be important in the pathogenesis of cough in these patients.

Adult↗
PubMed2001

Cardiac morbidity and mortality following carotid endarterectomy: the importance of diabetes and multiple Eagle risk factors.

The objectives of this study were to (1) determine cardiac morbidity and mortality in patients undergoing carotid endarterectomy (CEA) and (2) to determine whether any Eagle risk factors and/or the indication for CEA are associated with a higher risk of an adverse cardiac event. The records of 123 male patients who underwent CEA were retrospectively reviewed. The Eagle risk factors for adverse cardiac events, indications for CEA, and adverse cardiac events were recorded and analyzed. In males undergoing CEA, the presence of diabetes or multiple Eagle risk factors significantly increases the risk of an adverse postoperative cardiac event. There is no difference in cardiac event rate between symptomatic and asymptomatic CEA. Thus, asymptomatic CEA should be approached with caution in these higher cardiac risk patients.

Aged↗
PubMed2000

Effects of adding a leukotriene antagonist or a long-acting beta(2)-agonist in asthmatic patients with the glycine-16 beta(2)-adrenoceptor genotype.

PURPOSE: In the United Kingdom, about 40% of patients with asthma are homozygous for the glycine-16 beta(2)-adrenoceptor polymorphism, which predisposes them to agonist-induced down-regulation and desensitization of the beta(2)-adrenoceptor. We assessed the effects of adding treatment with either a long-acting beta(2)-agonist (inhaled formoterol, 12 microg twice daily) or a leukotriene receptor antagonist (oral zafirlukast, 20 mg twice daily) to inhaled corticosteroid therapy in patients with this genotype. SUBJECTS AND METHODS: We enrolled 24 patients with mild to moderate asthma who were being treated with inhaled corticosteroids. Patients were randomly assigned to receive one of three treatments (placebo, zafirlukast, or formoterol in addition to inhaled corticosteroids) for 1 week each in a crossover fashion, separated by a 1-week placebo run-in and washout period. Measurements of bronchoprotection (measured as the provocative dose of methacholine that produced a 20% decline in forced expiratory volume in 1 second [FEV(1)]), exhaled nitric oxide (a surrogate marker of airway inflammation), and symptoms were made before each treatment and 12 hours after the last dose of each treatment. RESULTS: Both formoterol and zafirlukast were equally effective in maintaining asthma control compared with placebo: the geometric mean-fold difference in the methacholine provocative dose was 1.5-fold (95% confidence interval [CI]: 1.1- to 2.2-fold) for zafirlukast and 1.9-fold (95% CI: 1.2- to 2.9-fold) for formoterol. As compared with placebo, zafirlukast caused a significant suppression in exhaled nitric oxide (1.7-fold difference in geometric mean values, 95% CI: 1.1- to 2.6-fold) but formoterol did not (1.2-fold difference, 95% CI: 0.8- to 1.9-fold). Diary cards showed significant (P <0.05) improvements in the peak flow with formoterol (morning and evening) and zafirlukast (evening) as compared with placebo. CONCLUSIONS: Formoterol and zafirlukast maintained asthma control in patients who might be genetically predisposed to fare worse with long-acting beta(2)-agonists. The reduction in exhaled nitric oxide with zafirlukast suggests that it may have anti-inflammatory effects in addition to those seen with inhaled corticosteroids.

Administration, Inhalation↗
PubMed2000

Bronchodilator response to albuterol after regular formoterol and effects of acute corticosteroid administration.

BACKGROUND: There is controversy about the development of bronchodilator subsensitivity after regular administration of long-acting beta(2)-agonists. OBJECTIVES: The purpose of the study was to evaluate whether regular treatment with formoterol affects the bronchodilator response to repeated puffs of albuterol, and also to assess the effects of acute administration of a bolus dose of IV or inhaled corticosteroid. MATERIALS AND METHODS: Twelve patients (mean [SD] age, 43 [15] years; FEV(1), 57 [17] % predicted) with stable, moderate to severe persistent asthma who were all taking inhaled corticosteroids were evaluated in a randomized, placebo-controlled, double-blind, double-dummy, crossover study. Patients received treatments each for 2 weeks followed by a bolus (IV/inhaled) of corticosteroid or placebo: (1) placebo inhaler bid + bolus placebo; (2) formoterol Turbuhaler 24 microg metered dosage bid (delivered dosage 18 microg bid) + placebo; (3) formoterol 24 microg bid + bolus IV hydrocortisone, 200 mg; or (4) formoterol 24 microg bid + bolus inhaled budesonide, 1,600 microg. Bronchodilator response to repeated puffs of albuterol (200 to 1,600 microg) for > 80 min was measured at 2 h after bolus administration of placebo or corticosteroid. The study was powered at the 80% level to detect a 20% difference in area under curve between 20 and 80 min (AUC) for FEV(1) response to albuterol as change from baseline (primary end point). RESULTS: There was significant subsensitivity (p = 0.01) of the mean albuterol FEV(1) response (as AUC, L x s) after formoterol alone (737) as compared to placebo (1,453) along with partial reversal by steroid administration: formoterol + hydrocortisone (1, 050), and formoterol + budesonide (942). There was a similar pattern of subsensitivity (p = 0.03) for the mean albuterol forced expiratory flow between 25% and 75% of vital capacity response (as AUC, L): placebo (2,149), formoterol alone (1,002), formoterol + hydrocortisone (1,402), and formoterol + budesonide (1,271). CONCLUSION: Regular treatment with formoterol produced significant bronchodilator subsensitivity to repeated puffs of albuterol, which was partially reversed by a bolus dose of systemic or inhaled corticosteroid.

Administration, Inhalation↗
PubMed2000

Functional antagonism with formoterol and salmeterol in asthmatic patients expressing the homozygous glycine-16 beta(2)-adrenoceptor polymorphism.

BACKGROUND: Formoterol and salmeterol differ in their relative intrinsic activity at airway beta(2)-adrenoceptors, with formoterol being a full agonist. The homozygous glycine-16 polymorphism of the beta(2)-adrenoceptor occurs in approximately 40% of patients and is known to predispose to agonist-induced downregulation and desensitization. OBJECTIVES: To evaluate possible differences in intrinsic beta(2)-adrenoceptor agonist activity between salmeterol and formoterol in terms of their functional antagonism against methacholine-induced bronchoconstriction (the primary end point) in genetically susceptible patients who exhibited the homozygous glycine-16 polymorphism. METHODS: Eighteen patients with mild-to-moderate persistent asthma receiving inhaled corticosteroid who expressed the homozygous glycine-16 genotype were randomized to completion (mean [SEM] age, 35.8 [3.2] years; mean FEV(1), 76.9 [2. 5]% predicted). Patients received three different treatments for 1 week in randomized, double-blind, crossover fashion, with a 1-week washout period between treatments: formoterol, 12 microg bid; salmeterol, 50 microg bid; and placebo. For each of the randomized treatment periods, there were three separate methacholine challenges: baseline after washout, 12 h after the first dose, and 12 h after the last dose. RESULTS: Both salmeterol and formoterol exhibited significantly (p < 0.05) greater bronchoprotection than placebo for their effects after single or repeated dosing, although there was no significant difference between the two drugs. The geometric mean fold protection vs placebo (95% confidence interval [CI]) for the first dose was 1.6-fold (95% CI, 1.1 to 2.2) for salmeterol and 1.9-fold (95% CI, 1.1 to 3.2) for formoterol, and for last dose was 1.6-fold (95% CI, 1.2 to 2.3) for salmeterol and 1. 9-fold (95% CI, 1.2 to 2.8) for formoterol. Salmeterol and formoterol produced significant (p < 0.05) increases in FEV(1) and forced expiratory flow after 25 to 75% of vital capacity has been expelled, after the first but not the last dose compared to placebo, while there were significant (p < 0.05) improvements in domiciliary peak flows during treatment with both drugs. CONCLUSION: Our results showed no difference between formoterol and salmeterol in the degree of functional antagonism against methacholine-induced bronchoconstriction at the end of a 12-h dosing interval in patients who expressed the homozygous glycine-16 genotype. There was a significant residual degree of bronchoprotection after 1 week of treatment, which was not significantly different compared to the first-dose effect.

Administration, Inhalation↗
PubMed2000

Effects of once-daily formoterol and budesonide given alone or in combination on surrogate inflammatory markers in asthmatic adults.

OBJECTIVES: We wished to evaluate the effects of once-daily combination therapy on surrogate inflammatory markers. METHODS: Fifteen patients with atopic persistent asthma were evaluated (mean age, 32.4 years; FEV(1), 75.2% predicted) in a randomized, double-blind, double-dummy, placebo-controlled crossover study with a 1-week placebo washout period, comparing the following once-daily nighttime treatments: (1) formoterol (FM), 12 microg, for 2 weeks and FM, 24 microg, for 2 weeks; or (2) budesonide (BUD), 400 microg, for 2 weeks and BUD, 800 microg, for 2 weeks; or (3) FM, 12 microg, plus BUD, 400 microg, for 2 weeks and FM, 24 microg, plus BUD, 800 microg, for 2 weeks. Adenosine monophosphate (AMP) bronchial challenge, exhaled nitric oxide (NO), and serum eosinophilic cationic protein (ECP) were evaluated at 12 h postdosing after administration of each placebo and after 2 and 4 weeks of each treatment. RESULTS: The results of AMP challenge (provocative concentration causing a 20% fall in FEV(1)) at 4 weeks showed significant (p<0.05) improvements after patients had received all active treatments compared to placebo (20 mg/mL), with FM plus BUD, 261 mg/mL, being superior (p<0.05) to FM alone, 82 mg/mL, but not to BUD, 201 mg/mL. NO and ECP showed significant (p<0.05) reductions compared to placebo with FM plus BUD or BUD alone but not with FM alone. Combination therapy was associated with optimal patient preference (rank order, FM plus BUD > FM > BUD; p<0.0005), highest domiciliary peak expiratory flow, and lowest rescue inhaler usage. All three treatments produced equivalent improvements in spirometry. CONCLUSIONS: Patients preferred once-daily combination therapy, but this had no greater effect on inflammatory markers than therapy with BUD alone. FM alone had no anti-inflammatory activity but exhibited bronchoprotection. This emphasizes the importance of first optimizing anti-inflammatory control with inhaled corticosteroids before considering adding a regular long-acting beta(2)-agonist.

Adenosine Monophosphate↗
PubMed1999

Comparative trough effects of formoterol and salmeterol on lymphocyte beta2-adrenoceptor--regulation and bronchodilatation.

OBJECTIVES: The primary aim of the present study was to evaluate comparative trough effects of formoterol and salmeterol on beta2-adrenoceptor regulation and bronchodilator response after regular twice-daily treatment, with a secondary aim to evaluate any possible association with beta2-adrenoceptor polymorphism. METHODS: Sixteen asthmatic subjects, with mean (SD) age 33(9) years, all taking inhaled corticosteroids and with a forced expiratory volume in 1 s (FEV1) of 81(12)% predicted were recruited to take part in a randomised single-blind, three-way cross-over study. The subjects received three treatments each for 1 week, with 1-week washout periods in between: (1) formoterol dry powder, 12 microg twice daily, (2) salmeterol dry powder, 50 microg twice daily, or (3) placebo, twice daily. Spirometry and lymphocyte beta2-adrenoceptor parameters were measured before the first dose and 12 h after the last dose of each treatment, as well as domiciliary peak flow during each treatment. RESULTS: There were no differences in beta2-adrenoceptor density (Bmax) between the three treatments prior to the first dose; whereas, after the last dose, Bmax was lower with both active treatments than with placebo, but was significant for salmeterol only--a 1.2-fold geometric mean fold difference (95% CI 1- to 1.4-fold), P = 0.04. Compared with placebo, there were n = 9 of 16 subjects with salmeterol and n = 6 of 16 with formoterol who had a greater than 15% fall in Bmax. Post-hoc trend analysis of polymorphism showed that the propensity for downregulation appeared to be related to the occurrence of an allelic substitution of glycine at codon 16-8 of 13 for salmeterol versus 5 of 13 for formoterol with a greater than 15% fall compared with placebo. There were no significant differences between salmeterol and formoterol in terms of mean or individual values for downregulation. There was evidence of persistent bronchodilator activity with both active treatments compared with placebo; this was significant for forced expiratory flow rate between 25% and 75% of vital capacity (FEF25-75)--the mean difference versus salmeterol was 0.39 1/s (95% CI 0.06-0.70), P = 0.02, and versus formoterol was 0.35 1/s (95% CI 0.16-0.53), P = 0.001. These effects were mirrored by significant improvements in morning peak flow rate compared with placebo--mean difference versus salmeterol was 24 1/min (95% CI 7-42), P = 0.01, and versus formoterol was 36 1/min (95% CI 25-48), P < 0.0001. CONCLUSION: There were no differences between regular treatment with formoterol and salmeterol in their effects on lymphocyte beta2-adrenoceptor regulation at the end of a 12-h dosing interval, with both drugs exhibiting a residual degree of bronchodilator activity at the same time point. Further studies to evaluate receptor regulation and bronchodilator response are required in susceptible patients who have the homozygous glycine-16 polymorphism.

Administration, Inhalation↗
PubMed1999

In vivo effect of albuterol on methacholine-contracted bronchi in conjunction with salmeterol and formoterol.

BACKGROUND: It has been shown in vitro that prior treatment with salmeterol and formoterol antagonizes the relaxant effect of albuterol in carbachol-contracted human bronchi. OBJECTIVES: The primary aim of this study was to evaluate whether there is a potential in vivo interaction between long- and short-acting beta2-agonists in the presence of increased airway tone induced by methacholine. In addition, a post hoc analysis was made to evaluate the effects of beta2-adrenoceptor polymorphisms. METHODS: Sixteen asthmatic subjects (mean age [+/-SD], 39 [13] years; FEV1, 81% [17%] of predicted value), all taking inhaled corticosteroids and having methacholine PD20 values of less than 500 micrograms, were randomized in double-blind, double-dummy, cross-over fashion to receive single doses of inhaled placebo, inhaled formoterol 12 micrograms, or inhaled salmeterol 50 micrograms followed 12 hours later by a single dose of inhaled albuterol 400 micrograms (low dose) or 1600 micrograms (high dose). Methacholine challenges were performed on each of 6 separate occasions 1 hour after albuterol. RESULTS: There was a greater numerical difference in geometric mean PD20 values between low- and high-dose albuterol after placebo dosing (671 micrograms vs 1080 micrograms, a 1.61-fold difference; P <.05) compared with low- and high-dose albuterol after formoterol dosing (660 micrograms vs 799 micrograms, a 1. 21-fold difference; P =.4), or after salmeterol dosing (568 micrograms vs 847 micrograms, a 1.49-fold difference; P =.055). PD20 values with high-dose albuterol in combination with formoterol or salmeterol were numerically lower than those found with high-dose albuterol in combination with placebo, but they were not significantly different. There was a significant difference between PD20 values with low-dose albuterol after dosing with formoterol (PD20 = 660 micrograms, a 1. 6-fold difference; P <.05) or with salmeterol (PD20 = 568 micrograms, a 1.9-fold difference; P <.05) compared with PD20 with high-dose albuterol after placebo dosing (PD20 = 1080 micrograms). Post hoc polymorphism analysis for pooled pretreatment with formoterol and salmeterol (excluding placebo pretreatment) showed significantly (P <.05) lower PD20 values with homozygous glycine-16 compared with heterozygous glycine/arginine-16 and significantly (P <.05) lower PD20 values with homozygous glutamate-27 compared with either heterozygous glutamate/glutamine-27 or homozygous glutamine-27. CONCLUSION: Compared with placebo, both salmeterol and formoterol caused a significant degree of antagonism of albuterol-induced bronchorelaxation in methacholine-contracted bronchi in vivo. This interaction could be caused by prolonged occupancy of airway beta2-adrenoceptors by long-acting beta2-agonists or by early tachyphylaxis 12 hours after a single-dose exposure. The degree of albuterol protection was also related to beta2-adrenoceptor polymorphism.

Adrenergic beta-Agonists↗
PubMed1999

A high dose of albuterol does not overcome bronchoprotective subsensitivity in asthmatic subjects receiving regular salmeterol or formoterol.

BACKGROUND: Regular treatment with inhaled, long-acting beta2 -agonists is associated with subsensitivity for bronchoprotective effects. It is not known whether a high dose of short-acting beta2 -agonist could overcome this subsensitivity. OBJECTIVES: The objective of this study was to investigate the acute effects of a high dose of inhaled albuterol on methacholine-induced bronchoconstriction in patients receiving regular treatment with salmeterol or formoterol. METHODS: Ten stable asthmatic subjects (mean age, 34 years; FEV1, 77% of predicted value), all taking inhaled corticosteroids (methacholine PD20 < 500 microg), were recruited into a randomized, single-blind, crossover study. After an initial 1-week run-in period, subjects underwent 3 separate treatment periods each of 9 days (separated by a washout of at least 5 days) comprising inhaled placebo twice daily, inhaled salmeterol dry powder 50 microg twice daily, or inhaled formoterol dry powder 12 microg twice daily. Methacholine challenge was performed 1 hour after the first dose and after 7 days of treatment. After 9 days of treatment, a third methacholine challenge was performed 1 hour after inhalation of a single 1600 microg dose of albuterol dry powder. RESULTS: There was significant (P <.001) improvement in geometric mean PD20 after the first dose of active treatment as compared with placebo (78 microg) versus salmeterol (266 microg, a 3.4-fold difference [95% CI 1.9 to 6.1]) and versus formoterol (318 microg, a 4.1-fold difference [95% CI 2.3 to 7.3]). This bronchoprotection diminished with regular treatment, although it remained significant (P <.01) compared with placebo (68 microg) versus salmeterol (144 microg, a 2.1-fold difference [95% CI 1.2 to 3.8]) and versus formoterol (230 microg, 3.4-fold difference [95% CI 1.9 to 6.2]). After 9 days, the protection afforded by a single dose of albuterol after placebo pretreatment (889 microg) was significantly (P =.005) higher in comparison with albuterol protection after salmeterol pretreatment (338 microg, a 2.7-fold difference [95% CI 1.1 to 6.8]) and after formoterol pretreatment (247 microg, a 3.6-fold difference [95% 1.4 to 9.1]). CONCLUSIONS: Thus in stable asthmatic subjects receiving regular salmeterol or formoterol, bronchoprotective subsensitivity was not overcome by administering a high dose of albuterol. Further studies are required to evaluate the clinical relevance of this pharmacologic phenomenon when albuterol is used in acute asthma.

Administration, Inhalation↗
PubMed1999

Effects of genetic polymorphism on ex vivo and in vivo function of beta2-adrenoceptors in asthmatic patients.

BACKGROUND: Genetic polymorphism determines agonist-induced down-regulation and desensitization of beta2-adrenoceptors. OBJECTIVES: The aim of the present study was to investigate the effects of genetic polymorphism on ex vivo (lymphocytes) and in vivo (bronchoprotection) function of beta2-adrenoceptors in asthmatic patients, having been washed out of previous beta2-agonist exposure. METHODS: Sixty patients with stable mild-to-moderate asthma were evaluated, with a post hoc analysis of genotype performed at end of study. Having withheld treatment with long-acting beta2-agonists for > or = 48 h and short-acting beta2-agonists for > or = 12 h, measurements of lymphocyte beta2-adrenoceptors were made for binding density, binding affinity, basal cyclic adenosine monophosphate (cAMP), and maximal cAMP response to isoproterenol (Emax). In addition, in 48 of these patients who were methacholine responsive (PD20 < 1,000 microg), the acute protective effect of formoterol as a 24-microg single dose (at 1 h) was also evaluated. Comparisons were made according to homozygous and heterozygous (Het) polymorphisms at codon 16 and codon 27. RESULTS: There were no significant differences in age, FEV1 percent predicted, or inhaled corticosteroid dose, when comparing mean values for polymorphisms at either codon-16 or codon 27. There were also no significant differences between polymorphisms for any of the measured lymphocyte beta2-adrenoceptor parameters apart from basal cAMP between Glu-27 and Het-27. Mean values for Emax (after-before isoproterenol as pmol/10(6) cells) were as follows: Gly-16 (3.4), Arg-16 (3.5), Het-16 (4.0), Glu-27 (3.9), Gln-27 (3.5), and Het-27 (3.7). Polylorphism had no significant effect on formoterol protection as doubling dose shift in methacholine PD20 (geometric mean): Gly-16 (5.3), Arg-16 (5.4), Het-16 (4.6), Glu-27 (5.3), Gln-27 (5.3), Het-27 (4.5). CONCLUSIONS: Our results show that genetic polymorphism at codon 16 or 27 does not influence stimulated coupling of lymphocyte beta2-adrenoceptors and similarly did not influence the degree of functional antagonism exhibited by formoterol. Thus, a single dose of beta2-agonist when used on demand affords equal protection against bronchoprotection regardless of genetic polymorphism.

Adenylyl Cyclases↗
PubMed1999

A bolus of inhaled budesonide rapidly reverses airway subsensitivity and beta2-adrenoceptor down-regulation after regular inhaled formoterol.

BACKGROUND: Subsensitivity of airway beta2-adrenoceptors develops readily in asthmatics receiving regular long-acting beta2-agonists. This subsensitivity may be rapidly reversed by using systemic corticosteroids. The purpose of the present study was to investigate whether the same acute facilitatory effects occur when using a bolus dose of inhaled corticosteroid. METHODS: Ten subjects with stable mild-to-moderate asthma, with a mean age of 27 years, mean (+/- SD) FEV1 of 2.95 L (0.94 L), 81% (15%) of predicted, all receiving inhaled corticosteroids, reactive to adenosine monophosphate (AMP) with a provocative concentration producing a 20% fall in FEV1 (PC20) < 200 mg/mL, were recruited into a randomized double-blind crossover study. The subjects received two separate 1-week treatment periods with formoterol dry powder, 24 microg bid, with an initial 1-week run-in and a 1-week washout period between the treatments. A single dose of placebo or budesonide turbuhaler, 1,600 microg, was taken in conjunction with the last dose of both treatment periods. AMP challenge was performed 2 h after the first and last dose of formoterol. Blood for lymphocyte beta2-adrenoceptor density (Bmax) was also measured before and after treatment with formoterol. RESULTS: There was no significant difference in the geometric mean PC20 after the first dose of formoterol comparing the two treatment periods: 362 mg/mL vs 391 mg/mL. The PC20 after the last dose of formoterol was significantly higher (p < 0.05) in conjunction with budesonide than with placebo: 427 mg/mL vs 99 mg/mL, amounting to a 4.3-fold difference (95% confidence interval [CI], 1.1 to 16.6). For comparison within each treatment period, there was significant subsensitivity (p < 0.05) between the first and last dose of formoterol when the latter was given with placebo: 391 mg/mL vs 99 mg/mL, a 3.9-fold fall (95% CI, 1.0 to 15.2), but not when the latter was given with budesonide: 362 mg/mL vs 427 mg/mL, a 1.2-fold rise (95% CI, 0.5 to 2.8). Lymphocyte 02-adrenoceptor density (geometric mean Bmax: fmol/10(6) cells) also showed significant down-regulation (p < 0.05) by formoterol given with placebo: preformoterol 2.53 vs postformoterol 1.91, but not by formoterol given with budesonide: preformoterol 2.43 vs postformoterol 2.67. The Bmax was significantly higher (p < 0.05) with formoterol + budesonide as compared to formoterol + placebo, amounting to a 1.40-fold difference (95% CI, 1.09 to 1.80). CONCLUSION: We have shown that a bolus dose of inhaled budesonide rapidly reverses subsensitivity to AMP bronchoprotection and associated beta2-adrenoceptor down-regulation in asthmatics taking regular formoterol. Further studies are indicated to assess whether high-dose inhaled corticosteroids should be administered as soon as possible along with beta2-agonists during an acute episode of bronchoconstriction.

Adenosine Monophosphate↗