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  • 1
    Electronic Resource
    Electronic Resource
    Allergen-induced increase in non-allergic bronchial reactivity (1977)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 7 (1977), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19–40% FEV1 fall) in all thirteen, additional definite late asthmatic responses (17–29% FEV1 fall) in four, and equivocal late asthmatic responses (5–11% FEV1 fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1977.tb01481.x
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  • 2
    Electronic Resource
    Electronic Resource
    Appearance of allergen-induced increases in airway responsiveness only after repeated allergen inhalations in two subjects (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 19 (1989), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Observations in two subjects undergoing three allergen challenges for a drug study suggested ‘priming’ of the late sequelae, namely allergen-induced increase in airway responsiveness. Both subjects had rhinitis and asthma limited to the ragweed season, near normal out-of-season histamine PC20, and extreme IgE sensitivity to ragweed. Both had an isolated early response with no change in histamine PC20 after the first allergen challenge. Significant (3.5- to 5.8-fold) reductions in histamine PC20 occurred after the second and third allergen challenge in Subject 1, and after the third challenge in Subject 2; this was associated with equivocal 5–8% late responses. Such a ‘priming’ effect, the prevalence of which is not known, may be important in the pathogenesis of naturally occurring allergic asthma, and in the design of clinical trials involving repeated allergen inhalations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1989.tb02368.x
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  • 3
    Electronic Resource
    Electronic Resource
    Familial atopy in Australian pedigrees: adventitious linkage to chromosome 8 is not confirmed nor is there evidence of linkage to the high affinity IgE receptor (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 24 (1994), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Atopy frequently displays autosomal dominant inheritance and recent studies have favoured genetic linkage between atopy and the human chromosome 11q13. We have studied 12 extended families with aggregation of atopy consistent with autosomal dominant inheritance. The families have been studied for linkage of asthma and atopy to loci on chromosome 8p following the observation that one family suggested preliminary evidence of linkage to an anonymous hypervariable locus cloned from a DNA fingerprint and mapped to 8pter-p22. Subsequent analysis shows this putative linkage to be adventitious as the remaining 11 families do not support linkage between atopy and 8p, We have analysed the same families for evidence of linkage of atopy to loci on 11q13. In these families there is no evidence of association between atopy and the 11q loci stronger than that expected by chance alone; furthermore there is no suggestion subpopulation of these families display linkage between atopy and the loci. In addition neither the 8p loci nor the 11q loci exhibit evidence of linkage to atopy by affected sib-pair analysis. This also conflicts with previously published data for 11q.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1994.tb01809.x
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of Sch1000 in allergen-induced asthma (1978)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 8 (1978), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Carefully controlled allergen inhalation tests were carried out in twelve subjects to provoke early asthmatic responses with a mean maximum FEV1 fall of 30·7 ± 5·2% (mean ± s.d.). Four subjects had additional late asthmatic responses with a maximum mean FEV1 fall of 21·0 ± 5·9%. The tests were repeated at intervals of 7 days in an identical way, following inhalation of Sch1000 (80 μg) and placebo, each given 45 min before the onset of the early asthmatic response. This dose of Sch1000 produced a marked and uniform inhibition of methacholine-induced bronchoconstriction in the same subjects. The allergen-induced responses were reproducible in eleven out of the twelve subjects; the coefficient of variation for the decrease in FEV1 in the early responses being ±7% and in the late response ±43%. Sch1000 produced a slight and variable inhibition of early asthmatic responses (P〈0·02) and no inhibition of late asthmatic responses. We examined the relationship between the degree of inhibition of the early asthmatic response by Sch1000 and: (a) the degree of inhibition produced by Sch1000 on histamine- and methacholine-induced bronchoconstriction; (b) the level of non-specific bronchial reactivity measured by inhaled histamine and methacholine; and (c) the degree of bronchodilatation produced by Sch1000. No relationship was found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1978.tb00471.x
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  • 5
    Electronic Resource
    Electronic Resource
    Inhibition of allergen-induced asthma by three forms of sodium cromoglycate (1981)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 11 (1981), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effect of three forms of sodium cromoglycate (SCG), 20 mg, on allergen-induced early asthmatic responses was examined in ten stable asthmatics. Dose response allergen inhalation tests were performed on five occasions at intervals of from 1 to 2 weeks to determine the provocation concentration producing a 20% reduction (PC20 allergen) in FEV1. Placebo was given before the first and the last tests to determine the reproducibility of responses to allergen over the study period; reduced responsiveness was observed in eight of the ten subjects. Major changes in levels-of specific serum antibodies of the IgE and IgG classes did not serve to explain the changes in bronchial responses although there was a trend which suggested IgG-related desensitization. The observed changes in bronchial responses and antibody levels illustrate the requirement for tests of reproducibility of responses by the use of placebo controls at the beginning and end of a series of allergen inhalation challenges.SCG as (i) a micronized powder with lactose, (ii) micropellets without lactose, or (iii) an aerosol, were inhaled double-blind, in random order, 5 min before the additional three allergen inhalation tests. PC20 allergen was reduced following SCG in seven subjects; the differences were statistically significant for the group. There was no observed difference in efficacy between the different forms of SCG. In this study, the efficacy of SCG could not be related to age, atopic status, the initial level of allergen-specific IgE antibody, baseline FEV1, level of bronchial responsiveness to inhaled histamine or an effect of SCG on responsiveness to histamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1981.tb01568.x
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  • 6
    Electronic Resource
    Electronic Resource
    THE EFFECT OF INHALED FENOTEROL AND IPRATROPIUM BROMIDE ON PROPRANOLOL INDUCED BRONCHOCONSTRICTION IN THE ASTHMATIC AIRWAYS (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 17 (1990), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The provocative dose of inhaled propranolol, (PC20P, mg/mL) needed to induce a 20% reduction in the forced expired volume in 1 s (FEV1, L) was determined for 15 adult asthmatics following randomized pre-treatment with placebo, ipratropium bromide (40, 160 μg) and fenoterol (200, 800 μg) aerosols using a double-blind protocol.2. Fenoterol 200 μg, 800 μg increased the baseline FEV1 0.28±0.16, 0.32±0.16 L (P= 0.04, P= 0.008 respectively). Fenoterol 800 μg moved the PC20P rightwards from placebo geometric mean 10.95, 95% Confidence Intervals (95% CI) 4.43–27.22 mg/mL to mean 20.41, 95% CI 10.13 to 40.64 mg/mL (P= 0.01). Fenoterol 200 μg was not protective; mean PC20 16.22, 95% CI 7.83–34.35 mg/mL (P= 0.08). Neither 40 or 160 μg ipratropium changed the FEV1 or PC20P values compared with placebo; increase in FEV1 0.15±0.27 L (P= 0.22), 0.24±0.12 L (P= 0.14) and geometric mean PC20P 16.59±0.57 mg/mL 95% CI 8.01–34.51 mg/mL (P= 0.90), 15.48±0.66 mg/mL, 95% CI 6.72–36.05 mg/mL (P= 0.34) respectively after ipratropium treatments.3. Bronchoconstriction induced by inhaled propranolol (P) appears to be only weakly antagonized by inhaled β-agonist and not reduced by antimuscarinic anticholinergic aerosol. This finding argues against the activation of a cholinergic reflex to explain propranolol induced bronchoconstriction (PIB).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1990.tb01363.x
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  • 7
    Electronic Resource
    Electronic Resource
    THE EFFECT OF TRIFLUOPERAZINE ON BRONCHIAL RESPONSIVENESS IN ASTHMA (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 15 (1988), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The protective effects of oral trifluoperazine (TFP) (7mg) against standardized methacholine and histamine inhalation tests (MIT and HIT) were examined 2 and 22 h post-treatment in eight stable asthmatics using a randomized double-blind protocol.2. A preliminary study tested whether a preceding MIT influenced the result of a subsequent HIT.3. The mean baseline forced expiratory volumes in 1 s (FEV1) were similar prior to placebo and TFP. The mean FEV1 values 2 h after ingestion of placebo or TFP were not different from the baseline values.4. TFP did not alter bronchial responsiveness to inhaled methacholine or histamine 2 h postingestion, but at 22 h the PC20 methacholine was greater than placebo, while PC20 histamine did not change. This change in methacholine responsiveness was not clinically significant.5. There was a correlation between geometric mean provocative concentration of histamine to cause 20% fall in FEV (PC20H) for HIT performed in isolation ('separate day') and for HIT performed after MIT (‘same day’).6. The effect of inhaled TFP (10 mg/ml, nebulized for 5 min) was examined single-blind and placebo-controlled in a separate group of six stable asthmatics.7. Inhaled TFP had a bronchoconstrictor effect in all six asthmatics. The mean fall in FEV1 was 36.4% after inhaled TFP and 2.1% after saline.8. In the asthmatics studied, ingested TFP exhibited a weak anticholinergic effect 22 h pest-treatment, but a brisk spontaneously self reverting bronchoconstrictor response was invariably seen when TFP was inhaled.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1988.tb01101.x
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  • 8
    Electronic Resource
    Electronic Resource
    COMBINED BRONCHODILATOR PROTECTION AGAINST HISTAMINE-INDUCED BRONCHOCONSTRICTION IN MAN (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 14 (1987), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY1. Sixteen stable asthmatics had the protective effects of inhaled fenoterol (200 μg) and inhaled ipratropium bromide (60 μg) against standardized histamine inhalation tests at 1 h examined in a randomized double blind fashion.2. There was no significant difference in the baseline forced expired volume in 1 s (FEV1) for the two study days (P 〉0.05).3. There was an increase in FEV, at 1 h on the fenoterol and ipratropium day compared with the fenoterol day (0.26 versus 0.17 1; P 〈 0.05).4. The geometric mean provocative concentration of histamine to cause a 20% fall in FEV, (PC20) was 6.31 mg/ml after fenoterol and 8.51 mg/ml after fenoterol and ipratropium (P= 0.038).5. There was no significant relationship between bronchodilator effect of the bronchodilators and the increase in PC20 from pre-study values, r= 0.307 (P=0.25) for fenoterol alone and r=0.195 (P=0.47) for fenoterol and ipratropium.6. The relationship between pre-study histamine responsiveness and the increase in PC20 caused by the bronchodilators just failed to reach statistical significance, r= -0.441 (P= 0.09) for fenoterol alone and r= -0.47 (P=0.06) for fenoterol and ipratropium.7. The study has shown a greater right shift of histamine responsiveness for combined inhaled fenoterol and ipratropium compared with inhaled fenoterol alone in this group of asthmatics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1987.tb00961.x
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  • 9
    Electronic Resource
    Electronic Resource
    The effect of hypoxaemia on drug disposition in chronic respiratory failure (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 77-82 
    Details
    ISSN: 1432-1041
    Keywords: Key words Hypoxaemia ; Pharmacokinetics ; Pharmacodynamics; frusemide ; paracetamol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The influence of hypoxaemia on the disposition of two common drugs has been examined in ten adults with stable chronic respiratory failure. Methods: There were two experimental periods in this cross-over study: during these periods supplemental oxygen was either withheld or administered to impose clinical hypoxaemia or maintain normoxaemia, respectively. Each participant received either oral (40 mg) or intravenous (20 mg) frusemide combined with oral paracetamol (500 mg) on consecutive days of the two experimental periods. Results: The total (bound plus unbound) plasma clearance of frusemide during hypoxaemia (arterial oxygen tension, PaO2 ≤ 50 Torr) was not significantly different from the value during normoxaemia (PaO2 ≥ 60 Torr) [76.9 and 62.4 ml ⋅ min−1]. The volume of distribution was not affected by acute hypoxaemia (121 ml ⋅ kg−1 without and 109 ml ⋅ kg−1 with oxygen; P 〉 0.05). Renal and non-renal clearances of frusemide were similar during the period of hypoxaemia (31 and 38 ml ⋅ min−1, respectively) compared to respective values during supplemental oxygen delivery (29 and 32 ml ⋅ min−1). The absolute bioavailability of frusemide during hypoxaemia (0.62) was not different to that obtained during normoxaemia (0.56). The combined sodium and potassium excretion rate (expressed as a function of the frusemide excretion rate) was not altered by changing the oxygen tension. The pharmacokinetics of paracetamol were unaffected by hypoxaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050072
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  • 10
    Electronic Resource
    Electronic Resource
    The effect of bucindolol on the airway function of asthmatics (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 559-565 
    Details
    ISSN: 1432-1041
    Keywords: bucindolol ; asthma ; bronchoconstriction ; airway function ; histamine responsiveness ; bronchodilator responsiveness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The airway and cardiovascular effects of separate single oral doses of 50, 100 and 200 mg of bucindolol were compared to those of placebo in a double-blind trial in 16 patients with mild to moderately severe asthma. Heart rate (HR), blood pressure (BP), forced vital capacity (FVC), forced expired volume in one second (FEV1), maximum expiratory flow at 50% of vital capacity (FEF50) and maximum expiratory flow at 75% of expired vital capacity (FEF75) were measured before and at intervals for 4 h, when salbutamol (200 µg) was inhaled and the measurements repeated 15 min later. There was an interval of at least 4 days between each drug treatment day. Four of the 16 patients developed clinically significant bronchoconstriction with 50 mg (3) or 100 mg (1) of bucindolol and were withdrawn from the study. The remaining patients showed impaired bronchodilator response to salbutamol for each bucindolol dose as compared to placebo. No significant BP or HR effects were measured. Two patients withdrew because of circumstances unrelated to bucindolol induced bronchoconstriction. The development of bucindolol induced bronchoconstriction in this group of mild to moderate asthmatics was not predicted by the level of baseline pulmonary function, or the level of histamine responsiveness. However, there was a weak relationship between bucindolol induced bronchoconstriction and salbutamol induced bronchodilation. There was no definitive asthmatic characteristic to predict the likelihood of significant bucindolol induced bronchoconstriction in this asthmatic population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542415
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