Tumour necrosis factor(TNF)-a levels are elevated in airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to its pathogenesis. A guanine to adenine substitution at position -308 of the TNF-a gene promoter (TNF1/2) has been associated with chronic bronchitis of various aetiologies in a Taiwanese population. The authors performed a study investigating association of the polymorphism with smoking-related COPD in Caucasians.Frequencies of TNF1/2 alleles in 86 Caucasians (52 males) with COPD were compared with 63 (52 males) asymptomatic smoker/exsmoker control subjects and a population control of 199 (99 males) blood donors. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic deoxyribonucleic acid (DNA) obtained from peripheral blood.There were no significant differences in TNF1/2 allele frequencies between groups: 0.85/0.15 in COPD, 0.85/0.15 in smoker control subjects, 0.83/0.17 in population control subjects. Within the COPD group there was no association of TNF1/2 alleles with indices of airflow obstruction (% predicted forced expiratory volume in one second (FEV1) and % predicted FEV1/vital capacity ratio) nor gas transfer (% predicted carbon monoxide transfer coefficient and % predicted carbon monoxide diffusing capacity of the lung).It is concluded that: 1) the tumour necrosis factor gene promoter allele does not influence the risk of developing chronic obstructive pulmonary disease in a Caucasian population of smokers; and 2) there is no association of the tumour necrosis factor gene promoter genotype with severity of airflow obstruction nor degree of emphysema in chronic obstructive pulmonary disease. Eur Respir J 2000; 15: 281±284.
Abstractbronchodilatation, 1 reduction in diurnal variation in peak expiratory flow, improvement in Background -Salbutamol is the most widely prescribed short acting 2 agonist daytime and nocturnal symptoms, reduction in requirement for a short acting bronchodilator, 2 3and salmeterol is the first long acting inhaled 2 agonist. The dose equivalence of and increased quality of life 4 in asthmatic patients. Bronchodilatation 5 6 and protection salmeterol and salbutamol is disputed. Estimates of weight-for-weight dose ratio against non-specific bronchial challenge with histamine 7 or methacholine 8 are maintained for have ranged from 1:2 to 1:16. A study was undertaken to clarify the true dose ratio.at least 12 hours after a single dose of salmeterol compared with 4-6 hours after salbutamol. Methods -The bronchoprotection afforded against repeated methacholine chalSalmeterol and salbutamol have similar 2 receptor selectivity 9 but dose equivalence is lenge by inhaled salmeterol 25 g and 100 g and salbutamol 100 g and 400 g disputed, estimates of the weight-for-weight dose ratio ranging from 1:2 to 1:16 in single was compared in a randomised, double blind, placebo controlled, crossover trial. dose studies.5 7 10 11 In the light of continuing debate regarding a possible association between Subjects were 16 stable asthmatics with a baseline forced expiratory volume in one the use of 2 agonists and increasing asthma morbidity and mortality worldwide and consecond (FEV 1 ) of [65% predicted, screening concentration provoking a fall in FEV 1 cern about relative potencies of different agents, 12 it is important that the relative poof 20% (PC 20 FEV 1 ) of Ζ8 mg/ml, and a shift in PC 20 FEV 1 of more than two doubling tencies of these two drugs be defined.Increased responsiveness to non-specific concentration steps following inhalation of salbutamol 400 g. On five separate oc-bronchoconstrictor agents is a characteristic feature of clinical asthma 13 and inhaled hiscasions subjects underwent methacholine challenge before and 30 and 120 minutes tamine or methacholine bronchoprovocation tests are commonly used in diagnosis in patients after drug administration. PD 20 FEV 1 was calculated for each challenge. FEV 1 at 90 who present with vague or atypical symptoms. 14The aim of this placebo controlled study was minutes after drug administration was also recorded.to compare the potency of salmeterol and salbutamol in asthmatic subjects by measurement Results -Bronchoprotection afforded by salmeterol was increased at 120 minutes of the protection afforded by salmeterol 25 g and 100 g and salbutamol 100 g and 400 g compared with 30 minutes and protection by salbutamol was decreased. Protection against repeated methacholine challenge. The
Frusemide attenuates propranolol-induced bronchoconstriction, a property shared with sodium cromoglycate. Both drugs block other indirect challenges and the present study lends further support to the suggestion that frusemide and cromoglycate share a similar mechanism of action in the airways.
Atrial natriuretic peptide (ANP) causes mast cell degranulation in rats in vivo and in vitro but is bronchodilator in humans. The aim of this study was to investigate the wheal and flare dose-response to intradermal injection of a-human ANP in normal humans. Eight normal subjects received five 30 gl injections containing 1, 10, 39, 78, 117 pmol ANP and one each of normal saline, histamine 675 pmol and substance P 30 pmol. Maximum ANP flare response was greater but not significantly than that to saline at 1.55 ± 0.6 (mean ± s.e. mean) compared with 0.42 ± 0.17 cm2, but much less than to histamine 9.86 ± 0.97 or to substance P 12.5 ± 1.2. Maximum ANP wheal response was significantly greater than that to saline at 0.38 ± 0.08 compared with 0.18 ± 0.05 cm2 (difference between means 0.20, 95% CI 0.05, 0.35), but much less than to histamine 0.75 ± 0.06 or to substance P 1.05 ± 0.08 cm2. No dose-response to ANP was demonstrated, though responses to the highest dose differed significantly from those to the lowest dose studied. We conclude that human cutaneous responses to ANP differ from those of animals and that the skin is less responsive than other tissues in humans.
Lactose is commonly used as a carrier for inhaled drugs. Twenty healthy volunteers without respiratory symptoms inhaled seven different doses of lactose and a placebo (empty) dose through the four place Diskhaler® device, in order to determine the lowest dose that could be reliably sensed. The minimum dose for which all subjects reported taste or feel sensations was 10 mg. This has implications regarding the amount of carrier used in future drug delivery systems.
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