Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma

Kerrebijn, K. F.; Essen-Zandvliet, E. E. M. Van; Neijens, H. J.

doi:10.1016/s0091-6749(87)80163-x

Cited by 404 publications

(119 citation statements)

References 13 publications

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“…Acutely, this property of (± )salbuta mol is masked by the bronchodilator action of (-)salbuta mol, but following sustained infusion of (±)salbuta mol over several days, increased sensitivity of the airways can be demonstrated to antigen (9) and to airway spas mogens (10). Such findings are consistent with clinical reports of exacerbation of airway hyperreactivity follow ing regular administration of (±)fenoterol (11), (±)ter butaline (12)(13)(14) and (±)salbutamol (15); loss of protec tion against constrictor stimuli despite persisting bron chodilator responses, as reported for (±)salbutamol (16) and (±)salmeterol (17); and intensification of late-onset reactions to inhaled allergen, as following inhalation of (±)rimiterol (18).…”

supporting

confidence: 89%

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

Hoshiko

Morley

1993

Japanese Journal of Pharmacology

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ABSTRACT-In guinea pigs passively sensitized to ovalbumin, sustained (6 days) subcutaneous infusion of (±)salbutamol (1 mg/kg/day) induced significant airway obstruction and heightened responsivity to airway spasmogens. Of these animals, a substantial proportion (78/235) were too responsive to injected spasmogens to permit infusion of ovalbumin or died following infusion of ovalbumin; yet there were few deaths (2/166) amongst the sensitized animals not exposed to (±)salbutamol.In comparison to the animals not exposed to (± )salbutamol, infusion of ovalbumin led to exaggerated responsivity of the airways to leukotriene C4, leukotriene E4, histamine, serotonin and acetylcholine, but not to prostaglandin F2a or bradykinin. The capacity of sustained exposure to high doses of (±)salbutamol to induce airway hyperreactivity to allergic mediators may account for an association between asthma death and regular, excessive use of sympathomimetics.

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supporting

confidence: 89%

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

Hoshiko

Morley

1993

Japanese Journal of Pharmacology

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“…While these results might reflect spontaneous change over time, they are in accordance with a well-known study by KERREBIJN et al [20], who investigated the effect of long-term treatment with ICS or β-agonists on the bronchial responsiveness in children with asthma. Twelve children aged 7-16 yrs, were treated with BUD 600 µg·day -1 and 7 with terbutaline for 6 months.…”

Section: Discussionsupporting

confidence: 91%

One year follow-up study of endocrine and lung function of asthmatic children on inhaled budesonide

Nikolaizik¹,

Preece²,

Warner³

1997

Eur Respir J

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To weigh the benefits and risks of long-term treatment, 12 children with moderately severe asthma were assessed in a follow-up study on budesonide 200 µg b.i.d.After 1 yr, the nocturnal cortisol production was significantly reduced by 19%, but no greater compared to 2 and 4 weeks of treatment. Growth and growth hormone levels were normal. Lung function tests were significantly better, not only versus baseline values but also versus 2 and 4 weeks of treatment.We conclude that systemic effects of inhaled corticosteroids in conventionally low doses do not accumulate with length of treatment, whilst lung function parameters will continue to improve. Therefore, inhaled corticosteroids once started in asthmatic children not controlled on other medications should be continued, but their use should be carefully considered and the minimal dose required to control the asthma employed. Eur Respir J 1997; 10: 2596-2601 Inhaled corticosteroids (ICS) are the principal drugs used in the management of moderate-to-severe childhood as well as adult asthma [1,2]. However, awareness of the possible systemic effects of ICS in children has been a source of concern, particularly when they are used in high doses [3]. Previous studies of the systemic effects of ICS have employed very insensitive techniques, such as the measurement of morning cortisol, and have failed to show any significant effect even at moderately high doses [4]. However, integrated overnight plasma cortisol concentrations or urinary-free cortisol have been suggested as more sensitive tests of reduced hypothalamic pituitary adrenal axis function and as being superior to stimulation tests [5,6].In a cross-sectional study of plasma cortisol measured every 20 min during sleep in 19 asthmatic children, we demonstrated that there was a dose-related effect of inhaled beclomethasone dipropionate (BDP) on overnight cortisol production, despite the fact that there was no difference in the height of the morning peak of cortisol [7]. As this study did not account for the effect of asthma itself, we conducted a subsequent prospective cross-over study of integrated plasma cortisol concentrations and urinary-free cortisol in 12 children commencing ICS for the first time. Both BDP or budesonide (BUD), at a dose of 200 µg b.i.d. for 2 weeks in randomized order, caused identical significant suppressive effects on overnight cortisol production [8]. We found similar suppression in a controlled study administering either a single dose of 400 µg of BUD in the evening to healthy adults, or administering 400 µg twice daily for 2 weeks [9].The above studies were of very short duration and there remained a concern that there might be a cumulative effect of continuing ICS over longer periods. Indeed, nocturnal serum cortisol production was reduced by 27% after 2 weeks and 35% after 4 weeks of treatment in the paediatric study, with similar apparent increases in effects in suppression of urinary-free cortisol (33 and 48%, respectively). We therefore, repeated the studies on the same patients af...

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“…The use of inhaled corticosteroids is also related to a decrease in eosinophil count [1,38] and in the severity of airway hyperresponsiveness [38,[39][40][41] in asthmatics. In some studies of COLD, inhaled corticosteroids have had a beneficial effect on FEV 1 [2,42], symptoms [1,2], and severity of airway responsiveness [2].…”

Section: Discussionmentioning

confidence: 99%

Chronic respiratory symptoms and airway responsiveness to methacholine are associated with eosinophilia in older men: the Normative Aging Study

Annema¹,

Sparrow²,

O’Connor³

et al. 1995

Eur Respir J

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C Ch hr ro on ni ic c r re es sp pi ir ra at to or ry y s sy ym mp pt to om ms s a an nd d a ai ir rw wa ay y r re es sp po on ns si iv ve en ne es ss s t to o m me et th ha ac ch ho ol li in ne e a ar re e a as ss so oc ci ia at te ed d w wi it th h e eo os si in no op ph hi il li ia a i in n o ol ld de er r m me en n: : T Th he e N No or rm ma at ti iv ve e A Ag gi in ng g S St tu ud dy y ABSTRACT: Identification of subsets of patients with chronic obstructive lung disease (COLD) in order to determine disease outcomes and, possibly, the effects of treatment is an area of clinical interest. At present, it remains unclear which patients with COLD are most likely to benefit from anti-inflammatory therapy. We investigated this question in a community-dwelling sample of men. In this study, the relationship of chronic respiratory symptoms, airway responsiveness to methacholine, and skin test reactivity to peripheral-blood eosinophil and neutrophil counts was examined among 894 male participants in the Normative Aging Study (mean age 60 yrs; range 41-90 yrs). The symptoms considered were asthma, persistent wheeze, dyspnoea, chronic cough and phlegm. Responsiveness to methacholine was defined as a provocative dose producing a 20% fall in forced expiratory volume in one second (PD 20 FEV 1 ) of ≤8.6 µmol, a positive skin test as a wheal diameter of ≥5 mm after subtraction of the diameter of any wheal reaction to a glycerin control, and eosinophilia as an eosinophil count of ≥275 cells·mm -3 in peripheral blood.Chronic symptoms (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.4-2.7), airway responsiveness (OR 1.7; CI 1.1-2.7), and the combination of symptoms and airway responsiveness (OR 3.4; CI 2.0-5.6) were positively and significantly related to peripheral-blood eosinophil counts. These relationships remained significant after adjustment for the effects of age and smoking, and after exclusion of asthmatic subjects. Symptoms and airway responsiveness combined were not significantly related to neutrophil counts.These data suggest that increased airway responsiveness to methacholine is associated with elevated peripheral-blood eosinophil counts in subjects with chronic respiratory symptoms. Asymptomatic subjects with increased airway responsiveness also have increases in peripheral-blood eosinophil counts.

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Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma

Cited by 404 publications

References 13 publications

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

One year follow-up study of endocrine and lung function of asthmatic children on inhaled budesonide

Chronic respiratory symptoms and airway responsiveness to methacholine are associated with eosinophilia in older men: the Normative Aging Study

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