Growth And The Growth Hormone-Insulin Like Growth Factor 1 Axis In Children With Chronic Inflammation:Current Evidence, Gaps In Knowledge And Future Directions

Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt is often seen during adolescence. The underlying inflammatory state mediated by pro-inflammatory cytokines, prolonged use of glucocorticoid and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the growth hormone-insulin like growth factor axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate studies further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biologic therapy may lead to improvement of growth in some of these children but approximately one third continue to grow slowly. There is increasing evidence that the use of relatively high dose recombinant human growth hormone may lead to partial catch up growth in chronic inflammatory conditions, although long term follow-up data is currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis, systemic abnormalities of the growth hormone-insulin like growth factor axis and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human growth hormone in these conditions and discuss the role of recombinant human insulin like growth factor-1

Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial

Background Asthma guidelines recommend that long-acting inhaled beta -agonists should be used as maintenance therapy for patients with asthma inadequately controlled on an inhaled corticosteroid. We studied the safety and efficacy of the long acting beta -agonist formoterol compared with terbutaline, each taken as needed, in patients with moderate to severe asthma. Methods Patients were taking an inhaled corticosteroid (mean dose 870 mug daily) and had a forced expiratory volume in 1 a (FEV1) of at least 50% predicted (mean 74%). Those requiring an inhaled beta -agonist three to eight times a day during the study run-in period (362 of 621 who started) were randomly assigned formoterol 4.5 mug or terbutaline 0.5 mg as needed by Turbuhaler in daily doses up to 54 mug and 6 mg, respectively, for 12 weeks in a double-blind, parallel-group study. Analyses were by intention to treat. Findings The 362 randomised patients (157 men, 205 women) had a mean age of 47 years. Patients taking formoterol had a longer time to their first severe asthma exacerbation (relative-risk ratio 0.55 [95% CI 0.34-0 8.9]), took fewer inhalations of study drug, and had larger increases in FEV1 (5%) and morning and evening peak expiratory flow (mean difference in increase 11 L/min and 8 L/min) than those taking terbutaline. No safety issues were identified. Interpretation When taken as needed, formoterol 4.5 mug provided better asthma control than terbutaline 0.5 mg in patients requiring moderate doses of relief medication despite inhaled corticosteroid treatment. Safety studies should be extended to a wider population of patients with asthma

Formoterol used as needed improves health-related quality of life in asthmatic patients uncontrolled with inhaled corticosteroids

AbstractClinical benefits have been shown to occur when using the long-acting β2-agonist formoterol 4.5μg for as-needed medication rather than terbutaline 500μg in patients with unstable asthma taking an inhaled corticosteroid. This study compared their effects on health-related quality of life and the relation with conventional clinical indices in the same population. 362 asthmatics were randomized to use either formoterol 4.5μg or terbutaline 500μg as needed, both inhaled via Turbuhaler®. The Asthma Quality of Life Questionnaire (AQLQ) was practised at enrolment and completed by 341 patients after randomization and at 4, 8, and 12 weeks. Clinical indices were measured at the same time points. Mean overall AQLQ scores were comparable at baseline, being 4.90 in the formoterol and 4.82 in the terbutaline group and improved during treatment by 0.41 and 0.17 units, respectively (mean difference 0.24, 95% CI 0.08, 0.39, P<0.005). Mean improvement in the symptom domain was 0.49 units when using formoterol. Correlations between changes in clinical indices and changes in AQLQ scores during the 12-week period were weak (maximum r value=0.37). When used for as-needed medication, formoterol 4.5μg provided an improvement in asthma-specific quality of life and to a somewhat greater extent than the widely used terbutaline 500μg. The symptom domain in AQLQ showed almost 0.5 units improvement after formoterol, a change that is considered to be clinically relevant

Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial

BACKGROUND: Asthma guidelines recommend that long-acting inhaled beta-agonists should be used as maintenance therapy for patients with asthma inadequately controlled on an inhaled corticosteroid. We studied the safety and efficacy of the long-acting beta-agonist formoterol compared with terbutaline, each taken as needed, in patients with moderate to severe asthma. METHODS: Patients were taking an inhaled corticosteroid (mean dose 870 microg daily) and had a forced expiratory volume in 1 s (FEV1) of at least 50% predicted (mean 74%). Those requiring an inhaled beta-agonist three to eight times a day during the study run-in period (362 of 621 who started) were randomly assigned formoterol 4.5 microg or terbutaline 0.5 mg as needed by Turbuhaler in daily doses up to 54 microg and 6 mg, respectively, for 12 weeks in a double-blind, parallel-group study. Analyses were by intention to treat. FINDINGS: The 362 randomised patients (157 men, 205 women) had a mean age of 47 years. Patients taking formoterol had a longer time to their first severe asthma exacerbation (relative-risk ratio 0.55 [95% CI 0.34-0.89]), took fewer inhalations of study drug, and had larger increases in FEV1 (5%) and morning and evening peak expiratory flow (mean difference in increase 11 L/min and 8 L/min) than those taking terbutaline. No safety issues were identified. INTERPRETATION: When taken as needed, formoterol 4.5 microg provided better asthma control than terbutaline 0.5 mg in patients requiring moderate doses of relief medication despite inhaled corticosteroid treatment. Safety studies should be extended to a wider population of patients with asthma