Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma

Kamada, Alan K.; Hill, Malcolm; Iklé, David; Brenner, Anne Manon; Szefler, Stanley J.

doi:10.1016/0091-6749(93)90345-g

Cited by 92 publications

(67 citation statements)

References 15 publications

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“…Three clinical trials examined the use of macrolides recruited in pediatric and adolescent individuals, 73,74,76 of which two included individuals with severe asthma. 73,74 One trial (of individuals 6-17 years of age) included individuals requiring maintenance oral corticosteroids and found that troleandomycin allowed for a greater decrease in the oral corticosteroid dose.…”

Section: Efficacy Adolescent and Pediatric Individualsmentioning

confidence: 99%

“…There was no subgroup analysis by asthma severity and only five studies included individuals who would be classified as having severe asthma. 36,42,[73][74][75] Since the publication of that review, one additional RCT was published. 36 This trial included 420 individuals, which is a larger sample size than in the trials included in the above-mentioned Cochrane review.…”

Section: Introductionmentioning

confidence: 99%

“…A small pediatric study 73 reported that troleandomycin allowed for a greater reduction in oral methylprednisolone compared to placebo. In contrast, a larger adult study found that the use of troleandomycin did not allow for a decrease in oral corticosteroid dose compared to placebo, although both groups showed a decrease from baseline corticosteroid dose.…”

mentioning

confidence: 99%

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Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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RATIONALE: While severe asthma affects approximately 5% of all individuals with asthma, this small minority of individuals accounts for a large proportion of the asthma-related costs. Greater understanding of the pathophysiology of asthma combined with the emergence of novel biologic therapies for severe asthma supported the need for a thorough review of the diagnosis, investigation, phenotyping, and management of severe asthma. OBJECTIVES: We aimed to propose a practical approach to distinguish uncontrolled asthma due to inadequate asthma management from severe asthma despite optimal asthma management. Moreover, based on emerging scientific evidence, we sought to provide guidance for characterizing individuals with severe asthma and considering a phenotype-specific management. We also aimed to review other novel new potential therapeutic approaches. METHODS: We systematically reviewed the relevant literature focusing on randomized controlled trials and when available, systematic reviews of randomized controlled trials. The proposed key messages, based on scientific evidence and expert opinion, were agreed upon by unanimous consensus. MAIN RESULTS: We defined severe asthma and outlined its significant impact from the societal and patient perspectives. We outlined a practical approach to distinguish severe from uncontrolled but not severe asthma, based on stepwise investigation and management of potential reasons for uncontrolled asthma. After reviewing the current evidence we concluded that: 1) Several biomarkers (e.g. sputum or blood eosinophil count, total IgE, or FeNO) can help identify potential responders to new therapeutic options; 2) Tiotropium may be considered as an add-on therapy for individuals 12 years of age and over with severe asthma uncontrolled despite combination ICS/LABA therapy; 3) The chronic use of macrolides may decrease asthma exacerbations in individuals 18 years of age and over with severe asthma independent of their inflammatory profile; 4) Children aged 6 years and older and adults who are sensitized to at least one relevant perennial allergen and who remain poorly controlled asthmatics despite high dose ICS and a second controller can benefit from the addition of anti-IgE therapy to reduce asthma exacerbations; due to the known risk of side effects associated with high-dose ICS in children, omalizumab should also be considered in children and adolescents who repeatedly exacerbate or have poor control when therapy is stepped down from high-dose to moderate-dose ICS and at least one other controller; 5) Anti-IL5 therapies may be considered for adults 18 years of age and over with severe eosinophilic asthma who experience recurrent asthma exacerbations in spite of high doses of ICS in addition to at least one other controller; and 6) Although bronchial thermoplasty has shown a decrease in asthma exacerbations in one study, its role in the treatment of severe asthma remains uncertain. CONCLUSIONS: After reviewing existing and emerging therapies for severe asthma, we developed ke...

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Section: Efficacy Adolescent and Pediatric Individualsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

View full text Add to dashboard Cite

show abstract

“…Early studies have reported conflicting results [53][54][55][56][57]. Recently, SUTHERLAND et al [58] evaluated the effect of 16 weeks of either clarithromycin or placebo, added to fluticasone, on asthma control in individuals with or without lower airway PCR evidence of M. pneumoniae or C. pneumoniae.…”

Section: Asthmamentioning

confidence: 99%

Long-term macrolide treatment for chronic respiratory disease

2012

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Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert antiinflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain.With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials. @ERSpublications Several studies evaluating macrolide antibiotics for the treatment of chronic respiratory diseases are underway

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“…[3][4][5] Macrolide and ketolide antibiotics have been specifically evaluated because they are believed to have anti-inflammatory actions [6][7][8][9] in addition to their antimicrobial activity, which includes effectiveness against Mycoplasma pneumoniae and Chlamydophila pneumoniae, "atypical bacteria" that commonly infect the respiratory tract. [10][11][12][13] The studies evaluating antibiotics as an asthma therapy have mixed results, showing inconsistent evidence of benefit, although common bacterial pathogens (eg, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) are frequently present in the airways of wheezing children. 14 In accordance, neither US 2 nor international 15 guidelines for asthma management currently recommend antibiotic treatment for asthma exacerbations.…”

mentioning

confidence: 99%

Antibiotic Prescribing During Pediatric Ambulatory Care Visits for Asthma

et al. 2011

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OBJECTIVE: National guidelines do not recommend antibiotics as an asthma therapy. We sought to examine the frequency of inappropriate antibiotic prescribing during US ambulatory care pediatric asthma visits as well as the patient, provider, and systemic variables associated with such practice. PATIENTS AND METHODS: Data from the National Ambulatory Medical Care Surveys and National Hospital Ambulatory Medical Care Survey were examined to assess office and emergency-department asthma visits made by children (aged <18 years) for frequencies of antibiotic prescription. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to assess the presence of coexisting conditions warranting antibiotics. Multivariable logistic regression models assessed associations with the prescription of antibiotics. RESULTS: From 1998 to 2007, an estimated 60.4 million visits occurred for asthma without another ICD-9 code justifying antibiotic prescription. Antibiotics were prescribed during 16% of these visits, most commonly macrolides (48.8%). In multivariate analysis, controlling for patient age, gender, race, insurance type, region, and controller medication use, systemic corticosteroid prescription (odds ratio [OR]: 2.69 [95% confidence interval (CI): 1.68–4.30]) and treatment during the winter (OR: 1.92 [95% CI: 1.05–3.52]) were associated with an increased likelihood of antibiotic prescription, whereas treatment in an emergency department was associated with decreased likelihood (OR: 0.48 [95% CI: 0.26–0.89]). A second multivariate analysis of only office-based visits demonstrated that asthma education during the visits was associated with reduced antibiotic prescriptions (OR: 0.46 [95% CI: 0.24–0.86]). CONCLUSIONS: Antibiotics are prescribed during nearly 1 in 6 US pediatric ambulatory care visits for asthma, ∼1 million prescriptions annually, when antibiotic need is undocumented. Additional education and interventions are needed to prevent unnecessary antibiotic prescribing for asthma.

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Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma

Cited by 92 publications

References 15 publications

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Long-term macrolide treatment for chronic respiratory disease

Antibiotic Prescribing During Pediatric Ambulatory Care Visits for Asthma

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