Roxithromycin Reduces the Degree of Bronchial Hyperresponsiveness in Children With Asthma

doi:10.1378/chest.106.2.458

Chest

Volume 106, Issue 2, August 1994, Pages 458-461

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We evaluated the effects of a new semisynthetic macrolide antibiotic, roxithromycin, on the bronchial hyperresponsiveness to histamine in children with asthma. Twelve hospitalized asthmatic children, aged 11 to 15 years (mean age, 12.9 years), were enrolled in this study. They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects. The PC20 value 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p<0.05, p<0.01, respectively). No significant change was observed in serum theophylline concentrations during this study. Serum cortisol level in the morning did not change after the administration of roxithromycin for 4 weeks. These results suggest that administration of roxithromycin may act favorably in the treatment of childhood asthma.

Section snippets

Subjects

Twelve children with atopic or nonatopic asthma (8 boys and 4 girls, with a mean age of 12.9 years), institutionalized for long periods for the control of asthma, were enrolled in this study. Their mean hospitalized period was 1.6 years. The clinical diagnosis of bronchial asthma was based on a characteristic history of recurrent attacks of dyspnea with perceptible wheezing. The diagnosis was made after more than a year of follow-up. Causative allergens such as house dust mite were determined

Results

The mean values of PC20 in study patients were 0.62 ± 0.21 mg/ml (mean±SEM), 0.52 ± 0.22 mg/ml, 0.88 ± 0.29 mg/ml, and 1.73 ± 0.58 mg/ml before, and at 2, 4, and 8 weeks after the roxithromycin administration, respectively. Mean values of PC20 4 and 8 weeks after the drug administration were significantly higher than values before administration (p<0.05, p<0.01, respectively, Fig 1).

The results of baseline FEV₁ (percent of normal predicted) before and after the administration of roxithromycin

Discussion

We have shown that administration of roxithromycin reduces the bronchial hyperresponsiveness in children with asthma after the use of the drug for more than 4 weeks.

Bronchial hyperresponsiveness is a feature of asthma and possibly results from airway inflammation.¹²^,¹³ We have already reported a close relationship between the ability of polymorphonuclear leukocytes to generate active oxygen species and the degree of bronchial hyperresponsiveness to histamine in children with asthma.¹⁴ O’Byrne

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Antibiotics as Instigators of Microbial Dysbiosis: Implications for Asthma and Allergy
2018, Trends in Immunology
The human body and its resident microbiota form a complex ecosystem, shaped by both inherited and environmental factors. The use of antibiotics represents an extreme example of environmental pressure and can broadly disrupt the microbial landscape. The benefits that antibiotics have brought to modern medicine are unquestionable; however, their overuse comes with consequences, including the potential for secondary infections by opportunistic pathogens and the spread of antibiotic resistance. Here, we discuss the implications of microbial dysbiosis driven by antibiotics, with a focus on potential links with allergy and asthma. We review epidemiological data on humans, as well as mechanistic studies performed in animal models, and highlight gaps in current knowledge, which if addressed, could drive the design of novel therapeutic strategies and improved clinical care.
Additional treatment with clarithromycin reduces fever duration in patients with influenza
2014, Respiratory Investigation
Influenza virus infection-induced inflammatory responses are associated with fever and other symptoms. Although macrolide antibiotics (macrolides) provide anti-inflammatory effects, these effects have not been well studied in influenza patients.
We examined the effects of clarithromycin on influenza symptoms. A randomized, prospective, and open-label study was performed between December 2010 and March 2011 and between December 2012 and March 2013 in patients with pandemic A/H1 2009 influenza or seasonal influenza virus infections. Patients aged >15 years received either neuraminidase inhibitors (control group) or clarithromycin plus neuraminidase inhibitors (clarithromycin group). Body temperature and other symptoms were recorded for 5 days after initiating treatment. Serum interleukin (IL)-6 and IL-8 levels were also measured.
Herein, 79 patients were enrolled over the two influenza seasons, and data from 63 patients were analyzed. All patients showed fever and other symptoms, including rhinorrhea (n=38), cough (n=50), sore throat (n=39), arthralgia or myalgia (n=46), and general malaise (n=50). Fever duration was approximately 42% shorter in patients with temperatures ≥38.5 °C (p=0.02), decreasing from 42 h to 24 h. Among patients with pandemic influenza infections (n=20), the rhinorrhea improvement rate was higher in the clarithromycin group (p=0.03; 88% vs. 20%). Serum IL-6 levels decreased 5 days after treatment, but no differences between the two groups were detected.
Clarithromycin may have the additional clinical benefit of improving fever, the main symptom of influenza, in patients treated with neuraminidase inhibitors.
Why use long-term macrolide therapy in pediatric pulmonology?
2014, Archives de Pediatrie
Les macrolides sont une des plus anciennes classes d’antibiotiques à large spectre. En plus de leur action antibactérienne, ils exercent une action anti-inflammatoire et immunomodulatrice. Depuis l’observation de bénéfices spectaculaires sur la fonction respiratoire et la survie de patients atteints de panbronchiolites diffuses, les macrolides ont été prescrits au long cours dans différentes maladies respiratoires chroniques. Cette mise au point examine les résultats des essais thérapeutiques ayant évalué les effets d’un traitement prolongé par macrolides dans le traitement de la mucoviscidose, des dilatations des bronches non liées à la mucoviscidose, et de l’asthme, ciblant plus particulièrement les études ayant inclus des enfants. De nouvelles indications des macrolides au long cours sont discutées, comme les affections parenchymateuses diffuses.
Macrolides are well-known antibiotics exerting antimicrobial as well as anti-inflammatory and immunomodulatory effects. Since the observation of a dramatic improvement in lung disease and survival in patients with diffuse panbronchiolitis, macrolides have been used over the long term in several chronic respiratory diseases. This review describes the results of trials that have evaluated long-term macrolides in the treatment of cystic fibrosis, non-cystic fibrosis bronchiectasis, and asthma, particularly focusing on the impact on children. It also provides new insights on the potential effects of macrolides on diffuse parenchymal lung diseases.
Role of long term antibiotics in chronic respiratory diseases
2013, Respiratory Medicine
Citation Excerpt :
Erythromycin, clarithromycin and troleandomycin have been reported to reduce methylpredinsolone clearance in asthmatics29–32 besides independently manifesting anti-inflammatory activity to those of corticosteroids and theophyllines. Roxithromycin and azithromycin do not inhibit the cytochrome P450 system, but still are effective in reducing bronchial hyperresponsiveness (BHR).33,34 Moreover macrolides by inhibiting IL-6 and IL-8 may possibly lead to improvements in FEV1 in asthmatics.35,36
Antibiotics are commonly used in the management of respiratory disorders such as cystic fibrosis (CF), non-CF bronchiectasis, asthma and COPD. In those conditions long-term antibiotics can be delivered as nebulised aerosols or administered orally. In CF, nebulised colomycin or tobramycin improve lung function, reduce number of exacerbations and improve quality of life (QoL). Oral antibiotics, such as macrolides, have acquired wide use not only as anti-microbial agents but also due to their anti-inflammatory and pro-kinetic properties. In CF, macrolides such as azithromycin have been shown to improve the lung function and reduce frequency of infective exacerbations. Similarly macrolides have been shown to have some benefits in COPD including reduction in a number of exacerbations. In asthma, macrolides have been reported to improve some subjective parameters, bronchial hyperresponsiveness and airway inflammation; however have no benefits on lung function or overall asthma control. Macrolides have also been used with beneficial effects in less common disorders such as diffuse panbronchiolitis or post-transplant bronchiolitis obliterans syndrome. In this review we describe our current knowledge the use of long-term antibiotics in conditions such as CF, non-CF bronchiectasis, asthma and COPD together with up-to-date clinical and scientific evidence to support our understanding of the use of antibiotics in those conditions.
A trial of clarithromycin for the treatment of suboptimally controlled asthma
2010, Journal of Allergy and Clinical Immunology
Citation Excerpt :
This occurred despite the fact that all participants were being treated concurrently with fluticasone and suggests that nonantibiotic effects of clarithromycin on airway smooth muscle functional or inflammatory phenotype can be seen even in patients treated with ICSs. The improvement in airway hyperresponsiveness with clarithromycin in patients with asthma already receiving ICSs is of interest, augments previous reports from small uncontrolled clinical studies,23,24 and supports previous observations that macrolides might modulate this effect through nonantimicrobial pathways including alteration of cholinergic signaling pathways or attenuation of endothelin-1 expression by airway epithelial cells.25-27 In addition, although clarithromycin did not have a beneficial effect on exhaled nitric oxide or asthma-specific quality of life, it was weakly associated with a reduction in the need for rescue albuterol use, both in PCR-negative subjects and in the population as a whole.
PCR studies have demonstrated evidence of Mycoplasma pneumoniae and Chlamydophila pneumoniae in the lower airways of patients with asthma.
To test the hypothesis that clarithromycin would improve asthma control in individuals with mild-to-moderate persistent asthma that was not well controlled despite treatment with low-dose inhaled corticosteroids.
Adults with an Asthma Control Questionnaire score ≥1.5 after a 4-week period of treatment with fluticasone propionate were entered into a PCR-stratified randomized, controlled trial to evaluate 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.
A total of 92 participants were randomized. Twelve (13%) subjects demonstrated PCR evidence of M pneumoniae or C pneumoniae in endobronchial biopsies; 80 were PCR-negative for both organisms. In PCR-positive participants, clarithromycin yielded a 0.4 ± 0.4 unit improvement in the Asthma Control Questionnaire score, with a 0.1 ± 0.3 unit improvement in those allocated to placebo. This between-group difference of 0.3 ± 0.5 (P = .6) was neither clinically nor statistically significant. In PCR-negative participants, a nonsignificant between-group difference of 0.2 ± 0.2 units (P = .3) was observed. Clarithromycin did not improve lung function or airway inflammation but did improve airway hyperresponsiveness, increasing the methacholine PC₂₀ by 1.2 ± 0.5 doubling doses (P = .02) in the study population.
Adding clarithromycin to fluticasone in adults with mild-to-moderate persistent asthma that was suboptimally controlled by low-dose inhaled corticosteroids alone did not further improve asthma control. Although there was an improvement in airway hyperresponsiveness with clarithromycin, this benefit was not accompanied by improvements in other secondary outcomes.
Clarithromycin suppresses airway hyperresponsiveness and inflammation in mouse models of asthma
2009, European Journal of Pharmacology
Macrolide antibiotics, a class of potent antimicrobials, also possess immunomodulatory/anti-inflammatory properties. These properties are considered fundamental for the efficacy of macrolide antibiotics in the treatment of diffuse panbronchiolitis and cystic fibrosis. In patients with asthma, macrolide antibiotics have been reported to reduce airway hyperresponsiveness and improve pulmonary function. However, their beneficial actions in asthmatics possibly could be attributed to antimicrobial activity against atypical pathogens (e.g. Chlamydia pneumoniae), corticosteroid-sparing effect (inhibition of exogenous corticosteroid metabolism), and/or their anti-inflammatory/immunomodulatory effects. In order to investigate whether efficacy of macrolide antibiotics in asthma results from their immunomodulatory/anti-inflammatory activity, the influence of clarithromycin pretreatment (2 h before challenge) was examined on ovalbumin-induced airway hyperresponsiveness and airway inflammation in the mouse. Clarithromycin treatment (200 mg/kg intraperitoneally) decreased IL-4, IL-5, IL-13, CXCL2 and CCL2 concentrations in bronchoalveolar lavage fluid and markedly reduced inflammatory cell accumulation in bronchoalveolar lavage fluid and into the lungs, as revealed by histopathological examination. Furthermore, clarithromycin-induced reduction in inflammation was accompanied by normalization of airway hyperresponsiveness. In summary, in ovalbumin-induced mouse models, clarithromycin efficiently inhibited two important pathological characteristics of asthma, airway hyperresponsiveness and inflammation. These data suggest that the efficacy of clarithromycin, as well as of other macrolide antibiotics, in asthmatic patients could be attributed to their anti-inflammatory/immunomodulatory properties, and not only to their antimicrobial activity or exogenous corticosteroid-sparing effects.

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: Revision accepted December 21

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Clinical Investigations: AsthmaRoxithromycin Reduces the Degree of Bronchial Hyperresponsiveness in Children With Asthma

Section snippets

Subjects

Results

Discussion

J Allergy Clin Immunol

J Allergy

J Allergy Clin Immunol

Chest

Chest

J Invest Dermatol

J Invest Dermatol

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

Clinical Investigations: Asthma
Roxithromycin Reduces the Degree of Bronchial Hyperresponsiveness in Children With Asthma