Long-term macrolide therapy in chronic obstructive pulmonary disease

Parameswaran, G. Iyer; Sethi, Sanjay

doi:10.1503/cmaj.121573

Cited by 15 publications

(13 citation statements)

References 35 publications

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“…There is growing evidence that certain antibiotics exert their clinically beneficial effects not only by killing or inhibiting the growth of bacterial pathogens, but also by their anti-inflammatory or immunomodulatory activities [ 36 ]. For instance, it is well known that the immunomodulatory properties of macrolide antibiotics have been used to successfully treat several chronic inflammatory lung disorders and improve the long-term outcome of patients with pulmonary disease [ 37 ]. Minocycline has a variety of biological properties that are independent of its anti-microbial activity, among which are the anti-inflammatory activity [ 25 , 26 ] and its ease in crossing the blood–brain barrier [ 38 ] because of its high lipid solubility [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can be downregulated by minocycline: possible implications for long-term treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis

Saito

Sejima

Naito

et al. 2017

Virol J

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BackgroundChemokine (C-C motif) ligand 1 (CCL1) is produced by activated monocytes/ macrophages and T-lymphocytes, and acts as a potent attractant for Th2 cells and a subset of T-regulatory (Treg) cells. Previous reports have indicated that CCL1 is overexpressed in adult T-cell leukemia cells, mediating an autocrine anti-apoptotic loop. Because CCL1 is also known as a potent chemoattractant that plays a major role in inflammatory processes, we investigated the role of CCL1 in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP).ResultsThe results showed that: (1) CCL1 was preferentially expressed in HAM/TSP-derived HTLV-1-infected T-cell lines, (2) CCL1 expression was induced along with Tax expression in the Tax-inducible T-cell line JPX9, (3) transient Tax expression in an HTLV-1-negative T-cell line activated the CCL1 gene promoter, (4) plasma levels of CCL1 were significantly higher in patients with HAM/TSP than in HTLV-1-seronegative patients with multiple sclerosis and HTLV-1-infected asymptomatic healthy carriers, and (5) minocycline inhibited the production of CCL1 in HTLV-1-infected T-cell lines.ConclusionsThe present results suggest that elevated CCL1 levels may be associated with the pathogenesis of HAM/TSP. Although further studies are required to determine the in vivo significance, minocycline may be considered as a potential candidate for the long-term treatment of HAM/TSP via its anti-inflammatory effects, which includes the inhibition of CCL1 expression.

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Section: Discussionmentioning

confidence: 99%

The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can be downregulated by minocycline: possible implications for long-term treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis

Saito

Sejima

Naito

et al. 2017

Virol J

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“…Usual initial empirical treatment is aminopenicillin with clavulanic acid, doxycycline or macrolide treatment due to their additional anti-inflammatory properties [36,102]. Studies suggest that long-term or intermittent antibiotic therapy may have a beneficial effect on the outcome of COPD patients and may improve quality of life by reducing exacerbation frequency or by prolonging time to next exacerbation through local and systemic effects [103][104][105][106][107]. Antibiotic therapy may reduce exacerbation frequency by eradicating colonising bacteria with the potential to cause infection, however there is limited information to support this hypothesis [35].…”

Section: The Role Of Antibioticsmentioning

confidence: 99%

New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways

et al. 2019

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Chronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD) drive clinical and functional decline in COPD and are associated with accelerated loss of lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and consequently constitute a significant comorbidity in COPD. However, current pharmacological interventions are ineffective in preventing infectious exacerbations and their treatment is compromised by the rapid development of antibiotic resistance. Thus, alternative preventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infection of surrounding structures. Thus, disruption of bacterial–host cell interactions with receptor antagonists or modulation of the ensuing inflammatory profile present attractive avenues for therapeutic development. This review explores key mediators of pathogen–host interactions that may offer new therapeutic targets with the potential to prevent viral/bacterial-mediated AECOPD. There are several conceptual and methodological hurdles hampering the development of new therapies that require further research and resolution.

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“…Macrolides are critical antibiotics for the treatment of both M. avium complex and M. abscessus complex pulmonary disease, and are one of the only oral antibiotics with activity against these difficult-to-treat species [107]. Unfortunately, long-term use is often associated with gastrointestinal intolerance, QT elongation, and reversible hearing impairment [108]. Two formulations of inhaled azithromycin have currently been reported—a nebulized formulation and a dry powder.…”

Section: Ongoing Drug Development Programsmentioning

confidence: 99%

Inhaled Antibiotics for Mycobacterial Lung Disease

Banaschewski¹,

Hofmann²

2019

Pharmaceutics

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Mycobacterial lung diseases are an increasing global health concern. Tuberculosis and nontuberculous mycobacteria differ in disease severity, epidemiology, and treatment strategies, but there are also a number of similarities. Pathophysiology and disease progression appear to be relatively similar between these two clinical diagnoses, and as a result these difficult to treat pulmonary infections often require similarly extensive treatment durations of multiple systemic drugs. In an effort to improve treatment outcomes for all mycobacterial lung diseases, a significant body of research has investigated the use of inhaled antibiotics. This review discusses previous research into inhaled development programs, as well as ongoing research of inhaled therapies for both nontuberculous mycobacterial lung disease, and tuberculosis. Due to the similarities between the causative agents, this review will also discuss the potential cross-fertilization of development programs between these similar-yet-different diseases. Finally, we will discuss some of the perceived difficulties in developing a clinically utilized inhaled antibiotic for mycobacterial diseases, and potential arguments in favor of the approach.

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Long-term macrolide therapy in chronic obstructive pulmonary disease

Cited by 15 publications

References 35 publications

The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can be downregulated by minocycline: possible implications for long-term treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis

The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can be downregulated by minocycline: possible implications for long-term treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis

New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways

Inhaled Antibiotics for Mycobacterial Lung Disease

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