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Aerosol-Based Efficient Delivery of Clarithromycin, a Macrolide Antimicrobial Agent, to Lung Epithelial Lining Fluid and Alveolar Macrophages for Treatment of Respiratory Infections

Background: Macrolide antimicrobial agents are generally given by the oral route for the treatment of respiratory infections caused by pathogenic microorganisms infected in lung epithelial lining fluid (ELF) and alveolar macrophages (AMs). However, because macrolides distribute to many different tissues via the blood after oral administration, systemic side effects are frequently induced. In contrast with oral administration, aerosolization may be an efficient method for delivering macrolides directly to ELF and AMs. In this study, the efficacy of aerosol-based delivery of clarithromycin (CAM), as a model macrolide, for the treatment of respiratory infections was evaluated by comparison with oral administration.

Method: The aerosol formulation of CAM (0.2 mg/kg) was administered to rat lungs using a Liquid MicroSprayer®. The oral formulation of CAM (50 mg/kg) was used for comparison. Time courses of concentrations of CAM in ELF and AMs following administration were obtained, and then the bioavailability (BA) was calculated. In addition, the area under the concentrations of CAM in ELF and AMs—time curve/minimum inhibitory concentration at which 90% of isolates ratio [area under the curve (AUC/MIC90)] were calculated to estimate the antibacterial effects in ELF and AMs.

Results: The BA of CAM in ELF and AMs following administration of aerosol formulation were markedly greater than that following administration of oral formulation. This indicates that the aerosol formulation is more effective in delivering CAM to ELF and AMs, compared with the oral formulation, despite a low dose. The AUC/MIC90 of CAM in ELF and AMs were markedly higher than the effective values. This indicates that the aerosol formulation could be useful for the treatment of respiratory infections caused by pathogenic microorganisms infected in ELF and AMs.

Conclusions: This study suggests that aerosol formulation of macrolides is an effective pulmonary drug delivery system for the treatment of respiratory infections.

COPD patients at increased risk for peptic ulcer bleeding

Patients with chronic obstructive pulmonary disease are nearly twice as likely to develop peptic ulcer bleeding as the general population, suggest study findings that also identified a number of important risk factors in these patients. (Source: MedWire News - Respiratory)

Comparison of inhaled corticosteroids and leukotriene receptor antagonists in adolescents and adults with mild‐moderate asthma: a meta‐analysis

Inhaled corticosteroids (ICS) and oral leukotriene receptor antagonists (LTRA) are effective drugs used in the management of asthma as controller monotherapy in adolescents and adults, although there are debates as to which one is better.

Objectives:  To thoroughly compare the efficacy and tolerability of ICS versus LTRA in adolescents and adults with mild to moderate asthma. Methods: Relative database were searched for the review. Randomized controlled trials of more than or equal to 4 weeks’ treatment duration comparing ICS with LTRA were reviewed.

Results and conclusion:  24 trials with 6197 randomized adolescents and adults with mild to moderate asthma met the inclusion criteria with a minimum duration of 4 weeks’ treatment. Significant differences favour...

Vitamin D and asthma.

Vitamin D and asthma.

Am J Respir Crit Care Med. 2012 Jan 15;185(2):124-32

Authors: Paul G, Brehm JM, Alcorn JF, Holguín F, Aujla SJ, Celedón JC

Abstract
Vitamin D deficiency and asthma are common conditions that share risk factors such as African American ethnicity, inner-city residence, and obesity. This review provides a critical examination of current experimental and epidemiologic evidence of a causal association between vitamin D status and asthma or asthma morbidity, including potential protective mechanisms such as antiviral effects and enhanced steroid responsiveness. Because most published epidemiologic studies of vitamin D and asthma or asthma morbidity are observational, a recommendation for or against vitamin D supplementation as preventive or secondary treatment for asthma is not advisable and must await results of ongoing clinical trials. Should these trials confirm a beneficial effect of vitamin D, others will be needed to assess the role of vitamin D supplementation to prevent or treat asthma in different groups such as infants, children of school age, and ethnic minorities.

PMID: 22016447 [PubMed - in process]

Alpha-nicotinic acetylcholine receptor and tobacco smoke exposure: Effects on bronchial hyperresponsiveness in children.

Alpha-nicotinic acetylcholine receptor and tobacco smoke exposure: Effects on bronchial hyperresponsiveness in children.

Pediatr Allergy Immunol. 2012 Feb;23(1):40-49

Authors: Torjussen TM, Lødrup Carlsen KC, Munthe-Kaas MC, Mowinckel P, Carlsen KH, Helms PJ, Gerritsen J, Whyte MK, Lenney W, Undlien DE, Shianna KV, Zhu G, Pillai SG

Abstract
To cite this article: Torjussen TM, Lødrup Carlsen KC, Munthe-Kaas MC, Mowinckel P, Carlsen K-H, Helms PJ, Gerritsen J, Whyte MK, Lenney W, Undlien DE, Shianna KV, Zhu G, Pillai SG. Alpha-nicotinic acetylcholine receptor and tobacco smoke exposure: Effects on bronchial hyperresponsiveness in children. Pediatric Allergy Immunology 2012: 23: 40-49. ABSTRACT: Background:  The CHRNA 3 and 5 genes on chromosome 15 encode the alpha subunits of the nicotinic acetylcholine receptor, mediating airway cholinergic activity. Polymorphisms are associated with cigarette smoking, chronic obstructive pulmonary disease, and lung cancer. Aims:  To determine possible associations between CHRNA 3/5 SNP rs8034191 and asthma or lung function in children in one local and one replicate multinational population, and assess if tobacco smoke modified the associations. Materials and methods:  The rs8034191 SNP genotyped in 551 children from the environment and childhood asthma (ECA) birth cohort study in Oslo, Norway, and in 516 families from six European centers [the Genetics of Asthma International Network (GAIN) study] was tested for genotypic or allelic associations to current or history of asthma, allergic sensitization (≥ one positive skin prick tests), bronchial hyperresponsiveness (BHR), and lung function (FEV(1%) of predicted and FEV(1) /FVC ratio over/ below the 5th percentile). Results:  Although the TT and CT genotypes at SNP rs 8034191 were overall significantly associated with BHR (OR = 3.9, 95% CI 1.5-10.0, p = 0.005), stratified analyses according to exposure to maternal smoking in-utero or indoor smoking at 10 yrs of age showed significant association (OR = 4.4, 95% CI 1.5-12.6, p = 0.006 and OR 5.6, 95% CI 1.7-18.5, p = 0.004, respectively) only in the non-exposed and not in exposed children. The SNP-BHR association was replicated in the non-tobacco-smoke-exposed subjects in one of the GAIN centers (BHR associated with the T allele (p = 0.034)), but not in the collated GAIN populations. Asthma, allergic sensitization, and lung function were not associated with the rs8034191 alleles. Conclusion:  An interaction between tobacco smoke exposure and a CHRNA3/5 polymorphism was found for BHR in children, but CHRNA3/5 was not associated with asthma or lung function.

PMID: 22017462 [PubMed - as supplied by publisher]

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