Abstract
Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic inflammatory lung disease characterized by irreversible dilation of the bronchi, symptoms of persistent cough and expectoration, and recurrent infective exacerbations. The prevalence of NCFBE is on the increase in the United States and Europe, but no licensed therapies are currently available for its treatment. Although there are many similarities between NCFBE and cystic fibrosis (CF) in terms of respiratory symptoms, airway microbiology, and disease progression, there are key differences, for example, in response to treatment, suggesting differences in pathogenesis. This review discusses possible reasons underlying differences in response to inhaled antibiotics in people with CF and NCFBE. Pseudomonas aeruginosa infections are associated with the most severe forms of bronchiectasis. Suboptimal levels of antibiotics in the lung increase the mutation frequency of P. aeruginosa and lead to the development of mucoid strains characterized by formation of a protective polysaccharide biofilm. Mucoid strains of P. aeruginosa are associated with a chronic infection stage, requiring long-term antibiotic therapy. Inhaled antibiotics provide targeted delivery to the lung with minimal systemic toxicity and adverse events compared with oral/intravenous routes of administration, and they could be alternative treatment options to help address some of the treatment challenges in the management of severe cases of NCFBE. This review provides an overview of completed and ongoing trials that evaluated inhaled antibiotic therapy for NCFBE. Recently, several investigators conducted phase 3 randomized controlled trials with inhaled aztreonam and ciprofloxacin in patients with NCFBE. While the aztreonam trial results were not associated with significant clinical benefit in NCFBE, initial results reported from the inhaled ciprofloxacin (dry powder for inhalation and liposome-encapsulated/dual-release formulations) trials hold promise. A more targeted approach could identify specific populations of NCFBE patients who benefit from inhaled antibiotics.
Highlights
Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic inflammatory lung disease characterized by irreversible dilation of the bronchi, symptoms of persistent cough and expectoration, and recurrent infective exacerbations
The incidence of NCFBE in the United States is estimated at 52 cases per 100,000 population.[1]. Its prevalence is on the increase in the United States and Europe despite childhood vaccination programs and the widespread use of antibiotics to treat respiratory infections.[2,3,4] According to an analysis of the Medicare Part B database, the prevalence of bronchiectasis increased by 8.74% each year between 2000 and 2007.(5) This increase could be either due to a greater utilization of chest computed tomography (CT) scans resulting in an increase in diagnosis or due to unidentified etiologic factor(s) causing a real increase in prevalence in an aging population.[5]
NCFBE is an underdiagnosed chronic inflammatory lung disease that is associated with significant morbidity and mortality, for which no licensed therapies are currently available
Summary
Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic inflammatory lung disease characterized by irreversible dilation of the bronchi, symptoms of persistent cough and expectoration, and recurrent infective exacerbations. Macrolides have positive immunomodulatory effects, including reduced airway inflammation and airway damage, with decrease in mucus hypersecretion and less biofilm formation.[57,120] Long-term use of oral macrolides in patients with NCFBE improves respiratory symptoms and quality of life, while reducing the decline in lung function and the frequency of acute exacerbations (Table 2).(121) Some inhaled macrolide formulations have not been clinically tested.[122,123,124,125,126] Concerns with long-term use of macrolides include the potential for macrolide resistance and emergence of new pathogens.[127] Increasing use of macrolides, especially azithromycin, is associated with a consistent increase in macrolide resistance at the population level.[25] Increasing macrolide-resistant strains in the community could influence the clinical outcomes of macrolide therapy, especially when a large number of patients use macrolides on a long-term basis and become carriers of macrolide-resistant organisms.[25]. Rates of treatmentemergent adverse events and serious adverse events were similar across treatment arms in both studies.[134,135,136]
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