The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

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Educational aimsTo recognise the clinical and radiological presentation of the spectrum of diseases associated with bronchiectasis.To understand variation in the aetiology, microbiology and burden of bronchiectasis and cystic fibrosis across different global healthcare systems.Bronchiectasis is the term used to refer to dilatation of the bronchi that is usually permanent and is associated with a clinical syndrome of cough, sputum production and recurrent respiratory infections. It can be caused by a range of inherited and acquired disorders, or may be idiopathic in nature. The most well recognised inherited disorder in Western countries is cystic fibrosis (CF), an autosomal recessive condition that leads to progressive bronchiectasis, bacterial infection and premature mortality.Both bronchiectasis due to CF and bronchiectasis due to other conditions are placing an increasing burden on healthcare systems internationally. Treatments for CF are becoming more effective leading to more adult patients with complex healthcare needs. Bronchiectasis not due to CF is becoming increasingly recognised, particularly in the elderly population. Recognition is important and can lead to identification of the underlying cause, appropriate treatment and improved quality of life. The disease is highly diverse in its presentation, requiring all respiratory physicians to have knowledge of the different “bronchiectasis syndromes”. The most common aetiologies and presenting syndromes vary depending on geography, with nontuberculous mycobacterial disease predominating in some parts of North America, post-infectious and idiopathic disease predominating in Western Europe, and post-tuberculosis bronchiectasis dominating in South Asia and Eastern Europe.Ongoing global collaborative studies will greatly advance our understanding of the international impact of bronchiectasis and CF.

Administration of medications via aerosolization is potentially an ideal strategy to treat airway diseases. This delivery method ensures high concentrations of the medication in the targeted tissues, the airways, with generally lower systemic absorption and systemic adverse effects. Aerosolized antibiotics have been tested as treatment for bacterial infections in patients with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and ventilator-associated pneumonia (VAP). The most successful application of this to date is treatment of infections in patients with CF. It has been hypothesized that similar success would be seen in NCFB and in difficult-to-treat hospital-acquired infections such as VAP. This review summarizes the available evidence supporting the use of aerosolized antibiotics and addresses the specific considerations that clinicians should recognize when prescribing an aerosolized antibiotic for patients with CF, NCFB, and VAP.

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Interleukin (IL)-13 has been associated with multiple inflammatory features of asthma. It affects multiple cellular lines in asthma and is a key mediator in airway hyperreactivity and remodeling. Periostin, an extracellular protein, has been used as a surrogate marker of IL-13 activity and has been linked to airway remodeling by inducing subepithelial fibrosis. Lebrikizumab is a humanized monoclonal antibody that targets IL-13. Studies have demonstrated promising results with lebrikizumab therapy in asthma with regard to pulmonary function and exacerbation rates, especially on those patients with surrogate markers of T helper cell type 2-driven inflammation (ie, elevated immunoglobulin E levels, eosinophil counts, periostin levels). Lebrikizumab appears to be a safe therapy, but there are ongoing studies evaluating its efficacy and safety profile. Other therapies that target IL-13 and the receptor of IL-4/IL-13 have been studied, but future studies are needed to determine their role in the treatment of asthma.

SummaryAimsNon‐cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive respiratory disorder characterised by irreversibly and abnormally dilated airways, persistent cough, excessive sputum production and recurrent pulmonary infections. In the last several decades, its prevalence has increased, making it likely to be encountered in the primary care setting. The aim was to review the clinical presentation and diagnosis of NCFB, with an emphasis on the role of computed tomography (CT).MethodsFor this review, trials and reports were identified from PubMed/Medline and ClinicalTrials.gov from the US NIH and the Cochrane Register of Controlled Trials. The search used keywords: bronchiectasis, non‐cystic fibrosis bronchiectasis, chronic pulmonary infection and computed tomography. No date/language restrictions were used.ResultsNon‐cystic fibrosis bronchiectasis often coexists with other respiratory conditions, such as chronic obstructive pulmonary disease. The prevalence of NCFB is increasing, particularly in women and older individuals, possibly as a result of increased physician awareness and widespread use of CT, which is the gold standard for the diagnosis of NCFB. CT can assist in identifying an underlying cause of NCFB and determining the extent and severity of the disease.DiscussionNon‐cystic fibrosis bronchiectasis should be suspected in the primary care setting in patients with chronic cough, purulent sputum and frequent respiratory infections that tend to resolve slowly or partially. Early diagnosis and determination of the extent and severity of the disease by CT and other tests are critical to establish therapy to improve quality of life and potentially slow progressive decline of lung function in patients with NCFB .

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