LAUSR

ABSTRACT Introduction: Non-cystic fibrosis bronchiectasis (NCFB) results from a permanent and progressive destruction of the airways leading to poor lung function. NCFB is characterized by recurrent lung infection, sputum production, and cough, often requiring long-term antibiotic therapy and hospitalization. At present, there are no approved therapies available. Clinical trials of inhaled antibiotics have shown promise against sputum bacterial load, but mixed results on clinical outcomes. Areas covered: The objective of this review is to provide an overview of NCFB and critically evaluate the evidence supporting the outcome measures used in recent clinical trials of inhaled antibiotics. These include quantitative changes in bacterial load, sputum purulence and yield, inflammatory markers, and lung function, as well as clinical changes in exacerbations, exacerbation frequency, hospitalizations, and health-related quality of life. Expert commentary: Recently completed large trials of inhaled antibiotics in NCFB did not consistently meet pre-specified end points, suggesting that we have not yet found the best enrollment criteria or outcome measures to evaluate efficacy, although reduced exacerbation frequency may be clinically most meaningful. Future trials may focus on specific patient populations at high risk with new information obtained through analyses of large international patient registries. Abbreviations: 6-MWT: Six-Minute Walk Test; AIR-BX: Aztreonam for Inhalation Solution in Patients with Non-Cystic Fibrosis Bronchiectasis trial; BSI: Bronchiectasis Severity Index; CAT: COPD Assessment Test; CF: Cystic Fibrosis; CFTR: Cystic Fibrosis Transmembrane Conductance Regulator; CFU: Colony-Forming Units; COPD: Chronic Obstructive Pulmonary Disease; CRP: C-Reactive Protein; DPI: Dry Powder for Inhalation; EMA: European Medicines Agency; ERS: European Respiratory Society; FACED: FEV1, Age, Chronic colonization by P. aeruginosa, Extension of bronchiectasis and Dyspnea; FDA: US Food and Drug Administration; FEV1: Forced Expiration in 1 s; FVC: Forced Vital Capacity; HFCC: High-Frequency Chest Compression; HRCT: High-Resolution Computed Tomography; HRQoL: Health-Related Quality of Life; LCQ: Leicester Cough Questionnaire; MID: Minimal Important Difference; NCFB: Non-Cystic Fibrosis Bronchiectasis; NTM: Nontuberculous Mycobacteria; ORBIT: Once-daily Respiratory Bronchiectasis Inhalation Treatment trial; PRO: Patient-Reported Outcomes; QoL-B: Quality of Life-Bronchiectasis; SGRQ: St. George’s Respiratory Questionnaire; SWT: Shuttle Walk Test; TORCH: Towards a Revolution in COPD Health trial; UPLIFT: Understanding Potential Long-term Impacts on Function with Tiotropium trial