What Is New In Small Airways Research
Ves Dimov, MD
Allergist/Immunologist at Cleveland Clinic
Clinical Associate Professor
FAU Charles E. Schmidt College of Medicine
Aging is associated with small airway abnormality regardless of respiratory symptoms
Aging is associated with reduced forced expiratory volume in the first second (FEV1) to forced vital capacity (FVC) ratio (FEV1/FVC), hyperinflation and alveolar enlargement, but little is known about how age affects small airways.
This study used inspiratory/expiratory CTs to identify functional small airway abnormality (PRMFSA) and emphysema (PRMEMPH) in the SPIROMICS cohort. Among 580 never- and ever-smokers without obstruction or respiratory impairment, PRMFSA increased 2.7% per decade.
In never- and ever-smokers without airflow obstruction, aging is associated with increased FVC and CT-defined functional small airway abnormality regardless of respiratory symptoms.
Source: Martinez CH, Diaz AA, Meldrum C, Curtis JK, Cooper CB et al. Age and Small Airway Imaging Abnormalities in Subjects With and Without Airflow Obstruction in SPIROMICS. American Journal of Respiratory Critical Care Medicine 2016; published online ahead of print, August 26. (doi:10.1164/rccm.201604-0871OC)
Image source: Wikipedia, Flow-volume loop, public domain
Benralizumab, IL-5 receptor monoclonal antibody, reduced exacerbations in severe, uncontrolled asthma with blood eosinophils 300 cells per μL or greater
Benralizumab is a humanized, anti-interleukin-5 receptor α monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils.
This randomized, double-blind, placebo-controlled, phase 3 study (CALIMA) included 303 sites in 11 countries, and enrolled 1,300 patients aged 12–75 years with severe asthma uncontrolled by medium-dosage to high-dosage inhaled corticosteroids plus long-acting β₂-agonists (ICS plus LABA). Patients were randomly assigned to receive 56 weeks of benralizumab 30 mg every 4 weeks vs. every 8 weeks vs placebo (all subcutaneous injection).
Benralizumab resulted in lower annual exacerbation rates. It also significantly improved pre-bronchodilator FEV1.
Source: FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet 2016; 388(10056): 2128–2141. (doi:10.1016/S0140-6736(16)31322-8).
Dilemmas, confusion, and misconceptions related to small airways directed therapy
Over the last decade, there is increasing evidence that the small airways, i. e. airways less than 2 mm in internal diameter, contribute significantly to the pathophysiology and clinical expression of asthma and chronic obstructive pulmonary disease (COPD).
Advanced physiological methods of assessing small airway responses have contributed to better understanding of the pathology.
Small particle aerosol formulations better target the distal lung. Small particle aerosols of corticosteroid, bronchodilator or their combination, enables a higher total lung deposition, better peripheral lung penetration, and provides added clinical benefit, compared to large particle aerosol treatment.
However, a number of questions remain unanswered on the pragmatic approach relevant in order for clinicians to consider the role of small airways directed therapy in the day-to-day management of their patients with asthma and COPD.
Source: Lavorini F, Pedersen S, Usmani OS. Dilemmas, confusion, and misconceptions related to small airways directed therapy. Chest 2016; In Press. (doi:10.1016/j.chest.2016.07.035)