Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: A systematic review

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 3; pp. 646 - 657
• Main Authors: van der Wiel, Erica, MD, ten Hacken, Nick H.T., MD, PhD, Postma, Dirkje S., MD, PhD, van den Berge, Maarten, MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.03.2013; Elsevier; Elsevier Limited
• Subjects: Air Pollution - adverse effects; Allergens - adverse effects; Allergy and Immunology; Asthma; Asthma - etiology; Asthma - physiopathology; asthma control; Biological and medical sciences; Bronchial Hyperreactivity; Catheters; Chronic obstructive pulmonary disease, asthma; Exercise; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hypersensitivity; Immunopathology; Inflammation; Inventories; Literature reviews; Lung - physiopathology; Lung diseases; Medical sciences; montelukast; Nitrogen; phenotypes; Pneumology; Provocation tests; Respiratory system; Respiratory tract; Reviews; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Small-airways disease; Steroid hormones; Studies; Ventilation; HFA; PM 2.5; R5-R20; FEF 25%-75; Ventilation heterogeneity generated in the conductive lung zone; Particulate matter less than 10 μm in diameter; R20; Hydrofluoroalkane; R5; Sacin; Single-breath nitrogen test; Inhaled corticosteroid; PM 10; asthma; asthma control; FEF 50; Scond; Nitric oxide; AX; Beclomethasone dipropionate; MBNW; DPI; Resistance of the respiratory system at 20 Hz; Mass median aerodynamic diameter; CFC; NO; Resistance of the respiratory system at 5 Hz; RV; Chlorofluorocarbon; TLC; BHR; BDP; HDM; Difference between R5 and R20; Bronchoalveolar lavage; Forced expiratory flow at 50% of forced vital capacity; Dry powder inhaler; Total lung capacity; MMAD; House dust mite; Forced expiratory flow at 25% to 75% of forced vital capacity; BAL; ACQ; Asthma Control Questionnaire; PEF; Residual volume; phenotypes; SBNT; Small-airways disease; Multiple-breath nitrogen washout test; Ventilation heterogeneity generated in the acinar lung zone; Bronchial hyperresponsiveness; ICS; Peak expiratory flow; Reactance area; Particulate matter less than 2.5 μm in diameter; PM2.5; FEF25%-75; FEF50; PM10; Lung disease; Immunopathology; Respiratory disease; Evidence-based practice; Clinical form; Systematic review; Respiratory system; Evidence-based medicine; Asthma; Respiratory tract; Symptomatology; Phenotype; Immunology; Dysfunction; Bronchus disease; Obstructive pulmonary disease
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.12.1567

Traditionally, asthma has been considered a disease that predominantly involves the large airways. Today, this concept is being challenged, and increasing evidence has become available showing that abnormalities in the small airways also contribute to the clinical expression of asthma. The small airways can be affected by inflammation, remodeling, and changes in the surrounding tissue, all contributing to small-airways dysfunction. In this article we have performed a systematic review of the literature on the association between small-airways dysfunction and clinical signs and symptoms of asthma. This review shows that small-airways dysfunction associates with worse control of asthma, higher numbers of exacerbations, the presence of nocturnal asthma, more severe bronchial hyperresponsiveness, exercise-induced asthma, and the late-phase allergic response. Importantly, small-airways dysfunction can already be present in patients with mild asthma. Our review provides suggestive evidence that a better response of the small airways to inhaled steroids or montelukast associates with better asthma control. For this reason, an early recognition of small-airways dysfunction is important because it enables the physician to start timely treatment to target the small airways. It is important to develop simpler and more reliable tools (eg, questionnaires or bronchial provocation tests with small-particle stimuli) to assess the presence and extent of small-airways dysfunction in daily clinical practice.