期刊
CHRONIC OBSTRUCTIVE PULMONARY DISEASES-JOURNAL OF THE COPD FOUNDATION
卷 7, 期 3, 页码 272-279出版社
COPD FOUNDATION
DOI: 10.15326/jcopdf.7.3.2019.0179
关键词
aerosol; inhaler; COPD; therapeutic; small airways
Inhalation therapy is integral in the management of patients with chronic obstructive pulmonary disease (COPD). Specifically, intravenous augmentation therapy is available to patients with alpha-1 antitrypsin deficiency (AATD), although there is insufficient alpha-1 antitrypsin (AAT) delivery to the lungs to modify airways inflammation. In contrast, the inhaled route allows replacement therapy to reach the target site of action and with higher AAT levels. Patients certainly support the inhalation route as an alternative to intravenous injections, obviating repetitive needle insertion and allowing treatment empowerment rather than dependency on traveling to specialized units. The difficulty with inhalation has been the ability to target the formulation to the pathophysiological site of disease: the emphysematous lung parenchyma of the small alveolated airways. Recent advances have suggested nebulizers as being able to deliver an adequate dose, consistently and reproducibly, and, coupled with developments in formulation science, allowed replacement therapy to reach the epithelial lining fluid of the small airways. The bench science has been translated to the first randomized, placebo-controlled clinical trial to study the effects of nebulized AAT, which, although not meeting the primary endpoint of prolonging time to first exacerbation, showed this treatment modality was safe and achievable in a large patient cohort. Indeed, learning from this trial suggests the importance of choosing the right clinical endpoints, and recent key advances in lung physiology indices allow better assessment of the silent zone of small airways disease. Knowledge from other respiratory diseases will complement treating patients with AATD, where there is considerable innovation in aerosol science and inhalation medicine directed at utilizing the inhaled route. Indeed, it could be postulated that the inhaled route may not only achieve local pulmonary therapeutic benefit, but through systemic absorption and controlled pharmacokinetic profiling, the formulation may reach and treat liver disease.
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