Targeting the Small Airway in Asthma and COPD

曾敬閔 醫師, 振興醫院

COPD and asthma have different risk factors and pathogenesis, but they share a pathophysiologic hallmark characterized by small airways disease. Although difficult to explore and measure, modifications of distal airways' pathophysiology and biology represent an early sign of obstructive disease and should be researched and assessed in everyday clinical practice. In the last 15 years, computed microtomography scans have shed light on the anatomy and physiology of the so-called silent zone, and research devoted to investigate the effect of inhaled treatments on small airway pathophysiology has been increasing. This narrative review offers a historical summary of researchers and landmark studies that reported, defined, and advanced the research on small airways. We then discuss the latest findings on the role and characteristics of the small airways' inflammatory and cellular structure, and we describe the assessment tools available to detect small airways dysfunction in COPD and asthma and the effect of bronchodilators and inhaled steroids on functional and biological biomarkers. Finally, we analyze the newest technological therapeutic advances aimed at small airways treatment in terms of inhalation devices and small particle size molecules.

Reference:

1.      J.C. Hogg, P.T. Macklem, W.M. Thurlbeck Site and nature of airway obstruction in chronic obstructive lung disease, N Engl J Med, 278 (25) (1968), pp. 1355-1360

2.      E. Crisafulli, R. Pisi, M. Aiello, et al. Prevalence of small-airway dysfunction among COPD patients with different GOLD stages and its role in the impact of disease, Respiration, 93 (1) (2017), pp. 32-41

How IOS Detection Tools Can Help Diagnose SAD and Treating Patients Early

羅柏鈞 醫師, 衛生福利部桃園醫院

Small airway dysfunction is a pathological component of chronic obstructive pulmonary disease (COPD) and Asthma, and impulse oscillometry is an easy-to-administer, effort-independent non-invasive test reflecting small airway dysfunction. We aimed to compare the impulse oscillometry (IOS) measurements between COPD and Asthma patients and investigate their correlation with severity of both diseases and other conventional parameters.

Small airways are defined as those with a diameter of less than 2 mm and are called the silent zone of the lung. It is proposed that the pathology of small airways occurs before the appearance of symptoms or abnormal spirometry1 . With appreciation of the importance of small airways, there has been a remarkable increase in publications on small airways since 2010. Although small airways dysfunction in asthma has been well described, the involvement of small airways in chronic obstructive pulmonary disease (COPD), an obstructive disease, and particularly in interstitial lung disease with a restrictive pattern, has been understudied.

IOS is advantageous in COPD and IPF patients who cannot exhale due to severe dyspnea, as it is easy to administer and reflects small airway resistance better. Diagnosis of small airway dysfunction may be beneficial in the management of patients with Asthma and COPD.

Reference:

1) Hogg JC, Paré PD, Hackett TL. The Contribution of Small Airway Obstruction to the Pathogenesis of Chronic Obstructive Pulmonary Disease. Physiol Rev 2017; 97: 529-552.

2) Postma DS, Brightling C, Baldi S, Van den Berge M, Fabbri LM, Gagnatelli A, Papi A, Van der Molen T, Rabe KF, Siddiqui S, Singh D, Nicolini G, Kraft M; ATLANTIS study group. Exploring the relevanc and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study. Lancet Respir Med 2019; 7: 402-416.

Optimization of COPD & Asthma Patients Treatment: from clinical trials to new real world experience

黃俊凱 醫師 國立台灣大學醫學院附設醫院

Objective Evidence of the efficacy of single-inhaler triple therapy in COPD patients inferred from RCTs has not been assessed in a real-world setting in Austria. In this non-interventional study (NIS) tolerability and effectiveness of extrafine beclometasone-dipropionate, formoterol-fumarate and glycopyrronium (Trimbow® 87/5/9μg) was evaluated in COPD patients. Methods A prospective NIS was conducted over 52 weeks in 24 sites in Austria. Eligible COPD patients had an indication for treatment with single-inhaler BDP/FF/G. In this study tolerability, lung function, exacerbation rate, symptom scores and CAT scores were recorded. Results 265 patients with moderate to very severe airflow limitation (GOLD Grade 2-4: 96.2%) and persistent symptoms (GOLD B: 62.3%, GOLD D: 34%) according to the 2018 GOLD Report were included. After 52 weeks, a significant improvement was detected in lung function (FEV1, FEV1% predicted and FVC; p<0.001) and symptoms (cough, sputum and shortness of breath; p<0.001). A clinically relevant improvement in CAT score observed at 12 weeks persisted after 52 weeks in GOLD B and GOLD D patients (p<0.001), paralleled by a significant reduction of moderate and severe exacerbations by 57.4% and 27.3%, respectively (p<0.001). After 52 weeks, 93.7% of the patients continued the treatment. Of 21 adverse events reported 16 were non-serious, five were serious, none were deemed drug related. Conclusions The present results support the tolerability and effectiveness of extrafine BDP/FF/G in COPD patients in a real-world setting, showing an improvement in lung function, symptom control and a significant reduction in exacerbations.

The single-inhaler triple therapy studies reported here evaluated an extrafine formulation to enhance lung deposition and small airway delivery. It remains to be seen whether the treatment effects reported here are “class effects” that are also seen with other single-inhaler triple therapies. There are relatively few classes of drugs available in COPD, and the single-inhaler triple therapy studies reported here should reassure practicing clinicians that the stepwise approach toward triple therapy is a rational and effective option.

Reference:

1.      Gold Reports for Personal Use - Global Initiative for Chronic Obstructive Lung Disease - GOLD, (n.d.). https://goldcopd.org/gold-reports/ (accessed January 15, 2020).

2.      G.J. Rodrigo, H. Neffen, A systematic review of the efficacy and safety of a fixed-dose combination of umeclidinium and vilanterol for the treatment of COPD, Chest. 148 (2015) 397–407. https://doi.org/10.1378/chest.15-0084.

Inhalation Device Formulation Matters ? Finding the Right Device to Improve Respiratory Therapy

周百謙 醫師, 臺北醫學大學附設醫院

There are many different inhaler devices and medications on the market for the treatment of asthma and chronic obstructive pulmonary disease, with over 230 drug-delivery system combinations available. However, despite the abundance of effective treatment options, the achieved disease control in clinical practice often remains unsatisfactory. In this context, a key determining factor is the match or mismatch of an inhalation device with the characteristics or needs of an individual patient. Indeed, to date, no ideal device exists that fits all patients, and a personalized approach needs to be considered. Several useful choice-guiding algorithms have been developed in the recent years to improve inhaler–patient matching, but a comprehensive tool that translates the multifactorial complexity of inhalation therapy into a user-friendly algorithm is still lacking. To address this, a multidisciplinary expert panel has developed an evidence-based practical treatment tool that allows a straightforward way of choosing the right inhaler for each patient.

Reference:

1.      Adv Ther. 2022; 39(3): 1149–1163. Published online 2022 Jan 26. doi: 10.1007/s12325-021-02034-9

2.      Corradi M, Chrystyn H, Cosio BG, Pirozynski M, Loukides S, Louis R, Spinola M, Usmani OS. NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma. Expert Opin Drug Deliv. 2014;11(9):1497–1506.