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      Critical Inhaler Handling Error Is an Independent Risk Factor for Frequent Exacerbations of Chronic Obstructive Pulmonary Disease: Interim Results of a Single Center Prospective Study

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          Chronic obstructive pulmonary disease (COPD) acute exacerbations are significant causes of morbidity and mortality. “Frequent exacerbator” phenotypes are considered a distinct subgroup and this phenotype has a negative effect on lung function, quality of life, activity, hospital admission, and mortality. We assess inhaler handling technique and adherence, and evaluate risk factors associated with frequent exacerbations in COPD patients.


          This study was a cross-sectional, case-control study. We prospectively enrolled 189 COPD patients from Yeungnam University Hospital from January 2018 to November 2018. Subjects were tested regarding their inhaler technique in face-to-face interviews with an advanced practice nurse of inhaler upon study entry. Frequency of moderate to severe COPD exacerbations were reviewed via electronic medical records during 12 months prior to study entry. Frequent exacerbations were defined as ≥2 moderate to severe exacerbations in the prior 12 months. Multivariate logistic regression was performed to identify risk factors for frequent exacerbations.


          Among 189 COPD patients, 50 (26.5%) were frequent exacerbators. Based on univariate analyses, body mass index (BMI) < 25 kg/m 2, lower forced expiratory volume in 1 s (FEV 1), higher mMRC, lower feeling of satisfaction with the inhaler, and any critical errors were potential risk factors for frequent exacerbations. Multivariate logistic regression analyses revealed that BMI < 25 kg/m 2 (OR, 2.855, 95% CI, 1.247–6.534; p=0.013), higher mMRC (OR, 1.625, 95% CI, 1.072–2.463; p=0.022), and any critical error (OR, 2.020, 95% CI, 1.021–3.999; p=0.044) were risk factors.


          Any critical error, BMI < 25 kg/m 2 and high mMRC are independent risk factors for frequent exacerbations in COPD patients. Careful monitoring and education around inhaler devices, particularly in frequent exacerbators, are important components of COPD treatment.

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          Most cited references 19

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          Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD.

          Incorrect usage of inhaler devices might have a major influence on the clinical effectiveness of the delivered drug. This issue is poorly addressed in management guidelines. This article presents the results of a systematic literature review of studies evaluating incorrect use of established dry powder inhalers (DPIs) by patients with asthma or chronic obstructive pulmonary disease (COPD). Overall, we found that between 4% and 94% of patients, depending on the type of inhaler and method of assessment, do not use their inhalers correctly. The most common errors made included failure to exhale before actuation, failure to breath-hold after inhalation, incorrect positioning of the inhaler, incorrect rotation sequence, and failure to execute a forceful and deep inhalation. Inefficient DPI technique may lead to insufficient drug delivery and hence to insufficient lung deposition. As many as 25% of patients have never received verbal inhaler technique instruction, and for those that do, the quality and duration of instruction is not adequate and not reinforced by follow-up checks. This review demonstrates that incorrect DPI technique with established DPIs is common among patients with asthma and COPD, and suggests that poor inhalation technique has detrimental consequences for clinical efficacy. Regular assessment and reinforcement of correct inhalation technique are considered by health professionals and caregivers to be an essential component of successful asthma management. Improvement of asthma and COPD management could be achieved by new DPIs that are easy to use correctly and are forgiving of poor inhalation technique, thus ensuring more successful drug delivery.
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            Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease

            Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.
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              Chronic obstructive pulmonary disease exacerbation and inhaler device handling: real-life assessment of 2935 patients.

              Acute exacerbations of chronic obstructive pulmonary disease (COPD) can be prevented by inhaled treatment. Errors in inhaler handling, not taken into account in clinical trials, could impact drug delivery and minimise treatment benefit. We aimed to assess real-life inhaler device handling in COPD patients and its association with COPD exacerbations.To this end, 212 general practitioners and 50 pulmonologists assessed the handling of 3393 devices used for continuous treatment of COPD in 2935 patients. Handling errors were observed in over 50% of handlings, regardless of the device used. Critical errors compromising drug delivery were respectively made in 15.4%, 21.2%, 29.3%, 43.8%, 46.9% and 32.1% of inhalation assessment tests with Breezhaler® (n=876), Diskus® (n=452), Handihaler® (n=598), pressurised metered-dose inhaler (pMDI) (n=422), Respimat® (n=625) and Turbuhaler® (n=420).The proportion of patients requiring hospitalisation or emergency room visits in the past 3 months for severe COPD exacerbation was 3.3% (95% CI 2.0-4.5) in the absence of error and 6.9% (95% CI 5.3-8.5) in the presence of critical error (OR 1.86, 95% CI 1.14-3.04, p<0.05).Handling errors of inhaler devices are underestimated in real life and are associated with an increased rate of severe COPD exacerbation. Training in inhaler use is an integral part of COPD management.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of Chronic Obstructive Pulmonary Disease
                02 December 2019
                : 14
                : 2767-2775
                [1 ]Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, College of Medicine, Yeungnam University , Daegu, South Korea
                Author notes
                Correspondence: Kwan Ho Lee Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center , 170 Hyunchung-Ro, Nam-Gu, Daegu42415, South Korea Email
                © 2019 Ahn et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (

                Page count
                Figures: 1, Tables: 4, References: 38, Pages: 9
                This work was supported by the Yeungnam University Research Fund in 2019.
                Original Research

                Respiratory medicine

                copd, inhalation therapy, drug use error, disease exacerbation


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