device (EMD) to monitor adherence to ICS in children aged. 6 years and older who ... Queensland Children's Medical Research Institute. Brisbane, Australia.
Correspondence Assessing Adherence to Inhaled Medication in Difficult-to-Treat Asthma
determined individuals can subvert electronic monitoring by actuating but not inhaling medication.
To the Editor:
Author disclosures are available with the text of this letter at www.atsjournals.org.
McNicholl and colleagues provide some interesting insights and highlight the importance of nonadherence to inhaled corticosteroids (ICS) in difficult-to-treat asthma in their article (1). However, we would like to respectfully argue against their conclusion that fractional exhaled nitric oxide (FENO) suppression is likely to provide clinical utility in the management of difficult to treat asthma. The authors used pharmacy records and patient report as the gold standard for adherence. As the authors concede, patient reports (2, 3) and, to a lesser extent, pharmacy records (4) have been shown to overestimate adherence. Even if adherence was accurately assessed in the 21 subjects assigned as having optimal adherence, data from the study indicate that FENO suppression has a sensitivity of only 0.67 and specificity of 0.95. In addition, FENO is relatively expensive and time consuming and would limit application to tertiary care. There would also be significant costs and inconvenience associated with direct observation of medication received twice daily for multiple days. Critically, only 40 (17%) of the 229 screened subjects were suitable and/or willing to participate in the study protocol. In summary, the procedure would be costly, inconvenient, suitable for a minority of subjects, and arguably not superior to the combination of a review of pharmacy records, a sensitive patient interview, and serum cortisol assay. Our recent practice has been to use an electronic monitoring device (EMD) to monitor adherence to ICS in children aged 6 years and older who report optimal adherence and have poorly controlled asthma despite having received individualized asthma education and the prescription of high-dose ICS (.500 mg fluticasone per day) and a long-acting b-agonist. Over the last 6 months, 15 subjects in our clinic met these criteria. Thirteen subjects returned for review 1 month later (87% effective take-up rate). One subject reported being too embarrassed to return, and one subject with complex social issues was taken into state care. The mean adherence to twice-daily dosing documented by the EMD during the first month of monitoring was 49.5%. During subsequent months, adherence was discussed with patients as part of their care, and in all cases, adherence increased above 80%. Only one subject achieved adherence greater than 90% and continued to have regular symptoms and reduced lung function over 2 months of monitoring. This subject was prescribed 1,000 mg fluticasone per day, 50 mg prednisolone daily, and 10 mg montelukast daily. She was admitted to the hospital, at which time her serum cortisol level was within the normal range. Over 5 days of hospital admission, during which she was given only the above prescribed medication, her FEV1 rose from 52% predicted to 84% predicted, and her symptoms improved significantly. It has become apparent that she was actuating her device twice daily but not inhaling the ICS and was not taking her other medication. She has subsequently experienced sustained improvement in her clinical and social functioning after intensive work with our pediatric mental health team. Our experience suggests that EMDs can be used economically to detect suboptimal adherence in the majority of subjects with difficult-to-treat asthma. However, we concede that no one system can effectively evaluate adherence in all subjects. A small proportion of subjects will find overt monitoring too confronting even when conducted sensitively, others will have their management complicated by their social circumstances, and finally, some
Scott Williams Burgess, Ph.D. Mater Children’s Hospital Brisbane, Australia Andrew Tai, Ph.D. Women’s and Children’s Hospital Adelaide, Australia Peter David Sly, D.Sc. Queensland Children’s Medical Research Institute Brisbane, Australia
References 1. McNicholl DM, Stevenson M, McGarvey LP, Heaney LG. The utility of fractional exhaled nitric oxide suppression in the identification of nonadherence in difficult asthma. Am J Respir Crit Care Med 2012;186:1102–1108. 2. Bender B, Wamboldt FS, O’Connor SL, Rand C, Szefler S, Milgrom H, Wamboldt MZ. Measurement of children’s asthma medication adherence by self report, mother report, canister weight, and Doser CT. Ann Allergy Asthma Immunol 2000;85:416–421. 3. Burgess SW, Sly PD, Morawska A, Devadason SG. Assessing adherence and factors associated with adherence in young children with asthma. Respirology 2008;13:559–563. 4. Choo PW, Rand CS, Inui TS, Lee ML, Cain E, Cordeiro-Breault M, Canning C, Platt R. Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy. Med Care 1999;37:846–857. Copyright ª 2013 by the American Thoracic Society
Reply From the Authors:
We are grateful to Dr. Burgess and colleagues for their interest in our study (1), giving us the opportunity to clarify the role of fractional exhaled nitric oxide (FENO) suppression in the identification of nonadherence in difficult asthma. They seem to have misinterpreted some of the details in our manuscript and also confuse identifying nonadherence with trying to improve adherence, which are two different, albeit related, issues. Our test is specifically about clinical phenotyping and identifying nonadherence in an adult difficult asthma service with two principal aims: (1) to allow nonadherence to potentially be addressed and improved in the clinic and (2) to prevent progression to expensive complex therapies parentally administered, such as omalizumab, when adherence to standard therapy would achieve asthma control. Comparison of the FENO suppression test against the composite adherence measure used as a reference standard demonstrates that this is a highly specific test with a strong positive predictive value (0.92 [95% confidence interval, 0.67–0.99]) (1). As a result, this reduces the risk of incorrectly identifying a patient as nonadherent, deterioration in the patient–doctor relationship due to false accusation, and inappropriate changes in management. The diagnostic odds ratio of 42 (95% confidence interval, 4.5–392) suggests that this is a viable test (1). In relation to expense, we are currently validating remote monitoring for the test using remote FENO measurement and an inhaler
