A Nebulizer Chronolog Inhaler Use
DONALD P. TASHKIN, M.D., LOS hgeies, caiifornia, CYNTHIA RAND, Pm., Bait/more, Mary/and, MITCHELL NIDES, Ph.D., MICHAEL SIMMONS, h Angeles, cabfornia, ROBERTWISE, M.D., Baitimore, Mary/and, ANNE H. COULSON, VIRGINIA LI, Ph.D., HENRY GONG, JR., M.D., loshgeles, Ca/ifoma
The Lung Health Study is a lo-center 5-year clinical trial sponsored by the National Heart, Lung, and Blood Institute to evaluate the effectiveness of early intervention in chronic obstructive pulmonary disease (COPD). The specific objectives of the trial are to determine whether the accelerated decline in lung function characteristic of COPD and morbidity due to COPD can be reduced by special intervention at a relatively early stage in the evolution of the disease. Special intervention consists of a smoking-cessation program and the use of an inhaled bronchodilator to suppress airway hyperreactivity. The use of the inhaler canister is monitored every 4 months by canister weighing and, at two of the 10 centers, by an electronic recording device, the Nebulizer Chronolog’“. Among trial participants assigned the latter device, results from the first 4 months of the study indicate that only 52% of trial participants who were uninformed as to the nature of the chronolog used their inhaler at least twice daily as measured by the chronolog, compared with 87% as determined by self-report. Satisfactory or good compliance was achieved by 52% of these subjects as measured by the ehronolog compared with 85% as assessed by canister weighing. Eighteen percent of uninformed participants “dumped” their inhalers within a 3-hour time period, contributing to the inaccuracy of canister weights as an indicator of compliance. Feedback of information to the participants from the chronolog improved the level of compliance and eliminated the “dumping” phenomenon. We conclude that,
Fromthe Departmentof Medicine, UCLA School of Medicine, Los Angeles, California (D.P.T., M.S., H.G.); UCLA School of Public Health, Los Angeles, Calrfornia (M.N., A.H.C., V.L.); and Johns Hopkrns Universrty, Baltrmore, Maryland (C.R., R.W.). Supported by contracts NOl-HR-46022 and NOl-HR.46016 from the Divrsron of Lung Diseases, National Heart Long, and Blood Inshtute, USPHS, Bethesda, Maryland. Requests for reprints should be addressed to Donald P. Tashkin, M.D., UCLA Medrcal School, Room 37-131 CHS, Los Angeles, Calrfornra 90024.
when accurate determinations of compliance are important, as in a drug trial, objective medication monitors should be considered. Electronic monitoring of inhaler use can provide valuable feedback, which encourages improved compliance. hronic obstructive pulmonary disease (COPD) accounts for 3-4% of all deaths and ranks fifth among the leading causes of death in the United States [l]. Established risk factors for the development of COPD include persistent cigarette smoking and reduced lung function [Z]. Forced expiratory volume in 1 second (FEVJ normally falls very gradually over a lifetime. However, susceptible smokers lose considerably more lung function on an annual basis than nonsmokers or smokers who are not susceptible to the harmful effects of smoking on lung function . Increased bronchial reactivity is associated with an accelerated decline in lung function in individuals with and without established COPD [4-61. Moreover, the intensity of cigarette smoking and the degree of airways reactivity appear to interact to produce greater declines in FEVi . According to one hypothesis , if periodic bronchoconstrietion can be prevented, emphysema might also be prevented. Thus, smoking cessation and bronchodilation might check the decline in lung function. Against this background, the National Heart, Lung, and Blood Institute has sponsored a major lo-center study of early intervention for COPD, known as the Lung Health Study . The aims of this study are to identify cigarette smokers who have early COPD and to determine whether smoking cessation will alter the course of their disease. A secondary objective is to determine whether or not the regular use of a bronchodilator can add to the benefit of smoking cessation alone by slowing the accelerated decline in lung function characteristic of COPD and by reducing respiratory morbidity. Before the objectives of the Lung Health Study can be met, the investigators involved must answer two questions: first, will the study participants actually stop smoking; and second, will they use the
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bronchodilator despite the fact that most of them are asymptomatic? We report here a preliminary analysis of compliance with inhaler use over the first 4 months of the study in 237 study participants who received a Nebulizer Chronolog.
MATERIALSAND METHODS Initial Screening Recruitment into the Lung Health Study began in November 1986 and ended in January 1989. During this time, a total of 5,887 men and women between 35 and 59 years of age were enrolled in the study at all 10 centers. All participants had evidence of mild to moderate airflow obstruction, as indicated by an FEV1/forced vital capacity (FVC) ratio 170% and an FEVl of 55-90% of predicted [91, but were otherwise in good health. Smokers were considered eligible for the study only after they had completed a rigorous three-stage screening procedure in which they underwent pulmonary function testing and were questioned about their general health, any complicating medical illnesses, and willingness to consider smoking cessation. Smoking Cessation and Bronchodilator Therapy Participants were randomized to one of two groups: usual care and special intervention. Participants in the usual care group were told of their abnormal pulmonary function but given no recommendations for their health care. They were asked to return on an annual basis for repeated pulmonary function tests. All participants in the special intervention group received the benefit of an intensive &week, group-based, smoking-cessation program, consisting of individual and group support, education concerning the harmful effects of tobacco and the benefits of smoking cessation, counseling in behavior modification techniques, and nicotine replacement (in the form of nicotine-containing chewing gum) under medical supervision. In a second, double-blind randomization procedure, participants in the special intervention group were individually assigned to receive either a placebo inhaler or a bronchodilator inhaler (ipratropium bromide). Participants were strongly encouraged to use the inhaler, which, they were told, would probably add to the benefit of smoking cessation. Recommendations for inhaler use were two actuations 1 minute apart three times a day. Follow-up Visits Participants in the special intervention group are currently followed every 4 months, at which time smoking cessation and compliance with inhaler use are monitored. The occasion is also used to encourage and enhance compliance. 4A-34s
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Monitoring of Inhaler Use At all 10 centers, responses to questions concerning inhaler use were validated every 4 months by canister weighing with a precalibrated Sartorius portable electronic balance with digital readout (model 1002; Brinkmann Instruments Company, Westbury, NY). Canisters were weighed both when issued and returned; the difference between these weights was divided by the number of days between issuance and return to determine the average daily usage. At two of the 10 centers (Johns Hopkins University and UCLA), a Nebulizer Chronolog was used as an additional objective measure of inhaler compliance. The Nebulizer Chronolog (Forefront Engineering Corporation, Denver, CO) is a small, portable electronic device that houses a metered-dose inhaler canister. Each actuation of the canister triggers a microswitch in the Nebulizer Chronolog. The chronolog memory records and stores the date and clock time (within 4 minutes) of each actuation up to 4,096 actuations and is read out by an IBM PC in a day/hour/minute format by a specially designed computer interface. The battery in the chronolog can function for at least 6 months and can be changed by the investigator. The device has been used in a clinical drug trial [lo] and in two epidemiologic studies [11,12] and has been found reliable. At the Johns Hopkins University and UCLA study centers, 237 special intervention participants received the Nebulizer Chronolog on a sequential basis. Forty (17%) of these either forgot to bring their chronologs to the clinic for reading, missed their first 4-month follow-up appointment, or received chronologs that malfunctioned (dead battery, improperly initialized, or other technical problem). A total of 197 participants returned for their follow-up appointments with a Nebulizer Chronolog that yielded usable results. Eighty-five (43%) of the latter participants did not know that the chronolog was actually recording the exact time and date of each actuation (uninformed group). The remaining 112 were informed of the function of the chronolog and were given feedback of the information derived from the chronolog in an attempt to enhance compliance (feedback group). To reduce the possibility of contamination, assignment to the uninformed or feedback category was uniform for all participants in any group attending the same 1.2 week intensive smoking-cessation program. For the feedback participants, the chronolog memory was read by the interventionist on several occasions over the course of this 12-week program. If the feedback participants were not using the bronchodilator three times per day at appropriately spaced intervals or were not using two actuations
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per set, that information was given to them and the interventionist worked with them to improve adherence to the prescribed regimen. Those feedback participants for whom the chronolog revealed good compliance were congratulated and encouraged to continue their proper inhaler use.
AIRWAYS DISEASE / TASHKIN ET AL
TABLE I Definitions of Compliance Ratings Determined by Canister Weights Canister Weight” k/day)
Canister Weight Canisters were weighed to determine compliance. If participants took six inhalations from the inhaler over the course of the day as prescribed (two actuations, three times a day), this would lead to a loss of weight from the canister of approximately 0.4 g a day (1 actuation = 0.067 g; 6 actuations = 0.402 g/day). Since the weight of the canister was measured at the beginning of the study, mean daily canister weight loss could be measured at the 4-month follow-up visit. The definitions of compliance ratings are shown in Table I.
Chronolog Functional “Weight” A concept of chronolog functional “weight” was developed to compare the results obtained from the Nebulizer Chronolog with those obtained from canister weights. An inhaler use was defined as a set of actuations composed of all actuations within a 3-hour period. The first actuation after the end of each 3-hour set began a new set. The chronolog “weights” ignore any actuations in excess of the recommended dose of two actuations per set as functionally unimportant on the assumption that two inhalations of the bronchodilator aerosol elicit a maximal or near-maximal response. Thus, each set of actuations, irrespective of whether two or more actuations were associated with the set, was assigned a “weight” of only two actuations (0.13 g). If only one actuation was used, it was assigned a “weight” of 0.067 g. The number of sets with two or more actuations or with only one actuation was multiplied by 0.13 g or 0.067 g, respectively, over the time interval to determine the chronolog functional “weight. ” RESULTS Monitoring of Bronchodilator Use CHRONOLOG VERSUS SELF-REPORTS: Of the 85 uninformed participants who returned for their 4-month follow-up visit and had a technically functioning chronolog, 87% reported that they used the inhaler at least twice a day, whereas only 52% actually used the inhaler two or more times daily according to the chronolog record. These observations indicate that, according to self-reports, many participants overestimated their frequency of use.
Overcompiiance Good %$actory
0.35-0.45 0.20-0.34 0.10-0.19 co.10
‘See text for definition of chronolog functional weight.
In the feedback group of 112 participants with functioning chronologs who returned for their 4-month follow-up visit, 89% reported using the inhaler at least twice daily and 78% actually used the inhaler two or more times a day according to the chronolog. This proportion of feedback participants with satisfactory compliance with the prescribed frequency of inhaler use, as assessed by the chronolog, was significantly greater than the proportion of compliant uninformed participants (p
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inhaler than patients with symptomatic bronchospastic disease because they receive no immediate benefit from their use of the inhaler that might reenforce their motivation to use it in the prescribed manner, and they may be falsely persuaded that they have been assigned an inactive placebo rather than the active bronchodilator because of the absence of perceptible physiologic effects.
The use of the Nebulizer Chronolog allowed objective assessment of compliance with metereddose inhaler use; comparison of compliance measured by the chronolog with compliance measured by other techniques, including canister weights and self-reports; and determination of whether the information derived from the chronolog could be used to enhance participant compliance. With the aid of ACKNOWLEDGMENT the chronolog, we demonstrated that self-report Currently, the principal investigators at the Lung Health Study clinical centers are and canister weighing overestimated the particiC. Bailey, M.D., UAB Lung Health Center, Birmingham, Alabama: Murray D. pants’ inhaler use. We also found that feedback to William Altose, M.D., Veterans Hospital, Brecksville, Ohio; William A. Conway, Jr., M.D., Lung participants regarding their measured usage dur- Health Study, Detroit, Michigan; Gregory R. Owens, M.D., University of Pittsburgh, ing follow-up visits had a positive effect on compliDivision of Pulmonary Medrcine, Pittsburgh, Pennsylvania; A. Sonia Buist, M.D., ance. In addition, we believe we have identified for OHSU Lung Health Study, Portland, Oregon; Paul L. Enright, M.D., Mayo Clinrc, Rochester, Minnesota; Richard E. Kanner, M.D., University of Utah Medical Center, the first time a type of noncompliant participant in Salt Lake City, Utah; Nrcholas R. Anthonisen, M.D., University of Manitoba, Winnrpeg, a clinical trial involving a metered-dose inhaler who Manitoba: and Donald P. Tashkin, M.D., Department of Medicine, UCLA School of Medicine, Los Angeles, California. ~ hides the fact of noncompliance from the investigaThe authors are grateful to Boehrrnger Ingelherm, Inc., for purchase of the Nebutor by “dumping” most or all of the contents of one lizer Chronologs. or more canisters in a short period of time, usually just before returning for a follow-up visit. 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Tashkin DP, Ashutosh K, Bleecker ER et al. Comparrson of the anticholinergic persuade them that they are inhaling an “active” bronchodilator lpratropium bromide with metaproterenol in chronic obstructrve puldrug. It might be expected, therefore, that the par- monary drsease. A go-day multi-center study. Am J Med 1986; 81 (Suppl 5A): 81ticipants would be less likely to use the prescribed 90.
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