Our analysis has characterized asthma controller medication use over time among children and adolescents with asthma enrolled in CAMPCS. We found that most participants reported well-controlled asthma symptoms and that no asthma controller medication was used during a 4-year observational period. Inhaled corticosteroid use continued to decrease during the study period and was not countered by a significant increased use of alternate asthma controller medications, such as LTRA. Among a subgroup of participants who were recommended to continue receiving ICS therapy at the outset of the observational period, reported rates of ICS use were higher but also diminished over time.
Our results illustrate trends in asthma medication use over time in a large cohort of participants with mild-to-moderate asthma. We observed a decline in the proportion of patients using ICS over time, with many patients reporting no use of an asthma controller medication during the 4-year observational period. Such a trend is not entirely surprising, because the cohort was mainly composed of adolescent patients. One explanation may be the natural history of asthma, demonstrated in previous epidemiologic studies, which has shown remission in asthma symptoms over time17–19
; only a few children who report minimal symptoms during adolescence continue to have symptoms into adulthood.20,21
Even among patients without true remission, symptoms may improve over time. Patients and health care providers likely make decisions about asthma controller medication use based on their current symptoms. In the setting of well-controlled asthma, they choose to discontinue controller therapy. This is illustrated by the subgroup recommended to continue ICS therapy at the outset of the CAMPCS follow-up period. Among this subgroup, rates of reported ICS use decreased over time and because these participants reported well-controlled asthma symptoms during most of the clinical encounters, we can speculate that they or their treating clinicians made the decision to discontinue use of controller therapy. Such decisions are consistent with asthma treatment guidelines; a step-down approach to therapy is recommended for patients whose asthma symptoms are well controlled.1
In our analysis of asthma control over time, we found that female sex and clinician-evaluated asthma severity were independently associated with not well-controlled asthma. Such sex differences in asthma outcomes have been seen in other studies, with adolescent girls demonstrating worse asthma outcomes.22–24
Airway responsiveness is more severe in postpubertal females with asthma than in males25
and may contribute to increased asthma severity, increased episodes of poor control, and asthma medication use. An association between level of control and asthma severity is not surprising and has also been reported.26,27
In contrast, our findings revealed that participant age was unrelated to poor asthma control. Finally, contrary to our initial hypothesis that consistent ICS use would be associated with well-controlled asthma, participants who reported consistent ICS use were more likely to report not well-controlled asthma over time. This suggests that there are individuals who report not well-controlled asthma despite seemingly appropriate therapy.
In the multivariate analysis, we controlled for several accepted markers of asthma severity, including pulmonary function and clinician-rated severity evaluation, yet the association of increased medication use and not well-controlled asthma persisted. This may be the result of residual confounding by asthma severity, and the reported use of asthma medications would thus be interpreted as an additional marker of asthma disease severity.
However, other explanations should be considered, including patient nonadherence or other potential patient comorbidities. Depression has been shown to affect both asthma severity and control,28
and self-report of medication adherence tends to result in overestimating the patient's adherence. Patients or their parents often try to please their physicians by reporting what they think their physician wants to hear. This is supported by evidence from clinical trials that the mean number of doses taken, as recorded in diaries, is significantly higher than the number actually taken, as recorded by the monitoring devices, and most patients overestimate use of medication.29,30
In a 6-month ancillary study31
focusing on adherence among the CAMP posttrial observation cohort, monthly telephone encounters were conducted by nurses who had no prior relationship and no subsequent contact with the participants. In this study, low ICS adherence was associated with more frequent asthma symptoms. However, our data did not include other measures of medication adherence, and participants who were reporting consistent ICS use and poor control during their encounters may have been poorly adherent despite reporting taking ICS as prescribed.
An alternative explanation for our findings may be an inherent variability in response to asthma therapy, particularly the existence of relative steroid resistance. Variability in response to ICS has been demonstrated in other studies,32,33
and high rates of uncontrolled asthma have been identified in other populations in the setting of standard asthma medication use.34,35
In the current analysis, we have identified a subgroup of children and adolescents who did not achieve asthma control despite seemingly appropriate therapy. This subgroup may have relative steroid resistance, possibly as the result of genetic factors such as steroid receptor polymorphisms.36–38
A recent analysis of clinical data from the CAMP trial has examined a cohort with persistently poor response to ICSs, as defined by lung function response and exacerbations.39
Our current study supports the concept of steroid resistance, not just in the clinical trial setting but longitudinally in cohorts as well. In fact, given that many children with asthma improve their asthma control to the level that they are either asymptomatic or need only intermittent reliever therapy, our findings illustrate the natural history of a subgroup of asthmatic patients who may be predisposed to steroid resistance. Future work is needed to better characterize such individuals who do not achieve asthma control despite ICS or other appropriate controller therapy.
Our analysis has several limitations. Because CAMPCS is an observational study, and not a randomized trial of differing strategies for ICS use, the determinants of the different patterns of ICS use among patients are unclear. We did not have access to data on whether asthma medication was being prescribed by each participant's physician. We also did not have data on ICS dose regimens; therefore, it is possible that some participants were not receiving sufficient ICS doses to achieve asthma control.
In conclusion, we found low reported use of ICS and other asthma controller medications during the 4-year observational period of children and adolescents with mild-to-moderate asthma in the CAMP posttrial observation period, even among participants who received a recommendation to continue receiving ICS therapy at the end of the CAMP trial. In general, these children continued to have well-controlled asthma, suggesting that patients and clinicians are stepping down therapy in an appropriate manner based on current symptoms. However, we also identified a subgroup of children and adolescents who are not achieving well-controlled asthma despite reporting consistent use of ICSs. Medication nonadherence or the coexistence of asthma-related comorbidities may explain these findings and should be investigated in children and adolescents with difficult to control asthma. However, further study of the role of relative steroid resistance and its impact on the management of patients may help to better understand the relationship between medication use and asthma control.