In this multivariable analysis of a claims-linked survey study assessing symptom burden in patients with COPD receiving LAMA monotherapy, multiple patient-level factors that can influence symptom burden, as measured by CAT, were identified. In particular, patients with a long history of COPD diagnosis and who are current smokers were predicted to have a higher symptom burden as shown by an increase in CAT score of ≥ 2 points, which is the estimated minimal clinically important difference (MCID) . This may be a reflection of disease progression and/or indicate that these patients may benefit from additional therapeutic intervention. It is interesting to note that baseline exacerbation counts were highly significant predictors of symptom burden; the effect did not meet the MCID threshold of ≥ 2 points. This may be due to factors that were not observed in this study, such as the time between the last exacerbation and patient survey. Similarly, other clinical or patient-level factors not assessed in this study may mediate the relationship between exacerbations and symptom burden. Other observational research has shown a stronger relationship between symptom burden and exacerbation rate , suggesting this is an important area for further research. Depression is an important comorbidity in patients with COPD and can have negative effects on mortality, rate of COPD exacerbation, length of hospital stay, quality of life (QoL), and functional status . In this study, diagnosis of and/or treatment for depression was related to increased symptom burden when interacted with age (although it did not meet the estimated MCID of a CAT score ≥ 2 points). This association between CAT score and depression is consistent with previous studies , including prior evidence that suggests that age and high levels of symptoms are independent predictors of depression in patients with COPD, and are associated with a lower patient-reported health status .
The role of validated PROs in assessment of COPD has become increasingly important due to growing recognition of their value in reflecting the symptom burden and health status of individual patients [9, 20]. The mMRC dyspnea scale is a valid and reliable measure of breathlessness, relates well to other measures of health status, and can be predictive of mortality risk [6, 9, 21–23]. However, a more comprehensive assessment of symptoms, that goes beyond breathlessness, is now recommended . The St George’s Respiratory Questionnaire (SGRQ) is the most widely documented tool for assessment for health status in COPD; however, with 50 questionnaire items, it is often considered to be too complex and burdensome for use in routine clinical practice [6, 20]. The CAT was developed as a more focused measure of symptom burden in COPD for routine clinical use; consisting of eight items, it is shorter and simpler to use than the SGRQ while providing a broader measure of symptom burden than the mMRC [10, 20, 24, 25]. The CAT has been found to be a reliable, appropriate, and responsive instrument for measuring symptom burden in patients with COPD [6, 10, 24, 26, 27], and has demonstrated good correlation with established QoL questionnaires, including the SGRQ, and other relevant measures of disease severity [28, 29]. This is consistent with published data, where a high level of correlation between measures of COPD symptom burden was noted, with > 70% of patients obtaining high scores on at least two PROs (Supplementary Table 1) .
The CAT can be used at a single point in time, is easy to use in clinical practice, and can improve patient−physician communication during routine clinical visits. In real-world studies, the CAT has demonstrated predictive value for future incidence of exacerbations  and all-cause mortality . It is responsive to changes in health status following acute exacerbations or pulmonary rehabilitation , and it correlates with lung function impairment, exacerbation rates and number of comorbidities . The development and use of the CAT in clinical trials, and continued use in real-world assessments, will ensure that key COPD concepts are reliably measured and that relevant treatment effects are being captured .
Standard of care for patients with COPD should include measures of symptom burden, such as the CAT, to evaluate patient outcomes . Physicians should consider the use of instruments such as the CAT on a continuous basis as it has been shown to be responsive to recovery from an exacerbation , and to predict treatment failure . It is important, however, for physicians to be aware of factors that may influence the CAT score both at diagnosis and on a continual basis . As demonstrated in this study, factors such as time since COPD diagnosis, smoking status, rural versus urban location of residence, baseline counts of exacerbations, and number of office visits are important predictors of symptom burden as indicated by the observed increase in CAT score. The use of the CAT in this way may allow COPD treatment to be better targeted and patient management to be optimized, as well as potentially contributing to the amelioration of both the clinical and economic burden associated with COPD.
Claims-linked survey studies are associated with a number of limitations. The presence of a diagnosis code on a medical claim does not indicate conclusive evidence of the disease, as the diagnosis code may have been incorrectly coded or included as a rule-out criterion. Patients with a diagnosis of asthma were not excluded from the study and spirometry data were not available to confirm the COPD diagnoses. However, to help address these limitations, multiple pharmacy claims and diagnosis codes were required for inclusion. The study is also subject to limitations of survey data, including sampling, coverage, and measurement error. For example, treatment adherence was not measured in this study and the database does not provide information on whether a prescription was redeemed, which may have impacted outcomes. However, it is unlikely that this population has different patterns of adherence than other insured patient populations with COPD . Finally, the study population was made up of patients with commercial health plan coverage and MA enrollees, and therefore the results of the study may not be reflective of uninsured populations, younger patients with COPD, or generalizable to populations outside the United States. For instance, the mean age of patients and proportion of females in our study was higher than typically reported for COPD populations , and the level of education was fairly low.