Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice

Abstract

Purpose: Acute, severe asthma exacerbations can be difficult to predict and thus prevent. Patients who have frequent exacerbations are of particular concern. Practical exacerbation predictors are needed for these patients in the primary-care setting.

Patients and methods: Medical records of 130,547 asthma patients aged 12-80 years from the UK Optimum Patient Care Research Database and Clinical Practice Research Datalink, 1990-2013, were examined for 1 year before (baseline) and 1 year after (outcome) their most recent blood eosinophil count. Baseline variables predictive (P<0.05) of exacerbation in the outcome year were compared between patients who had two or more exacerbations and those who had no exacerbation or only one exacerbation, using uni- and multivariable logistic regression models. Exacerbation was defined as asthma-related hospital attendance/admission (emergency or inpatient) or acute oral corticosteroid (OCS) course.

Results: Blood eosinophil count >400/µL (versus ≤400/µL) increased the likelihood of two or more exacerbations >1.4-fold (odds ratio [OR]: 1.48 (95% confidence interval [CI]: 1.39, 1.58); P<0.001). Variables that significantly increased the odds by up to 1.4-fold included increasing age (per year), female gender (versus male), being overweight or obese (versus normal body mass index), being a smoker (versus nonsmoker), having anxiety/depression, diabetes, eczema, gastroesophageal reflux disease, or rhinitis, and prescription for acetaminophen or nonsteroidal anti-inflammatory drugs. Compared with treatment at British Thoracic Society step 2 (daily controller ± reliever), treatment at step 0 (none) or 1 (as-needed reliever) increased the odds by 1.2- and 1.6-fold, respectively, and treatment at step 3, 4, or 5 increased the odds by 1.3-, 1.9-, or 3.1-fold, respectively (all P<0.05). Acute OCS use was the single best predictor of two or more exacerbations. Even one course increased the odds by more than threefold (OR: 3.75 [95% CI: 3.50, 4.01]; P<0.001), and three or more courses increased the odds by >25-fold (OR: 25.7 [95% CI: 23.9, 27.6]; P<0.001).

Conclusion: Blood eosinophil count and several other variables routinely available in patient records may be used to predict frequent asthma exacerbations.

Keywords: exacerbator; hospitalization; multiple; risk.

Figure 1

CONSORT diagram of the patient selection process. Abbreviation: resp, respiratory.

Figure 2

Odds of two or more exacerbations (versus 0 or 1) in the next year. Notes: (A) Demographic and clinical indices; (this multivariable model also includes the predictors shown in B). *Prescription for nonsteroidal anti-inflammatory drugs was interchangeable with acetaminophen prescription and similarly increased the likelihood of two or more exacerbations in the next year (odds ratio: 1.12 [95% CI: 1.06, 1.18]; P<0.001). (B) Asthma treatment and control; (this multivariable model also includes the predictors shown in A). ^†Hospital, asthma indicates asthma-related hospital attendance/admission (here, at least one outpatient attendance) during the baseline year. *Treatment step was interchangeable with average daily short-acting β2 agonist or inhaled corticosteroid dosage. (C) Average daily SABA and ICS dosages when these variables replaced treatment step in the multivariable model. Reference category for each variable is none (0 µg/day). Abbreviations: Blood eosin, blood eosinophil count; BMI, body mass index; CI, confidence interval; FP, fluticasone propionate; GERD, gastroesophageal reflux disease; GP, general practitioner; ICS, inhaled corticosteroid; LRTI, lower respiratory tract infection; OCS, oral corticosteroid; SABA short-acting β2 agonist.

Figure 2

Odds of two or more exacerbations (versus 0 or 1) in the next year. Notes: (A) Demographic and clinical indices; (this multivariable model also includes the predictors shown in B). *Prescription for nonsteroidal anti-inflammatory drugs was interchangeable with acetaminophen prescription and similarly increased the likelihood of two or more exacerbations in the next year (odds ratio: 1.12 [95% CI: 1.06, 1.18]; P<0.001). (B) Asthma treatment and control; (this multivariable model also includes the predictors shown in A). ^†Hospital, asthma indicates asthma-related hospital attendance/admission (here, at least one outpatient attendance) during the baseline year. *Treatment step was interchangeable with average daily short-acting β2 agonist or inhaled corticosteroid dosage. (C) Average daily SABA and ICS dosages when these variables replaced treatment step in the multivariable model. Reference category for each variable is none (0 µg/day). Abbreviations: Blood eosin, blood eosinophil count; BMI, body mass index; CI, confidence interval; FP, fluticasone propionate; GERD, gastroesophageal reflux disease; GP, general practitioner; ICS, inhaled corticosteroid; LRTI, lower respiratory tract infection; OCS, oral corticosteroid; SABA short-acting β2 agonist.

Figure 3

HES subset: odds of at least one inpatient admission for asthma (versus 0) in the next year. Notes: The HES subset comprised 47,718 patients (37% of the full study group). ^†Hospital, asthma 1+, at least one asthma-related hospital attendance/admission during the baseline year (data from clinic records). Abbreviations: Blood eosin, blood eosinophil count; CI, confidence interval; equiv, equivalents; FP, fluticasone propionate; GP, general practitioner; HES, Hospital Episode Statistics; ICS, inhaled corticosteroid; LRTI, lower respiratory tract infection; OCS, oral corticosteroid.