The Long-Term Burden of COPD Exacerbations During Maintenance Therapy and Lung Function Decline

Marjan Kerkhof; Jaco Voorham; Paul Dorinsky; Claudia Cabrera; Patrick Darken; Janwillem W H Kocks; Mohsen Sadatsafavi; Don D Sin; Victoria Carter; David B Price

doi:10.2147/COPD.S253812

The Long-Term Burden of COPD Exacerbations During Maintenance Therapy and Lung Function Decline

Int J Chron Obstruct Pulmon Dis. 2020 Aug 6:15:1909-1918. doi: 10.2147/COPD.S253812. eCollection 2020.

Authors

Marjan Kerkhof¹, Jaco Voorham¹, Paul Dorinsky², Claudia Cabrera^{3

4}, Patrick Darken⁵, Janwillem W H Kocks^{1

6}, Mohsen Sadatsafavi^{7

8}, Don D Sin^{7

8}, Victoria Carter¹, David B Price^{1

9}

Affiliations

¹ Observational & Pragmatic Research Institute Pte Ltd, Singapore, Singapore.
² AstraZeneca, Durham, NC, USA.
³ AstraZeneca, Mölndal, Sweden.
⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
⁵ AstraZeneca, Morristown, NJ, USA.
⁶ General Practitioners Research Institute, Groningen, The Netherlands.
⁷ Respiratory Evaluation Sciences Program, Collaboration for Outcomes Research and Evaluation, University of British Columbia, Vancouver, BC, Canada.
⁸ Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada.
⁹ Academic Primary Care, University of Aberdeen, Aberdeen, UK.

Abstract

Introduction: Early identification of preventable risk factors of COPD progression is important. Whether exacerbations have a negative impact on disease progression is largely unknown. We investigated whether the long-term occurrence of exacerbations is associated with lung function decline at early stages of COPD.

Methods: Patients diagnosed with mild/moderate COPD (obstruction and FEV₁% predicted 50-90%), aged ≥35 years, and a smoking history, who had ≥6 years of UK electronic medical records after initiation of maintenance therapy were studied. Multilevel mixed-effect linear regression was performed to determine the association between the count of any year in which the patient had ≥1 exacerbation over a 6-year period and FEV₁ decline, adjusted for sex, age, anthropometrics and smoking habits. Exacerbations were defined as any prescription for an acute oral corticosteroid course and/or lower respiratory-related antibiotics and/or any COPD-related emergency or inpatient hospitalization.

Results: Of 11,337 patients included (mean age 65 years; 49% female) 31.6%, 23.3%, 16.6%, 11.6%, 8.1%, 5.3% and 3.4% had 0, 1, 2, 3, 4, 5 and 6 years with ≥1 exacerbation. The mean annual FEV₁ decline accelerated by 1.50 mL/year (95% Confidence Interval 1.02; 1.98) with every additional year with ≥1 exacerbation from 31.0 mL/year in subjects without any exacerbation to 40.0 mL/year in patients experiencing ≥1 exacerbation every year. Patients with more years with ≥1 exacerbation had a lower mean FEV₁ at first diagnosis: 14.7 mL (11.7; 17.8) lower with every additional year with exacerbations. When counting years with ≥2 exacerbations, greater effects were observed (2.19 [1.50; 2.88] mL/year excess decline per year with ≥2 exacerbations; 16.5 mL [12.1; 20.8] lower FEV₁ at diagnosis).

Conclusion: Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies.

Keywords: COPD; exacerbations; inhalation therapy; observational study; spirometry.

MeSH terms

Aged
Disease Progression
Female
Forced Expiratory Volume
Humans
Lung
Male
Pulmonary Disease, Chronic Obstructive* / diagnosis
Pulmonary Disease, Chronic Obstructive* / drug therapy
Pulmonary Disease, Chronic Obstructive* / epidemiology
Respiratory Function Tests

Grants and funding

This study is funded by AstraZeneca. AstraZeneca participated in the study design and reporting.