Association Between Chronic Obstructive Pulmonary Disease and Gastroesophageal Reflux Disease

A National Cross-sectional Cohort Study

Jinhee Kim; Jin Hwa Lee; Yuri Kim; Kyungjoo Kim; Yeon-Mok Oh; Kwang Ha Yoo; Chin Kook Rhee; Hyoung Kyu Yoon; Young Sam Kim; Yong Bum Park; Sei Won Lee; Sang Do Lee


BMC Pulm Med. 2013;13(51) 

In This Article


Data Source and Ethical Considerations

The present study used the National Health Insurance claims data for medical services provided to Koreans aged ≥ 40 years between January 1, 2009 and December 31, 2009. These data were provided by the Korean Health Insurance Review and Assessment Service (HIRA), which was established to review claims data and assess healthcare in Korea and is under the responsibility of a single agency independent from insurers, providers, and other interested parties. All Koreans are covered under the national health insurance system, and the HIRA database contains all information regarding submitted claims and prescriptions.

The HIRA claims database comprises general item, medical treatment, diagnosis, and prescription databases. The general item database contains information such as patient identifier, age, sex, and insurance type; hospital name, type, location, and medical department; and medical cost, number of days hospitalized and/or receiving outpatient, intensive care unit (ICU), and/or emergency room (ER) care. The medical treatment database contains information such as patient identifier, detailed medical treatment records, and drug administration (brand name, total days of medication, single dose, daily dose, and unit cost). The diagnosis database contains information such as patient identifier, main diagnosis, and submain diagnoses, recorded according to the International Classification of Diseases, 10th Revision (ICD-10). The prescription database contains information such as patient identifier and outpatient prescriptions. All databases were linked using a mutual identifier.

The National Evidence-Based Healthcare Collaborating Agency (NECA) ethics committee approved the present study (PIRB11-022).

Study Population

The subjects of the current study were patients aged ≥40 years with COPD recorded as ICD-10 codes J42.x–J44.x (except J430) for the principal or additional diagnoses who were given prescriptions including at least one of the following medications (including oral, injected, or inhaled), at least twice per year: combinations in a single inhaler of inhaled corticosteroids (ICSs) and long-acting beta-2 agonists (LABAs), long-acting muscarinic antagonists (LAMAs), LABAs, short-acting muscarinic antagonists (SAMAs), inhalers with both short-acting beta-2 agonists (SABAs) and SAMAs, oral beta-2 agonists, or theophylline.

Patients with more than one claim per year due to cancer (C00.x–C97.x) and/or cerebrovascular disease (I60.x–I69.x) were excluded from this study because the enormous expenses claimed for treatment of these diseases were difficult to distinguish from COPD- and GERD-related medical services. Additionally, through consultation with six physicians of pulmonary medicine, we decided to exclude patients with more than one claim per year for hiatal hernia (K449), gastric surgery (K910–K913), Zollinger-Ellison syndrome (E164), systemic sclerosis (M34), achalasia (K220), pyloric obstruction (K311–K315), obesity (E66.x), alcoholic liver disease (K70.x), or ascites (K7151, R18, C786, A1830) because these diseases increase the risk for GERD.

Among subjects in the present study, 39,987 patients with COPD used medical services more than once per year for GERD (K21, K210, K219), and 101,070 patients with COPD did not have GERD.


Baseline Characteristics. The variables considered to be baseline characteristics were sex, age, insurance type, hospitalization and ICU hospitalization, number of ER visits, presence of chest X-rays, spirometry, chest CT, esophagogastroduodenoscopy, 24-h esophageal pH monitoring and esophagography, COPD severity, and comorbidity. The 'severe' COPD group comprised patients who visited a tertiary medical institution and were prescribed ICS + LABA + LAMA, ICS + LABA + oral corticosteroid (OCS), or LAMA + OCS more than once per year, and the 'not severe' group comprised the remaining study subjects. ER visits were defined as cases in which an outpatient or hospitalization claim was made for emergency medical service fees or in which additional holiday/night service fees were incurred. Co-morbidities included ischemic heart disease (I20.x–I25.x, except I20.1), osteoporosis (M80.x–M82.x), depressive disorder (F32.x–F33.x), arthritis (M05.x–M09.x, M13.x), diabetes mellitus (E10.x–E14.x), congestive heart failure (I50, I50.0, I50.1, I50.9), hypertension (I10.x), anemia (D50.x–D53.x, D63.x), metabolic syndrome (E66, E78.0, E78.4, E78.5), Barrett's esophagus (B227), gastric ulcer (K25.x), duodenal ulcer (K26.x), peptic ulcer (K27.x–K28.x), and gastroduodenitis (K29.x).

Medications Used. Medications considered in the present study included ICSs, ICSs/LABAs, LAMAs, LABAs, leukotriene receptor antagonists (LTRAs), OCSs, SAMAs, SABAs, SABAs/SAMAs, oral beta-2 agonists, and theophylline covering all form of drug such as oral medications, injections, and inhalations.

Exacerbation of COPD. Exacerbation was defined as hospitalization or ER visits. Only subjects who were admitted to the department of internal medicine and received systemic corticosteroids during at least three days or recorded as ICD code for COPD exacerbation were included. Cases receiving systemic corticosteroids and inhaled short-acting bronchodilators at ER visits were included.

Statistical Analyses

Data were analyzed using the SAS statistical program (ver. 9.2 [SAS Institute]); details of the analytical methods were as follows.

First, frequencies and percentages were calculated to enable comparison of baseline characteristics between COPD patients with GERD and those without GERD; the chi-squared test was used for categorical data, and the t-test was used for continuous data.

Second, the difference in medication usage between groups was determined using frequencies and percentages.

Third, univariate logistic regression was performed to understand the relationship between the general characteristics of patients with COPD and the presence of GERD, and multiple logistic regression was performed, with general characteristic variables included in the model.

Fourth, univariate logistic regression was performed to understand the relationship between the co-morbidity of patients with COPD and the presence of GERD, and the relationship between the medication usage of patients with COPD and the presence of GERD. Additionally, multiple logistic regression analysis was performed with adjustment for sex, age, type of health insurance, history of hospitalization and ICU hospitalization, category of ER visit, and COPD severity.

Fifth, univariate logistic regression was performed to understand the relationship between the presence of GERD in patients with COPD and the exacerbation of COPD, and multiple logistic regression was performed with adjustment for sex, age, type of health insurance, and COPD severity.