COPD: An Independent Risk Factor for Peptic Ulcer Bleeding
COPD: An Independent Risk Factor for Peptic Ulcer Bleeding
In the present study, COPD patients (HR: 1.93; 95% CI, 1.73–2.17) have significantly higher risk of developing ulcer bleeding after adjustments for possible confounding factors such as age, gender, comorbidities (i.e. hypertension, diabetes, coronary heart disease, heart failure, chronic renal disease, and history of peptic ulcer disease) and ulcerogenic medication (e.g. NSAIDs, ASA, steroids, clopidogrel, ticlopidine and warfarin). Older age, male gender, hypertension, diabetes, heart failure, chronic renal disease, peptic ulcer history and NSAIDs use are important risk factors for ulcer bleeding in COPD patients.
The original study design aimed to match all major comorbid medical diseases (i.e. hypertension, diabetes, coronary heart disease, heart failure, chronic renal disease and history of peptic ulcer disease) and concurrent ulcerogenic medication between the COPD and control groups. However, it failed in comorbid disease matching because COPD patients had higher proportions of other comorbidities. This may reflect the actual real-life conditions and coincide with a recent concept that COPD is no longer a localised inflammatory disease limited to the lungs but is a systemic inflammatory disease that may be associated with other systemic diseases like hypertension, diabetes, cardiovascular disease or chronic kidney disease.
During the 8-year follow-up period, COPD patients indeed had a higher risk of developing peptic ulcer bleeding than the general population (Figure 1). Previous studies also showed that smoking and COPD were risk factors of peptic ulcer disease. The present study found that COPD patients had a higher proportion of peptic ulcer disease history (22.1 vs. 10.2%, P < 0.001). Previously, most studies for evaluating the risk factors of peptic ulcer bleeding mainly focused on NSAIDs or aspirin use, or H. pylori infection. Very few studies delved on the relationship between peptic ulcer bleeding and smoking or COPD. A population-based cohort study in Denmark showed that smoking was a risk factor for ulcer perforation but not for ulcer bleeding. The other case–control study found that patients with co-existing lung disease increased the risk of ulcer bleeding (OR:2.5, 95% CI 1.40–4.46) but did not specify the associated lung disease. The present study is the first large-scale, longitudinal, population-based cohort study to clarify that COPD indeed increases the risk of peptic ulcer bleeding.
There may be several reasons why COPD increases ulcer bleeding risk. First, COPD is characterised not only by chronic local but also by systemic inflammation. Thus, COPD patients are exposed to oxidative stress secondary to chronic hypoxia and produce reactive oxygen species (ROS) that may damage gastric or small intestinal mucosa. Second, COPD patients share other smoking-related chronic diseases, such as hypertension, coronary artery disease, or heart failure, and have more instances using anti-platelet agents, which protect against cardiovascular events but increase ulcer bleeding risk. Third, COPD patients often need steroids for controlling lung inflammation. Steroid-induced peptic ulcer disease is controversial but steroids reportedly delay peptic ulcer healing. Despite the multifaceted hypothesis and associated confounding factors, the present study shows that COPD (HR 1.93, 95% CI 1.73–2.17) remains an independent risk factor of ulcer bleeding after adjusting for confounding factors like hypertension, coronary artery disease, heart failure and ulcerogenic medication, including NSAIDs, anti-platelet agents and steroids.
The current study has several limitations. First, this is a retrospective cohort study with observations based on hospitalised patients with peptic ulcer bleeding. Certain selection biases may exist such that caution must be taken in extrapolating the results. Second, it is well known that H. pylori infection is an important risk factor for ulcer bleeding, but we did not have H. pylori prevalence in the NHIR database. However, the issue whether COPD patients really have higher H. pylori seroprevalence is still controversial and there even may be no association between H. pylori infection and COPD in a published study. Therefore, further large-scale study is needed for evaluation the prevalence of H. pylori infection in COPD patients. Third, although smoking is an important risk factor for both COPD and peptic ulcer, such information is not available from the NHIR database. However, emerging evidence supports that risk factors other than smoking play important parts of developing COPD. An estimated 25–45% of patients with COPD have never smoked. Therefore, a prospective study is warranted to clarify the role of smoking in COPD patients with ulcer bleeding. Finally, although socioeconomic status could be also a possible confounder in COPD patients with ulcer bleeding, the socioeconomic status was unavailable in our database.
Discussion
In the present study, COPD patients (HR: 1.93; 95% CI, 1.73–2.17) have significantly higher risk of developing ulcer bleeding after adjustments for possible confounding factors such as age, gender, comorbidities (i.e. hypertension, diabetes, coronary heart disease, heart failure, chronic renal disease, and history of peptic ulcer disease) and ulcerogenic medication (e.g. NSAIDs, ASA, steroids, clopidogrel, ticlopidine and warfarin). Older age, male gender, hypertension, diabetes, heart failure, chronic renal disease, peptic ulcer history and NSAIDs use are important risk factors for ulcer bleeding in COPD patients.
The original study design aimed to match all major comorbid medical diseases (i.e. hypertension, diabetes, coronary heart disease, heart failure, chronic renal disease and history of peptic ulcer disease) and concurrent ulcerogenic medication between the COPD and control groups. However, it failed in comorbid disease matching because COPD patients had higher proportions of other comorbidities. This may reflect the actual real-life conditions and coincide with a recent concept that COPD is no longer a localised inflammatory disease limited to the lungs but is a systemic inflammatory disease that may be associated with other systemic diseases like hypertension, diabetes, cardiovascular disease or chronic kidney disease.
During the 8-year follow-up period, COPD patients indeed had a higher risk of developing peptic ulcer bleeding than the general population (Figure 1). Previous studies also showed that smoking and COPD were risk factors of peptic ulcer disease. The present study found that COPD patients had a higher proportion of peptic ulcer disease history (22.1 vs. 10.2%, P < 0.001). Previously, most studies for evaluating the risk factors of peptic ulcer bleeding mainly focused on NSAIDs or aspirin use, or H. pylori infection. Very few studies delved on the relationship between peptic ulcer bleeding and smoking or COPD. A population-based cohort study in Denmark showed that smoking was a risk factor for ulcer perforation but not for ulcer bleeding. The other case–control study found that patients with co-existing lung disease increased the risk of ulcer bleeding (OR:2.5, 95% CI 1.40–4.46) but did not specify the associated lung disease. The present study is the first large-scale, longitudinal, population-based cohort study to clarify that COPD indeed increases the risk of peptic ulcer bleeding.
There may be several reasons why COPD increases ulcer bleeding risk. First, COPD is characterised not only by chronic local but also by systemic inflammation. Thus, COPD patients are exposed to oxidative stress secondary to chronic hypoxia and produce reactive oxygen species (ROS) that may damage gastric or small intestinal mucosa. Second, COPD patients share other smoking-related chronic diseases, such as hypertension, coronary artery disease, or heart failure, and have more instances using anti-platelet agents, which protect against cardiovascular events but increase ulcer bleeding risk. Third, COPD patients often need steroids for controlling lung inflammation. Steroid-induced peptic ulcer disease is controversial but steroids reportedly delay peptic ulcer healing. Despite the multifaceted hypothesis and associated confounding factors, the present study shows that COPD (HR 1.93, 95% CI 1.73–2.17) remains an independent risk factor of ulcer bleeding after adjusting for confounding factors like hypertension, coronary artery disease, heart failure and ulcerogenic medication, including NSAIDs, anti-platelet agents and steroids.
Limitations
The current study has several limitations. First, this is a retrospective cohort study with observations based on hospitalised patients with peptic ulcer bleeding. Certain selection biases may exist such that caution must be taken in extrapolating the results. Second, it is well known that H. pylori infection is an important risk factor for ulcer bleeding, but we did not have H. pylori prevalence in the NHIR database. However, the issue whether COPD patients really have higher H. pylori seroprevalence is still controversial and there even may be no association between H. pylori infection and COPD in a published study. Therefore, further large-scale study is needed for evaluation the prevalence of H. pylori infection in COPD patients. Third, although smoking is an important risk factor for both COPD and peptic ulcer, such information is not available from the NHIR database. However, emerging evidence supports that risk factors other than smoking play important parts of developing COPD. An estimated 25–45% of patients with COPD have never smoked. Therefore, a prospective study is warranted to clarify the role of smoking in COPD patients with ulcer bleeding. Finally, although socioeconomic status could be also a possible confounder in COPD patients with ulcer bleeding, the socioeconomic status was unavailable in our database.