In this cohort study of patients with aSAH, we found that compared to patients without COPD, patients with COPD have increased odds of in-hospital death and poor functional outcome at discharge. Moreover, COPD is associated with an increased incidence of seizures and infectious complications, especially pneumonia, which may contribute to the increased mortality and poorer outcomes observed in aSAH patients with COPD.
Several mechanisms may explain the association between COPD and poor outcomes. First, COPD causes spillover of multiple pro-inflammatory markers into the circulation, leading to chronic low-grade systemic inflammation, ultimately resulting in unstable plaque formation and prothrombotic events. Second, COPD especially during exacerbation are hypoxemic and hypercapnic at baseline which may increase their susceptibility to brain injury. The intraneural hypoxemia can occur in approximately 40–50% of patients with mild COPD. Third, COPD have associated comorbid conditions after stroke, such as seizure. Fourth, COPD are commonly treated with corticosteroids, and hospitalized patients on corticosteroids have a heightened risk of nosocomial infection.
Though COPD is known to be a risk for mortality in patients undergoing surgery and in the critically ill, there is a lack of scientific literature on COPD in patients with aSAH. The only study related to this topic assessed the association between mortality and COPD in stroke patients. In agreement with the current study, the previous study suggested that COPD was modestly associated with overall stroke mortality. In subgroup analysis of that study, the greater risks of mortality were seen in patients with intracerebral hemorrhage and patients with ischemic stroke, but not in patients with SAH (adjusted OR 0.98, 95% CI 0.85–1.13). However, the previous study was limited by the epidemiologic study design that was unadjusted for important confounders (hemorrhage severity, smoking and any co-morbidity), which led to the uncertainty of their conclusions.
This study found an association of COPD with poor functional outcome in patients with aSAH. While such an association has not been previously assessed in patients with aSAH, a study found that COPD increased the incidence of discharge to nursing homes and rehabilitation facilities after surgery, and another study found that the discharge destination is a surrogate for mRS functional outcome in stroke survivors. More research is needed to confirm the association of COPD with poor functional outcome in patients with aSAH.
The association between seizures and COPD in patients were also found in patients with stroke from another study, where in a cohort of 237 patients with stroke, COPD was found to be a risk factor for seizures. There are no reliable clinical guidelines for managing post-stroke seizures, and currently no evidence for prophylactic use in patients at risk of an epileptic episode as a complication from stroke. The European Stroke Organization Guidelines do not support the prophylactic use of antiepileptic drugs (class IV, level C). The American Heart Association/American Stroke Association Guidelines state that antiepileptic drugs may be considered in the immediate post-hemorrhagic period and for patients with known risk factors for delayed seizure disorder. Our study provides evidence that COPD is a risk factor for seizures in patients with aSAH, suggesting that antiepileptic drugs may be considered in these patients.
In this study, COPD was associated with an increased frequency of a variety of infection complications. In a cohort study by Lee et al, COPD is an independent risk factor for pneumonia and septic shock after total shoulder arthroplasty. Yakubek et al. published a study found that in patients undergoing total hip arthroplasty, patients with COPD are more likely to experience pneumonia and deep surgical site infection.
Two large randomized clinical trials conducted in patients hospitalized for stroke found that prophylactic antibiotics did not reduce the incidence of pneumonia.[9, 10] A possible explanation for the lack of benefit is that the included patients have a general risk for pneumonia but not high risk, with 7–16% patients developing pneumonia in the control group. In the present study, half of the patients with COPD have pneumonia. The use of prophylactic antibiotics in patients with COPD may reduce the risk of progression to clinically overt pneumonia better than in general patients.
Strengths and limitations
One of the major strengths of our study is the high-quality, standardized, single-institution database, the large sample size, and the use of PSM to adjust for confounders. However, the limitations of this study must also be considered. First, pulmonary function testing was not recorded in our database, and long-term data were not available. This is a retrospective study, and thus data were not recorded for the aim of this study, limiting the strength of our conclusions. Moreover, recall bias may also be present because the medical history of a few cases with altered mental status were collected from their relatives.