September 14, 2009 (Vienna, Austria) — Adult patients hospitalized with community-acquired pneumonia (CAP) have significantly shorter long-term survival than patients hospitalized for medical conditions other than CAP, according to data released here at the European Respiratory Society 19th Annual Congress.
Importantly, the shorter survival remained significant after controlling for age and multiple comorbidities. The shorter survival was seen even after discharge with a clinical "cure."
"The results undermine the longstanding notion that CAP is an acute infection with a short-term impact on survival," study coauthor Paula Peyrani, MD, director of clinical research in the Division of Infectious Diseases at the University of Louisville, Kentucky, told Medscape Pulmonary Medicine.
For the study, the investigators tracked all patients hospitalized in a medical ward at the Veterans Affairs Medical Center in Louisville from June 2001 to March 2006. The study included 624 patients who were hospitalized because of CAP (CAP+) and 6347 patients who were hospitalized for any other medical condition (CAP−).
"Because CAP has been viewed as an acute infection, the final follow-up visit to evaluate a patient's outcome typically occurs about a month after the initial diagnosis," Dr. Peyrani explained. "While a resolution of symptoms at 30 days has usually been regarded as evidence that the patient has survived CAP, recent data have suggested that CAP may influence survival long after patients are considered clinically cured."
In the study, CAP was defined as the presence of a new pulmonary infiltrate on chest X-ray or computed tomography scan at the time of hospitalization, plus at least one of the following criteria: new or increased cough, abnormal temperature (<35.6°C or >38.7°C), or abnormal serum leukocyte count (leukocytosis, left shift, or leucopenia), as defined by local laboratory values.
Patients with CAP were more likely to be elderly and have a higher modified Charlson Comorbidity Index. The mean length of follow-up was 7.5 years.
The study found significantly lower survival in CAP+ versus CAP− patients (P <.0001). The 50% survival rate for CAP+ patients occurred at 34 months vs 84 months for CAP− patients.
The shorter survival in the CAP+ cohort remained significant after adjusting for elderly age (≥65 years), neoplastic disease, chronic obstructive pulmonary disease, renal disease, liver disease, heart diseases (combined ischemic heart disease and other heart diseases), hemiparesis, connective tissue disease, dementia, peptic ulcer disease, AIDS, and diabetes mellitus.
Effects of Comorbidities on Mortality and Comorbidity Score Weights
|Variable||Hazard Ratio||95% Confidence Interval||P Value||Weight|
|Neoplastic disease||4.6||4.2 – 5.1||<.0001||5|
|COPD||1.8||1.64 – 1.93||<.0001||2|
|Renal disease||1.6||1.27 – 2.03||<.0001||2|
|Liver disease||2.8||2.27 – 3.45||<.0001||3|
|Heart disease||1.7||1.54 – 1.84||<.0001||2|
|Hemiparesis||1.7||1.02 – 2.83||.040||2|
|Connective tissue disease||0.86||0.77 – 0.96||.008||*|
|Dementia||3.0||2.16 – 4.3||<.0001||3|
|Peptic ulcer disease||1.3||1.03 – 1.65||.028||1|
|AIDS||1.2||0.70 – 2.08||.507||*|
|Diabetes mellitus||1.1||1.04 – 1.22||.003||*|
* Variable not included if hazard ratio ≤ 1.3
Although the cause of the decreased long-term survival is not yet clear, it may be that the systemic inflammatory response produced by CAP accelerates the natural course of medical comorbidities such as atherosclerosis, Dr. Peyrani suggested. This hypothesis, she said, is bolstered by a recent study that showed reduced long-term survival in CAP+ patients who were clinically cured but had increased interleukin 6 and interleukin 10 levels at the time of hospital discharge.
Finally, she emphasized that additional studies are needed to understand the pathophysiology of long-term CAP outcomes before it will be possible to develop treatment strategies that might theoretically involve the use of immunomodulatory therapy.
Andrew Wilson, MBBS, a respiratory medicine physician at Princess Margaret Hospital in Perth, Australia, told Medscape Pulmonary Medicine that the study raises an interesting hypothesis and added that the "striking association between CAP and subsequent mortality may mean that the patient has a poorly controlled underlying medical condition and/or that hospitalized pneumonias in the current age are inherently severe."
He also said that future studies need to look more closely at comorbidities in hospitalized patients. "Ideally, you would want to look at hospitalized and nonhospitalized patients in a community cohort, which would allow you to examine the spectrum of pneumonia; however, such a study may be logistically difficult."
Neither Dr. Peyrani nor Dr. Wilson has disclosed any relevant financial relationships.
European Respiratory Society (ERS) 19th Annual Congress: Abstract 1784. Presented September 14, 2009.
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