The potential utility of eosinopenia has not been evaluated in hospitalized AECOPD patients with CAP. The current study showed that eosinopenia (< 50/µL) was a strong predictor of 18-month mortality. In addition, the eosinopenia group had significantly elevated CRP and procalcitonin, which indicated that eosinopenia was associated with more severe infection. Therefore, eosinopenia may be helpful for physicians to identify patients with high risk of mortality and optimize management strategies accordingly. Prospective studies are warranted to evaluate if adopting this strategy could improve prognosis of hospitalized AECOPD patients with CAP.
COPD is one of the most important cause of death worldwide, which was worsened by exacerbations.(2) The CAP occurs commonly in patients with COPD as impairment in lung defense, especially in those older than 65 years.(16) COPD is reported as a comorbidity in at least one third of hospitalized patients with CAP.(4) There is a controversy about the impact of COPD on mortality of patients hospitalized for CAP.(17) Several studies supported that COPD patients with CAP had higher mortality.(13, 18–20) However, some studies and meta-analysis showed that mortality was not increased in patients with COPD hospitalized with CAP.(21–23) Regardless of co-existence of CAP, AECOPD caused high mortality worldwide, which warranted attention from physicians. So a simple, accessible and cheap marker to identify those patients with high risk of mortality was helpful in practice, especially in developing countries. Eosinopenia gained our attention, which was further examined in the current study.
Normally, eosinophil account for only a small part of white blood cells in blood. Its roles have been extensively investigated in asthma and COPD. High blood eosinophil count was a reliable predictor of response to inhaled corticosteroid in COPD. (24–27) Furthermore, oral corticosteroid during AECOPD had better effect in patients with high blood eosinophil count.(28) However studies about low blood eosinophil count or eosinopenia was relatively limited. Eosinopenia could be caused by either acute infection or acute stress, so it was not a biomarker of infection status. In essence, the eosinopenia of acute infection has been assumed to be a secondary expression of adrenal corticosteroid stimulation produced by the stress of the infection.(29, 30) Therefore it was suggested that eosinopenia was a response to the acute inflammatory process rather than to a specific type of pathogen.
The principal finding of the current study was that eosinopenia (< 50/µL) was a strong predictor of 18-month mortality. This finding was in agreement with previous studies. Numerous studies supported that eosinopenia was strongly associated with increased mortality in various clinical settings and diseases. In a large retrospective cohort study of 2311 patients with bacteremia, eosinopenia (< 50/µL) was associated with a 4.77-fold increase in risk of dying compared with a normal eosinophil count.(31) Yip et al. found that eosinopenia(< 10/µL) on ICU discharge was associated with increased post-ICU mortality.(32) Similarly eosinopenia (< 40/µL) at ICU admission was reported to be an independent predictor of 28-day mortality.(8) Eosinopenia was reported to be able to predict mortality not only in adults but also in children.(5)
A strong association between eosinopenia and mortality in AECOPD had also been described by some studies. A study by Holland et al reported that eosinopenia (< 40/µL) was associated with higher in-hospital mortality.(10) Moreover eosinopenia was identified as one of five strongest predictors of inpatient mortality in hospitalized AECOPD patients as part of the Dyspnea, Eosinopenia, Consolidation, Acidemia and atrial Fibrillation (DECAF) score.(11) MacDonald et al further demonstrated that eosinopenia (< 50/µL) were strongly associated with higher 12-month mortality in hospitalized AECOPD patients.(12) In our dataset, eosinopenia (< 50/µL) was associated with increased mortality at 18 months. So our findings corroborated with MacDonald’s, but our study population was different from MacDonald’s. In our study, only hospitalized AECOPD patients with confirmed CAP were analyzed; in MacDonald’s study, hospitalized AECOPD patients with all causes were included. Based on detection of chest X-ray consolidation provided by supplemental data, it was roughly estimated that there were 43 cases of pneumonia out of 242 cases in MacDonald’s study. So there were more hospitalized AECOPD patients with CAP in our study than MacDonald’s (59 vs 43). Moreover in our study, the diagnosis of CAP was based on chest CT, which was more reliable. But still the study population was relatively small, further studies with a larger population were warranted.
Another important finding of our study was that the eosinopenia group had significantly elevated CRP and procalcitonin. The CRP and procalcitonin were commonly used biomarkers for infection, and procalcitonin is a diagnostic marker of the presence of a bacterially induced systemic inflammatory reaction.(33) Our finding indicated that eosinopenia was associated with more severe infection status. This finding was consistent with previous reports conducted in various clinical settings. The study by Gil et al in a department of internal medicine demonstrated that an inflammatory syndrome associated with eosinopenia (< 40/µL) was related to bacterial infectious diseases.(34) Similarly, another study in ICU by Abidi et al showed that eosinopenia was a reliable marker of sepsis, and was associated with the severity of sepsis.(35) Moreover the study in general internal medicine setting, excluding ICU and ED, revealed that eosinopenia was a useful predictor of bloodstream infection.(7) In ED, eosinopenia(< 10/µL) was reported to present a specificity of 94% for the diagnosis of infection. As above-mentioned, eosinopenia could be caused by acute stress secondary to both infection and non-infection stimuli. The association between eosinopenia (< 50/µL) and higher mortality found in this survey could therefore be partially explained both by more severe infection status and higher stress levels induced by infection.
The current study has a potentially important implication for physicians, especially in developing countries. As a cheap test for early identification of patients at high risk of death on admission, eosinopenia may help physicians in making management strategy. Once identified, a strategy of more aggressive diagnostic and therapeutic interventions may be warranted. The pro and con of such strategy are needed to be verified by prospective cohort studies.
Some limitations of the study merit consideration. First, the present study was a retrospective study performed in a single institution, so there were inherent problems related to this design. Second, patients were identified as having AECOPD by medical history instead of pulmonary function, which has been demonstrated in past studies to be the same method as that used to identify other comorbid conditions included to create the PSI score. The severity of COPD between two groups could not be compared, although the PaO2 and PaCO2 was similar.
In conclusion, eosinopenia (< 50/µL) was a strong predictor of 18-month mortality in hospitalized AECOPD patients with CAP. Moreover eosinopenia was associated with more severe infection. Eosinophil count at admission can be used as a prognosis marker of mortality in hospitalized AECOPD patients with CAP. It may become a helpful clinical tool.