Infection is a major cause of morbidity and mortality among patients with COPD.28
In COPD patients presenting to the hospital with dyspnea, our study demonstrates a wide variety of viral and bacterial pathogens, as well as a high incidence of pneumonia. Recently, use of procalcitonin to guide clinical decisions has been shown to reduce antibiotic use significantly in patients with respiratory illnesses without compromising composite patient outcomes in a number of randomized interventional trials.13
Although procalcitonin-guided decisions have been promulgated as a method to “rule out” bacterial infection, the 0.25 ng/mL threshold for recommending antibiotic treatment is not based on microbiologic data. Recovery without antibiotics or with an abbreviated course has been equated with the absence of a bacterial infection. The lack of microbiologic correlation with procalcitonin levels is likely to slow endorsement of procalcitonin-guided management in respiratory illness.19
Ours is the first study in the US to examine the utility of procalcitonin levels in patients with COPD, and consistent with the European literature, we found that a high procalcitonin level was relatively specific for invasive bacterial disease such as pneumonia.32
In addition, elevated procalcitonin values in the AECOPD group correlated with higher temperature, white blood cells, and more severe illness, suggesting the possibility of occult pneumonia. Thus, high procalcitonin values may alert clinicians to the presence of bacterial pneumonia when the chest radiograph results are negative or ambiguous.
However, our results also indicate that minor elevations at the low end of the procalcitonin spectrum do not correlate with bacterial infection for subjects with AECOPD alone. It has been estimated that approximately 40%–50% of AECOPD cases are due to bacterial infections.34
The precise contribution of bacterial infection is difficult to define because the airways of COPD patients may be chronically colonized.3
Acquisition of new strains of Haemophilus influenzae
and Moraxella catarrhalis,
rather than bacterial load, appears to be the most important factor in the pathogenesis of acute exacerbations.35
This factor has not been accounted for in AECOPD antibiotic trials and might explain the modest beneficial effects of antimicrobial treatments observed.
We accept that some subjects who were classified as having bacterial infection in our study were colonized rather than infected. However, only 17% of patients overall with AECOPD and without pneumonia, and only 25% of those with evidence of bacterial infection had procalcitonin levels ≥0.25 ng/mL. While it is possible that this small subgroup represents those who will actually benefit from antibiotic treatment, such a conclusion is premature. Notably, of those with procalcitonin levels <0.25 ng/mL, 57% had three Anthonisen criteria, suggesting they would benefit from antibiotic treatment based on past studies.36
Thus, only two conclusions are possible, ie, either the contribution of bacterial infection in AECOPD has been markedly overestimated or procalcitonin values do not differentiate bacterial bronchitis from viral or noninfectious etiologies.
Our study adds to the growing body of literature which questions the utility of procalcitonin levels to discriminate viral-associated from bacterial-associated AECOPD. In a study by Daniels et al, procalcitonin levels were measured in outpatients enrolled in a trial of doxycycline for AECOPD.37
A significant benefit of doxycycline was noted for patients with procalcitonin levels <0.1 ng/mL. In this study, as well as in two additional reports, no differences in procalcitonin levels were noted in patients with or without bacteria in sputum during exacerbation.32
Our study provides the most rigorous microbiologic analysis of moderate to severe illness requiring hospitalization to date, particularly for subjects who were deemed negative for bacterial infection. Unlike prior studies, we did not consider patients to be free of bacterial infection unless adequate samples were taken in a timely fashion and without antibiotic use prior to hospitalization.
Our study had several limitations. The number of patients with documented bacterial infection was relatively small. However, large numbers of subjects are not needed to show that a test is insensitive, especially if missing even a few patients with potentially treatable bacterial infections is considered unacceptable. Because medical information was restricted to that available in the hospital medical record, we could not classify the stage of COPD using GOLD criteria in our subjects. Lastly, we did not test for rhinovirus, a common pathogen in this population, although this omission does not invalidate the findings for those patients with a viral or bacterial infection identified.
In conclusion, we found that elevated serum procalcitonin levels are associated with more severe illness in patients hospitalized with symptoms of AECOPD and that high values may alert clinicians to the possibility of pneumonia. However, low procalcitonin values do not “rule out” bacterial infection in AECOPD. Before procalcitonin-based treatment algorithms are endorsed, additional studies in COPD patients should be performed. Clinical trials focusing on antibiotic benefit are needed specifically in patients with nonpneumonic exacerbations associated with low procalcitonin values.