To our knowledge, this is the first study evaluating the diagnostic performance of LUS combined with PCT for the diagnosis of pneumonia in the ED. Research on the diagnosis of pneumonia is usually hampered by difficulties in obtaining a systematic comparison with CT scan. The lack of a gold standard that supports the visual diagnosis of pneumonia, may lower the significance of many studies. One strength of our study is that the final diagnosis of pneumonia in all patients is supported by a post hoc review of the clinical chart, and based on the detection of typical consolidations at chest CT read by an expert radiologist. In many previous studies LUS showed to be an accurate bedside tool for the diagnosis of pneumonia [8, 15–17]. In our study LUS alone ruled in pneumonia with a good positive likelihood ratio and ruled out this condition with a moderate negative likelihood ratio. The superiority of LUS over CXR is reported in literature . In our study, despite the two methods showed similar specificities, the sensitivity of LUS was superior to CXR. We have to consider that in 8% of patients, pulmonary ultrasound examination was limited only to the anterior-lateral areas and that 33% of all false negative cases belong to this group. In these patients, most dependent pulmonary areas were not scanned and consolidations were not detected and this was the cause of a reduction in overall sensitivity of LUS for the diagnosis of pneumonia.
Procalcitonin is an emerging biomarker, whose practical application is increasingly common, not only in the diagnosis and follow-up of sepsis but also in pneumonia . A PCT value below the threshold level makes unlikely a severe pneumonia with bacteraemia and is used to withhold antibiotic therapy [19–21]. Müller et al. analysed data from two randomized prospective studies with a total of 545 patients with suspected infection of the lower respiratory tract. In their post-hoc analysis, they found that the diagnostic accuracy to predict radiographically suspected community acquired pneumonia was significantly higher for PCT (87%) than for WBC (64%) . In our study, the diagnostic accuracy of PCT, although inferior to the performance obtained by Müller et al., was still higher than WBC (49%).
The lower accuracy of PCT found in our study compared with the study by Müller may be due to a different selection of patients and to the different gold standard used for the diagnosis of pneumonia.
Despite its known role in the confirmation of bacteraemia in sepsis, in our study PCT alone was not sufficiently accurate in the diagnosis of pneumonia. This can be explained considering that while the final diagnosis of pneumonia was only confirmed in presence of typical clinical signs with at least one typical consolidation detected at chest CT, we cannot confirm that in our patients the radiologic consolidations were always due to a bacterial infection with bacteraemia. The majority of patients with a final diagnosis of pneumonia were in a stable condition and showed an isolated pulmonary infection not necessarily associated with bacteraemia. It is well known that in cases of localized organ infections, PCT is usually lower as compared to septicaemia with positive blood cultures .
No previous studies evaluated the association of LUS and PCT for the bedside diagnosis of pneumonia in the ED. However, a recent study by Zagli et al. performed on critically ill patients in the intensive care unit, evaluated a new score, CEPPIS (chest echography and procalcitonin pulmonary infection score), based on a combination of PCT and LUS for the diagnosis of ventilator associated pneumonia (VAP) . The new proposed score differed from the traditional clinical pulmonary infection score (CPSI) basically in two items: WBC was replaced by PCT and CXR by LUS. The study showed that sensitivity of CEPPIS (80.5%) was superior then CPSI (39.8%) for the diagnosis of VAP, while specificity was similar (85.2 vs 83.3%). There are many methodological differences between the study of Zagli et al. and our study, but both showed that the sensitivity of LUS/PCT is superior to other diagnostic approach based on CXR in the diagnosis of pneumonia.
In our study the association of a negative LUS examination with a PCT level <0.25 ng/ml significantly improved sensitivity of LUS for the diagnosis of pneumonia, reducing the occurrence of false negative diagnoses and decreasing the negative LR. We can argue that the clinician, in approximately one-third of “difficult” diagnosis in patients with unexplained respiratory symptoms, may rule-out pneumonia with a sufficient level of certainty by combining LUS and PCT. On the other hand, our study showed that when LUS visualizes a consolidation with the typical ultrasonography features, the specificity and positive predictive value for the diagnosis of pneumonia is not significantly influenced by the addiction of PCT.
Lung ultrasonography is a powerful, cheap, easy to perform, and safe tool for the diagnosis of many pulmonary conditions at bedside and its use is exponentially increasing among specialists and general practitioners in and out of hospitals. Moreover, the diagnostic accuracy of LUS for pneumonia is at least as good as CXR in different settings and patients. Considering that a point-of care PCT measurement will become available for clinical practice , the results of this preliminary study opens new perspectives for improving the diagnostic approach to pneumonia at the bedside, by combining LUS and PCT in the general population. Further studies could also evaluate the usefulness of this combined diagnostic strategy in some subgroup of patients where CXR is less accurate or contraindicated such as bedridden patients in particular patients in invasive and not invasive ventilation, immunocompromised patients and pregnant women. Furthermore, using multiple biomarkers combined with LUS could further increase diagnostic accuracy of physicians and be useful to triage patients at the bedside in many different clinical scenarios.
A questionable characteristic of our protocol is that patients were not enrolled on the basis of a direct suspicion for pneumonia. We concentrated our study on patients with respiratory complains, who demanded CT scan for ambiguous diagnosis. In case of suspected uncomplicated lung infection, where the diagnosis is mainly based on clinical findings and CXR, it is unusual to undergo CT scans. Thus, our specific patient population does not allow generalization of our results. However, a systematic application of CT studies in all suspected low respiratory tract infection is not feasible because it does not represent a standard of care, and it is not ethical for its radiation burden and not sustainable for high cost. Another limitation of our study, is that the final diagnosis of pneumonia was based on the detection of a consolidation at chest CT, while the possibility of interstitial pneumonia was not considered. We have also to consider that it is not known if the consolidation identified at chest CT was due to bacterial, viral or other germ infection. Regarding the comparison between LUS and CXR, a consideration should be done on the criteria of enrolment. In fact, the patients enrolled in the study underwent chest CT once the physician was aware of CXR results, and this could have selected a population with not diagnostic CXR. Thus, this criteria probably affected the low sensitivity of CXR. However, in the real practice, the role of LUS is often to confirm negative chest films in patients with high suspicion of pneumonia. Thus, the difference in sensitivity between the two methodologies is still confirmed. Indeed, the fact that in our study the majority of CXR were not performed in the up-right position, may have influenced more significantly the comparison between the two methods. The anterior-posterior radiographic view is undoubtedly less accurate for the study of the lungs. However, the evaluation of sub-optimal chest films is largely representative of the real daily practice and the main cause of inconclusive CXR studies. Finally, the lack of systematic and consecutive PCT assays in the population studied may have biased our results. Indeed, a PCT assay was only based on the personal judgement of the attending physician facing challenging diagnostic situations and was independent from the study protocol. However, these situations are exactly those deserving more accurate and sometimes alternative diagnostic tools, that is the possible future role of a combined LUS/PCT protocol.