Background
The classic clinical presentation of community-acquired pneumonia (CAP) is a febrile patient with respiratory signs and symptoms. In practice, however, the presentation of pneumonia varies. The symptoms and signs that can accompany pneumonia are non-specific, and no single symptom, sign, or combination thereof is a reliable predictor of the illness [
1‐
3]. Some patients with pneumonia may not exhibit respiratory symptoms, others may not develop fever [
3‐
5]. In particular elderly individuals and those with immunocompromising illnesses are less likely to develop fever [
4,
6]. Therefore, radiographic criteria are often used for defining CAP [
1,
3].
To date, chest X-ray (CXR) is the initial imaging modality of choice for detecting chest pathology. Although readily available, the diagnostic accuracy of CXR is limited [
7‐
9]. Chest computed tomography (CT) is a three-dimensional projection technique without the disadvantage of over-projection, visualizing anatomy, and pathology better than CXR [
10,
11]. With the advent of ultra-low-dose CT (ULDCT) the disadvantage of the higher radiation dose is largely overcome while diagnostic quality is preserved. In a systematic review and in a prospective study in the ED setting the sensitivity and specificity for diagnosing consolidations with ULDCT were 87–100% and 92–100%, respectively [
12,
13]. Three prospective studies, one investigating patients in an outpatient clinic with ULDCT and the other two investigating patients in an emergency department (ED) setting with early chest CT, showed that (ULD)CT leads to an earlier diagnosis of pneumonia, which significantly affected clinical management and resulted in a significantly higher perceived confidence of the radiologist [
8,
14,
15].
Pneumonia’s heterogeneous clinical presentation and, to some extent, the limited value of clinical diagnostic signs raise the question of whether pulmonary imaging should be considered in undifferentiated febrile patients who do not exhibit obvious respiratory symptoms. In four studies investigating either patients with neutropenic fever, with a fever of unknown origin, or febrile patients at the ED without respiratory symptoms, the yield of CXR varied between 2 and 5% [
16‐
19]. The yield of pulmonary imaging in patients with a suspected infection but no respiratory symptoms or signs is therefore probably limited. It is currently unknown whether ULDCT also outperforms CXR in this group.
We recently reported the results of the OPTIMACT trial, a multicentre, non-inferiority, randomized clinical trial evaluating the health outcomes effect of replacing CXR by ULDCT in the diagnostic work-up of patients suspected of non-traumatic pulmonary disease at the ED [
20]. The purpose of the sub-study reported here was to evaluate the yield of ULDCT and CXR in patients with a suspected infection who did not exhibit respiratory symptoms or signs, but in whom pulmonary infection needed to be ruled out. We hypothesized that ULDCT would result in a greater number of pneumonia diagnoses than CXR.
Discussion
In this analysis of the OPTIMACT trial, we observed that pneumonia can occur in patients with fever or elevated CRP even if they do not show respiratory signs or symptoms. In total, 22 patients (10%) were diagnosed with pneumonia. ULDCT had a significantly higher sensitivity in the detection of pneumonia than CXR: 93% versus 50%. The cases of pneumonia we found were clinically significant, most patients required admission and were prescribed antibiotics. According to our findings, clinical characteristics or comorbidities alone cannot be used to identify patients with or without pneumonia, compatible with earlier observations that no single symptom, sign, or comorbidity is predictive of pneumonia [
1‐
3], but on average more patients had a fever and CRP was higher in those diagnosed with pneumonia.
To our knowledge, only one other study has been done to investigate the yield of pulmonary imaging in ED patients who have a fever or elevated CRP without respiratory signs or symptoms [
19]. This prospective cross-sectional study identified one single factor, a reliable history, that could discriminate between patients diagnosed with pneumonia and those who were not. The medical history was scored as reliable if the patient was not confused and had no language barrier or cognitive or verbal impairment. We did not see an association with pneumonia for any of the individual patient characteristics or clinical parameters that would construct a measure for reliable history. Most notably, no difference existed in the proportions of pneumonia and non-pneumonia in patients presenting with confusion. Interestingly, the proportion with pneumonia in our study group (10%; ULDCT 12%, CXR 7%) was relatively high compared with the overall proportion of 5% in the aforementioned cross-sectional study on this subject [
19]. That trial relied on CXR to diagnose pneumonia. In our study, we relied on ULDCT or CXR. Our results clearly showed the higher sensitivity of ULDCT for the detection of pneumonia. The difference between both studies might also partly be explained by a different selection of subjects. The cross-sectional trial included patients from a regional hospital [
19]. In our study, patients came from a university hospital and a regional teaching hospital. This can explain the notably high proportion of immunocompromised patients in our study group (40% versus 29%).
Compared to CXR, ULDCT had a significantly greater sensitivity for detecting pneumonia. A retrospective study in patients presenting with non-traumatic thoracic emergencies at the ED described CXR’s similarly low sensitivity (37.7%) for pneumonic consolidations when compared to conventional chest CT [
7]. Another retrospective study reported 27% underdiagnoses of pneumonia in a series of 97 patients undergoing both CXR and conventional CT [
10]. A recent systematic review and prospective study in an ED setting confirmed the high diagnostic accuracy of ULDCT, with a sensitivity for consolidations between 87 and 100% [
12,
13]. Although the negative predictive value of both techniques is high (ULDCT 99%, CXR 96%), the very high sensitivity and very high negative predictive value of ULDCT is especially important when the prevalence of the disease is low and when in vulnerable, immunocompromised patients’ pneumonia has to be ruled out with certainty. This finding is in line with two prospective studies that suggested that the potential benefit of (ULD) chest CT lies in ruling out pneumonia and reducing the overdiagnosis of pneumonia [
8,
15].
There were remarkably few patients with cardiovascular and pulmonary comorbidities in our group, which is likely due to the inclusion and exclusion criteria used. It is rare for patients afflicted with cardiovascular or pulmonary comorbidities to have no respiratory symptoms or signs [
23]. Compared to the overall OPTIMACT study group, the patients in this analysis were more likely to have a history of malignancies, to have recently undergone chemotherapy, or to be immunocompromised. Even though these patients had no obvious respiratory signs or symptoms, the decision was made to perform pulmonary imaging. It is conceivable that, even when there are no apparent signs of respiratory disease, physicians are more likely to request pulmonary imaging in such patients.
Due to the pragmatic nature of the OPTIMACT trial, concealment of allocation was not possible. This may have influenced the behavior of physicians in including patients in the ULDCT or CXR months and may explain the higher proportion of patients with hematologic malignancies and recent chemotherapy in the ULDCT group. However, in our study group, we did not find a relationship between comorbidities and the presence of pneumonia. Second, due to the nature of this study, patients underwent either ULDCT or CXR, not both. Estimation of sensitivity and specificity was performed based on independent samples, while a more precise comparison would have been made in paired samples (i.e., CXR and ULDCT performed on the same patient). However, that would have prevented the evaluation of patient outcomes per diagnostic arm. Nonetheless, given the sample size, our results provide strong indications that ULDCT outperforms CXR in the detection of pneumonia in patients without respiratory signs or symptoms. The day-28 diagnosis was used as a reference standard, but results of the diagnostic strategy, ULDCT or CXR, were incorporated in the day-28 diagnosis, and this may have influenced the outcome. The influence is probably limited because the follow-up period of 28 days results in a post hoc day-28 diagnosis that uses all clinical, radiological, and microbiological data obtained during follow-up, including additional imaging and the natural course of the disease.
Finally, due to the small number of patients who were diagnosed with pneumonia, we had limited power to find patient characteristics that were indicative or predictive of pneumonia in patients without respiratory signs or symptoms.
Despite these limitations, this study’s strengths should also be highlighted. It was performed in the EDs of a tertiary and a large regional teaching hospital, where it included the complete spectrum of patients who present at the ED and who, according to the physician, require pulmonary imaging. This means that the results of this study are generalizable to other settings. Furthermore, this study was longitudinal in design, with a follow-up period of 28 days, and therefore the diagnosis of pneumonia could be established considering all clinical, radiological, and microbiological data from participants available after 28 days of follow-up. In this way, the clinical diagnosis of pneumonia could be established much more reliably than would have been possible when only the data from the moment of imaging would have been available.
In conclusion, our results imply that pulmonary imaging can at least be considered in patients who have a fever, low core body temperature, or elevated CRP without respiratory symptoms or signs. When the objective is to exclude pneumonia from the differential diagnosis in this patient group, for instance, because the patient is immunosuppressed, ULDCT’s improved sensitivity compared to CXR is a significant advantage.
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