The rapid and accurate diagnosis of patients with respiratory symptoms is a common challenge for outpatient clinicians. When patients present with fever or respiratory symptoms and a normal leukocyte count, the diagnosis of a URTI is usually considered first. Our study revealed that 32% of those patients were ultimately confirmed to have pneumonia by chest CT. Therefore, it is necessary for physicians to appropriately order chest radiography and even chest CT. In a multicenter prospective study, researchers found that 3% of patients were found to have pneumonia on CT but not on concurrent chest radiography.[16] These patients had similar clinical characteristics to those with pneumonia on chest radiography, [16] emphasizing the importance of chest CT.
It is crucial for physicians to recognize pneumonia in patients who present with fever or respiratory symptoms and order a chest CT appropriately, especially during the epidemic of COVID-19. To our knowledge, this is the first study to explore the predictors and calculate the associated cutoff values for the identification of pneumonia in patients with normal or low leukocyte counts. There were 63 patients diagnosed with pneumonia among 195 patients in our study. Older age, cough, higher temperature and higher hsCRP level were found to be associated with pneumonia.
The median age of patients with pneumonia was 40 years (IQR 34–60) in this study, ranging from 20 years to 86 years. With increasing age, the risk for pneumonia increased. As a previous study revealed that advanced age is one of the independent prognostic predictors of mortality in patients with CAP, [17, 18] it was also associated with readmission[19].
Cough is a common symptom in patients presenting at the emergency department[1] and represents infectious or non-infectious lung disease. It was identified in 73% of the patients with pneumonia and 32% of the patients with URTI in this study. Pneumonia caused by some pathogens is characterized by a dry cough and even the absence of a fever[8]. Therefore, even without fever, cough was an indication of pneumonia.
It had been demonstrated in a previous study that temperature is a good predictor of pneumonia.[10] In our study, the median maximum body temperature was 37.5 °C (IQR 37.4–37.8 °C) in the group of patients with URTI and 38.5 °C (IQR 38.0-38.8 °C) in patients with pneumonia (p < 0.001). There were 8 patients diagnosed with pneumonia without a fever. The etiology in these 8 patients was SARS-CoV-2 in 4 patients and K. pneumonia in one patient, leaving 3 patients in whom no pathogen was detected. Eighty-seven percent patients experienced a temperature higher than 37.3 °C. We used a cutoff value of 37.8 °C based on the ROC analysis to predict pneumonia. This was similar to a prospective cohort study conducted by Moore M et al. [10]. Therefore, the diagnosis of pneumonia and more examinations should be considered once the temperature exceeds 37.8 °C.
CRP is an acute-phase protein that indicates acute inflammatory responses. It was identified as a predictor of pneumonia in several studies.[11, 20–22] A CRP level ≤ 10 mg/L was useful for ruling out CAP in most patients.[11]Steurer et al found there was no pneumonia diagnosed when the CRP levels were < 10 mg/L or if the CRP levels were between 11 and 50 mg/L and the patient did not complain of dyspnea and fever associated with cough.[23] However, some researchers found that the CRP level did not improve the prediction of pneumonia; instead, it can help clinicians make a decision regarding the use of antibiotics. [24, 25] In contrast to previous studies[11, 20], we found that a hsCRP level of 1.64 mg/L had a negative likelihood ratio of 0.07 in the ROC analysis, which means it was a strong predictor of the absence of pneumonia in patients with normal or low leukocyte counts. Further investigations showed that three patients had a hsCRP level less than 1.64 mg/L in the pneumonia group, two of whom were diagnosed with COVID-19 according to the Chinese management guidelines (version 7.0)[15]. Most cases with pneumonia had a higher hsCRP.
The overall detection rate of pathogens in this study was 10% in all patients and 19% in patients with pneumonia, which was lower than that previously reported[26, 27]. A population-based study showed the detection of pathogens in 853 (38%) patients, of which viruses accounted for 22%.[26] In adults, viruses, particularly influenza, rhinovirus, and coronavirus, cause one-third of cases of pneumonia.[28] In this study, the prevalence of viral infection was 14% in patients with pneumonia, with SARS-Cov-2 being the most common virus, followed by influenza virus. One important reason was that all patients screened were outpatients, and few of them had the opportunity to undergo further etiology detection. It is worth noting that the COVID-19 pandemic is still a crisis. [29, 30]A prospective study is needed with more examinations of pathogens in the future.
There are several limitations of our study. First, due to the retrospective study design, there may be some selection bias. The interpretation of our findings might be limited by the study design and sample size. Second, there were no data about physical examinations owing to the thick protective suits worn by medical staff, which may have resulted in missing risk factors such as crackles that were observed in a previous study[10]. Third, this study was performed in a single-center setting, and patients were included during the epidemic of COVID-19, which may have affected the results. However, by including adult patients from the fever clinic of a Class A tertiary comprehensive hospital in China, we believe our study population is representative of cases presenting with acute fever and respiratory symptoms.