ORIGINAL ARTICLE • Retrospective Analysis of the Diagnostic Accuracy of Lung Ultrasound for Pulmonary Embolism in Patients with and without Pleuritic Chest Pain
Pleuritic chest pain – sharp chest pain exacerbated by breathing or coughing – is a common presenting symptom in the emergency department (ED) and requires a careful differential diagnosis between benign conditions such as musculoskeletal pain, and more serious diseases like pulmonary embolism (PE), pneumothorax, pneumonia with pleuritis and cancer. Among these conditions, PE is a major cause of morbidity, mortality, and hospitalization.
Pleuritic pain is reported in up to 65% of patients in patients with PE when distal emboli cause a pulmonary infarction. PE diagnosis, however, can be challenging in the ED because clinical signs and symptoms are non-specific.
Definitive diagnosis often requires multidetector computed tomography pulmonary angiography (MCTPA) that is not feasible in unstable patients, may not be available 24 h a day in all institutions, causes radiation exposure, and it can cause side effects due to contrast medium injection. Therefore, while MCTPA remains the standard reference for PE, alternative bedside diagnostic tools that are non-invasive and readily available are of great importance in the clinical practice.
The role of LUS in the diagnosis of PE is limited to those cases in which MCTPA is contraindicated or not feasible. However, a well localized pleuritic pain is often present in patients in which parietal pleura is involved in a peripheral pulmonary infarction and therefore, focalizing LUS exam in the painful area indicated by the patient can simplify and make more effective the search for the infarcted areas of the lung.
To investigate these hypotheses, the authors analyzed existing data from three published studies to compare the diagnostic performance of LUS in two subgroups of patients with suspected acute PE, classified for presence or absence of pleuritic chest pain.
Study design and setting
The authors combined individual patient data from one prospective monocentric study and two prospective multicentric studies enrolling consecutive patients with suspected PE.
One investigator, who was not a co-author of the three original studies included in the analysis, used the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews-2 (QUADAS-2) tool to assess the methodological quality.
This tool is composed of two parts: risks of bias and concerns regarding applicability. The former was assessed in four domains patient selection, index test, reference standard and flow and timing, and the latter was assessed in three domains patient selection, index test and reference standard.
Two studies enrolled patients suspected of PE without differentiating the risk score and one study enrolled patients with Wells score > 4 (likely) or a positive d-dimer that underwent MCTPA.
The Wells score included the following items:
- Clinical signs and symptoms of deep vein thrombosis (DVT): + 3
- PE is most likely diagnosis or equally likely: + 3
- Heart rate > 100 bpm: + 1.5)
- Immobilization at least 3 days or surgery in the previous 4 weeks: + 1.5
- Previous objectively diagnosed PE or DVT: + 1.5
- Hemoptysis: + 1
- Malignancy with treatment within 6 months or palliative care: + 1
Patients were categorized as PE likely if Wells score was > 4 and PE unlikely if ≤ 4. Cut-off values for d-dimer was < 500 ng/ml and not age adjusted.
All studies reported whether patients had pleuritic chest pain, that was defined as acute onset sharp pain exacerbated by breathing or coughing.
In all studies LUS was performed by scanning the whole chest in 2 anterior, 2 lateral and 2 posterior chest areas per side. In each area, all the intercostal spaces were scanned searching for pulmonary infarctions.
Investigators performing LUS were blinded to diagnostic tests results and to all the clinical information except for symptoms of presentation and visible physical signs.
The pattern considered positive for lung infarction was visualization of a pleural-based anechoic consolidation, wedge or round shaped, with sharp margins, without air bronchograms, of a minimum size measured at the pleural level of 0.5 cm with or without an associated small pleural effusion.
Source study with quality assessment, and patient characteristics
872 patients suspected of PE enrolled in the three studies. Among them, 279 (32%) were diagnosed with PE.
D-dimer, measured in 808 patients, was positive in 340 out of 549 patients without PE (61.9%) and in 244 out of 259 with PE (94%, p < 0.001).
Five patients with wells score ≤ 4 (unlikely) and negative d-dimer had a final diagnosis of PE; 4 out of these 5 patients presented with pleuritic chest pain.
Lung ultrasound examination
Sensitivity of LUS for the diagnosis of PE in patients with pleuritic chest pain (81.5%, 95% CI 70–90.1) was superior to patients without pleuritic chest pain (49.5%, 95% CI 38.8–77.6, p < 0.001).
Specificity was similar (95.4% for patients with pleuritic chest pain and 94.8% for patients without, p = 0.86).
Two studies reporting the findings of a simplified LUS exam focused on the painful chest area and was applied in 156 patients. This simplified LUS showed similar sensitivity and specificity when compared to the whole chest LUS examination, respectively, 78.7%, 95% CI 64.3–89.3 vs 83%, 95% CI 69.2–92.3, p = 0.48 for sensitivity and 95.4%, 95% CI 89.6–98.5 vs 94.5%, 95% CI 88.4–98, p = 1 for specificity.
Strategies to rule‑out PE: wells score + d‑dimer vs wells score + LUS
To evaluate the most efficient strategy to rule-out PE, the authors compared the conventional approach recommended by international guidelines, i.e., i.e., Wells score unlikely combined with negative d-dimer measurement, and a LUS-based approach, i.e., Wells score unlikely combined with negative LUS.
For this evaluation, data are derived from 451 patients enrolled in two studies without differentiation for pleuritic pain. The analysis showed that the failure rate of the conventional approach was significantly lower when compared to the LUS-based approach (4.1% vs 12.4% p = 0.01). However, considering the subgroup of 141 patients complaining of pleuritic chest pain at presentation, the LUS-based approach had a nonsignificant lower failure rate and higher sensitivity than the conventional approach (respectively, 3.7% vs 6.7%, p = 0.42 and 93% vs 90.7%, p = 1), but was significantly more efficient (56.7% vs 42.5%; p = 0.02).
The author concluded that the sensitivity of LUS for the diagnosis of PE is increased when the patients present pleuritic chest pain.
They also believe based on the study, in patients suspected of PE with pleuritic chest pain, a diagnostic strategy based on Wells score and LUS, whether performed on the whole chest or limited to a single scan in the painful chest area, is more efficient for ruling out PE compared to the conventional strategy based on Wells score and d-dimer.