Signs and symptoms in adult patients with acute dyspnea: a systematic review and meta-analysis
Authors: Renier Walter , Winckelmann Karin Hoogma-von , Verbakel Jan Y. , Aertgeerts Bert , Buntinx Frank 
Published: December 2017

Introduction
Rapid and accurate diagnosis of patients with a new episode of acute dyspnea is a common challenge for Primary Care or Emergency Physicians.

Objective
To determine the diagnostic accuracy of signs and symptoms in adult patients with a new episode of acute dyspnea presenting to a GP or an Emergency Physician (EP).

Patients and methods
This was a diagnostic systematic review. Using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, EMBASE, tracing references, and by contacting experts, studies were identified on the diagnostic accuracy of additional signs and symptoms in adult patients with acute or suddenly worsening dyspnea, presenting to a GP or an EP. Study quality was assessed using QUADAS and results were pooled using a random-effects model. Sensitivity, specificity, positive and negative likelihood ratio (NLR), and positive and negative predictive values for a diagnosis of heart failure (HF) were calculated for the combination of acute dyspnea and each additional sign or symptom in the selected studies.

Results
Eight of the 24 identified studies were carried out in the ED and provided us with all the required data, including 4737 patients. All publications reported HF; two studies additionally investigated pulmonary embolism, acute exacerbations of chronic obstructive pulmonary disease or asthma, acute pulmonary infectious diseases, or acute coronary syndrome. The prevalence of HF in patients with acute dyspnea ranged from 25 to 59%. Heterogeneity was present in all analyses.
Comparing signs and symptoms, sensitivity was very poor for the presence of fever (0.05) and sputum production (0.06), and poor for fatigue (0.36–0.76), orthopnea (0.2–0.76), paroxysmal nocturnal dyspnea (0.23–0.70), elevated jugular venous pressure (0.19–0.70), rales (0.32–0.88), and peripheral edema (0.29–0.77). Specificity was poor for fatigue (0.28–0.69), moderate for the presence of fever (0.76–0.88), sputum production (0.73–0.89), orthopnea (0.49–0.92), paroxysmal nocturnal dyspnea (0.52–0.93), and rales (0.31–0.98), and good for elevated jugular venous pressure (0.75–0.97) and peripheral edema (0.67–0.89).
For all other signs and symptoms, sensitivities varied between 0.20 and 0.43; specificities for symptoms varied widely between 0.37 and 0.91 and those of signs between 0.20 and 1.0.
The pooled sensitivities, however, remained poor: below 0.55. Pooled specificity of most signs ranged between 0.69 and 0.88. The positive likelihood ratio was between 0.64 and 4.11 and the NLR was between 0.59 and 1.29 with one outlier: rales (pooled NLR=0.35).

Conclusion
This systematic review, which only included patients from ED settings, did not identify any single sign or symptom that had acceptable sensitivity to be useful in ruling out a diagnosis of HF, chronic obstructive pulmonary disease, asthma, or pulmonary embolism. Elevated jugular venous pressure (0.88, pooled odds ratio: 7), added third heart sound (0.97), and lung crepitations (0.77, pooled odds ratio: 11) are useful in ruling in HF.