Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers

Abstract

The diagnosis of Pneumocystis pneumonia (PCP) relies on microscopic visualization of Pneumocystis jirovecii organisms or DNA detection in pulmonary specimens. This study aimed to assess the usefulness of (1-3)-β-d-glucan (BG), Krebs von den Lungen-6 antigen (KL-6), lactate dehydrogenase (LDH) and S-adenosyl methionine (SAM) as serologic biomarkers in the diagnosis of PCP. Serum levels of BG, KL-6, LDH and SAM were investigated in 145 Portuguese patients, 50 patients from the Netherlands, 25 Spanish patients and 40 Portuguese blood donors. Data on clinical presentation, chest imaging and gasometry tests were available. PCP cases were confirmed by microscopy and PCR techniques. A cost-effectiveness analysis was performed. BG was found to be the most reliable serologic biomarker for PCP diagnosis, followed by KL-6, LDH and SAM. The BG/KL-6 combination test was the most accurate serologic approach for PCP diagnosis, with 94.3% sensitivity and 89.6% specificity. Although less sensitive/specific than the reference standard classic methods based on bronchoalveolar lavage followed by microscopic or molecular detection of P. jirovecii organisms, the BG/KL-6 test may provide a less onerous procedure for PCP diagnosis, as it uses a minimally invasive and inexpensive specimen (blood), which may be also a major benefit for the patient's care. The BG/KL-6 combination test should be interpreted within the clinical context, and it may be used as a preliminary screening test in patients with primary suspicion of PCP, or as an alternative diagnostic procedure in patients with respiratory failure or in children, avoiding the associated risk of complications by the use of bronchoscopy.

Pneumocystis jiroveci pneumonia (PCP) in patients receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast cancer: incidence and risk factors

“…PCP cases were designated as probable in patients who presented with progressive dyspnea and bilateral diffuse alveolar infiltrates on chest imaging and had an elevated serum BG value (Fungitell assay, Associates of Cape Cod, Falmouth, MA), responded to PCP treatment, and had no alternative diagnosis identified, consistent with many reports of the utility of BG as a non-invasive test with reasonable sensitivity and specificity in this setting [14][15][16][17][18][19][20][21][22]. All PCP cases were adjudicated by two physician investigators including an Infectious Diseases specialist.…”

“…This reflects emerging evidence for the use of BG as a mycologic marker for PCP, including BG assessment in participants of a prospective clinical trial [22], and a recent meta-analysis demonstrating 94.8 % sensitivity and 86.3 % specificity of BG as a PCP diagnostic in a variety of immunocompromised populations [17]. Given its diagnostic utility and the potential to eliminate bronchoscopy-associated risk, BG testing for PCP diagnosis has become standard practice at our institution and many others [14][15][16][17][18][19][20][21][22]. It is difficult to exclude a contribution of drug-induced pneumonitis to the clinical presentation of some of the patients with PCP in our series.…”

Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients withPneumocystisPneumonia

“…Although LDH is a nonspecific biomarker and also increases in many other diseases, an elevated LDH level has been noted in many patients with PCP [18] and has been utilized for diagnosis of PCP [19–22]. Few articles or guidelines have assessed the utility of LDH in predicting severity of disease progression.…”

Serological diagnosis of pneumocystosis: production of a synthetic recombinant antigen for immunodetection of Pneumocystis jirovecii

“…Elevated serum levels of the lactate dehydrogenase (LDH), (1–3)-β -D-glucan and Krebs von den Lungen-6 antigen (KL-6), as well as low serological levels of S-adenosylmethionine (SAM), have been related to PcP and proposed as markers of the disease789101112131415. However, the use of these metabolites in PcP diagnosis is complex because their serum levels are not strictly specific to P. jirovecii infection.…”