Biomarkers Present in Sputum May Predict Onset of Inflammation Attacks in CF Patients

Certain molecules present in the sputum — “coughed-up” material from the trachea and lungs — can help to predict the onset of an inflammation attack in patients with cystic fibrosis (CF), a new study by researchers at the University of California reported.

The study, “Metabolomics Of Pulmonary Exacerbations Reveals The Personalized Nature Of Cystic Fibrosis Disease,” was published in the journal PeerJ.

CF patients can experience intermittent pulmonary exacerbations (CFPE) that negatively affect lung function and promote disease progression. These events are characterized by an acute increase in symptom severity, such as cough, sputum production, chest pain and fevers, and require increased use of antibiotic, anti-inflammatories, and lung clearance therapies. To date, these events have been poorly defined clinically.

“Clinicians rely on symptoms common across patients or those that a single patient has previously experienced to provide some indication that a CFPE is occurring,” the authors wrote. “Biomarkers that predict pulmonary exacerbations are needed to supplement existing clinical and physiological assessments.”

To search for possible biomarkers that may assist in the prediction of these events, researchers analyzed sputum samples from 11 CF patients (at least three samples per patient), collected during one of four clinical states: exacerbation (samples collected during a CFPE event, when the need for antibiotics increased), treatment (samples gathered during the treatment), post-treatment (samples collected immediately after treatment), and stable (samples collected at routine clinical visits).

Results indicated that, although there was a large number of molecules specific to each clinical state, the sputum’s particular composition during exacerbation was more similar within the same patient than between different patients sharing the same state. In fact, only two known factors were increased among patients experiencing an exacerbation, the platelet activating factor (PAF) and a related lipid (PC lipid). This supports the view that, although global biomarkers may not be easy to find, sputum contains molecules that can help in the personalized prognosis of a CFPE event.

Since most of the sputum molecules were patient-specific, the team analyzed 37 samples from one patient, collected over some four years and capturing four exacerbation events, looking for markers that were always present whenever a CFPE event occurred.

Researchers observed that, in this patient, PAF, related lipids, and ceramide were significantly increased during CFPEs. These molecules are potent inducers of inflammation, meaning that an increase in their levels promotes an increase in inflammatory processes.

“Although there was not a universal signature of exacerbation, personalized approaches to biomarker development show promise, as a large number of [molecules] were unique to this clinical state,” the authors concluded. “Here, PAF and ceramide are potentially useful biomarkers as inflammatory lipids indicating the potential onset of a CFPE. Monitoring … PAF and ceramide pathways may provide information about inflammatory processes occurring prior to and during a CFPE event.”