Abstract

Saliva has numerous practical advantages as a diagnostic bio-sample for management of long term conditions. We have previously demonstrated that C-reactive protein (CRP), procalcitonin (PCT) and neutrophil elastase (NE) can be reliably and reproducibly detected in saliva, offering useful information on health status. This study explores whether proactive monitoring of target analytes provides early warning of COPD exacerbations and re-exacerbation events.

Salivary CRP, PCT and NE levels were determined weekly in 55 subjects with established COPD, known to be frequent exacerbators [GOLD Stage I, 7; Stage II, 24; Stage III, 19; Stage IV, 5]. Daily symptom scores were collected using a self-assessment electronic diary. Participants were monitored throughout their stable, prodromal (defined as the 7 days prior to exacerbation onset), exacerbation and post-treatment recovery periods. All three salivary biomarkers could distinguish stable status from onset of patient-defined exacerbations (CRP: p < 0.003, PCT: p < 0.001, NE: p < 0.01); CRP median increase was 1.82 ng/ml, [interquartile range 4.79]; PCT 0.03 ng/ml [0.10] and NE 364 ng/ml [76]. Interestingly, increases over stable baseline were also observed in the prodromal period for salivary CRP 0.53 ng/ml [2.73], (p < 0.001), PCT 0.08 ng/ml [0.01], (p < 0.01) and NE 519 ng/ml [568], (p < 0.007), occurring at 5.4 ± 1.8 days prior to patient-defined onset. Importantly, in those COPD patients experiencing more than 1 exacerbation (n = 15), re-exacerbator salivary CRP was significantly higher at the index exacerbation, 4.08 ng/ml [0.21], (p < 0.04) with a mean time of 11 ± 8 days to re-exacerbation after treatment completion. Diary symptom analysis showed subjective deterioration in symptom trajectory 4 days prior to exacerbation onset (p < 0.01), with re-exacerbators demonstrating a higher baseline symptom burden in the post-treatment period compared to single exacerbators (p < 0.01).

In conclusion, salivary biomarker levels can complement patient self-assessment to provide clinically useful cues to enable earlier identification of exacerbations in COPD; salivary CRP potentially offers additional information on re-exacerbation risk. These results support opportunities for patient-reported events and salivary biomarkers to be used synergistically in future near-patient COPD diagnostics for enhanced self-management and prompt exacerbation intervention.