IP-10 and neopterin show promise as biomarkers for lung disease exacerbations

By Afsaneh Gray, medwireNews Reporter

Australian researchers have identified interferon-γ inducible protein (IP)-10 and neopterin as promising sputum markers of acute exacerbations of obstructive lung disease.

They also found that exhaled breath condensate (EBC) pH was significantly lower in patients during exacerbations than after recovery.

"Better understanding of exacerbations is vitally important for improving treatment, decreasing morbidity and preventing complications in lung diseases," say Geoffrey Warwick (St Vincent's Hospital, Darlinghurst, New South Wales) and colleagues.

EBC, induced sputum, and blood levels of C-reactive protein were determined in 84 study participants who presented with exacerbations of chronic obstructive pulmonary disease (COPD; n=29), or asthma (n=28), and otherwise healthy controls with symptoms of respiratory tract infection (n=28). Patients were invited to return when clinically stable for repeat investigations; 15 controls, 18 asthmatics, and 18 COPD patients did so.

Pooling the results from all patient groups revealed a significant decrease in EBC pH when measured immediately in acute patients compared with when stable (5.54 vs 6.04). EBC IP-10 levels were higher in acutely unwell patients than in those who were stable (6.41 vs 2.73). However, no significant differences in EBC biomarker levels were observed between different disease subtypes.

In induced sputum, IP-10 and neopterin were significantly increased when results across patient groups were combined, at 188.6 pg/mL during exacerbations versus 5.40 pg/mL after exacerbations for IP-10, and 15.81 nmol/L versus 5.38 nmol/L for neopterin.

In patients with asthma, interleukin (IL)-6 was also higher during acute presentations compared with when stable, at 557.7 pg/mL versus 240.4 pg/mL.

Serum C-reactive protein (CRP) was significantly raised during exacerbations; however, the authors point out that "CRP is not produced directly within the lung and is increased in several other inflammatory conditions."

Comparison of sputum cell counts between patients from the different subgroups revealed that inflammation was predominantly neutrophilic in patients with asthma, whereas eosinophils predominated in the COPD group. But many of the patients with asthma were taking inhaled corticosteroids, and this may have suppressed their eosinophil response, the researchers suggest.

"Given the lack of a universally recognised definition of exacerbation, there might be a role for a biomarker to define an exacerbation, although an EBC biomarker might have proved simpler to apply in a research setting than the sputum biomarkers we identified," Warwick et al conclude in Respirology.

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