Airway and systemic inflammation predict COPD exacerbation

By Lucy Piper, Senior MedwireNews Reporter

Researchers have found a link between increased airway and systemic inflammation and frequent exacerbations in patients with chronic obstructive pulmonary disease (COPD).

The findings suggest a “vicious cycle” whereby frequent exacerbations in COPD patients aggravate airway inflammation, leading to increased systemic inflammation and future exacerbations.

This process might also extend to asthma patients, as frequent asthma exacerbations were significantly associated with systemic inflammation, although there was only a trend towards an association with airway inflammation. This may be due to the small sample size, the researchers suggest.

They assessed sputum interleukin (IL)-1β and IL-1 receptor antagonist proteins, as a measure of airway inflammation, and IL-6 and C-reactive protein (CRP), as a measure of systemic inflammation in 140 patients; 81 with COPD and 59 with asthma.

Over a 12-month follow-up period, 94 patients experienced a total of 21 exacerbations, at a rate of 1.10 per asthma patient and 1.67 per COPD patient. Frequent exacerbations of two or more were experienced by 36.4% of patients.

Experiencing frequent exacerbations was associated with significantly upregulated sputum IL-1β gene expression at baseline in COPD patients and significantly increased IL-6 levels (≥1.55 pg/mL) in asthma and COPD patients. CRP levels were also elevated, at 4.12 mg/L or above, in asthma patients with frequent exacerbations but not those with COPD.

Univariate regression analysis showed that upregulated IL-1β gene expression and protein levels significantly increased the risk of frequent COPD exacerbations 1.26-fold and 1.32-fold, respectively, while elevated IL-6 levels increased the risk of frequent exacerbations in both COPD and asthma 1.01-fold and 1.10-fold, respectively.

Researcher Peter Gibson (John Hunter Hospital, New Lambton, Australia) and co-investigators note in CHEST that these factors, along with a history of frequent exacerbations in the past year, also independently predicted future exacerbation frequency in COPD patients.

They propose that a history of frequent exacerbations directly predicts the risk of future exacerbations, but there is also an indirect effect of past exacerbations via the up-regulation of IL-1β and a subsequent increase in IL-6 systemic inflammation.

And as a result they believe that “[a]nti-inflammatory therapies targeting the airway IL-1β-systemic inflammatory pathway, which break the vicious cycle of inflammation leading to exacerbations, show promise as a strategy for preventing exacerbations.”

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