(JM test 4)High CRP level tied to earlier death in patients with ILD

Increased levels of serum C-reactive protein (CRP) may contribute to shorter survival in patients with idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (fHP), rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), or systemic sclerosis (SSc)-associated ILD at 5 years.

“To our knowledge, this is the first study to report an association between CRP and survival across a range of ILDs,” the investigators said. “This could suggest common inflammatory pathways with an adverse impact on disease behaviour.”

This retrospective study included ILD patients first presenting to the Royal Brompton Hospital between January 2010 and December 2019. Clinically measured CRP levels, baseline demographics, and lung function measures were obtained from the participants. Finally, the association between CRP level and 5-year mortality was examined by performing Cox regression analysis.

Of the patients, 422 had IPF, 233 had fHP, 111 had RA-ILD, and 86 had SSc-ILD. Those with a recent history of infection were excluded from the analysis. [Respirology 2024;29:228-234]

Higher CRP levels independently correlated with reduced 5-year survival across ILD diseases on both univariable analysis and after adjusting for age, gender, smoking history, immunosuppressive therapy, and baseline disease severity: IPF (hazard ratio [HR], 1.3, 95 percent confidence interval [CI], 1.1‒1.5; p=0.003), fHP (HR, 1.5, 95 percent CI, 1.2‒1.9; p=0.001), RA-ILD (HR, 1.4, 95 percent CI, 1.1‒1.84; p=0.01), and SSc-ILD (HR, 2.7, 95 percent CI, 1.6‒4.5; p<0.001).

Inflammatory state

An earlier study showed that serum interleukin 6, an acute phase protein inducing CRP synthesis, also predicts early demise in SSc-ILD patients. [J Rheumatol 2013;40:435-446]

Previous studies also reported the association of increased CRP with poor outcomes in cancer patients, regardless of cancer type, with elevated risk of cardiovascular, cerebrovascular, and all-cause mortality in hospital-based cohorts. [ESMO Open 2019;4:e000531; PLoS One 2015;10:e0116206]

These findings suggest “a nonspecific lethal effect of an increased inflammatory systemic state, possibly related to regulation of the innate immune/inflammatory response,” according to the investigators.

“Interestingly, the strongest relationship between CRP and mortality was seen in SSc-ILD, while the weakest was seen in IPF, in keeping with the hypothesis that systemic inflammation plays a lesser role in IPF than in CTD-ILDs and fHP,” they added.

The mechanisms behind the association between an increased systemic inflammatory state and shorter survival included involuntary weight loss, reduced functional status, and cardiovascular disease, as seen in other chronic lung diseases. [Am J Respir Crit Care Med 1994;150:1453-1455; Thorax 2006;61:17-22; Circulation 2003;107:1514-1519]

CRP could also produce a pathogenic effect on the severity of lung tissue damage or aberrant wound healing by intensifying pre-existing inflammation and tissue injury. [Ther Apher Dial 2019;23:494-496]

“[T]he link between serum CRP and earlier mortality across IPF, fHP, RA-ILD, and SSc-ILD is an interesting finding with potential pathogenetic implications requiring further study,” the investigators said.

“Replication in independent prospective cohorts is required to confirm our findings and to identify potential clinically applicable CRP thresholds to provide prognostic separation,” they added.