Calprotectin’s Role as Biomarker in CRSwNP Investigated in Italian Study

Conflicting prior study results on the effectiveness of calprotectin expression as a protective or pathologic response among persons with chronic rhinosinusitis with nasal polyps (CRSwNP) spurred this new investigation.

Differing levels of calprotectin in the nasal secretions of patients who have chronic rhinosinusitis with nasal polyps (CRSwNP) compared with control patients indicate this member of the S100 protein family has potential to be used as a biomarker of non–type 2 inflammation, according to new study results published in Acta Otorhinolaryngologica Italica.

This knowledge, the study authors added, is important to improve targeted therapy efforts in the space, “bearing in mind that biologics may offer greater efficacy in type-2 inflammatory disease and that future studies should be performed to determine if high levels of calprotectin in nasal secretions may be predictive of poor response to type-2 biologics in CRSwNP.”

The study group consisted of patients with CRSwNP who were classified by dominant cellular pattern into eosinophilic CRSwNP (EOS-CRSwNP/pure type 2; n = 15), noneosinophilic CRSwNP (non–EOS-CRSwNP/pure type 1 or type 3; n = 12), and mixed CRSwNP (type 2/3 or type 1/2 (n = 14), and there were 3 control groups: nonallergic rhinitis (NAR; n = 13), nonallergic eosinophilic syndrome (NARES; N = 10), and healthy (n = 12). A chemiluminescent immunoassay was used for nasal secretion detection.

Patients were enrolled between October 2019 and January 2021 from A. Hospital Foundation IRCCS in Italy. To be included in this analysis, they had to have CRSwNP as outlined in the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 and significant nasal symptoms (score > 20) according to the Sino-nasal Outcome Test (SNOT-22).

Among the CRSwNP group, the most common disease endotype was type 2 (n = 15), followed by type 1/2 (n = 10), type 3 (n = 6), and type 1 and type 2/3 (n = 5 each). Mean (SD) eosinophil count/high-powered field (HPF) was highest in the type 2 inflammation group, at 36.2 (8.2), and mean neutrophil count/HPF was highest in the type 2/3 group, at 41.3 (10.6).

Mean calprotectin levels were highest (when considering singular types, not mixed types) in the nasal secretions of type 1 and type 3 CRSwNP vs healthy controls: 170.37 (70.2) vs 77.3 (31.6) ng/mL and 434.73 (100.2) vs 77.3 (31.6) ng/mL, respectively. Type 2 CRSwNP, meanwhile, had significantly lower levels of calprotectin vs controls: 31.6 (15.8) vs 77.3 (31.6) ng/mL. Overall, however, the highest calprotectin levels were in type 3, followed by mixed type 2/3 (270.86 [89.2] ng/mL) and mixed type 1/2 (268.42 [87.2]). Type 2 CRSwNP had the lowest calprotectin level of 31.6 (15.8) ng/mL.

When looking specifically at the dominant cellular pattern, calprotectin levels were markedly higher in the non–EOS-CRSwNP and mixed CRSwNP groups vs the healthy control group: 324.5 (159.7) vs 77.3 (31.6) ng/mL and 269.6 (94.5) vs 77.3 (31.6) ng/mL, respectively. That of the EOS-CRSwNP was again lower, at 31.6 (15.8) ng/mL vs 77.3 (31.6) ng/mL.

Calprotectin was higher in persons with nonatopic vs atopic disease (P > .05) and in patients with asthma vs those who did not have asthma (P > .05). In addition, significant correlations were seen between calprotectin levels and the following:

  • Neutrophilic count/HPF in all patients (P < .01)
  • Neutrophilic count/HPF in all patients with CRSwNP (P < .01)
  • Eosinophil count/HPF (P > .05)
  • Increasing total of endoscopic sinus surgeries (P < .05)

“To our knowledge, this is the first study analyzing calprotectin levels in nasal secretions based on different CRSwNP endotypes. The conflicting data in the literature regarding calprotectin in nasal secretions may be explained by the heterogeneity of the disease and the different proportion of non–type 2 endotypes included in different series,” the authors wrote. “For this reason, we suggest that the levels of calprotectin should always be defined based on endotypes of the disease and on the proportion of neutrophilic infiltration in mixed patterns.”

To make progress in the field, they suggest additional investigations into the potential of high levels of calprotectin in nasal secretions as predictors of poor response to type 2 biologics in CRSwNP.


De Corso E, Baroni S, Onori ME, et al. Calprotectin in nasal secretion: a new biomarker of non-type 2 inflammation in CRSwNP. Acta Otorhinolaryngal Ital. Published online June 30, 2022. doi:10.14639/0392-100X-N1800