Bench to beside: linking inflammation to clinical symptoms in CRS
Published online: June 14, 2019
Chronic rhinosinusitis (CRS) is chronic inflammatory disease of the sinonasal mucosa affecting approximately 12.5% of Americans with health care costs exceeding $22 billion annually. Patients with CRS report a variety of symptoms including runny nose, nasal congestion, post-nasal drip, sinus pressure, headache, smell loss, cough, and fatigue. Current treatment options for CRS patients remain limited and typically are not tailored to a patient’s specific constellation of clinical symptoms. Recent laboratory studies have reported differences in inflammatory marker profiles in CRS suggesting different underlying mechanisms may be contributing to disease in subsets of CRS patients. However, a relationship between these inflammatory markers (endotype) and clinical symptoms (phenotype) is not well defined.
In the recent study by Stevens et al. published in The Journal of Allergy and Clinical Immunology: In Practice, associations between inflammatory markers and clinical symptoms were examined within a tertiary care surgical population of CRS patients with or without nasal polyps (CRSwNP and CRSsNP respectively). Gene expression and/or protein levels of different inflammatory markers were measured in sinonasal tissues. Patients were then classified as having either a type 1, type 2, or type 3 endotype if the expression of IFNy, Charcot Leiden Crystal (CLC)/Eosinophil Cationic Protein (ECP), or IL-17a respectively was greater than the 90% percentile of what was measured in control sinus tissue. Separately (and in a blinded fashion), electronic medical records were reviewed for the same surgical patients to obtain a variety of demographic and clinical parameters. Following this review, the clinical and laboratory data was analyzed together to evaluate for any specific associations.
The type 2 endotype was the most common inflammatory endotype detected among all CRS patients as well as those with CRSsNP or CRSwNP on subgroup analysis. In regard to clinical symptoms, rhinorrhea, sinus pressure/pain, headache/migraine, fatigue and cough were more often reported by patients with CRSsNP than patients with CRSwNP. On the other hand, smell loss as well as a history of atopy and asthma was more frequently reported among patients with CRSwNP. Among all patients with CRS, those with a type 2 endotype were more likely to have nasal polyps, asthma, and smell loss but were less likely to report rhinorrhea and cough. The type 1 endotype was more common in females while the type 3 endotype was associated with the presence of intra-operative pus. When controlling for age, sex, nasal polyps, asthma, and atopy, smell loss remained associated with the type 2 endotype and intraoperative pus with the type 3 endotype. Interestingly, headache/migraine was associated with the presence of a type 2 endotype in CRSsNP patients but not with the type 2 endotype in CRSwNP. In both CRSsNP and CRSwNP patients, the presence of intraoperative pus correlated with the type 3 endotype.
In conclusion, this study found an association between specific clinical presentations and inflammatory endotypes in CRS. These findings may lead to the design of more precise and personalized medicines strategies in CRS and ultimately to a more targeted approach to managing patients with this disease.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.