Understanding Systemic and Local Inflammation Induced by Nasal Polyposis: Role of the Allergic Phenotype

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by persistent symptoms associated to the development of nasal polyps. To this day, the molecular mechanisms involved are still not well defined. However, it has been suggested that a sustained inflammation as allergy is involved in its onset. In this exploratory study, the aim was to investigate the effect of the allergic status in the development of CRSwNP. To achieve this, we recruited 22 patients with CRSwNP and classified them in non-allergic and allergic using ImmunoCAP ISAC molecular diagnosis. Plasma samples were analyzed using liquid chromatography coupled to mass spectrometry (LC-MS). Subsequently, significant metabolites from plasma that were commercially available were then analyzed by targeted analysis in some nasal polyps. Additionally, nasal polyp and nasal mucosa samples were examined for eosinophils, neutrophils, CD3+ and CD11c+ cells, as well as collagen deposition and goblet cell hyperplasia. We found that 9 out of the 22 patients were sensitized to some aeroallergens (named as allergic CRSwNP). The other 13 patients had no sensitizations (non-allergic CRSwNP). Regarding metabolomics, bilirubin, cortisol, lysophosphatidylcholines (LPCs) 16:0, 18:0 and 20:4 and lysophosphatidylinositol (LPI) 20:4, which are usually related to a sustained allergic inflammation, were unexpectedly increased in plasma of non-allergic CRSwNP compared to allergic CRSwNP. LPC 16:0, LPC 18:0 and LPI 20:4 followed the same trend in nasal polyp as they did in plasma. Comparison of nasal polyps with nasal mucosa showed a significant increase in eosinophils (p < 0.001) and neutrophils (p < 0.01) in allergic CRSwNP. There were more eosinophils in polyps of non-allergic CRSwNP than in their nasal mucosa (p < 0.01). Polyps from non-allergic CRSwNP had less eosinophils than the polyps of allergic CRSwNP (p < 0.05) and reduced amounts of collagen compared to their nasal mucosa (p < 0.001). Our data suggests that there is a systemic inflammatory response associated to CRSwNP in the absence of allergy, which could be accountable for the nasal polyp development. Allergic CRSwNP presented a higher number of eosinophils in nasal polyps, suggesting that eosinophilia might be connected to the development of nasal polyps in this phenotype.

Understanding uncontrolled severe allergic asthma by integration of omic and clinical data

“…From a practical point of view, it uses very sensitive and specific techniques, such as LC-MS, which allows the simultaneous detection of a great variety of metabolites in each biological sample. 23,24 In this study, we performed an untargeted metabolomic analysis in all samples from each experimental group, what results, after a complex and laborious statistical analysis, into the identification of several significant signals that conform the metabolomic signature of UC group. Therefore, this study should be understood as exploratory.…”

“…In fact, the metabolome has been described to be closely linked to the phenotype of a disease and can be an extremely useful tool when evaluating the effect of treatments. From a practical point of view, it uses very sensitive and specific techniques, such as LC‐MS, which allows the simultaneous detection of a great variety of metabolites in each biological sample 23,24 …”

Comparative study of clinical symptoms of chronic rhinosinusitis with nasal polyps patients

“…There were no significant differences in comparing eosinophilic granulocyte counts in the polyp tissue between the SIgE‐positive and the SIgE‐negative groups, which suggested that the eosinophilic granulocytes might not increase when CRS w NP patients have allergic reactions. It suggests that the relationship between the general allergic reaction status and the degree of infiltration and activation of eosinophilic granulocyte in local tissues is uncertain 7,8 . It shows that the stimulation of sensitinogen to SIgE‐positive CRS w NP patients does not induce an inflammatory response of eosinophilic granulocyte in the nasal polyps, but there is an independent pathophysiological mechanism of inflammation maintenance 25 .…”

“…The impact of allergic reactions on the occurrence and development of CRS w NP is still inconclusive 7,8 . Still, available data support that serum IgE is associated with CRS w NP 9–11 .…”

Development of a Novel Targeted Metabolomic LC-QqQ-MS Method in Allergic Inflammation

“…In recent years, by using non-targeted metabolomics in combination with transcriptomics and proteomics in different allergic disease severity models, we have identified new biological systems and associated promising potential biomarker candidates [ 16 , 17 , 18 , 19 , 20 ]. Furthermore, the combined analysis of these studies has allowed us to identify metabolites potentially related to energy metabolism, sphingolipid, phospholipid pathways, and platelet function associated with the severe phenotype [ 21 , 22 ].…”