Photo Credit: Artur Plawgo
Emerging research shows mast cells play a role in the etiology of chronic rhinosinusitis with nasal polyps and may be a new treatment target for the condition.
“Despite extensive research, the underlying mechanisms driving [chronic rhinosinusitis with nasal polyps (CRSwNP)] remain a complex puzzle, highlighting the urgent need for a more comprehensive understanding,” Carlo Ennio Michele Pucillo, MD, and colleagues wrote. “Mast cells, key immune cells involved in tissue inflammation and remodeling, have emerged as significant players in the pathogenesis of CRSwNP. Given the persistent nature of CRSwNP and the limitations of current treatment options, there is a pressing need for innovative approaches that address the underlying mechanisms of the disease.”
Specifically, research suggests that mast cells are involved in the immunopathogenesis of CRSwNP and could serve as a potential therapeutic target, according to Dr. Pucillo and colleagues.
For a study published in Biomedicines, the researchers performed a systematic review of existing evidence on the role of mast cells in CRSwNP. They used the MEDLINE PubMed and Cochrane Library databases to search for research on the topic published between January 1, 2014, and November 1, 2024.
Clinical Relevance of Mast Cells in CRSwNP
The analysis included 62 studies. Dr. Pucillo and colleagues covered six primary topics in their review. Evidence for the clinical importance of mast cells in CRSwNP was discussed within sections on mast cells as drivers of mucosal T2 inflammation in CRSwNP; mast cells in the pathophysiology of aspirin-exacerbated respiratory disease (AERD); and the diagnostic and prognostic utility of mast cells in CRSwNP.
Mast Cells & T2 Inflammation
The researchers point to “the seminal paper” by Tetsuji Takabayashi and colleagues that showed “a significant abundance” of specific types of mast cells in the epithelium and the nasal polyp glands, as well as a strong correlation between the levels of tryptase and eosinophil cationic protein in nasal tissue extracts. In the last decade, studies have identified other activating and inhibitory molecules and pathways for mast cells in CRSwNP, including tuft cells and microbial cells. These results illustrate a need to manage a potentially treatable trigger by disrupting or reducing the bacterial biofilm, according to Dr. Pucillo and colleagues, who cite a strategy like local antibiotics as one potential option.
Mast Cells in the Pathophysiology of AERD
AERD—the association between CRSwNP, asthma, and acetylsalicylic acid hypersensitivity—is an inflammatory syndrome with an unknown cause. Dr. Pucillo and colleagues described molecular changes in the sinonasal microenvironment among patients with AERD, noting that the interaction between nasal epithelial cells and mast cells provides insight into this dysregulation. Another study found that mast cells “are the preeminent cells in orchestrating the AERD inflammatory response.”
Diagnostic & Prognostic Utility of Mast Cells
While the researchers noted that evidence on the clinical and prognostic role of mast cells in CRSwNP is highly variable, they also described several ways mast cells could serve as prognostic and predictive factors in treating nasal polyps.
For example, one study in their review found a positive correlation between membrane IgE-positive cells and the radiological severity score in patients with CRSwNP. Another small study found that the number of mast cells in resected polyps negatively correlated with the risk for recurrence. The researchers also described a study in which, after the exclusion of AERD, mast cells were more abundant in patients with plasma cell-dominant CRSwNP versus eosinophil-dominant cases; subjective symptoms measured by the sinonasal outcome test 22 were worse in the former group.
Dr. Pucillo and colleagues point to the potential of nasal cytology for translating basic research into clinical practice, citing one study that found the cytology and immunohistochemistry of nasal polyps to be comparable for the measuring of intraepithelial mast cells (P=0.002). In addition, a histological cut-off of six intraepithelial mast cells was determined as a potential marker to identify severe CRSwNP (P<0.001).
Targeting Mast Cells to Improve Treatments
“Recent studies have identified distinct [mast cell] phenotypes in nasal polyps, suggesting their crucial role in the development and progression of this disorder,” the researchers wrote. “As our understanding of the molecular mechanisms underlying CRSwNP continues to evolve, future research may uncover novel therapeutic strategies that directly target [mast cells] or their downstream signaling pathways. By targeting [mast cells], it may be possible to develop more effective and personalized treatments for CRSwNP, improving the quality of life for patients with this debilitating condition.”
