Nasal Polyposis: More than a Chronic Inflammatory Disorder—A Disease of Mechanical Dysfunction—The São Paulo Position

Abstract

Introduction The importance of our study lies in the fact that we have demonstrated the occurrence of mechanical dysfunction within polypoid tissues, which promotes the development of polyps in the nasal cavity. Objective To change the paradigm of nasal polyposis (NP). In this new conception, the chronic nasal inflammatory process that occurs in response to allergies, to pollution, to changes in the epithelial barrier, or to other factors is merely the trigger of the development of the disease in individuals with a genetic predisposition to an abnormal tissue remodeling process, which leads to a derangement of the mechanical properties of the nasal mucosa and, consequently, allows it to grow unchecked. Data Synthesis We propose a fundamentally new approach to intervening in the pathological process of NP, addressing biomechanical properties, fluid dynamics, and the concept of surface tension. Conclusion The incorporation of biomechanical knowledge into our understanding of NP provides a new perspective to help elucidate the physiology and the pathology of nasal polyps, and new avenues for the treatment and cure of NP.

Alterations in cellular force parameters and cell projections in Nasal polyps-derived fibroblasts

“…In this regard, two primary agents are closely involved in tissue mechanical properties: extracellular matrix and cells. The importance of composition of extracellular matrix on nasal polypoid tissues' mechanical properties has been previously demonstrated [10,12,33], but the role of nasal polypoid cells in this mechanical dysfunction continues to remain unclear. In this context, the fibroblasts act in the tissue remodeling and amplification of inflammation through extracellular matrix-cell cross-talking [36,37], act on the pillars of nasal polyp development [38].…”

“…The lower cellular spreading area combined with a lower traction force on the tissue (and its ability to cause tissue deformation) may share a correlation with the mechanical dysfunction observed in Nasal Polyps. The lower traction force exerted by fibroblast on polypoid tissue has an impact on the interstitial hydrostatic pressure that could significantly favor edema formation and tissue growth in Nasal Polyps [10][11][12]33]. The increase in the interstitial hydrostatic pressure becomes a goal to be achieved to balance the impaired pressure force dynamic found in nasal polyposis that favors the edema formation [10,11,33].…”

“…The lower traction force exerted by fibroblast on polypoid tissue has an impact on the interstitial hydrostatic pressure that could significantly favor edema formation and tissue growth in Nasal Polyps [10][11][12]33]. The increase in the interstitial hydrostatic pressure becomes a goal to be achieved to balance the impaired pressure force dynamic found in nasal polyposis that favors the edema formation [10,11,33]. As we highlighted earlier, the importance of interactions between cells and the surrounding extracellular matrices are critical for fibroblast differentiation, cell signaling, biochemical regulation and tissue morphogenesis.…”

“…The application of TFM in fibroblasts allows the evaluation of the relationship between cytoskeletal components and cellular motility [30], oscillations of force-mediated calcium levels [31] and dynamic control of the nuclear position during the alteration of shape in these cells [32]. In the context of tissues mechanical properties, it is essential to assess the cellular role in nasal polyp tissue mechanical dysfunction [33]. In this study, we aim to evaluate the fibroblast morphology and its cellular traction force in fibroblasts primary cell cultures of healthy individuals (as controls) and from patients with CRSwNP.…”

Montelukast Has no Impact on the Systemic Production of TGFβ-1 in Patients with Nasal Polyposis Associated with Aspirin Intolerance

“…[1][2][3] This inability to properly elevate interstitial hydrostatic pressure in the polypoid nasal mucosa is closely related to the unique makeup of its extracellular matrix, which develops as the result of an anomalous tissue remodeling process. 4,5 In this context, transforming growth factor beta 1 (TGFβ-1) plays a pivotal role in the remodeling process of abnormal tissue in cases of NP. [6][7][8][9] In a previous study, 10 we demonstrated that fibroblasts isolated from patients with chronic rhinosinusitis without NP exhibit increased matrix metalloproteinase 1 (MMP1) and cysteinyl leukotriene receptor 1 (CysLTR1) after stimulation with leukotriene D4 (LTD4), with an additional increase occurring in the presence of TGF-β1.…”