Analysis of human neutrophils from nasal polyps by single-cell RNA sequencing reveals roles of neutrophils in chronic rhinosinusitis.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 (T2) inflammation. Recent studies, including our own, suggest that neutrophils are also elevated in T2 nasal polyps (NP) and that elevated neutrophils display an activated phenotype. However, the actual roles of neutrophils in NP pathogenesis in T2 CRSwNP are still largely unclear.

Evidence that oncostatin M synergizes with IL-4 signaling to induce TSLP expression in chronic rhinosinusitis with nasal polyps.

Background: Oncostatin M (OSM) may promote type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) by inducing thymic stromal lymphopoietin (TSLP).

Objective: We sought to study the impact of OSM on TSLP synthesis and release from nasal epithelial cells (NECs).

Methods: OSM receptors, IL-4 receptors (IL-4R), and TSLP were evaluated in mucosal tissue and primary NECs from patients with CRSwNP by quantitative PCR and immunofluorescence.

Elevation of activated neutrophils in chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is well characterized by type 2 (T2) inflammation characterized by eosinophilia in Western countries. However, the presence and roles of neutrophils in T2 CRSwNP are poorly understood.

Objective: We sought to clarify accumulation and inflammatory roles of neutrophils in CRSwNP in a Western population.

Studies of the role of basophils in aspirin-exacerbated respiratory disease pathogenesis.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type 2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear.

Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps.

Background: Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) is a common disease that is characterized by multiple inflammatory endotypes. However, the molecular mechanisms in CRSsNP are poorly understood compared with those of polypoid CRS.

Objective: Our aim was to identify mechanisms and biomarkers associated with inflammatory endotypes underpinning CRSsNP.

Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated.

TNF induces production of type 2 cytokines in human group 2 innate lymphoid cells.

TNF receptor II is expressed on ILC2s and TNF is able to induce production of type 2 cytokines in human ILC2s. TNF may play a role in causing or amplifying type 2 immunity contributing to health and disease.

Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation in the nose and paranasal sinuses. Inflammation in CRS is also heterogeneous and is mainly characterized by type 2 (T2) inflammation, but subsets of patients show type 1 (T1) and type 3 (T3) inflammation. Whether inflammatory endotypes are associated with clinical phenotypes has yet to be explored in detail.

Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines. However, the presence of various types of ILC in CRS is poorly understood.

Chronic airway inflammation provides a unique environment for B cell activation and antibody production.

Background: B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans.

Proprotein convertases generate a highly functional heterodimeric form of thymic stromal lymphopoietin in humans.

Rationale: Thymic stromal lymphopoietin (TSLP) is known to be elevated and truncated in nasal polyps (NPs) of patients with chronic rhinosinusitis and might play a significant role in type 2 inflammation in this disease. However, neither the structure nor the role of the truncated products of TSLP has been studied.

Objective: We sought to investigate the mechanisms of truncation of TSLP in NPs and the function of the truncated products.

Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois.

CRSsNP is a heterogenous disease but type 2 inflammation in CRSsNP was more common than type 1 inflammation among patients in Chicago, Illinois. Distinct therapeutic strategies may be needed depending on the type of inflammation found in CRSsNP.

Elevated presence of myeloid dendritic cells in nasal polyps of patients with chronic rhinosinusitis.

Background: Although chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2 inflammation, the mechanism underlying the onset and amplification of this inflammation has not been fully elucidated. Dendritic cells (DCs) are major antigen-presenting cells, central inducers of adaptive immunity and critical regulators of many inflammatory diseases. However, the presence of DCs in CRS, especially in nasal polyps (NPs), has not been extensively studied.

Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with TH2-dominant inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine that triggers dendritic cell-mediated TH2 inflammatory responses and that enhances IL-1-dependent TH2 cytokine production in mast cells. Although increased TSLP mRNA levels have been found in nasal polyps (NPs), expression of TSLP protein and its function in patients with chronic rhinosinusitis (CRS) have not been fully explored.

Airway epithelial cells activate TH2 cytokine production in mast cells through IL-1 and thymic stromal lymphopoietin.

Background: Airway epithelial cells are important regulators of innate and adaptive immunity. Although mast cells are known to play a central role in manifestations of allergic inflammation and are found in the epithelium in patients with T(H)2-related diseases, their role is incompletely understood.

Objectives: The objective of this study was to investigate the role of airway epithelial cells in the production of T(H)2 cytokines in mast cells.

Achy breaky makey wakey heart? A randomised crossover trial of musical prompts.

Objective: Compared with no music (NM), does listening to 'Achy breaky heart' (ABH) or 'Disco science' (DS) increase the proportion of prehospital professionals delivering chest compressions at 2010 guideline-compliant rates of 100-120 bpm and 50-60 mm depths?

Methods: A randomised crossover trial recruiting at an Australian ambulance conference. Volunteers performed three 1-min sequences of continuous chest compressions on a manikin accompanied by NM, repeated choruses of ABH and DS, prerandomised for order.

Results: 37 of 74 participants were men; median age 37 years; 61% were paramedics, 20% students and 19% other health professionals.

Increased expression of CC chemokine ligand 18 in patients with chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with T(H)2-dominant inflammation, including eosinophilia, which is in contrast to chronic rhinosinusitis (CRS) without nasal polyps (NPs). CC chemokine ligand 18 (CCL18)/pulmonary and activation-regulated chemokine is known to recruit naive T cells, B cells, and immature dendritic cells, as well as to activate fibroblasts. CCL18 is thought to be involved in T(H)2-related inflammatory diseases, including asthma and atopic dermatitis.

Increased expression of the chemokine CCL23 in eosinophilic chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous chronic disease characterized by local inflammation of the sinonasal tissues. The pathogenesis of CRS remains controversial, but it has been associated with the accumulation of various immune and inflammatory cells in sinus tissue.

Objectives: The objective of this study was to investigate the expression of the chemokine CCL23, which is known to bind to CCR1 and recruit monocytes, macrophages, and dendritic cells, in patients with CRS.

Regulation and function of the IL-1 family cytokine IL-1F9 in human bronchial epithelial cells.

The IL-1 family of cytokines, which now includes 11 members, is well known to participate in inflammation. Although the most recently recognized IL-1 family cytokines (IL-1F5-11) have been shown to be expressed in airway epithelial cells, the regulation of their expression and function in the epithelium has not been extensively studied. We investigated the regulation of IL-1F5-11 in primary normal human bronchial epithelial cells.

Programmable oligomers targeting 5'-GGGG-3' in the minor groove of DNA and NF-kappaB binding inhibition.

A series of hairpin oligomers containing benzimidazole (Bi) and imidazopyridine (Ip) rings were synthesized and screened to target 5'-WGGGGW-3', a core sequence in the DNA-binding site of NF-kappaB, a prolific transcription factor important in biology and disease. Five Bi and Ip containing oligomers bound to the 5'-WGGGGW-3' site with high affinity. One of the oligomers (Im-Im-Im-Im-gamma-Py-Bi-Py-Bi-beta-Dp) was able to inhibit DNA binding by the transcription factor NF-kappaB.