This study used nasal lavage fluid for metabolomics to explore its feasibility, and applied it to the clinical metabolomics study of Xiaoqinglong Decoction in the treatment of allergic rhinitis(AR), aiming to investigate the molecular mechanism of Xiaoqing-long Decoction in the treatment of AR through differential changes in local nasal metabolism. AR patients were selected as the research subjects, and nasal lavage fluid was collected as the sample. Metabolomics analysis using liquid chromatography-mass spectrometry was performed on normal group, AR group, and Xiaoqinglong Decoction group. The differences in metabolic profiles among the groups were compared using principal component analysis and partial least squares discriminant analysis, and differential metabolites were identified and subjected to corresponding metabolic pathway analysis. The results showed that Xiaoqinglong Decoction significantly improved the symptoms of AR patients. The metabolomics analysis revealed 20 differential metabolites between AR group and Xiaoqinglong Decoction group. The core metabolite with a trending return in comparison to normal group was trimethyladipic acid. The metabolites were involved in multiple pathways, including β-alanine metabolism, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. The feasibility of applying nasal lavage fluid in nasal metabolomics was preliminarily demonstrated. Differential metabolites and enriched pathways in the treatment of AR patients with Xiaoqinglong Decoction were identified, indicating that it may improve rhinitis symptoms through the regulation of various metabolites, including antioxidant effects and correction of Th1/Th2 imbalance.
Humans ; Nasal Lavage Fluid ; Rhinitis, Allergic/drug therapy* ; Metabolomics/methods* ; Metabolome

Bronchoalveolar Lavage Fluid/virology* ; COVID-19/virology* ; Feces/virology* ; Genome, Viral ; Humans ; Mouth Mucosa/virology* ; Multiplex Polymerase Chain Reaction ; Nasal Mucosa/virology* ; SARS-CoV-2/genetics* ; Sputum/virology* ; Whole Genome Sequencing

PURPOSE: It remains unknown whether local inhibition of Nuclear factor-kappa B (NF-κB) could have therapeutic value in the treatment of allergic rhinitis (AR). This study aimed to evaluate the effect of selective NF-κB inhibition using NF-κB decoy oligodeoxynucleotides (ODNs) for the local treatment of AR in ovalbumin (OVA)-sensitized wild-type mice. METHODS: BALB/c mice were sensitized with OVA and alum, and then challenged intranasally with OVA. NF-κB decoy ODNs were given intranasally to the treatment group, and NF-κB scrambled ODNs were given to the sham treatment group. Allergic symptom scores, eosinophil infiltration, cytokine levels in the nasal mucosa, nasal lavage fluid, and spleen cell culture, serum total and OVA-specific immunoglobulins, as well as intercellular adhesion molecure-1 (ICAM-1) in the nasal mucosa, were analyzed. RESULTS: NF-κB decoy ODNs significantly reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. They also suppressed serum levels of total IgE, OVA-specific IgE, and IgG1. IL-5 and TNF-α levels and the expression of ICAM-1 were decreased in the nasal mucosa of the treatment group compared to the positive control and sham treatment groups. In addition, IL-6 levels were significantly decreased in the nasal lavage fluid of the treatment group. Furthermore, NF-κB decoy ODNs significantly reduced expression of the systemic Th2 cytokines, IL-4 and IL-5 in spleen cell culture. CONCLUSIONS: This study demonstrates for the first time that local NF-κB inhibition using NF-κB decoy ODNs suppressed the allergic response in a murine AR model. This shows the therapeutic potential of local NF-κB inhibition in the control of AR.
Animals ; Anti-Allergic Agents ; Cell Culture Techniques ; Cytokines ; Eosinophils ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Intercellular Adhesion Molecule-1 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Mice ; Nasal Lavage Fluid ; Nasal Mucosa ; NF-kappa B ; Oligodeoxyribonucleotides* ; Ovalbumin ; Ovum ; Placebos ; Rhinitis, Allergic* ; Spleen

PURPOSE: Extensive data support the influence of the upper airway on lower airway inflammation and pathophysiology in allergic disease. However, few studies have focused on allergic inflammation in the nose after an isolated lower airway allergen challenge, a situation that can exist clinically when human subjects breathe primarily through the mouth, as occurs when nasally congested. This study used a mouse model to investigate whether upper airway inflammation and hyperresponsiveness were induced by an isolated lower airway allergen challenge. METHODS: BALB/c mice were sensitized by systemic intraperitoneal injection of ovalbumin/saline and challenged with intratracheal ovalbumin/saline. Inflammation in the nose and lungs was assessed by cytology and histology of nasal tissues and bronchoalveolar lavage fluid (BALF), while nasal airway resistance and response were measured over 3 days post-challenge. RESULTS: Intratracheal application of an allergen in anaesthetized mice resulted in exclusive deposition in the lower airway. Compared to control animals, ovalbumin-sensitized mice after challenge showed bronchial hyperreactivity and increased IL-5 in the serum BALF, as well as eosinophil infiltration in the lungs. However, nasal histology of the ovalbumin-sensitized mice showed no increase in eosinophil infiltration. The nasal lavage fluid revealed no increase in eosinophils or IL-5, and the nasal airway resistance did not increase after challenge either. CONCLUSIONS: In a mouse allergy model, exclusive allergen challenge of the lower airway can elicit a pulmonary and systemic allergic response, but does not induce upper airway inflammatory or physiological responses.
Airway Resistance ; Animals ; Asthma* ; Bronchial Hyperreactivity ; Bronchoalveolar Lavage Fluid ; Eosinophils ; Estrogens, Conjugated (USP) ; Humans ; Hypersensitivity ; Inflammation* ; Injections, Intraperitoneal ; Interleukin-5 ; Lung ; Mice ; Mouth ; Nasal Lavage Fluid ; Nose* ; Rhinitis

Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alter native measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g., serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.
Adult ; Asthma ; Biomarkers ; Body Fluids ; Bone Marrow ; Bronchoalveolar Lavage Fluid ; Child ; Eosinophil Cationic Protein ; Eosinophil-Derived Neurotoxin ; Eosinophils ; Humans ; Inflammation ; Nasal Lavage ; Respiratory Function Tests ; Sputum

Rhinitis is a common airway disease that can affect patient's quality of life and social activities. Rhinitis comprises heterogenous diseases and classified as allergic rhinitis (AR) or nonallergic rhinitis (NAR) based on the clinical history, skin prick test, and serum-specific IgE to aeroallergens. It is important to differentiate between AR and NAR, as management differs for each. However, classification of NAR is controversial and the specific mechanisms responsible for NAR remain unclear. Recently, the entopy of local allergic rhinitis (LAR) has been raised if positive response to nasal provocation test, and elevated specific IgE and inflammatory mediators such as tryptase and eosinophilic cationic peptide in the nasal lavage fluids are shown in patients with NAR. About 47-62.5% of patients previously diagnosed with NAR actually have LAR. LAR shares similar nasal symptoms with AR, such as itching, sneezing, rhinorrhea, and nasal obstruction. LAR shows a good response to nasal corticosteroids and oral antihistamines. However, its natural history and role of immunotherapy need to be elucidated.
Adrenal Cortex Hormones ; Classification ; Diagnosis, Differential ; Eosinophils ; Histamine Antagonists ; Humans ; Immunoglobulin E ; Immunotherapy ; Nasal Lavage Fluid ; Nasal Obstruction ; Nasal Provocation Tests ; Natural History ; Pruritus ; Quality of Life ; Rhinitis* ; Skin ; Sneezing ; Tryptases

In recent decades, titanium dioxide (TiO2) nanoparticles have been used in various applications, including paints, coatings, and food. However, data are lacking on the toxicological aspects associated with their use. The aim of this study was to assess the inhalation toxicity of TiO2 nanoparticles in rats by using inhalation exposure. Male Wistar rats were exposed to TiO2 nanoparticles for 2 weeks (6 hr/day, 5 days/week) at a mean mass concentration of 11.39 +/- 0.31 mg/m3. We performed time-course necropsies at 1, 7, and 15 days after exposure. Lung inflammation and injury were assessed on the basis of the total and individual cell counts in bronchoalveolar lavage fluid (BALF), and by biochemical assays, including an assay for lactate dehydrogenase (LDH). Furthermore, histopathological examination was performed to investigate the lungs and nasal cavity of rats. There were no statistically significant changes in the number of BALF cells, results of biochemical assays of BALF and serum, and results of cytokine analysis. However, we did observe histopathological changes in the nasal cavity tissue. Lesions were observed at post-exposure days 1 and 7, which resolved at post-exposure day 15. We also calculated the actual amounts of TiO2 nanoparticles inhaled by the rats. The results showed that the degree of toxicity induced by TiO2 nanoparticles correlated with the delivered quantities. In particular, exposure to small particles with a size of approximately 20 nm resulted in toxicity, even if the total particle number was relatively low.
Animals ; Bronchoalveolar Lavage Fluid ; Cell Count ; Humans ; Inhalation ; Inhalation Exposure ; L-Lactate Dehydrogenase ; Lung ; Male ; Nanoparticles ; Nasal Cavity ; Paint ; Pneumonia ; Rats ; Rats, Wistar ; Titanium

OBJECTIVES: Silver has long been known as a strong antimicrobial and disinfectant. Several types of nano-silver coated products have been developed. However, the antimicrobial and disinfectant characteristics of nano-silver have not been well studied. The aim of this study was to investigate the effect of nano-silver on allergic inflammation in a mouse model. METHODS: Female BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide on days 0, 7, 14, and 21. Mice were challenged with intranasal instillation of OVA. Nano-silver was also administered nasally prior to intranasal instillation of OVA. Severity of allergic rhinitis was assessed according to nasal symptoms, serum OVA-specific IgE level, interleukin (IL)-4, IL-10, and interferon (INF)-gamma levels in nasal lavage fluid. Hematoxylin-eosin stain and periodic acid-Schiff stain were performed for evaluation of histological change. RESULTS: Nano-silver attenuated manifestation of nasal symptoms in sensitized mice and inhibited production of OVA-specific IgE, IL-4, and IL-10, however, it had no effect on INF-gamma level. In addition, the degree of inflammatory cell infiltration and goblet cell hyperplasia was attenuated by nano-silver. CONCLUSION: These results suggest that nano-silver may effectively reduce allergic inflammation in a mouse model of allergic rhinitis. Through its properties as an anti-inflammatory agent, nano-silver may be a useful therapeutic strategy.
Animals ; Female ; Goblet Cells ; Humans ; Hydroxides ; Hyperplasia ; Immunoglobulin E ; Inflammation ; Injections, Intraperitoneal ; Interferons ; Interleukin-10 ; Interleukin-4 ; Interleukins ; Mice ; Nasal Lavage Fluid ; Ovalbumin ; Ovum ; Rhinitis ; Rhinitis, Allergic, Perennial ; Silver

BACKGROUND AND OBJECTIVES: Chitin is a recognition element for tissue infiltration by innate cells implicated in allergy and asthma. Chitinases are characterized by the ability to cleave chitin. YKL-40, the chitinase-like protein, was increased during Th2-type inflammation in an exaggerated manner in tissues of patients with asthma. However, the relationship of YKL-40 level to allergic rhinitis has not been evaluated. Hence, we evaluated the relationship between the YKL-40 level in the blood and nasal lavage fluid and allergic inflammation in nasal cavity. We also evaluated the nature of association between several important factors (eosinophil count and total IgE) in the blood and nasal lavage fluid of allergic rhinitis patients. SUBJECTS AND METHOD: The concentrations of the YKL-40 levels in the blood and nasal lavage fluid were compared between allergic rhinitis patients and healthy controls. We evaluated the YKL-40 levels in the blood and nasal lavage fluid and also evaluated symptom severity, eosinophil count, and total IgE. RESULTS: The blood YKL-40 level was not significantly increased in allergic rhinitis (49 pg/mL) than in control (44 pg/mL)(p>0.05). The YKL-40 levels in the nasal lavage fluid was not significantly increased in allergic rhinitis (1568 pg/mL) than in control (1248 pg/mL)(p>0.05). The YKL-40 levels in blood and nasal lavage fluid were not associated with important factors such as symptom severity, eosinophil count, and total IgE in allergic rhinitis patients. CONCLUSION: There is no association between the YKL-40 level in the blood and nasal lavage fluid, allergic inflammation in nasal cavity.
Asthma ; Chitin ; Chitinase ; Eosinophils ; Humans ; Hypersensitivity ; Immunoglobulin E ; Inflammation ; Nasal Cavity ; Nasal Lavage ; Nasal Lavage Fluid ; Rhinitis ; Rhinitis, Allergic, Perennial

BACKGROUND AND OBJECTIVES: The effect of nasal exposure to staphylococcal enterotoxin in the pathogenesis of allergic rhinitis remains controversial. We sought to determine the effect of increasing doses of intranasally applied Staphylococcus aureus enterotoxin B (SEB) on the respiratory mucosa, especially the nasal mucosa. MATERIALS AND METHODS: Nasal application of SEB was performed on four occasions (days 0-4-8-12) in unsensitized BALB/c mice. Control mice were intranasally treated with phosphate buffered saline (PBS), and 5 ng, 50 ng, 500 ng, and 5 microg of SEB was applied to the respective experimental group. The concentrations of IL-4, IL-5, and IFN-gamma in bronchoalveolar lavage fluid (BALF), nasal lavage fluid (NLF) and serum were compared among groups. Also, the counts of total inflammatory cells, macrophages, lymphocytes, neutrophils, eosinophils, and basophils in BALF and NLF were compared among the groups. Pathologic studies for inflammatory cell infiltration in the nasal mucosa and peribronchial area were conducted. RESULTS: IL-4 and IFN-gamma showed higher concentrations with increasing stimulation dose of SEB in NLF and serum. The IL-5 concentration showed a tendency to increase in NLF and serum, but these changes were not statistically significant. Total inflammatory cell count, especially macrophage count, in BALF and NLF was higher with increasing stimulation dose of SEB. Infiltration of inflammatory cells into the nasal mucosa showed a tendency to increase in a dose-dependent manner. CONCLUSION: These results suggest that nasal exposure to SEB may induce Th1 and Th2 inflammatory responses in the respiratory mucosa, especially the nasal mucosa.
Animals ; Basophils ; Bronchoalveolar Lavage Fluid ; Cell Count ; Enterotoxins ; Eosinophils ; Interleukin-4 ; Interleukin-5 ; Lymphocytes ; Macrophages ; Mice ; Mucous Membrane ; Nasal Lavage Fluid ; Nasal Mucosa ; Neutrophils ; Respiratory Mucosa ; Rhinitis ; Rhinitis, Allergic, Perennial ; Staphylococcus aureus