Current Update of Local Allergic Rhinitis / 대한이비인후과학회지

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy. The symptoms, duration, severity, and comorbidities of LAR are similar to those of allergic rhinitis. Although pathophysiology of LAR is not fully understood, in some patients specific IgE can be demonstrated in the nasal secretions. The diagnosis currently relies on the positive results of nasal provocation test. Nasal provocation test has shown high sensitivity and specificity with safety, and is considered as the gold standard. LAR patients benefit from the same therapeutic strategies as allergic rhinitis patients, including the avoidance of allergen exposure and the pharmacotherapy. Effectiveness and safety of allergen immunotherapy open a window of treatment opportunity in LAR. This review provides a current update on LAR.

Contemporary Review of Olfactory Dysfunction in COVID-19

The pandemic of coronavirus disease 2019 (COVID-19) is an extreme threat to international health care, resulting in more than two million deaths. Data reveal that olfactory disorder is a characteristic symptom of COVID-19 and has unique clinical manifestations. The olfactory dysfunction induced by COVID-19 has sudden onset, short duration, and rapid recovery, with anosmia often the only symptom. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) affects the human body by binding to angiotensin converting enzyme 2 (ACE2) of the olfactory epithelium. However, the etiology of COVID-19-induced olfactory dysfunction is unclear. In many countries, vaccines for COVID-19 in human are beginning to be administered. Conventional conservative treatments are common for olfactory disorders caused by COVID-19. Rhinologists should be aware of olfactory dysfunction to avoid delayed diagnosis of COVID-19. The article reviews the latest scientific evidence of anosmia in COVID-19.

Contemporary Review of Olfactory Dysfunction in COVID-19

The pandemic of coronavirus disease 2019 (COVID-19) is an extreme threat to international health care, resulting in more than two million deaths. Data reveal that olfactory disorder is a characteristic symptom of COVID-19 and has unique clinical manifestations. The olfactory dysfunction induced by COVID-19 has sudden onset, short duration, and rapid recovery, with anosmia often the only symptom. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) affects the human body by binding to angiotensin converting enzyme 2 (ACE2) of the olfactory epithelium. However, the etiology of COVID-19-induced olfactory dysfunction is unclear. In many countries, vaccines for COVID-19 in human are beginning to be administered. Conventional conservative treatments are common for olfactory disorders caused by COVID-19. Rhinologists should be aware of olfactory dysfunction to avoid delayed diagnosis of COVID-19. The article reviews the latest scientific evidence of anosmia in COVID-19.

Footsteps of the Innovations in Rhinology

Rhinology is the study of nose, paranasal sinus, and nasopharynx. The nose is the most prominent structure on the human face and has been a subject of study since ancient human civilization. The history of rhinology has reflected the sociocultural aspects of the times, and rhinology has achieved remarkable growth with innovative discoveries by numerous pioneers. The focus of surgical procedures of the paranasal sinus shifted from mucosal stripping to functional endoscopic surgery with advancement of technology. Furthermore, the field of rhinology is gradually expanding due to cutting-edge technologies such as image-guided surgery, three-dimensional endoscopy, and robotic surgery. Additional clinical experiences and technological developments are expected to further advance rhinology.

Histamine Induced Production of Chemokine CXCL8 Through H1R/PLC and NF-κB Signaling Pathways in Nasal Fibroblasts

Background and Objectives@#Histamine has been suggested to play an important role during allergic and inflammatory reactions, affecting allergic rhinitis and chronic rhinosinusitis. CXCL8 is a pro-inflammatory chemokine and a critical factor that causes many airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.Materials and Method: Histamine cytotoxicity was measured by MTT assay. Real-time polymerase chain reaction was used to identify histamine type 1 receptor in nasal fibroblasts. The fibroblasts were then treated with histamine with or without a histamine type 1 receptor antagonist and the CXCL8 protein was assessed using an enzyme-linked immunosorbent assay (ELISA). The downstream signaling molecules, including phospholipase C and phospho-p50, were evaluated by western blot and immunofluorescent staining. @*Results@#Histamine had no significant cytotoxic effect until the concentration reached 1,000 μM. Histamine type 1 receptor mRNA was expressed in nasal fibroblasts. CXCL8 protein expression level was significantly increased following histamine stimulation. However, the expression level of CXCL8 decreased when phospholipase C was inhibited by U73122. Histamine increased phospho-p50 expression as seen in western blot results. The BAY11-7082, NF-κB inhibitor significantly reduced CXCL8 production in histamine-stimulated nasal fibroblasts. @*Conclusion@#Histamine can induce the production of NF-κB controlled-chemokine CXCL8 by nasal fibroblasts, which supports a role for histamine in upper airway inflammatory diseases.

The Relationship between the Causative Allergens of Allergic Diseases and Environments in Korea Over a 8-Year-Period: Based on Skin Prick Test from 2006 to 2015

BACKGROUND AND OBJECTIVES: The present study evaluated the results of skin prick test using 55 allergens at 20 centers in the Republic of Korea in 2006, 2010, and 2014–2015. The aim was to assess changes in the positive rate of allergens according to temporal, regional, and environmental factors. MATERIALS AND METHODS: In total, 20 hospitals were selected based on the population distribution in the Republic of Korea. A skin prick test panel comprising 55 aeroallergens was distributed to 18 hospitals for this prospective study. The 2006 and 2010 skin prick test results were collected and analyzed retrospectively from 20 hospitals, while the 2014/2015 skin prick test results (from June 2014 to May 2015) were collected prospectively from 18 hospitals. RESULTS: A total of 14,897 SPT test results were analyzed: 4,319 in 2006, 7,431 in 2010, and 1,852 in 2014/2015. The overall rate of skin prick test positivity to more than two allergens was significantly higher in males than females. The positive rates of alder pollens and birch, oak and ragweed pollen positivity were increased in older patients. Several positive rates were increased according to the temperature in spring. The positive rates for beech pollen, birch pollen, hazel pollen, oak pollen, Tyrophagus putrescentiae, mugwort, cat, Acarus siro, Lepidoglyphus destructor and Tyrophagus putrescentiae were significantly increased, while those of Cult rye pollen and dandelion were significantly decreased over the three test periods. The overall positive rate for allergens in Jeju province varied significantly from Seoul and other cities. CONCLUSION: Change in the positive rate of multiple aeroallergens was evaluated in the Republic of Korea over time. Our findings can be used to recommend aeroallergens suitable for inclusion in skin prick test panels in the Republic of Korea and will facilitate further investigation of changes in the patterns of allergic diseases.

Epigenetic Regulation of Nasal Polyp Formation

Nasal polyposis is a multi-factorial disease associated with chronic inflammation of the paranasal sinuses. Myofibroblast differentiation and extracellular matrix (ECM) accumulation are involved in the pathogenesis of nasal polyposis. Epigenetics, DNA methylation, and chromatin modifications are critical for generating cellular diversity and for maintaining distinct gene expression profiles. Based on our recent study that evaluated the inhibitory effect of Trichostatin A on myofibroblast differentiation in nasal polyposis, we hypothesized that HDAC inhibition is associated with myofibroblast differentiation and extracellular matrix accumulation in nasal polyposis and suggested that Trischostatin A may be useful as an inhibitor of nasal polyp growth and thus has potential to be used as a novel treatment option for nasal polyposis. In this review, we present general concept of epigenetics and results of recent research that elucidate the role of epigenetics in the pathogenesis of nasal polyps.

Clinical Characteristics of Lacrimal Sac Tumors: Report of Ten Cases

BACKGROUND AND OBJECTIVES: To review our experience with lacrimal sac tumors in an effort to identify features, to evaluate the results of various methods of management, and to compare our data with previous studies. METHODS: We reviewed the medical records of all patients with lacrimal sac tumors who were managed in our institution between January 1990 and December 2015. The pre-operative clinical data, imaging, operation notes, and follow-up records were reviewed for each patient. RESULTS: The study group consisted of four men and six women with a mean age of 47.6 years. Most patients experienced long-standing epiphora, for a mean period of 20 months. Two of the tumors were benign, and eight of them were malignant. The benign tumors were treated with dacryocystectomy. All but one malignant tumor were treated with medial or total maxillectomy. Adjuvant radiotherapy was administered to four patients with malignant tumors. In the eight patients with malignant tumors, the mean follow-up period was 65 months. CONCLUSIONS: Important characteristics of lacrimal sac tumors include dacryocystitis, epiphora, and in some cases, a palpable medial canthal area mass. Wide en bloc resection via medial or total maxillectomy and/or postoperative radiotherapy are proper treatments for malignant lesions of the lacrimal sac.

Efficacy and Safety of Guardcel Nasal Packing After Endoscopic Sinus Surgery: A Prospective, Single-Blind, Randomized Controlled Study

OBJECTIVES: Nasal packing after endoscopic sinus surgery is frequently used to control postoperative bleeding, enhance the wound healing process, and prevent lateralization of the middle turbinate, which causes insufficient ventilation. Many biodegradable materials have been developed to reduce pain and mucosal damage during packing removal. The purpose of this study was to compare the efficacy of Guardcel (Genewel Co.) middle meatal packing with a traditional nonabsorbable middle meatal packing, Merocel (Medtronic Xomed), on wound healing and patient satisfaction. METHODS: In this prospective, single-blind, randomized controlled study, we enrolled 32 consecutive patients (64 nostrils) undergoing bilateral endoscopic sinus surgery at Korea University Guro Hospital from February 2015 to August 2015. Guardcel and Merocel were inserted postoperatively into a randomly assigned side. Objective findings about bleeding, hemostasis, adhesion, and infection were evaluated with nasal endoscopy. Patients’ symptoms including pain and nasal obstruction were evaluated with a visual analog scale. Each evaluation was done at 2–3 days, 1 week, 2 weeks, and 4 weeks after surgery. RESULTS: At 2–3 days after endoscopic sinus surgery, the Guardcel side had a significantly less hemostasis time than the Merocel side (P=0.001). During this period, the pain during packing removal was significantly lower on the Guardcel-inserted side than the Merocel-inserted side (P=0.002). At two weeks after surgery, the adhesion score on the Guardcel side was significantly lower than that of the Merocel side (P=0.011). Other parameters during the study follow-up periods were not statistically significant. There were no severe adverse reactions. CONCLUSION: Guardcel, a newly developed packing material, appeared to shorten the hemostasis time and reduce pain sensation at 2–3 days after surgery; it also prevented adhesion formation 2 weeks after surgery when compared with the control. Guardcel can be an effective and safe candidate to replace conventional packing materials after endoscopic sinus surgery.

Histopathologic Diagnosis Associated with Delayed Diagnosis of Inferior Turbinate Pathology / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Conditions of inferior turbinate other than hypertrophy are rare and its morphology of inferior turbinate is variable. Therefore, the diagnosis of this fatal disease is often delayed. In the present study, histopathologic characteristics of inferior turbinate lesions associated with delayed diagnosis are determined by reviewing the clinical and diagnostic outcomes in patients with inferior turbinate lesions. MATERIALS AND METHOD: The medical records of patients who underwent endoscopic inferior turbinate biopsy following histopathologic evaluation from 2002 to 2013 were retrospectively reviewed, including the previous medical history, physical examination, radiologic findings, histopathologic results, therapy, and follow-up examination. RESULTS: A total 21 patients were included. The most common primary symptoms were nasal obstruction and frequent epistaxis. Diagnosed were 9 benign tumors, 7 malignant tumors, 2 infectious lesions, and 3 autoimmune lesions. Six of 21 patients visited more than three different hospitals before visiting our hospital. One-third of the cases with delayed diagnosis were malignant tumors, which included mucosal melanoma and natural killer/T cell lymphoma. CONCLUSION: In patients with nasal obstruction unresponsive to multiple therapeutic attempts, inferior turbinate neoplasia should be suspected to avoid delaying diagnosis and proper treatment.

Long-term Subjective and Objective Outcomes of Adenotonsillectomy in Korean Children With Obstructive Sleep Apnea Syndrome

OBJECTIVES: Adenotonsillar hypertrophy is the most common etiology in pediatric obstructive sleep apnea syndrome (OSAS), and adenotonsillectomy is the mainstay of treatment modalities. This study evaluates the long-term effectiveness of adenotonsillectomy in children with OSAS. METHODS: Subjective symptoms evaluated with a 7-point Likert scale and objective respiratory disturbances evaluated by polysomnography were compared before and after adenotonsillectomy. RESULTS: A total of 17 children with OSAS aged 4-15 years (mean age, 6.65+/-3.02 years; male:female, 13:4) completed the study. The mean follow-up period was 57 months (range, 30 to 98 months). Significant changes were found in apnea-hypopnea index (from 12.49+/-12.96 to 1.96+/-2.01, P<0.001), apnea index (from 5.64+/-7.57 to 0.53+/-0.78, P=0.006), minimum SaO2 (from 81.88+/-14.36 to 92.76+/-4.31, P=0.003), snoring (from 43.28+/-70.63 to 10.70+/-13.72, P=0.042), and arousal index (from 19.58+/-7.57 to 11.36+/-3.99, P=0.006) after adenotonsillectomy. Significant changes were also found after surgery in most of symptoms including snoring, witnessed apnea, morning headache, mouth breathing, gasping during sleep, restless sleep, nasal obstruction, and difficulty with morning arousal. Long-term surgical cure rate and response rate were 47.1% (8/17) and 70.6% (12/17), respectively. CONCLUSION: Most of subjective OSAS symptoms and objective respiratory disturbances improved continuously about 5 years after adenotonsillectomy in children with OSAS. However, close follow-up and a sufficient observation period are necessary because of the risk for long-term incomplete resolution.

Antiallergic Effects of Trichostatin A in a Murine Model of Allergic Rhinitis

OBJECTIVES: Trichostatin A (TSA), an inhibitor of histone deacetylase, has been shown to play an important role in attenuating asthmatic inflammation. However, the effect of TSA in allergic rhinitis is not known. The aims of this study were to investigate the effect of TSA on allergic nasal inflammation and on the induction of regulatory T cells in a murine model of allergic rhinitis. METHODS: BALB/c mice were sensitized intraperitoneally with ovalbumin (OVA) and then challenged intranasally with OVA. TSA (1 mg/kg) was given to the treatment group, and multiple parameters of allergic responses were evaluated to determine the effects of TSA on allergic rhinitis. Allergic nasal symptom scores, including frequency of rubbing and sneezing, were checked. Eosinophil infiltrations were stained with Chromotrope 2R, and the expression levels of OVA-specific IgE, T-helper 1 (Th1) cytokine (interferon-gamma [IFN-gamma]), Th2 cytokines (interleukin [IL] 4 and IL-5) and Treg (Foxp3, IL-10, and transforming growth factor-beta [TGF-beta]) were measured by quantitative reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay. RESULTS: TSA reduced the scores of allergic nasal symptoms and the amount of eosinophil infiltration into the nasal mucosa. TSA suppressed OVA-specific IgE levels and reduced expression of the IL-4 and IL-5. However, the expression of IFN-gamma was unchanged in the treatment group. The levels of Foxp3, IL-10, and TGF-beta were increased in pretreatment with TSA as compared to control group. CONCLUSION: This study shows that TSA induced antiallergic effects by decreasing eosinophilic infiltration and Th2 cytokines in a murine model of allergic rhinitis via regulation of Tregs. Thus, TSA may be considered a potentially therapeutic agent in treating allergic rhinitis.

Inhibitory Effect of Delphinidin on Extracellular Matrix Production via the MAPK/NF-kappaB Pathway in Nasal Polyp-Derived Fibroblasts

PURPOSE: Nasal polyps are associated with chronic inflammation of the mucous membranes in the nose and paranasal sinuses and involved in extracellular matrix (ECM) accumulation. Delphinidin promotes ECM degradation in hepatitis and cardiac fibrosis. The aims of this study were to examine the inhibitory effect of delphinidin on TGF-beta1-induced myofibroblast differentiation and ECM accumulation, and to determine the underlying mechanisms in nasal polyp-derived fibroblasts (NPDFs). METHODS: NPDFs were stimulated with TGF-beta1, with or without delphinidin, and the expression levels of alpha-SMA, fibronectin, and collagen type I were determined by RT-PCR, Western blot analysis, and collagen assay. The expression of alpha-SMA protein was measured by immunocytochemical staining. Mitogen-activated protein kinase and NF-kappaB activation induced by TGF-beta1 were determined by Western blot analysis. The transcriptional activity of NF-kappaB was measured by luciferase assay. RESULTS: The expression levels of alpha-SMA, fibronectin, and collagen type I increased in TGF-beta1-stimulated NPDFs. In TGF-beta1-induced NPDFs, delphinidin inhibited the expression of alpha-SMA, fibronectin, and collagen. Inhibitors of MAPK and NF-kappaB blocked the expression of alpha-SMA, fibronectin, and collagen type I. Delphinidin suppressed the activation of MAPK and NF-kappaB induced by TGF-beta1 stimulation. CONCLUSIONS: These results suggest that delphinidin may inhibit TGF-beta1-induced myofibroblast differentiation and ECM production through the MAPK/NF-kappaB signaling pathway in NPDFs.

Comparison of Intranasal Ciclesonide, Oral Levocetirizine, and Combination Treatment for Allergic Rhinitis

PURPOSE: To evaluate the efficacy and safety of once-daily ciclesonide in comparison to both levocetirizine alone, and a ciclesonide/levocetirizine combination in patients with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). METHODS: Subjects exhibiting moderate to severe allergic rhinitis for longer than 1 year were randomized in an open-label, 3-arm, parallel group, multicenter study. Subjects received 200 microg ciclesonide, 5 mg levocetirizine, or a combination of both. Changes from baseline until the end-of-study visit (2 weeks following) were evaluated by reflective total nasal symptom scores (rTNSSs), reflective total ocular symptom scores (rTOSSs), physician-assessed overall nasal signs and symptoms severity (PANS), and rhinoconjunctivitis quality-of-life questionnaires (RQLQ). RESULTS: Significant improvements in rTNSS, PANS, and RQLQ in the ciclesonide monotherapy group were observed in comparison to the levocetirizine alone group. Three individual symptoms of rTNSS, including runny nose, nasal itching, and congestion, were improved in the ciclesonide-treated group. rTOSS scores for ciclesonide monotherapy improved from baseline, but no superiority over levocetirizine was shown. The absolute score and changes in rTNSS and PANS were positively correlated. Ciclesonide spray was more effective than levocetirizine in reducing nasal symptoms in both SAR and PAR patients. Ciclesonide and levocetrizine were well tolerated alone and in combination. CONCLUSIONS: Our results provide support for an AR and its Impact on Asthma (ARIA) recommendation stipulating that ciclesonide is superior to levocetirizine for the treatment of AR, with tolerable safety. Addition of levocetirizine to ciclesonide did not give further clinical benefit over monotherapy.

Sublingual Immunotherapy in Asian Children: 2-Year Follow-Up Results

BACKGROUNDS: House-dust mites are the main cause of allergic rhinitis in Asia, for which immunotherapy (SLIT) is a currently accepted treatment. However, few studies have evaluated the efficiency of SLIT on Asian children with allergic rhinitis for a period longer than one year. The aim of this study was to investigate the efficacy and safety of SLIT for Asian children with allergic rhinitis due to house-dust mites over a 2-year period. MATERIALS AND METHODS: This study included 65 patients who had allergic rhinitis due to Dermatophagoides pteronyssinus and Dermatophagoides farinae. All patients were treated with SLIT (Staloral(R)). Symptom scores and quality of life were evaluated by using questionnaires over two years. The medication score was assessed monthly by a diary medication card and serologic tests were evaluated before and two years after the start of treatment. Adverse effects and dropout rates were also investigated. RESULTS: All nasal and non-nasal symptoms and quality of life were significantly improved after two years of treatment. Furthermore, the total medication score decreased significantly and the serologic tests showed a significant change two years after the start of SLIT. Although minor adverse effects were reported, no systemic reactions were observed. The dropout rate was 40%. CONCLUSION: SLIT is an efficient and safe therapeutic tool for a period of two years in Asian children with allergic rhinitis to house-dust mites.

A Case of Frontal Mococele Treated with Transblepharoplasty Approach Combined with Endoscopic Approach

In recent years, endoscopic sinus marsupialization has become the treatment of choice for the treatment of paranasal sinus mucoceles due to its noninvasiveness and successful outcome. However, mucoceles located at the lateral portion of the frontal sinus and protruding into the orbit with erosion of the frontal sinus floor arestill difficult to address with standard endoscopic sinus surgery techniques. Here, we report a case of a mucocele located atthe lateral side of the frontal sinus and successfully marsupialized with a transblepharoplasty approach combined with an endoscopic approach.

Sinocutaneous Fistula Induced by Long-Standing, Retained, Non-Absorbable Nasal Packing in The Paranasal Sinus

Orbital complications after endoscopic sinus surgery (ESS), such as optic nerve or medial rectus injuries, are well known, but isolated complete oculomotor nerve palsy has never been reported. In this case, a 31-year-old male was transferred to our hospital after ESS. Physical examination showed complete left oculomotor nerve palsy, with a bony defect on the sellar floor, which had not fully recovered after more than 1 year. We hypothesized that blunt trauma could be the main cause of the oculomotor palsy. Surgeons performing ESS must keep in mind the possibility of oculomotor palsy due to blunt trauma, especially when operating around the sphenoid and posterior ethmoid sinus.

Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors/Akt/NF-kappaB Pathways in Nasal Polyp-Derived Fibroblasts

PURPOSE: Interleukin 6 (IL-6) and IL-8 participate in the pathogenesis of chronic rhinosinusitis with nasal polyps, and their levels are increased by prostaglandin E2 (PGE2) in different cell types. The purposes of this study were to determine whether PGE2 has any effect on the increase in the levels of IL-6 and IL-8 in nasal polyp-derived fibroblasts (NPDFs) and subsequently investigate the possible mechanism of this effect. METHODS: Different concentrations of PGE2 were used to stimulate NPDFs at different time intervals. NPDFs were treated with agonists and antagonists of E prostanoid (EP) receptors. To determine the signaling pathway for the expression of PGE2-induced IL-6 and IL-8, PGE2 was treated with Akt and NF-kappaB inhibitors in NPDFs. Reverse transcription-polymerase chain reaction for IL-6 and IL-8 mRNAs was performed. IL-6 and IL-8 levels were measured byenzyme-linked immunosorbent assay (ELISA). The activation of Akt and NF-kappaB was evaluated by western blot analysis. RESULTS: PGE2 significantly increased the mRNA and protein expression levels of IL-6 and IL-8 in NPDFs. The EP2 and EP4 agonists and antagonists induced and inhibited IL-6 expression. However, the EP4 agonist and antagonist were only observed to induce and inhibit IL-8 expression level. The Akt and NF-kappaB inhibitors significantly blocked PGE2-induced expression of IL-6 and IL-8. CONCLUSIONS: PGE2 increases IL-6 expression via EP2 and EP4 receptors, and IL-8 expression via the EP4 receptor in NPDFs. It also activates the Akt and NF-kappaB signal pathways for the production of IL-6 and IL-8 in NPDFs. These results suggest that signaling pathway for IL-6 and IL-8 expression induced by PGE2 might be a useful therapeutic target for the treatment of nasal polyposis.

Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-kappaB Pathways in Nasal Fibroblasts

PURPOSE: Based on the close relationship between histamine and interleukin 6 (IL-6), we hypothesized that histamine may regulate the production of cytokines, such as IL-6, during allergic inflammation. Here, we examined the role of histamine in IL-6 production and histamine receptor activity in nasal fibroblasts, along with the mechanisms underlying these effects. METHODS: Experiments were performed using nasal fibroblasts from 8 normal patients. RT-PCR was used to identify the major histamine receptors expressed in nasal fibroblasts. Fibroblasts were then treated with histamine with or without histamine-receptor antagonists, and monitored for IL-6 production using an ELISA. Four potential downstream signaling molecules, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-kappaB, were evaluated by Western blot, and a luciferase reporter assay. RESULTS: Elevated expression was seen for all histamine receptors, with IL-6 protein levels increasing significantly following histamine stimulation. Among the histamine-receptor specific antagonists, only the H1R antagonist significantly decreased IL-6 production in histamine-stimulated nasal fibroblasts. Histamine increased the expression level of phosphorylated p38 (pp38), pERK, and pJNK, as well as NF-kappaB induction. The H1R antagonist actively suppressed pp38 and NF-kappaB expression in histamine-induced nasal fibroblasts, but not pERK and pJNK. The p38 inhibitor strongly attenuated IL-6 production in histamine-stimulated nasal fibroblasts. CONCLUSIONS: The data presented here suggest that antihistamines may be involved in the regulation of cytokines, such as IL-6, due to the role of histamine as an inflammatory mediator in nasal fibroblasts.

Role of Caffeic Acid on Collagen Production in Nasal Polyp-Derived Fibroblasts

OBJECTIVES: Caffeic acids are known to have anti-oxidant, anti-inflammatory, immunomodulatory, and tissue reparative effects. The purposes of this study were to determine the effect of caffeic acid on transforming growth factor (TGF) beta1-induced myofibroblast differentiation and collagen production, and to determine whether caffeic acid is involved in the antioxidant effect in nasal polyp-derived fibroblasts (NPDFs). METHODS: NPDFs were pretreated with caffeic acid (1-10 microM) for 2 hours and stimulated with TGF-beta1 (5 ng/mL) for 24 hours. The expression of alpha-smooth muscle actin (SMA), collagen types I and III, and Nox4 mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of alpha-SMA protein was determined by actin ned by immunofluorescence microscopy. The amount of total soluble collagen production was analyzed by the Sircol collagen dye-binding assay. The reactive oxygen species (ROS) generated by NPDFs were determined using 2',7'-dichlorfluorescein-diacetate. siNox4 was used to determine the effect of Nox4. RESULTS: The expression of alpha-SMA and production of collagen were significantly increased following TGF-beta1 treatment. In contrast, the level of expression of alpha-SMA and the level of production of collagen were decreased by pretreatment with caffeic acid. The activation of Nox4 and the subsequent production of ROS were also reduced by pretreatment with caffeic acid. The expression of alpha-SMA was prevented by inhibition of ROS generation with siNox4. CONCLUSION: Caffeic acid may inhibit TGF-beta1-induced differentiation of fibroblasts into myofibroblasts and collagen production by regulating ROS.