Treatment Of Chronic Airway Diseases Research Articles

The clinical efficacy of type 2 monoclonal antibodies in eosinophil-associated chronic airway diseases: a meta-analysis.

Anti-type 2 inflammation therapy has been proposed as a treatment strategy for eosinophil-associated chronic airway disorders that could reduce exacerbations and improve lung function. We performed a meta-analysis of randomized controlled trials to assess the effectiveness of type 2 monoclonal antibodies (anti-T2s) for eosinophil-associated chronic airway disorders. PubMed, Embase, Web of Science, and Cochrane Library were searched from their inception to 21 August 2022. Randomized clinical trials evaluating the effectiveness of anti-T2s versus placebo in the treatment of chronic airway diseases were selected. The outcomes were exacerbation rate and change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) from baseline. The Cochrane Risk of Bias Assessment Tool 1.0 was used to evaluate the risk of bias, and the random-effects or fixed-effect model were used to pool the data. Thirty-eight articles concerning forty-one randomized clinical trials with 17,115 patients were included. Compared with placebo, anti-T2s therapy yielded a significant reduction in exacerbation rate in COPD and asthma (Rate Ratio (RR)=0.89, 95%CI, 0.83-0.95, I2 = 29.4%; RR= 0.59, 95%CI, 0.52-0.68, I2 = 83.9%, respectively) and improvement in FEV1 in asthma (Standard Mean Difference (SMD)=0.09, 95%CI, 0.08-0.11, I2 = 42.6%). Anti-T2s therapy had no effect on FEV1 improvement in COPD (SMD=0.05, 95%CI, -0.01-0.10, I2 = 69.8%). Despite inconsistent findings across trials, anti-T2s had a positive overall impact on patients' exacerbation rate in asthma and COPD and FEV1 in asthma. Anti-T2s may be effective in treating chronic airway illnesses related to eosinophils. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022362280.

Interventional treatment of chronic airway diseases: new era is coming

经由呼吸内镜介导的介入治疗方法，为支气管哮喘、慢性阻塞性肺疾病等慢性气道疾病开拓了一类全新的治疗手段，其疗效获得临床验证与专家认可。而各类介入治疗方法的规范应用与推广，不同患者治疗方案选择的精准化与个体化是目前临床急需解决的问题。相信通过呼吸介入方法与其他药物、非药物治疗方法的有机结合，将为慢性气道疾病患者带来福音。.

A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future.

Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) – understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis.

Upregulation of miR-92a contributes to blocking goblet cell metaplasia by targeting MUC5AC in asthma

As a chronic airway disease, asthma has two characteristics, tissue remodeling and airway inflammation. This research focused on miR-92a to explore how it works in asthma. We revealed that the expressions of miR-92a were decreased in both serum and lung tissues from ovalbumin-induced asthma mouse. Bioinformatics analysis, quantitative polymerase chain reaction (qPCR) and dual luciferase assay revealed that miR-92a targets MUC5AC, which was linked to mucus hypersecretion in the pulmonary tracts. By injecting miR-92a-mimics into the trachea, both the airway hyper-reactivity and airway inflammation can be alleviated in an asthma mouse model which is induced by ovalbumin. Moreover, the goblet cell phenotype of asthmatic mice is significantly reduced by the action of miR-92a. Furthermore, miR-92a blocked interleukin (IL)-13-induced MUC5AC luciferase activity in 16HBE. Together, upregulation of miR-92a expression in asthmatic mice plays a role in blocking goblet cell metaplasia by targeting MUC5AC, and thus in the treatment of chronic airway diseases, miR-92a can prevent epithelial remodeling, which is a reasonable method.

Conventional and Nanotechnology Based Approaches to Combat Chronic Obstructive Pulmonary Disease: Implications for Chronic Airway Diseases.

Chronic obstructive pulmonary disease (COPD) is the most prevalent obstructive lung disease worldwide characterized by decline in lung function. It is associated with airway obstruction, oxidative stress, chronic inflammation, mucus hypersecretion, and enhanced autophagy and cellular senescence. Cigarette smoke being the major risk factor, other secondary risk factors such as the exposure to air pollutants, occupational exposure to gases and fumes in developing countries, also contribute to the pathogenesis of COPD. Conventional therapeutic strategies of COPD are based on anti-oxidant and anti-inflammatory drugs. However, traditional anti-oxidant pharmacological therapies are commonly used to alleviate the impact of COPD as they have many associated repercussions such as low diffusion rate and inappropriate drug pharmacokinetics. Recent advances in nanotechnology and stem cell research have shed new light on the current treatment of chronic airway disease. This review is focused on some of the anti-oxidant therapies currently used in the treatment and management of COPD with more emphasis on the recent advances in nanotechnology-based therapeutics including stem cell and gene therapy approaches for the treatment of chronic airway disease such as COPD and asthma.

Optimizing inhalation technique using web-based videos in obstructive lung diseases

BackgroundInhaled agents are widely used in the treatment of chronic airway diseases. Correct technique is required to ensure appropriate drug deposition, but poor technique is common. This study investigated whether inhalation technique could be improved by patient training using short videos from the German Airway League. MethodsOutpatients from a university hospital respiratory clinic who had incorrect inhalation technique were asked to demonstrate this again immediately after viewing the training videos, and after 4–8 weeks' follow-up. Inhalation technique was rated by a study nurse using specific checklists. ResultsOne hundred and twelve patients with obstructive lung disease treated with inhaled bronchodilators or corticosteroids were included. More than half (51.8%) had at least one mistake in inhalation technique at baseline. Of these, most (88%) understood the training videos, 76% demonstrated correct device use immediately after training, and 72% were still able to demonstrate correct inhalation technique at follow-up (p = 0.0008 for trend). In addition, the number of mistakes decreased significantly after video training (by 1.82 [95% confidence interval 1.39–2.25]; p < 0.0001 vs. baseline). ConclusionsGerman Airway League inhalation technique training videos were easy to understand and effectively improved inhalation technique in patients with airway diseases.

Clinical Studies of Statins in Asthma and COPD.

Immunomodulatory effects of statins in vitro and in experimental models of asthma and COPD could potentially be relevant to the treatment of chronic airway diseases. This article provides an overview of the evidence from the key clinical studies on the effects of statins on clinical outcomes and inflammatory biomarkers in asthma and COPD. Future directions for clinical studies of statins in asthma and COPD are discussed. A small number of randomized controlled trials (RCTs) in adults with mild to moderate asthma suggest that short-term statin treatment does not improve lung function or symptom control, except for a possible improvement in quality of life and symptoms in smokers with asthma. Several observation studies report that statin use in asthma is associated with a reduced risk of asthma-related emergency department visits, oral corticosteroid dispensing or hospital admissions. Statins treatment in asthma may have modest local anti-inflammatory effects in the airways. There is a need for a large RCT examining the effects of statins on reducing exacerbations, particularly in severe asthma. In COPD, observational studies suggest that statin use is associated with reduced morbidity and/or mortality, whereas a large RCT concluded that simvastatin did not reduce exacerbations in patients with COPD that had no cardiovascular indication for statin treatment. It is possible that a subgroup of COPD patients with cardiovascular indications for statins and/or systemic inflammation may obtain clinical benefit from statin treatment. Understanding the immunomodulatory effects of statins in asthma and COPD may lead to the development of novel targeted interventions.

Effect of Bakumondo-to on cytochrome P450 activities in rat liver microsomes

Bakumondo-to is a traditional herbal medicine. It has been widely used for the treatment of chronic airway diseases. Recently, it was reported that several herbal medicines affected cytochrome P450 (CYP). However, there is little information about the effects of Bakumondo-to on CYP activities. In this study, we evaluated the effects of Bakumondo-to on CYP activities in rat liver microsomes. Rats were orally treated twice a day with Bakumondo-to at doses of 2.0g/kg body weight/day for 4days. CYP activities were determined in liver microsomes isolated from treated rats. CYP1A2, CYP2C, and CYP3A activities were measured using their specific substrates [7-methoxyresorufin, 7-methoxy-4-(trifluoromethyl)-coumarin, and 7-benzyloxyquinoline, respectively]. Bakumondo-to decreased CYP1A2 activity by 42.5±7.8%, increased CYP2C activity by 158.0±29.6%, and decreased CYP3A activity to 81.5±7.8% of the control level. Activities were expressed as percentages of the control.Bakumondo-to induced CYP2C activity and decreased CYP1A2 activity; it may cause drug-herbal interactions. It is suggested that combinations of Bakumondo-to and drugs that are metabolized by CYP1A2 and CYP2C should be carefully used in clinical settings.

The Editor takes a closer look at some of this month's articles

Clinical & Experimental AllergyVolume 44, Issue 10 p. 1205-1205 Editor's ChoiceFree Access The Editor takes a closer look at some of this month's articles First published: 22 September 2014 https://doi.org/10.1111/cea.12396AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Adherence: the key to success in treatment of chronic airway disease The main cause for treatment failure in asthma and rhinitis is suboptimal adherence to inhaled corticosteroids 1. The need to take these medications regularly to obtain maximum effect even when asymptomatic is a particular problem for seasonal allergic rhinitis (hay fever) where symptoms are often episodic. The reasons for suboptimal adherence are complex, but the key to successful management is good education both in the rationale for treatment and inhaler technique. Telemedicine has found its way into most corners of health care, but there is relatively little published on its potential role in allergic disease. Therefore, Pizzulli and colleagues (pp. 1246–1254) have undertaken an original study looking at the value of telemonitoring on adherence to topical corticosteroids in children with severe hay fever. They demonstrated an improvement in both adherence and disease knowledge, and the informatics platform was positively received by the study participants. No improvement was seen in disease control, but pollen counts were low during the study period, and the study may also have been relatively underpowered for treatment efficacy endpoints. Antonio Pizzulli Estimated frequency (normal approximation) of daily consumption of mometasone in 63 children with hay fever, by allocation to AllergyMonitor or to usual care. [see figure 3 in A. Pizzulli et al. (pp. 1246–1254)]. Asthma and viral exacerbations: basophils get in on the act It is well established that upper respiratory tract viral infections particularly with rhinovirus are associated with the majority of exacerbations of asthma. The mechanisms involved have been studied in detail although the precise pathways involved remain elusive. Basophils have been relatively ignored as a player in the rhinovirus–asthma axis. However, the role of basophils may need to be reconsidered following the paper by Agrawal et al. (pp. 1266–1273), in which they have made the original observation that basophils become activated after rhinovirus infection with the maximal effect seen as late as 3 weeks after infection. A deterioration in asthma control is often prolonged after rhinovirus infection including an increase in airways hyperresponsiveness that can last for several weeks. It is intriguing to think that basophils, often the bridesmaid to mast cells, may be responsible. Rachana Agrawal Basophile Granulocyte. [Photo credit: User CS99 at German Wikipedia; Wikimedia Commons]. Patterns of inflammation in asthma: does it depend on your age? Asthma can start at any age, and there is an increasing interest in whether asthma that develops in older people is in any way different to asthma that develops in childhood or early adulthood. Evidence that this might be the case comes from a paper by Brandenberger and colleagues (pp. 1282–1292), who investigated the nature of the inflammatory response to house dust mite challenge in young and old mice. Interestingly, they found that whereas there was more airway hyperresponsiveness in young mice, there was a greater inflammatory response in the older mice which included a Th17-neutrophilic component. One might speculate that this may be due to the development of a different microbiota in the airways of the older mice. As steroid responsiveness is closely linked to Th2 responses in asthma, this raises the possibility that older asthmatics may be more resistant to inhaled corticosteroids. This observation now needs to be translated into clinical asthma. Christina Brandenberger Representative light photomicrographs of lung tissue sections stained with haematoxylin and eosin, showing a peribronchiolar and perivascular mixed inflammatory cell infiltration in HDM mice (arrows). b: bronchiolar airspace, a: alveoli, v: blood vessel, scale bar: 50 lm. [see figure 1b in Brandenberger et al. (pp. 1282–1292)]. Reference 1Bourdin A, Halimi L, Vachier I et al. Adherence in severe asthma. Clin Exp Allergy 2012; 42: 1566– 74. Caption to cover illustration: Patient taking a mannitol bronchial challenge test for diagnosing asthma (Image courtesy of Dr Brian Lipworth, Scottish Centre for Respiratory Research, Univ of Dundee Ninewells Hospital and Medical School). This logo highlights the Editor's Choice articles on the cover and the first page of each of the articles. Volume44, Issue10October 2014Pages 1205-1205 ReferencesRelatedInformation

Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases.

Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction, and mucus secretion. It has an inflammatory effect by inducing attraction, survival and cytokine release from inflammatory cells. Muscarinic receptors throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3 receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were approved for the treatment of chronic obstructive pulmonary disease (COPD) in Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than for M2 receptors, and dissociate more slowly from the M3 receptors than they do from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of neutrophil chemotactic activity and migration of alveolar neutrophils, decrease of several cytokines in the bronchoalveolar lavage (BAL) including interleukin (IL)-6, tumor necrosis factor (TNF)-α and leukotriene (LT)B4] and antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the clinic, LAMAs showed a significant improvement of forced expiratory volume in 1 second (FEV1), quality of life, dyspnea and reduced the number of exacerbations in COPD and more recently in asthma. This review will focus on the three LAMAs approved in Europe in the treatment of chronic airway diseases.

QUALITY CONTROL IMPROVED THE DIAGNOSIS AND TREATMENT FOR ASTHMA AND COPD BASED ON THE GUIDELINES OF GINA AND GOLD IN SHANGHAI

PURPOSE: In order improve the qualities of diagnosis and treatment for respiratory diseases, Shanghai Clinical Quality Control Center for Respiratory Diseases (SQCRD) was set up in 2004. SQCRD was enpowered to make guideline, held training course and inspect the clinical work for respiratory diseases in 58 hospitals in Shanghai, and serves as a platform to improve the qualities for diagnosis and treatment of chronic airway diseases. To improve qualities of diagnosis and treatment for asthma and COPD based on the guidelines of Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Diseases (GOLD) in Shanghai.

Effects of baicalin and wogonin on mucin release from cultured airway epithelial cells

Scutellaria baicalensis Georgi has been used for the treatment of diverse chronic inflammatory diseases including respiratory disease in oriental medicine and its major components - baicalin, baicalein and wogonin - were reported to have various biological effects. This study investigated whether baicalin, baicalein and wogonin affect basal and ATP-induced mucin release from cultured airway epithelial cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled using (3)H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on (3)H-mucin release. The results were as follows: (1) Baicalein did not affect both basal and ATP-induced mucin release significantly. (2) Baicalin and wogonin increased basal mucin release at the highest concentrations (10(-3) m). (3) However, baicalin and wogonin significantly inhibited ATP-induced mucin release. It is concluded that baicalin and wogonin can slightly increase basal mucin release whereas they can inhibit ATP-induced mucin release, by directly acting on airway mucin-secreting cells. It is suggested that baicalin and wogonin be further investigated for the possible use as mucoregulators during the treatment of chronic airway diseases.

The pharmacologic approach to airway clearance: Mucoactive agents

The term "mucoactive agent" refers to any medication used to improve the clearance of airway secretions. It is not synonymous with the word "mucolytic" as this strictly means a drug that decreases the viscosity of secretions. In many cases, decreased viscosity will adversely affect cough transport. For this reason many of the older mucolytic agents such as acetylcysteine are not effective for the therapy of lung disease and their use is not recommended. I review here the many classes of mucoactive agents and identify a number of medications with great promise for the treatment of chronic airway disease.

The use of computed tomography to assess asthma severity

Chronic inflammation in asthma can also lead to airway remodeling, which contributes to airway narrowing. It may be possible to assess and quantify the extent of airway remodeling in vivo using computed tomography. This review examines recent developments in the evaluation of asthma severity using computed tomography, and the effect of treatment assessed by computed tomography. Asthma patients have thicker airways on computed tomography scans than do healthy control individuals, and the degree of thickening is related to the severity of disease, airflow obstruction, and airway reactivity. Recent studies have indicated that patients with severe asthma and irreversible airflow obstruction had longer disease duration, a greater inflammatory process and more airway abnormalities, assessed by high-resolution computed tomography, suggestive of airway remodeling. Other studies have shown that high-resolution computed tomography lung density correlates with airflow limitation and lung volume (but not with lung transfer factor), and also correlates with patient age and severity of asthma. More recently, two publications demonstrated the effect of treatment on airway wall thickness and lung density assessed by computed tomography in patients with asthma. High-resolution computed tomography is one of the most useful tools for imaging airways and parenchyma. Computed tomography scanning may be useful in determining which patients might benefit from more or less treatment. With additional advances in technology, it is likely that quantitative assessment by computed tomography will ultimately be a valuable tool for the study and treatment of chronic airway diseases.

Effects of Ursolic Acid, Betulin and Sulfur-Containing Compounds on Mucin Release from Airway Goblet Cells

In this study, we investigated whether ursolic acid, betulin and 2 kinds of sulfur-containing compounds--NAC and MESNA--affect mucin release from airway goblet cells and compared the possible activities of these agents with the inhibitory action on mucin release by PLL and the stimulatory action by ATP. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled using 3H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on 3H-mucin release. The results were as follows: ursolic acid, betulin, MESNA and NAC increased mucin release (40-50 % above control) at the highest concentrations (10(-5) M-10(-3) M). We conclude that ursolic acid and betulin can stimulate mucin release by directly acting on airway mucin-secreting cells and suggest that these agents be further investigated for the possible use as mucoregulators in the treatment of chronic airway diseases.

Effects of betaine, coumarin and flavonoids on mucin release from cultured hamster tracheal surface epithelial cells.

Betaine, coumarin, hesperidin and kaempferol are the components derived from Lycium chinense, Angelicae decursiva, Poncirus trifoliata and Polygonatum odoratum, respectively. These plants have been used for the treatment of respiratory diseases in oriental medicine and their respective components were reported to have various biological effects. In this study, we investigated whether these natural products affect mucin release from cultured hamster tracheal surface epithelial cells and compared the possible activities of these agents with the inhibitory action on mucin release by poly-L-lysine and the stimulatory action by adenosine triphosphate. Confluent primary hamster tracheal surface epithelial cells were metabolically radiolabeled using (3)H-glucosamine for 24 h and treated for 30 min in the presence of varying concentrations of each agent to assess the effects on (3)H-mucin release. The results were as follows: (i) Coumarin and kaempferol did not affect mucin release significantly; (ii) Betaine and hesperidin increased mucin release at the highest concentration; (iii) Poly-L-lysine inhibited and adenosine triphosphate increased mucin release. We conclude that betaine and hesperidin can increase mucin release by direct acting on airway mucin-secreting cells and suggest these agents be further studied for the possible use as mild expectorants during the treatment of chronic airway diseases.

Effects of baicalein, berberine, curcumin and hesperidin on mucin release from airway goblet cells.

Baicalein, berberine, curcumin and hesperidin are the major components derived from Scutellaria baicalensis, Coptis japonica, Curcuma longa and Poncirus trifoliata, respectively. These plants have been used for the treatment of diverse chronic inflammatory diseases including respiratory disease in oriental medicine and their respective major components were reported to have various biological effects including anti-inflammatory activity. In the present study, we investigated whether these four natural products affect mucin release from airway goblet cells and compared the possible activities of these agents with the inhibitory action on mucin release by PLL and the stimulatory action by ATP. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled using 3H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on 3H-mucin release. The results were as follows: (i) baicalein did not affect mucin release significantly; (ii) berberine, curcumin and hesperidin increased mucin release at the highest concentration (10 - 4 M); (iii) PLL inhibited and ATP increased mucin release. We conclude that berberine, curcumin and hesperidin can increase mucin release by directly acting on airway mucin-secreting cells and suggest that these agents be further studied for possible use as mild expectorants during the treatment of chronic airway diseases. Abbreviations. PLL:poly- L-lysine ATP:adenosine triphosphate HTSE:hamster tracheal surface epithelial DMSO:dimethylsulfoxide IL-12:interleukin-12 PBS:phosphate-buffered saline

Glucocorticoid-like and Glucocorticoid-unlike Regulation of Gene Expression by Bakumondo-to(Mai-Men-Dong-Tang) in Airway Epithelial Cells.

Since many patients are still dying from asthma and COPD, developing more effective drugs with little side-effect which can be taken for a long time, is very important. Clinical usage of herbal medicines for chronic airway diseases has been increasing. Bakumondo-to is a useful herbal medicine with little side-effect for the treatment of chronic airway diseases. There are some similarities of pharmacological profile of herbal medicines to those of glucocorticoids. Although the regulation of gene expression by glucocorticoids has been clarified, that of Bakumondo-to is not well known. Elucidation of the mechanism of Bakumondo-to will be helpful in establishing a more effective treatment of chronic airway diseases. This article focuses on the regulation of gene expression by Bakumondo-to in airway epithelial cells, and describes the increase in mRNA expression for β-adrenergic receptors by Bakumondo-to and in glucocorticoid-sensitive promoter activity. We also discuss the mechanisms of the regulatory action of Bakumondo-to.

Effect of Roxithromycin on IL-8 Synthesis and Proliferation of Nasal Polyp Fibroblasts

Although several studies have demonstrated that low-dose, long-term 14-member macrolides (erythromycin (EM), roxithromycin (RXM), clarithromycin (CAM)) are effective in the treatment of chronic airway diseases like chronic sinusitis and diffuse panbronchiolitis (DPB), the mechanism of action of these drugs is not yet clear. Both these airway diseases are associated with an increase in the proliferation of fibroblasts. Moreover, fibroblasts are also an important source of proinflammatory cytokines such as interleukin-8 (IL-8), that play an important role in the pathogenesis of nasal polyps. Therefore, using primary fibroblast lines derived from nasal polyps, we investigated the effect of RXM on the synthesis of IL-8 and proliferation of nasal polyp fibroblasts (NPF). These fibroblasts were either treated with lipopolysaccharide (LPS) and RXM for 24 h, or pre-incubated with RXM for 24 h and then treated with LPS and RXM for 24 h. The level of IL-8 mRNA in NPF was analysed by reverse transcriptase-polymerase chain (RT-PCR) and the level of IL-8 in culture supernatants was measured by ELISA. Next, the proliferative capacity of NPF after treatment with RXM was analysed by cell counting and 3 H-thymidine uptake. RXM had no effect on LPS-induced IL-8 synthesis by NPF. On the other hand, RXM suppressed the proliferation of NPF in a dose-dependent manner. These findings suggest that, although RXM cannot directly inhibit the synthesis of IL-8, it probably reduces IL-8 production by inhibiting the proliferation of NPF.