The effects of nodakenin on airway inflammation,hyper-responsiveness and remodeling in a murine model of allergic asthma

Context: Nodakenin is a major coumarin glucoside in the root of Peucedanum decursivum Maxim, a commonly used traditional Chinese medicine for the treatment of asthma and chronic bronchitis for thousands of years.

Objective: In this work, the anti-asthma potential of nodakenin was studied by investigation of its effect to suppress airway inflammation, hyper-responsiveness and remodeling in a murine model of chronic asthma.

Materials and methods: BALB/c mice sensitized to ovalbumin (OVA) were challenged with aerosolized OVA for 8 weeks, orally administered with nodakenin at doses of 5, 10 and 20?mg/kg before each OVA challenge.

Results: Compared with the model group, nodakenin treatment markedly inhibited airway inflammation, hyper-responsiveness and remodeling, showing improvement in subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia, and decreased levels of interleukin (IL)-4, IL-5, IL-13 and matrix metalloproteinase-2/-9 in bronchoalveolar lavage fluid, and the level of OVA-specific IgE in serum. In addition, the NF-κB DNA-binding activity in lung tissues was also reduced by nodakenin treatment.

Conclusions: These data indicated that nodakenin might mitigate the development of chronic experimental allergic asthma.     

The involvement of matrix metalloproteinase-9 in airway inflammation of patients with acute asthma

BACKGROUND: Bronchial asthma is an inflammatory disease of the airway characterized by airway remodelling, and is due at least in part to an excess of extracellular matrix (ECM) deposition in the airway wall, which leads to subepithelial collagen deposition. Matrix metalloproteinase-9 (MMP-9) is the major proteolytic enzyme that induces bronchial remodelling in asthma. MMP-9 is also important in the migration of inflammatory cells through basement membrane components. OBJECTIVES: We evaluated whether airway inflammatory cells correlated with levels of MMP-9 in acute asthma and we examined the time course of sputum levels of MMP-9 activity in patients with spontaneous asthma exacerbation. METHODS: We performed zymographic analysis and checked levels of MMP-9 by means of enzyme immunoassay. MMP-9 levels were also evaluated during a spontaneous attack of asthma. RESULTS: Pro-MMP-9 activities and concentrations of MMP-9 in asthmatic patients significantly exceeded those of control subjects (P < 0.01). The activities of pro-MMP-9 were significantly higher in acute asthmatic patients than in stable asthmatic patients (P < 0.01). The elevated MMP-9 activities significantly decreased after 7 and 28 days of therapy. In acute asthmatic patients, the levels of sputum MMP-9 significantly correlated with the total macrophage + neutrophil + eosinophil cell numbers. CONCLUSION: These data suggest that airway inflammation after asthma exacerbation correlates with the overproduction of MMP-9, which then leads to airway remodelling.     

DC-derived TSLP promotes Th2 polarization in LPS-primed allergic airway inflammation

Thymic stromal lymphopoietin (TSLP) plays important roles in the pathogenesis of allergic diseases. Whether and how TSLP is involved in the initial priming of T helper type‐2 (Th2) differentiation against harmless antigen remains unclear. Using an intranasal sensitization protocol with OVA and LPS, we showed that TSLP signaling is required for low‐dose LPS‐induced Th2 inflammation, but not for high‐dose LPS‐induced Th1 immunity. We further demonstrated that low‐dose LPS‐activated bone marrow‐derived dendritic cells expressed relatively high Tslp but low Il12a, and were able to prime naïve DO11.10 T cells to differentiate into Th2 cells in a TSLP‐dependent manner. After transfer into wild‐type recipient mice, the low‐dose LPS‐activated OVA‐loaded dendritic cells (DCs) induced airway eosinophilia, but primed neutrophil‐dominated airway inflammation when TSLP‐deficient DCs were used. These studies demonstrate that TSLP released by DCs in response to a low concentration of LPS plays a role in priming Th2 differentiation and thus may serve as a polarizing third signal, in addition to antigen/MHC class II and co‐stimulatory factors, from antigen‐presenting DCs to direct effector T‐cell differentiation.     

Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma

Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and in contact with mucosal surfaces generate superoxide anion (O2*-). In the presence of iron, O2*- may be converted to more reactive oxygen radicals, such as to H2O2 and/or *OH, which may augment antigen-induced airway inflammation. The aim of the study was to examine the impact of lactoferrin (LF), an iron-binding protein, on ragweed (Ambrosia artemisiifolia) pollen extract (RWE)-induced cellular oxidative stress levels in cultured bronchial epithelial cells and accumulation of inflammatory and mucin-producing cells in airways in a mouse model of allergic airway inflammation. Results show that LF lowered RWE-induced increase in cellular reactive oxygen species (ROS) levels in bronchial epithelial cells. Most importantly, LF significantly decreased accumulation of eosinophils into airways and subepithelium of intranasally challenged, sensitized mice. LF also prevented development of mucin-producing cells. Amb a 1, the major allergenic ragweed pollen antigen lacking NADPH oxidase activity, induced low-grade airway inflammation. When administered along with glucose oxidase (G-ox), a superoxide-generating enzyme, Amb a 1 induced robust airway inflammation, which was significantly lowered by LF. Surprisingly, LF decreased also inflammation caused by Amb a 1 alone. Iron-saturated hololactoferrin had only a marginal effect on RWE-induced cellular ROS levels and RWE- or Amb a 1 plus G-ox-induced inflammation. We postulate that free iron in the airways chemically reduces O2*- to more reactive species which augment antigen-induced inflammation in a mouse model of asthma. Our results suggest the utility of LF in human allergic inflammatory disorders.     

薯蓣皂苷减轻卵清蛋白诱导的过敏性哮喘小鼠的气道炎症

目的探讨薯蓣皂苷对卵清蛋白(ovalbumin,OVA)诱导的过敏性哮喘小鼠中过敏性支气管炎的影响及机制。方法24只小鼠随机分为对照组、OVA组、OVA+30 mg/kg薯蓣皂苷组和OVA+60 mg/kg薯蓣皂苷组,每组纳入6只小鼠。全自动生化仪检测各组支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中嗜中性粒细胞、嗜酸性粒细胞和单核细胞的数量;ELISA法检测BALF中促炎因子IL-1β、IL-4、IL-5和TNF-α的含量;PAS染色法观察肺组织黏液分泌情况并对黏液分泌程度进行评分;免疫组化法观察肺组织p-NF-κB p65的表达和分布情况;Western blotting法检测肺组织中p-IκB和NF-κB p65的蛋白表达水平。结果薯蓣皂苷可降低过敏性哮喘小鼠BALF中炎性细胞数量,同时降低BALF中促炎因子IL-1β、IL-4、IL-5和TNF-α的水平以及肺部黏液的分泌和NF-κB的活化水平。结论薯蓣皂苷能减轻过敏性哮喘小鼠的气道炎症,且其抗炎作用与抑制NF-κB活化有关。     

Lipocalin2 protects against airway inflammation and hyperresponsiveness in a murine model of allergic airway disease

Background Allergen‐induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways. Objective The aim of this study was to identify possible mediators of airway inflammation (AI) in a model of allergic AI via microarray comparisons and to analyse one of these mediators, Lipocalin2 (Lcn2), for its role in a murine model of allergic airway disease. Methods Gene microarrays were used to identify genes with at least a twofold increase in gene expression in the lungs of two separate mouse strains with high and low allergic susceptibility, respectively. Validation of mRNA data was obtained by Western blotting, followed by functional analysis of one of the identified genes, Lcn2, in mice with targeted disruption of specific gene expression. Epithelial cell cultures were undertaken to define induction requirements and possible mechanistic basis of the results observed in the Lcn2 knock‐out mice. Results Lcn2 was up‐regulated upon allergen sensitization and airway challenges in lung tissues of both mouse strains and retraced on the protein level in bronchoalveolar lavage fluids. Functional relevance was assessed in mice genetically deficient for Lcn2, which showed enhanced airway resistance and increased AI associated with decreased apoptosis of lung inflammatory cells, compared with wild‐type controls. Similarly, application of Lcn2‐blocking antibodies before airway challenges resulted in increased inflammation and reduced apoptosis. Conclusion These data indicate a protective role for Lcn2 in allergic airway disease, suggesting a pro‐apoptotic effect as the underlying mechanism. Cite this as: A. M. Dittrich, M. Krokowski, H.‐A. Meyer, D. Quarcoo, A. Avagyan, B. Ahrens, S. M. Kube, M. Witzenrath, C. Loddenkemper, J. B. Cowland and E. Hamelmann, Clinical & Experimental Allergy, 2010 (40) 1689–1700.     

The involvement of type 1a angiotensin II receptors in the regulation of airway inflammation in a murine model of allergic asthma

BACKGROUND: There has been increasing evidence suggesting the involvement of angiotensin II (Ang II) and type 1 Ang II receptors (AT1) in the pathogenesis of bronchial asthma. However, whether such an involvement would promote or suppress the pathophysiology of asthma is controversial. OBJECTIVE: The aim of this study was to investigate the role of AT1 in the development of allergic airway inflammation. METHODS: Agtr1a+/+ [wild-type C57BL/6 mice (WT)] and Agtr1a-/- mice [AT1a knockout mice (AT1aKO)] with a genetic background of C57BL/6 were systemically sensitized to ovalbumin (OVA), followed by OVA inhalation. OVA-specific IgE in serum obtained just before the inhalation was measured. Bronchoalveolar lavage (BAL) fluid and lung tissues were obtained at various time-points. Cell numbers and differentiation, and cytokine contents in BAL fluids were determined. Peribronchial accumulation of eosinophils and mucus inclusions in the bronchial epithelium were evaluated in lung tissues stained histochemically. Cell numbers and differentiation in BAL fluids of the mice were also determined after lipopolysaccharide (LPS) inhalation. RESULTS: The levels of OVA-specific IgE in AT1aKO were significantly higher than those in WT. The numbers of total cell, eosinophils and lymphocytes in BAL fluids 7 days after OVA inhalation in AT1aKO were significantly higher than those in WT. Airway inflammation in bronchial tissues in terms of eosinophil accumulation and mucus hypersecretion in AT1aKO was also stronger than in WT. The contents of IL-4, IL-5 and IL-13, but not IFN-gamma, in BAL fluids of AT1aKO were significantly higher than those of WT. In contrast, neutrophil accumulation in BAL fluids after LPS inhalation was significantly higher in WT than in AT1aKO. CONCLUSION: AT1a might be involved in the negative regulation of the development of allergic airway inflammation through polarizing the T-helper (Th) balance towards Th1 predominance. Therefore, it would be of clinical importance to investigate the effects of long-term administration of AT1 blockers on the Th1/Th2 balance in hypertensive patients with bronchial asthma.     

Composition of the immunoglobulin classic antigen-binding site regulates allergic airway inflammation in a murine model of experimental asthma

Background When bound to mast cell FcɛRI, IgE serves as antigen receptor for allergic reactions, permitting specific identification of the allergen. Although the core of the classic antigen-binding site is heavy chain complementarity determining region 3 (CDR-H3), recent studies suggest that allergens might also bind IgE in a superantigen-like fashion outside the classic antigen-binding site.
Objective We sought to evaluate the contribution of the classic CDR-H3-centric antigen-binding site to the development of an allergic phenotype.
Methods Using a murine model of experimental asthma, we characterized a gene-targeted mouse strain expressing an altered range of CDR-H3s (ΔD-iD mice) in response to the hydrophobic allergen ovalbumin (OVA). Mutant and wild-type ( wt ) mice were sensitized intraperitoneally with OVA; non-sensitized mice served as controls.
Results We found the composition of the classic CDR-H3-centric antigen-binding site to be critical for the development of characteristic aspects of allergic asthma. (i) Compared with wt animals, ΔD-iD mice showed a significantly less pronounced OVA -induced rise in allergen-specific IgE levels and hence in total serum IgE levels. (ii) In addition, ΔD-iD mice demonstrated a significant reduction in eosinophilic airway inflammation, as well as in interleukin-4 (IL-4), IL-5 and IL-13 levels in BAL fluids.
Conclusion Allergic sensitization and airway inflammation depend on the composition of the predominant CDR-H3 repertoire, suggesting that the classic CDR-H3-centric antigen-binding site plays a crucial role in creating the immunological interface between allergen and IgE. Our results further emphasize a central role of IgE, not only in mediating but also in regulating the allergic immune response.     

Anti-inflammatory effects of tilmicosin in a noninfectious mouse model of allergic asthma

Tilmicosin, a semi-synthetic tylosin-derived macrolide antibiotic commonly used by veterinarians, has been shown to possess anti-inflammatory activity. However, possible use in asthma treatment has not yet been studied. In this study, we investigated the anti-inflammatory properties of tilmicosin using a murine asthma model. BALB/c mice were sensitized and challenged by intraperitoneal (i.p.) or nasal administration of ovalbumin. Tilmicosin (10 and 20?mg/kg) treatment resulted in a marked reduction in the presence of several types of immune cells and cytokines in the bronchoalveolar lavage fluids of mice. Levels of ovalbumin-specific Immunoglobulin E (IgE) were significantly decreased following treatment with tilmicosin (10 and 20?mg/kg). Histological studies using H&E (haematoxylin and eosin) and AB-PAS (alcian blue-periodic acid-Schiff) staining demonstrated that tilmicosin substantially inhibited both ovalbumin-induced inflammatory cells in lung tissues and goblet cell hyperplasia in the airway. These findings provided new insight into the immunopharmacological role of tilmicosin in terms of its effects in a murine model of asthma.     

Effect of an inhibitor of Jun N-terminal protein kinase, SP600125, in single allergen challenge in sensitized rats

Jun N-terminal kinase (JNK) has been implicated in the pathogenesis of inflammatory diseases including asthma. We examined the effect of SP600125 (anthra [1,9-cd] pyrazol-6 (2H)-one), a novel inhibitor of JNK in a model of asthma. Brown-Norway rats were sensitized to ovalbumin and treated with SP600125 intraperitoneally (90 mg/kg in total). SP600125 inhibited allergen-induced, increased activity of phosphorylated c-jun but not of phosphorylated-MAPKAPK2, indicative of activation of p38 MAPK, in the lung. SP600125 inhibited macrophage (P < 0.04), lymphocyte (P < 0.05), eosinophil (P < 0.04) and neutrophil (P < 0.005) numbers in bronchoalveolar lavage. Eosinophil and T-cell accumulation in the airways, mRNA expression for interleukin-1beta, tumour necrosis factor-beta, interleukin-3, interleukin-4 and interleukin-5, serum levels of allergen-specific immunoglobulin E and bronchial hyperresponsiveness were not affected by SP600125. Selective inhibition of JNK reduced inflammatory cell egress into the airway lumen after single allergen exposure. The role of JNK mitogen-activated protein kinase activation may be limited in the pathogenesis of bronchial hyperresponsiveness after single allergen exposure.     

Effect of salmeterol on allergen-induced airway inflammation in mild allergic asthma

A previous study suggested that the long-acting beta2-adrenergic agonist salmeterol (SM) had inhibitory effects on bronchial mucosal inflammation 6 hours after allergen exposure. To further evaluate the influence of SM on allergen-induced airway inflammation. We studied, in a randomized, double-blind, cross-over trial, 16 mild asthmatic patients who had a dual asthmatic response to allergen inhalation. Subjects received 50 microg of SM or placebo (P), twice daily for 1 week each, separated by a 2-week wash-out period. At the end of each treatment period, after withholding SM for 24 h, they had a methacholine inhalation test (medication was resumed after the test), followed 24 h later by an AC with the concentration of allergen that had induced a LAR at baseline. Airway inflammation was assessed 24 h after the AC by bronchoalveolar lavage (BAL) (n = 16) and bronchial biopsies (n = 13). As expected, SM improved baseline FEV1 and PC20 (P < or = 0.009) and decreased the allergen-induced early bronchoconstrictive response. There were no significant differences in BAL cell counts after the two treatments. On bronchial biopsies, numbers (median, mm2) of submucosal CD45 (P: 43 +/- 23; SM: 161 +/- 43, P = 0.031), CD45Ro (P: 37 +/- 19; SM: 126 +/- 41, P = 0.047) and AA1 positive cells (P: 38 +/- 6, SM: 65 +/- 17, P = 0.006) were significantly higher after SM than P treatment. The numbers of CD4 (P: 11 +/- 10; SM: 32 +/- 7, P = 0.085), HLA-DR (P: 65 +/- 30; SM: 116 +/- 36, P = 0.079) and EG2 positive cells (P: 25 +/- 15; SM: 38 +/- 26, P = 0.09) tended to increase with SM treatment. In summary, compared to placebo, 1 week of regular use of SM is associated with an increase in bronchial inflammatory cells 24 h after AC. This is in keeping with the recommendation that salmeterol should only be used with an anti-inflammatory agent, particularly in the context of significant allergen exposure.     

Sex-related splenocyte function in a murine model of allergic asthma

Background The prevalence and severity of asthma are higher among boys than girls, but the ratios are reversed after puberty. These observations strongly suggest that sex hormones have a role in the pathogenesis of the disease. However, the mechanisms underlying the gender differences in asthma are not fully understood.
Objective The aim of this study was to investigate sex differences in allergic inflammation in terms of immune function.
Methods Male and female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA). OVA-specific IgE in serum and airway inflammation were compared between sexes. Splenocytes from OVA-sensitized male or female donor mice were transferred to male or female naïve recipient mice. Subsequently, the recipient mice were challenged, followed by the evaluation of OVA-specific IgE and airway inflammation. Cytokines secreted from splenocytes of the sensitized mice were measured.
Results The levels of OVA-specific IgE and the allergen-induced airway inflammation were higher in female than in the male mice. The contents of T-helper type 2 (Th2) cytokines, IL-4, IL-5 and IL-13, in the bronchoalveolar lavage fluid from female mice were higher than those from male mice. The airway inflammation in female recipients transferred with splenocytes from female donors was more severe than that in any other combination of recipients and donors. Splenocytes from the sensitized female mice produced more of the Th2 cytokine, IL-5, than those from the sensitized male mice upon stimulation with OVA.
Conclusion Our findings suggest that the sex difference in allergic airway inflammation may be attributable to the sex difference in not only the hormonal environment but also in the immune cells themselves.     

Trichostatin A attenuates airway inflammation in mouse asthma model

BACKGROUND: Histone deacetylase (HDAC) inhibition has been demonstrated to change the expression of a restricted set of cellular genes. T cells are essential in the pathogenesis of allergen-induced airway inflammation. It was recently reported that treatment with HDAC inhibitors induces a T cell-suppressive effect. OBJECTIVE: The purpose of this study was to determine whether treatment with trichostatin A (TSA), a representative HDAC inhibitor, would reduce allergen-induced airway inflammation in a mouse asthma model. METHODS: BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA) and challenged with an aerosol of OVA. TSA (1 mg/kg body weight) was injected intraperitoneally every 2 days beginning on day 1. Mouse lungs were assayed immunohistochemically for HDAC1, a major HDAC subtype, and for infiltration of CD4+ cells. The effect of TSA on airway hyper-responsiveness (AHR) was determined, and the bronchoalveolar lavage fluid (BALF) of these mice was assayed for the number and types of inflammatory cells, and for the concentrations of IL-4, IL-5, and IgE. RESULTS: HDAC1 was localized within most airway cells and infiltrating inflammatory cells of asthmatic lungs. Treatment with TSA significantly attenuated AHR, as well as the numbers of eosinophils and lymphocytes in BALF. TSA also reduced infiltration of CD4+ and inflammatory cells and mucus occlusions in lung tissue, and decreased the concentrations of IL-4, IL-5, and IgE in BALF. CONCLUSION: TSA attenuated the development of allergic airway inflammation by decreasing expression of the Th2 cytokines, IL-4 and IL-5, and IgE, which resulted from reduced T cell infiltration. Our results suggest that HDAC inhibition may attenuate the development of asthma by a T cell suppressive effect.     

The airway inflammatory response in allergic asthma and its relationship to clinical disease

Endobronchial biopsy and lavage studies have revealed the presence of mast cell, eosinophil, T-lymphocyte and epithelial cell activation in asthma, along with the structural changes of tissue eosinophil infiltration, loss of superficial columnar ciliated epithelial cells and enhanced collagen deposition in the laminar reticularis. As these cellular and structural changes underlie the clinical features of asthma, i.e., symptom expression, variable airflow obstruction and bronchial hyperresponsiveness, an understanding of their induction and regulation is essential to the understanding of the asthmatic process. The acute airway response to allergen has been studied by the technique of local endobronchial allergen challenge with direct airway sampling in asthma. These studies identify allergen-mast cell interaction as the initial airway event, with mediator release inducing bronchoconstriction and enhancing vascular permeability. As preformed cytokines are present in mast cells, cytokine release from this cell population is likely to initiate the process of endothelial cell activation, with upregulation of cell adhesion molecules, and tissue cell recruitment. Subsequent cytokine elaboration from airway macrophages and T-lymphocytes will perpetuate this response while in chronic clinical disease T-lymphocytes, mast cells, matrix tissue, epithelial cells and eosinophils themselves are all likely to contribute to the cytokine pool within the airways and thus to the regulation of inflammatory cell migration and activation.     

Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma

BACKGROUND: Sex hormones might affect the severity and evolution of bronchial asthma. From existing literature, there exists, however, no convincing evidence for either exacerbation or improvement of allergic symptoms by progesterone. OBJECTIVE: This study was aimed to explore the effect of exogenously administered progesterone in a mouse model of allergic asthma. METHODS: BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA followed by chronic inhalation of nebulized OVA or physiologic saline (Sal). Medroxyprogesterone acetate or placebo was instilled daily into the oesophagus before and during the inhalatory OVA challenge phase. RESULTS: Progesterone worsened allergic airway inflammation in OVA-challenged mice, as evidenced by enhanced bronchial responsiveness to inhaled metacholine and increased bronchial eosinophilia. Elevated airway eosinophilia corresponded with higher bronchial and systemic IL-5 levels in the progesterone group. The ratio of IL-4/IFN-gamma levels in bronchoalveolar lavage fluid and numbers of eosinophil colony-forming units in the bone marrow were also elevated in the latter group. Progesterone, however, did not influence allergen-specific IgE production, nor did it affect bronchial responses in Sal-challenged mice. CONCLUSION: Our data show that exogenously administered progesterone aggravates the phenotype of eosinophilic airway inflammation in mice by enhancing systemic IL-5 production. Progesterone also increases bronchial hyper-reactivity.     

屋尘螨在诱导BALB/c小鼠混合型气道炎症中的作用及致病机制探讨

目的 探讨屋尘螨(HDM)抗原在小鼠模型中诱导混合型气道炎症中的作用及其机理,为支气管哮喘的临床诊断和治疗提供理论依据.方法 BALB/c小鼠于实验第0天、7天、14天、21天、28天和35天进行PBS或HDM提取液(50μg或100 μg)滴鼻.采用头体积描记法测量小鼠的气道反应性;对支气管肺泡灌洗液(BAL)进行细胞计数和分类;酶联免疫法(ELISA)检测BAL中CXCL1、CXCL2、CCL11 (eotaxin)、IL-5、IFNγ、IL-10和IL-17的含量及血清总IgE,HDM特异性IgG1、IgG2a;采用实时荧光定量PCR检测肺组织中相关基因mRNA表达;并对肺组织PAS染色后进行病理学观察.结果 HDM抗原引起了以中性粒细胞和嗜酸性粒细胞为主的混合型气道炎症、血清HDM特异性IgG1的升高及高脚杯细胞增生(GCH)等组织学变化,其混合型气道炎症可能与CXCL1和IL-5等细胞因子的分泌增多有关,是固有免疫和适应性免疫共同活化的结果.这种炎症表型在经高浓度HDM(100 μg)致敏的小鼠中表现得更为显著.结论 HDM过敏原在小鼠模型中诱导了中性粒细胞和嗜酸性粒细胞的共同活化.     

Influence of smoking on airway inflammation and remodelling in asthma

Background Although exposure to tobacco smoke has been associated with increased morbidity and mortality, cigarette smoking is still common in the asthmatic population. Induced sputum neutrophilia has been observed in asthmatic smokers, but the effects of regular smoking on their bronchial mucosa morphology remain to be defined. This study documents the inflammatory and remodelling features in bronchial biopsies of smoking compared with non‐smoking asthmatics. Methods We analysed bronchial biopsies from 24 steroid‐naïve young subjects with mild asthma: 12 non‐smoking and 12 currently smoking subjects. In addition to airway morphology assessment, inflammation and remodelling were analysed by immunohistochemistry using antibodies against CD3, CD68, major basic protein, neutrophil elastase, and tryptase. Expression of the cytokines IL‐4, IL‐5, IL‐8, IFN‐γ, transforming growth factor‐β, and TNF was determined by in situ hybridization. Results Compared with non‐smoking asthmatic subjects, smoking asthmatics' bronchial mucosa showed squamous cell metaplasia, in addition to increased expression of subepithelial neutrophil elastase, IFN‐γ, and intraepithelial IL‐8. Conclusions Smoking status modifies morphological and inflammatory processes in young subjects with mild asthma. The changes may possibly affect asthma treatment responses and clinical outcomes.