Structural changes and airway remodelling in occupational asthma at a mean interval of 14 years after cessation of exposure

Background Occupational asthma (OA) may cause alterations of airways with inflammation and remodelling after cessation of exposure. Although the long‐term clinical, functional and induced sputum sequelae have been examined in workers removed from exposure, the long‐term pathological outcomes are unknown. Objective We aimed to investigate whether airway inflammation and remodelling were present in bronchial biopsies of subjects with prior OA but without evidence of persisting asthma at a mean interval of 14 years after cessation of exposure. Methods Ten clinically and functionally asymptomatic subjects with a prior diagnosis of OA were recruited and underwent bronchoscopy, bronchoalveolar lavage and bronchial biopsy. Comparisons were made with biopsies from normal control subjects. Epithelial detachment, epithelial metaplasia, mucous gland and airway smooth muscle (ASM) areas as well as the distance between the epithelium and ASM were measured by image analysis. The amount of collagen present was assessed by van Gieson staining. The numbers of TGF‐β1‐ and eosinophil cationic protein (ECP)‐positive cells were evaluated by specific immunostaining. Results Statistically significant increases were found in the numbers of TGF‐β1‐ and ECP‐positive cells and in the amount of subepithelial fibrosis present in the biopsies of subjects with prior OA compared with control biopsies. The distance between the epithelium and ASM was significantly reduced in the OA group. Increases in epithelial metaplasia, ASM mass, mucous gland numbers, collagen deposition and eosinophilia in the OA group were not statistically significant. There was no evidence of ongoing inflammation in the group with prior OA as assessed by the number of T lymphocytes present. Conclusion Some aspects of airway inflammation and remodelling persist in subjects with prior OA long after cessation of exposure even in the absence of clinical, sputum and functional abnormalities. These findings are relevant to the assessment of long‐term sequelae in subjects with OA when reviewed after cessation of exposure.     

Bronchial inflammation in corticosteroid-sensitive and corticosteroid-resistant asthma at baseline and on oral corticosteroid treatment

BACKGROUND: Pathophysiology of corticosteroid (CS)-resistant asthma remains incompletely understood. OBJECTIVE: To determine if failure of asthma to clinically improve with CS is due to a defective response of airway bronchial inflammation to these drugs. METHODS: Twenty-one asthmatics having a decreased baseline FEV1 that improved >or= 30% with inhaled beta2 agonist got bronchial biopsies before and at the end of an oral CS treatment (methylprednisolone 40 mg daily for 14 days). They were arbitrarily divided into two groups according to baseline FEV1 improvement following this treatment: >or= 23% designated as CS-sensitive (CSS) (n = 10) and < 15% as CS-resistant (CSR) (n = 11). RESULTS: Before oral CS, counts of bronchial mucosa inflammatory cells identified by immunohistochemistry (CD3, MBP, tryptase, CD68, neutrophil elastase and CD25 for lymphocytes, eosinophils, mast cells, macrophages, neutrophils and IL-2 receptors, respectively) were similar in CSS and CSR subjects. Oral CS decreased CD3+ cell counts (medians: 60-20 cells/mm(2); P = 0.014) and MBP+ cell counts (medians: 19-4 cells/mm(2); P = 0.03) in CSS asthmatics, but only tryptase+ cell counts in CSR asthmatics (medians: 30-18 cells/mm(2); P = 0.05). Few bronchial neutrophil elastase+ cells were observed and their counts were similar in the two groups of asthmatics before and when on oral CS (all medians: = 2 cells/mm(2)). CONCLUSIONS: These data show that, in these subjects with moderate to severe asthma, lymphocytes and eosinophils constitute most of the inflammatory cells infiltrating the bronchial mucosa. They also demonstrated that clinical impaired response to CS is associated with a persistent bronchial mucosa cellular infiltrate despite oral CS treatment. Additional studies are required to determine the role of this CS-resistant bronchial inflammation in the impaired asthma clinical response to these drugs.     

Bronchial hyperresponsiveness and airway inflammation in adolescents with asymptomatic childhood asthma

BACKGROUND: About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with "outgrown" childhood asthma. METHODS: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-alpha and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-alpha in sputum correlated significantly with BHR. CONCLUSIONS: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.     

Interleukin-18-deficient mice exhibit diminished chronic inflammation and airway remodelling in ovalbumin-induced asthma model

Interleukin (IL)-18, which is produced by activated monocytes/macrophages and airway epithelial cells, is suggested to contribute to the pathophysiology of asthma by modulating airway inflammation. However, the involvement of IL-18 on modulating chronic airway inflammation and airway remodelling, which are characterized in a refractory asthma model exposed to long-term antigen, has not been investigated sufficiently. We examined the role of IL-18 in chronic airway inflammation and airway remodelling by long-term antigen exposure. IL-18-deficient and C57BL/6-wild-type mice were sensitized by ovalbumin (OVA) and were then exposed to aerosolized OVA twice a week for 12 weeks. We assessed airway inflammation by assessing the infiltration of cells into the airspace and lung tissues, and airway remodelling by airway mucus expression, peribronchial fibrosis and smooth muscle thickness. In IL-18-deficient mice, when exposed to OVA, the total cells and neutrophils of the bronchoalveolar lavage fluid (BALF) were diminished, as were the number of infiltrated cells in the lung tissues. IL-18-deficient mice exposed to OVA after 12 weeks showed significantly decreased levels of interferon (IFN)-gamma, IL-13 and transforming growth factor (TGF)-beta1 in the BALF. The airway hyperresponsiveness to acetyl-beta-methacholine chloride was inhibited in IL-18-deficient mice in comparison with wild-type mice. In addition, IL-18-deficient mice exposed to OVA had fewer significant features of airway remodelling. These findings suggest that IL-18 may enhance chronic airway inflammation and airway remodelling through the production of IFN-gamma, IL-13 and TGF-beta1 in the OVA-induced asthma mouse model.     

Natural killer T cells are dispensable in the development of allergen-induced airway hyperresponsiveness, inflammation and remodelling in a mouse model of chronic asthma

Natural killer T (NK T) cells have been shown to play an essential role in the development of allergen-induced airway hyperresponsiveness (AHR) and/or airway inflammation in mouse models of acute asthma. Recently, NK T cells have been reported to be required for the development of AHR in a virus induced chronic asthma model. We investigated whether NK T cells were required for the development of allergen-induced AHR, airway inflammation and airway remodelling in a mouse model of chronic asthma. CD1d^−/− mice that lack NK T cells were used for the experiments. In the chronic model, AHR, eosinophilic inflammation, remodelling characteristics including mucus metaplasia, subepithelial fibrosis and increased mass of the airway smooth muscle, T helper type 2 (Th2) immune response and immunoglobulin (Ig)E production were equally increased in both CD1d^−/− mice and wild-type mice. However, in the acute model, AHR, eosinophilic inflammation, Th2 immune response and IgE production were significantly decreased in the CD1d^−/− mice compared to wild-type. CD1d-dependent NK T cells may not be required for the development of allergen-induced AHR, eosinophilic airway inflammation and airway remodelling in chronic asthma model, although they play a role in the development of AHR and eosinophilic inflammation in acute asthma model.     

The effect of a single inhaled dose of a VLA-4 antagonist on allergen-induced airway responses and airway inflammation in patients with asthma

Adhesion molecule very late antigen-4 (VLA-4) is implicated in the recruitment and activation of inflammatory cells in asthma, including eosinophils, T cells and mast cells. VLA-4 antagonists have been proposed as a new anti-inflammatory treatment modality for asthma. Therefore, we investigated whether a single inhaled dose of VLA-4 antagonist GW559090X could protect against allergen-induced changes in airway responses and airway inflammation in patients with asthma. We performed a randomized, double-blind, three-way crossover study with single inhaled doses of 3 mg of GW559090X, 500 microg of fluticasone propionate (FP) or placebo in 15 patients with mild intermittent asthma, controlled with short-acting beta(2)-agonists only. All patients developed a late asthmatic response (LAR) after allergen inhalation during screening. Study medication was administered 30 min prior to allergen challenge. Pre-dose and 24 h post-dose PC20 methacholine and levels of exhaled nitric oxide (eNO) were determined. At the given dose, VLA-4 antagonist GW559090X did not attenuate the early asthmatic response (EAR) when compared with placebo: mean AUC0-2 h(+/-SEM) (%fall h): 27.2+/-3.7 and 21.9+/-3.0 respectively (P=0.33); nor the LAR: mean AUC3-8 h(+/-SEM) (%fall h): 98.8+/-12.9 and 94.8+/-6.8 respectively (P=0.84). However, pretreatment with FP did attenuate both EAR and LAR when compared with placebo: mean AUC0-2 h11.6+/-3.3 (P=0.024) and mean AUC3-8 h 6.3+/-7.6 (P<0.001). None of these treatments had an effect on allergen-induced changes in airway hyper-responsiveness or eNO levels. These findings suggest that VLA-4 may not play a major role in allergen-induced airway responses and inflammation in asthma.     

地塞米松降低吸烟大鼠气道反应性及上调气道平滑肌细胞BKca表达

目的观察雾化吸入地塞米松对吸烟大鼠气道的反应性及支气管平滑肌高电导的钙激活的钾通道(BKca)蛋白和mRNA表达的影响。方法复制大鼠吸烟模型后雾化吸入地塞米松治疗,测定气道反应性;采用HE染色,免疫组织化学染色和原位杂交等方法检测肺组织病理形态学改变和BKca的表达。结果①吸烟组的气道反应性明显高于正常对照组(P<0.05),而吸烟加雾化吸入地塞米松治疗组的气道反应性显著低于吸烟组(P<0.05),但仍高于正常对照组;②吸烟组肺组织出现较轻的炎症反应,吸烟加雾化吸入地塞米松治疗组无炎症反应;③吸烟组大气道和小气道BKcamRNA和蛋白表达低于正常对照组,吸烟加雾化吸入地塞米松治疗组BKcamRNA表达高于吸烟组。结论吸烟引起的气道反应性的增高与气道的炎症反应不平行,雾化吸入地塞米松治疗可降低吸烟引起的气道高反应性,其机制之一可能是降低吸烟对大鼠气道平滑肌BKca表达的抑制作用。     

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.     

Eosinophilic airway inflammation and the prognosis of childhood asthma

BACKGROUND: Eosinophilic airway inflammation is a key pathophysiological feature of asthma that can predict treatment response. However, the prognostic value of sputum eosinophilia is not established. OBJECTIVE: The aim of this study was to determine the influence of induced sputum eosinophilia on the prognosis of childhood asthma. METHODS: A cohort of children with asthma was evaluated by induced sputum analysis at inception and classified as having either eosinophilic asthma (EA) (sputum eosinophils >2.5%) or non-eosinophilic asthma (NEA). After a mean follow-up period of 5 years, eligible subjects (n=83) were contacted and 69 subjects (33 EA, 36 NEA) evaluated. The children had a mean age of 15.9 years, and 61% were male. RESULTS: Children with EA reported more wheeze during the follow-up period (27% vs. 6% wheezed most years; P<0.0001), increased night waking during the past 12 months (28% vs. 3% reported weekly waking; P=0.01), and greater impairment of quality of life due to asthma (P=0.04). Subsequent beta2-agonist use was increased in children with EA (P=0.02), although there was no difference in corticosteroid use. In EA, subsequent forced expiratory volume in 1 s/forced vital capacity was lower (79% vs. 86%; P=0.01) and grass pollen allergy was more prevalent (77% vs. 27%; P=0.006). CONCLUSION: In children, eosinophilic airway inflammation is associated with deteriorating asthma over time. This is consistent with the hypothesis that airway inflammation has an adverse impact on the prognosis of childhood asthma, and suggests a role for monitoring inflammation in asthma management.     

Mannitol challenge for assessment of airway responsiveness,airway inflammation and inflammatory phenotype in asthma

Background Assessment of airway inflammation in asthma is becoming increasingly important, as the inflammatory phenotype underpins the treatment response. Objective This study aimed to evaluate mannitol as a tool for assessing airway responsiveness and airway inflammation in asthma, compared with hypertonic saline. Methods Fifty‐five subjects with stable asthma completed a hypertonic (4.5%) saline challenge and a mannitol challenge at two separate visits, performed 48–72 h apart, in random order. Results Induced sputum was obtained from 49 (89%) subjects during the saline challenge and 42 (76%) subjects during the mannitol challenge (P>0.05). There was a significant correlation between the greatest percentage fall in forced expiratory volume in 1 s (FEV₁) (r=0.6, P<0.0001), the dose–response slope (r=0.73), cumulative dose (r=0.55) and PD15 (r=0.46) for mannitol and hypertonic saline. The greatest percentage fall in FEV₁ to mannitol was less in non‐eosinophilic asthma. There was a lower total cell count in mannitol vs. hypertonic‐saline‐induced sputum. However, sputum eosinophils and neutrophils were not significantly different. Using mannitol, a higher proportion of subjects were classified as having eosinophilic asthma. There were no differences in IL‐8, neutrophil elastase or matrix‐metalloproteinase 9 concentrations in sputum samples induced with mannitol or hypertonic saline. Conclusion We conclude that mannitol can be used to induce good‐quality sputum, useful for analysis of inflammatory mediators and for predicting the inflammatory phenotype in asthma. Cite this as: L. G. Wood, H. Powell and P. G. Gibson, Clinical & Experimental Allergy, 2010 (40) 232–241.     

Airway inflammation and cough sensitivity in cough-variant asthma

BACKGROUND: Mechanisms underlying cough and bronchoconstriction in patients with cough-variant asthma (CVA) are not well established. Differences in location or degree of activation of eosinophils and allergic cytokines have been suggested as the likely causes. To address this issue, we have carried out a comparative study of airway inflammatory markers between patients with CVA and classic asthma (CA). The relationship between these markers with airway hyperresponsiveness (AHR) and cough sensitivity has also been studied. METHODS: Twenty-seven non-smokers and steroid-naive patients with CVA (12) and CA (15) were examined. Capsaicin challenge, histamine bronchoprovocation test, nitric oxide levels in exhaled air and sputum induction were performed in all of them. Differential cell sputum recount and supernatant concentrations of eosinophil granule-derived cationic proteins (ECP), interleukin (IL)5, IL8 and tumour necrosis factor (TNF)-alpha were also measured. RESULTS: There were no significant differences in either the inflammatory pattern of soluble markers or differential cell counts between CA and CVA. Histamine PC20 was correlated with IL-5 in CVA, whereas it was associated with sputum eosinophilia in CA. Cough sensitivity (log C5) and histamine PC20 were inversely related in CA. CONCLUSIONS: Although the pattern of inflammatory sputum markers in patients with asthma and cough-variant asthma is similar, its relation with bronchial hyperreactivity and cough sensitivity is different in each group.     

Allergen-induced bronchial inflammation is associated with decreased levels of surfactant proteins A and D in a murine model of asthma

Background Increasing evidence suggests that pulmonary surfactant protein A (SP‐A) and D (SP‐D) participate in the lung defence against pathogens. However, the role of surfactant proteins in the pathogenesis of allergen‐induced airway inflammation has not been elucidated. In this study we examined the levels and distributions of SP‐A and SP‐D in a dust mite (Dermatophagoides pteronyssinus, Der p) allergen‐induced murine model of asthma. Methods The concentration of SP‐A and SP‐D in the bronchoalveolar lavage fluid (BALF) and the distribution of surfactant proteins in the lung were assayed by ELISA and immunohistochemistry methods, respectively. The effect of surfactant proteins on allergen‐induced pulmonary lymphocyte proliferation was also studied. Results We demonstrated that there were marked reductions of SP‐A and SP‐D levels in the BALF of Der p‐sensitized BALB/c mice at 48–72 h after allergen challenge (AC). Both purified SP‐A and SP‐D were able to suppress, in a dose dependent manner, Der p‐stimulated intrapulmonary lymphocyte proliferation of naïve mice with saline or allergen challenge, or of Der p‐sensitized mice with saline challenge. On the contrary, this suppressive effect was mild (< 9%) on lymphocytes from sensitized mice after AC. Conclusion These results indicated the involvement of pulmonary surfactant proteins in the allergic bronchial inflammation of sensitized mice.     

Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma

Background Tiotropium bromide, a long acting muscarinic receptor inhibitor, is a potent agent for patients with bronchial asthma as well as chronic obstructive pulmonary disease. Objective The aim of this study was to evaluate whether tiotropium bromide can inhibit allergen‐induced acute and chronic airway inflammation, T helper (Th)2 cytokine production, and airway remodelling in a murine model of asthma. Methods Balb/c mice were sensitized and challenged acutely or chronically to ovalbumin (OVA). The impact of tiotropium bromide was assessed using these mice models by histologic, morphometric, and molecular techniques. Moreover, the effect of tiotropium bromide on Th2 cytokine production from purified human peripheral blood mononuclear cells (PBMCs) was assessed. Results Treatment with tiotropium bromide significantly reduced airway inflammation and the Th2 cytokine production in bronchoalveolar lavage fluid (BALF) in both acute and chronic models of asthma. The levels of TGF‐β1 were also reduced by tiotropium bromide in BALF in a chronic model. The goblet cell metaplasia, thickness of airway smooth muscle, and airway fibrosis were all significantly decreased in tiotropium bromide‐treated mice. Moreover, airway hyperresponsiveness (AHR) to serotonin was significantly abrogated by tiotropium bromide in a chronic model. Th2 cytokine production from spleen cells isolated from OVA‐sensitized mice was also significantly inhibited by tiotropium bromide and 4‐diphenylacetoxy‐N‐methylpiperidine methiodide, which is a selective antagonist to the M3 receptor. Finally, treatment with tiotropium bromide inhibited the Th2 cytokine production from PBMCs. Conclusion These results indicate that tiotropium bromide can inhibit Th2 cytokine production and airway inflammation, and thus may reduce airway remodelling and AHR in a murine model of asthma. Cite this as: S. Ohta, N. Oda, T. Yokoe, A. Tanaka, Y. Yamamoto, Y. Watanabe, K. Minoguchi, T. Ohnishi, T. Hirose, H. Nagase, K. Ohta and M. Adachi, Clinical & Experimental Allergy, 2010 (40) 1266–1275.     

Inter-relationships between airway inflammation, reticular basement membrane thickening and bronchial hyper-reactivity to methacholine in asthma; a systematic bronchoalveolar lavage and airway biopsy analysis

Background Asthma is accepted as a disease characterized by airway inflammation, with evidence that airway structural changes, or ‘remodelling’ occurs. There are few studies relating airway physiology, inflammation and remodelling, however. We have carried out a study of inter‐relationships between airway inflammation, airway remodelling, reticular basement membrane (RBM) thickening, and bronchial hyper‐reactivity (BHR), before and after high‐dose inhaled corticosteroid (fluticasone propionate 750 μg b.d.), in a group of relatively mild but symptomatic, steroid naïve asthma patients. Methods Double‐blind, randomized, placebo‐controlled, parallel group study of inhaled corticosteroid (ICS) in 35 asthmatics, with bronchoalveolar lavage (BAL) and airway endobronchial biopsy (EBB) for inflammatory cell profiles and EBB for airway remodelling carried out at baseline, 3 and 12 months. Results At baseline RBM thickening was related to BAL mast cells and EBB eosinophil counts. In turn baseline log EBB EG2 eosinophil count, log%BAL epithelial cells and log RBM thickness explained 55% of the variability in BHR. Conclusion We provide new information that airway inflammation, remodelling, and BHR in asthma are inter‐related and improved by ICS therapy. Our data potentially support the need for early and long‐term intervention with ICS even in relatively mild asthmatics, and the need to further assess the potential merit of longitudinal BHR testing in management of some patients, as this may reflect both airway inflammation and remodelling.     

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.     

Cystic fibrosis airway epithelium remodelling: involvement of inflammation

Chronic inflammation is a hallmark of cystic fibrosis (CF) lung disease and airway epithelium damage and remodelling are important components of lung pathology progression in CF. Whether this remodelling is secondary to deleterious infectious and inflammatory mediators, or to alterations of CF human airway epithelial (HAE) cells, such as their hyper inflammatory phenotype or their basic cystic fibrosis transmembrane conductance regulator (CFTR) default, remains debated. In this study, we evaluated the involvement of alterations of CF HAE cells in airway epithelium remodelling. HAE cells from non‐CF and CF patients were cultured in an air–liquid interface, with and without inflammatory stimulation, along the regeneration process, and the remodelling of the reconstituted epithelium was analysed. We confirmed that CF HAE cells showed a hyperinflammatory phenotype which was lost with time. In comparison to non‐CF epithelium, CF epithelium regeneration in the absence of exogenous inflammation was higher and exhibited basal cell hyperplasia. This remodelling was mimicked by inflammatory stimulation of non‐CF cells and was absent when CF HAE cells were no longer hyperinflamed. Moreover, the number of goblet cells was similar in non‐CF and CF cultures and increased equally under inflammatory stimulation. Finally, whatever the inflammatory environment, CF cultures showed a delay in ciliated cell differentiation. In conclusion, alterations of CF HAE cells partly regulate airway epithelium remodelling following injury and regeneration. This remodelling, together with goblet cell hyperplasia induced by exogenous inflammation and alteration of ciliated cell differentiation, may worsen mucociliary clearance impairment, leading to injury. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.