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Background Fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown. Objective To provide a comprehensive analysis on the range of filamentous fungi isolated in sputum from people with asthma and report the relationship with their clinico-immunological features of their disease. Methods We recruited 126 subjects with a diagnosis of asthma, 94% with moderate-severe disease, and 18 healthy volunteers. At a single stable visit, subjects underwent spirometry; sputum fungal culture and a sputum cell differential count; skin prick testing to both common aeroallergens and an extended fungal panel; specific IgE to Aspergillus fumigatus. Fungi were identified by morphology and species identity was confirmed by sequencing. Four patients had allergic bronchopulmonary aspergillosis. Results Forty-eight percent of asthma subjects were IgE-sensitized to one fungal allergen and 22% to ≥ 2. Twenty-seven different taxa of filamentous fungi were isolated from 54% of their sputa, more than one species being detected in 17%. This compared with 3 (17%) healthy controls culturing any fungus ( P < 0.01). Aspergillus species were most frequently cultured in isolation followed by Penicillium species. Post-bronchodilator FEV1 (% predicted) in the subjects with asthma was 71(± 25) in those with a positive fungal culture vs. 83 (± 25) in those culture-negative, ( P < 0.01). Conclusion and Clinical Relevance Numerous thermotolerant fungi other than A. fumigatus can be cultured from sputum of people with moderate-to-severe asthma; a positive culture is associated with an impaired post-bronchodilator FEV1, which might be partly responsible for the development of fixed airflow obstruction in asthma. Sensitization to these fungi is also common. [ABSTRACT FROM AUTHOR]

Rationale: The importance of Aspergillus fumigatus sensitization and colonization of the airways in patients with asthma is unclear.Objectives: To define the relationship between the clinical and laboratory features of A. fumigatus-associated asthma.Methods: We studied 79 patients with asthma (89% classed as GINA 4 or 5) classified into 3 groups according to A. fumigatus sensitization: (1) IgE-sensitized (immediate cutaneous reactivity > 3 mm and/or IgE > 0.35 kU/L); (2) IgG-only-sensitized (IgG > 40 mg/L); and (3) nonsensitized. These were compared with 14 healthy control subjects. Sputum culture was focused toward detection of A. fumigatus and compared with clinical assessment data.Measurements and Main Results: A. fumigatus was cultured from 63% of IgE-sensitized patients with asthma (n = 40), 39% of IgG-only-sensitized patients with asthma (n = 13), 31% of nonsensitized patients with asthma (n = 26) and 7% of healthy control subjects (n = 14). Patients sensitized to A. fumigatus compared with nonsensitized patients with asthma had lower lung function (postbronchodilator FEV₁ % predicted, mean [SEM]: 68 [±5]% versus 88 [±5]%; P < 0.05), more bronchiectasis (68% versus 35%; P < 0.05), and more sputum neutrophils (median [interquartile range]: 80.9 [50.1-94.1]% versus 49.5 [21.2-71.4]%; P < 0.01). In a multilinear regression model, A. fumigatus-IgE sensitization and sputum neutrophil differential cell count were important predictors of lung function (P = 0.016), supported by culture of A. fumigatus (P = 0.046) and eosinophil differential cell count (P = 0.024).Conclusions: A. fumigatus detection in sputum is associated with A. fumigatus-IgE sensitization, neutrophilic airway inflammation, and reduced lung function. This supports the concept that development of fixed airflow obstruction in asthma is consequent upon the damaging effects of airway colonization with A. fumigatus. [ABSTRACT FROM AUTHOR]

Background: Airway smooth muscle (ASM) hyperplasia is a hallmark of asthma that is associated with disease severity and persistent airflow obstruction. Objectives: We sought to investigate whether fibrocytes, a population of peripheral blood mesenchymal progenitors, are recruited to the ASM compartment in asthma. Methods: We assessed the number of fibrocytes in bronchial biopsy specimens and peripheral blood from subjects with mild-to-severe refractory asthma versus healthy control subjects. In vitro we investigated potential mechanisms controlling fibrocyte migration toward the ASM bundle. Results: Fifty-one subjects with asthma and 33 control subjects were studied. In bronchial biopsy specimens, the number of fibrocytes was increased in the lamina propria of subjects with severe refractory asthma (median [interquartile range] number, 1.9/mm2 [1.7/mm2]) versus healthy control subjects (median [interquartile range] number, 0/mm2 [0.3/mm2], P < .0001) and in the ASM bundle of subjects with asthma of all severities (subjects with severe asthma, median [interquartile range] number, 3.8/mm2 [9.4/mm2]; subjects with mild-to-moderate asthma, median [interquartile range] number, 1.1/mm2 [2.4/mm2]); healthy control subjects, (median [interquartile range] number, 0/mm2 [0/mm2]); P = .0004). In the peripheral blood the fibrocyte number was also increased in subjects with severe refractory asthma (median [interquartile range] number, 1.4 × 104/mL [2.6 × 104/mL]) versus healthy control subjects (median [interquartile range] number, 0.4 × 104/mL [1.0 × 104/mL], P = .002). We identified that in vitro ASM promotes fibrocyte chemotaxis and chemokinesis (distance of migration after 4.5 hours, 31 μm [2.9 μm] vs 17 μm [2.4 μm], P = .0001), which was in part mediated by platelet-derived growth factor (mean inhibition by neutralizing antibody, 16% [95% CI, 2% to 32%], P = .03) but not by activation of chemokine receptors. Conclusion: This study provides the first evidence that fibrocytes are present in the ASM compartment in asthma and that ASM can augment fibrocyte migration. The importance of fibrocytes in the development of ASM hyperplasia and airway dysfunction in asthma remains to be determined. [Copyright &y& Elsevier]

Background: Nonasthmatic eosinophilic bronchitis (EB) has emerged as a useful tool to study the structural and inflammatory mechanisms of airway hyperresponsiveness (AHR) in asthma. We have previously shown that vascular remodeling and reticular basement membrane (RBM) thickening are present in EB. However, it is not known whether other features of structural remodeling including increased airway smooth muscle (ASM) mass, matrix deposition, and glandular hyperplasia are also present in EB. Objectives: We sought to determine whether structural remodeling occurs in EB and is associated with AHR and airflow limitation. Methods: Forty-two patients with asthma, 21 patients with EB, and 19 healthy volunteers were recruited. ASM area, RBM thickness, collagen 3 deposition, glandular area, mast cells, and granulocytes were assessed in bronchial biopsy samples. Results: Nonasthmatic eosinophilic bronchitis and asthma were associated with a significant increase in ASM mass and RBM thickness compared with healthy subjects. In contrast, we did not observe any significant differences in collagen 3 deposition in the lamina propria and ASM or the % area of glands in the lamina propria. Univariate analysis demonstrated that mast cell numbers in the ASM were the only feature of remodeling associated with AHR (β = –0.51; P = .004). Stepwise linear regression revealed that a combination of mast cell numbers in the ASM (β = –0.43) and disease duration (β = –0.25; model-adjusted R 2 = 0.26; P = .027) best modeled AHR. Conclusion: Mast cell localization to the ASM bundle, but not structural remodeling of the airway wall, is associated with AHR in asthma. [Copyright &y& Elsevier]

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Background: The importance of IL-13 in the asthma paradigm is supported by increased expression in human subjects, particularly in patients with mild-to-moderate asthma. However, the role of IL-13 in severe asthma needs to be further defined. Objective: We sought to assess IL-13 expression in sputum and bronchial biopsy specimens from subjects with mild-to-severe asthma. Methods: Sputum IL-13 concentrations were measured in 32 control subjects, 34 subjects with mild asthma, 21 subjects with moderate asthma, and 26 subjects with severe asthma. Enumeration of mast cells, eosinophils, and IL-13+ cells in the bronchial submucosa and airway smooth muscle (ASM) bundle was performed in 7 control subjects, 14 subjects with mild asthma, 7 subjects with moderate asthma, and 7 subjects with severe asthma. Results: The proportion of subjects with measurable IL-13 in the sputum was increased in the mild asthma group (15/34) and severe asthma group (10/26) compared with that seen in the control group (4/32; P = .004). IL-13+ cells were increased within the submucosa in all asthma severity groups compared with control subjects (P = .006). The number of IL-13+ cells were increased within the ASM bundle in the severe asthma group compared with that seen in the other groups (P < .05). Asthma control questionnaire scores positively correlated with sputum IL-13 concentrations (Rs = 0.35, P = .04) and mast cells in the ASM bundle (Rs = 0.7, P = .007). IL-13+ cells within the submucosa and ASM correlated with sputum eosinophilia (Rs = 0.4, P ≤ .05). Conclusions: IL-13 overexpression in sputum and bronchial biopsy specimens is a feature of severe asthma. [Copyright &y& Elsevier]

Rationale: Increased vascularity and expression of vascular endothelial growth factor (VEGF) are recognized features of the asthmatic airway. The association of vascular remodeling with airway hyperresponsiveness (AHR) is unclear. Objective: To assess vascular remodeling and sputum VEGF concentration in subjects with asthma, subjects with nonasthmatic eosinophilic bronchitis (EB), and healthy controls. Methods: In cohort 1, 19 patients with asthma (Global Initiative for Asthma [GINA] 1-2, n = 9; GINA 3-5, n = 10), 10 patients with EB, and 11 healthy matched controls were recruited. Expression of the endothelial marker EN4 was assessed in bronchial biopsy samples. Vessels were counted using the validated mean Chalkley count by a blind observer. For cohort 2, a second independent cohort of 31 patients with asthma (GINA 1-2, n = 11; GINA 3-5, n = 20), 14 patients with EB, and 15 matched controls was recruited. Induced sputum supernatant VEGF was measured by ELISA. Results: The mean chalkley count was significantly greater in GINA 3-5 asthma (5.2 [0.4]) and EB (4.8 [0.3]) compared with controls (3.5 [0.5]) and demonstrated a significant inverse correlation with the postbronchodilator FEV1% predicted in patients with asthma (R 2 = 0.28; P = .02). Sputum VEGF concentration was also increased in GINA 3-5 asthma (2365 [1361-4110] pg/g) and EB (4699 [2818-7834] pg/g) compared with controls (1094 [676-1774] pg/g) and was inversely related to postbronchodilator FEV1% predicted in asthma (R 2 = 0.2; P = .01). Conclusion: Vascular remodeling is a feature of asthma, and EB and is inversely associated with the postbronchodilator FEV1 in asthma, suggesting that vascular remodeling is associated with airflow obstruction but not AHR. Clinical implications: Vascular remodeling is dissociated from AHR in asthma and associated with airflow limitation. [Copyright &y& Elsevier]

RATIONALE: Airway smooth muscle (ASM) hyperplasia is a feature of asthma, and increases with disease severity. We hypothesized that this results from migration of ASM or progenitors in response to chemokines derived from ASM or mast cells within the ASM bundle. OBJECTIVES: To examine expression of the chemokine receptor, CC chemokine receptor (CCR) 7, in vivo by ASM in patients with asthma and healthy control subjects, and by primary cultures of ASM and fibroblasts; to define expression of its ligands, CC chemokine ligand (CCL) 19 and CCL21, in bronchial biopsies, and primary cultures of ASM and mast cells; and to investigate CCR7's role in ASM migration and repair. METHODS: ASM was isolated from bronchoscopy and resection tissue. Receptor and chemokine expression was examined by immunohistochemistry, immunofluorescence, flow cytometry, ELISA, and reverse transcriptase-polymerase chain reaction. CCR7 function was examined by intracellular calcium measurements, chemotaxis, wound healing assays, and measurement of cell proliferation. MEASUREMENTS AND MAIN RESULTS: ASM, myofibroblasts, and fibroblasts expressed CCR7. CCL19, but not CCL21, was highly expressed in bronchial biopsies by mast cells and vessels in asthma of all severities, ASM in severe disease, and ex vivo ASM and mast cells. ASM CCR7 activation by CCL19-mediated intracellular calcium elevation and concentration-dependent migration, but not proliferation. Importantly, mast cell and ASM-derived CCL19 mediated ASM migration and repair. CONCLUSIONS: The CCL19/CCR7 axis may play an important role in the development of ASM hyperplasia in asthma. [ABSTRACT FROM AUTHOR]

Background: The Th2 cytokine interleukin (IL)-13 is implicated in the development of various allergic diseases including asthma. The IL-13 receptor, IL-13Rα1, is expressed on most leukocytes, except T-cells. Evidence to support IL-13Rα1 expression on mast cells is limited. Methods: We investigated: (i) IL-13Rα1 expression by human lung mast cells (HLMC); (ii) the number of IL-13Rα1 + bronchial submucosal mast cells in subjects with asthma and normal controls and (iii) the effect of IL-13 priming on HLMC expression of high-affinity IgE receptor (FcϵRI), stem cell factor receptor (CD117), histamine release, proliferation, and survival. Results: Human lung mast cell expressed IL-13Rα1 mRNA. IL-13Rα1 was highly expressed on the surface HLMC (82 ± 9%). Bronchial submucosal mast cell IL-13Rα1 expression was higher in asthmatics (86 ± 2%) than normal controls (78 ± 2%; P = 0.015). IL-13 priming for 30 min did not increase HLMC histamine release, in the presence or absence of SCF or in response to IgE/anti-IgE activation. IL-13 priming for 5 days upregulated HLMC FcϵRI expression (22% increase in fluorescent intensity; P = 0.003), increased histamine release following IgE/anti-IgE activation by 56% ( P = 0.03) and increased proliferation by 50% ( P = 0.003) without affecting cell survival or CD117 expression. The IL-13 specific neutralizing antibody CAT-354 inhibited all IL-13 mediated effects. Conclusion: Human lung mast cell express IL-13Rα1 and activation by IL-13 for 5 days increased FcϵRI expression and proliferation. Histamine release was not affected by short-term priming with IL-13, but was upregulated by priming for 5 days suggesting that this effect was mediated by the increased FcϵRI expression. These data support the view that targeting IL-13 may be beneficial in the treatment of asthma. [ABSTRACT FROM AUTHOR]

Mast cells contribute to the pathogenesis of asthma and allergy through the release of a plethora of pro-inflammatory mediators and cytokines. Their study is hampered by the difficult access to human tissue samples. Human mast cells have been cultured from CD34+ progenitors in the bone marrow of normal volunteers following iliac crest bone marrow biopsy but this is invasive. Hip bone marrow could provide a more convenient less invasive source of mast cell progenitors.To characterize mast cells cultured from human bone marrow obtained at routine hip surgery.Mononuclear cells were isolated from the bone marrow reamings of patients undergoing routine hip replacement surgery and were cultured with recombinant stem cell factor (SCF), IL-6 and IL-10. Cell surface markers were examined using flow cytometry, protease expression monitored using immunohistochemistry, histamine measured by radioenzymic assay, Ca2+ responses analysed using ratiometric Ca2+ imaging, and ion currents recorded via the patch-clamp technique.Mast cells were absent at baseline, but accounted for 65±7% of cells after 8–12 weeks of culture, equating to a mean 0.6±0.14× 106 mast cells per culture. Fifty-three percent of tryptase+ cells also contained chymase. The remaining cells comprised a population of large CD1a+ HLA-DR+ and FcℇRIα+ cells, most likely dendritic cells. All mast cells expressed CD117 and the high-affinity IgE receptorα-chain (FcℇRIα) constitutively, and developed a Ca2+ response following IgE-dependent activation. These cells exhibited 7.8±2.9% net IgE-dependent histamine release, and demonstrated a similar ion channel profile to human lung mast cells. In particular, the intermediate conductance Ca2+-activated K+ channel opened following IgE-dependent activation.Mast cells grown from human hip marrow provide a rich non-invasive source of functionally mature mast cells. In addition, this culture system may be useful for the generation of FcℇRIα+ dendritic cells. [ABSTRACT FROM AUTHOR]

Previous studies have shown evidence of airway inflammation in patients with chronic cough and have suggested that the cough may be due to release of tussive mediators and activation of afferent sensory nerve endings. We measured the concentration of various proinflammatory and tussive mediators in induced sputum supernatants from 20 patients with cough variant asthma or eosinophilic bronchitis, 20 patients with nonasthmatic chronic cough, 22 patients with idiopathic chronic cough, and 18 healthy control subjects. We measured histamine, cysteinyl-leukotrienes, prostanoids (prostaglandin D2 and prostaglandin E2), and interleukin-8 by enzyme immunoassay. The median sputum histamine concentrations were significantly higher in patients with idiopathic chronic cough (8.0 ng/ml) and cough variant asthma/eosinophilic bronchitis (10.2 ng/ml) than in normal subjects (2.6 ng/ml; 95% confidence interval of difference from idiopathic chronic cough, 0.8 to 25.8 [p = 0.009] and 95% confidence interval of difference from cough variant asthma/eosinophilic bronchitis, 1.1 to 20.1 [p = 0.01]). Median sputum prostaglandin D2 and prostaglandin E2 concentrations were significantly higher in all categories of chronic cough. Our findings support the view that there is release of inflammatory and tussive mediators in patients with chronic cough and suggest that there might be similarities in the mechanism of cough in a diverse range of conditions. [ABSTRACT FROM AUTHOR]

Focuses on the role of eosinophils as key effector cells in allergic disease. Biology of eosinophils; Immunopathology of asthma and other allergic diseases; Relationship of eosinophils and disease severity; Eosinophils and anti-inflammatory drugs in asthma.

Background Treatment decisions in asthma are based on assessments of symptoms and simple measures of lung function, which do not relate closely to underlying eosinophilic airway inflammation. We aimed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a standard management strategy.Methods We recruited 74 patients with moderate to severe asthma from hospital clinics and randomly allocated them to management either by standard British Thoracic Society asthma guidelines (BTS management group) or by normalisation of the induced sputum eosinophil count and reduction of symptoms (sputum management group). We assessed patients nine times over 12 months. The results were used to manage those in the sputum management group, but were not disclosed in the BTS group. The primary outcomes were the number of severe exacerbations and control of eosinophilic inflammation, measured by induced sputum eosinophil count. Analyses were by intention to treat.Findings The sputum eosinophil count was 63% (95% CI 24–100) lower over 12 months in the sputum management group than in the BTS management group (p=0·002). Patients in the sputum management group had significantly fewer severe asthma exacerbations than did patients in the BTS management group (35 vs 109; p=0·01) and significantly fewer patients were admitted to hospital with asthma (one vs six, p=0·047). The average daily dose of inhaled or oral corticosteroids did not differ between the two groups.Interpretation A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment. [Copyright &y& Elsevier]

Allergic mucosal inflammation is characterized by tissue infiltration with eosinophils. and associated activation of mast cells and T lymphocytes. Tumour necrosis factor (TNF) alpha/cachectin is a candidate cytokine relevant to the pathogenesis of these events through its capacity to upregulate the expression of endothelial cell adhesion molecules, mediate granulocyte chemoattraction, and activate eosinophils, mast cells and T cells. To investigate the presence and localization of TNFα in the nasal mucosa in allergic rhinitis, nasal biopsies from perennial rhinitic (n=13) and non-rhinitic volunteers (n=11) were embedded in glycol methacrylate and immunostained with a monoclonal antibody directed against TNFα, and adjacent 2µm sections stained for tryptase, CD3 and eosinophil cationic protein. This identified positive immunostaining for TNFα in the submucosa of' both the rhinitic and normal subjects (median cell counts 13 and 23 cells/mm² respectively, P=0.24) with cellular localization to mast cells but not to T-lymphocytes or eosinophils. In a subsequent study of seven atopic subjects, nasal allergen challenge produced increases in lavage levels of histamine and albumin, which was associated with significant release of TNF& as early as 2 mm post-allergen when compared with the saline control day (P=0.05). This difference was also apparent when studying the area under the curve both at 30 and 60 mm posts challenge t-test (P=0.015 and 0.02 respectively). These findings which both locate immunoreactive TNFα to nasal mast cells and identify its release following in vivo exposure to allergen. provide evidence for mast cells as an important source of this cytokine in patients with allergic rhinitis. [ABSTRACT FROM AUTHOR]

Investigates the anti-inflammatory effects of long-acting beta-agonists in asthma. Results of early studies showing that short-acting beta-agonists failed to prevent the late asthmatic response; Comparison between inhaled long-acting beta-agonists and short-acting drugs; Recommendations that long-acting beta-agonists should only be prescribed to patients already receiving inhaled corticosteroids.

Background It is increasingly recognised that sub-optimal adherence to prescribed medication regimes is common in patients with difficult asthma and may be associated with adverse clinical outcomes. Simple reliable methods of measuring non-adherence have not been developed and clinicians' judgement is often relied upon as the only assessment of adherence. We have previously shown that checking prescription data are a useful method of investigating non-adherence in this patient population. We aimed to determine how well a clinician's judgement of adherence correlated to adherence as measured by prescription issue data. Methods Adult asthma patients attending a difficult asthma clinic during July/August 2010 were included. GP retrospective prescription issue data and hospital dispensing data for asthma medications, patient demographics and clinical outcome data were collated. The medication adherence score was calculated as the number of doses issued/number of doses prescribed 3 100 for a mean duration of 12 months. Clinicians with an expertise in the management of difficult asthma were asked to stratify each patient according to their perceived adherence, classified as adherent (=80% adherence score; partially adherent 50%-79%; non-adherent <50%). Agreement between clinician judgement and adherence score was analysed using a weighted κ coefficient. Logistic regression was performed to determine whether any clinical features could predict better agreement. Results Data from 63 consecutive patients was included in the analysis (41 female, median (range) age 51.2(61.3)). Clinicians suspected non-adherence in 11/63 (17.4%) of patients, partial non-adherence in 23/63 (36.5 %) and good adherence in 29/63 (46%). Agreement between clinician assessment and prescription issue data were seen in only 23/63 (36.5%) of cases and overall agreement using a weighted κ coefficient was poor (weighted agreement 63.5%, expected agreement 58.8%, κ 0.11, SE 0.1, z=1.16, p=0.12). There was no relationship between patients' age, gender, Juniper asthma control score, prescribed inhaled corticosteroid dose or FEV1 percent predicted and the chances of agreement or disagreement between the two methods. Conclusions Clinical judgement alone appears to be a poor predictor of adherence to medication in patients with difficult asthma. The assessment of non-adherence requires objective measurements. Prescription issue data are one such measurement; but further work is required. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a common progressive interstitial lung disease and current treatments are ineffective. The Ca2+-activated K+ channel KCa3.1 modulates the activity of several structural and inflammatory cells which play important roles in model diseases characterised by tissue remodelling and fibrosis. We hypothesise that KCa3.1-dependent cell processes are a common denominator in IPF. We have therefore examined KCa3.1 expression and function in human myofibroblasts derived from patients with IPF and non-fibrotic controls (NFC). IPF tissue was obtained from diagnostic lung biopsies, and NFC tissue from healthy lung removed at surgery for carcinoma. Myofibroblasts grown in vitro were characterised by Western blot, immunofluorescence and RT-PCR to determine KCa3.1 channel expression. Patch clamp electrophysiology was used to demonstrate functional KCa3.1 channels. Wound healing and proliferation assays were performed using two specific KCa3.1 blockers (TRAM-34, ICA-17043 [Senicapoc]). Both NFC and IPF myofibroblasts expressed KCa3.1 channel mRNA and protein. Using the KCa3.1 channel opener 1-EBIO, KCa3.1 ion currents were elicited in 59% of NFC and 77% of IPF myofibroblasts tested (p=0.0411). These currents were blocked by TRAM-34 (200 nM). The 1-EBIO-induced currents were significantly larger in IPF cells compared to NFC cells (p=0.0124). Basic fibroblast growth factor (bFGF) (10 ng/ml) significantly increased the frequency of KCa3.1 currents across groups (p=0.0046). Similarly bFGF stimulation significantly increased myofibroblast wound healing (p=0.002). Following KCa3.1 blockade bFGF-stimulated wound healing was attenuated dose-dependently. Thus at the 48 h time-point wound healing was reduced by 22.2611.1% and 27.369.5% for TRAM-34, 20 nM and 200 nM respectively (p=0.0467 across groups), and reduced by 16.968.1% and 24.466.6% for ICA-17043, 10 nM and 100 nM respectively (p=0.0076 across groups). KCa3.1 blockade had no effect on myofibroblast proliferation. We show for the first time that human lung myofibroblasts express the KCa3.1 K+ channel. KCa3.1 currents are larger and more frequently present in cells from patients with IPF, and functional channel expression is increased by pro-fibrotic growth factors. KCa3.1 inhibition attenuates bFGF stimulated myofibroblast wound healing. These findings raise the possibility that blocking the KCa3.1 channel will inhibit pathological myofibroblast function in IPF, and thus offer a novel approach to IPF therapy. [ABSTRACT FROM AUTHOR]