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Abstract Background Patients with chronic asthma have thicker intrapulmonary airways measured on high resolution computed tomography (HRCT). We determined whether the presence of lower airway bacteria was associated with increased airway wall thickness. Methods In 56 patients with stable severe asthma, sputum specimens obtained either spontaneously or after induction with hypertonic saline were cultured for bacteria and thoracic HRCT scans obtained. Wall thickness (WT) and area (WA) expressed as a ratio of airway diameter (D) and total area, respectively, were measured at five levels. Results Positive bacterial cultures were obtained in 29 patients, with H. influenzae, P. aeruginosa and S. aureus being the commonest strains. Logistic regression analysis showed that this was associated with the duration of asthma and the exacerbations during the past year. In airways > 2 mm, there was no significant difference in WA (67.5 ± 5.4 vs 66.4 ± 5.4) and WT/D (21.6 ± 2.7 vs 21.3 ± 2.4) between the culture negative versus positive groups. Similarly, in airways (≤ 2 mm), there were no significant differences in these parameters. The ratio of √wall area to Pi was negatively correlated with FEV1% predicted (p < 0.05). Conclusions Bacterial colonization of the lower airways is common in patients with chronic severe asthma and is linked to the duration of asthma and having had exacerbations in the past year, but not with an increase in airway wall thickness.

Background: Airway wall remodelling and inflammation are features of chronic asthma. Transforming growth factor beta (TGF-beta) has been implicated in these processes.Aim: To determine the effect of allergen challenge on airway inflammation and remodelling and whether TGF-beta isoforms and the Smad signalling pathways are involved.Methods: Thirteen patients with atopic asthma underwent inhalational challenge with 0.9% saline, followed by allergen 3-4 weeks later. After both challenges, fibreoptic bronchoscopy was undertaken to obtain bronchial biopsies and tissue samples were processed for immunohistochemistry and examined by microscopy.Results: Forced expiratory volume in 1 s (FEV(1)) fell after allergen challenge (mean (SE) -28.1 (0.9)% at 30 min with a late response at 7 hours (-23.0 (1.2)%). Allergen challenge caused an increase in neutrophils and eosinophils in the bronchial mucosa compared with saline. Sub-basement membrane (SBM) thickness did not change after allergen, but tenascin deposition in SBM was increased. Intranuclear (activated) Smad 2/3 and Smad 4 detected by immunohistochemistry were increased after allergen challenge in epithelial and subepithelial cells of bronchial biopsies. No inhibitory Smad (Smad 7) protein was detected. TGF-beta isoforms 1, 2 and 3 were expressed predominantly in bronchial epithelium after saline and allergen challenges, but only TGF-beta(2) expression was increased after allergen. Double immunostaining showed an increase in TGF-beta(2) positive eosinophils and neutrophils but not in TGF-beta(1) positive eosinophils and neutrophils after allergen challenge.Conclusions: TGF-beta(2) may contribute to the remodelling changes in allergic asthma following single allergen exposure. [ABSTRACT FROM AUTHOR]

Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild-moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort.The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs.37% of asthmatics (45% nonsmoking severe asthma, n=49; 33% of smoking or ex-smoking severe asthma, n=18; and 28% mild-moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher exhaled nitric oxide fraction ( F eNO ) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. F eNO (≥30 ppb) and blood eosinophils (≥300 cells·µL -1 ) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression.T2-high severe asthma can be predicted to some extent from raised levels of F eNO , blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high., Competing Interests: Conflict of interest: S. Pavlidis has nothing to disclose. Conflict of interest: K. Takahashi reports personal fees from Asahi General Hospital, during the conduct of the study. Conflict of interest: F. Ng Kee Kwong has nothing to disclose. Conflict of interest: J. Xie has nothing to disclose. Conflict of interest: U. Hoda has nothing to disclose. Conflict of interest: K. Sun has nothing to disclose. Conflict of interest: V. Elyasigomari has nothing to disclose. Conflict of interest: P. Agapow has nothing to disclose. Conflict of interest: M. Loza is employed by Janssen R&D and owns stock in parent company Johnson & Johnson, outside the submitted work. Conflict of interest: F. Baribaud reports being an employee of Janssen R&D and being a share holder of Johnson & Johnson. Conflict of interest: P. Chanez has provided consultancy services for Boehringer Ingelheim, Johnson & Johnson, GlaxoSmithKline, Merck Sharp & Dohme, AstraZeneca, Novartis, Teva, Chiesi, Sanofi and SNCF; served on advisory boards for Almirall, Boehringer Ingelheim, Johnson & Johnson, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi and Sanofi; received lecture fees from Boehringer Ingelheim, Centocor, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Boston Scientific and ALK; and received industry-sponsored grants from Roche, Boston Scientific, Boehringer Ingelheim, Centocor, GlaxoSmithKline, AstraZeneca, ALK, Novartis, Teva, ABscience and Chiesi. Conflict of interest: S.J. Fowler reports grants from IMI, during the conduct of the study; personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim and Novartis, outside the submitted work. Conflict of interest: D.E. Shaw reports personal fees for advisory board work from GSK, AZ, Teva and Boehringer Ingelheim, outside the submitted work. Conflict of interest: L.J. Fleming reports personal fees for advisory board work from Novartis, Vectura and Boehringer Ingelheim, grants from Asthma UK and BLF, and personal fees for speaking engagements from Novartis, outside the submitted work. Conflict of interest: P.H. Howarth reports grants from IMI, during the conduct of the study; part-time employment by GSK as Global Medical Expert, outside the submitted work. Conflict of interest: A.R. Sousa has nothing to disclose. Conflict of interest: J. Corfield has nothing to disclose. Conflict of interest: C. Auffray reports grants (U-BIOPRED Consortium IMI number 115010) from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: B. De Meulder reports grants (U-BIOPRED Consortium IMI number 115010) from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: R. Knowles is an employee of Knowles Consulting Ltd, outside the submitted work; and is a former employee (to 2011) and current shareholder in GlaxoSmithKline Ltd, and drug discovery consultant for Knowles Consulting Ltd, Peptinnovate Ltd and Imperial College London. Conflict of interest: P.J. Sterk reports grants from Innovative Medicines Initiative (IMI), during the conduct of the study. Conflict of interest: Y. Guo has nothing to disclose. Conflict of interest: I.M. Adcock reports personal fees for advisory board work from GSK, A-Z, Novartis, Boehringer Ingelheim and Vectura, grants from Pfizer, GSK, MRC, EU, BI and IMI, and personal fees for speaking from AZ and BI, outside the submitted work. Conflict of interest: R. Djukanovic reports personal fees for lectures at company sponsored symposia and consulting on advisory boards from TEVA, grants and personal fees for lectures at company sponsored symposia and consulting on advisory boards from Novartis, and personal fees for consultancy from and hold shares in Synairgen, outside the submitted work. Conflict of interest: K.F. Chung reports grants and personal fees for advisory board work from GlaxoSmithKline, personal fees for advisory board work and speaking from AstraZeneca and Novartis, grants and personal fees for advisory board work and speaking from Merck, and personal fees for advisory board work from Boehringer Ingelheim, TEVA and Menlo Therapeutics, outside the submitted work., (Copyright ©ERS 2019.)