Background: Cilomilast, a phosphodiesterase-4 (PDE4) selective inhibitor, has anti-inflammatory effects in vitro and in vivo and reduces COPD exacerbations. We tested the hypothesis that cilomilast inhibits virus-induced airway epithelial intercellular adhesion molecule-1 (ICAM-1) expression and inflammatory cytokine/chemoattractants, IL-6, CXCL8, and CCL5 production in vitro. Methods: BEAS-2B bronchial epithelial cells were incubated with 0.5–2 MOI (multiplicity of infection–infectious units/cell) of rhinovirus 16 (RV16). Then, 0.1–10 μM cilomilast or 10 nM dexamethasone, as inhibition control, were added pre- or post-1 h RV16 infection. Supernatant and cells were sampled at 8, 24, 48, and 72 h after infection. Cell surface ICAM-1 expression was detected by immunogold labelling and visualised by high-resolution scanning electron microscopy (HR-SEM), while IL-6, CXCL8, and CCL5 protein release and mRNA expression were measured using an ELISA and RT-PCR. Results: Cilomilast significantly decreased RV16-induced ICAM-1 expression to approximately 45% (p < 0.01). CXCL8 protein/mRNA production was reduced by about 41% (p < 0.05), whereas IL-6 protein/mRNA production was increased to between 41–81% (p < 0.001). There was a trend to reduction by cilomilast of RV16-induced CCL5. Conclusions: Cilomilast has differential effects on RV16-induced ICAM-1 and interleukins, inhibiting virus-induced ICAM-1 expression and CXCL8 while increasing IL-6 production. These in vitro effects may help to explain the beneficial actions of this PDE4 inhibitor in vivo.

The SARS-CoV-2 pandemic has triggered a transition towards telemedicine for delivering outpatient care. The evidence base for telemedicine is heterogeneous and its efficacy remains debated. We, therefore, designed a mixed-methods semi-structured survey to evaluate patients' and clinicians' experiences of outpatient telemedicine clinics during the pandemic. One-hundred and eighty-eight patients and 69 clinicians from two hospitals in Gloucestershire completed the survey. The quantitative results for patients rated in-person and telemedicine appointments similarly in all areas except communication (p<0.001) and overall quality (p=0.004), both in favour of in-person consultations, while clinicians rated all aspects of telemedicine appointments as inferior, with the exception of convenience (p=0.643). Qualitative analysis highlighted themes of communication and relationship building difficulties, confidentiality concerns, loss of visual inspection as a clinical tool and debatable time efficiency associated with telemedicine. Significant adaptation of current telemedicine services is required before it will be integrated into current practice.

Background: The role of ethnicity in severe asthma remains unclear although profound differences in outcomes and biologic phenotypes are evident when comparing countries globally. Aims: To assess the effects of ethnicity on disease control, exacerbations, biological phenotype and treatment in UK severe asthma. Methods: Multivariate comparison of demographics, asthma control, phenotypic presentation, medications and healthcare utilisation between White and Ethnic Minority Groups (EMGs) patients in UK primary (Optimum Patient Care Research Database [OPCRD]; n=13,936) and specialist (UK Severe Asthma Registry [UKSAR]; n=3,402) care. Results: EMG patients had higher levels of uncontrolled disease when measured using the asthma control questionnaire in the UKSAR (OR: 1.47; 95% CI: 1.12, 1.93) and the Royal College of Physicians 3 Questions in the OPCRD (OR: 1.82; 95% CI: 1.27, 2.60). Although exacerbation rates were similar, EMG patients were more likely to have attended ED (OR: 1.55; 95% CI: 1.26, 1.92) or been admitted to hospital (OR: 1.31; 95% CI: 1.07, 1.59) due to their asthma the year prior to specialist referral. Atopic disease was more common in EMG severe asthma in both UKSAR (OR: 1.32; 95% CI: 1.07, 1.63) and OPCRD (OR: 1.67; 95% CI: 1.26, 2.21). EMG patients were less likely to be using maintenance oral corticosteroids at specialist referral (OR: 0.75; [95% CI: 0.61, 0.92]) and were less commonly adherent with their maintenance medications in both UKSAR (OR: 0.65; 95% CI: 0.48, 0.87) and OPCRD (OR: 0.73; 95% CI: 0.60, 0.88). Conclusions: EMG patients had worse asthma control and increased emergency healthcare utilisation, with higher rates of atopy and distinct medication usage patterns.

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Background: Respiratory infections with rhinoviruses (RV) are strongly associated with development and exacerbations of asthma, and they pose an additional health risk for subjects with allergy. Objective: How RV infections and chronic allergic diseases are linked and what role RV plays in the breaking of tolerance in regulatory T (Treg) cells is unknown. Therefore, this study aims to investigate the effects of RV on Treg cells. Methods: Treg cells were isolated from subjects with asthma and controls after experimental infection with the RV-A16 (RV16) and analyzed with next-generation sequencing. Additionally, suppression assays, quantitative PCR assays, and protein quantifications were performed with Treg cells after in vitro RV16 infection. Results: RV16 induced a strong antiviral response in Treg cells from subjects with asthma and controls, including the upregulation of IFI44L, MX1, ISG15, IRF7, and STAT1. In subjects with asthma, the inflammatory response was exaggerated and showed a dysregulated immune response compared with that in the controls. Furthermore, subjects with asthma failed to upregulate several immunosuppressive molecules such as CTLA4 and CD69, and they upregulated the inflammasome-related genes PYCARD and AIM2. Additionally, RV16 reduced the suppressive capacity of Treg cells from healthy subjects and subjects with asthma in vitro and increased TH2 cell-type cytokine production. Conclusions: Treg cells from healthy subjects and subjects with asthma displayed an antiviral response after RV infection and showed reduced suppressive capacity. These data suggest that Treg cell function might be altered or impaired during RV infections, which might play an important role in the association between RV and the development of asthma and asthma exacerbations.

BACKGROUND:Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients.METHODS:We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA-sequencing. Rhinovirus-derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B-cell differentiation in response rhinovirus stimulation. Protein expression of pro-inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay.RESULTS:B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN-alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro. B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co-stimulation with rhinovirus and IFN-alpha upregulated pro-inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression.CONCLUSION:These findings add to the understanding of systemic effects of rhinovirus infections on B-cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses.

BACKGROUND: Understanding the effects of ethnicity in severe asthma is important for optimal personalized patient care. OBJECTIVE: To assess ethnic differences in disease control, exacerbations, biological phenotype, and treatment in severe asthma in the United Kingdom. METHODS: We compared demographics, type 2 biomarkers, lung function, asthma control, medications, and health care use between White and underrepresented ethnic group patients in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD). RESULTS: A total of 3637 patients (665 from the underrepresented ethnic group) were included from UKSAR and 10,549 (577 from the underrepresented ethnic group) from OPCRD. Patients in the underrepresented ethnic group had higher levels of uncontrolled disease when measurements were made using the asthma control questionnaire in UKSAR (odds ratio [OR] = 1.47; 95% confidence interval [CI], 1.12-1.93) and the Royal College of Physicians 3 Questions in OPCRD (OR = 1.82; 95% CI, 1.27-2.60). Although exacerbation rates were similar, patients in the underrepresented ethnic group were more likely to have recently attended the emergency department (OR = 1.55; 95% CI, 1.26-1.92) or to have been hospitalized (OR = 1.31; 95% CI, 1.07-1.59) owing to asthma. Inflammatory biomarkers were consistently higher in the underrepresented ethnic group, including blood eosinophils in OPCRD (ratio = 1.12; 95% CI, 1.05-1.20) and in UKSAR blood eosinophils (ratio = 1.16; 95% CI, 1.06-1.27), FeNO (ratio = 1.14; 95% CI, 1.04-1.26), and IgE (ratio = 1.70; 95% CI, 1.47-1.97). Patients in the underrepresented ethnic group were more likely to be atopic in the UKSAR (OR = 1.32; 95% CI, 1.07-1.63) and OPCRD (OR = 1.67; 95% CI, 1.26-2.21), and less likely to be using maintenance oral corticosteroids at referral (OR = 0.75; 95% CI, 0.61-0.92). CONCLUSIONS: Severe asthma patients from underrepresented ethnic groups presented with a higher disease burden and were more likely to attend the emergency department. They had a distinct phenotypic presentation and differences in medicine use, with higher levels of type 2 biomarkers. (C) 2021 American Academy of Allergy, Asthma & Immunology

BACKGROUND:Respiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity.OBJECTIVES:We sought to determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16-induced COPD exacerbations and its relationship to disease severity.METHODS:Bronchial mucosal inflammatory cell phenotypes were determined at preinfection baseline and following experimental RV infection in 17 Global Initiative for Chronic Obstructive Lung Disease stage II subjects with COPD and as controls 20 smokers and 11 nonsmokers with normal lung function. No subject had a history of asthma/allergic rhinitis: all had negative results for aeroallergen skin prick tests.RESULTS:RV infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T lymphocytes in patients with COPD and nonsmokers. Monocytes/macrophages, CD4+ T lymphocytes, and CD20+ B lymphocytes were increased in all subjects. At baseline, compared with nonsmokers, subjects with COPD and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T lymphocytes but fewer numbers of CD4+ T lymphocytes and CD20+ B lymphocytes. The virus-induced inflammatory cells in patients with COPD were positively associated with virus load, illness severity, and reductions in lung function.CONCLUSIONS:Experimental RV infection induces bronchial mucosal eosinophilia and neutrophilia only in patients with COPD and monocytes/macrophages and lymphocytes in both patients with COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load and illness severity. Antiviral/anti-inflammatory therapies could attenuate bronchial inflammation and ameliorate virus-induced COPD exacerbations.

BACKGROUND:The UK Severe Asthma Registry (UKSAR) is the world's largest national severe asthma registry collecting standardised data on referrals to UK specialist services. Novel biologic therapies have transformed the management of type 2(T2)-high severe asthma but have highlighted unmet need in patients with persisting symptoms despite suppression of T2-cytokine pathways with corticosteroids.METHODS:Demographic, clinical and treatments characteristics for patients meeting European Respiratory Society / American Thoracic Society severe asthma criteria were examined for 2225 patients attending 15 specialist severe asthma centres. We assessed differences in biomarker low patients (fractional exhaled nitric oxide (FeNO) <25 ppb, blood eosinophils <150/μL) compared with a biomarker high population (FeNO ≥25 ppb, blood eosinophils ≥150/µL).RESULTS:Age (mean 49.6 (14.3) y), age of asthma onset (24.2 (19.1) y) and female predominance (62.4%) were consistent with prior severe asthma cohorts. Poor symptom control (Asthma Control Questionnaire-6: 2.9 (1.4)) with high exacerbation rate (4 (IQR: 2, 7)) were common despite high-dose treatment (51.7% on maintenance oral corticosteroids (mOCS)). 68.9% were prescribed biologic therapies including mepolizumab (50.3%), benralizumab (26.1%) and omalizumab (22.6%). T2-low patients had higher body mass index (32.1 vs 30.2, p<0.001), depression/anxiety prevalence (12.3% vs 7.6%, p=0.04) and mOCS use (57.9% vs 42.1%, p<0.001). Many T2-low asthmatics had evidence of a historically elevated blood eosinophil count (0.35 (0.13, 0.60)).CONCLUSIONS:The UKSAR describes the characteristics of a large cohort of asthmatics referred to UK specialist severe asthma services. It offers the prospect of providing novel insights across a range of research areas and highlights substantial unmet need with poor asthma control, impaired lung function and high exacerbation rates. T2-high phenotypes predominate with significant differences apparent from T2-low patients. However, T2-low patients frequently have prior blood eosinophilia consistent with possible excessive corticosteroid exposure.

BACKGROUND:The innate immune system senses viral infection through pattern recognition receptors (PRRs), leading to type I interferon production. The role of type I interferon and PPRs in rhinovirus-induced asthma exacerbations in vivo are uncertain. OBJECTIVES:We sought to compare bronchial mucosal type I interferon and PRR expression at baseline and after rhinovirus infection in atopic asthmatic patients and control subjects. METHODS:Immunohistochemistry was used to detect expression of IFN-α, IFN-β, and the PRRs: Toll-like receptor 3, melanoma differentiation-associated gene 5, and retinoic acid-inducible protein I in bronchial biopsy specimens from 10 atopic asthmatic patients and 15 nonasthmatic nonatopic control subjects at baseline and on day 4 and 6 weeks after rhinovirus infection. RESULTS:We observed IFN-α/β deficiency in the bronchial epithelium at 3 time points in asthmatic patients in vivo. Lower epithelial IFN-α/β expression was related to greater viral load, worse airway symptoms, airway hyperresponsiveness, and reductions in lung function during rhinovirus infection. We found lower frequencies of bronchial subepithelial monocytes/macrophages expressing IFN-α/β in asthmatic patients during infection. Interferon deficiency at baseline was not accompanied by deficient PRR expression in asthmatic patients. Both epithelial and subepithelial PRR expression were induced during rhinovirus infection. Rhinovirus infection-increased numbers of subepithelial interferon/PRR-expressing inflammatory cells were related to greater viral load, airway hyperresponsiveness, and reductions in lung function. CONCLUSIONS:Bronchial epithelial IFN-α/β expression and numbers of subepithelial IFN-α/β-expressing monocytes/macrophages during infection were both deficient in asthmatic patients. Lower epithelial IFN-α/β expression was associated with adverse clinical outcomes after rhinovirus infection in vivo. Increases in numbers of subepithelial cells expressing interferon/PRRs during infection were also related to greater viral load/illness severity.

Background Severe asthma service specification (NHS England Service Specification No. 170002/S) advocates the development of regional severe asthma networks to improve patient outcomes and manage delivery of expensive treatments. The Birmingham Regional Severe Asthma Service (BRSAS) established a hub and spoke model including nine spokes. BRSAS orchestrates care within the region and conducts regular regional multidisciplinary meetings (MDT) to formulate management plans. Aim To explore the clinical utility of the severe asthma network model of treatment delivery. Methods All cases discussed at the BRSAS regional MDTs between July 2014 and March 2018 were reviewed. Cases were submitted online via a standardised severe/difficult to treat asthma proforma and data entered into a central database by an administrator. Questions for MDT included proposals for specialised treatment including biological therapy and bronchial thermoplasty (BT) and complex clinical issues managed at the respective sites were recorded. Results A total of 23 MDTs were conducted over this study period that included 152 case submissions and (147 patients, mean age 46.6±14.1 years, 86 (57%) females, (mean 6.6 (6.39) per MDT). The main MDT questions were consideration for biological therapy (97/152 (63.8%), Mepolizumab 49 (50.5%), Omalizumab 30 (30.9%) or either 16 (16.5%), bronchial thermoplasty 5 (3.29%). Other questions were for confirmation of diagnosis (n=29), and use of macrolides (n=2), anti-fungal (n=2) and corticosteroid sparing agents (n=2). 6 (12.2%) cases were not approved for Mepolizumab and 7 (23.3%) for Omalizumab. Out of the 17 who were eligible for Mepolizumab and Omalizumab, 12 (70.6%) were approved for Omalizumab. 2/5 were accepted for BT. The most common reasons for non-approval of biological treatment were absence of eosinophilia (Mepolizumab), lack of allergy to a perennial allergen (Omalizumab) and requirement to treat coexisting comorbidities. Conclusion Our regional severe asthma MDT service has enabled provision of effective use of expensive therapies and strengthened collaborations among our partners enabling delivery of more standardised care closer to the patient's home.

Background: Fibre-optic bronchoscopy (FOB) is a research tool in asthma and COPD with a good safety record in stable patients. There is no data regarding adverse events for FOB in patients with asthma/COPD exacerbations. Aims: To evaluate the safety of FOB in subjects participating in experimental rhinovirus infection studies. Methods: We reviewed the records of these subjects from a single centre since 2000. Subjects had FOB at baseline and convalescence (stable) and during the virus-induced exacerbation (infection) with biopsies, brushings and BAL. Results: The clinical characteristics of the subjects are in Table 1 . There were no adverse events in the asthma studies and 3 in the COPD studies. Two subjects developed lower respiratory tract infections requiring antibiotics. In 1 subject (non-smoker) this occurred at the infection FOB and the subject was withdrawn. In the other subject (COPD) this occurred at the baseline FOB and he continued in the study and had 2 other uneventful FOB. One subject (smoker) had FOB terminated due to hypoxia. Conclusions: The incidence of adverse events in research FOB in asthma and COPD exacerbations is low.

Background The nature of bronchial mucosal inflammation and its physiologic and clinical significance in rhinovirus-induced asthma exacerbations is unclear. We investigated bronchial mucosal inflammatory response and its association with physiologic and clinical outcomes in an experimental model of rhinovirus-induced asthma exacerbations. Methods We used immunohistochemistry methods to detect phenotypes of inflammatory cells infiltrating the bronchial mucosa before and after experimental rhinovirus infection in 10 subjects with asthma and 15 normal subjects. Results Compared with baseline, rhinovirus infection significantly increased the number of epithelial (P = .005) and subepithelial (P = .017) neutrophils in subjects with asthma only and subepithelial CD68+ macrophages in both subjects with asthma (P = .009) and normal subjects (P = .018) but more so in those with asthma (P = .021). Numbers of CD45+, CD68+, and CD20+ cells; neutrophils; and eosinophils at day 4 postinfection were positively associated with virus load (r = 0.50-0.72, P = .016-0.03). At acute infection in subjects with asthma, CD4+ cells correlated with chest symptom scores (r = 0.69, P = .029), the fall in the 10% fall in FEV1 (PC10) correlated with neutrophils (r = −0.89, P = .029), the PC10 correlated inversely with CD4+ (r = −0.67, P = .023) and CD8+ cells (r = −0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = −0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = −0.72, P = .03), whereas higher subepithelial mast cell counts were significantly associated with a lower maximum percent fall in peak expiratory flow (r = 0.8, P = .024). Conclusions In subjects with asthma, rhinovirus infection induces bronchial mucosal neutrophilia and more severe monocyte/macrophage infiltration than in normal subjects. Airway neutrophils, eosinophils, and T and B lymphocytes during infection are related to virus load and physiologic and clinical severity, whereas mast cells are related to greater lung function.

BACKGROUND:COPD is associated with increased numbers of T cells in the lungs, particularly CD8+ T cells. The mechanisms of increased T cells are unknown but may be related to repeated virus infections in COPD patients. We analysed lymphocyte subsets in blood and bronchoalveolar lavage in smokers and COPD subjects during experimental rhinovirus infections.METHODS:Lymphocytes were isolated from blood and bronchoalveolar lavage from COPD subjects and non-obstructed smokers prior to, and following experimental rhinovirus infection. Lymphocyte surface markers and intracellular cytokines were analysed using flow cytometry.RESULTS:Following rhinovirus infection CD4+ and CD8+ T cell numbers in the COPD subjects were significantly reduced in blood and CD3+ and CD8+ T cells increased in bronchoalveolar lavage compared to baseline. T cells did not increase in BAL in the control subjects. CD3+ T cells correlated with virus load.CONCLUSIONS:Following rhinovirus infection T cells move from the circulation to the lung. Repeated virus infections may contribute to T cell accumulation in COPD patients.

BACKGROUNDSurface major histocompatibility complex class I-related chain (MIC) A and B molecules are increased by IL-15 and have a role in the activation of natural killer group 2 member D-positive natural killer and CD8 T cells. MICA and MICB also exist in soluble forms (sMICA and sMICB). Rhinoviruses (RVs) are the major cause of asthma exacerbations, and IL-15 levels are decreased in the airways of subjects with asthma. The role of MIC molecules in immune responses in the lung has not been studied. Here, we determine the relationship between MICA and MICB and RV infection in vitro in respiratory epithelial cells and in vivo in healthy subjects and subjects with asthma.METHODSSurface MICA and MICB, as well as sMICA and sMICB, in respiratory epithelial cells were measured in vitro in response to RV infection and exposure to IL-15. Levels of sMICA and sMICB in serum, sputum, and BAL were measured and correlated with blood and bronchoalveolar immune cells in healthy subjects and subjects with asthma before and during RV infection.RESULTSRV increased MICA and MICB in vitro in epithelial cells. Exogenous IL-15 upregulated sMICB levels in RV-infected epithelial cells. Levels of sMICB molecules in serum were increased in healthy subjects compared with subjects with stable asthma. Following RV infection, airway levels of sMIC are upregulated, and there are positive correlations between sputum MICB levels and the percentage of bronchoalveolar natural killer cells in healthy subjects but not subjects with asthma.CONCLUSIONSRV infection induces MIC molecules in respiratory epithelial cells in vitro and in vivo. Induction of MICB molecules is impaired in subjects with asthma, suggesting these molecules may have a role in the antiviral immune response to RV infections.

Background COPD exacerbations are associated with neutrophilic airway inflammation. Adhesion molecules on the surface of neutrophils may play a key role in their movement from blood to the airways. We analysed adhesion molecule expression on blood and sputum neutrophils from COPD subjects and non-obstructed smokers during experimental rhinovirus infections. Methods Blood and sputum were collected from 9 COPD subjects and 10 smoking and age-matched control subjects at baseline, and neutrophil expression of the adhesion molecules and activation markers measured using flow cytometry. The markers examined were CD62L and CD162 (mediating initial steps of neutrophil rolling and capture), CD11a and CD11b (required for firm neutrophil adhesion), CD31 and CD54 (involved in neutrophil transmigration through the endothelial monolayer) and CD63 and CD66b (neutrophil activation markers). Subjects were then experimentally infected with rhinovirus-16 and repeat samples collected for neutrophil analysis at post-infection time points. Results At baseline there were no differences in adhesion molecule expression between the COPD and non-COPD subjects. Expression of CD11a, CD31, CD62L and CD162 was reduced on sputum neutrophils compared to blood neutrophils. Following rhinovirus infection expression of CD11a expression on blood neutrophils was significantly reduced in both subject groups. CD11b, CD62L and CD162 expression was significantly reduced only in the COPD subjects. Blood neutrophil CD11b expression correlated inversely with inflammatory markers and symptom scores in COPD subjects. Conclusion Following rhinovirus infection neutrophils with higher surface expression of adhesion molecules are likely preferentially recruited to the lungs. CD11b may be a key molecule involved in neutrophil trafficking in COPD exacerbations.

Introduction: Pulmonary Hypertension (PH) is defined as raised Pulmonary Arterial Systolic Pressure ≥25mmHg at rest on Right Heart Catheterisation (ESC/ERS, 2009). Chronic Thromoboembolic Pulmonary Hypertension (CTEPH) is a complication of pulmonary embolism (PE), with a reported cumulative incidence of 3.1% at 1 year (Pengo et al, 2004). Patients with evidence of PH or Right Ventricular Dysfunction (RVD) during admission should undergo echocardiography after discharge (usually after 3-6 months) to establish PH resolution (ESC/ERS, 2009) Objective: To assess if radiological evidence of RVD affects follow-up after PE. Methods: Retrospective analysis of all patients diagnosed with PE on Computed Tomography Pulmonary Angiography (CTPA) in 2010 in a single Trust. CTPA reports were stratified according to presence or absence of RVD and echocardiography reports reviewed for signs of PH. Results: 19.3%(329/1702) of CTPA scans revealed PE: Central (28.6%); Submassive (28.0%); Peripheral (44.4%). Figure 1 summarises the main findings. Conclusions: RV strain is often not commented on in CTPA reports. Despite low numbers in some groups, it seems radiological evidence of RVD may be useful in deciding which patients need echocardiography after acute PE.

The importance of NF‐κB activation and deficient anti‐viral interferon induction in the pathogenesis of rhinovirus‐induced asthma exacerbations is poorly understood. We provide the first in vivo evidence in man and mouse that rhinovirus infection enhanced bronchial epithelial cell NF‐κB p65 nuclear expression, NF‐κB p65 DNA binding in lung tissue and NF‐κB‐regulated airway inflammation. In vitro inhibition of NF‐κB reduced rhinovirus‐induced pro‐inflammatory cytokines but did not affect type I/III interferon induction. Rhinovirus‐infected p65‐deficient mice exhibited reduced neutrophilic inflammation, yet interferon induction, antiviral responses and virus loads were unaffected, indicating that NF‐κB p65 is required for pro‐inflammatory responses, but redundant in interferon induction by rhinoviruses in vivo. Conversely, IFNAR1−/− mice exhibited enhanced neutrophilic inflammation with impaired antiviral immunity and increased rhinovirus replication, demonstrating that interferon signalling was critical to antiviral immunity. We thus provide new mechanistic insights into rhinovirus infection and demonstrate the therapeutic potential of targeting NF‐κB p65 (to suppress inflammation but preserve anti‐viral immunity) and type I IFN signalling (to enhance deficient anti‐viral immunity) to treat rhinovirus‐induced exacerbations of airway diseases. See accompanying article http://dx.doi.org/10.1002/emmm.201202032 The authors show that targeting NF‐κB p65 may be a reasonable therapeutic strategy for asthma exacerbations, specifically addressing inflammation without compromising beneficial anti‐viral immunity.