'We need to start building up what's called herd immunity': Scientific dissensus and public broadcasting in the Covid-19 pandemic.

This article uses content and thematic analyses to examine how UK public service broadcasting (PSB) reported on the Covid-19 pandemic prior to the first lockdown on March 23, 2020. This was a period when the British government's response to the pandemic was being heavily criticised by the World Health Organisation and other parts of the scientific community. This paper finds that in PSB these criticisms were muted and partially given. Instead, broadcasting explained in detail-and directly endorsed-government policy, including the 'herd immunity' approach. Most coverage of international responses focused on the United States and Europe with little attention paid to states that had successfully suppressed the virus. When such states were featured their public health measures were not explained nor compared to the UK's strategy with the consequence that PSB was unable to alert the public to measures that could have contained the virus and saved lives. These patterns in PSB coverage can be explained by the close links between key lobby journalists and the government's communication machine as well as the broader political and social contexts surrounding broadcasting at the onset of the pandemic.

Stability of Phosphatidylethanol in Dry Blood Spot Cards.

BACKGROUND: The analysis of phosphatidylethanol, a promising direct ethanol metabolite, in dry blood spots (PEth-DBS) is advantageous due to ease of storage, transportation and minimal invasiveness of capillary blood collection. One potential application of PEth-DBS is to confirm prenatal alcohol exposure in newborns suspected of FASD; however, stability of PEth-DBS is largely unknown. METHODS: Phlebotomized samples from 31 adults with a history of alcoholism, admitted to the University of New Mexico Emergency Department, were analyzed for blood alcohol content and pipetted onto DBS cards (13 spots per patient). The first spot was analyzed within 2 weeks of collection for a baseline PEth; the remaining 12 spots were allocated into three temperature conditions (room temperature, 4°C, -80°C) for the repeated measures analysis. In addition, 5 newborn DBS samples with a baseline PEth>LOD were obtained from a prospective cohort at UNM and re-analyzed at 4 months after storage at -80°C. A mixed linear model was fitted to examine the effects of temperature, time and temperature-time interaction on PEth degradation over the first 9 months. RESULTS: The baseline PEth levels were 592.8 ± 86.7 ng/ml and 18.3 ± 4.8 ng/ml in adult and newborn samples, respectively. All DBS samples remained positive in successive samples in all temperature conditions. Results of mixed linear model demonstrated a significant effect of temperature (P < 0.001) on PEth degradation over 9 months. CONCLUSIONS: PEth-DBS appears to be relatively stable, especially when stored at lower temperatures. These initial results are encouraging and highlight the PEth-DBS potential in retrospective assessment of alcohol exposure.

A cross-sectional study of patterns of airway dysfunction, symptoms and morbidity in primary care asthma.

BACKGROUND: Most patients with asthma are managed exclusively in primary care. Little is known about the patterns of airway dysfunction in these patients and how these relate to other aspects of the disease. AIMS: We set out to assess this in a cross-sectional study of 262 patients. METHODS: Symptoms, spirometry, airway responsiveness, reversibility, and airway inflammation were all assessed. Exacerbations requiring oral corticosteroids in the preceding year were enumerated. RESULTS: Patients had heterogeneous patterns of airway dysfunction. Those with a post-bronchodilator forced expiratory volume in 1 sec/ forced vital capacity ratio of <0.7 had more exacerbations in the previous year (2.2 vs. 0.8; mean difference 1.4; 95% CI 0.4 to 2.4; p=0.007). Patients with normal results had less inflammation (proportion with a sputum eosinophil count of >1.9%, 20% vs. 48%, χ²=14.8, df=3; p<0.001) and fewer exacerbations (0.5 vs. 1.4; mean difference -0.9; 95% CI -1.4 to -0.4; p=0.001) but similar symptom scores (6.2 vs. 6.9; p=0.2) compared with patients with any abnormality. CONCLUSIONS: Patients with a diagnosis of asthma have mixed patterns of physiological impairment; many have no airflow obstruction or airway hyper-responsiveness. The physiological characterisation of asthma is not related to symptoms and is of little value in predicting exacerbations or eosinophilic airway inflammation.

Evidence of a role of tumor necrosis factor alpha in refractory asthma.

BACKGROUND: The development of tumor necrosis factor alpha (TNF-alpha) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma. METHODS: We measured markers of TNF-alpha activity on peripheral-blood monocytes in 10 patients with refractory asthma, 10 patients with mild-to-moderate asthma, and 10 control subjects. We also investigated the effects of treatment with the soluble TNF-alpha receptor etanercept (25 mg twice weekly) in the patients with refractory asthma in a placebo-controlled, double-blind, crossover pilot study. RESULTS: As compared with patients with mild-to-moderate asthma and controls, patients with refractory asthma had increased expression of membrane-bound TNF-alpha, TNF-alpha receptor 1, and TNF-alpha-converting enzyme by peripheral-blood monocytes. In the clinical trial, as compared with placebo, 10 weeks of treatment with etanercept was associated with a significant increase in the concentration of methacholine required to provoke a 20 percent decrease in the forced expiratory volume in one second (FEV1) (mean difference in doubling concentration changes between etanercept and placebo, 3.5; 95 percent confidence interval, 0.07 to 7.0; P=0.05), an improvement in the asthma-related quality-of-life score (by 0.85 point; 95 percent confidence interval, 0.16 to 1.54 on a 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilator FEV1 (95 percent confidence interval, 0.08 to 0.55; P=0.01). CONCLUSIONS: Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.).

Targeting TNF-alpha: a novel therapeutic approach for asthma.

Approximately 5% to 10% of patients with asthma have severe disease that is refractory or poorly responsive to inhaled corticosteroid therapy. These patients represent an important unmet clinical need because they experience considerable morbidity and mortality and consume a disproportionately large amount of health care resources. TNF-alpha is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. Evidence is emerging to suggest that it might play an important role in severe refractory disease. The development of novel TNF-alpha antagonists has allowed us to test the role of this cytokine in vivo. Preliminary studies have demonstrated an improvement in asthma quality of life, lung function, and airway hyperresponsiveness and a reduction in exacerbation frequency in patients treated with anti-TNF-alpha therapy. However, there is marked heterogeneity in response, suggesting that benefit is likely to be reserved to a small subgroup. Importantly, where efficacy is reported, this also needs to be considered in the context of concerns about the safety of anti-TNF-alpha therapies. Therefore the challenge for clinicians is to evaluate the risk/benefit ratio of these therapies in individual patients with asthma.

Increased sputum and bronchial biopsy IL-13 expression in severe asthma.

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 (R(s) = 0.35, P = .04) and mast cells in the ASM bundle (R(s) = 0.7, P = .007). IL-13+ cells within the submucosa and ASM correlated with sputum eosinophilia (R(s) = 0.4, P < or = .05). CONCLUSIONS: IL-13 overexpression in sputum and bronchial biopsy specimens is a feature of severe asthma.

TNF-alpha in asthma.

Although only 5-10% of patients with asthma are relatively unresponsive to treatment with inhaled corticosteroids, refractory asthma represents an important condition, as these patients suffer considerable morbidity and mortality and consume a disproportionately large amount of health resource. Treatment options are limited and there is a large unmet clinical need for additional therapies. Tumour necrosis factor (TNF)-alpha is a pro-inflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma, and which has recently been highlighted as potentially important in refractory asthma. The development of neutralising biological agents against TNF-alpha has allowed us to test the role of this cytokine in vivo. Preliminary studies have demonstrated an improvement in lung function, airway hyperresponsiveness and asthma quality-of-life, together with a reduction in exacerbation frequency, in patients treated with anti-TNF-alpha therapy.

Treatment approaches for dual diagnosis clients in England.

INTRODUCTION: Dual diagnosis (DD, co-occurrence of substance use and mental health problems) prevalence data in England are limited to specific regions and reported rates vary widely. Reliable information on actual service provision for dual diagnosis clients has not been collated. Thus a national survey was carried out to estimate dual diagnosis prevalence in treatment populations and describe the service provision available for this client population in drug/alcohol (DAS) and mental health services (MHS). DESIGN: A questionnaire was sent to managers of 706 DAS and 2374 MHS. Overall, 249 (39%) DAS and 493 (23%) MHS participated in the survey. RESULTS: In both DAS and MHS, around 32% of clients were estimated to have dual diagnosis problems. However, fewer than 50% of services reported assessing clients for both problem areas. Regarding specific treatment approaches, most services (DAS: 88%, MHS: 87%) indicated working jointly with other agencies. Significantly fewer services used joint protocols (DAS: 55%, MHS: 48%) or shared care arrangements, including access to external drug/alcohol or mental health teams (DAS: 47%, MHS: 54%). Only 25% of DAS and 17% of MHS employed dual diagnosis specialists. CONCLUSIONS: Dual diagnosis clients constitute a substantial proportion of clients in both DAS and MHS in England. Despite recent policy initiatives, joint working approaches tend to remain unstructured.

Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma.

BACKGROUND: Non-eosinophilic asthma is a potentially important clinicopathological phenotype since there is evidence that it responds poorly to inhaled corticosteroid therapy. However, little is known about the underlying airway immunopathology and there are no data from placebo-controlled studies examining the effect of inhaled corticosteroids. METHODS: Airway immunopathology was investigated using induced sputum, bronchial biopsies, bronchial wash and bronchoalveolar lavage in 12 patients with symptomatic eosinophilic asthma, 11 patients with non-eosinophilic asthma and 10 healthy controls. The patients with non-eosinophilic asthma and 6 different patients with eosinophilic asthma entered a randomised, double-blind, placebo-controlled crossover study in which the effects of inhaled mometasone 400 microg once daily for 8 weeks on airway responsiveness and asthma quality of life were investigated. RESULTS: Patients with non-eosinophilic asthma had absence of eosinophils in the mucosa (median 4.4 cells/mm(2) vs 23 cells/mm(2) in eosinophilic asthma and 0 cells/mm(2) in normal controls; p = 0.03) and normal subepithelial layer thickness (5.8 microm vs 10.3 microm in eosinophilic asthma and 5.1 microm in controls, p = 0.002). Non-eosinophilic and eosinophilic asthma groups had increased mast cell numbers in the airway smooth muscle compared with normal controls (9 vs 8 vs 0 cells/mm(2), p = 0.016). Compared with placebo, 8 weeks of treatment with inhaled mometasone led to less improvement in methacholine PC(20) (0.5 vs 5.5 doubling concentrations, 95% CI of difference 1.1 to 9.1; p = 0.018) and asthma quality of life (0.2 vs 1.0 points, 95% CI of difference 0.27 to 1.43; p = 0.008). CONCLUSIONS: Non-eosinophilic asthma represents a pathologically distinct disease phenotype which is characterised by the absence of airway eosinophilia, normal subepithelial layer thickness and a poor short-term response to treatment with inhaled corticosteroids.

Tumor necrosis factor-alpha: a promising therapeutic target for asthma?

Asthma is a disease that encompasses a variety of features including airway smooth muscle abnormalities, airway inflammation, and structural changes in the airway. Historically, it has been classified depending on the severity of the disease, the frequency of symptoms, and the level of treatment required to control them. Severe or refractory asthma accounts for approximately 10% of the patient population with asthma and for about 30% of the healthcare costs of this disease. It is often associated with conditions that might lead to activation of innate immunity in the lung, and it has been suggested that some of the features of severe asthma might be due to upregulation of the tumor necrosis factor-alpha (TNFalpha) pathway. In support of this, studies have shown that severe asthma is associated with an increased presence of TNFalpha within the airway and an increase in TNFalpha expression on peripheral blood mononuclear cells. Moreover, TNFalpha has the ability to induce several of the pro-inflammatory changes associated with severe asthma. Interest in the role of TNFalpha in severe asthma has increased following reports that antagonism with etanercept or infliximab is associated with improvement in asthma control in patients with severe asthma. In this article, we discuss the biology, function, and clinical effects of TNFalpha with particular reference to severe asthma.

Rethinking balance and impartiality in journalism? How the BBC attempted and failed to change the paradigm.

This article reconsiders the concepts of balance and impartiality in journalism, in the context of a quantitative content analysis of sourcing patterns in BBC news programming on radio, television and online in 2007 and 2012. Impartiality is the cornerstone of principles of public service broadcasting at the BBC and other broadcasters modelled on it. However, the article suggests that in the case of the BBC, it is principally put into practice through juxtaposing the positions of the two main political parties - Conservative and Labour. On this basis, the article develops the idea of the 'paradigm of impartiality-as-balance.' This paradigm prevails despite the news organisation's commitment to representing a broader range of opinion. The paradigm of impartiality-as-balance means that only a narrow range of views and voices are heard on the most contentious and important issues. Further, it results in reporting that focuses on party-political conflict, to the detriment of a journalism which provides much-needed context.

Chemokine concentrations and mast cell chemotactic activity in BAL fluid in patients with eosinophilic bronchitis and asthma, and in normal control subjects.

BACKGROUND: Asthma and eosinophilic bronchitis share many immunopathologic features including increased numbers of eosinophils and mast cells in the superficial airway. The mast cell chemotactic activity of airway secretions has not been assessed in patients with eosinophilic bronchitis. OBJECTIVES: To investigate the concentration of chemokines in bronchial wash samples and BAL fluid, and the mast cell chemotactic activity in BAL fluid from subjects with asthma and eosinophilic bronchitis, and from healthy control subjects. METHODS: We measured the concentrations of CCL11, CXCL8, and CXCL10 in bronchial wash samples and BAL fluid from 14 subjects with eosinophilic bronchitis, 14 subjects with asthma, and 15 healthy control subjects. Mast cell chemotaxis to BAL fluid from these subjects was examined using the human mast cell line HMC-1. RESULTS: The bronchial wash sample and BAL fluid concentrations of CXCL10 and CXCL8 was increased in subjects with eosinophilic bronchitis compared to those in subjects with asthma and healthy control subjects (p < 0.05). The CCL11 concentration was below the limit of detection in most subjects. BAL fluid from subjects with eosinophilic bronchitis was chemotactic for mast cells (1.4-fold migration compared to a control, 95% confidence interval, 1.1 to 1.9; p = 0.04) and was inhibited by blocking CXCR1 (45% inhibition; p = 0.002), CXCR3 (38% inhibition; p = 0.034), or both (65% inhibition; p = 0.01). BAL fluid from the subjects with asthma and healthy control subjects was not chemotactic for mast cells. Mast cell migration to BAL fluid was correlated with the concentration of CXCL8 (r = 0.42; p = 0.031) and CXCL10 (r = 0.52; p = 0.007). CONCLUSION: In subjects with eosinophilic bronchitis, CXCL8 and CXCL10 concentrations were elevated in airway secretions. These chemokines may play a key role in mast cell recruitment to the superficial airway in this condition.

The use of exhaled nitric oxide to guide asthma management: a randomized controlled trial.

RATIONALE: Current asthma guidelines recommend adjusting antiinflammatory treatment on the basis of the results of lung function tests and symptom assessment, neither of which are closely associated with airway inflammation. OBJECTIVES: We tested the hypothesis that titrating corticosteroid dose using the concentration of exhaled nitric oxide in exhaled breath (Fe(NO)) results in fewer asthma exacerbations and more efficient use of corticosteroids, when compared with traditional management. METHODS: One hundred eighteen participants with a primary care diagnosis of asthma were randomized to a single-blind trial of corticosteroid therapy based on either Fe(NO) measurements (n = 58) or British Thoracic Society guidelines (n = 60). Participants were assessed monthly for 4 months and then every 2 months for a further 8 months. The primary outcome was the number of severe asthma exacerbations. Analyses were by intention to treat. MEASUREMENTS AND MAIN RESULTS: The estimated mean (SD) exacerbation frequency was 0.33 per patient per year (0.69) in the Fe(NO) group and 0.42 (0.79) in the control group (mean difference, -21%; 95% confidence interval [CI], -57 to 43%; p = 0.43). Overall the Fe(NO) group used 11% more inhaled corticosteroid (95% CI, -17 to 42%; p = 0.40), although the final daily dose of inhaled corticosteroid was lower in the Fe(NO) group (557 vs. 895 microg; mean difference, 338 microg; 95% CI, -640 to -37; p = 0.028). CONCLUSIONS: An asthma treatment strategy based on the measurement of exhaled nitric oxide did not result in a large reduction in asthma exacerbations or in the total amount of inhaled corticosteroid therapy used over 12 mo, when compared with current asthma guidelines. Clinical trial registered with www.controlled-trials.com (ISRCTN08067387).

IL-4-expressing bronchoalveolar T cells from asthmatic and healthy subjects preferentially express CCR 3 and CCR 4.

BACKGROUND: The concept of the polarization of chemokine receptor expression by T(H)1 and T(H)2 cells provides an attractive mechanism for their differential recruitment to tissue, which could be subject to disease-specific therapeutic intervention. The paradigm that T(H)1 cells preferentially express CXCR 3 and CCR 5 and T(H)2 cells preferentially express CCR 3, CCR 4, and CCR 8 has been well established in the setting of in vitro polarized cell lines; however, the situation in vivo appears less clear-cut. OBJECTIVE: We sought to investigate whether this pattern of polarization can be demonstrated in human lung tissue. METHODS: We used single-cell analysis to investigate the relationship between chemokine receptor expression and cytokine production on peripheral blood and bronchoalveolar lavage fluid T cells in patients with asthma, a putative T(H)2 disease, as well as in healthy control subjects. RESULTS: We have found in both asthmatic and control subjects that IL-4-expressing blood and bronchoalveolar lavage fluid T cells are significantly more likely to express the T(H)2 type 2 chemokine receptors CCR 3 and CCR 4, with 10-fold and 2-fold differences in expression, respectively, compared with IFN-gamma-expressing cells. CONCLUSION: We have provided evidence that polarization of T(H)2-type chemokine receptors on IL-4-expressing cells can be demonstrated in an in vivo setting and therefore that these cells might indeed be susceptible to differential patterns of recruitment as a result of expression of the relevant chemokines at inflammatory sites.

Eosinophilic bronchitis: clinical features, management and pathogenesis.

Eosinophilic bronchitis is a common and treatable cause of chronic cough. The major pathological feature is eosinophilic airway inflammation, similar to that seen in asthma. However, the associated airway dysfunction is quite different, with evidence of heightened cough reflex sensitivity, but no variable airflow obstruction or airway hyperresponsiveness. Recent evidence suggests that the differences in functional association are related to differences in localization of mast cells in airway wall, with airway smooth muscle infiltration occurring in asthma and epithelial infiltration in eosinophilic bronchitis. Diagnosis is usually made with induced sputum analysis after exclusion of other causes for chronic cough on clinical, radiological and lung function assessment. The cough responds well to inhaled corticosteroids but dose and duration of treatment remain unclear. Little is known about the natural history of this condition. However, some patients with COPD without a history of previous asthma have sputum eosinophilia, so one possibility is that some cases of eosinophilic bronchitis may develop fixed airflow obstruction. Further study of this interesting condition will increase our understanding of airway inflammation and airway responsiveness, leading to novel targets for therapeutics for both eosinophilic bronchitis and asthma.

Sputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis.

BACKGROUND: Nonasthmatic eosinophilic bronchitis is a condition characterized by the presence of eosinophilic airway inflammation in the absence of airflow obstruction or airway hyperresponsiveness. In asthma, the T H 2-type cytokine IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness. Whether the expression of IL-13 is different between these 2 conditions is unknown. OBJECTIVE: We sought to investigate whether IL-13 expression is increased in asthma compared with eosinophilic bronchitis. METHODS: Sputum samples from subjects with mild asthma (n = 30) and eosinophilic bronchitis (n = 15) and normal controls (n = 16) were dialyzed, and IL-13 concentration was measured by ELISA. In a subgroup of these patients, IL-13 protein expression in bronchial biopsies was assessed by immunohistochemistry. RESULTS: The concentration of sputum IL-13 was higher in patients with mild asthma than in normal controls ( P = .03) and in patients with eosinophilic bronchitis ( P = .03). The median (interquartile range) number of IL-13 + cells/mm 2 submucosa was significantly higher in asthma 4 (8) than eosinophilic bronchitis 1.7 (1.9) and normal controls 0.5 (1.1; P = .004). Eighty-three percent of the cells expressing IL-13 in the submucosa were eosinophils, and 8% were mast cells. The median (interquartile range) proportion of eosinophils that expressed IL-13 was higher in the subjects with asthma, 16 (10)%, than those with eosinophilic bronchitis, 7 (3)% ( P = .02). CONCLUSION: The increased expression of IL-13 in asthma compared with eosinophilic bronchitis supports the concept that IL-13 may play a critical role in the pathophysiology of asthma.