Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules: the SPUtNIk diagnostic accuracy study and economic modelling.

BACKGROUND: Current pathways recommend positron emission tomography-computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach. OBJECTIVES: To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography-computerised tomography in the NHS for solitary pulmonary nodules. Systematic reviews and a health economic evaluation contributed to the decision-analytic modelling to assess the likely costs and health outcomes resulting from incorporation of dynamic contrast-enhanced computerised tomography into management strategies. DESIGN: Multicentre comparative accuracy trial. SETTING: Secondary or tertiary outpatient settings at 16 hospitals in the UK. PARTICIPANTS: Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included. INTERVENTIONS: Baseline positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography with 2 years' follow-up. MAIN OUTCOME MEASURES: Primary outcome measures were sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computerised tomography. Incremental cost-effectiveness ratios compared management strategies that used dynamic contrast-enhanced computerised tomography with management strategies that did not use dynamic contrast-enhanced computerised tomography. RESULTS: A total of 380 patients were recruited (median age 69 years). Of 312 patients with matched dynamic contrast-enhanced computer tomography and positron emission tomography-computerised tomography examinations, 191 (61%) were cancer patients. The sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography were 72.8% (95% confidence interval 66.1% to 78.6%), 81.8% (95% confidence interval 74.0% to 87.7%), 76.3% (95% confidence interval 71.3% to 80.7%) and 95.3% (95% confidence interval 91.3% to 97.5%), 29.8% (95% confidence interval 22.3% to 38.4%) and 69.9% (95% confidence interval 64.6% to 74.7%), respectively. Exploratory modelling showed that maximum standardised uptake values had the best diagnostic accuracy, with an area under the curve of 0.87, which increased to 0.90 if combined with dynamic contrast-enhanced computerised tomography peak enhancement. The economic analysis showed that, over 24 months, dynamic contrast-enhanced computerised tomography was less costly (£3305, 95% confidence interval £2952 to £3746) than positron emission tomography-computerised tomography (£4013, 95% confidence interval £3673 to £4498) or a strategy combining the two tests (£4058, 95% confidence interval £3702 to £4547). Positron emission tomography-computerised tomography led to more patients with malignant nodules being correctly managed, 0.44 on average (95% confidence interval 0.39 to 0.49), compared with 0.40 (95% confidence interval 0.35 to 0.45); using both tests further increased this (0.47, 95% confidence interval 0.42 to 0.51). LIMITATIONS: The high prevalence of malignancy in nodules observed in this trial, compared with that observed in nodules identified within screening programmes, limits the generalisation of the current results to nodules identified by screening. CONCLUSIONS: Findings from this research indicate that positron emission tomography-computerised tomography is more accurate than dynamic contrast-enhanced computerised tomography for the characterisation of solitary pulmonary nodules. A combination of maximum standardised uptake value and peak enhancement had the highest accuracy with a small increase in costs. Findings from this research also indicate that a combined positron emission tomography-dynamic contrast-enhanced computerised tomography approach with a slightly higher willingness to pay to avoid missing small cancers or to avoid a 'watch and wait' policy may be an approach to consider. FUTURE WORK: Integration of the dynamic contrast-enhanced component into the positron emission tomography-computerised tomography examination and the feasibility of dynamic contrast-enhanced computerised tomography at lung screening for the characterisation of solitary pulmonary nodules should be explored, together with a lower radiation dose protocol. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018112215 and CRD42019124299, and the trial is registered as ISRCTN30784948 and ClinicalTrials.gov NCT02013063. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 17. See the NIHR Journals Library website for further project information.

A nodule found on a lung scan can cause concern as it may be a sign of cancer. Finding lung cancer nodules when they are small (i.e. < 3 cm) is very important. Most nodules are not cancerous. Computerised tomography (cross-sectional images created from multiple X-rays) and positron emission tomography­computerised tomography (a technique that uses a radioactive tracer combined with computerised tomography) are used to see whether or not a nodule is cancerous; although they perform well, improvements are required. This study compared dynamic contrast-enhanced computerised tomography with positron emission tomography­computerised tomography scans to find out which test is best. Dynamic contrast-enhanced computerised tomography involves injection of a special dye into the bloodstream, followed by repeated scans of the nodule over several minutes. We assessed the costs to the NHS of undertaking the different scans, relative to their benefits, to judge which option was the best value for money. We recruited 380 patients from 16 hospitals across England and Scotland, of whom 312 had both dynamic contrast-enhanced computerised tomography and positron emission tomography­computerised tomography scans. We found that current positron emission tomography­computerised tomography is more accurate, providing a correct diagnosis in 76% of cases, than the new dynamic contrast-enhanced computerised tomography, which provides a correct diagnosis in 70% of cases. Although dynamic contrast-enhanced computerised tomography cannot replace positron emission tomography­computerised tomography, it may represent good-value use of NHS resources, especially if it is performed before positron emission tomography­computerised tomography and they are used in combination. Although more research is required, it may be possible in the future to perform dynamic contrast-enhanced computerised tomography at the same time as positron emission tomography­computerised tomography in patients with suspected lung cancer or if a lung nodule is found on a lung screening programme at the time of the computerised tomography examination. This may reduce the need for some people to have positron emission tomography­computerised tomography.

Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper.

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.

Placebo effects in allergen immunotherapy: an experts' opinion.

Placebo effects are common in medicine. Randomised clinical trials help us to understand their magnitude in different therapies. There are particular problems with placebo effects in allergen immunotherapy (AIT) as it is difficult to blind the active treatment and the endpoints are largely subjective. This may explain why large placebo effects are often found in AIT trials. Patients receiving open label AIT get the benefit of the active and placebo components but it can be difficult to say how much benefit is due to the active component. The use of active placebos has been proposed but brings its own problems (ethical and scientific). An EAACI Task Force has been established to address these issues. Here we review the current literature on the placebo effect in general, with a special focus on AIT trials, and indicate what we believe to be important considerations and unmet needs in AIT trial design.

Effects of controlled diesel exhaust exposure on apoptosis and proliferation markers in bronchial epithelium - an in vivo bronchoscopy study on asthmatics, rhinitics and healthy subjects.

BACKGROUND: Epidemiological evidence demonstrates that exposure to traffic-derived pollution worsens respiratory symptoms in asthmatics, but controlled human exposure studies have failed to provide a mechanism for this effect. Here we investigated whether diesel exhaust (DE) would induce apoptosis or proliferation in the bronchial epithelium in vivo and thus contribute to respiratory symptoms. METHODS: Moderate (n = 16) and mild (n = 16) asthmatics, atopic non-asthmatic controls (rhinitics) (n = 13) and healthy controls (n = 21) were exposed to filtered air or DE (100 µg/m(3)) for 2 h, on two separate occasions. Bronchial biopsies were taken 18 h post-exposure and immunohistochemically analysed for pro-apoptotic and anti-apoptotic proteins (Bad, Bak, p85 PARP, Fas, Bcl-2) and a marker of proliferation (Ki67). Positive staining was assessed within the epithelium using computerized image analysis. RESULTS: No evidence of epithelial apoptosis or proliferation was observed in healthy, allergic or asthmatic airways following DE challenge. CONCLUSION: In the present study, we investigated whether DE exposure would affect markers of proliferation and apoptosis in the bronchial epithelium of asthmatics, rhinitics and healthy controls, providing a mechanistic basis for the reported increased airway sensitivity in asthmatics to air pollutants. In this first in vivo exposure investigation, we found no evidence of diesel exhaust-induced effects on these processes in the subject groups investigated.

The effects of expressive writing on lung function, quality of life, medication use, and symptoms in adults with asthma: a randomized controlled trial.

OBJECTIVES: Asthma is a chronic condition affecting 300 million people worldwide. Management involves adherence to pharmacological treatments such as corticosteroids and ß-agonists, but residual symptoms persist. As asthma symptoms are exacerbated by stress, one possible adjunct to pharmacological treatment is expressive writing (EW). EW involves the disclosure of traumatic experiences which is thought to facilitate cognitive and emotional processing, helping to reduce physiological stress associated with inhibiting emotions. A previous trial reported short-term improvements in lung function. This study aimed to assess whether EW can improve lung function, quality of life, symptoms, and medication use in patients with asthma. METHODS: Adults (18-45 years) diagnosed as having asthma requiring regular inhaled corticosteroids were recruited from 28 general practices in South East England (n = 146). In this double-blind randomized controlled trial, participants were allocated either EW or nonemotional writing instructions and asked to write for 20 minutes for 3 consecutive days. Lung function (forced expired volume in 1 second [FEV1]% predicted), quality of life (Mark's Asthma Quality of Life Questionnaire), asthma symptoms (Wasserfallen Symptom Score Questionnaire), and medication use (inhaled corticosteroids and ß-agonist) were recorded at baseline, 1, 3, 6, and 12 months. RESULTS: Hierarchical linear modeling indicated no significant main effects between time and condition on any outcomes. Post hoc analyses revealed that EW improved lung function by 14% for 12 months for participants with less than 80% FEV1% predicted at baseline (ß = 0.93, p = .002) whereas no improvement was observed in the control condition (ß = 0.10, p = .667). CONCLUSIONS: EW seems to be beneficial for patients with moderate asthma (<80% FEV1% predicted). Future studies of EW require stratification of patients by asthma severity. TRIAL REGISTRATION: ISRCTN82986307.

Factors associated with good adherence to self-care behaviours amongst adolescents with food allergy.

BACKGROUND: Our understanding of factors which affect adherence to health sustaining self-care behaviours in adolescents with food allergy is limited. This study used the Health Belief Model to explore the relationship between food allergic adolescents' health beliefs, demographic, structural and social psychological factors with adherence to self-care behaviours, including allergen avoidance and carrying emergency medication. METHODS: A cross-sectional study of 188 13- to 19- olds identified from hospital prescribed auto-injectable epinephrine for food allergy. Data were collected on demographics, structural factors, social psychological factors, health beliefs and current adherence behaviour using a postal questionnaire. RESULTS: Full adherence was reported by 16% of participants. Multivariate analysis indicated that adherence was more likely to be reported if the adolescents belonged to a support group (OR = 2.54, (1.04, 6.20) 95% CI), had an anaphylaxis management plan (OR = 3.22, (1.18, 8.81) 95% CI), perceived their food allergy to be more severe (OR = 1.24, (1.01, 1.52) 95% CI) and perceived fewer barriers to disease management (OR = 0.87, (0.79, 0.96) 95% CI). CONCLUSIONS: Membership of a patient support group and having an anaphylaxis management plan were associated with good adherence to self-care behaviours in adolescents with food allergy. Our results suggest that interventions to improve provision and utilisation of management plans, address adolescents' perceptions of the severity of anaphylaxis and reduce barriers to disease management may facilitate good adherence behaviours than focussing on knowledge-based interventions.

Autocrine ligands of the epithelial growth factor receptor mediate inflammatory responses to diesel exhaust particles.

BACKGROUND: Diesel exhaust is associated with cardiovascular and respiratory mortality and morbidity. Acute exposure leads to increased IL-8 expression and airway neutrophilia, however the mechanism of this response is unknown. OBJECTIVES: As cigarette smoke-induced IL-8 expression by epithelial cells involves transactivation of the epidermal growth factor receptor (EGFR), we studied the effects of diesel exhaust particles (DEP) on IL-8 release and the role of the EGFR. METHODS: Primary bronchial epithelial cells (PBEC) were exposed to DEPs or carbon black. IL-8 and EGFR ligand expression (transforming growth factor alpha (TGFα), heparin-binding EGF-like growth factor, and amphiregulin (AR)) were assessed by quantitative RT-PCR and ELISA. RESULTS: DEP, but not carbon black, caused a dose-dependent increase in mitogen-activated protein kinase (MAPK) activation and IL-8 expression, however above 50 µg/ml there was an increase in cytotoxicity. At 50 µg/ml, DEPs stimulated transcription and release of IL-8 and EGFR ligands. IL-8 release was blocked by EGFR neutralizing antibodies, an EGFR-selective tyrosine kinase inhibitor and by the metalloprotease inhibitor, GM6001, which blocks EGFR ligand shedding. Neutralizing antibodies to AR, TGFα and heparin-binding (HB)-EGF reduced DEP-induced IL-8 by >50%. Conclusion Expression of IL-8 in response to DEPs is dependent on EGFR activation and that autocrine production of EGFR ligands makes a substantial contribution to this response. CAPSULE SUMMARY: This study identifies a mechanism whereby diesel particles stimulates IL-8 release from bronchial epithelial cells. This mechanism may help to explain the recruitment of neutrophils into the airways of people exposed to particulate air pollution.

Explaining adherence to self-care behaviours amongst adolescents with food allergy: a comparison of the health belief model and the common sense self-regulation model.

OBJECTIVES: To identify explanations for adherence to self-care behaviours amongst adolescents with food allergy-induced anaphylaxis using two social cognition models: the health belief model (HBM) and the common sense self-regulation model (CS-SRM). DESIGN: Cross-sectional self-completion questionnaire study to gain initial evidence of the two models' feasibility/effectiveness in explaining adherence in an adolescent food-allergic population. METHODS: Participants aged 13-19 years with a diagnosis of severe food allergy and a prescription of an adrenaline auto-injector were recruited from hospital outpatients. Adherence to self-care behaviours was measured in addition to constructs from the HBM and CS-SRM. RESULTS: One hundred and eighty-eight food-allergic adolescents completed the questionnaire. The HBM, specifically the constructs perceived severity and barriers, accounted for 21% of the explained variance in adherence behaviours. CS-SRM constructs, illness identity, timeline cyclical beliefs and emotional representations explained 25% of the variance. CONCLUSIONS: Both models performed similarly in explaining adherence to self-care behaviours in adolescents with food allergy. Interventions designed to elicit personal barriers to adherence and to address perceptions of severity and the unpredictable nature of symptoms may be more effective in improving adherence to self-care behaviours than current interventions.

Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals.

BACKGROUND: Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We sought to utilise our short-term CD154 detection method to further analyse the relationship between these T cell subsets and investigate differences between seasonal and perennial allergens. Using peripheral blood samples from grass-allergic, cat-allergic and healthy non-atopic subjects, we compared the frequencies and phenotype of CD154-positive T helper cells following stimulation with seasonal (grass) and perennial (cat dander) allergens. RESULTS: We identified a higher frequency of CD154+ T cells in grass-allergic individuals compared to healthy controls; this difference was not evident following stimulation with cat allergen. Activated Th1, Th2 and Tr1-like cells, that co-express IFNγ, IL4 and IL10, respectively, were identified in varying proportions in grass-allergic, cat-allergic and non-allergic individuals. We confirmed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. This relationship was dysregulated in grass-allergic individuals with no correlation between the T cell subsets and a higher Th2: Th1 ratio. We confirmed previous reports of a late-differentiated T cell phenotype in response to seasonal allergens compared to early-differentiated T cell responses to perennial allergens. CONCLUSIONS: The findings confirm our existing work illustrating an important balance between Th1, Th2 and Tr1-like responses to allergens in health, where Th2 responses are frequently observed, but balanced by Th1 and regulatory responses. We confirm previous tetramer-based reports of phenotypic differences in T cells responding to seasonal and perennial allergens.

Characterisation of CD154+ T cells following ex vivo birch allergen stimulation defines a close relationship between T cell subsets in healthy volunteers.

BACKGROUND: Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We hypothesised that the relationship between these T cell subsets could be better defined using a short-term allergen stimulation system followed by direct analysis of CD154-positive T cells. Using peripheral blood samples from birch pollinosis patients and healthy non-atopic controls, we sought to explore the frequencies and phenotype of birch-stimulated CD154-positive T helper cells following ex vivo birch allergen stimulation. RESULTS: Activated CD154-positive Th1, Th2 and Tr1-like cells, that co-expressed IFNγ, IL-4 and IL-10 respectively, were identified in both birch-allergic and non-allergic participants. We observed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. The relationship between Th1, Th2 and Tr1-like responses was dysregulated in birch-allergic patients, with abrogation of the IL-10 response and a higher Th2: Th1 ratio. A close correlation was observed between Th2 cell frequency and the absolute concentration of birch-specific IgE within the birch-allergic group, and we confirmed previous reports of a more differentiated T cell phenotype in allergic subjects. CONCLUSIONS: The findings demonstrate an important balance between IFNγ, IL-4 and IL-10 T cell responses to birch allergen in health, where Th2 responses to allergens were frequently observed, but apparently balanced by Th1 and regulatory responses. The detection of CD154 positive T cells after short-term antigen stimulation may be a useful method for the detection of T cell responses to allergens when cost, speed and convenience are priorities.

Assessment of specific immunotherapy efficacy using a novel placebo score-based method.

BACKGROUND: In trials of allergen immunotherapy, allergen exposure is typically assessed by pollen counts, but these may misrepresent exposure if performed remotely from multiple study centers. OBJECTIVE: To assess whether symptomatology in placebo-treated patients is a better measure of local allergen burden at individual centers in such trials. METHODS: Data from a multicenter, placebo-controlled trial of preseasonal grass pollen immunotherapy were reanalyzed to identify the 4 weeks at each center in which the placebo-treated subjects had the highest combined symptom/medication scores (CSMS). The difference in CSMS between active and placebo groups was compared during the 4 peak placebo score weeks (PlSW) and the 4 peak pollen count weeks (PoCW). RESULTS: The benefit of immunotherapy over placebo in the PlSW analysis (18.5%) was greater than in the PoCW analysis (13.6%), with increased statistical significance (P = .0001, .0038, respectively). Similar improved discrimination was observed when analyzing benefits in subgroups of patients with severe symptoms, a high disease burden, and in different geographical locations. CONCLUSION: This novel PlSW analysis results in better discrimination of the effects of allergen immunotherapy compared with placebo and may be widely applicable in similar studies, both prospectively and retrospectively.

Ultrashort-specific immunotherapy successfully treats seasonal allergic rhinoconjunctivitis to grass pollen.

Specific immunotherapy is a well-established treatment for allergic rhinoconjunctivitis; conventional regimens are lengthy, however, reducing convenience and cost-effectiveness. This study evaluated the efficacy and safety of an ultrashort course (four doses) of the immunotherapy Grass Modified Allergen Tyrosine Adsorbate (Allergy Therapeutics, Worthing, U.K.) monophosphoryl lipid A (MATA MPL). Subjects were randomized to receive four injections of either Grass MATA MPL (n = 514; 300-2000 standardized units/injection) or placebo (n = 514) before the grass pollen season. They used electronic diaries to record allergy symptoms and medication use during the pollen season. The primary end point was the difference between the mean combined symptom and medication scores in the Grass MATA MPL and placebo groups during the 4 local peak pollen weeks. The injection course was completed by 95.3 and 97.7% of the Grass MATA MPL and placebo groups, respectively, and was well tolerated. Grass MATA MPL treatment afforded a 13.4% benefit over placebo in the 4 peak pollen weeks (p = 0.0038). The benefit in subjects with 28 complete diary entries during the 4 peak pollen weeks was 26.9% (p = 0.0031). Significant benefits over placebo were observed in subjects with severe symptoms (17.1%; p = 0.0023), in those who had a history of allergic rhinoconjunctivitis for up to 35 years (up to 37.2%; p = 0.0059) and at sites with a higher burden of disease (38.3%; p < 0.0001). The ultrashort course of Grass MATA MPL was well tolerated and provided a significant benefit over placebo in relieving allergy symptoms.

Allergen immunotherapy.

Specific immunotherapy (SIT) involves the administration of allergen extracts to achieve clinical tolerance of those allergens that cause symptoms in patients with allergic conditions. Immunotherapy is effective in patients with mild forms of allergic disease and also in those who do not respond well to standard drug therapy. Most SIT is given by means of injection, but there is increasing interest in performing SIT through the sublingual route. SIT remains the treatment of choice for patients with systemic allergic reactions to wasp and bee stings and should be considered as an option in patients with allergic rhinitis, asthma, or both. SIT can modify the course of allergic disease by reducing the risk of new allergic sensitizations and inhibiting the development of clinical asthma in children treated for allergic rhinitis. The precise mechanisms responsible for the beneficial effects of SIT remain a matter of research and debate. An effect on regulatory T cells seems most probable and is associated with switching of allergen-specific B cells toward IgG4 production. Few direct comparisons of SIT and drug therapy have been made. Existing data suggest that the effects of SIT take longer to develop, but once established, SIT achieves long-lasting relief of allergic symptoms, whereas the benefits of drugs only last as long as they are continued.

Early suppression of NFkappaB and IL-8 in bronchial epithelium after ozone exposure in healthy human subjects.

Exposure to elevated concentrations of ozone, a common air pollutant, has been associated with numerous adverse health effects. We have previously reported the time-course of ozone-induced airway inflammation, demonstrating an early up-regulation of vascular endothelial adhesion molecules in bronchial mucosa at 1.5 hours, followed by a neutrophilic infiltration 6 hours after exposure to 0.2 ppm ozone. We hypothesized that the neutrophilic infiltration in the bronchial mucosa would reflect an early increase in bronchial epithelial expression of redox-sensitive transcription factors and kinases regulating neutrophil chemoattractant expression. To test this hypothesis, endobronchial biopsies were obtained from healthy human subjects (n = 11) 1.5 hours after 0.2 ppm of ozone and filtered air exposures (lasting for 2 hours) and stained for mitogen-activated protein kinases (MAPKs), transcription factors, and neutrophil chemoattractants. Total epithelial staining was quantified, as well as the extent of nuclear translocation. Contrary to expectation, ozone significantly suppressed total and nuclear expression of nuclear factor kappaB (NFkappaB) in bronchial epithelial cells (p = 0.02 and p = 0.003 respectively). Similarly, the total staining for phosphorylated C-jun was suppressed (p = 0.021). Expression of interleukin 8 (IL-8) in the bronchial epithelium was likewise decreased after ozone (p = 0.018), while GRO-alpha, ENA-78, C-fos, p-p38, p-JNK, and p-ERK stainings were unchanged. These data suggest that the redox-sensitive NFkappaB and activator protein 1 (AP-1) pathways within the human bronchial epithelium do not seem to be involved in the early inflammatory cell recruitment pathways in healthy subjects exposed to ozone.

Is structured allergy history sufficient when assessing patients with asthma and rhinitis in general practice?

BACKGROUND: Many United Kingdom patients with asthma and rhinitis are allergic, but in primary care few diagnostic and management decisions are made with formal allergy assessment. Arguably, knowing a patient's atopic status might be helpful in distinguishing the cause of disease and in selecting appropriate treatments. OBJECTIVES: Our objective was to estimate the extent to which a formal allergy assessment (a structured allergy history and skin prick tests to 5 common aeroallergens) would improve the precision of allergy diagnosis compared with a patient's self-report or the structured allergy history alone. METHODS: One hundred twenty-seven patients with asthma, rhinitis, or both were recruited from 4 general practices in Wessex, United Kingdom. Allergy status based on the patient's opinion and on structured allergy history alone was compared with formal allergy assessment. Assessments were validated by an independent allergy specialist reviewing the files. Patients were given written advice specific to their allergies and followed up 3 months later to assess satisfaction, recall, and effect on health and behavior. RESULTS: Self-reporting misclassified allergic status in many patients. A structured allergy history alone was little better and resulted in false-positive rates for cat allergy of 32%, grass pollen of 48%, house dust mite of 75%, tree pollen of 54%, and dog of 27% compared with formal allergy assessment. Skin prick testing combined with a structured history was essential to reach a correct causative diagnosis. Three months later, 41% patients had made changes to lifestyle, medications, or both, and 18% reported clinical improvement. CONCLUSIONS: Skin prick testing improves the accuracy of an assessment of allergic status based on patient opinion or a structured allergy history alone.