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Biomedical subjects

Neil Barnes

Publications and source records attributed to Neil Barnes.

10 recordsLinked to original sources
PubMed2006

Most difficult asthma originates primarily in adult life.

Epidemiological studies indicate that most asthma starts in childhood. However, the characteristics of adults with difficult asthma differ from the general asthma population. Difficult asthma as defined by poor control despite high dose inhaled steroids and long acting beta 2 agonists disproportionately affects women, more often has onset in adult life and is less frequently associated with atopy, and therefore appears to be a distinct phenotype. If an alternative definition of difficult asthma that is life threatening asthma is used then many of the behavioural traits may have their origin in childhood. Patients with severe and difficult asthma form a specific subgroup of asthmatic patients with high medical need and research specifically into this group of patients is now needed.

Adult↗
PubMed2005

The national montelukast survey.

BACKGROUND: Randomized controlled trials have demonstrated the efficacy of montelukast for treating asthma; whether this can be extrapolated to clinical effectiveness in routine practice has yet to be established. OBJECTIVE: To examine the use, effectiveness, and tolerability of montelukast in clinical practice for treating asthma and to explore prognostic factors that could predict a favorable response to the drug. METHODS: This was a retrospective, cross-sectional, observational study of clinical outcomes seen in patients prescribed montelukast for asthma that used routinely collected clinical information. Data were collected on all consenting patients who had been prescribed montelukast for asthma irrespective of the continuation or duration of treatment. Independent observers, treating physicians, and patients assessed certain outcomes after the initiation of montelukast, including the general asthma response and changes in activity-related symptoms. RESULTS: Fifty-six centers in the United Kingdom (20 primary care and 36 secondary care) participated. The analysis was based on 1351 eligible patients for whom essential data were available. Eight hundred thirty patients (66.4%; 95% CI, 63.8% to 69.0%) were recorded as having shown an improvement in their asthma control, and 103 (8.2%; 95% CI, 6.8% to 9.9%) experienced a dramatic improvement. The greatest proportion of patients responding was seen in those with mild to moderate asthma. Montelukast was well tolerated; no new adverse events were recorded. CONCLUSIONS: Montelukast is an effective, well-tolerated treatment for asthma in routine practice. The overall response rate and tolerability seen in this survey are similar to those reported in randomized clinical trials.

Acetates↗
PubMed2004

Specialist nurse intervention to reduce unscheduled asthma care in a deprived multiethnic area: the east London randomised controlled trial for high risk asthma (ELECTRA).

OBJECTIVE: To determine whether asthma specialist nurses, using a liaison model of care, reduce unscheduled care in a deprived multiethnic area. DESIGN: Cluster randomised controlled trial. SETTING: 44 general practices in two boroughs in east London. PARTICIPANTS: 324 people aged 4-60 years admitted to or attending hospital or the general practitioner out of hours service with acute asthma; 164 (50%) were South Asian patients, 108 (34%) were white patients, and 52 (16%) were from other, largely African and Afro-Caribbean, ethnicities. INTERVENTION: Patient review in a nurse led clinic and liaison with general practitioners and practice nurses comprising educational outreach, promotion of guidelines for high risk asthma, and ongoing clinical support. Control practices received a visit promoting standard asthma guidelines; control patients were checked for inhaler technique. MAIN OUTCOME MEASURES: Percentage of participants receiving unscheduled care for acute asthma over one year and time to first unscheduled attendance. RESULTS: Primary outcome data were available for 319 of 324 (98%) participants. Intervention delayed time to first attendance with acute asthma (hazard ratio 0.73, 95% confidence interval 0.54 to 1.00; median 194 days for intervention and 126 days for control) and reduced the percentage of participants attending with acute asthma (58% (101/174) v 68% (99/145); odds ratio 0.62, 0.38 to 1.01). In analyses of prespecified subgroups the difference in effect on ethnic groups was not significant, but results were consistent with greater benefit for white patients than for South Asian patients or those from other ethnic groups. CONCLUSION: Asthma specialist nurses using a liaison model of care reduced unscheduled care for asthma in a deprived multiethnic health district. Ethnic groups may not benefit equally from specialist nurse intervention.

Adolescent↗
PubMed2004

Evaluating the effectiveness of asthma treatment in real-life practice.

RATIONALE, AIMS AND OBJECTIVES: The randomized controlled trial (RCT) is considered the gold standard methodology for determining the efficacy and tolerability of new treatments. However, RCTs cannot provide information on the effectiveness of interventions as they are used in real life. This study was conducted to investigate the effectiveness of montelukast, a leukotriene receptor antagonist, in the real-world management of asthma, through a large-scale, retrospective, observational study: the National Montelukast Survey. METHODS: In order to ensure a robust methodology for the National Montelukast Survey we performed three pilot studies involving a total of almost 400 patients. During the pilots, the design of the study was extensively modified from a simple prescriber questionnaire used in the first pilot to the 'triangulated' methodology encompassing the perspectives of patient, prescriber and independent observer used in the National Montelukast Survey. Good levels of interobserver agreement confirmed the robustness of the final methodology. CONCLUSIONS: Achieving a robust methodology was dependent on the extensive piloting. It is possible to collect reliable observational data relating to treatment outcomes. We believe our methods are likely to have more widespread applicability and offer a potential improvement over postmarketing surveillance.

Acetates↗
PubMed2004

Courtesy calls.

Explore the source record for details and available documents.

Adult↗
PubMed2003

Autoantibodies to interferon-gamma in a patient with selective susceptibility to mycobacterial infection and organ-specific autoimmunity.

We evaluated a patient with disseminated Mycobacterium tuberculosis and Mycobacterium chelonae infection, of which he died. He also developed autoimmune (type I) diabetes and primary hypothyroidism. His serum contained a high titer of immunoglobulin G autoantibody to interferon-gamma (IFN-gamma) capable of blocking in vitro responses to this cytokine by peripheral blood mononuclear cells from normal donors. These results suggest that autoantibodies to IFN-gamma can induce susceptibility to disseminated mycobacterial infection, which may be refractory to chemotherapy.

Autoantibodies↗
PubMed2003

Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics.

Eosinophil-derived TGF-beta has been implicated in remodeling events in asthma. We hypothesized that reduction of bronchial mucosal eosinophils with anti-IL-5 would reduce markers of airway remodeling. Bronchial biopsies were obtained before and after three infusions of a humanized, anti-IL-5 monoclonal antibody (mepolizumab) in 24 atopic asthmatics in a randomized, double-blind, placebo-controlled study. The thickness and density of tenascin, lumican, and procollagen III in the reticular basement membrane (RBM) were quantified immunohistochemically by confocal microscopy. Expression of TGF-beta1 mRNA by airway eosinophils was assessed by in situ hybridization, and TGF-beta1 protein was measured in bronchoalveolar lavage (BAL) fluid by ELISA. At baseline, airway eosinophil infiltration and ECM protein deposition was increased in the RBM of asthmatics compared with nonasthmatic controls. Treating asthmatics with anti-IL-5 antibody, which specifically decreased airway eosinophil numbers, significantly reduced the expression of tenascin, lumican, and procollagen III in the bronchial mucosal RBM when compared with placebo. In addition, anti-IL-5 treatment was associated with a significant reduction in the numbers and percentage of airway eosinophils expressing mRNA for TGF-beta1 and the concentration of TGF-beta1 in BAL fluid. Therefore eosinophils may contribute to tissue remodeling processes in asthma by regulating the deposition of ECM proteins.

Antibodies, Monoclonal↗
PubMed2002

Gene expression and immunolocalization of 15-lipoxygenase isozymes in the airway mucosa of smokers with chronic bronchitis.

15-lipoxygenase (15-LO) has been implicated in the inflammation of chronic bronchitis (CB), but it is unclear which of its isoforms, 15-LOa or 15-LOb, is primarily involved. To detect 15-LO gene (mRNA) and protein expression, we have applied in situ hybridization (ISH) and immunohistochemistry (IHC), respectively, to bronchial biopsies obtained from 7 healthy nonsmokers (HNS), 5 healthy smokers (HS), and 8 smokers with CB, and additionally include the airways of lungs resected from 11 asymptomatic smokers (AS) and 11 smokers with CB. Compared with HNS, biopsies in CB demonstrated increased numbers of 15-LOa mRNA+ cells (median: HNS = 31.3/mm(2) versus CB = 84.9/mm(2), P < 0.01) and protein+ cells (HNS = 2.9/mm(2) versus CB = 32.1/mm(2), P < 0.01). The HS group also showed a significant increase in protein+ cells (HNS = 2.9/mm(2) versus HS = 14/mm(2), P < 0.05). In the resected airways, 15-LOa protein+ cells in the submucosal glands of the CB group were more numerous than in the AS group (AS = 33/mm(2) versus CB = 208/mm(2); P < 0.001). 15-LOa mRNA+ and protein+ cells consistently outnumbered 15-LOb by approximately 7- and 5-fold, respectively (P < 0.01). Quantitative reverse transcriptase polymerase chain reaction of complementary biopsies confirmed the increased levels of 15-LOa in CB compared with that in either HNS or HS (P < 0.05). There was no difference between the subject groups with respect to 15-LOb expression. The numbers of cells expressing mRNA for 15-LOa in CB showed a positive association with those expressing interleukin (IL)-4 mRNA (r = 0.80; P < 0.01). We conclude that the upregulation of 15-LO activity in the airways of HS and of smokers with CB primarily involves the 15-LOa isoform: the functional consequences of its association the upregulation of IL-4 in chronic bronchitis requires further study.

Adult↗