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Biomedical subjects

J G Ayres

Publications and source records attributed to J G Ayres.

At least 19 recordsLinked to original sources
PubMed2006

Defining and investigating occupational asthma: a consensus approach.

BACKGROUND: At present there is no internationally agreed definition of occupational asthma and there is a lack of guidance regarding the resources that should be readily available to physicians running specialist occupational asthma services. AIMS: To agree a working definition of occupational asthma and to develop a framework of resources necessary to run a specialist occupational asthma clinic. METHOD: A modified RAND appropriateness method was used to gain a consensus of opinion from an expert panel of clinicians running specialist occupational asthma clinics in the UK. RESULTS: Consensus was reached over 10 terms defining occupational asthma including: occupational asthma is defined as asthma induced by exposure in the working environment to airborne dusts vapours or fumes, with or without pre-existing asthma; occupational asthma encompasses the terms "sensitiser-induced asthma" and "acute irritant-induced asthma" (reactive airways dysfunction syndrome (RADS)); acute irritant-induced asthma is a type of occupational asthma where there is no latency and no immunological sensitisation and should only be used when a single high exposure has occurred; and the term "work-related asthma" can be used to include occupational asthma, acute irritant-induced asthma (RADS) and aggravation of pre-existing asthma. Disagreement arose on whether low dose irritant-induced asthma existed, but the panel agreed that if it did exist they would include it in the definition of "work-related asthma". The panel agreed on a set of 18 resources which should be available to a specialist occupational asthma service. These included pre-bronchodilator FEV1 and FVC (% predicted); peak flow monitoring (and plotting of results, OASYS II analysis); non-specific provocation challenge in the laboratory and specific IgE to a wide variety of occupational agents. CONCLUSION: It is hoped that the outcome of this process will improve uniformity of definition and investigation of occupational asthma across the UK.

Asthma↗
PubMed2005

Defining and investigating difficult asthma: developing quality indicators.

BACKGROUND: There is no agreed definition of 'difficult asthma' or what investigations should be available to investigate these patients. Patients with difficult asthma remain symptomatic on high levels of treatment and are high users of medical resources. AIM: To develop a set of quality indicators for the definition and investigation of difficult asthma. METHOD: Modified RAND Appropriateness Method was used. An expert panel composed of nine hospital asthma specialists who run 'difficult' asthma clinics and were identified from a short list of key workers in the field. Indicators were rated as necessary to define and investigate difficult asthma. RESULTS: Difficult asthma was defined as 'symptoms persisting beyond therapy consistent with step 4 of the British Thoracic Society (BTS) guidelines' (high dose inhaled corticosteroids and long acting beta(2)-agonists). Eighty-three indicators were identified (40 relating to definition and 43 relating to investigations). Of these 32 (39%) were rated as necessary: 7 out of 40 (18%) for defining difficult asthma and 23 out of 43 (53%) for investigations. Indicators of high medical resource usage were characteristic of the 'difficult' nature of the management of patient with difficult asthma. A framework for the investigation of these patients was created. CONCLUSION: The listed performance indicators identify a range of requirements that are necessary to define difficult asthma. Targeting of real needs in this group of patients will lead to better patient care and reduction of 'waste' in provision of healthcare.

Anti-Asthmatic Agents↗
PubMed2005

Deaths certified as asthma and use of medical services: a national case-control study.

BACKGROUND: Studies have linked asthma death to either increased or decreased use of medical services. METHODS: A population based case-control study of asthma deaths in 1994-8 was performed in 22 English, six Scottish, and five Welsh health authorities/boards. All 681 subjects who died were under the age of 65 years with asthma in Part I on the death certificates. After exclusions, 532 hospital controls were matched to 532 cases for age, district, and date of asthma admission/death. Data were extracted blind from primary care records. RESULTS: The median age of the subjects who died was 53 years; 60% of cases and 64% of controls were female. There was little difference in outpatient attendance (55% and 55%), hospital admission for asthma (51% and 54%), and median inpatient days (20 days and 15 days) in the previous 5 years. After mutual adjustment and adjustment for sex, using conditional logistic regression, three variables were independently associated with asthma death: fewer general practice contacts (odds ratio 0.82 (95% confidence interval (CI) 0.74 to 0.91) per 5 contacts) in the previous year, more home visits (1.14 (95% CI 1.08 to 1.21) per visit) in the previous year, and fewer peak expiratory flow recordings (0.83 (95% CI 0.74 to 0.92) per occasion) in the previous 3 months. These associations were similar after adjustment for markers of severity, psychosocial factors, systemic steroids, short acting bronchodilators and antibiotics, although the association with peak flow was weakened and just lost significance. CONCLUSION: Asthma death is associated with less use of primary care services. Both practice and patient factors may be involved and a better understanding of these may offer possibilities for reducing asthma death.

Administration, Inhalation↗
PubMed2005

Effect of inhaled sulphur dioxide and carbon particles on heart rate variability and markers of inflammation and coagulation in human subjects.

OBJECTIVE: To measure the inflammatory and autonomic responses of healthy humans and patients with coronary artery disease to controlled concentrations of two specific components of vehicle derived air pollution, carbon particles and sulphur dioxide (SO2). METHODS: Placebo controlled, double blind, random order human challenge study examining the effects of carbon particles (50 microg/m3) and SO2 (200 parts per billion (ppb)) on heart rate variability (HRV) and circulating markers of inflammation and coagulation in healthy volunteers and patients with stable angina. RESULTS: In healthy volunteers, markers of cardiac vagal control did not fall in response to particle exposure but, compared with the response to air, increased transiently immediately after exposure (root mean square of successive RR interval differences (RMSSD) 15 (5) ms with carbon particles and 4 (3) ms) with air, p < 0.05). SO2 exposure resulted in no immediate change but a significant reduction in HRV markers of cardiac vagal control at four hours (RMSSD -2 (3.6) ms with air, -7 (2.7) ms with SO2, p < 0.05). No such changes were seen in patients with stable angina. Neither pollutant caused any change in markers of inflammation or coagulation at zero, four, or 24 hours. CONCLUSION: In healthy volunteers, short term exposure to pure carbon particles does not cause adverse effects on HRV or a systemic inflammatory response. The adverse effects of vehicle derived particulates are likely to be caused by more reactive species found on the particle surface. SO2 exposure does, however, reduce cardiac vagal control, a response that would be expected to increase susceptibility to ventricular arrhythmia.

Aged↗
PubMed2005

Air pollution and the heart.

Despite legislation, leading to dramatic decreases in levels of air pollution since the time of the great smogs, a large body of epidemiological evidence has demonstrated that pollution continues to have adverse effects on human health. One striking finding from the epidemiological data is that patients with cardiovascular disease are susceptible to acute rises in ambient pollutants. Mortality and hospital admissions for myocardial infarction, congestive cardiac failure and cardiac arrhythmia all increase with a rise in the concentration of both particulate and gaseous pollutants. Before concluding that this association is a causal one, plausible pathophysiological mechanisms are required. Evidence is accumulating in support of two mechanistic hypotheses: inhalation of pollutants might provoke a local inflammatory response with the consequent release into the circulation of pro-thrombotic and inflammatory cytokines. A systemic response of this nature would put individuals with coronary atheroma at increased risk of cardiac events; exposure to pollutants may have an adverse effect on cardiac autonomic control, leading to an increased risk of arrhythmia in susceptible patients. Clarification of the pollutants involved and the precise mechanisms of action is essential in designing measures by which susceptible individuals might be protected from the adverse cardiovascular effects of air pollution.

Air Pollution↗
PubMed2005

Long-term persistence of Coxiella burnetii after acute primary Q fever.

BACKGROUND: Long-term persistence of C. burnetii in infected animals was established in the 1950s and 60s, but the implications for human Q fever are not fully explored. AIM: To compare the prevalence of markers of infection in a cohort of Q fever patients in Australia (up to 5 years after infection) with those in the 1989 Birmingham cohort (12 years after infection). DESIGN: Case follow-up study. METHODS: C. burnetii was tested for by: (i) antibodies to Phase 1 and 2 antigens in the three immunoglobulin classes; (ii) detection of DNA in bone marrow and peripheral blood mononuclear cells by PCR assays directed against several different targets in the genome; and (iii) attempts to isolate coxiellas in cell culture or mice from PCR-positive samples. Amplicon specificity was verified by fluorometric probing and by sequencing. Cross-contamination was excluded by extensive use of non-template controls, and in particular by the use of certain IS1111a target sequences. RESULTS: Irrespective of clinical state, both groups remained seropositive, principally exhibiting medium levels of IgG antibody against C. burnetii Phase 2 antigen. C. burnetii genomic DNA was detected by PCR in 65% of bone marrow aspirates from Australian patients and approximately 88% of Birmingham patients. No coxiella were isolated from PCR positive samples. DISCUSSION: We propose a provisional model for persistence. In Q fever without sequelae, the process is largely confined to the bone marrow. In Q fever fatigue syndrome (QFS), it is modulated by the patient's immunogenetic background to give higher levels of coxiella genomes in bone marrow and increased shedding into the peripheral blood. In Q fever endocarditis, late pregnancy, or during iatrogenic or other immunosuppression, the multiplication cycle is prolonged, and a potential source of live organisms.

Animals↗
PubMed2004

Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergic asthma.

BACKGROUND: Patients with poorly controlled asthma have greater morbidity and mortality. This study evaluated the efficacy and tolerability of omalizumab in patients with poorly controlled, moderate-to-severe allergic asthma. METHODS: This was a randomized, open-label, multicentre, parallel-group study. A total of 312 patients (12-73 years) receiving >/=400 microg/day (adolescent) or >/=800 microg/day (adult) inhaled beclomethasone dipropionate, or equivalent were included. Patients received best standard care (BSC) with or without omalizumab [at least 0.016 mg/kg/IgE (IU/ml) every 4 weeks] for 12 months. RESULTS: The annualized mean number of asthma deterioration-related incidents was reduced from 9.76 with BSC alone (n = 106) to 4.92 per patient-year with omalizumab (n = 206) (P < 0.001). Mean clinically significant asthma exacerbation rates were 2.86 and 1.12 per patient-year, respectively (P < 0.001). Omalizumab-treated patients (41.4%) required rescue medication <1 day/week compared with 20.7% for BSC alone (P < 0.001). Omalizumab improved absolute forced expiratory volume in 1 s (FEV(1)) compared with BSC alone (2.48 and 2.28 l, respectively; P < 0.05) and reduced symptom scores relative to BSC alone (decrease of 6.5 and 0.7 respectively; P < 0.001). Omalizumab was well-tolerated. CONCLUSIONS: Omalizumab administered as add-on therapy to BSC benefits patients with poorly controlled, moderate-to-severe allergic asthma.

Adolescent↗
PubMed2004

Particulate air pollution and panel studies in children: a systematic review.

BACKGROUND: Panel studies have been used to investigate the short term effects of outdoor particulate air pollution across a wide range of environmental settings. AIMS: To systematically review the results of such studies in children, estimate summary measures of effect, and investigate potential sources of heterogeneity. METHODS: Studies were identified by searching electronic databases to June 2002, including those where outcomes and particulate level measurements were made at least daily for > or =8 weeks, and analysed using an appropriate regression model. Study results were compared using forest plots, and fixed and random effects summary effect estimates obtained. Publication bias was considered using a funnel plot. RESULTS: Twenty two studies were identified, all except two reporting PM10 (24 hour mean) >50 microg x m(-3). Reported effects of PM10 on PEF were widely spread and smaller than those for PM2.5 (fixed effects summary: -0.012 v -0.063 l x min(-1) per microg x m(-3) rise). A similar pattern was evident for symptoms. Random effects models produced larger estimates. Overall, in between-study comparisons, panels of children with diagnosed asthma or pre-existing respiratory symptoms appeared less affected by PM10 levels than those without, and effect estimates were larger where studies were conducted in higher ozone conditions. Larger PM10 effect estimates were obtained from studies using generalised estimating equations to model autocorrelation and where results were derived by pooling subject specific regression coefficients. A funnel plot of PM10 results for PEF was markedly asymmetrical. CONCLUSIONS: The majority of identified studies indicate an adverse effect of particulate air pollution that is greater for PM2.5 than PM10. However, results show considerable heterogeneity and there is evidence consistent with publication bias, so limited confidence may be placed on summary estimates of effect. The possibility of interaction between particle and ozone effects merits further investigation, as does variability due to analytical differences that alter the interpretation of final estimates.

Air Pollutants↗
PubMed2004

Zafirlukast for severe recurrent vulvovaginal candidiasis: an open label pilot study.

BACKGROUND: Recurrent vulvovaginal candidiasis (VVC) has been linked to allergic disease, particularly allergic rhinitis. OBJECTIVE: A pilot study to assess the possible use of the leukotriene receptor antagonist zafirlukast as a treatment for recurrent VVC. METHODS: 20 women with six or more symptomatic attacks of VVC in the past year (at least four proved microbiologically). Clinical atopy determined by the International Study for Asthma and Allergies in Childhood (ISAAC) questionnaire assessed blindly. Monitoring by daily symptom diary and self taken vaginal swabs. Treatment with zafirlukast 20 mg twice daily for 24 weeks or until three microbiologically confirmed episodes of VVC. Response assessed by daily symptom diary and self taken vaginal swabs. Subjective response scales for improvement, side effects, and change in other allergic disease completed when stopping treatment. Semistructured telephone interview 1 year after stopping medication. RESULTS: 14 patients (70%) reported a subjective response on the improvement response scale. Six (30%) showed a complete response with no further symptomatic attacks of VVC or negative swabs when symptomatic. Seven (37%) remained symptom free 18 months after entering the study-that is, 12 months after stopping therapy. 11 (58%) remained symptom free for at least 3 months after stopping therapy. This does not include one patient who remained symptom free but continued on zafirlukast because of an improvement in her asthma. There was no clear relation between response and atopic status. Six of nine atopic subjective responders reported improvements in other allergic symptoms. Side effects were minimal; one seemed clearly attributable to the drug. CONCLUSION: Zafirlukast offers a potential new treatment for recurrent VVC that requires confirmation in controlled studies.

Adult↗
PubMed2003

Exhaled nitric oxide in cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

Exhaled nitric oxide (NO) is thought to be a marker of asthmatic inflammation. Levels in cystic fibrosis (CF) are generally low. This study aimed to measure exhaled NO in CF patients at high risk of developing ABPA and patients at low risk. We studied nine patients at high risk of developing ABPA and 36 at low risk. The two groups were similar in age and spirometry. All patients in the high-risk group were taking oral or inhaled glucocorticoids, compared to 56% in the low-risk group (P=0.02). The exhaled NO levels were lower in the high-risk group than in the low-risk group (2.0 vs. 3.6 ppb), mean difference (95% CI) 1.6 (-3.6 to 0.4) ppb, P=0.001. On subgroup analysis of patients on oral glucocorticoids, the exhaled NO levels were significantly lower in patients with a high risk of developing ABPA (n=7) than patients with a low risk (n=8) (P=0.011). The number of patients who were on inhaled, but not oral glucocorticoids was too small to analyse usefully. Exhaled NO levels were lower in CF patients with a high risk of developing ABPA and on glucocorticoids. This may be because oral glucocorticoids exert a greater effect on exhaled NO than inhaled glucocorticoids. Alternatively, inducible nitric oxide synthase may be down-regulated by Aspergillus toxin.

Adolescent↗
PubMed2003

Cost-effectiveness of fluticasone propionate in the treatment of chronic obstructive pulmonary disease: a double-blind randomized, placebo-controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating disease and places a large financial burden on health-care systems and society. We prospectively evaluated the cost-effectiveness offluticasone propionate (FP) treatment in patients with moderate-to-severe COPD, who were symptomatic on regular bronchodilator therapy. METHODS: An economic analysis was performed in a 6-month, randomized, double-blind clinical trial comparing FP 1,000 microg/day with placebo in 281 patients aged 45-79 years with symptomatic moderate-to-severe COPD. Data on clinical efficacy, health-care resource use and productivity loss associated with the management of COPD were prospectively collected. The main outcome measures were the incremental cost-effectiveness of achieving a > or = 10% improvement in FEV1 and of remaining exacerbation-free throughout the study. The economic evaluation was costed from the perspective of the NHS (direct costs) and of society (direct and indirect costs). RESULTS: FP was significantly more effective than placebo in terms of the proportions of patients demonstrating a > or = 10% improvement in FEV1 (32 vs. 19%; P = 0.02) and remaining free of moderate/severe exacerbations (75 vs. 63%; P = 0.02). The difference between the groups in total costs was not significantly different. Incremental cost-effectiveness analyses showed that the additional clinical benefits of FP relativeto placebo, in terms of a > or = 10% improvement in FEV1 or an increased number of patients free of moderate/severe exacerbations, were achieved at minimal additional costs from an NHS perspective (additional 0.25 pounds per day for bath) or at a net saving from a societal perspective. Sensitivity analysis showed that these results were robust to changes in the underlying assumptions. CONCLUSIONS: Treatment with FP was associated with statistically significant clinical benefits in patients with moderate-to-severe COPD currently symptomatic on regular bronchodilator therapy. As the differences in direct and total costs compared with placebo were small and non-significant, this treatment can be considered cost-effective in this patient population.

Aged↗
PubMed2003

Why cardiologists should be interested in air pollution.

Despite major improvements in air quality resulting from increasingly stringent legislation, there remains a strong association between daily mortality and current levels of air pollution. Growing epidemiological evidence suggests that many, perhaps the majority, of these deaths are caused by cardiovascular disease.

Acute Disease↗
PubMed2003

The effect of sulphurous air pollutant exposures on symptoms, lung function, exhaled nitric oxide, and nasal epithelial lining fluid antioxidant concentrations in normal and asthmatic adults.

AIMS: To explore the effects in normal and asthmatic adults of exposure to 200 ppb sulphur dioxide (SO2) and 200 microg/m3 and 2000 microg/m3 aerosols of ammonium bisulphate (AB) and sulphuric acid (SA) (MMD 0.3 microm). METHODS: Exposures were placebo controlled, for one hour at rest, double blind in random order. DeltaFEV1 was the primary outcome; secondary outcomes included symptoms, ventilation, exhaled nitric oxide (NO) concentrations, and nasal lavage fluid ascorbic (AA) and uric acid (UA) concentrations. RESULTS: There were no significant changes in spirometry or symptoms with any exposure in either group. SO2 exposure was associated with an increased respiratory rate relative to air exposure in the asthmatic group (SO2: 958.9 breaths/hour; air: 906.8 breaths/hour) but the mean volume breathed did not differ significantly (SO2: 318.8 litres; air: 311.4 litres). AB exposures were associated with a significant rise in [NO] in the asthmatic (+1.51 ppb, and +1.39 ppb), but not in the normal group. Mean pre- and post-exposure [AA] tended to be higher in the normal than in the asthmatic group. Within each group, [AA] did not change significantly with any exposure. Post-exposure [UA] were greater than pre-exposure concentrations for all exposures, significantly so in the normal group for all exposures except SO2. There were no significant differences in the mean change in [UA] for any exposure relative to air. CONCLUSIONS: The pollutant exposure concentrations employed in this study were generally much greater than ambient. It is unlikely that short lived exposures at lower concentrations would show significant effects, but effects of longer term lower concentration exposures cannot be ruled out.

Adult↗
PubMed2003

Respiratory effects of sulphur dioxide: a hierarchical multicity analysis in the APHEA 2 study.

BACKGROUND: Sulphur dioxide (SO(2)) was associated with hospital admissions for asthma in children in the original APHEA study, but not with other respiratory admissions. AIMS: To assess the association between daily levels of SO(2) and daily levels of respiratory admissions in a larger and more recent study. METHODS: Time series of daily counts of hospital emergency admissions were constructed for asthma at ages 0-14 years and 15-64 years, COPD and asthma, and all respiratory admissions at ages 65+ years in the cities of Birmingham, London, Milan, Paris, Rome, Stockholm, and in the Netherlands for periods of varying duration between the years 1988 and 1997. A two stage hierarchical modelling approach was used. In the first stage generalised additive Poisson regression models were fitted in each city controlling for weather and season. These results were then combined across cities in a second stage ecological regression that looked at potential effect modifiers. RESULTS: For an increase of 10 micro g/m(3) of SO(2) the daily number of admissions for asthma in children increased 1.3% (95% CI 0.4% to 2.2%). Effect modification among cities by levels of other air pollutants or temperature was not found. The SO(2) effect disappeared after controlling for PM(10) or CO, but correlation among these pollutants was very high. Other respiratory admissions were not associated with SO(2). CONCLUSION: SO(2) is associated with asthma admissions in children, indicating that reduction in current air pollution levels could lead to a decrease in the number of asthma admissions in children in Europe.

Adolescent↗
PubMed2002

Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort.

BACKGROUND: Some patients exposed to Q fever (Coxiella burnetii infection) may develop chronic fatigue. AIM: To determine whether subjects involved in the West Midlands Q fever outbreak of 1989 had increased fatigue, compared to non-exposed controls, 10 years after exposure. DESIGN: Matched cohort study comparing cases to age-, sex- and smoking-history-matched controls not exposed to Q fever. METHODS: A postal questionnaire was sent to subjects at home, followed by further assessment in hospital, including a physical examination and blood tests. RESULTS: Of 108 Q-exposed subjects, 70 (64.8%) had fatigue, 37 idiopathic chronic fatigue (ICF) (34.3%), vs. 29/80 (36.3%) and 12 (15.0%), respectively, in controls. In 77 matched pairs, fatigue was commoner in Q-exposed subjects than in controls: 50 (64.9%) vs. 27 (35.1%), p<0.0001. ICF was found in 25 (32.5%) of Q-exposed patients and 11(14.3%) of controls (p=0.01). There were 36 (46.8%) GHQ cases in Q-exposed subjects, vs. 18 (23.4%) controls (p=0.004). A matched analysis of those more intensively studied showed fatigue in 48 (66.7%) Q-exposed patients and 25 (34.7%) controls, (p<0.0001), ICF in 25 (34.7%) Q-exposed and 10 (13.9%) controls (p=0.004), and chronic fatigue syndrome (CFS) in 14 (19.4%) Q-exposed patients and three (4.2%) controls (p=0.003). Thirty-four (47.2%) Q-exposed patients were GHQ cases compared to 17 (23.6%) controls (p=0.004). DISCUSSION: Subjects who were exposed to Coxiella in 1989 had more fatigue than did controls, and some fulfilled the criteria for CFS. Whether this is due to ongoing antigen persistence or to the psychological effects of prolonged medical follow-up is uncertain.

Case-Control Studies↗