Model-based evaluation of the long-term cost-effectiveness of systematic case-finding for COPD in primary care.

INTRODUCTION: 'One-off' systematic case-finding for COPD using a respiratory screening questionnaire is more effective and cost-effective than routine care at identifying new cases. However, it is not known whether early diagnosis and treatment is beneficial in the longer term. We estimated the long-term cost-effectiveness of a regular case-finding programme in primary care. METHODS: A Markov decision analytic model was developed to compare the cost-effectiveness of a 3-yearly systematic case-finding programme targeted to ever smokers aged ≥50 years with the current routine diagnostic process in UK primary care. Patient-level data on case-finding pathways was obtained from a large randomised controlled trial. Information on the natural history of COPD and treatment effects was obtained from a linked COPD cohort, UK primary care database and published literature. The discounted lifetime cost per quality-adjusted life-year (QALY) gained was calculated from a health service perspective. RESULTS: The incremental cost-effectiveness ratio of systematic case-finding versus current care was £16 596 per additional QALY gained, with a 78% probability of cost-effectiveness at a £20 000 per QALY willingness-to-pay threshold. The base case result was robust to multiple one-way sensitivity analyses. The main drivers were response rate to the initial screening questionnaire and attendance rate for the confirmatory spirometry test. DISCUSSION: Regular systematic case-finding for COPD using a screening questionnaire in primary care is likely to be cost-effective in the long-term despite uncertainties in treatment effectiveness. Further knowledge of the natural history of case-found patients and the effectiveness of their management will improve confidence to implement such an approach.

Birmingham COPD Cohort: a cross-sectional analysis of the factors associated with the likelihood of being in paid employment among people with COPD.

BACKGROUND: Employment rates among those with chronic obstructive pulmonary disease (COPD) are lower than those without COPD, but little is known about the factors that affect COPD patients' ability to work. METHODS: Multivariable analysis of the Birmingham COPD Cohort Study baseline data was used to assess the associations between lifestyle, clinical, and occupational characteristics and likelihood of being in paid employment among working-age COPD patients. RESULTS: In total, 608 of 1,889 COPD participants were of working age, of whom 248 (40.8%) were in work. Older age (60-64 years vs 30-49 years: odds ratio [OR] =0.28; 95% confidence interval [CI] =0.12-0.65), lower educational level (no formal qualification vs degree/higher level: OR =0.43; 95% CI =0.19-0.97), poorer prognostic score (highest vs lowest quartile of modified body mass index, airflow obstruction, dyspnea, and exercise (BODE) score: OR =0.10; 95% CI =0.03-0.33), and history of high occupational exposure to vapors, gases, dusts, or fumes (VGDF; high VGDF vs no VGDF exposure: OR =0.32; 95% CI =0.12-0.85) were associated with a lower probability of being employed. Only the degree of breathlessness of BODE was significantly associated with employment. CONCLUSION: This is the first study to comprehensively assess the characteristics associated with employment in a community sample of people with COPD. Future interventions should focus on managing breathlessness and reducing occupational exposures to VGDF to improve the work capability among those with COPD.

Targeted case finding for chronic obstructive pulmonary disease versus routine practice in primary care (TargetCOPD): a cluster-randomised controlled trial.

BACKGROUND: Many individuals with chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. Health-care organisations are implementing case-finding programmes without good evidence of which are the most effective and cost-effective approaches. We assessed the effectiveness and cost-effectiveness of two alternative approaches to targeted case finding for COPD compared with routine practice. METHODS: In this cluster-randomised controlled trial, participating general practices in the West Midlands, UK, were randomly assigned (1:1), via a computer-generated block randomisation sequence, to either a targeted case-finding group or a routine care group. Eligible patients were ever-smokers aged 40-79 years without a previously recorded diagnosis of COPD. Patients in the targeted case-finding group were further randomly assigned (1:1) via their household to receive either a screening questionnaire at the general practitioner (GP) consultation (opportunistic) or a screening questionnaire at the GP consultation plus a mailed questionnaire (active). Respondents reporting relevant respiratory symptoms were invited for post-bronchodilator spirometry. Patients, clinicians, and investigators were not masked to allocation, but group allocation was concealed from the researchers who performed the spirometry assessments. Primary outcomes were the percentage of the eligible population diagnosed with COPD within 1 year (defined as post-bronchodilator forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] ratio <0·7 in patients with symptoms or a new diagnosis on their GP record) and cost per new COPD diagnosis. Multiple logistic and Poisson regression were used to estimate effect sizes. Costs were obtained from the trial. This trial is registered with ISRCTN, number ISRCTN14930255. FINDINGS: From Aug 10, 2012, to June 22, 2014, 74 818 eligible patients from 54 diverse general practices were randomly assigned and completed the trial. At 1 year, 1278 (4%) cases of COPD were newly detected in 32 789 eligible patients in the targeted case-finding group compared with 337 (1%) cases in 42 029 patients in the routine care group (adjusted odds ratio [OR] 7·45 [95% CI 4·80-11·55], p<0·0001). The percentage of newly detected COPD cases was higher in the active case-finding group (822 [5%] of 15 378) than in the opportunistic case-finding group (370 [2%] of 15 387; adjusted OR 2·34 [2·06-2·66], p<0·0001; adjusted risk difference 2·9 per 100 patients [95% CI 2·3-3·6], p<0·0001). Active case finding was more cost-effective than opportunistic case finding (£333 vs £376 per case detected, respectively). INTERPRETATION: In this well established primary care system, routine practice identified few new cases of COPD. An active targeted approach to case finding including mailed screening questionnaires before spirometry is a cost-effective way to identify undiagnosed patients and has the potential to improve their health. FUNDING: National Institute for Health Research.

A Preliminary Assessment of the Role of Ambient Nitric Oxide Exposure in Hospitalization with Respiratory Syncytial Virus Bronchiolitis.

Some in vitro studies have indicated a possible link between respiratory syncytial virus (RSV) infection and exposure to Nitric Oxide (NO). However, these studies used much higher NO concentrations than normally found in the ambient environment. This preliminary study explored whether an association was present with short-term exposure to NO in the environment. RSV-related admission data between November 2011 and February 2012 were obtained from Sheffield Children's Hospital. The dates of admission were linked to contemporaneous ambient NO derived from sentinel air monitors. The case-crossover design was used to study the relationship between daily RSV admissions and NO, controlling for temperature and relative humidity. We found little evidence of association between daily RSV admission rates and exposure to ambient NO at different lags or average exposure across several lags. The findings should, however, be viewed with caution due to the low number of events observed during the time frame. It is possible that the apparent lack of association may be accounted for by the timing of the seasonal RSV epidemic in relation to peaks in NO concentrations. A larger study incorporating a wider range of RSV and NO peaks would determine whether said peaks enhanced the number of RSV hospitalizations in children.

Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial.

BACKGROUND: In 2002-04, we did a randomised controlled trial in southern Nepal, and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to investigate whether these differences would be sustained. METHODS: For this follow-up study, we identified children from the original trial and measured anthropometry, body composition with bioelectrical impedance (with population-specific isotope calibration), blood pressure, and renal dimensions by ultrasound. We documented socioeconomic status, household food security, and air pollution. Main outcomes of the follow-up at 8 years were Z scores for weight-for-age, height-for-age, and body-mass index (BMI)-for-age according to WHO Child Growth Standards for children aged 5-19 years, and blood pressure. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN88625934. FINDINGS: Between Sept 21, 2011, and Dec 7, 2012, we assessed 841 children (422 in the control group and 419 in the intervention group). Unadjusted differences (intervention minus control) in Z scores were 0·05 for weight-for-age (95% CI -0·09 to 0·19), 0·02 in height-for-age (-0·10 to 0·15), and 0·04 in BMI-for-age (-0·09 to 0·18). We recorded no difference in blood pressure. Adjusted differences were similar for all outcomes. INTERPRETATION: We recorded no differences in phenotype between children born to mothers who received antenatal multiple micronutrient or iron and folate supplements at age 8·5 years. Our findings did not extend to physiological differences or potential longer-term effects. FUNDING: The Wellcome Trust.

TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol.

BACKGROUND: Many people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach. METHODS/DESIGN: In this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations.All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants.The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure.A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and primary care staff views of each approach. DISCUSSION: This will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first. TRIAL REGISTRATION: Current controlled trials ISRCTN14930255.

Using PM2.5 concentrations to estimate the health burden from solid fuel combustion, with application to Irish and Scottish homes.

BACKGROUND: This study estimates the potential population health burden from exposure to combustion-derived particulate air pollution in domestic settings in Ireland and Scotland. METHODS: The study focused on solid fuel combustion used for heating and the use of gas for cooking. PM2.5 (particulate matter with an aerodynamic diameter < 2.5 µm) was used as the pollutant mixture indicator. Measured PM2.5 concentrations in homes using solid fuels were adjusted for other sources of PM2.5 by subtracting PM2.5 concentrations in homes using gas for cooking but not solid fuel heating. Health burden was estimated for exposure indoors 6 pm - midnight, or all day (24-hour), by combining estimated attributable annual PM2.5 exposures with (i) selected epidemiological functions linking PM2.5 with mortality and morbidity (involving some re-scaling from PM10 to PM2.5, and adjustments 'translating' from concentrations to exposures) and (ii) on the current population exposed and background rates of morbidity and mortality. RESULTS: PM2.5 concentrations in coal and wood burning homes were similar to homes using gas for cooking, used here as a baseline (mean 24-hr PM2.5 concentrations 8.6 µg/m3) and so health impacts were not calculated. Concentrations of PM2.5 in homes using peat were higher (24-hr mean 15.6 µg/m3); however, health impacts were calculated for the exposed population in Ireland only; the proportion exposed in Scotland was very small. The assessment for winter evening exposure (estimated annual average increase of 2.11 µg/m3 over baseline) estimated 21 additional annual cases of all-cause mortality, 55 of chronic bronchitis, and 30,100 and 38,000 annual lower respiratory symptom days (including cough) and restricted activity days respectively. CONCLUSION: New methods for estimating the potential health burden of combustion-generated pollution from solid fuels in Irish and Scottish homes are provided. The methodology involves several approximations and uncertainties but is consistent with a wider movement towards quantifying risks in PM2.5 irrespective of source. Results show an effect of indoor smoke from using peat (but not wood or coal) for heating and cooking; but they do not suggest that this is a major public health issue.

Leukotriene antagonists as first-line or add-on asthma-controller therapy.

BACKGROUND: Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS: We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≥1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS: Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS: Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group. (Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others; Controlled Clinical Trials number, ISRCTN99132811.).

Costs of occupational asthma in the UK.

OBJECTIVES: To estimate the social costs of occupational asthma in the UK. METHODS: A desk-top approach using cost-of-illness methodology was employed, defining direct and indirect lifetime costs for six scenarios: a male and a female worker each exposed to isocyanates, latex and biocides (eg, glutaraldehyde) or flour. The numbers of new cases annually in each industry were estimated from Survey of Work-related and Occupational Respiratory Disease (SWORD) data. The main outcome measure was the current value total working lifetime costs of new cases annually for each scenario. RESULTS: Assuming 209 new cases of occupational asthma in the six scenarios in the year 2003, the present value total lifetime costs were estimated to be £25.3-27.3 million (2004 prices). Grossing up for all estimated cases of occupational asthma in the UK in 2003, this came to £70-100 million. About 49% of these costs were borne by the individual, 48% by the state and 3% by the employer. CONCLUSIONS: The cost to society of occupational asthma in the UK is high. Given that the number of newly diagnosed cases is likely to be underestimated by at least one-third, these costs may be as large as £95-135 million. Each year a new stream of lifetime costs will be added as a newly diagnosed cohort is identified. Approaches to reduce the burden of occupational asthma have a strong economic justification. However, the economic burden falls on the state and the individual, not on the employer. The incentive for employers to act is thus weak.

Cost effectiveness of leukotriene receptor antagonists versus inhaled corticosteroids for initial asthma controller therapy: a pragmatic trial.

BACKGROUND: Information is lacking on the relative effectiveness and cost effectiveness--in a primary-care setting--of leukotriene receptor antagonists (LTRAs) as an alternative to inhaled corticosteroids (ICS) for initial asthma controller therapy. OBJECTIVE: To compare the cost effectiveness of LTRAs versus ICS for patients initiating asthma controller therapy. METHODS: An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 12-80 years with asthma and symptoms requiring regular anti-inflammatory therapy (n = 326) were randomly assigned to LTRAs (n = 162) or ICS (n = 164). The main outcome measures were the incremental costs per point improvement in the Mini Asthma Quality of Life Questionnaire, per point improvement in the Asthma Control Questionnaire and per QALY gained from the UK NHS and societal perspectives. RESULTS: Over 2 years, resource use was similar between the two treatment groups, but the cost to society per patient was significantly higher for the LTRA group, at pounds sterling 711 versus pounds sterling 433 for the ICS group (adjusted difference pounds sterling 204; 95% CI 74, 308) [year 2005 values]. Cost differences were driven primarily by differences in prescription drug costs, particularly study drug costs. There was a nonsignificant (imputed, adjusted) difference between treatment groups, favouring ICS, in QALYs gained at 2 years of -0.073 (95% CI -0.143, 0.010). Therapy with LTRAs was, on average, a dominated strategy, and, at a threshold for willingness to pay of pounds sterling 30,000 per QALY gained, the probability of LTRAs being cost effective compared with ICS was approximately 3% from both societal and NHS perspectives. CONCLUSIONS: There is a very low probability of LTRAs being cost effective in the UK, at 2005 values, compared with ICS for initial asthma controller therapy. TRIAL REGISTRATION: UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.

Cost effectiveness of leukotriene receptor antagonists versus long-acting beta-2 agonists as add-on therapy to inhaled corticosteroids for asthma: a pragmatic trial.

BACKGROUND: Information is lacking on the relative effectiveness and cost effectiveness--in a real-life primary-care setting--of leukotriene receptor antagonists (LTRAs) and long-acting beta2 adrenergic receptor agonists (beta2 agonists) as add-on therapy for patients whose asthma symptoms are not controlled on low-dose inhaled corticosteroids (ICS). OBJECTIVE: To estimate the cost effectiveness of LTRAs compared with long-acting beta2 agonists as add-on therapy for patients whose asthma symptoms are not controlled on low-dose ICS. METHODS: An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 12-80 years with asthma insufficiently controlled with ICS (n = 361) were randomly assigned to add-on LTRAs (n = 176) or long-acting beta2 agonists (n = 185). The main outcome measures were the incremental cost per point improvement in the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), per point improvement in the Asthma Control Questionnaire (ACQ) and per QALY gained from perspectives of the UK NHS and society. RESULTS: Over 2 years, the societal cost per patient receiving LTRAs was pounds sterling 1157 versus pounds sterling 952 for long-acting beta2 agonists, a (significant, adjusted) increase of pounds sterling 214 (95% CI 2, 411) [year 2005 values]. Patients receiving LTRAs experienced a non-significant incremental gain of 0.009 QALYs (95% CI -0.077, 0.103). The incremental cost per QALY gained from the societal (NHS) perspective was pounds sterling 22,589 (pounds sterling 11,919). Uncertainty around this point estimate suggested that, given a maximum willingness to pay of pounds sterling 30,000 per QALY gained, the probability that LTRAs are a cost-effective alternative to long-acting beta2 agonists as add-on therapy was approximately 52% from both societal and NHS perspectives. CONCLUSIONS: On balance, these results marginally favour the repositioning of LTRAs as a cost-effective alternative to long-acting beta2 agonists as add-on therapy to ICS for asthma. However, there is much uncertainty surrounding the incremental cost effectiveness because of similarity of clinical benefit and broad confidence intervals for differences in healthcare costs. TRIAL REGISTRATION: UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.

UK smoke-free legislation: changes in PM2.5 concentrations in bars in Scotland, England, and Wales.

OBJECTIVE: Evaluate the effect of smoke-free legislation on fine particulate [particulate matter <2.5 microm in diameter (PM(2.5))] air pollution levels in bars in Scotland, England, and Wales. DESIGN: Air quality was measured in 106 randomly selected bars in Scotland, England, and Wales before and after the introduction of smoking restrictions. METHODS: PM(2.5) concentrations were measured covertly for 30-min periods before smoke-free legislation was introduced, again at 1-2 months post-ban (except Wales) and then at 12-months post-baseline (except Scotland). In Scotland and England, overt measurements were carried out to assess bar workers' full-shift personal exposures to PM(2.5). Postcode data were used to determine socio-economic status of the bar location. RESULTS: PM(2.5) levels prior to smoke-free legislation were highest in Scotland (median 197 microg m(-3)), followed by Wales (median 184 microg m(-3)) and England (median 92 microg m(-3)). All three countries experienced a substantial reduction in PM(2.5) concentrations following the introduction of the legislation with the median reduction ranging from 84 to 93%. Personal exposure reductions were also within this range. There was evidence that bars located in more deprived postcodes had higher PM(2.5) levels prior to the legislation. CONCLUSIONS: Prior to legislation PM(2.5) concentrations within bars across the UK were much higher than the 65 microg m(-3) 'unhealthy' threshold for outdoor air quality as set by the US Environmental Protection Agency. Concentrations in Scottish and Welsh bars were, on average, two or more times greater than in English bars for which seasonal influences may be responsible. Legislation in all three countries produced improvements in indoor air quality that are consistent with other international studies.

Expectations and changing attitudes of bar workers before and after the implementation of smoke-free legislation in Scotland.

BACKGROUND: In Scotland on March 26, 2006 a comprehensive prohibition on smoking in all enclosed public places was introduced. This study examines bar workers' attitudes towards a smoke-free working environment. METHODS: An intervention study comparing bar workers' opinions before and after the implementation of the smoke-free legislation. Bars were randomly selected in three Scottish cities (Glasgow, Edinburgh & Aberdeen) and towns (Aberdeenshire & Borders). Bar workers were recruited from 72 bars that agreed to participate from 159 approached. Pre- and post-implementation attitudes towards legislation, second-hand smoke and smoke-free working environments were compared. RESULTS: Initially the majority of bar workers agreed with the proposed legislation on smoking (69%) and the need for it to protect the health of workers (80%), although almost half (49%) thought the legislation would damage business. In 266 bar workers seen at both surveys, a significant positive attitudinal change towards the legislation was seen. Post-implementation, support for the legislation rose to 79%, bar workers continued to believe it was needed to protect health (81%) and concerns about the impact on business were expressed by fewer than 20%. Only the statement that the legislation would encourage smokers to quit showed reduced support, from 70% pre-implementation to fewer than 60% post-implementation. Initial acceptance was greater among younger bar workers; older workers, initially more sceptical, became less so with experience of the legislation's effects. CONCLUSION: This study shows that bar workers had generally positive attitudes towards the legislation prior to implementation, which became stronger after implementation. The affirmative attitudes of these key stakeholders are likely to contribute towards the creation of 'smoke-free' as the new social norm.

Community-acquired pneumonia on the intensive care unit: secondary analysis of 17,869 cases in the ICNARC Case Mix Programme Database.

INTRODUCTION: This paper describes the case mix, outcome and activity for admissions to intensive care units (ICUs) with community-acquired pneumonia (CAP). METHODS: We conducted a secondary analysis of a high quality clinical database, the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, of 301,871 admissions to 172 adult ICUs across England, Wales and Northern Ireland, 1995 to 2004. Cases of CAP were identified from pneumonia admissions excluding nosocomial pneumonias and the immuno-compromised. It was not possible to review data from the time of hospital admission; therefore, some patients who developed hospital-acquired/nosocomial pneumonia may have been included. RESULTS: We identified 17,869 cases of CAP (5.9% of all ICU admissions). There was a 128% increase in admissions for CAP from 12.8 per unit to 29.2 per unit during the study period compared to only a 24% rise in total ICU admissions (p < 0.001). Eighty-five percent of admissions were from within the same hospital. Fifty-nine percent of cases were admitted to the ICU < 2 days, 21.5% between 2 and 7 days, and 19.5% > 7 days after hospital admission. Between 1995 and 1999 and 2000 and 2004 there was a rise in admissions from accident and emergency (14.8% to 16.8%; p < 0.001) and high dependency units (6.9% to 11.9%; p < 0.001) within the same hospital, those aged > 74 (18.5 to 26.1%; p < 0.001), and mean APACHE II score (6.83 to 6.91; p < 0.001). There was a fall in past history of severe respiratory problems (8.7% to 6.4%; p < 0.001), renal replacement therapy (1.6% to 1.2%; p < 0.01), steroid treatment (3.4% to 2.8%; p < 0.05), sedation/paralysis (50.2% to 40.4%; p < 0.001), cardiopulmonary resuscitation prior to admission (7.5% to 5.5%; p < 0.001), and septic shock (7.3% to 6.6%; p < 0.001). ICU mortality was 34.9% and ultimate hospital mortality 49.4%. Mortality was 46.3% in those admitted to the ICU within 2 days of hospital admission rising to 50.4% in those admitted at 2 to 7 days and 57.6% in those admitted after 7 days following hospital admission. CONCLUSION: CAP makes up a small, but important and rising, proportion of adult ICU admissions. Survival of over half of all cases vindicates the use of ICU facilities in CAP management. Nevertheless, overall mortality remains high, especially in those admitted later in their hospital stay.

Assessment of bronchial responsiveness following exposure to inhaled occupational and environmental agents.

Inhalation of a range of agents can result in airway inflammation and/or irritation. This may result in occupational asthma or reactive airways dysfunction syndrome. Reactive airways dysfunction syndrome follows a single large exposure to a chemical agent but is now frequently embraced under the wider term of irritant-induced asthma, a term that also includes asthma due to persistent, lower dose irritant exposures. Bronchial hyperresponsiveness is a hallmark of both occupational asthma and reactive airways dysfunction syndrome, although some patients with occupational asthma may occasionally have typical clinical features without increased bronchial hyperresponsiveness. Following removal of the causal agent in occupational asthma, bronchial hyperresponsiveness generally returns towards normal over a 2-year period, although some individuals demonstrate increased bronchial hyperresponsiveness for longer. Measurement of specific bronchial hyperresponsiveness to the primary causal agent in occupational asthma is used diagnostically but not for assessing prognosis. Bronchial hyperresponsiveness to inhaled methacholine can be measured across individual workshifts to assess work-related change. It may also be measured at the end of a work period when exposure has occurred, and compared with values following a period away from work. There have been no direct, systematic comparisons of changes in methacholine responsiveness in the diagnosis of occupational asthma compared with the more frequently used serial peak flow measurements. Patients with reactive airways dysfunction syndrome classically exhibit non-specific bronchial hyperresponsiveness, which can be readily measured by evaluating responses to inhaled methacholine. Bronchial hyperresponsiveness in reactive airways dysfunction syndrome can persist for many years after initial exposure and serial changes can be used to assess recovery and subsequent disability over time.

Characteristics and outcome for admissions to adult, general critical care units with acute severe asthma: a secondary analysis of the ICNARC Case Mix Programme Database.

INTRODUCTION: This report describes the case mix, outcome and activity (duration of intensive care unit [ICU] and hospital stay, inter-hospital transfer, and readmissions to the ICU) for admissions to ICUs for acute severe asthma, and investigates the effect of case mix factors on outcome. METHODS: We conducted a secondary analysis of data from a high-quality clinical database (the Intensive Care National Audit and Research Centre [ICNARC] Case Mix Programme Database) of 129,647 admissions to 128 adult, general critical care units across England, Wales and Northern Ireland over the period 1995-2001. RESULTS: Asthma accounted for 2152 (1.7%) admissions, and in 57% mechanical ventilation was employed during the first 24 hours in the ICU. A total of 147 (7.1%) patients died in intensive care and 199 (9.8%) died before discharge from hospital. The mean age was 43.6 years, and the ratio of women to men was 2:1. Median length of stay was 1.5 days in the ICU and 8 days in hospital. Older age, female sex, having received cardiopulmonary resuscitation (CPR) within 24 hours before admission, having suffered a neurological insult during the first 24 hours in the ICU, higher heart rate, and hypercapnia were associated with greater risk for in-hospital death after adjusting for Acute Physiology and Chronic Health Evaluation II score. CPR before admission, neurological insult, hypoxaemia and hypercapnia were associated with receipt of mechanical ventilation after adjusting for Acute Physiology and Chronic Health Evaluation II score. CONCLUSION: ICU admission for asthma is relatively uncommon but remains associated with appreciable in-hospital mortality. The greatest determinant of poor hospital survival in asthma patients was receipt of CPR within 24 hours before admission to ICU. Clinical management of these patients should be directed at preventing cardiac arrest before admission.