Does BCG vaccination protect against childhood asthma? Final results from the Manchester Community Asthma Study retrospective cohort study and updated systematic review and meta-analysis.

BACKGROUND: The Manchester Community Asthma Study (MANCAS) found a protective effect against the risk of wheeze at age 6 to 11 years for children given neonatal BCG vaccination. Our subsequent systematic review and meta-analysis suggested that BCG vaccination did not protect against allergic sensitization but might have exerted a protective effect against nonatopic asthma. OBJECTIVES: We sought to assess whether the protective effect of BCG vaccination on wheeze observed in the MANCAS cohort was maintained at age 13 to 17 years and to incorporate the findings from this final MANCAS analysis into an updated systematic review and meta-analysis. METHODS: BCG vaccination status was determined from health records and respiratory outcomes from questionnaire responses. We updated the systematic review and used fixed-effects and random-effects modeling to undertake meta-analyses. RESULTS: There were 1608 participants in the final MANCAS analysis. The 12-month prevalence of wheeze was 15.1%. There was no difference in prevalence between those who were and were not BCG vaccinated (15.8% vs 14.3%; relative risk, 1.05; 95% CI, 0.94-1.19). The updated meta-analysis incorporated 4 new studies: this showed that the protective effect of BCG vaccination against the development of asthma identified in our previous meta-analysis was attenuated (odds ratio, 0.95; 95% CI, 0.89-1.00). No protective effect of BCG was seen for sensitization, eczema/atopic dermatitis, rhinoconjunctivitis, or allergy in general. CONCLUSIONS: Taken together, the final results of the MANCAS cohort and the updated systematic review and meta-analysis provide clearer evidence that any protective effect of BCG vaccination on childhood asthma is likely to be transient.

Prevalence of respiratory symptoms at two time points in a population of children in Manchester--a cohort study.

OBJECTIVE: Although the prevalence of asthma and atopy has been noted to have increased in recent decades, patterns of asthma prevalence have, traditionally, been difficult to track. Most reports on trends in childhood asthma have been cross-sectional measuring the prevalence in cohorts of similar aged children at different time points. The aim of this paper is to report on the prevalence of symptoms in the same cohort at two separate time points. DESIGN: Retrospective cohort study. SETTING: Community-based study, Central Manchester. PARTICIPANTS: MANCAS1, study n=5086, participation n=2414. MANCAS2, study n=6338, participation n=1608. Children born in a hospital in Manchester within specified dates and still living or attending a school in Central Manchester were eligible for inclusion. Children on an 'at-risk' register or living with short-term carers were excluded. OUTCOME MEASURES: Data on respiratory symptoms were collected at two separate time points using parent completed questionnaires. RESULTS: Response rate for MANCAS1 was 47.5% and 25.4% for MANCAS2. There were 801 individuals for whom a response to both studies was received. There was a significant reduction in the prevalence of night cough (29.5% vs 18.3%, McNemar <0.01) and antibiotic use for respiratory infections (9.1% vs 4.3%, McNemar <0.01) between the two study time points. The prevalence of hay fever/eczema increased (41.6% vs 46.9%, McNemar <0.01) between the two studies. There was no significant difference in the prevalence of wheeze, exercise-induced wheeze or asthma medication. CONCLUSIONS: Although this report of respiratory symptom prevalence in the same population at two time points over a 7-year period shows a constant burden of asthma symptoms, there is some suggestion of variability in asthma symptom prevalence within the cohort as the children matured while the burden of allergy symptoms increased.

Temporal change in health-related quality of life: a longitudinal study in general practice 1999-2004.

BACKGROUND: In order to assess and plan for changing healthcare needs, the lack of available information regarding temporal changes in the health-related quality of life of a population must be addressed. AIM: This paper aims to describe such changes over 5 years in a general population. DESIGN OF STUDY: Longitudinal postal questionnaire study. SETTING: UK general practice. METHOD: This was a longitudinal postal questionnaire study in two general practice populations, using the generic instrument EQ-5D to measure health-related quality of life. Individuals were included if they responded to three postal surveys in 1999, 2001, and 2004 and there were three consecutive values of EQ-5D(index) available between 1999 and 2004. RESULTS: A total of 2498 subjects were included in the study. After adjustment for potential confounders (including ageing), health-related quality of life declined significantly over the observation period. The change in EQ-5D(index) was from 0.79 to 0.74 and for EQ-5D(vas) 76.8 to 73.3 (P for both trends <0.001). CONCLUSION: Health-related quality of life deteriorated in these populations over 5 years. In an era of improvements in mortality, this has important implications for the use of health-related quality of life data in healthcare planning and resource allocation.

How do common chronic conditions affect health-related quality of life?

BACKGROUND: Comorbidity is common. National Institute for Health and Clinical Excellence (NICE) guidelines have been created to make best use of resources to improve patients' quality of life but do not currently take account of comorbidity. The effect of multiple chronic conditions with regard to health-related quality of life (HRQoL) is poorly researched. Criticisms of previous research have been due to patient-defined chronic conditions, lack of quantification of the effects of confounding factors, selection of affected patients only, small sample sizes, and upper age limits. AIM: This study aims to address these issues, looking into the impact of combinations of chronic conditions on HRQoL. DESIGN OF THE STUDY: Participants filled in a questionnaire containing general health information, specific respiratory questions, and the EQ-5D measure of HRQoL. The questionnaires were then matched up to their GP records to obtain their disease status for six common chronic diseases (asthma, chronic obstructive pulmonary disease, ischaemic heart disease, hypertension, diabetes, and cerebrovascular disease). METHOD: Data from a mailed questionnaire were analysed from 5169 patients aged >16 years from two general practices in Wythenshawe, Manchester in 2004. Completion of the questionnaire was taken to indicate consent to participate. RESULTS: Significant correlations were found between a lower HRQoL and increasing numbers of chronic conditions (P<0.001), increasing age, possible obstructive airway disease, lack of higher education, smoking, and female sex. These all remained significant following regression, except for sex, with number of chronic conditions being a strong predictor of the weighted health state index score, EQ-5D(index) (coefficient = -0.079, P<0.001). CONCLUSION: Increasing numbers of chronic conditions have a strong negative effect on HRQoL.

Prevalence of respiratory symptoms, features of asthma, and characteristics associated with respiratory disease, in 6-11 year olds in Manchester.

AIMS: This paper describes the prevalence of respiratory symptoms, features of asthma, and characteristics associated with respiratory disease in 6-11 year old children in an historical cohort study. METHODS: The study included 5086 children, all born in the same maternity unit in the north west of England over a four-year period. The prevalence of respiratory symptoms, features of asthma, and characteristics associated with respiratory disease were determined by the use of parent-completed questionnaires. Skin prick tests were used to ascertain atopic status. RESULTS: The response was 47.5%. The prevalence of wheeze, asthma medication use and atopic sensitisation were 20.3%, 16.2% and 37.1% respectively. Wheeze and atopy were significantly more prevalent in boys (22.4% versus 17.9% and 43.0% versus 29.3%, respectively). CONCLUSIONS: This study identified a high prevalence of respiratory disease in this population and provides a baseline for monitoring trends in respiratory disease in 6-11 year old children.

Factors influencing the response to postal questionnaire surveys about respiratory symptoms.

BACKGROUND: Response rates to postal questionnaires have been falling in recent years. AIM: To examine factors affecting the response to five postal respiratory questionnaire surveys. DESIGN: Cross sectional study. SETTING: General practice. METHOD: Five surveys were conducted in all adults registered with two UK general practices using an ECRHQ-based questionnaire, with two reminders at 4-week intervals. RESULTS: Response rates declined over time (1993 - 71.2%; 1995 - 70.5%; 1999 - 65.5%; 2001 - 65.3%; 2004 - 46.9%). Age and gender of non-responders were available for 2001 and 2004: responders were older (mean 48.8 years vs 37.6, p<0.001; 50.5 vs 38.8, p<0.001) and more likely to be female (54.9% vs 44.9%, p<0.001; 55.3% vs 48.5%, p<0.001). The response rate was increased by 18% (2004) and 23% (2001) by the use of two reminders. Early responders were older and more likely to be females, but were less likely to smoke than late responders after reminders. There was no important association between respiratory symptoms and associated feature prevalence and stage of response. CONCLUSION: Declining response rates may represent reduced motivation and reluctance to share personal information. Qualitative exploration of late/non-response could help reduce bias when planning and analysing such surveys. The use of two reminders is an important factor in improving response.

Long term prognosis in preschool children with wheeze: longitudinal postal questionnaire study 1993-2004.

OBJECTIVES: To follow a population of preschool children with and without parent reported wheeze over a period of 6-11 years to determine prognosis and its important predictive factors. DESIGN: Longitudinal series of five postal surveys based on the international study of asthma and allergies in childhood questionnaire carried out between 1993 and 2004. SETTING: Two general practice populations, south Manchester. PARTICIPANTS: 628 children aged less than 5 years at recruitment and those with at least six years' follow-up data. MAIN OUTCOME MEASURES: Parent completed questionnaire data for respiratory symptoms and associated features. RESULTS: Of 628 children included in the study, 201 (32%) had parent reported wheeze at the first observation (baseline), of whom 27% also reported the symptom on the second occasion (persistent asthma). The only important baseline predictors of persistent asthma were exercise induced wheeze (odds ratio 3.94, 95% confidence interval 1.72 to 9.00) and a history of atopic disorders (4.44, 1.94 to 10.13). The presence of both predictors indicated a likelihood of 53.2% of developing asthma; if only one feature was present this decreased to 17.2%, whereas if neither was present the likelihood was 10.9%. Family history of asthma was not predictive of persistent asthma among children with preschool wheeze. CONCLUSION: Using two simple predictive factors (baseline parent reported exercise induced wheeze and a history of atopic disorders), it is possible to estimate the likelihood of future asthma in children presenting with preschool wheeze. The absence of baseline exercise induced wheeze and a history of atopic disorders reduces the likelihood of subsequent asthma by a factor of five.

The estimated prevalence of chronic obstructive pulmonary disease in a general practice population.

OBJECTIVE: To estimate the prevalence of chronic obstructive pulmonary disease (COPD) in a general practice population in the UK. METHOD: Four postal respiratory questionnaire surveys were carried out between 1993 and 2001. Subjects from the 2001 study were invited for spirometry if they were aged 30 years or more, had indicated that they were 'ever smokers' in any of the surveys, and/or had been considered to have likely obstructive airways disease on the basis of their replies to the 2001 questionnaire. RESULTS: 2646 subjects were invited for spirometry of whom 871 (32.9%) attended. Results were available for 825 participants. 163 of these subjects were categorised as having COPD. The estimated prevalence in the whole population was 4.1% with the highest prevalence (14.7%) in those aged 60-69 years. In those aged over 40 years it was 9.6%. CONCLUSION: This study suggests that the prevalence of COPD is much higher than the previous estimates of between 1 and 2%.

Is the prevalence of wheeze in children altered by neonatal BCG vaccination?

BACKGROUND: The prevalence of asthma and atopic disease has increased in recent decades, but precise reasons for this increase are unknown. BCG vaccination is thought to be among a group of vaccines capable of manipulating the immune system toward T(H)1 dominance and therefore reducing the likelihood of atopic disease. OBJECTIVE: The aim of this study was to determine the influence of neonatal BCG vaccination on the prevalence of wheeze in a large community population of children. METHOD: In a historical cohort study, a parent-completed questionnaire was used to identify the prevalence of wheeze in BCG-vaccinated and nonvaccinated children in Manchester, England. RESULTS: There were 2414 participants aged between 6 and 11 years. In a univariate analysis neonatal BCG vaccination was associated with a significantly lower prevalence of wheeze (odds ratio, 0.69; 95% CI, 0.55-0.86), and statistical significance was retained when the analysis was adjusted for potential confounders (odds ratio, 0.68; 95% CI, 0.53-0.87). CONCLUSION: These results demonstrate an association between asthma symptom prevalence and neonatal BCG vaccination, relating to a possible 27% reduction in prevalence, and are therefore of considerable public health importance. CLINICAL IMPLICATIONS: The capacity of neonatal BCG vaccination to reduce the prevalence of respiratory symptoms in children warrants further investigation.

The diagnostic accuracies of chronic obstructive pulmonary disease (COPD) in general practice: The results of the MAGIC (Manchester Airways Group Identifying COPD) study.

BACKGROUND: Although it is generally accepted that chronic obstructive pulmonary disease (COPD) is underdiagnosed, there is little objective information concerning the size of the problem in the UK. METHOD: Patients from two general practices were offered spirometry if they were aged 30 or older, had reported ever smoking in one of four postal respiratory surveys (1993-2001), and/or reported four or more symptoms or risk factors in 2001 indicating likely obstructive airways disease. RESULTS: Of 2646 subjects invited, 871 attended and 825 had adequate spirometry results for analysis. In all, 163 patients had spirometrically-confirmed COPD; 103 of these (63.2%) had no recorded COPD in their practice records, including 14 out of 31 (45.2%) whose spirometry results classified them as having severe or very severe COPD. CONCLUSION: This study found a considerable under-recording of COPD in two general practices. This may be due to a combination of administrative and diagnostic problems (including the under-use of spirometers), and a reluctance of patients to present with their symptoms. These results have important implications in terms of unmet need and resource utilisation.

Temporal change in the prevalence of respiratory symptoms and obstructive airways disease 1993-2001.

BACKGROUND: There has been little available information regarding secular changes in the prevalence of respiratory symptoms since the mid-1990s. AIM: To examine changes in the prevalence of respiratory symptoms for 1993-2001. DESIGN OF STUDY: A series of postal questionnaire surveys. SETTING: Two general practice populations, including all age groups. METHOD: Four postal respiratory questionnaire surveys were conducted between 1993 and 2001. Subjects who replied to two or more surveys (8058 adults and 2350 children) were included in the main analyses. Validated scoring systems were used to define obstructive airways disease in adults and asthma in children. RESULTS: Over the 8-year observation period there were increases among adults in the crude prevalence of wheeze, being woken by cough, receipt of current asthma medication, and of obstructive airways disease, compared with decreases in children for wheeze, night cough, asthma attacks, and asthma. For adults, adjusted odds ratios per year of secular increase were 1.03 (95% confidence interval [CI] = 1.02 to 1.03) for wheeze, 1.03 (95% CI = 1.02 to 1.03) for being woken by cough, 1.03 (95% CI = 1.02 to 1.04) for asthma medication, and 1.02 (95% CI = 1.01 to 1.03) for obstructive airways disease. These increases were greater in those aged over 44 years, in males, and in those without a family history of asthma or a history of hayfever or eczema. Corresponding decreases for children were 0.94 (95% CI = 0.92 to 0.97) for wheeze, 0.93 (95% CI = 0.91 to 0.96) for night cough, 0.93 (95% CI = 0.90 to 0.95) for asthma attacks and 0.98 (95% CI = 0.95 to 1.00) for asthma. CONCLUSION: The increases found in adults are more likely to be due to chronic obstructive pulmonary disease (COPD) than asthma. This is supported by the decreases in symptom and asthma prevalence in children.