Mary F Linehan

BCG vaccination and allergy: a systematic review and meta-analysis

BACKGROUND There is conflicting evidence on whether BCG vaccination might represent an effective primary preventative strategy against the development of allergic sensitization and disease. OBJECTIVES We sought to systematically review the relationship between BCG vaccination and the risk of sensitization, eczema/atopic dermatitis, allergic rhinoconjunctivitis, asthma, and other allergic conditions, such as food allergy and anaphylaxis. METHODS Four international databases were searched for published epidemiologic or interventional studies. Additional online study databases were searched and vaccine manufacturers and a panel of international experts were contacted in an attempt to locate unpublished or ongoing studies. Quality assessment was undertaken by using internationally established criteria. Meta-analyses were undertaken by using fixed- or random-effects modeling. Funnel plots were used to assess for the risk of publication bias. RESULTS We identified 767 articles, of which 17 satisfied our inclusion criteria; there was only 1 randomized controlled trial, with the remaining studies being epidemiologic investigations. Meta-analyses did not show any protective effect of vaccination against the risk of sensitization, as judged by specific IgE tests (odds ratio [OR], 1.31; 95% CI, 1.07-1.60) or skin prick testing (OR, 0.87; 95% CI, 0.67-1.13); the risk of atopic eczema/dermatitis (OR, 0.84; 95% CI, 0.64-1.09); or the risk of allergic rhinoconjunctivitis (OR, 1.07; 95% CI, 0.89-1.28). BCG vaccination was associated with a protective effect against the risk of asthma (OR, 0.73; 95% CI, 0.56-0.95), although this might be explained by publication bias. CONCLUSIONS BCG vaccination is unlikely to be associated with protection against the risk of allergic sensitization and disease. The observed possible benefit in relation to the development of asthma is unlikely to be due to allergic sensitization.

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.

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.

Smoking, respiratory symptoms and likely asthma in young people: evidence from postal questionnaire surveys in the Wythenshawe Community Asthma Project (WYCAP)

BackgroundAlthough it is recognised that smoking is a major risk factor for subjects with chronic obstructive pulmonary disease and is associated with respiratory symptoms, there is less agreement concerning the relationship between asthma and smoking. This study aims to examine the relationship between cigarette smoking and asthma prevalence.MethodData were used from two postal questionnaire surveys (1999 and 2001) in two general practice populations, using a respiratory questionnaire based on the ECRHQ and a generic quality of life questionnaire (EQ-5D). Only subjects less than 45 years old were included in the survey. An empirical definition of likely asthma was used based on respiratory questionnaire responses. Smoking was examined according to three categories, current smoker, ex smoker and never smoker.ResultsAlmost 3500 subjects were included in the analyses. Current smokers had a higher prevalence of likely asthma compared to never smokers, odds ratio (OR) 1.59 (95% confidence interval (CI) 1.24 to 2.04). and also compared to ex smokers OR 1.79 (CI 1.25 to 2.56), but there was no difference between ex smokers and never smokers (OR 1.00 (0.75–1.35)). Current smoking was also positively associated with all symptoms but not with a history of hayfever/eczema.ConclusionAlthough the positive association found between current smoking and obstructive airways disease is likely to be due to the effect of cigarettes on asthma, it could reflect an association with early COPD (GOLD stages 0 or 1). Smoking cessation has a beneficial effect on the prevalence of respiratory symptoms and is therefore of paramount importance among these young adults.

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.

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.

Does BCG vaccination protect against childhood asthma

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.

Does BCG vaccination protect against childhood asthma? Final results from MANCAS 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.