22. Safety: asthma.
| Study ID and design | Population | Outcome definition | Exposure MMR/MMRV vaccine | Findings | Crude data | Estimate (95% CI) |
|
cb‐DeStefano 2002 Cohort study |
Children (0 to 6 years) enrolled in VSD project (4 HMOs) between 1991 and 1997 (n = 167,240) |
Asthma: a child had to meet 1 of the following criteria: (1) at least 1 diagnosis of asthma ICD‐9 Code 493 and at least 1 prescription for an asthma medication; the first diagnosis and first prescription had to be within a 2‐year period. Asthma medications included oral or inhaled beta‐agonists, theophyllin, oral or inhaled corticosteroids, cromolyn sodium, adrenergic drugs not elsewhere specified, and unclassified asthma medications; (2) at least 1 prescription for an inhaled beta‐agonist and at least 1 prescription for cromolyn within a 2 year period; (3) at least 5 prescriptions for asthma medications during a 2‐year period. (Total asthma cases n = 18,407) |
MMR vaccine: not reported Exposure to MMR vaccine (and other vaccines). Vaccinations were ascertained through computerised immunisation tracking systems, and onset of asthma was identified through computerised data on medical care encounters and medication dispensing. |
Conclusion: there is no association between MMR vaccine and the risk of asthma. | Not reported |
rr (95% CI)(*) 0.97 (0.91 to 1.04) (*) adjusted rr estimated from a proportional hazard regression model stratified by HMO and month and year of birth, gender, low birthweight status |
|
cb‐McKeever 2004 Cohort study |
Children (n = 16,470) aged from 20 months to 11 years, accounting for 69,602 person‐years n = 29,238 n = 20,845 vaccinated n = 8393 unvaccinated |
Asthma: diagnoses of asthma/wheeze and eczema from the Oxford Medical Information System (which was derived from the ICD‐8) and Read codes (hierarchical codes commonly used in GP practices in England) diagnoses of asthma n = 1753 n = 28 (amongst unvaccinated) |
MMR vaccine: not reported Vaccination status extracted from West Midlands General Practice Research Database. Data are presented stratified by consulting frequency in first 18 months (a1) 0 to 6 (a2) 7 to 10 (a3) 11 to 16 (a4) > 16 |
Conclusion: the study data suggest that currently recommended routine vaccinations are not a risk factor for asthma or eczema. In this observational study analysing computerised primary care records, the authors found an association between MMR and DPT vaccination and the incidence of asthma and eczema, but these associations appeared to be limited to the minority of children who rarely seek care from a GP. This limited association is more likely to be the result of bias than a biological effect. |
Cases vaccinated/PT‐years versus cases unvaccinated/PT‐years ‐‐‐‐‐‐‐‐‐‐‐‐All‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ (a) 1725/65,597 versus 28/4006 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ stratified by consulting frequency in first 18 months (a1) 165/12,462 versus 5/2843 (a2) 351/17,522 versus 7/425 (a3) 601/20,693 versus 8/452 (a4) 608 /14,920 versus 8/286 |
rr (95% CI)(*) (a) 2.2 (1.50 to 3.21) (a1) 7.18 (2.95 to 17.49) (a2) 0.95 (0.45 to 2.01) (a3) 1.36 (0.68 to 2.73) (a4) 1.21 (0.60 to 2.43) (*) Adjusted rr estimated from a proportional hazard regression model stratified by consulting frequency, parental smoking, parental allergic disease, maternal age, number of older siblings, use of antibiotics early in life, year of birth, and GP practice. |
|
cb‐Hviid 2008 Cohort study |
Danish birth cohorts 1991 to 2003 followed up between 1 January 1991 and 31 December 2003, or between 1 and 5 years of age |
Asthma hospitalisation: inpatient hospitalisation with asthma diagnosis (occurred between 1 January 1992 and 31 December 2004)
n = 871,234 children (vaccine coverage 85%) PT = 2,926,406 (person‐years) n = 26,880 hospitalisations amongst 17,885 children ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ Anti‐asthma medication: prescription of the following cases of anti‐asthma medications have been considered:
n = 600,938 children (vaccine coverage 84%) PT = 1,858,199 (person‐years) n = 833,424 prescriptions anti‐asthma medication amongst 248,907 children |
MMR vaccine: Measles Moraten strain, Mumps Jeryl Lynn strain, Rubella Wistar RA 27/3 strain. Dates of MMR vaccination were obtained from the National Board of Health. |
Conclusion: these results are compatible not with an increased risk of asthma following MMR vaccination, but rather with the hypothesis that MMR vaccination is associated with a reduced risk of asthma‐like disease in young children. | (a) Asthma (b) Status asthmaticus (c) Anti‐asthma medication |
rr (95% CI)(*) (a) 0.75 (0.73 to 0.78) (b) 0.63 (0.49 to 0.82) (c) 0.92 (0.91 to 0.92) (*) Adjusted for age, calendar period, hospitalisations propensity in infancy, birthweight, place of birth, mother’s country of birth, infant vaccine compliance, birth order, maternal age at birth, and child’s sex. Log‐linear Poisson regression. |
|
cb‐Benke 2004 Cohort study |
Participants were aged between 22 and 44 years n = 309 | Participants were surveyed by a validated interviewer‐administered questionnaire covering: history of asthma; details of home and occupation environment; smoking history; medications; dietary information; and respiratory symptoms. The respiratory symptoms included wheezing or whistling in the chest, shortness of breath, chest tightness, and cough and phlegm during the previous 12 months. Atopy was assessed by skin prick testing to common aeroallergens. |
MMR vaccine not described Questionnaire included vaccination history questions, which were not included in the questionnaire used by the other study centres. Vaccination history included measles or MMR vaccinations; hepatitis B; Bacille Calmette‐Guérin (BCG); oral polio vaccine (OPV); and diphtheria, tetanus, and whooping cough (DTP). |
Conclusion: there was no significant association observed for participants diagnosed with asthma who had received measles or MMR vaccinations compared with those who did not receive measles or MMR vaccinations. | (a) Asthma (b) Atopy |
RR (95% CI) (a) 1.33 (0.98 to 1.80) (b) 1.07 (0.88 to 1.30) |
|
cb‐Timmermann 2015 Cohort study |
n = 640 children were followed from birth. Follow‐up examinations at ages 5, 7 and 13 years included a physical examination and a maternal questionnaire about the child’s health. |
Asthma (and dermatitis eczema) At child's age 5, parents were asked whether the child was suspected to suffer from asthma or had been diagnosed with asthma, hypersensitivity, or allergy. At ages 5, 7, and 13 years, the same paediatrician determined the presence of current wheezing by auscultation. At the same ages, the paediatrician also examined all children for dermatitis/eczema. At age 13, the findings from this examination were graded according to a score for atopic dermatitis (SCORAD). At age 7, a blood sample was drawn and total IgE and grass‐specific IgE were quantified. At age 13, parents were asked whether the child had ever suffered from asthma. In accordance with the International Study of Asthma and Allergies in Childhood (ISAAC), they were also asked to indicate whether the child had (i) suffered from wheezing in the past 12 months, (ii) suffered from sneezing, running, or blocked‐up nose except for when the child had a cold or was sick in the past 12 months and, if so, whether it had been accompanied by itching running/tearing eyes (current rhinoconjunctivitis symptoms), and (iii) whether the child had ever suffered from an itching rash that comes and goes for at least 6 months (eczema ever). At age 13, the children underwent a skin prick test with extracts of 5 common allergens (birch/grass pollen, dog/cat dander, and house dust mite (Dermatophagoides pteronyssinus)). |
MMR vaccine: not described The Faroe Islands follow the Danish vaccination schedule, in which MMR vaccination, at the time of this study, was administered at age 15 months and 12 years (Fig. 1). There were no specific contraindications. At the 5‐year examination, the child’s vaccination card was inspected and all vaccination dates were registered. At child's age 13, the mothers were asked whether the child had received the MMR vaccination scheduled at 12 years of age. |
Conclusion: the authors' findings support the notion that MMR vaccination may provide beneficial effects in preventing childhood allergy and asthma. |
Asthma (a) 5 years old (b) 13 years old |
OR (95% CI) (a) 0.33 (0.12 to 0.90)(*) (b) 0.22 (0.08 to 0.56)(*) (a) 0.32 (0.10 to 1.05)(*)(**) (b) 0.16 (0.05 to 0.53)(*)(**) RR (95% CI)(***) (a) 0.44 (0.18 to 0.93)(*) (b) 0.35 (0.14 to 0.71)(*) (*) Adjusted OR (logistic regression model) for birthweight and family history of chronic bronchitis/asthma. The analyses at age 13 years are additionally adjusted for whether the child had received the second MMR vaccine before the 13‐year examination. (**) Additional adjustment for sex, premature birth, maternal smoking during pregnancy, log (cord blood IgE), breastfeeding, number of older siblings, number of younger siblings, parental smoking in the home, day care, family history of eczema in children/allergic eczema/hay fever, family history of allergy, and age at the examination. (***) OR converted in RR (a) CER = 0.36 (b) CER = 0.47 |
ACT: Asthma Control Test CER: control event rate CI: confidence interval DPT: diphtheria, pertussis, and tetanus vaccine GP: general practice HMO: health maintenance organisation ICD: International Classification of Diseases IgE: Immunoglobulin E incidence: cases/PT MMR: measles, mumps, rubella vaccine MMRV: measles, mumps, rubella, and varicella vaccine OR: odds ratio PT: person‐time rr: rate ratio (relative incidence, incidence rate ratio) RR: risk ratio (relative risk) VSD: Vaccine Safety Datalink