Indian Pediatrics 2002; 39:254-258  

BCG, Tuberculin Skin-Test Results and Asthma Prevalence in School Children in North London

A. Pahari, S. Welch and S. Lingam

From the Academic Department of Child Health, St. Ann’s Hospital, London, United Kingdom.

Correspondence to: Dr. A Pahari, Department of Pediatric Infectious Diseases, 6th Floor, QEQM Building, St. Mary’s Hospital, Praed Street, London W2 1NY, United Kingdom.

E-mail: [email protected]

Manuscript received: August 1, 2001, Initial review completed: September 9, 2001,
Revision accepted: November 15, 2001.

Objective: To test whether there is any relationship between asthma prevalence and BCG immunization or tuberculin skin test reaction. Design: Cross-sectional survey. Setting: Secondary school in Haringey, North London, UK. Subjects: 780 children aged 11-18 years (median 13.35 years). Interventions: Administration of tuberculin skin test and questionnaire. Main outcome measures: Diagnosis of asthma, presence of nocturnal cough, exercise-induced wheeze or wheeze with viral respiratory infections; diameter of induration with tuberculin skin test; history of BCG immunization. Results: 57 of 629 children (8.5%) had a significantly positive Mantoux reaction(³15 millimeters of induration). Children with and without a history of BCG immunization did not differ significantly in prevalence of asthma diagnosis (11.8% vs 14.1%, p >0.6), exercise-induced wheeze (16.9% vs 21.2%, p >0.4), viral-induced wheeze (15.4% vs 7%, p >0.6) or nocturnal cough (32.3% vs 32.7%, p >0.6). We also found no significant correlation of the prevalence of asthma diagnosis or symptoms with diameter of Mantoux test reaction. Conclusions: There is no evidence of an effect of BCG immunization or tuberculin reactivity on the incidence of asthma in secondary school children in Haringey, North London and the exposure to tuberculosis is high in these children.

Key words: Asthma, BCG vaccine, Tuberculin test.

ASTHMA is an atopic disorder character-ized by activation and recruitment of eosinophils to the lungs resulting in chronic swelling and inflammation of airways(1). The prevalence of asthma in westernized societies has risen steadily in this century, doubling in the last 20 years. Asthma now affects one child in seven in Great Britain and in the United States it causes one-third of pediatric emergency-room visits. Asthma is familial, and genome wide searches have shown that many genetic loci predispose to the disease(2). The genetic makeup of a stable population is unlikely to change, so the cause of the increasing prevalence must lie in the environment. Even though the reasons for the increase are not precisely known, it has been noticed that the increase in atopic disorders inversely correlates with a steady decline in the extent of population exposure to major infectious diseases such as tuberculosis, measles, whooping cough, and influenza(3,4). This effect outweighs the effect of exposure to environmental pollution(5). Various animal studies have shown that BCG infection suppresses allergic sensitization, suppresses allergen induced airway eosinophilia and development of increased airway reactivity in mouse models(1,6).

Bronchial asthma is characterized by "type 2" T-helper cell (Th-2) response, altered airway reactivity to inhaled allergens and chronic inflammation of airways. Th-2 type lymphocytes secrete interleukins IL-4 and IL-5 leading to enhanced production of class E immunoglobulin (IgE) by B cells and the generation and recruitment of eosinophils, respectively. Infection and immunization induce characteristics Th-1 responses and produce interferon gamma (IFN-g), which is viewed as a powerful suppresser of Th-2 activity. Mycobacteria are among the most potent inducers of Th-1 type responses. By skewing the cytokine microenvironment towards preferential proliferation of Th-1 cells, mycobacteria may protect against Th-2 dependent atopic diseases. In 1997 Shirakawa and colleagues(3) presented evidence for a novel environmental cause of asthma. They found inverse association between tuberculin responses and atopic disorder. They studied 867 school children after age 12, and showed a clear negative relation between delayed hypersensitivity (DHT) responses and the presence of asthma and concentration of serum IgE. Children with positive DHT responses to tuberculin had serum cytokine concentrations suggestive of predominant Th-1 responses, in contrast to the Th-2 profiles seen in children with negative DHTs. A Scandinavian study(7) found no association between BCG and atopic disease in children with atopic heredity. A recent study by Gruber and colleagues from Germany(8) did not support the hypothesis that BCG vaccination in early infancy is associated with a markedly decreased risk of atopic sensitisation or allergy. They studied 774 children from a prospectively followed birth cohort until the age of 7 years. Their findings of clinical and serologic correlates of atopy were not signi-ficantly different between children with a skin test diameter equal to 5 mm and those with a smaller diameter. We compared tuberculin skin test reactions with the presence of asthma in school children in London.

In October 1998, a teacher at a secondary school in Haringey, north London, was diagnosed with sputum positive pulmonary tuberculosis. The ensuing screening program at the school provided us with the opportunity to conduct this study. Haringey is an inner city area with a high immigrant and ethnic minority population. Respiratory problems, including asthma and tuberculosis, are common in school children in this area. We took the opportunity of having to conduct tuberculin skin testing in the whole school to investigate whether there was any relationship between tuberculin reaction and asthma in this population.

We sent information letters, consent forms and questionnaires to parents of all children attending the school. Questions included BCG vaccination and tuberculosis contact history, as well as whether there was a diagnosis of asthma or presence of possible symptoms. Subsequently, we visited the school over a two-week period. All children were examined for a BCG scar, and ten units of tuberculin purified protein derivative were administered intradermally in a volume of 0.1 ml.

Seventy-two hours later, we visited the school again and measured the diameter of the skin reaction in two dimensions. All injections and readings were done by one of the investigators (AP) and specifically trained nurses. Children with a largest diameter of 15 millimetres or above were referred for chest X-ray and clinical review; children with a largest diameter below 5 mm were offered BCG immunization. Statistical analysis was performed using SPSS version 10.

The school had 780 children on its register, of whom 663 had a tuberculin skin test; 57 (8.6%) of these had a reaction of 15 mm or more of induration. A total of 329 children (135 boys, 41% and 194 girls, 59%) agreed to participate in our study and answered the questionnaire. The age range was 11 to 18 years (median 13.35 years) and 76 children (23%) were born outside the UK.

The prevalence of asthma-related symp-toms did not vary between groups with or without a history of BCG immunization (Table I). Analyzing neonatal BCG separately made no difference to this (data not shown). Asthma prevalence also did not vary with degree of skin test-positivity (Table II). A 10 mm cut-off is shown here for ease of comparison, as this was used in the Japanese study. Taking 5 or 15 mm cut-offs or analyzing diameter as a continuous variable did not alter the results.

Table II__Prevalence of Asthma Symptoms by Size of Mantoux Reaction

Our data show no effect of BCG vaccination status or tuberculin skin reactivity on asthma prevalence in an ethnically diverse population with widespread use of BCG and exposure to Mycobacteria. Interpretation of these data is limited by the fact that only 50% of tuberculin tested children completed the questionnaire. The lack of association bet-ween prevalence of asthma-related symptoms and BCG or skin test positivity is at odds with the Japanese data. Despite the wide-spread use of BCG and likely exposure to tuberculo-sis in our study, there is no evidence that this has resulted in a decreased prevalence of asthma.

The potential effectiveness of BCG in reducing atopy has a plausible biological explanation, but the strong association seen in Japan has not been duplicated in our study or others in Europe. Gruber(8) speculated that possible reasons might include differences between BCG preparations used in Europe and Japan. We also note that the dose of tuber-culin used in skin testing, and the cut-off for defining a positive test vary between studies.

Gruber(8) also suggests that there may be an early effect of BCG that is later out-weighed by other environmental factors, although there were no statistically significant changes to confirm this. In this study, we recorded environmental factors including type of housing, central heating and exposure to passive smoking, and found no effect on asthma prevalence. A larger study would be required to separate the influences of other environmental factors. Our data do not exclude a small effect of BCG in reducing asthma prevalence by about 5%; larger numbers would also be required to distinguish a small effect of BCG in infancy from natural exposure to Mycobacteria or vaccination later in childhood.

It is possible that there are genetic differences between Japanese and European populations, but there is no strong reason to believe that this is the cause of the differing observations. More significant might be the differences between the BCG vaccination regimens. The Japanese children were skin-tested 3 times, in infancy and at 6 and 12 years; children with negative tests were vaccinated irrespective of previous vaccination status. Such intensive regimens are not used in Europe.

We conclude that more data are needed on the effects of age, environment and BCG regimen before BCG vaccination can be advocated to reduce the incidence of atopy.

We thank the children who took part in this study and their families, staff at the school, the school and specialist tuberculosis nursing services of Haringey and Jerry Levy, research division, for help with data entry.

Contributors: SL conceived and supervised the study. AP conducted the study. SW carried out the statistical analysis. SW and AP reviewed the subject and wrote the text of this article. AP will act as the guarantor for the manuscript.

Funding: None.

Competing interests: None stated.

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