Asthma, Allergy, and Medication Exposure in Early Childhood: A Catch-22 of Care

Living on the Island of Hawai'i has certain considerations concerning asthma as we have the highest prevalence among children in the United States.

Biological Basis
Asthma is a chronic disorder that is characterized by lung airway inflammation. This inflammation is caused and perpetuated by an inappropriate immune response, an increase in airway responsiveness, and airflow obstruction. Asthma symptoms can be mild, moderate, and severe and may include wheezing, cough, and chest tightness, among other life-threatening implications. Asthma and the closely associated allergic diseases of atopic dermatitis, allergic rhinitis, and immunoglobulin E-medicated food allergy are characterized by inflammatory T-helper cell responses of the T-helper 2 phenotype initiating and perpetuating symptoms (Devereux, 2006). Further mediators in the process include cytokines secreted by T-helper 2 cells, interleukin-4 and interleukin-13, which contribute to elevated immunoglobulin E, mast-cell regulation, and eosinophilic inflammation.

The prevalence of asthma as the world’s most common chronic disorder (Devereux, 2006) has encouraged a plethora of studies examining prenatal and postnatal exposures, environment, family history, and has resulted in an increase in awareness and subsequent diagnosis. The following discourse examines three such studies that pertain to medication exposure among infants and the association and subsequent development of asthma and allergies. Asthma predominates as a Western disease and the possible correlation between high medication usage and antibiotic usage, in particular, may depict the pitfalls of easy access and excess usage. As the following studies suggest, use of such common over-the-counter medications such as paracetamol and prescribed medications such as antibiotics in early childhood may result in a debilitating asthmatic disease requiring additional medications and/or medical attention. This seeming paradox, when adequately examined, illustrated, and exposed may result in the reduction of unintentional parentally and/or physician-induced asthma and allergies.

Research Findings
Bakkeheim et. al. (2010) examined the role of paracetamol in early infancy and the associated risk of developing childhood allergies and asthma. Paracetamol or acetaminophen is a common analgesic and antipyretic that is readily used on infants and children for fever, teething, and to alleviate general pain and discomfort. Commonly known as Tylenol, its label specifies, “Give your child Infants' Tylenol products to reduce fever and for the temporary relief of minor aches and pains associated with:Cold. Flu. Headache. Sore throat. Toothache and teething.” Its usage was examined in this prospective cohort study that included 1019 children at birth who were then reexamined at 10 years of age. Their prenatal exposure through maternal paracetamol use or postnatal exposure during the first 6 months of life were documented. Subsequent outcomes at the 10 year reexamination period included existing asthma diagnosis, a history of asthma, allergic sensitization, and/or allergic rhinitis.

Bakkeheim’s research resulted in the finding that maternal paracetomol use in the first trimester only increased the risk for allergic rhinitis with an odds ratio of 2.30 for both male and female children. The significant findings of the study related to paracetamol use until 6 months of age in girls, resulting in an increased risk of allergic sensitization (odds ratio of 2.20) and a history of asthma (odds ratio of 2.20 as well) in 10 year olds.

Further research by Risnes et. al. (2010) also examined the role of medication exposure in regards to antibiotic exposure within the first 6 months of life and the development of asthma and allergy at 6 years of age. This study included a cohort of 1401 children whose hospital records and physician records were examined to document antibiotic exposure. At 6 years of age, maternal interviews were conducted to determine whether the child had experienced an allergic reaction, if blood immunoglobulin E or a skin prink had been conducted, and the results of such testing. Those children who experienced an allergic reaction and had a positive blood or skin prick test were classified as allergy positive. Children diagnosed with asthma and who had a positive allergy test were determined to have allergic asthma.

The research findings included an increased risk of asthma (odds ratio of 1.52) among those children who had been prescribed antibiotics in infancy. The adverse effect of antibiotics use was particularly evident in children who had no family history of asthma (odds ratio 1.89). In addition, the odds ratio of a positive blood immunoglobulin E or skin prink test was 1.59 among those with early antibiotic exposure.

Sobko et. al. (2010) examined the role that neonatal sepsis and early antibiotic therapy have on bacterial colonization and immune activation in infancy and childhood. These were investigated for their implications in allergy and asthma development. This cohort study utilized a validated questionnaire by the International Study of Asthma and Allergies in Children. The three cohorts in this study that were screened examined different perinatal exposures of infection and medication exposure to antibiotics.

The research findings concluded that asthma was more prevalent after neonatal sepsis and antibiotic therapy with an adjusted odds ratio 1.63 as compared with a control group. Also documented was increased atopic eczema after neonatal sepsis (odds ratio 1.39). These findings resulted in the conclusion that neonatal sepsis is associated with an increased risk for later development of asthma and that early antibiotic exposure may be the contributing factor in this association. This study also examined the confounding bias that may occur in regards to infection and subsequent antibiotic use. Infection without the subsequent use of antibiotics did not result in the associated increase.

Public Health Application
All three studies addressed the development of childhood asthma as a result of medications (either paracetamol or antibiotics) given to children prior to 6 months of age. Collectively, they suggest that paracetamol and antibiotic usage may contribute to asthma and allergies. The public health application should pertain to preventing exposure to these medications during the 6 month infancy time-period and curbing exposure throughout early childhood. While public education efforts regarding the use of these medications in infancy is essential to curbing usage and limiting exposure, the particulars of paracetamol and antibiotics usage are unique in the way that these medications are distributed and can possibly be managed more effectively.

For example, in the use of paracetamol, the Tylenol Concentrated Infant Drops’ label specifies that its use for children under the age of 2 should be done with a doctor’s consultation. While this labeling may be intended to provide a caregiver with encouragement in contacting a child’s physician when a child is ill, this may not always occur. Therefore, specific dosing and age parameters are more efficient and useful guidelines. The label guidelines should specify that use in children less than 6 months of age has been associated with the development of asthma and allergy. Albeit this association was gender specific (Bakkenheim et. al., 2010), such considerations would need to be further researched prior to possibly ever attaching a gender-specific label to medication. In the event that a physician is contacted regarding use, the physician should adequately inform and encourage proper and limited usage.

Similar to paracetamol in that there are avenues to curbing usage, antibiotics have an additional barrier to usage, the physicians themselves. The distribution of prescriptions for antibiotic medications are limited to physicians and in some states, physicians’ assistants and registered nurses. Regardless of the persistence of parents/ caregivers, physician should address the issue of antibiotic over-prescription, especially among infants who may suffer the additional consequences of asthma and allergies. Patient awareness and education is a key contributing factor to reducing parental demand for antibiotics, but ultimately, it is a physician’s determination whether or not to prescribe antibiotics and to determine at what age they believe it is beneficial or detrimental to the current and future health status of their patients. Further physician education and awareness may also be a key component in reducing usage of antibiotics among infants.

References
Bakkehaim, E. , Mowincckel, P., Carlsen, K. H., Haland, G., Carlsen, K. (2010). Paracetamol in early infancy: the risk of childhood allergy and asthma. Acta Paediatricia, 100, 90-96.
Devereux, G. (2006). The increase in the prevalence of asthma and allergy: Food for thought. Nature Reviews Immunology, 6 (11), 869-874.
Johnson, M.D. (2010). Human Biology: Concepts and current issues. San Francisco. CA: Pearson Benjamin Cummings.
Risnes, K., Belanger, K., Murk, W., Bracken, M. (2010) Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children. American Journal of Epidemiology, 173, 3, 310-318.
.Sobko T, Schiött J, Ehlin A, Lundberg J, Montgomery S, Norman M. (2010). Neonatal sepsis, antibiotic therapy and later risk of asthma and allergy. Paediatr Perinat Epidemiol. 24(1):88-92.
Tantisira, K.G., & Weiss, S.T. (2006). The pharmacogenetics of asthma therapy. Current Drug Targets, 7 (12), 1697-1708.
Umetsu, D.T. & DeKruyff, R.H. (2006). The regulation of allergy and asthma. Immunological Reviews, 212 (1), 238-255.