Infectious Triggers of Asthma in Children

Abstract & Commentary

Synopsis: Mycoplasma pneumoniae may causally contribute to the development of asthma, as well as serve as a trigger for recurrent wheezing.

Source: Biscardi S, et al. Mycoplasma pneumoniae and Asthma in Children. Clin Infect Dis. 2004;38:1341-1346.

A prospective study from 1999-2001 in Paris of 170 children 2-15 years of age hospitalized with acute severe asthma included serologic testing of acute and convalescent sera (2-4 weeks later) for IgM and IgG Mycoplasma pneumoniae antibodies, and testing of acute serum for Chlamydia pneumoniae IgM antibodies. PCR testing was performed for M. pneumoniae and C. pneumoniae on nasopharyngeal aspirates from 95 children.

By serologic criteria of specific IgM present in either the initial or second serum sample or with a > 4-fold increase in IgG titers, 26 of 51 (50%) children with their first presentation of asthma, and 24 of 119 (20%) children with a history of asthma (P < 0.01) were diagnosed with acute M. pneumoniae infection. Among children who also had PCR testing, only 7 of 35 (20%) tests among children with their first presentation of asthma, and 5 of 60 tests (8.3%) among children with recurrent asthma, were positive. All children the positive PCR tests also had serologic evidence of M. pneumoniae infection. All 4 children with their first episode of asthma and M. pneumoniae infection that was untreated, were rehospitalized with another severe asthma attack within 3 weeks, including 2 children requiring intensive care.

C. pneumoniae was diagnosed among children with their first presentation of asthma serologically in 3 of 51 (5.8%) children, and also by PCR for 1 child. Among children with recurrent asthma, C. pneumoniae was diagnosed serologically in 4 of 119 (3.4%) children, and also by PCR in 2 children. Using immunofluorescence testing and culture of nasopharyngeal specimens, respiratory syncytial virus was detected in children with initial or recurrent asthma in 2 (4%) and 14 (12%), respectively, and influenza A or B virus was detected in 0 and 4 (3%), respectively. No adenovirus or parainfluenza viruses were detected. Bordetella pertussis was diagnosed in 2 children with their initial presentation of asthma and in 1 child with recurrent asthma. They were unable to test for rhinoviruses.

By comparison, a control group of 113 children with stable asthma and 39 children with allergic rhinitis found serological evidence of acute M. pneumoniae infection in 8 of 152 (5.2%) children (P < 0.005 compared with each of the other groups), and C. pneumoniae in 3 of 120 (2.5%) children (not significant compared with each of the other groups).

Of those children with their first presentation of asthma, 15 of 26 children with acute M. pneumoniae infection and all 3 with acute C. pneumoniae infection developed recurrence of asthma. Thus, 62% of children with either infection developed recurrent asthma, compared to only 6 of 22 (27%) who did not have an infection (P < 0.05). Those with acute infection also had significantly lower serum IgE levels, and less frequent history of allergy or family history of asthma

Comment by Hal B. Jenson, MD, FAAP

This study shows that half of first cases of severe asthma episodes among these children were associated with serological evidence of acute M. pneumoniae infections, which are frequently mild or even asymptomatic. Children with acute M. pneumoniae or C. pneumoniae infection were also less "allergic" or less destined to develop recurrent asthma. These novel findings suggest that M. pneumoniae may play a causal role in the development of recurrent asthma in children. This study also shows that children with untreated M. pneumoniae infection during their initial episode of asthma are at increased risk of recurrent severe attacks. These clinical findings substantiate findings from an animal model in mice of asthma, which found that M. pneumoniae increased bronchial airway resistance and resulted in persistent M. pneumoniae infection at 2 months.

Acute viral infections (eg, rhinoviruses, coronaviruses, respiratory syncytial virus, influenza viruses, and parainfluenza viruses) and chronic infections (eg, M. pneumoniae, C. pneumoniae, and adenoviruses) are common triggers of asthma exacerbations among children. Chronic M. pneumoniae infections, diagnosed by PCR of bronchoalveolar lavage, are frequent among adults with asthma and appear to contribute to repeat severe asthma exacerbations. One impediment to replicating these adult studies in children is the inability to obtain bronchoalveolar lavage specimens. The lower level of M. pneumoniae infection diagnosed by PCR in this study reflects the limitations resulting from the necessity to rely on nasopharyngeal aspirates from children. Thus, serological testing for diagnosis of M. pneumoniae infection in children is essential.

Acute M. pneumoniae infection should be suspected in children presenting with their first episode of severe asthma, especially if their history does not suggest risk for allergic disease or if they require early rehospitalization. It is plausible that macrolide treatment of acute infection may alter the progression to chronic M. pneumoniae infection and prevent subsequent recurrent episodes of asthma. The primary obstacles to studying whether the outcome of M. pneumoniae infection can be altered by treatment, and to currently recommending or implementing a strategy for routine M. pneumoniae testing and treatment, are the lack of rapid, sensitive diagnostic tests and the need to rely on serologic diagnosis, which is time-consuming and often requires a convalescent serum.

Hal B. Jenson, MD, FAAP, Chair, Department of Pediatrics, Director, Center for Pediatric Research, Eastern Virginia Medical School and Children’s Hospital of the King’s Daughters, Norfolk, VA, and Associate Editor for Infectious Disease Alert.