Mechanisms of asthma and allergic inflammation
Human rhinovirus in bronchial epithelium of infants with recurrent respiratory symptoms

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Background

Human rhinoviruses (HRVs) are a common cause of upper respiratory tract infections. There is growing evidence that HRVs are also important in lower respiratory tract infections and often induce asthma exacerbations.

Objective

We evaluated the presence of HRV in the lower respiratory tract by obtaining bronchial biopsies from infants with recurrent asthmalike respiratory symptoms.

Methods

A total of 201 steroid-naive infants age 3 to 26 months with recurrent respiratory symptoms for at least 4 weeks within the preceding 2 months were studied for lung function using body plethysmography. Bronchoscopy was performed in 68 children, and bronchial biopsies were available from 59 infants for HRV detection with in situ hybridization.

Results

Human rhinovirus was detected in 21 of 47 (45%) specimens. Abnormal lung function (decreased airways conductance) was found in 18 of 21 (86%) HRV+ infants and in 15 of 26 (58%) HRV infants (P = .037). Occurrence of a respiratory infection in the 6 weeks preceding bronchoscopy correlated with HRV positivity (P = .036).

Conclusion

Human rhinovirus is frequently found in the lower airways in infants with recurrent respiratory symptoms, and the majority of these HRV+ infants also showed increased airway resistance.

Clinical implications

Human rhinovirus is a common pathogen causing upper and lower respiratory symptoms. Follow-up of these infants will reveal whether the presence of HRV in the bronchial biopsy and abnormal lung function with recurrent respiratory symptoms predicts subsequent asthma.

Section snippets

Subjects

Full-term infants (>36 weeks gestation) age 3 to 26 months with recurrent respiratory symptoms including dyspnea, cough, and/or wheeze for at least 4 weeks within the 8 weeks preceding their first visit were included. Exclusion criteria were use of inhaled corticosteroids within the 8 weeks preceding their lung function visit, a cumulative lifetime systemic corticosteroid use of more than 3 days at a dose of 2 mg/kg or inhaled corticosteroids for more than 4 weeks, nonwhite ethnicity, small for

Infants

Bronchoscopy was performed in 68 of 201 (34%) infants studied with plethysmography, and biopsies for HRV-ISH were available from 59 of these patients. Twelve biopsies were insufficient; thus, the number of specimens for HRV-ISH analysis was 47. The characteristics of these infants are shown in Table I. Bronchoscopy was performed, on average, 20 days (range, 5-111 days) after measurement of lung function.

HRV detection

Human rhinovirus was detected in 21 of 47 infants (45%). In a 3-category setting according

Discussion

We detected HRV by ISH from the lower respiratory tract in 45% of infants with recurrent respiratory symptoms. A positive HRV result correlated with abnormal lung function and occurrence of a respiratory infection during the preceding 6 weeks.

We used HRV-14 probe, which consists 249 nucleotides (nt 332-572) from 5′-untranslated region, and these nucleotide sequences have been shown to be very similar in all HRVs.25 HRV-14 represents genetically the HRV B-species (25 serotypes),26 and it is

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    Supported by Nummela Sanatorium Foundation, Hengitys and Terveys Foundation, Pediatric Research Foundation, Helsinki University Central Hospital Research Fund, Sigrid Juselius Foundation, and AstraZeneca Finland.

    Disclosure of potential conflict of interest: T. Haahtela is on the speakers' bureau for MSD, AstraZeneca, and Orion Pharma. The rest of the authors have declared that they have no conflict of interest.

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