Asthma and lower airway disease
Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations

https://doi.org/10.1016/j.jaci.2014.02.030Get rights and content

Background

Detection of either viral or bacterial pathogens is associated with wheezing in children; however, the influence of both bacteria and viruses on illness symptoms has not been described.

Objective

We evaluated bacterial detection during the peak rhinovirus season in children with and without asthma to determine whether an association exists between bacterial infection and the severity of rhinovirus-induced illnesses.

Methods

Three hundred eight children (166 with asthma and 142 without asthma) aged 4 to 12 years provided 5 consecutive weekly nasal samples during September and scored cold and asthma symptoms daily. Viral diagnostics and quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were performed on all nasal samples.

Results

Detection rates were 53%, 17%, and 11% for H influenzae, S pneumoniae, and M catarrhalis, respectively, with detection of rhinovirus increasing the risk of detecting bacteria within the same sample (odds ratio [OR], 2.0; 95% CI, 1.4-2.7; P < .0001) or the following week (OR, 1.6; 95% CI, 1.1-2.4; P = .02). In the absence of rhinovirus, S pneumoniae was associated with increased cold symptoms (mean, 2.7 [95% CI, 2.0-3.5] vs 1.8 [95% CI, 1.5-2.2]; P = .006) and moderate asthma exacerbations (18% [95% CI, 12% to 27%] vs 9.2% [95% CI, 6.7% to 12%]; P = .006). In the presence of rhinovirus, S pneumoniae was associated with increased moderate asthma exacerbations (22% [95% CI, 16% to 29%] vs 15% [95% CI, 11% to 20%]; P = .01). Furthermore, M catarrhalis detected alongside rhinovirus increased the likelihood of experiencing cold symptoms, asthma symptoms, or both compared with isolated detection of rhinovirus (OR, 2.0 [95% CI, 1.0-4.1]; P = .04). Regardless of rhinovirus status, H influenzae was not associated with respiratory symptoms.

Conclusion

Rhinovirus infection enhances detection of specific bacterial pathogens in children with and without asthma. Furthermore, these findings suggest that M catarrhalis and S pneumoniae contribute to the severity of respiratory tract illnesses, including asthma exacerbations.

Section snippets

Study subjects and design

Children included in this analysis were enrolled in a larger study (RhinoGen) to determine genetic correlates with more severe rhinovirus-induced illnesses. Of the 383 children participating in RhinoGen, 308 children aged 4 to 12 years submitted samples during a peak rhinovirus season. Starting the first Saturday of September 2007, 2008, or 2009, nasal samples were collected weekly for a total of 5 consecutive weeks. Children, with the help of their parents, were instructed to record upper

Subjects' characteristics

Of the 383 children enrolled in RhinoGen, 54 had insufficient quantity of nasal samples to allow analysis for both viruses and bacteria, whereas an additional 19 subjects did not submit at least 4 (80%) of the 5 scheduled nasal samples, and 2 additional subjects did not complete at least 40 days (80%) of symptom diaries. Therefore a total of 308 (80%) subjects were included in the final analysis (see Fig E1 in this article's Online Repository at www.jacionline.org).

Of the 308 subjects enrolled,

Discussion

In this study we tested 2 hypotheses to determine the role of bacterial pathogens in rhinovirus-induced respiratory symptoms and exacerbations of asthma. First, we predicted that detection of bacterial pathogens would be increased in children with asthma compared with their nonasthmatic counterparts; however, this was not the case. We also hypothesized that common bacterial pathogens contribute to rhinovirus-induced illness severity, and thus these bacteria would be more prevalent during

References (28)

  • J.P. Olenec et al.

    Weekly monitoring of children with asthma for infections and illness during common cold seasons

    J Allergy Clin Immunol

    (2010)
  • G.M. Abdeldaim et al.

    Detection of Haemophilus influenzae in respiratory secretions from pneumonia patients by quantitative real-time polymerase chain reaction

    Diagn Microbiol Infect Dis

    (2009)
  • O. Ruuskanen et al.

    Viral pneumonia

    Lancet

    (2011)
  • H. Bisgaard et al.

    Childhood asthma after bacterial colonization of the airway in neonates

    N Engl J Med

    (2007)
  • H. Bisgaard et al.

    Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study

    BMJ

    (2010)
  • P.A. Cardenas et al.

    Upper airways microbiota in antibiotic-naive wheezing and healthy infants from the tropics of rural Ecuador

    PLoS One

    (2012)
  • M. Hilty et al.

    Disordered microbial communities in asthmatic airways

    PLoS One

    (2010)
  • Y.J. Huang et al.

    Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma

    J Allergy Clin Immunol

    (2011)
  • V. Peltola et al.

    Temporal association between rhinovirus circulation in the community and invasive pneumococcal disease in children

    Pediatr Infect Dis J

    (2011)
  • K.M. Kloepfer et al.

    Increased H1N1 infection rate in children with asthma

    Am J Respir Crit Care Med

    (2012)
  • W.M. Lee et al.

    High-throughput, sensitive, and accurate multiplex PCR-microsphere flow cytometry system for large-scale comprehensive detection of respiratory viruses

    J Clin Microbiol

    (2007)
  • G.M. Abdeldaim et al.

    Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis

    BMC Microbiol

    (2010)
  • O. Greiner et al.

    Quantitative detection of Moraxella catarrhalis in nasopharyngeal secretions by real-time PCR

    J Clin Microbiol

    (2003)
  • Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma—summary report 2007

    J Allergy Clin Immunol

    (2007)
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    The following National Institutes of Health (NIH) grants supported this research: U19 AI070503-01 (RhinoGen); P01 HL070831 (Childhood Origins of Asthma); 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, NIH; and T32AI007635 (University of Wisconsin Allergy Research Training program).

    Disclosure of potential conflict of interest: K. M. Kloepfer, T. E. Pappas, M. D. Evans, and Y. A. Bochkov have received research support from the National Institutes of Health (NIH). R. E. Gangnon has received research support from the National Heart, Lung, and Blood Institute (NHLBI). D. J. Jackson has received consulting fees from GlaxoSmithKline and Genentech. R. F. Lemanske, Jr, has been supported by a grant, consultancy fees, and participation fees from the NIH; is a board member for the American Academy of Allergy, Asthma & Immunology (AAAAI); has received consultancy fees from Merck, Sepracor, SA Boney and Associates, GlaxoSmithKline, the American Institute of Research, Genentech, Double Helix Development, and Boehringer Ingelheim; is employed by the University of Wisconsin School of Medicine and Public Health; has received research support from the NHLBI and Pharmaxis; has received lecture fees from the Michigan Public Health Institute, Allegheny General Hospital, the American Academy of Pediatrics, West Allegheny Health Systems, California Chapter 4, AAP, the Colorado Allergy Society, the Pennsylvania Allergy and Asthma Association, Harvard Pilgrim Health, the California Society of Allergy, the NYC Allergy Society, the World Allergy Organization, the American College of Chest Physicians, APAPARI, and the Western Society of Allergy, Asthma, and Immunology; has received payment for manuscript preparation from the AAAAI; and has received royalties from Elsevier and UpToDate. J. E. Gern has received research support from the NIH, Merck, AstraZeneca, and GlaxoSmithKline and has received personal fees from GlaxoSmithKline, Biota, Centocor, Boehringer Ingelheim, MedImmune, Theraclone, Merck, and Gilead. The rest of the authors declare that they have no relevant conflicts of interest.

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