Top

Published in:

01-12-2013 | Pediatric Allergy and Immunology (JM Portnoy and CE Ciaccio, Section Editors)

Is Asthma an Infectious Disease? New Evidence

Author: T. Prescott Atkinson

Published in: Current Allergy and Asthma Reports | Issue 6/2013

Abstract

The pathogenetic mechanisms leading to asthma are likely to be diverse, influenced by multiple genetic polymorphisms as well as elements of the environment. Recent data on the microbiome of the airway have revealed intriguing differences between the number and diversity of microbial populations in healthy persons and asthmatics. There is convincing evidence that early viral infections, particularly with human rhinovirus and respiratory syncytial virus, are often associated with the development of chronic asthma and with exacerbations. Recent studies suggest that two unrelated types of atypical bacteria, Mycoplasma pneumoniae (Mpn) and Chlamydia pneumoniae, are present in the airways of a substantial proportion of the population, bringing up the possibility that the persistent presence of the organism may contribute to the asthmatic phenotype in a subset of patients. This review will examine the current data regarding a possible role for infection in chronic asthma with a particular focus on atypical bacterial infections.

Lemanske Jr RF. Is asthma an infectious disease?: Thomas A. Neff lecture. Chest. 2003;123:385S–90S.PubMedCrossRef

Metz G, Kraft M. Effects of atypical infections with Mycoplasma and Chlamydia on asthma. Immunol Allergy Clin North Am. 2010;30:575–85. vii–viii.PubMedCrossRef

Edwards MR, Bartlett NW, Hussell T, Openshaw P, Johnston SL. The microbiology of asthma. Nat Rev Microbiol. 2012;10:459–71.PubMed

Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet. 2006;368:804–13.PubMedCrossRef

Borish L, Culp JA. Asthma: a syndrome composed of heterogeneous diseases. Ann Allergy Asthma Immunol. 2008;101:1–8. quiz 8–11, 50.PubMedCrossRef

Holgate ST, Lemanske RF, O’Byrne PM, Kakumanu S, Busse WW: Asthma Pathogenesis. In Middleton’s Allergy: Principles and Practice, edn 7. Edited by Adkinson NF, Jr., Bochner BS, Busse WW, Holgate ST, Lemanske RF, Simons FER: Elsevier; 2009:893-919. vol 2.]

Bisgaard H, Bonnelykke K. Long-term studies of the natural history of asthma in childhood. J Allergy Clin Immunol. 2010;126:187–97. quiz 198–189.PubMedCrossRef

Martinez FD. New insights into the natural history of asthma: primary prevention on the horizon. J Allergy Clin Immunol. 2011;128:939–45.PubMedCrossRef

Gern JE, Rosenthal LA, Sorkness RL, Lemanske Jr RF. Effects of viral respiratory infections on lung development and childhood asthma. J Allergy Clin Immunol. 2005;115:668–74. quiz 675.PubMedCrossRef

10.

Lemanske RF. Viral infections and asthma inception. J Allergy Clin Immunol. 2004;114:1023–6.PubMedCrossRef

11.

Cheung DS, Grayson MH. Role of viruses in the development of atopic disease in pediatric patients. Curr Allergy Asthma Rep. 2012;12:613–20.PubMedCrossRef

12.

Merrell DS, Falkow S. Frontal and stealth attack strategies in microbial pathogenesis. Nature. 2004;430:250–6.PubMedCrossRef

13.

Bonnelykke K, Matheson MC, Pers TH, et al. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nat Genet. 2013;45:902–6.PubMedCrossRef

14.

March ME, Sleiman PM, Hakonarson H. Genetic polymorphisms and associated susceptibility to asthma. Int J Gen Med. 2013;6:253–65.PubMed

15.

Huang YJ: Asthma microbiome studies and the potential for new therapeutic strategies. Curr Allergy Asthma Rep 2013.

16.

Beck JM, Young VB, Huffnagle GB. The microbiome of the lung. Transl Res. 2012;160:258–66.PubMedCrossRef

17.

Han MK, Huang YJ, Lipuma JJ, et al. Significance of the microbiome in obstructive lung disease. Thorax. 2012;67:456–63.PubMedCrossRef

18.

• Huang YJ, Nelson CE, Brodie EL, et al.: Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J Allergy Clin Immunol 2011, 127:372-381 e371-373. The authors describe the results of analysis of studied the 16S rRNA profile in airway samples from 65 asthmatics and 10 normal controls. They also examine the degree of improvement in bronchial hyperreactivity in patients treated with 16 weeks of clarithromycin as a function of the diversity of their airway microbiome.

19.

• Hilty M, Burke C, Pedro H, et al.: Disordered microbial communities in asthmatic airways. PLoS One 2010, 5:8578. In this study the authors cloned and sequenced 16S rRNA sequences from three levels of airway from 5 COPD patients, 11 asthmatics and 8 control subjects to examine the microbiome in chronic lung diseases and healthy individuals.CrossRef

20.

Russell SL, Finlay BB. The impact of gut microbes in allergic diseases. Curr Opin Gastroenterol. 2012;28:563–9.PubMedCrossRef

21.

Azad MB, Kozyrskyj AL. Perinatal programming of asthma: the role of gut microbiota. Clin Dev Immunol. 2012;2012:932072.PubMedCrossRef

22.

Ly NP, Litonjua A, Gold DR, Celedon JC. Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol. 2011;127:1087–94. quiz 1095-1086.PubMedCrossRef

23.

Penders J, Thijs C, van den Brandt PA, et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut. 2007;56:661–7.PubMedCrossRef

24.

Kozyrskyj AL, Ernst P, Becker AB. Increased risk of childhood asthma from antibiotic use in early life. Chest. 2007;131:1753–9.PubMedCrossRef

25.

Droste JH, Wieringa MH, Weyler JJ, et al. Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease? Clin Exp Allergy. 2000;30:1547–53.PubMedCrossRef

26.

Russell SL, Gold MJ, Willing BP, et al. Perinatal antibiotic treatment affects murine microbiota, immune responses and allergic asthma. Gut Microbes. 2013;4:158–64.PubMedCrossRef

27.

Taube C, Muller A. The role of Helicobacter pylori infection in the development of allergic asthma. Expert Rev Respir Med. 2012;6:441–9.PubMedCrossRef

28.

Karimi K, Inman MD, Bienenstock J, Forsythe P. Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med. 2009;179:186–93.PubMedCrossRef

29.

James KM, Peebles Jr RS, Hartert TV. Response to infections in patients with asthma and atopic disease: an epiphenomenon or reflection of host susceptibility? J Allergy Clin Immunol. 2012;130:343–51.PubMedCrossRef

30.

Glezen WP. Asthma, influenza, and vaccination. J Allergy Clin Immunol. 2006;118:1199–206. quiz 1207–1198.PubMedCrossRef

31.

Klemets P, Lyytikainen O, Ruutu P, et al. Risk of invasive pneumococcal infections among working age adults with asthma. Thorax. 2010;65:698–702.PubMedCrossRef

32.

Talbot TR, Hartert TV, Mitchel E, et al. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med. 2005;352:2082–90.PubMedCrossRef

33.

Juhn YJ, Kita H, Yawn BP, et al. Increased risk of serious pneumococcal disease in patients with asthma. J Allergy Clin Immunol. 2008;122:719–23.PubMedCrossRef

34.

Jung JA, Kita H, Dhillon R, et al. Influence of asthma status on serotype-specific pneumococcal antibody levels. Postgrad Med. 2010;122:116–24.PubMedCrossRef

35.

Jung JA, Kita H, Yawn BP, et al. Increased risk of serious pneumococcal disease in patients with atopic conditions other than asthma. J Allergy Clin Immunol. 2010;125:217–21.PubMedCrossRef

36.

ACIP_Pneumococcal_Vaccines_Working_Group. Prevention of pneumococcal disease among infants and children — use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine. MMWR Morb Mortal Wkly Rep. 2010;59:1–19.

37.

ACIP_Pneumococcal_Vaccines_Working_Group. Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). MMWR Morb Mortal Wkly Rep. 2010;59:1102–6.

38.

Capili CR, Hettinger A, Rigelman-Hedberg N, et al. Increased risk of pertussis in patients with asthma. J Allergy Clin Immunol. 2012;129:957–63.PubMedCrossRef

39.

Stein RT. Long-term airway morbidity following viral LRTI in early infancy: recurrent wheezing or asthma? Paediatr Respir Rev. 2009;10 Suppl 1:29–31.PubMedCrossRef

40.

Jackson DJ, Lemanske Jr RF. The role of respiratory virus infections in childhood asthma inception. Immunol Allergy Clin North Am. 2010;30:513–522, vi.PubMedCrossRef

41.

Wu P, Hartert TV. Evidence for a causal relationship between respiratory syncytial virus infection and asthma. Expert Rev Anti Infect Ther. 2011;9:731–45.PubMedCrossRef

42.

Jartti T, Korppi M. Rhinovirus-induced bronchiolitis and asthma development. Pediatr Allergy Immunol. 2011;22:350–5.PubMedCrossRef

43.

Gavala ML, Bertics PJ, Gern JE. Rhinoviruses, allergic inflammation, and asthma. Immunol Rev. 2011;242:69–90.PubMedCrossRef

44.

Lotz MT, Peebles Jr RS. Mechanisms of respiratory syncytial virus modulation of airway immune responses. Curr Allergy Asthma Rep. 2012;12:380–7.PubMedCrossRef

45.

Sly PD, Kusel M, Holt PG. Do early-life viral infections cause asthma? J Allergy Clin Immunol. 2010;125:1202–5.PubMedCrossRef

46.

Simoes EA, Carbonell-Estrany X, Rieger CH, et al. The effect of respiratory syncytial virus on subsequent recurrent wheezing in atopic and nonatopic children. J Allergy Clin Immunol. 2010;126:256–62.PubMedCrossRef

47.

Papadopoulos NG, Christodoulou I, Rohde G, et al. Viruses and bacteria in acute asthma exacerbations–a GA(2) LEN-DARE systematic review. Allergy. 2011;66:458–68.PubMedCrossRef

48.

Busse WW, Lemanske Jr RF, Gern JE. Role of viral respiratory infections in asthma and asthma exacerbations. Lancet. 2010;376:826–34.PubMedCrossRef

49.

Sears MR. Epidemiology of asthma exacerbations. J Allergy Clin Immunol. 2008;122:662–8. quiz 669–670.PubMedCrossRef

50.

Khetsuriani N, Kazerouni NN, Erdman DD, et al. Prevalence of viral respiratory tract infections in children with asthma. J Allergy Clin Immunol. 2007;119:314–21.PubMedCrossRef

51.

Holt PG, Strickland DH, Sly PD. Virus infection and allergy in the development of asthma: what is the connection? Curr Opin Allergy Clin Immunol. 2012;12:151–7.PubMedCrossRef

52.

Gern JE. The ABCs of rhinoviruses, wheezing, and asthma. J Virol. 2010;84:7418–26.PubMedCrossRef

53.

Calhoun WJ, Swenson CA, Dick EC, et al. Experimental rhinovirus 16 infection potentiates histamine release after antigen bronchoprovocation in allergic subjects. Am Rev Respir Dis. 1991;144:1267–73.PubMedCrossRef

54.

Lemanske Jr RF, Dick EC, Swenson CA, et al. Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions. J Clin Invest. 1989;83:1–10.PubMedCrossRef

55.

Gern JE, Busse WW. The effects of rhinovirus infections on allergic airway responses. Am J Resp Crit Care Med. 1995;152:S40–5.PubMedCrossRef

56.

• Caliskan M, Bochkov YA, Kreiner-Moller E, et al.: Rhinovirus wheezing illness and genetic risk of childhood-onset asthma. N Engl J Med 2013, 368:1398-1407. The authors examined two large multicenter studies in children for risk of recurrent wheezing following viral infection in relation to polymorphisms at known genetic loci associated with asthma. They found that HRV but not RSV infection was associated with the development of wheezing in subjects bearing a chromosome 17q21 variant and with the expression level of two genes at that locus. PubMedCrossRef

57.

Eaton MD, Meiklejohn G, van Herick W. Studies on the etiology of primary atypical pneumonia. A filterable agent transmissible to cotton rats, hamsters, and chicken embryos. J Exp Med. 1944;79:649–68.PubMedCrossRef

58.

Atmar RL, Greenberg SB. Pneumonia caused by Mycoplasma pneumoniae and the TWAR agent. Semin Respir Infect. 1989;4:19–31.PubMed

59.

Yavlovich A, Tarshis M, Rottem S. Internalization and intracellular survival of Mycoplasma pneumoniae by non-phagocytic cells. FEMS Microbiol Lett. 2004;233:241–6.PubMedCrossRef

60.

Meseguer MA, Alvarez A, Rejas MT, et al. Mycoplasma pneumoniae: a reduced-genome intracellular bacterial pathogen. Infect Genet Evol. 2003;3:47–55.PubMedCrossRef

61.

Dallo SF, Baseman JB. Intracellular DNA replication and long-term survival of pathogenic Mycoplasmas. Microb Pathog. 2000;29:301–9.PubMedCrossRef

62.

Specjalski K, Jassem E. Chlamydophila pneumoniae, Mycoplasma pneumoniae infections, and asthma control. Allergy Asthma Proc. 2011;32:9–17.PubMedCrossRef

63.

Good Jr JT, Rollins DR, Martin RJ. Macrolides in the treatment of asthma. Curr Opin Pulm Med. 2012;18:76–84.PubMedCrossRef

64.

Sutherland ER, Martin RJ. Asthma and atypical bacterial infection. Chest. 2007;132:1962–6.PubMedCrossRef

65.

Roulis E, Polkinghorne A, Timms P. Chlamydia pneumoniae: modern insights into an ancient pathogen. Trends Microbiol. 2013;21:120–8.PubMedCrossRef

66.

Peeling RW, Brunham RC. Chlamydiae as pathogens: new species and new issues. Emerg Infect Dis. 1996;2:307–19.PubMedCrossRef

67.

Smieja M, Mahony J, Petrich A, et al. Association of circulating Chlamydia pneumoniae DNA with cardiovascular disease: a systematic review. BMC Infect Dis. 2002;2:21.PubMedCrossRef

68.

Hammerschlag MR. Chlamydia pneumoniae and asthma in children: diagnostic issues. Clin Infect Dis. 2004;39:1251–2. author reply 1252–1253.PubMedCrossRef

69.

Boman J, Gaydos CA. Polymerase chain reaction detection of Chlamydia pneumoniae in circulating white blood cells. J Infect Dis. 2000;181 Suppl 3:S452–4.PubMedCrossRef

70.

Apfalter P, Hammerschlag MR, Boman J. Reliability of nested PCR for the detection of Chlamydia pneumoniae in carotid artery atherosclerosis. Stroke. 2003;34:e73–5. author reply e73–75.PubMedCrossRef

71.

Poritz MA, Blaschke AJ, Byington CL, et al. FilmArray, an automated nested multiplex PCR system for multi-pathogen detection: development and application to respiratory tract infection. PLoS One. 2011;6:e26047.PubMedCrossRef

72.

Smith-Norowitz TA, Silverberg JI, Kusonruksa M, et al. Asthmatic children have increased specific anti-Mycoplasma pneumoniae IgM but not IgG or IgE-values independent of history of respiratory tract infection. Pediatr Infect Dis J. 2013;32:599–603.PubMedCrossRef

73.

Atkinson TP, Duffy LB, Pendley D, et al. Deficient immune response to Mycoplasma pneumoniae in childhood asthma. Allergy Asthma Proc. 2009;30:158–65.PubMedCrossRef

74.

Biberfeld G, Sterner G. A study of Mycoplasma pneumoniae infections in families. Scand J Infect Dis. 1969;1:39–46.PubMed

75.

• Peters J, Singh H, Brooks EG, et al.: Persistence of CARDS toxin-producing Mycoplasma pneumoniae in refractory asthma. Chest 2011 140(2):401-7. The authors use new, highly sensitive PCR and antigen-capture assays for the CARDS toxin gene and protein, respectively, to demonstrate that subjects with refractory asthma have a high prevalence of positivity (approximately 50%) for Mpn. Although intriguing, this study lacks normal control subjects. PubMedCrossRef

76.

Martin RJ, Kraft M, Chu HW, et al. A link between chronic asthma and chronic infection. J Allergy Clin Immunol. 2001;107:595–601.PubMedCrossRef

77.

Waites KB. What’s new in diagnostic testing and treatment approaches for Mycoplasma pneumoniae infections in children? Adv Exp Med Biol. 2011;719:47–57.PubMedCrossRef

78.

Sabato AR, Martin AJ, Marmion BP, et al. Mycoplasma pneumoniae: acute illness, antibiotics, and subsequent pulmonary function. Arch Dis Child. 1984;59:1034–7.PubMedCrossRef

79.

Wongtim S, Mogmued S. Methacholine inhalation challenge in patients with post-Mycoplasma pneumoniae pneumonia. Asian Pac J Allergy Immunol. 1995;13:5–10.PubMed

80.

Marc E, Chaussain M, Moulin F, et al. Reduced lung diffusion capacity after Mycoplasma pneumoniae pneumonia. Pediatr Infect Dis J. 2000;19:706–10.PubMedCrossRef

81.

Kjaer BB, Jensen JS, Nielsen KG, et al. Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood. Pediatr Pulmonol. 2008;43:567–75.PubMedCrossRef

82.

• Sutherland ER, King TS, Icitovic N, et al.: A trial of clarithromycin for the treatment of suboptimally controlled asthma. J Allergy Clin Immunol 2010, 126:747-753. In this study, while failing to achieve the power needed to test the effect of clarithromycin as an attempt to repeat the work of Kraft et al. [91], the authors yet found that 12% of chronic stable adult asthmatics were positive for Mpn. Samples from this study were also used the microbiome studies by Huang et al. [18•]. PubMedCrossRef

83.

Sasaki A, Ouchi K, Makata H, et al. The effect of inhaled corticosteroids on Chlamydophila pneumoniae and Mycoplasma pneumoniae infection in children with bronchial asthma. J Infect Chemother. 2009;15:99–103.PubMedCrossRef

84.

Chu HW, Campbell JA, Rino JG, et al. Inhaled fluticasone propionate reduces concentration of Mycoplasma pneumoniae, inflammation, and bronchial hyperresponsiveness in lungs of mice. J Infect Dis. 2004;189:1119–27.PubMedCrossRef

85.

Wood PR, Hill VL, Burks ML, et al. Mycoplasma pneumoniae in children with acute and refractory asthma. Ann Allergy Asthma Immunol. 2013;110:328–34. e321.PubMedCrossRef

86.

Kannan TR, Baseman JB. ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens. Proc Natl Acad Sci U S A. 2006;103:6724–9.PubMedCrossRef

87.

Medina JL, Coalson JJ, Brooks EG, et al. Mycoplasma pneumoniae CARDS toxin induces pulmonary eosinophilic and lymphocytic inflammation. Am J Respir Cell Mol Biol. 2012;46:815–22.PubMedCrossRef

88.

Hardy RD, Coalson JJ, Peters J, et al. Analysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxin. PLoS One. 2009;4:e7562.PubMedCrossRef

89.

Griffin MO, Ceballos G, Villarreal FJ. Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action. Pharmacol Res. 2011;63:102–7.PubMedCrossRef

90.

Reiter J, Demirel N, Mendy A, et al. Macrolides for the long-term management of asthma: A meta-analysis of randomized clinical trials. Allergy. 2013;68:1040–9.PubMedCrossRef

91.

Kraft M, Cassell GH, Pak J, Martin RJ. Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: Effect of clarithromycin. Chest. 2002;121:1782–8.PubMedCrossRef

92.

Daoud A, Gloria CJ, Taningco G, et al. Minocycline treatment results in reduced oral steroid requirements in adult asthma. Allergy Asthma Proc. 2008;29:286–94.PubMedCrossRef

Title: Is Asthma an Infectious Disease? New Evidence
Author: T. Prescott Atkinson
Publication date: 01-12-2013
Publisher: Springer US
Published in: Current Allergy and Asthma Reports / Issue 6/2013
Print ISSN: 1529-7322
Electronic ISSN: 1534-6315
DOI: https://doi.org/10.1007/s11882-013-0390-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Is Asthma an Infectious Disease? New Evidence

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2013

Pediatric Exercise-Induced Bronchoconstriction: Contemporary Developments in Epidemiology, Pathogenesis, Presentation, Diagnosis, and Therapy

Food-Dependent Exercise-Induced Anaphylaxis: Is Wheat Unique?

Will Sublingual Immunotherapy Offer Benefit for Asthma?

Molecular Basis for Downregulation of C5a-Mediated Inflammation by IgG1 Immune Complexes in Allergy and Asthma

Is Gluten a Cause of Gastrointestinal Symptoms in People Without Celiac Disease?

New Approaches to Modulating Idiopathic Pulmonary Fibrosis