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Published in: BMC Pulmonary Medicine 1/2017

Open Access 01-12-2017 | Research article

Detection of pathogens by real-time PCR in adult patients with acute exacerbation of bronchial asthma

Authors: Yutaka Yoshii, Kenichiro Shimizu, Miyuki Morozumi, Naoko Chiba, Kimiko Ubukata, Hironori Uruga, Shigeo Hanada, Hiroshi Wakui, Shunsuke Minagawa, Hiromichi Hara, Takanori Numata, Keisuke Saito, Jun Araya, Katsutoshi Nakayama, Kazuma Kishi, Kazuyoshi Kuwano

Published in: BMC Pulmonary Medicine | Issue 1/2017

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Abstract

Background

Respiratory tract infection is a major cause of acute exacerbation of bronchial asthma (AEBA). Although recent findings suggest that common bacteria are causally associated with AEBA, a comprehensive epidemiologic analysis of infectious pathogens including common/atypical bacteria and viruses in AEBA has not been performed. Accordingly, we attempted to detect pathogens during AEBA by using real-time polymerase chain reaction (PCR) in comparison to conventional methods.

Methods

We prospectively enroled adult patients with AEBA from August 2012 to March 2014. Infectious pathogens collected in nasopharyngeal swab and sputum samples were examined in each patient by conventional methods and real-time PCR, which can detect 6 bacterial and 11 viral pathogens. The causal association of these pathogens with AEBA severity and their frequency of monthly distribution were also examined.

Results

Among the 64 enroled patients, infectious pathogens were detected in 49 patients (76.6%) using real-time PCR and in 14 patients (21.9%) using conventional methods (p < 0.001). Real-time PCR detected bacteria in 29 patients (45.3%) and respiratory viruses in 28 patients (43.8%). Haemophilus influenzae was the most frequently detected microorganism (26.6%), followed by rhinovirus (15.6%). Influenza virus was the significant pathogen associated with severe AEBA. Moreover, AEBA occurred most frequently during November to January.

Conclusions

Real-time PCR was more useful than conventional methods to detect infectious pathogens in patients with AEBA. Accurate detection of pathogens with real-time PCR may enable the selection of appropriate anti-bacterial/viral agents as a part of the treatment for AEBA.
Literature
1.
2.
go back to reference Baxi SN, Phipatanakul W. The role of allergen exposure and avoidance in asthma. Adolesc Med State Art Rev. 2010;21:57–71.PubMedPubMedCentral Baxi SN, Phipatanakul W. The role of allergen exposure and avoidance in asthma. Adolesc Med State Art Rev. 2010;21:57–71.PubMedPubMedCentral
3.
go back to reference Bai TR, Vonk JM, Postma DS, Boezen HM. Severe exacerbations predict excess lung function decline in asthma. Eur Respir J. 2007;30:452–6.CrossRefPubMed Bai TR, Vonk JM, Postma DS, Boezen HM. Severe exacerbations predict excess lung function decline in asthma. Eur Respir J. 2007;30:452–6.CrossRefPubMed
4.
go back to reference Krishnan V, Diette GB, Rand CS, Bilderback AL, Merriman B, Hansel NN, et al. Mortality in patients hospitalized for asthma exacerbations in the United States. Am J Respir Crit Care Med. 2006;174:633–8.CrossRefPubMedPubMedCentral Krishnan V, Diette GB, Rand CS, Bilderback AL, Merriman B, Hansel NN, et al. Mortality in patients hospitalized for asthma exacerbations in the United States. Am J Respir Crit Care Med. 2006;174:633–8.CrossRefPubMedPubMedCentral
5.
go back to reference Kaur BP, Lahewala S, Arora S, Agnihotri K, Panaich SS, Secord E, et al. Asthma: hospitalization trends and predictors of in-hospital mortality and hospitalization costs in the USA (2001-2010). Int Arch Allergy Immunol. 2015;168:71–8.CrossRefPubMed Kaur BP, Lahewala S, Arora S, Agnihotri K, Panaich SS, Secord E, et al. Asthma: hospitalization trends and predictors of in-hospital mortality and hospitalization costs in the USA (2001-2010). Int Arch Allergy Immunol. 2015;168:71–8.CrossRefPubMed
6.
go back to reference Yamauchi Y, Yasunaga H, Matsui H, Hasegawa W, Jo T, Takami K, et al. Comparison of in-hospital mortality in patients with COPD, asthma and asthma-COPD overlap exacerbations. Respirology. 2015;20:940–6.CrossRefPubMed Yamauchi Y, Yasunaga H, Matsui H, Hasegawa W, Jo T, Takami K, et al. Comparison of in-hospital mortality in patients with COPD, asthma and asthma-COPD overlap exacerbations. Respirology. 2015;20:940–6.CrossRefPubMed
8.
go back to reference Atmar RL, Guy E, Guntupalli KK, Zimmerman JL, Bandi VD, Baxter BD, et al. Respiratory tract viral infections in inner-city asthmatic adults. Arch Intern Med. 1998;158:2453–9.CrossRefPubMed Atmar RL, Guy E, Guntupalli KK, Zimmerman JL, Bandi VD, Baxter BD, et al. Respiratory tract viral infections in inner-city asthmatic adults. Arch Intern Med. 1998;158:2453–9.CrossRefPubMed
9.
go back to reference Wark PA, Johnston SL, Moric I, Simpson JL, Hensley MJ, Gibson PG. Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma. Eur Respir J. 2002;19:68–75.CrossRefPubMed Wark PA, Johnston SL, Moric I, Simpson JL, Hensley MJ, Gibson PG. Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma. Eur Respir J. 2002;19:68–75.CrossRefPubMed
10.
go back to reference Tan WC, Xiang X, Qiu D, Ng TP, Lam SF, Hegele RG. Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease. Am J Med. 2003;115:272–7.CrossRefPubMed Tan WC, Xiang X, Qiu D, Ng TP, Lam SF, Hegele RG. Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease. Am J Med. 2003;115:272–7.CrossRefPubMed
11.
go back to reference Grissell TV, Powell H, Shafren DR, Boyle MJ, Hensley MJ, Jones PD, et al. Interleukin-10 gene expression in acute virus-induced asthma. Am J Respir Crit Care Med. 2005;172:433–9.CrossRefPubMed Grissell TV, Powell H, Shafren DR, Boyle MJ, Hensley MJ, Jones PD, et al. Interleukin-10 gene expression in acute virus-induced asthma. Am J Respir Crit Care Med. 2005;172:433–9.CrossRefPubMed
12.
go back to reference Miyashita N, Kubota Y, Nakajima M, Niki Y, Kawane H, Matsushima T. Chlamydia pneumoniae and exacerbations of asthma in adults. Ann Allergy Asthma Immunol. 1998;80:405–9.CrossRefPubMed Miyashita N, Kubota Y, Nakajima M, Niki Y, Kawane H, Matsushima T. Chlamydia pneumoniae and exacerbations of asthma in adults. Ann Allergy Asthma Immunol. 1998;80:405–9.CrossRefPubMed
13.
15.
go back to reference Lieberman D, Printz S, Ben-Yaakov M, Lazarovich Z, Ohana B, Friedman MG, et al. Atypical pathogen infection in adults with acute exacerbation of bronchial asthma. Am J Respir Crit Care Med. 2003;167:406–10.CrossRefPubMed Lieberman D, Printz S, Ben-Yaakov M, Lazarovich Z, Ohana B, Friedman MG, et al. Atypical pathogen infection in adults with acute exacerbation of bronchial asthma. Am J Respir Crit Care Med. 2003;167:406–10.CrossRefPubMed
17.
go back to reference Maffey AF, Barrero PR, Venialgo C, Fernandez F, Fuse VA, Saia M, et al. Viruses and atypical bacteria associated with asthma exacerbations in hospitalized children. Pediatr Pulmonol. 2010;45:619–25.CrossRefPubMed Maffey AF, Barrero PR, Venialgo C, Fernandez F, Fuse VA, Saia M, et al. Viruses and atypical bacteria associated with asthma exacerbations in hospitalized children. Pediatr Pulmonol. 2010;45:619–25.CrossRefPubMed
18.
20.
go back to reference Yoshii Y, Shimizu K, Morozumi M, Chiba N, Ubukata K, Uruga H, et al. Identification of pathogens by comprehensive real-time PCR versus conventional methods in community-acquired pneumonia in Japanese adults. Infect Dis (Lond). 2016;48:782–8.CrossRef Yoshii Y, Shimizu K, Morozumi M, Chiba N, Ubukata K, Uruga H, et al. Identification of pathogens by comprehensive real-time PCR versus conventional methods in community-acquired pneumonia in Japanese adults. Infect Dis (Lond). 2016;48:782–8.CrossRef
21.
go back to reference Shimizu K, Yoshii Y, Morozumi M, Chiba N, Ubukata K, Uruga H, et al. Pathogens in COPD exacerbations identified by comprehensive real-time PCR plus older methods. Int J Chron Obstruct Pulmon Dis. 2015;10:2009–16.CrossRefPubMedPubMedCentral Shimizu K, Yoshii Y, Morozumi M, Chiba N, Ubukata K, Uruga H, et al. Pathogens in COPD exacerbations identified by comprehensive real-time PCR plus older methods. Int J Chron Obstruct Pulmon Dis. 2015;10:2009–16.CrossRefPubMedPubMedCentral
22.
go back to reference Morozumi M, Nakayama E, Iwata S, Aoki Y, Hasegawa K, Kobayashi R, et al. Simultaneous detection of pathogens in clinical samples from patients with community-acquired pneumonia by real-time PCR with pathogen-specific molecular beacon probes. J Clin Microbiol. 2006;44:1440–6.CrossRefPubMedPubMedCentral Morozumi M, Nakayama E, Iwata S, Aoki Y, Hasegawa K, Kobayashi R, et al. Simultaneous detection of pathogens in clinical samples from patients with community-acquired pneumonia by real-time PCR with pathogen-specific molecular beacon probes. J Clin Microbiol. 2006;44:1440–6.CrossRefPubMedPubMedCentral
23.
go back to reference Hamano-Hasegawa K, Morozumi M, Nakayama E, Chiba N, Murayama SY, Takayanagi R, et al. Comprehensive detection of causative pathogens using real-time PCR to diagnose pediatric community-acquired pneumonia. J Infect Chemother. 2008;14:424–32.CrossRefPubMed Hamano-Hasegawa K, Morozumi M, Nakayama E, Chiba N, Murayama SY, Takayanagi R, et al. Comprehensive detection of causative pathogens using real-time PCR to diagnose pediatric community-acquired pneumonia. J Infect Chemother. 2008;14:424–32.CrossRefPubMed
24.
go back to reference Okada T, Morozumi M, Tajima T, Hasegawa M, Sakata H, Ohnari S, et al. Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children. Clin Infect Dis. 2012;55:1642–9.CrossRefPubMed Okada T, Morozumi M, Tajima T, Hasegawa M, Sakata H, Ohnari S, et al. Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children. Clin Infect Dis. 2012;55:1642–9.CrossRefPubMed
25.
go back to reference Iikura M, Hojo M, Koketsu R, Watanabe S, Sato A, Chino H, et al. The importance of bacterial and viral infections associated with adult asthma exacerbations in clinical practice. PLoS One. 2015;10:e0123584.CrossRefPubMedPubMedCentral Iikura M, Hojo M, Koketsu R, Watanabe S, Sato A, Chino H, et al. The importance of bacterial and viral infections associated with adult asthma exacerbations in clinical practice. PLoS One. 2015;10:e0123584.CrossRefPubMedPubMedCentral
26.
go back to reference Green BJ, Wiriyachaiporn S, Grainge C, Rogers GB, Kehagia V, Lau L, et al. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PLoS One. 2014;9:e100645.CrossRefPubMedPubMedCentral Green BJ, Wiriyachaiporn S, Grainge C, Rogers GB, Kehagia V, Lau L, et al. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PLoS One. 2014;9:e100645.CrossRefPubMedPubMedCentral
27.
go back to reference Wood LG, Simpson JL, Hansbro PM, Gibson PG. Potentially pathogenic bacteria cultured from the sputum of stable asthmatics are associated with increased 8-isoprostane and airway neutrophilia. Free Radic Res. 2010;44:146–54.CrossRefPubMed Wood LG, Simpson JL, Hansbro PM, Gibson PG. Potentially pathogenic bacteria cultured from the sputum of stable asthmatics are associated with increased 8-isoprostane and airway neutrophilia. Free Radic Res. 2010;44:146–54.CrossRefPubMed
28.
go back to reference Johnston SL, Blasi F, Black PN, Martin RJ, Farrell DJ, Nieman RB, et al. The effect of telithromycin in acute exacerbations of asthma. N Engl J Med. 2006;354:1589–600.CrossRefPubMed Johnston SL, Blasi F, Black PN, Martin RJ, Farrell DJ, Nieman RB, et al. The effect of telithromycin in acute exacerbations of asthma. N Engl J Med. 2006;354:1589–600.CrossRefPubMed
29.
go back to reference Cazzola M, Matera MG, Rossi F. Bronchial hyperresponsiveness and bacterial respiratory infections. Clin Ther. 1991;13:157–71.PubMed Cazzola M, Matera MG, Rossi F. Bronchial hyperresponsiveness and bacterial respiratory infections. Clin Ther. 1991;13:157–71.PubMed
30.
go back to reference Sandrock CE, Norris A. Infection in severe asthma exacerbations and critical asthma syndrome. Clin Rev Allergy Immunol. 2015;48:104–13.CrossRefPubMed Sandrock CE, Norris A. Infection in severe asthma exacerbations and critical asthma syndrome. Clin Rev Allergy Immunol. 2015;48:104–13.CrossRefPubMed
31.
go back to reference Yamaya M, Shinya K, Hatachi Y, Kubo H, Asada M, Yasuda H, et al. Clarithromycin inhibits type a seasonal influenza virus infection in human airway epithelial cells. J Pharmacol Exp Ther. 2010;333:81–90.CrossRefPubMed Yamaya M, Shinya K, Hatachi Y, Kubo H, Asada M, Yasuda H, et al. Clarithromycin inhibits type a seasonal influenza virus infection in human airway epithelial cells. J Pharmacol Exp Ther. 2010;333:81–90.CrossRefPubMed
32.
go back to reference Cates CJ, Rowe BH. Vaccines for preventing influenza in people with asthma. Cochrane Database Syst Rev. 2013;28:CD000364. Cates CJ, Rowe BH. Vaccines for preventing influenza in people with asthma. Cochrane Database Syst Rev. 2013;28:CD000364.
33.
go back to reference Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005;352:1749–59.CrossRefPubMed Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005;352:1749–59.CrossRefPubMed
34.
go back to reference Griffin MR, Coffey CS, Neuzil KM, Mitchel EF Jr, Wright PF, Edwards KM. Winter viruses: influenza- and respiratory syncytial virus-related morbidity in chronic lung disease. Arch Intern Med. 2002;162:1229–36.CrossRefPubMed Griffin MR, Coffey CS, Neuzil KM, Mitchel EF Jr, Wright PF, Edwards KM. Winter viruses: influenza- and respiratory syncytial virus-related morbidity in chronic lung disease. Arch Intern Med. 2002;162:1229–36.CrossRefPubMed
35.
go back to reference Teichtahl H, Buckmaster N, Pertnikovs E. The incidence of respiratory tract infection in adults requiring hospitalization for asthma. Chest. 1997;112:591–6.CrossRefPubMed Teichtahl H, Buckmaster N, Pertnikovs E. The incidence of respiratory tract infection in adults requiring hospitalization for asthma. Chest. 1997;112:591–6.CrossRefPubMed
36.
go back to reference Lemenager J, Benard Y, Langeard M. Haemophilus influenzae in respiratory pathology in adult. Sem Hop. 1983;59:1665–7. Article in FrenchPubMed Lemenager J, Benard Y, Langeard M. Haemophilus influenzae in respiratory pathology in adult. Sem Hop. 1983;59:1665–7. Article in FrenchPubMed
37.
go back to reference Johnston NW. The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbations. Proc Am Thorac Soc. 2007;4:591–6.CrossRefPubMed Johnston NW. The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbations. Proc Am Thorac Soc. 2007;4:591–6.CrossRefPubMed
Metadata
Title
Detection of pathogens by real-time PCR in adult patients with acute exacerbation of bronchial asthma
Authors
Yutaka Yoshii
Kenichiro Shimizu
Miyuki Morozumi
Naoko Chiba
Kimiko Ubukata
Hironori Uruga
Shigeo Hanada
Hiroshi Wakui
Shunsuke Minagawa
Hiromichi Hara
Takanori Numata
Keisuke Saito
Jun Araya
Katsutoshi Nakayama
Kazuma Kishi
Kazuyoshi Kuwano
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2017
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-017-0494-3

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