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Comparative Study
. 2012 Dec 1;186(11):1117-24.
doi: 10.1164/rccm.201205-0806OC. Epub 2012 Sep 28.

Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease

Patrick Mallia  1 , Joseph Footitt, Rosa Sotero, Annette Jepson, Marco Contoli, Maria-Belen Trujillo-Torralbo, Tatiana Kebadze, Julia Aniscenko, Gregory Oleszkiewicz, Katrina Gray, Simon D Message, Kazuhiro Ito, Peter J Barnes, Ian M Adcock, Alberto Papi, Luminita A Stanciu, Sarah L Elkin, Onn M Kon, Malcolm Johnson, Sebastian L Johnston
Affiliations
Comparative Study

Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease

Patrick Mallia et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with virus (mostly rhinovirus) and bacterial infections, but it is not known whether rhinovirus infections precipitate secondary bacterial infections.

Objectives: To investigate relationships between rhinovirus infection and bacterial infection and the role of antimicrobial peptides in COPD exacerbations.

Methods: We infected subjects with moderate COPD and smokers and nonsmokers with normal lung function with rhinovirus. Induced sputum was collected before and repeatedly after rhinovirus infection and virus and bacterial loads measured with quantitative polymerase chain reaction and culture. The antimicrobial peptides secretory leukoprotease inhibitor (SLPI), elafin, pentraxin, LL-37, α-defensins and β-defensin-2, and the protease neutrophil elastase were measured in sputum supernatants.

Measurements and main results: After rhinovirus infection, secondary bacterial infection was detected in 60% of subjects with COPD, 9.5% of smokers, and 10% of nonsmokers (P < 0.001). Sputum virus load peaked on Days 5-9 and bacterial load on Day 15. Sputum neutrophil elastase was significantly increased and SLPI and elafin significantly reduced after rhinovirus infection exclusively in subjects with COPD with secondary bacterial infections, and SLPI and elafin levels correlated inversely with bacterial load.

Conclusions: Rhinovirus infections are frequently followed by secondary bacterial infections in COPD and cleavage of the antimicrobial peptides SLPI and elafin by virus-induced neutrophil elastase may precipitate these secondary bacterial infections. Therapy targeting neutrophil elastase or enhancing innate immunity may be useful novel therapies for prevention of secondary bacterial infections in virus-induced COPD exacerbations.

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Figures

Figure 1.
Figure 1.
Time course of bacterial load. (A) Time course of bacterial load in subjects successfully infected with rhinovirus. (B) Time course of bacterial load in all subjects in whom rhinovirus infection was not confirmed but who underwent the same study procedures as the infected subjects. (C) Time course of sputum virus load and bacterial load in subjects with COPD. All data mean ± SEM. *P < 0.05 compared with baseline. ***P < 0.001 compared with baseline. †P < 0.05 compared with NS. #P < 0.05 compared with SMK. COPD = chronic obstructive pulmonary disease; NS = nonsmokers; SMK = smokers.
Figure 2.
Figure 2.
Clinical and inflammatory parameters in subjects with chronic obstructive pulmonary disease (COPD) with and without bacterial infection. (A) Total lower respiratory symptom scores. (B) Breathlessness scores. (C) Peak expiratory flow. (D) Total sputum inflammatory cells. (E) Sputum neutrophil numbers. (F) Sputum neutrophil elastase levels. All data mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 compared with baseline.
Figure 3.
Figure 3.
Levels of antimicrobial peptides in sputum in all subject groups. (A) Pentraxin 3. (B) LL-37. (C) α-defensins. (D) human β-defensin-2 (HBD-2). (E) Secretory leukoprotease inhibitor (SLPI). (F) Elafin. A, B, and C are mean ± SEM; D, E, and F are median ± IQR. *P < 0.05, **P < 0.01 and, ***P < 0.001 compared with baseline.
Figure 4.
Figure 4.
Change from baseline of levels of elafin and secretory leukoprotease inhibitor (SLPI) in sputum in subjects with chronic obstructive pulmonary disease (COPD) with and without bacterial infection. (A) Time course of sputum elafin. (B) Time course of sputum SLPI. (C) Change from baseline of sputum elafin levels on Days 9 and 12. (D) Change from baseline of sputum SLPI levels on Days 9 and 12. All data median ± IQR. *P < 0.05 compared with baseline, †P < 0.05 compared with subjects without bacterial infection.
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Comment in

  • Chance favors the prepared mind.
    Sethi S. Sethi S. Am J Respir Crit Care Med. 2012 Dec 1;186(11):1070-1. doi: 10.1164/rccm.201210-1800ED. Am J Respir Crit Care Med. 2012. PMID: 23204370 No abstract available.

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References

    1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006;3:e442. - PMC - PubMed
    1. Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418–1422 - PubMed
    1. Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002;57:847–852 - PMC - PubMed
    1. Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS, The GOLD Scientific Committee Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001;163:1256–1276 - PubMed
    1. Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P, Caramori G, Fabbri LM, Johnston SL. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med 2006;173:1114–1121 - PubMed

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