Factors associated with symptomatic rhinovirus infection in patients with COPD

https://doi.org/10.1016/j.jcv.2012.08.020Get rights and content

Abstract

Background

Human rhinoviruses (HRV) can be detected by RT-PCR in a large proportion of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) but can also be detected in COPD patients without symptoms.

Objectives

The purpose of this study was to compare host, virologic and environmental factors associated with symptomatic and asymptomatic HRV infection.

Study design

One hundred twenty-seven patients with COPD were evaluated every 2 months routinely and for all respiratory illnesses during a one year period. RT-PCR testing for HRV was performed on nasal and sputum samples. Amplification products were sequenced to assign species HRV-A, B or C. Clinical, virologic and environmental factors were compared for those infected with HRV compared to those without HRV infection as well as symptomatic HRV infection and asymptomatic HRV infection.

Results

HRVs were detected in 29 participants during 20 illnesses and 11 routine visits. HRV was detected in nasal samples from 15/102 (14.7%) illnesses compared to 2/685 (0.4%) routine visits (p < .0001). Sputum samples were also more frequently positive from illnesses than routine visits [14/72 (19.4%) vs. 16/310 (5.2%) p < .0001]. Contact with school age children was the only factor that was significantly associated with HRV infection and symptomatic HRV illness. Severity of underlying lung disease and virologic factors were not associated with symptomatic illness.

Conclusions

Contact with school aged children is a risk factor for both infection and symptomatic HRV illness. Attention to good hand hygiene and avoidance of direct contact with ill children may help patients with COPD avoid HRV related illness.

Section snippets

Background

For many years human rhinovirus (HRV) infections have been recognized as the most frequent causes of the common cold.1, 2 Older studies using viral culture for diagnosis demonstrated a range of clinical syndromes ranging from asymptomatic infection to sinusitis and bronchitis.3 The use of molecular diagnostics such as reverse transcriptase polymerase chain reaction (RT-PCR) has allowed a greater appreciation of HRVs as the cause of lower respiratory illness and recent studies frequently link

Objectives

The purpose of this study was to compare host, virologic and environmental factors associated with symptomatic HRV infection.

Study design

We took advantage of a prior study of COPD and respiratory syncytial virus (RSV) in which a cohort of patients with COPD were evaluated every 2 months and for all respiratory illnesses for one year.13 Testing for rhinovirus was performed on samples from this prospective study of 127 persons with COPD. Nasal and sputum samples were stored at minus 80 °C until testing.

Human rhinovirus (HRV)

The real time reverse transcriptase polymerase chain reaction (RT-PCR) assay was performed using the iScript one step RT-PCR kit (BioRad Laboratories, Hercules, CA). Primers and probes were based on the methods published by Lu et al. with the following modification for the forward primer (5′-CYGCCZGCGTGGY-3′).14 The amplification was performed on a BioRad iCylcer with the following conditions: 10 min at 48 °C, 3 min at 95 °C and 45 cycles of 15 s at 95 °C and 1 min at 60 °C.

Rhinovirus sequencing

The 187 base pair

Results

One hundred twenty-seven subjects were enrolled and 110 completed the study. Nine participants withdrew from the study due to ill health and 8 died. Most participants (97%) were cared for by a pulmonologist, 46% had chronic sputum production, and the mean smoking history was 49 pack-years. Seventy-one (56%) had pulmonary function test results available with a mean forced expiratory volume at one second (FEV1) of 44 ± 19% of predicted. Sixty-nine percent used inhaled steroids and 20% received

Discussion

Our study, similar to published reports, demonstrates that HRV infection is common among persons with COPD and accounted for 19% of the illnesses over a one year period.4, 5, 6, 7, 8, 9, 10, 11 Rates of HRV infection in AECOPD have varied widely ranging from 3 to 36% depending on the type of testing used.16, 17, 18 Many prior studies did not include COPD patients in the stable state and those that did typically used a case–control study design.8 Our study involved intensive sampling of subjects

Funding

None.

Ethical approval

The study was approved by the Rochester General Hospital and the University of Rochester Research Subjects Review Board.

Competing interests

None of the authors have financial conflicts of interest which could potentially bias the results of the study. Dr. Falsey has served as a consultant for sanofipasteur, GSK Biologics, Medimmune, AstraZeneca and Novartis. Dr. Walsh has served as a consultant for Novartis, Alnylam, AstraZeneca, Medimmune and Boehringer Ingelheim. Dr. Gandhi has no conflicts to declare.

References (42)

  • J.W. Brownlee et al.

    New developments in the epidemiology and clinical spectrum of rhinovirus infections

    Curr Opin Pediatr

    (2008)
  • K.E. Arden et al.

    Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections

    J Med Virol

    (2006)
  • A. Papi et al.

    Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations

    Am J Respir Crit Care Med

    (2006)
  • D.J. Jackson et al.

    Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children

    Am J Respir Crit Care Med

    (2008)
  • P. Mallia et al.

    Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation

    Am J Respir Crit Care Med

    (2011)
  • A.R. Falsey et al.

    Detection of respiratory syncytial virus in adults with chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2006)
  • X. Lu et al.

    Real-time reverse transcription-PCR assay for comprehensive detection of human rhinoviruses

    J Clin Microbiol

    (2008)
  • R.A. Pauwels et al.

    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)
  • R.O. Buscho et al.

    Infections with viruses and Mycoplasma pneumoniae during exacerbations of chronic bronchitis

    J Infect Dis

    (1978)
  • G. Rohde et al.

    respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case–control study

    Thorax

    (2003)
  • T. Seemungal et al.

    Respiratory viruses, symptoms, and inflammatory markers in acute axacerbations and stable chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2001)
  • Cited by (0)

    View full text