PCR Detection of Viral Nucleic Acid in Fatal Asthma: Is the Lower Respiratory Tract a Reservoir for Common Viruses?

Macek, V; Dakhama, Azzeddine; Hogg, James C.; Green, Francis Hy; Rubin, Bruce K.; Hegele, Richard G.

doi:10.1155/1999/938049

Cited by 28 publications

(12 citation statements)

References 24 publications

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“…5 Further, patient sampling considerations could affect results, as viral nucleic acid has been frequently detected in specimens obtained from lower respiratory tract of older children and adults. 32,33 Other pathogens could be added to further expand the qPCR panel, as warranted by advances in knowledge and in considering the design of future prospective studies.…”

Section: Utokaparch Et Almentioning

confidence: 99%

The Relationship Between Respiratory Viral Loads and Diagnosis in Children Presenting to a Pediatric Hospital Emergency Department

Utokaparch¹,

Marchant²,

Gosselink³

et al. 2011

Pediatric Infectious Disease Journal

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Section: Utokaparch Et Almentioning

confidence: 99%

The Relationship Between Respiratory Viral Loads and Diagnosis in Children Presenting to a Pediatric Hospital Emergency Department

Utokaparch¹,

Marchant²,

Gosselink³

et al. 2011

Pediatric Infectious Disease Journal

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“…Previous work in allergy-susceptible CH has shown that RSV can cause a persistent lung infection associated with AHR and airway inflammation (7,8,14), consistent with a possible role of RSV persistence in the pathogenesis of post-bronchiolitis sequelae. In contrast, other studies have implicated RSV persistence in the lungs but without a clear relationship to a particular clinical phenotype (9,10,12,13). Because Th1 responses are considered important for antiviral immunity, we hypothesized that a host genetic background for allergy susceptibility, manifested by Th2 skewing, would confer more severe consequences of RSV persistence.…”

Section: Discussionmentioning

confidence: 87%

T Helper 1 Background Protects Against Airway Hyperresponsiveness and Inflammation in Guinea Pigs With Persistent Respiratory Syncytial Virus Infection

et al. 2007

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A family history of allergy has been implicated in children who develop post-bronchiolitis wheezing and asthma. In a guinea pig model of respiratory syncytial virus (RSV) lung infection, we evaluated the role of host Th1 background (either genetic or induced) on the development of a persistent infection, nonspecific airway hyperresponsiveness (AHR) and airway inflammation. Allergy resistant/T helper 1 (Th1)-skewed strain 2 guinea pigs (STR2) and cytosine phosphate guanine oligodeoxynucleotides (CpG-ODN) (Th1 stimuli) pretreated Cam Hartley guinea pigs (CH) were inoculated with RSV and compared with virus-inoculated allergysusceptible/Th2-skewed CHs and to sham-inoculated STR2 and CH, 60 d post-inoculation. We measured titers of intrapulmonary RSV, lung interferon (IFN)-␥ and interleukin (IL)-5 mRNA expression, AHR and airway T cells and eosinophils. All virus-inoculated groups of animals showed evidence of persistent RSV lung infection; however, Th2-skewed guinea pigs had virus-associated AHR and significantly greater levels of airway T cells and eosinophils. In conclusion, RSV can establish persistent infection of the guinea pig lung regardless of host Th1/Th2 background; however; a host Th1 background limits the extent of virus-associated AHR and airway inflammation. Heterogeneity in virus-host interactions may be relevant to understanding why some children hospitalized for RSV bronchiolitis go on to develop recurrent wheezing/asthma symptoms. R SV is the most common cause of acute bronchiolitis, the leading cause of infant hospitalization in the developed world (1). A proportion of children hospitalized with acute bronchiolitis develop sequelae of recurrent wheezing and features of asthma for which allergic mechanisms (2-5) or a family history of allergy (6) have been implicated. In addition, studies in animal models have reported that RSV can establish a persistent, low-level infection in the lungs (7,8), and results of several cross-sectional (9 -11) and longitudinal studies (12) suggest that RSV can persistently infect the human lung.However, the consequences of chronic intrapulmonary RSV persistence are unclear (13).We have developed a guinea pig model of experimental RSV infection in which lung function and airway inflammation have been studied in association with RSV persistence (8,14). In this model, intranasal RSV inoculation of juvenile CH results in a productive lung infection that is associated with nonspecific AHR and airway inflammation by lymphocytes and granulocytes, including T cells and eosinophils (8,15,16). After resolution of the acute infection, CH develop a persistent lung infection characterized by ongoing, low-level RSV replication, AHR, and airway eosinophilia (8,14,15). These findings in guinea pigs suggest a possible role for RSV persistence in the pathogenesis of AHR and airway inflammation that have features similar to asthma (17).Importantly, CH are a genetically outbred strain that is highly susceptible to allergic sensitization relative to inbred STR2 or STR13 (18). S...

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“…Viral RNA can be detected in up to 15% of sputum samples from adults with chronic obstructive pulmonary disease during clinically stable periods [13][14][15][16]. The human lung is a reservoir for common respiratory viruses [17]. As is the case for bacterial sputum cultures, the presence of viral RNA in a sample from the upper airway does not define the etiology of CAP.…”

Section: Viruses In Cap In Adultsmentioning

confidence: 99%

Placebo‐Controlled Trials of Treatments for Community‐Acquired Pneumonia: Review of the Literature and Discussion of Feasibility and Potential Value

Murphy

2008

CLIN INFECT DIS

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Community-acquired pneumonia (CAP) has a broad range of clinical manifestations, from apparently self-limited illness to severe disease. This observation raises the question of whether to perform placebo-controlled trials involving patients with mild CAP to determine quantitatively the treatment effect of antibiotic therapy for CAP. A critical analysis of the literature reveals that most clinical trials underestimate the proportion of CAP cases of all severities that are caused by typical bacteria, particularly pneumococci. Studies that use vigorous diagnostic methods consistently report that the majority of CAP cases are caused by pneumococci. Currently, there is little evidence that viruses cause a substantial proportion of CAP cases in adults. Although relevant placebo-controlled trials have not been published in recent years, other evidence indicates that antibiotic therapy is unequivocally effective for pneumococcal pneumonia. The availability of effective therapy for Streptococcus pneumoniae pneumonia presents clinical, ethical, and pragmatic obstacles to the performance of placebo-controlled trials. Furthermore, if placebo-controlled trials were performed for mild CAP, patients with risk factors for pneumococcal pneumonia and patients with predictors of systemic illness would be excluded, thereby resulting in a highly selected population. On the basis of the data reviewed, there is no justification for placebo-controlled trials involving patients with CAP of any degree of severity.

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PCR Detection of Viral Nucleic Acid in Fatal Asthma: Is the Lower Respiratory Tract a Reservoir for Common Viruses?

Abstract: In fatal asthma, lower airway secretions do not show a specific pattern of viral nucleic acid. Intriguingly, these results suggest that the lower respiratory tract may act as a potential reservoir for common respiratory viruses.

Cited by 28 publications

References 24 publications

The Relationship Between Respiratory Viral Loads and Diagnosis in Children Presenting to a Pediatric Hospital Emergency Department

The Relationship Between Respiratory Viral Loads and Diagnosis in Children Presenting to a Pediatric Hospital Emergency Department

T Helper 1 Background Protects Against Airway Hyperresponsiveness and Inflammation in Guinea Pigs With Persistent Respiratory Syncytial Virus Infection

Placebo‐Controlled Trials of Treatments for Community‐Acquired Pneumonia: Review of the Literature and Discussion of Feasibility and Potential Value

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