Background: Electromagnetic navigation bronchoscopy (ENB) is an emerging endoscopic technique for the diagnosis of peripheral lung lesions. A thorough analysis of ENB's yield and safety is required for comparison to other sampling modalities. Objectives: To describe ENB's yield and safety profile. Methods: The MEDLINE and EMBASE databases were systematically searched for studies reporting ENB's yield for peripheral lung lesions. Two independent investigators extracted data and rated each study on a scale of methodological quality. Clearly defined performance outcomes were reconstructed and meta-analyzed. Subgroup analysis and meta-regression were used to identify possible sources of study heterogeneity. Results: A total of 15 trials were included (1,033 lung nodules). A positive and definitive diagnosis was obtained after 64.9% of all ENB procedures (95% CI 59.2-70.3). Overall diagnostic accuracy was 73.9% (95% CI 68.0-79.2). Sensitivity to detect cancer was 71.1% (95% CI 64.6-76.8), with a negative predictive value of 52.1% (95% CI 43.5-60.6). Pneumothorax occurred in 3.1% of patients, requiring chest tube drainage in 1.6% of these cases. Original trials identified 6 variables associated with higher ENB yields: nodule location in the upper or middle lobes, nodule size, lower registration error, presence of a bronchus sign on CT imaging, combined use of an ultrasonic radial probe, and catheter suctioning as a sampling technique. Heterogeneity exploration revealed that studies using general anesthesia or rapid on-site cytological evaluation reported better yields. Conclusions: ENB is effective and particularly safe. Prospective studies are needed to clarify the role of several variables conditioning the yield of this technique.

Rhinoviral infection can be persistent in lung transplant recipients with graft dysfunction, and the virus can be detected in the lung parenchyma. Given the potential clinical impact, chronic rhinoviral infection needs to be considered in lung transplant recipients.

Author Contributions: M.S. made a substantial contribution to the conception and design of the work and to the acquisition, analysis, and interpretation of data for the work; wrote the manuscript; critically revised the manuscript for important intellectual content; and gave final approval of the current version to be published. F.v.L. made a substantial contribution to the conception and design of the work and to the interpretation of data for the work, performed statistical analysis, wrote the manuscript, critically revised the manuscript for important intellectual content, and gave final approval of the current version to be published. P.R. made a substantial contribution to the conception and design of the work and to the interpretation of data for the work, critically revised the manuscript for important intellectual content, and gave final approval of the current version to be published. C.L. made a substantial contribution to the conception and design of the work and to the acquisition, analysis, and interpretation of data for the work; wrote the manuscript; critically revised the manuscript for important intellectual content; and gave final approval of the current version to be published. All other authors made a contribution to the acquisition of the data for the work, critically revised the manuscript for important intellectual content, and gave final approval of the current version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Rhinoviruses and enteroviruses are leading causes of respiratory infections. To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specifi c or generic real-time PCR assays. We then sequenced the 5′ untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples. Subsequent phylogenetic analysis identifi ed the large genotypic diversity of rhinoviruses circulating in humans. We identifi ed and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confi rming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens. Finally, we identifi ed recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host. This study clarifi es the diversity and explains the reasons for evolution of these viruses.H uman rhinoviruses (HRVs) and enteroviruses (HEVs) are leading causes of infection in humans. These 2 picornaviruses share an identical genomic organization, have similar functional RNA secondary structures, and are classifi ed within the same genus (www.ictvonline.org/virusTaxonomy.asp) because of their high sequence homology (1). However, despite their common genomic features, these 2 groups of viruses have different phenotypic characteristics. In vivo, rhinoviruses are restricted to the respiratory tract, whereas enteroviruses infect primarily the gastrointestinal tract and can spread to other sites such as the central nervous system. However, some enteroviruses exhibit specifi c respiratory tropism and thus have properties similar to rhinoviruses (2-5). In vitro, most HRVs and HEVs differ by their optimal growth temperature, acid tolerance, receptor usage, and cell tropism. The genomic basis for these phenotypic differences between similar viruses is not yet fully understood.HRVs and HEVs are characterized by ≈100 serotypes. Recently, molecular diagnostic tools have shown that this diversity expands beyond those predefi ned serotypes and encompasses also previously unrecognized rhinovirus and enterovirus genotypes. As an example, a new HRV lineage named HRV-C was recently identifi ed and now complements the 2 previously known A and B lineages (6-8) (N.J. Knowles, pers. comm.). The C lineage has not only a distinct phylogeny (9-16) but is also characterized by specifi c cis-acting RNA structures (17).In this study, we screened a large number of persons with acute respiratory diseases by using assays designed to overcome the diversity of both rhinoviruses and enteroviruses circulating in humans. Whenever possible, we systematically sequenced 5′ untranslated region (UTR), capsid protein VP1, and protease precursor 3CD regions of strains. Our goals were 1) to characterize the diversity of circulating rhinoviruses and, to a lesser extent, enteroviruses, to identify put...

Lung transplant recipients present an increased risk for severe complications associated with respiratory infections. We conducted a review of the literature examining the clinical relationship between viral respiratory infection and graft complications. Thirty-four studies describing the clinical impact of influenza, respiratory syncytial virus, parainfluenza, human metapneumovirus, rhinovirus, enterovirus, coronavirus, bocavirus or adenovirus were identified. The detection rate of respiratory viral infection ranged from 1.4% to 60%. Viruses were detected five times more frequently when respiratory symptoms were present [odds ratio (OR) = 4.97; 95% CI = 2.11-11.68]. Based on available observations, we could not observe an association between respiratory viral infection and acute rejection (OR = 1.35; 95% CI = 0.41-4.43). We found a pooled incidence of 18% (9/50) of bronchiolitis obliterans syndrome (BOS) in virus-positive cases compared to 11.6% (37/319) in virus-negative cases; however, limited number of BOS events did not allow to confirm the association. Our review confirms a causal relationship between respiratory viruses and respiratory symptoms, but cannot confirm a link between respiratory viruses and acute lung rejection. This is related in part to the heterogeneity and limitations of available studies. The link with BOS needs also to be reassessed in appropriate prospective studies.

BackgroundThe incidence and outcomes of respiratory viral infections in lung transplant recipients (LTR) are not well defined. The objective of this prospective study conducted from June 2008 to March 2011 was to characterise the incidence and outcomes of viral respiratory infections in LTR. Methods Patients were seen in three contexts: studyspecific screenings covering all seasons; routine posttransplantation follow-up; and emergency visits. Nasopharyngeal specimens were collected systematically and bronchoalveolar lavage (BAL) was performed when clinically indicated. All specimens underwent testing with a wide panel of molecular assays targeting respiratory viruses.Results One hundred and twelve LTR had 903 encounters: 570 (63%) were screening visits, 124 (14%) were routine post-transplantation follow-up and 209 (23%) were emergency visits. Respiratory viruses were identified in 174 encounters, 34 of these via BAL. The incidence of infection was 0.83 per patient-year (95% CI 0.45 to 1.52). The viral infection rates upon screening, routine and emergency visits were 14%, 15% and 34%, respectively ( p<0.001). Picornavirus was identified most frequently in nasopharyngeal (85/140; 60.7%) and BAL specimens (20/34; 59%). Asymptomatic viral carriage, mainly of picornaviruses, was found at 10% of screening visits. Infections were associated with transient lung function loss and high calcineurin inhibitor blood levels. The hospitalisation rate was 50% (95% CI 30% to 70.9%) for influenza and parainfluenza and 16.9% (95% CI 11.2% to 23.9%) for other viruses. Acute rejection was not associated with viral infection (OR 0.4, 95% CI 0.1 to 1.3). Conclusions There is a high incidence of viral infection in LTR; asymptomatic carriage is rare. Viral infections contribute significantly to this population's respiratory symptomatology. No temporal association was observed between infection and acute rejection.

The recently discovered HCoVs NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infection. Our study also suggests that coronaviruses contribute to respiratory symptoms in most cases.