1. Introduction
Infectious diseases remain most common causes of death among all patient
populations worldwide [1].
Pulmonary infections lead to more
deaths each year than any other infectious disease categories
[2].
Delayed identification of
etiologic pathogens in
pulmonary infections is the key
cause of treatment failure and death.
Current microbiological tests such
as culture-based methods often fail to identify the etiologic pathogens
in most cases of pulmonary infection, due largely to the limitations in
terms of sensitivity [3, 4],
speed and spectrums of available assay targets [5]. In these
situations, failing to identify the etiology microorganisms often
promotes the initiation of empiric
antibiotic therapy, which may lack
activity against an underlying microorganism, leading to treatment
failure, disease progression, and consequent adverse outcomes
[5, 6].
Swift identification of causative
microorganisms and tailoring of the antimicrobial regimen is highly
desirable, which would improve the prognosis of pulmonary infections due
to optimization of antimicrobial treatment.
Recent rapid advances in genomic
sequencing techniques and bioinformatics has made it possible for
metagenomic next-generation sequencing (mNGS) to be used in clinical
diagnostics. [7
~ 9]. mNGS is an unbiased approach that can
theoretically detect all microorganisms in a clinical sample
[10], which offers potential
alternatives for detecting etiologic microorganisms and distinguish them
from background commensal microorganisms, which might pave the way for
personalized medicine [11].
Several reports have attempted to detect pathogens using mNGS in
infectious diseases, such as central nervous system infections [12
~ 14], digestive infections
[15, 16], bloodstream
infections [7, 18] and
pulmonary infections [19
~ 23]. Published information on the use of mNGS in
diagnosing pulmonary infections is sparse, and the types of samples
tested by mNGS were mainly limited to percutaneous lung biopsy samples
[19] and bronchoalveolar
lavage fluid (BALF) samples [20 ~ 23].
Accurate sampling of peripheral
pulmonary lesions (PPLs), which were defined as lesions surrounded by
normal lung parenchyma presents challenges and were unlikely to be
visualized by bronchoscopy, is the key step. CT-guided percutaneous
needle biopsy has a high diagnostic yield for PPIs, but is more invasive
and with a relatively high incidence of complications, such as bleeding
or pneumothorax [24, 25].
Bronchoscopy remains an appropriate initial investigation for PPLs, due
to the lower complication rate
[26]. Most previous studies
have focused on the use of bronchoscopy in diagnosing malignancy. There
is little published information on the use of bronchoscopy in diagnosing
infectious PPLs.
The present study consists of two parts: on the one hand, we
retrospectively evaluate the performance of mNGS for samples from
infectious PPLs obtained using ultrathin bronchoscopy in conjunction
with virtual bronchoscopic navigation (VBN) and
rapid on-site cytological
evaluation (ROSE), and compare diagnostic accuracy of mNGS with
conventional cultures; on the other hand, we evaluate the comparative
diagnostic performance and microbial composition from different sampling
including
transbronchial
lung biopsy (TBLB), bronchial
needle brushing (BB) and BALF with mNGS.