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. 2023 Dec 21:10:1321515.
doi: 10.3389/fmed.2023.1321515. eCollection 2023.

Targeted next-generation sequencing for pulmonary infection diagnosis in patients unsuitable for bronchoalveolar lavage

Zhenfeng Deng  1 , Chunhong Li  1 , Yingjin Wang  2 , Fengwen Wu  2 , Chunfang Liang  2 , Wei Deng  2 , Yuanli Wang  2
Affiliations

Targeted next-generation sequencing for pulmonary infection diagnosis in patients unsuitable for bronchoalveolar lavage

Zhenfeng Deng et al. Front Med (Lausanne). .

Abstract

Background: Targeted next-generation sequencing (tNGS) has emerged as a rapid diagnostic technology for identifying a wide spectrum of pathogens responsible for pulmonary infections.

Methods: Sputum samples were collected from patients unable or unwilling to undergo bronchoalveolar lavage. These samples underwent tNGS analysis to diagnose pulmonary infections. Retrospective analysis was performed on clinical data, and the clinical efficacy of tNGS was compared to conventional microbiological tests (CMTs).

Results: This study included 209 pediatric and adult patients with confirmed pulmonary infections. tNGS detected 45 potential pathogens, whereas CMTs identified 23 pathogens. The overall microbial detection rate significantly differed between tNGS and CMTs (96.7% vs. 36.8%, p < 0.001). Among the 76 patients with concordant positive results from tNGS and CMTs, 86.8% (66/76) exhibited full or partial agreement. For highly pathogenic and rare/noncolonized microorganisms, tNGS, combined with comprehensive clinical review, directly guided pathogenic diagnosis and antibiotic treatment in 21 patients. This included infections caused by Mycobacterium tuberculosis complex, certain atypical pathogens, Aspergillus, and nontuberculous Mycobacteria. Among the enrolled population, 38.8% (81/209) of patients adjusted their treatment based on tNGS results. Furthermore, tNGS findings unveiled age-specific heterogeneity in pathogen distribution between children and adults.

Conclusion: CMTs often fall short in meeting the diagnostic needs of pulmonary infections. This study highlights how tNGS of sputum samples from patients who cannot or will not undergo bronchoalveolar lavage yield valuable insights into potential pathogens, thereby enhancing the diagnosis of pulmonary infections in specific cases.

Keywords: conventional microbiological tests; pathogenic diagnosis; pulmonary infection; targeted next-generation sequencing; ultra-multiplex polymerase chain reaction.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of the study.
Figure 2
Figure 2
Distribution of potential pathogens in the study cohort and the respective contributions of tNGS and CMTs for pathogen detection.
Figure 3
Figure 3
Consistency of pathogen detection results between tNGS and CMTs.
Figure 4
Figure 4
Heterogeneity in the pathogen spectrum between children and adults.
See this image and copyright information in PMC

References

    1. Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet. (2020) 396:1204–22. doi: 10.1016/S0140-6736(20)30925-9 - DOI - PMC - PubMed
    1. Caliendo AM, Gilbert DN, Ginocchio CC, Hanson KE, May L, Quinn TC, et al. Better tests, better care: improved diagnostics for infectious diseases. Clin Infect Dis. (2013) 57:S139–70. doi: 10.1093/cid/cit578 - DOI - PMC - PubMed
    1. Xie Y, Du J, Jin W, Teng X, Cheng R, Huang P, et al. Next generation sequencing for diagnosis of severe pneumonia: China, 2010–2018. J Infect. (2019) 78:158–69. doi: 10.1016/j.jinf.2018.09.004 - DOI - PubMed
    1. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. (2015) 373:415–27. doi: 10.1056/NEJMoa1500245 - DOI - PMC - PubMed
    1. Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. (2015) 372:835–45. doi: 10.1056/NEJMoa1405870 - DOI - PMC - PubMed

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