Diagnostic value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in connective tissue diseases patients with suspected pulmonary infection

Background Metagenomic next-generation sequencing (mNGS) is a broad-range pathogen detection technique that provides a culture-independent approach to the etiological diagnosis of infectious diseases. However, its value for lower respiratory tract pathogen detection and clinical management in patients with connective tissue diseases (CTD) remains to be further clarified. Methods We retrospectively enrolled 81 hospitalized patients with CTD at the Department of Rheumatology and Immunology, Shanxi Bethune Hospital, between May 2020 and June 2025.All patients had new or progressive pulmonary lesions on high-resolution computed tomography (HRCT), were clinically suspected of having pulmonary infection, and underwent bronchoalveolar lavage fluid (BALF) mNGS and conventional microbiological tests (CMTs) within 72 hours of admission. Final clinical classification was established by multidisciplinary team (MDT) assessment. Pathogen detection and agreement between mNGS and CMTs were compared. Results The median age was 57 years, and 62.9% of patients were female. The most common CTD types were IIM, RA, and SLE. Following MDT assessment, 66 patients (81.5%) were classified as having pulmonary infections, 39 (48.1%) had interstitial lung disease (ILD), 11(13.6%) required noninvasive or invasive mechanical ventilation, and the 30-day mortality rate was 13.6%. The overall pathogen detection rate was higher with mNGS than with CMTs (77.7% vs. 45.7%, P<0.05).mNGS detected 35 pathogen species, including 18 bacterial, 7 fungal, and 10 viral species, the corresponding detection rates were 55.6%, 50.6%, and 59.3%, respectively. Mixed infections were more common than single infections, with bacterial-fungal-viral coinfection being the most frequent pathogen and viruses being the most common copathogens. Using CMTs as the microbiological comparator, overall agreement was limited (kappa=0.368), with a positive percent agreement (PPA) of 93.3% and a negative percent agreement (NPA) of 41.7%. mNGS results were incorporated into subsequent comprehensive clinical decision-making and were associated with adjustments in anti-infective and immunosuppressive treatment strategies. Conclusion mNGS increased lower respiratory tract pathogens detection in CTD patients with suspected pulmonary infection, and may provide complementary information for distinguishing pulmonary infection from CTD-related pulmonary involvement and for individualized clinical decision-making. Its impact on long-term clinical outcomes requires confirmation in prospective, multicenter controlled studies.