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• W4226451707 abstract "PurposeChronic lung allograft dysfunction (CLAD) is the leading long-term contributor to mortality after lung transplant. The lung microbiome predicts subsequent development of CLAD, but whether lung bacteria differ between CLAD phenotypes is unknown.MethodsUsing a biorepository of acellular bronchoalveolar lavage (BAL) fluid, we identified specimens which were collected within 90 days of CLAD onset. CLAD phenotype was assigned based on the presence of absence of obstruction, restriction, and computed tomography (CT) scan opacities, in accordance with ISHLT guidelines. Bacterial DNA burden was measured with BioRad QX200 Droplet Digital PCR and 16S rRNA gene sequencing was performed using the Illumina MiSeq platform. Bacterial burden was compared using Wilcoxon rank-sum. Community composition was compared using PERMANOVA and mvabund (a model-based approach to analysis of multivariable abundance data).ResultsEighty (80) patients had a BAL specimen from near CLAD onset available for analysis. Of these, 41 (51%) had BOS, 13 (16%) had RAS, 6 (8%) had Mixed CLAD, and 20 (25%) had an undefined/unclassifiable phenotype. There were no differences in lung bacterial burden (p=0.56, Panel A) or overall community composition between CLAD phenotypes (p=0.53, Panel C). Shannon diversity index did differ between CLAD phenotypes, with lower average diversity observed in the patients with an unclassifiable CLAD phenotype (1.0 ± 0.4) vs. BOS (2.2 ± 0.8), RAS (2.1 ± 0.8), Mixed (2.1 ± 0.7), or undefined CLAD (2.1 ± 0.4, overall p=0.02, Panel B). This difference persisted even after accounting for clinical evidence of infection (BAL neutrophilia and bacterial culture results did not differ between groups).ConclusionLung microbiome characteristics are largely similar across CLAD phenotypes, although lower within-specimen diversity is seen in patients with unclassified CLAD. Chronic lung allograft dysfunction (CLAD) is the leading long-term contributor to mortality after lung transplant. The lung microbiome predicts subsequent development of CLAD, but whether lung bacteria differ between CLAD phenotypes is unknown. Using a biorepository of acellular bronchoalveolar lavage (BAL) fluid, we identified specimens which were collected within 90 days of CLAD onset. CLAD phenotype was assigned based on the presence of absence of obstruction, restriction, and computed tomography (CT) scan opacities, in accordance with ISHLT guidelines. Bacterial DNA burden was measured with BioRad QX200 Droplet Digital PCR and 16S rRNA gene sequencing was performed using the Illumina MiSeq platform. Bacterial burden was compared using Wilcoxon rank-sum. Community composition was compared using PERMANOVA and mvabund (a model-based approach to analysis of multivariable abundance data). Eighty (80) patients had a BAL specimen from near CLAD onset available for analysis. Of these, 41 (51%) had BOS, 13 (16%) had RAS, 6 (8%) had Mixed CLAD, and 20 (25%) had an undefined/unclassifiable phenotype. There were no differences in lung bacterial burden (p=0.56, Panel A) or overall community composition between CLAD phenotypes (p=0.53, Panel C). Shannon diversity index did differ between CLAD phenotypes, with lower average diversity observed in the patients with an unclassifiable CLAD phenotype (1.0 ± 0.4) vs. BOS (2.2 ± 0.8), RAS (2.1 ± 0.8), Mixed (2.1 ± 0.7), or undefined CLAD (2.1 ± 0.4, overall p=0.02, Panel B). This difference persisted even after accounting for clinical evidence of infection (BAL neutrophilia and bacterial culture results did not differ between groups). Lung microbiome characteristics are largely similar across CLAD phenotypes, although lower within-specimen diversity is seen in patients with unclassified CLAD." @default.
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• W4226451707 date "2022-04-01" @default.
• W4226451707 modified "2023-10-18" @default.
• W4226451707 title "The Lung Microbiome is Similar Across CLAD Phenotypes" @default.
• W4226451707 doi "https://doi.org/10.1016/j.healun.2022.01.704" @default.
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