Airway Lipopolysaccharide Predicts Future Pseudomonadota Colonization and is Associated With Chronic Lung Allograft Dysfunction in Lung Transplant Recipients Without Positive Cultures
Bibliographic record
Abstract
Abstract Background: Pathogens in the phylum Pseudomonadota – including Haemophilus, Neisseria, and Pseudomonas – are commonly implicated in lung infections and exacerbation of chronic lung diseases. Colonization of the lung allograft with Pseudomonadota has been previously associated with lung allograft inflammation and increased risk of chronic lung allograft dysfunction (CLAD). Our group and others have previously shown that, despite treatment, lung transplant recipients (LTRs) with positive Pseudomonadota bronchoalveolar lavage (BAL) cultures within the first-year post-transplant are at an increased risk of adverse outcomes. Lipopolysaccharide (LPS) is a component of the gram-negative cell wall and potent stimulator of the host immune response. We have previously shown that BAL LPS measured at 3-months post-transplant, in LTRs without positive BAL cultures, was associated with concurrent Pseudomonadota colonization and increased risk of future CLAD. Herein, we sought to: 1) validate our previous findings and 2) investigate whether BAL LPS could predict future Pseudomonadota infection. Methods: A total of 280 consecutive adult LTRs with available BAL at 3-months post-transplant and at least four post-transplant pulmonary function tests were included in this study. LPS was measured in BAL supernatant using the Limulus amebocyte lysate assay. Cox-PH models were used to assess the relationship between BAL LPS and time to CLAD. Logistic regression analysis was used to assess the relationship between BAL LPS and concurrent as well as future BAL Pseudomonadota culture positivity. Results: BAL LPS was higher in samples that concurrently were culture positive for gram negative bacteria (p=0.05) and specifically Pseudomonadota organisms (p<0.001). BAL LPS was associated with an increased risk of CLAD among all patients [HR 1.27 (1.12-1.45), p<0.001] and specifically among patients who had culture-negative BAL [1.33 (1.15-1.55), p<0.001]. Among LTRs with culture negative BAL at 3 months, BAL LPS predicted future BAL Pseudomonadota culture positivity within the next three months [OR 1.79 (1.31-2.48), p<0.001]. In this group, BAL LPS in the highest tertile was able to predict BAL Pseudomonadota culture positivity within the next three months with 85% sensitivity and 72% specificity. Conclusions: We substantiated our previous findings that elevated BAL LPS measured at 3-months post-transplant, even in the absence of positive cultures, was associated with an increased risk of CLAD. Moreover, elevated BAL LPS was able to predict future presence of pulmonary Pseudomonadota cultures. Future studies are needed to determine whether early treatment of elevated BAL LPS can prevent future Pseudomonadota infection and prolong allograft survival.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".