Molecular endotypes of CLAD (proposed framework)
Status: proposedEvidence level: proposed framework, abstract only
A proposal that CLAD be classified by its underlying biology (endotypes) rather than by the clinical phenotypes BOS and RAS alone. Proposed, not validated.
As of . Primary source: Burman et al. 2026, J Heart Lung Transplant (DOI; abstract only was read).
Summary
The abstract of the review by Burman and colleagues describes CLAD as the fibrotic manifestation of chronic rejection and a major barrier to long-term survival after lung transplantation. It describes CLAD as the final common pathway of diverse alloimmune injuries, augmented by non-alloimmune insults. The authors propose a shift from clinical phenotypes, namely BOS and RAS, toward biologically defined endotypes, which they suggest may better predict progression and therapeutic response. No validated endotype scheme is described in the abstract, and this record therefore carries the status proposed. The pathways linked below are those named in the abstract. Only the abstract of the source review was read; the full text was not read.
Sources and links
Related
Links from this record
- proposed in (abstract only): CLAD: translating basic science to clinical practice
- possibly related (editorial content unconfirmed): Toward molecular endotypes of CLAD: dancing around the truth hidden in the tissue
- possibly related (relationship unconfirmed): Distinct fibrotic, epithelial and immune transcriptomic programs in phenotypes of chronic lung allograft dysfunction
- proposed to be refined by: Bronchiolitis obliterans syndrome (BOS)
- proposed to be refined by: Restrictive allograft syndrome (RAS)
- pathway named in abstract: Cytotoxic and senescent T cells
- pathway named in abstract: Humoral (antibody-mediated) alloimmunity
- pathway named in abstract: Innate immune activation
- pathway named in abstract: Airway epithelial dysfunction
- pathway named in abstract: Aspiration
- pathway named in abstract: Microbial dysbiosis
- early window discussed: Acute lung allograft dysfunction (ALAD)
Linked from (derived)
- part of proposed framework: Airway epithelial dysfunction
- part of proposed framework: Aspiration
- part of proposed framework: Cytotoxic and senescent T cells
- part of proposed framework: Humoral (antibody-mediated) alloimmunity
- part of proposed framework: Innate immune activation
- part of proposed framework: Microbial dysbiosis
- candidate for endotype-guided use: Airway transcriptomic signatures
- candidate for endotype-guided use: Autoantibodies
- candidate for endotype-guided use: Donor-derived cell-free DNA
- candidate for endotype-guided use: Epithelial injury markers
- candidate for endotype-guided use: Microbiome-derived signals
- related to: A transcriptomic atlas of chronic lung allograft dysfunction.
- proposes: CLAD: translating basic science to clinical practice
- affects: Definitions and prognosis of ALAD and BLAD are not settled
- affects: Clinical CLAD phenotypes are hard to assign reproducibly
- affects: No validated molecular endotype scheme exists for CLAD
- affects: Human tissue studies are small and raw human sequence data are often not open
Known gaps in this record
- full text of the source review not read, so the evidence, citations and level of agreement for this item are missing
- funding and conflicts of interest of the source review not read
- no validated endotype definitions, thresholds or cross-centre reproducibility are recorded
- no link between the Ishiwata preprint or the Juvet editorial and this framework has been confirmed
Information resource only. Not medical advice. Not a substitute for the care of the patient's transplant team.