# The lungs after transplant: bronchiolitis obliterans syndrome

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## TL;DR

The smallest airways in the lung can scar shut after a donor transplant. It is the form of chronic GvHD that changes the outlook most, and it is usually silent until a lot of lung function has gone. It is found by breathing tests on a schedule rather than by waiting for breathlessness, so asking for spirometry is worth doing.

## Summary

Bronchiolitis obliterans syndrome is the pulmonary manifestation of chronic GvHD: fibrotic obliteration of the small airways producing fixed airflow obstruction. It is the only diagnostic manifestation of chronic GvHD in the lung under the NIH criteria, and the one organ whose involvement raises the global severity grade at every level. A European review of 317 patients transplanted in 2017 found restrictive lung disease among the atypical manifestations that drove non-relapse mortality, alongside renal involvement and peripheral neuropathy.

The diagnostic problem is that it is quiet. Airflow obstruction develops before a person notices it, and by the time breathlessness on exertion is obvious a substantial share of FEV1 has gone and the scarring is fixed. The 2014 NIH criteria therefore define the lung score by pulmonary function rather than by symptoms, which is an instruction to measure. The long-term follow-up recommendations from the international transplant societies include pulmonary function testing in survivors at risk, and the practical implication for a person after an allogeneic transplant is to have spirometry at planned intervals in the first years and whenever a new respiratory symptom appears, not only when one is severe.

Treatment is unsatisfying and the field says so. Systemic immunosuppression is escalated as it would be for chronic GvHD elsewhere, and inhaled treatment is added: an inhaled corticosteroid with a long-acting bronchodilator, with azithromycin and a leukotriene antagonist used in some centres as part of a combination approach. Ruxolitinib's randomised evidence in steroid-refractory chronic GvHD, REACH3, was in moderate or severe disease overall rather than in lung disease specifically, so the lung-specific evidence for any second-line agent is weaker than the evidence for the agents in general. Lung transplantation has been performed for end-stage disease in selected people. Prevention, which here means preventing and controlling chronic GvHD before the airways scar, carries more of the burden than treatment does.

The honest statement of the evidence: there is no randomised trial showing that any treatment restores lost FEV1 in established bronchiolitis obliterans syndrome. The realistic aim of treatment is to stop further loss. That is a reason to measure early rather than a reason not to treat.

Other late lung problems after transplant are not GvHD and should not be assumed to be: infection, including late viral and fungal infection in people on long immunosuppression; idiopathic pneumonia syndrome; cryptogenic organising pneumonia, which unlike bronchiolitis obliterans often responds well to steroids; and the restrictive pattern that follows chest radiotherapy or total body irradiation. Distinguishing them changes treatment, so a new or worsening breathing problem after transplant is an investigation rather than a diagnosis.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-10-02
- Also known as: bronchiolitis obliterans syndrome; BOS; pulmonary GvHD; obliterative bronchiolitis after transplant
- Tags: rejuvenation; survivorship; transplant; gvhd; lung
- Principle: Alloimmune injury to the bronchiolar epithelium is followed by fibroproliferative repair that narrows and then obliterates airways under 2 mm in diameter. Because these airways contribute little to total resistance until many are affected, large numbers can be lost before symptoms or even before FEV1 falls far, which is the physiological reason the condition is detected late unless it is screened for.
- Strengths: Detectable by spirometry, a cheap and widely available test, before symptoms appear; Scored explicitly in the NIH criteria, so it is not left to impression; Inhaled treatment adds little systemic immunosuppression; Recognised in the international long-term follow-up recommendations, so there is a basis for asking for the test
- Limitations: No treatment has been shown in a randomised trial to recover lost lung function; Second-line drug evidence comes from trials of chronic GvHD overall rather than of lung disease; Often diagnosed after fixed scarring has developed; Several other late lung problems look similar and need to be excluded

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Bronchiolitis_obliterans
- Jagasia et al., NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report (Biol Blood Marrow Transplant 2015): https://doi.org/10.1016/j.bbmt.2014.12.001
- Doering et al., Incidence and outcome of atypical manifestations of chronic graft-versus-host disease (Transplant Cell Ther 2023): https://doi.org/10.1016/j.jtct.2023.09.016
- Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012): https://doi.org/10.1016/j.bbmt.2011.12.519
- Zeiser et al., Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease, REACH3 (NEJM 2021): https://doi.org/10.1056/NEJMoa2033122
- Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017): https://doi.org/10.3324/haematol.2016.150250

## Connected records

- technologies: [After a transplant or cell therapy: what to ask for](https://onco.cc/technologies/rejuv-tx-what-to-ask-for/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Bone, eyes, kidneys and lungs after transplant](https://onco.cc/technologies/rejuv-tx-bone-eyes-kidneys-lungs/), [Chronic graft-versus-host disease](https://onco.cc/technologies/gvhd-chronic-overview/), [Chronic GvHD organ by organ: skin, mouth, eyes, gut, liver, joints and genital tract](https://onco.cc/technologies/gvhd-organ-by-organ/), [How chronic GvHD is diagnosed and scored: the NIH consensus criteria](https://onco.cc/technologies/gvhd-nih-consensus-criteria/), [Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/), [Total body and total marrow irradiation](https://onco.cc/technologies/total-body-irradiation/), [When steroids fail: ruxolitinib for steroid-refractory GvHD](https://onco.cc/technologies/gvhd-ruxolitinib-steroid-refractory/), [Who is supposed to be watching: EBMT, CIBMTR, FACT-JACIE, and what a survivor is actually offered](https://onco.cc/technologies/rejuv-tx-long-term-follow-up-frameworks/)
- fronts: [Recovery & Rejuvenation](https://onco.cc/fronts/rejuvenation/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- terms: [Graft-versus-host disease (GVHD) and graft-versus-leukaemia](https://onco.cc/terms/gvhd/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/)
- bottlenecks: [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)

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