New Chronic GVHD Pulmonary Phenotypes

By Elaine S. DeMeyer, RN, MSN, AOCN®, BMTCN® - Last Updated: December 7, 2022

Oncology nurses must know the potential pulmonary complications related to graft-versus-host disease (GVHD). Although acute pulmonary GVHD is rare, chronic pulmonary GVHD is devasting and challenging to treat. Sometimes referred to as PcGVHD, patients with chronic pulmonary GVHD have a lower Karnofsky performance status and a higher risk for death than patients without pulmonary disease.

What Are Common Pulmonary Toxicities With GVHD?

Due to prolonged immunosuppression with drugs to prevent or manage GVHD, pulmonary infection is a common cause of posttransplant pulmonary complications. In the pre-engraftment period, patients are at the highest risk for bacterial or fungal infections such as Candida and Aspergillus. After engraftment, patients are at higher risk for viral and fungal infections, particularly those receiving immunosuppressive medications for GVHD. As a result, dormant viral infections can be reactive, so viral titers are assessed in donors and patients during the pretransplant workup to anticipate viral reactivation.

In addition to numerous infections, bronchiolitis obliterans, also known as bronchiolitis obstructive syndrome (BOS), and cryptogenic organizing pneumonia (COP), formerly called bronchiolitis obliterans organizing pneumonia (BOOP), are linked with chronic GVHD.

What Is the Difference Between BOS and COP?

Both BOS and COP are obstructive pulmonary disorders associated with chronic GVHD. BOS affects the bronchioles—hence, its name—and COP primarily affects the alveoli.

  • This typical pulmonary complication results in bronchioles obstruction due to inflammation or fibrosis. ABO-mismatched stem cell transplant, unrelated donor or female donor, busulfan-based condition regimen, and chronic GVHD are risk factors for BOS.
  • Although “pneumonia” is in the name, COP is not a primary infection but rather a pattern of lung tissue repair after injury. COP is more common with chronic GVHD but can appear with acute GVHD. Other risk factors include myeloablative conditioning regimens, total body irradiation, and stem cell sources other than umbilical cord blood.

What Are the Characteristics of BOS Versus COP?

BOS and COP have both similar and unique symptoms, with COP often causing fever and bilateral crackles. Other significant differences are seen in the results of pulmonary function tests (PFTs).

Findings BOS COP


Nonproductive cough, dyspnea that worsens with activity Nonproductive cough, fever, flu-like symptoms, pleuritic chest pain, hemoptysis, fatigue
Chest auscultation Progressive wheezing with inspiration and expiration Bilateral crackles and inspiratory wheezing
Chest x-ray Normal or hyperinflation with diaphragmatic flattening, focal opacities, pneumothoraces Bilateral patchy infiltrates with a ground-glass or consolidation appearance
PFTs Normal DLCO, severely reduced FEV1 Severely reduced DLCO, reduced FEV1
Pathology Granulation tissue plugs in small airway lumens Granulation tissue plugs in small airway lumens, granulation tissues extends into alveolar ducts and alveoli

DLCO, diffusing capacity for carbon monoxide; FEV1, forced expiratory volume in the first second.

What Are the 4 Phenotypes of Pulmonary Chronic GVHD?

The International Society for Heart and Lung Transplantation (ISHLT) reviewed patient data from the National History Study of Clinical and Biological Factors Determining Outcomes in Chronic Graft-Versus-Host Disease (NCT0092235) to define chronic pulmonary GVHD further. As a result, the ISHLT adapted its 2019 criteria to define novel phenotypes of chronic pulmonary GVHD:

  1. Obstructive
  2. Restrictive
  3. Mixed obstructive/restrictive
  4. Undefined

The goal is for the adapted criteria to be a better tool to provide a framework for clinical practice and research of lung disease in chronic GVHD.

Oncology nurses have a critical role in the early recognition of pulmonary complications in patients with GVHD. Pulmonary symptoms may emerge over several weeks to months. Often patients do not remember the start of their nonproductive cough. As a result, they may not report problems until they have dyspnea or difficulties with activities of daily living. Nurses can educate patients on potentially troubling symptoms, how to monitor pulse oximetry at home, and when to report early signs of possible pulmonary complications.

Read More Recent Research on Graft-Versus-Host Disease