From the Guidelines
Chronic Lung Allograft Dysfunction (CLAD) after lung transplantation is diagnosed based on a persistent decline in lung function that cannot be attributed to other causes, with the primary criterion being a sustained decrease in forced expiratory volume in one second (FEV1) of at least 20% from the post-transplant baseline, persisting for at least three weeks, as stated in the guidelines by 1. The diagnosis of CLAD requires careful exclusion of other post-transplant complications that can cause delayed lung allograft dysfunction, such as infection, acute rejection, airway complications, or pleural disease, through various tests including pulmonary function tests, chest imaging, bronchoscopy with bronchoalveolar lavage, and sometimes lung biopsy, as outlined in the guidelines by 1, 2, 3. CLAD is further classified into two main phenotypes:
- Bronchiolitis Obliterans Syndrome (BOS), characterized by airflow obstruction with normal lung volumes,
- Restrictive Allograft Syndrome (RAS), which shows restrictive physiology with decreased lung volumes, as described in the studies by 4, 5, 6. Regular monitoring of lung function is essential for early detection, as CLAD represents a form of chronic rejection that significantly impacts long-term survival after lung transplantation, as highlighted in the guidelines by 7, 8, 9. Treatment options are limited once CLAD develops, making prevention through optimal immunosuppression and management of risk factors crucial, as emphasized in the studies by 1, 2. Some key points to consider in the diagnosis and management of CLAD include:
- The importance of ruling out other causes of lung function decline, as stated in the guidelines by 1, 2, 3
- The use of pulmonary function tests, chest imaging, and bronchoscopy with bronchoalveolar lavage in the diagnosis of CLAD, as outlined in the studies by 4, 5, 6
- The classification of CLAD into BOS and RAS phenotypes, as described in the guidelines by 1, 2
- The need for regular monitoring of lung function to detect CLAD early, as emphasized in the studies by 7, 8, 9
- The limited treatment options available once CLAD develops, making prevention crucial, as highlighted in the guidelines by 1, 2.
From the Research
Criteria for Chronic Lung Allograft Dysfunction (CLAD)
The criteria for CLAD after lung transplant include:
- A persistent fall in forced expiratory volume in 1 second (FEV1) associated with an obstructive ventilatory defect, as seen in bronchiolitis obliterans syndrome (BOS) 10, 11
- A restrictive form of chronic rejection, characterized by restrictive functional changes involving peripheral lung pathology, as seen in restrictive allograft syndrome (RAS) 11, 12
- Irreversible decline in FEV1 < 80% baseline, with the most accurate threshold to predict irreversible decline in total lung capacity and thus restrictive functional change being at 90% baseline 11
- Neutrophilic reversible allograft dysfunction, a distinct phenotype of chronic rejection with unique pathology and histopathological findings 12
Phenotypes of CLAD
There are three distinct phenotypes of CLAD:
- Bronchiolitis obliterans, characterized by small-airway pathology and obstructive pulmonary physiology 11, 12
- Neutrophilic reversible allograft dysfunction, characterized by neutrophilia in bronchoalveolar lavage 10, 12
- Restrictive allograft syndrome (RAS), characterized by restrictive functional changes involving peripheral lung pathology and interstitial lung disease on computed tomography findings 11, 12
Diagnosis of CLAD
Diagnosis of CLAD can be made using:
- Spirometry to measure FEV1 and detect a persistent fall in lung function 10, 11
- Computed tomography findings to detect interstitial lung disease and other restrictive changes 11
- Ventilation-weighted Fourier decomposition MRI to detect ventilated-weighted images during free-breathing and quantify regional fractional ventilation (RFV) 13
- Bronchoalveolar lavage to detect neutrophilia and other inflammatory changes 10, 12