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Chronic Lung Allograft Dysfunction (CLAD)


Bronchiolitis Obliterans Syndrome

Bronchiolits Obliterans refers to the permanent loss of lung allograft function due to airway remodeling and fibrosis.  It is uncommon in the first two years after lung transplant, but it eventually affects the majority of lung transplant recipients and is the leading cause of death beond the first year post transplant.


Because Bronchiolitis Obliterans is not readily demonstrated on transbronchial biospies, the term Bronchiolitis Obliterans Syndrome is applied to lung transplant recipients who demonstrate a sustained and presumed permanent drop in lung function that does not have another apparent cause (such as airway stenosis, infection, pulmonary edema or effusions)


BOS is defined as a 20% drop in FEV1 from the post transplant baseline.  This baseline is the average of the two best FEV1 results post transplant obtained at least three weeks apart.


BOS is graded as follows:

  • BOS 0     FEV1 >90@ of baseline and FEF25-75 > 75% of baseline
  • BOS 0p   FEV1 81-90% of baseline or FEF25-75 < 75 % of baseline
  • BOS 1     FEV1 66-80% of baseline
  • BOS2      FEV1 51-65% of baseline
  • BOS3      FEV1  ≤ 50% of baseline


The CT scan in BOS typically shows mosaic attenuation reflecting gas trapping, hyperinflated parenchyma, and areas of bronchiectasis. 


BOS is sometimes called "chronic rejection" but it is not strictly an immunologic phenomenon and does not typically respond to a steroid bolus.  However a steroid bolus may be tried if a component of acute rejection is suspected. 

Other factors promoting BOS include previous acute rejection, CMV infection, pneumonias and gastroesophageal reflux.

Sequelae of BOS include progressive dyspnea, impaired gas exchange, and bronchiectasis with recurrent infections.

Standard interventions include

  • Addition of low dose azithromycin (250 mg 3x/week)
  • Aggressive antireflux therapy including prokinetic medications when there is evidence of gastroparesis
    • domperidone 10 mg tid is used in this setting provided QTc is < 470 msec
    • Nissen fundoplication considered in patients withreflux that is refrractory to medical therapy
  • Consider change in immunosuppression regimen (change Csa to tacrolimus, or Azathioprine to Mycophenolic acid (Myfortic®)
  • Treat any infections
  • May evaluate for retransplant when patients have low lung function due to BOS. 
    • Typically patients must be under age 55 and without major comorbidities to be considered for retransplant.

Prophylactic use of low-dose azithromycin and fundoplication to prevent BOS have been advocated, but are not standard therapy in our program



Restrictive Allograft Syndrome

BOS is one form of Chronic Lung Allograft Dysfunction (CLAD).  The Total Lung Capacity in BOS is typically preserved.

Another form of CLAD is "Restrictive Allograft Syndrome" or RAS, defined by FE1 < 80% of baseline AND Total Lung Capacity < 90% of baseline. 

The CT scan in RAS typically shows upper zone predominant fibrotic changes with pleural thickening in a pattern reminiscent of pleuroparenchymal fibroelastosis.

Some cases of RAS have been associated with the presence of donor specific antibodies (DSA).

RAS has been associated with more rapid progression and a worse prognosis than BOS. 

See Sato et al. JHLTx 2011 30 (7) 735



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