Chronic lung allograft dysfunction other than bronchiolitis obliterans syndrome

Chronic lung allograft dysfunction (CLAD) is a relatively new term in the field of lung transplantation that was recently introduced because different phenotypes of chronic allograft rejection had been identified. For decades, the term bronchiolitis obliterans syndrome (BOS) has been used to reflect chronic rejection; clinically, it has been defined as a persistent, irreversible decline in forced expiratory volume in the first second of respiration (FEV₁) of at least 20% in comparison to the mean of the best two postoperative values in the absence of confounding factors such as acute rejection, infections, suture problems, or recurrence of native disease. ¹ The pathologic correlate of BOS was considered to be the presence of obliterative bronchiolitis (OB) lesions, which is basically filling of the bronchiolar lumen with a collagenous matrix that leads to obstructive airflow limitation. Other typical characteristics have included refractoriness to treatment and the presence of neutrophilic airway inflammation. ¹ As early as 1984, many remarkable findings in explanted lung specimens were described in one of the first publications on OB. ² Indeed, a progressive restrictive ventilatory defect developed in three of five patients. ^{3 , 4} Moreover, in addition to the typical OB lesions, significant pleural fibrosis was found in two of five patients. Later reports described a combination of a restrictive pulmonary function defect and severe pulmonary infiltrates in patients with end-stage BOS that was confirmed by computed tomography (CT). ⁵ These findings alone illustrate that not all patients experiencing chronic rejection manifest a strictly obstructive ventilatory defect and that clinical and pathophysiologic alterations other than OB occur in rejected grafts. ³