BOS update
Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria

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Background

When the original definition of BOS was formulated in 1993, the working group had several goals. The group aimed to provide a classification system for airway disease after lung transplantation that did not rely on histopathologic findings, was sensitive and specific, relied on diagnostic techniques available to all lung transplant physicians, and was relatively simple to understand and apply. The resulting classification system defined post-transplant pulmonary function using the forced

Background

Approximately 2.5% of lung transplant candidates are ≤17 years of age. In terms of the number of transplants, number of patients on the waiting list, and number of active centers, pediatric lung transplantation lags behind adult lung transplantation and other pediatric solid-organ transplantation. Published reports indicate an incidence of BO similar to that of adults,10, 11, 12 except in children <3 years old, in whom it may be lower.10

Airway inspection is particularly important in children to

Background

Many factors have been reported as risk factors for BOS. However, quality of data is often a problem because almost all existing information derives from retrospective studies with no control groups and reflects the experience of single centers. Numbers are small and often difficult to interpret. In some cases, risk factors seem to have been more important in the earlier years of lung transplantation, e.g., cytomegalovirus (CMV) infection. This may reflect a change in the risk environment

Background

Bronchiolitis obliterans is a cicatricial process that affects the small airways of the allograft lung. Conceptually, BO is thought to result from chronic lung rejection, although not exclusively. It progresses through a sequence of lymphohistiocytic-mediated cytotoxicity directed at the respiratory epithelium. The initial process is a lymphocytic infiltrate of the sub-mucosa of the airways with migration of lymphocytes through the basement membrane into the epithelium.57 At this site,

Background

The diagnostic criteria for BOS are based on a decrease in lung function. Various indirect measures or analyses have been undertaken to identify alternative early markers of a decrease in graft performance. Perhaps these markers can provide a surrogate means of predicting disease or of monitoring disease activity, with the aim of enabling early therapy to block a relentless decrease in lung function.

Background

Lung function is exquisitely sensitive to complications that affect the allograft, such as rejection, infection, and anastomotic complications. These complications often produce some degree of airflow obstruction and may lead to a pattern of functional deterioration, which is qualitatively similar to that seen in BOS. In addition, several complications that affect the native lung and disease progression in the native lung may contribute to changing pulmonary function. This section addresses (1)

Recommendations

  • 1.

    Infection, acute rejection, disease recurrence, and anastomotic complications can confound the diagnosis of BOS. These diagnoses should be excluded or treated before assigning a designation of BOS.

  • 2.

    Following single lung transplant for emphysema, native lung hyperinflation occasionally results in a functional and physiologic picture similar to BOS. In this setting, a precise diagnosis may be impossible and each case should be judged on its individual characteristics.

  • 3.

    A number of conditions can

Background

Although the fibrous obliteration of the bronchioles seen in BO probably is irreversible, the histologic lesions are often heterogeneous, with some airways showing inflammatory infiltrates potentially amenable to treatment. This probably explains why some patients show functional stabilization or improvement with treatment. Assessing response to therapy is difficult in individual patients because of the high variability of the disease response of an individual to an intervention.9, 120, 121, 122

Future studies

The committee recognizes that although BOS is the most common complication leading to chronic graft dysfunction and death of lung transplant recipients, it remains poorly understood. However, the course of disease progression may be quite variable for individual patients, suggesting a heterogeneous pathogenesis. Although lung function may decrease rapidly, leading to respiratory failure and death in some patients, other patients may survive for years with either stable or slowly progressive

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