Bronchodilator Response at Low Lung Volumes Predicts Bronchiolitis Obliterans in Lung Transplant Recipients

Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term lung allograft viability. The diagnosis often occurs after significant organ dysfunction is present, and BOS is often unresponsive to standard immunosuppressive agents. We have observed bronchodilator responses (BRs) at low lung volumes in many of our patients who have developed BOS. We therefore assessed whether BR could predict the development of BOS. We conducted a retrospective review of the clinical and pulmonary function laboratory records of 146 patients who underwent transplantation between March 1983 and November 1993. BR was defined as 25% or more increase in forced expiratory flow at 50% of vital capacity or 30% or more increase in forced expiratory flow at 75% of vital capacity. BOS was defined according to recently published FEV1 criteria. Bronchiolitis obliterans was defined histologically according to criteria of the Lung Rejection Study Group. Of the total population, 52 were excluded because of death or insufficient information. BRs of the small airways were seen in 31 patients (33%), 25 of whom developed BOS (83%). Approximately half of those with BR who developed BOS had evidence of acute rejection in the month prior to the onset of BR. Two thirds (four of six) of patients with BR not developing BOS had acute rejection in the previous month. The sensitivity of BR in predicting BOS was 51% with a specificity of 87%. The positive predictive value was 81%. BR appears to be useful as an early marker of BOS. The development of BR in selected patients should lead to closer monitoring and possibly a trial of augmented immunosuppression to arrest the establishment of BOS.