Hypertonic saline challenge predicts early onset bronchiolitis obliterans syndrome post-lung transplantation

Abstract

Bronchial hyperreactivity (BHR) is common following lung transplantation and may relate to acute rejection and early development of the bronchiolitis obliterans syndrome (BOS). We determined dose response slope to methacholine (DRSm) and hypertonic saline (DRSs) challenge in stable recipients within the first year post-transplant and examined the relationship to airway inflammation and subsequent outcome. 10 single (SL) and 18 bilateral (BL) stable lung transplant recipients (median time from transplant 190 days, range 98-364 days) underwent methacholine challenge followed by bronchoscopy and bronchoalveolar lavage (BAL). Hypertonic saline (4.5%) challenge was performed six days after bronchoscopy. 23 patients (82%) had a positive methacholine and 7 (23%) a positive saline challenge. Two patients refused saline challenge. Four patients had positive and 3 patients negative results to both challenges. Bronchoscopy revealed no evidence of acute rejection or clinically significant infection in any patient. Eight SL (80%) and 12 BL (66%) recipients have developed BOS (median follow-up 53 months, range 16-109 months). Time to BOS from transplant was significantly shorter in SL compared to BL recipients (median 531 v 1158 days, range 231-1134 v 238-2135 days, respectively, p,0.05). There was no significant relationship between DRSm and DRSs. DRSm was significantly related to baseline FEV1 (r(s)50.5, p,0.05) but not BAL cell counts. In contrast, DRSs was unrelated to FEV1 but significantly correlated with BAL total cell count (r(s)50.4, p,0.05). Time to BOS was significantly related to DRSs (r(s)5-0.6, p,0.05) and there was a non-significant relationship to DRSm (r(s)5-0.4, p50.06). Conclusion; BHR to methacholine is common following lung transplantation and may relate to denervation and airway calibre but not inflammation. Response to hypertonic saline reflects airway inflammation and predicts for early onset of BOS. Different patho-physiological mechanisms probably underlie the response to these non-specific stimuli but both provide complimentary information regarding the potential for BOS.