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Summary Background To evaluate the utility of home spirometry (HS) versus office spirometry (OS) in assessing treatment response to azithromycin in bronchiolitis obliterans syndrome (BOS). Methods 239 Lung transplant recipients were retrospectively studied. ΔFEV1 ± 10% from FEV1 at azithromycin initiation for ≥7 consecutive days in HS or ≥2 measures in OS were taken as cut-off for response or progression. Results Based upon HS, 161/239 (67%) patients were progressive despite macrolide, 19 of who exhibited transient improvement in FEV1 (11%). Time to progression was 29 (13–96) days earlier with HS than in OS. Forty-six (19%) recipients responded in HS after median 81 (22–343) days, whilst 22% remained stable. Concordance in azithromycin treatment response between OS and HS was observed in 210 of 239 patients (88%). Response or stabilization conferred significant improvement in survival ( p = 0.005). Transient azithromycin responders demonstrated improved survival when compared to azithromycin refractory patients ( p = 0.034). Conclusions HS identified azithromycin refractory patients significantly earlier than OS, possibly facilitating aggressive treatment escalation that may improve long-term outcome. Treatment response to azithromycin should be assessed 4 weeks after initiation. Responders demonstrated best survival, with even transient response conferring benefit. Macrolide-refractory BOS carried the worst prognosis.