Association between chronic bacterial airway infection and prognosis of bronchiolitis obliterans syndrome after hematopoietic cell transplantation

Abstract

Bronchiolitis obliterans syndrome (BOS) is a rare pulmonary complication of hematopoietic stem cell transplantation (HSCT) with high mortality. Chronic bacterial airway infection (CAI) causes exacerbation and progression of several airway diseases, and bacterial airway colonization was shown to be associated with BOS after lung transplantation.We assessed the association between CAI and clinical course in patients with BOS after HSCT. This retrospective study included 910 patients undergoing allogeneic HSCT between 2005 and 2013 at our institution. BOS diagnosis was reevaluated according to the 2014 US National Institutes of Health criteria. Sputum and bronchial lavage culture results, pulmonary function, and survival were compared between patients with and without CAI.Median follow-up was 974.5 (261.5–2748.5) days. BOS was diagnosed in 27 (3.0%) patients, including 18 males. Median age at BOS diagnosis was 45 (40.5–58) years. Nine patients had ≥2 positive sputum cultures for bacteria or one positive bronchial lavage culture for nontuberculous mycobacteria (CAI+), whereas 9 patients had negative sputum/bronchial lavage culture or only one positive sputum culture (CAI−). Median change in forced expiratory volume in 1 s within 6 months after BOS diagnosis and overall survival were significantly worse in CAI+ patients than in CAI− patients (−250 vs +260 mL, P = .002, and 1340 days vs not reached, P = .04, respectively). No other factors including patient demographics or transplant protocol affected prognosis. There were no differences in clinical characteristics of patients with and without CAI, except for the time from transplantation to BOS diagnosis (214 vs 768 days for CAI+ and CAI−, respectively; P = .02).CAI was associated with worse outcomes in patients with BOS after HSCT. Further prospective studies should assess the association between the airway microbiome and changes in pulmonary function after HSCT to improve prognosis.

Cathepsin B promotes collagen biosynthesis, which drives bronchiolitis obliterans syndrome

“…Similar to a recent study, we demonstrated that pro-inflammatory macrophages induced fibroblast activation [39]. BOS patients have shown a high incidence of bacterial infection, described as a source of lipopolysaccharide [40] and interferon-γ [41], that together could promote macrophage differentiation towards a pro-inflammatory phenotype in BOS. In vitro inhibition of CatB activity resulted in the prevention of fibroblast activation.…”

Noninfectious lung complications of hematopoietic cell transplantation

“…27 The cur rent inci dence is approx i ma tely 3% in pedi at ric and 3% to 6% in adult HCT. 1,[51][52][53] A chal lenge of this dis ease has been its insid i ous nature lead ing to mod er ate decline at diag no sis. The fre quent use of home devices to detect early de clines in lung func tion and the use of FEF25-75 as an indi ca tor may aid in the ear lier iden ti fi ca tion of BOS.…”

Long‐term pulmonary function testing in pediatric bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

“…18,35 In our cohort, all patients with BOS suffered from an acute or chronic GvHD of at least one organ site. Furthermore, we revealed that the mortality was significantly higher when three organ sites were affected by GvHD ( busulfan-based conditioning regimen, unrelated donor, gastroesophageal reflux disease, acute or chronic viral, and bacterial infections, 13,34,36 were investigated and displayed in Table 3. Seven patients suffered from infections after aHSCT, four patients received a busulfanbased conditioning regime, and four patients had an unrelated donor.…”