Hyperbaric oxygen therapy to prevent central airway stenosis after lung transplantation.

BACKGROUND: Central airway stenosis (CAS) is a severe airway complication after lung transplantation associated with bronchial ischemia and necrosis. We sought to determine whether hyperbaric oxygen therapy (HBOT), an established treatment for tissue ischemia, attenuates post-transplant bronchial injury. METHODS: We performed a randomized, controlled trial comparing usual care with HBOT (2 atm absolute for 2 hours × 20 sessions) in subjects with extensive airway necrosis 4 weeks after transplantation. Endobronchial biopsies were collected at 4, 7, and 10 weeks after transplantation for a quantitative polymerase chain reaction. Coprimary outcomes were incidence of airway stenting and acute cellular rejection (ACR) at 1 year. RESULTS: The trial was stopped after enrolling 20 subjects (n = 10 per group) after a pre-planned interim analysis showed no difference between usual care and HBOT groups in stenting (both 40%), ACR (70% and 40%, respectively), or CAS (40% and 60%, respectively). Time to first stent placement (median [interquartile range]) was significantly shorter in the HBOT group (150 [73-150] vs 186 [167-206] days, p < 0.05). HIF gene expression was significantly increased in donor tissues at 4, 7, and 10 weeks after transplantation but was not altered by HBOT. Subjects who developed CAS or required stenting had significantly higher HMOX1 and VEGFA expression at 4 weeks (both p < 0.05). Subjects who developed ACR had significant FLT1, TIE2, and KDR expression at 4 weeks (all p < 0.05). CONCLUSIONS: Incidence of CAS is high after severe, established airway necrosis after transplantation. HBOT does not reduce CAS severity or stenting. Elevated HMOX1 and VEGFA expressions appear to associate with airway complications.

Safety of hyperbaric oxygen therapy for management of central airway stenosis after lung transplant.

BACKGROUND: Central airway stenosis (CAS) is common after lung transplantation and causes significant post-transplant morbidity. It is often preceded by extensive airway necrosis, related to airway ischemia. Hyperbaric oxygen therapy (HBOT) is useful for ischemic grafts and may reduce the development of CAS. METHODS: The purpose of this study was to determine whether HBOT could be safely administered to lung transplant patients with extensive necrotic airway plaques. Secondarily, we assessed any effects of HBOT on the incidence and severity of CAS. Patients with extensive necrotic airway plaques within 1-2 months after lung transplantation were treated with HBOT along with standard care. These patients were compared with a contemporaneous reference group with similar plaques who did not receive HBOT. RESULTS: Ten patients received HBOT for 18.5 (interquartile range, IQR 11-20) sessions, starting at 40.5 (IQR 34-54) days after transplantation. HBOT was well tolerated. Incidence of CAS was similar between HBOT-treated patients and reference patients (70% vs 87%, respectively; P=.34), but fewer stents were required in HBOT patients (10% vs 56%, respectively; P=.03). CONCLUSIONS: This pilot study is the first to demonstrate HBOT safety in patients who develop necrotic airway plaques after lung transplantation. HBOT may reduce the need for airway stent placement in patients with CAS.

Therapeutic bronchoscopy improves spirometry, quality of life, and survival in central airway obstruction.

BACKGROUND: Central airway obstruction (CAO) occurs in patients with primary or metastatic lung malignancy and nonmalignant pulmonary disorders and results in significant adverse effects on respiratory function and quality of life. OBJECTIVES: The objective of this study was to assess the effect of therapeutic bronchoscopic interventions on spirometry, dyspnea, quality of life, and survival in patients with CAO. METHODS: We prospectively studied patients who underwent therapeutic rigid bronchoscopy for CAO. Spirometry, San Diego Shortness of Breath questionnaire (SOBQ), and SF-36 questionnaire responses were obtained before the procedure and at follow-up 6-8 weeks after the procedure. RESULTS: Fifty-three patients (24 malignant and 29 nonmalignant CAO), who underwent successful rigid bronchoscopic intervention, were enrolled. Airway stent placement and various debulking techniques including mechanical debridement and heat therapy were used. After bronchoscopy, there was a significant increase in forced vital capacity (2.2 ± 0.91 l before, 2.7 ± 0.80 l after, p = 0.009) and forced expiratory volume at 1 s (1.4 ± 0.60 l before, 1.8 ± 0.67 l after, p = 0.002). The SOBQ score improved from 55.8 ± 30.1 before the procedure to 37.9 ± 27.25 after the procedure (p = 0.002). In the SF-36, there was an improvement in almost all domains, with statistically significant improvement seen in several domains. Benefits were seen independent of the etiology of CAO, site of intervention or stent placement. The patients with malignant CAO, in whom airway patency could not be achieved, had a poor survival. CONCLUSIONS: Alleviation of CAO with therapeutic rigid bronchoscopy results in improvement in spirometry, shortness of breath, quality of life, and survival.

Ablative therapies for central airway obstruction.

Central airway obstruction (CAO) is seen in malignant and nonmalignant airway disorders and can lead to significant morbidity and mortality. Endobronchial ablative therapies are used in conjunction with mechanical debridement to achieve hemostasis and restore airway patency. These therapies can be classified into modalities with immediate or delayed effect. Therapies with immediate effect include heat therapies (such as electrocautery, argon plasma coagulation, and laser) and cryorecanalization using a cryoprobe for tissue extraction. These modalities can be used in severe CAO for immediate relief of obstruction. Therapies with delayed effect include cryotherapy, brachytherapy, and photodynamic therapy. These modalities should not be used for acutely symptomatic CAO, and typically require follow-up bronchoscopy for removal of debris from the airway. Multimodality approach typically leads to better outcomes.