A review of the potential applications and controversies of non‐invasive testing for biomarkers of aspiration in the lung transplant population

Abstract

Despite improvements in one-yr survival following lung transplantation, five-yr survival lags significantly behind the transplantation of other solid organs. The contrast in survival persists despite advancements in anti-rejection regimens, suggesting a non-alloimmune mechanism to chronic lung transplant failure. Notably, markers of aspiration have been demonstrated in bronchoalveolar lavage (BAL) fluid concurrent with bronchiolitis obliterans syndrome (BOS). This recent evidence has underscored gastro-esophageal reflux (GER) and its associated aspiration risk as a non-alloimmune mechanism of chronic lung transplant failure. Given the suggested safety and efficacy of laparoscopic anti-reflux procedures in the lung transplant population, identifying those at risk for aspiration is of prime importance, especially concerning the potential for long-term improvements in morbidity and mortality. Conventional diagnostic methods for GER and aspiration, such as pH monitoring and detecting pepsin and bile salts in BAL fluid, have gaps in their effectiveness. Therefore, we review the applications and controversies of a non-invasive method of defining reflux injury in the lung transplant population: the detection of biomarkers of aspiration in the exhaled breath condensate. Only by means of assay standardization and directed collaboration may such a non-invasive method be a realization in lung transplantation.

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

“…For this reason, committee members routinely test patients with new onset BOS for GOR. Proximal gastrointestinal tract motility studies and pH/impedance testing can be used to diagnose motility abnormalities and abnormal acid and/or non-acid GOR [129]. In addition, examination of BAL for markers of aspiration (e.g.…”

“…Nissen fundoplication and Toupet fundoplication) can be performed safely on lung transplant candidates with advanced lung disease or lung transplant recipients with documented abnormal GOR [123,124,[127][128][129][132][133][134][135][136][137][138], thereby preventing reflux, aspiration of gastric secretions and related sequelae.…”

Reflux aspiration in children with neurodisability—a significant problem, but can we measure it?

“…Authors have called for assay standardization as a priority, so that normative values can be established for pediatric and adult age groups [67]. For this to happen, a method capable of accurate quantitative measurement needs to be established, which works for all clinical samples.…”

International practical guidelines on diagnosis, prevention and treatment of bronchiolitis obliterans syndrome

“…По этой причине члены Комитета в своих клиниках, как правило, обследуют больных с началом СОБ для исключения ГЭР. Исследование двигательной ак тивности проксимальных отделов желудочно ки шечного тракта и измерение рН / импеданса помога ет выявить нарушения моторики и патологический кислотный / некислотный ГЭР [129]. Кроме того, показателем микроаспирации или ГЭР считается появление в БАС маркеров аспирации (например, липидов, пепсина и желчных кислот) [66,130,131].…”

“…Антирефлюксное хирургическое лечение (напри мер, фундопликация по Ниссену или Тупе) может быть безопасно выполнено у кандидатов на тран сплантацию с поздними стадиями хронических ле гочных заболеваний или у перенесших трансплан тацию легких с подтвержденным ГЭР [123,124,[127][128][129][132][133][134][135][136][137][138]; тем самым предотвращаются дальнейший рефлюкс и аспирация желудочного со держимого и связанные с ними осложнения.…”