Transbronchial cryobiopsy (TBCB) is feasible and of additional diagnostic benefit in patients that suffer from severe ARDS even during ECMO treatment. In our case series all TBCB revealed a sufficient histopathological characterization in patients suffering from unexplained ARDS.
TBCB was extensively analyzed especially in the diagnostic workflow of ILD. In this context it is broadly accepted that TBCB equally contributes to the final diagnosis when compared to surgical lung biopsy [6, 7]. Compared to surgical lung biopsy the lower rate of complications of TBCB and the comparable diagnostic yield is advantageous.
Recently TBCB has been reported in two retrospective series in a small number of patients with acute hypoxemic respiratory failure (AHRF) and ARDS without severe adverse events. However, these patients were investigated at a quite early moment after hospital admission, there is no information about the severity of the individual respiratory situation, especially need for mechanical ventilation [8, 9, 10].
In our patients we usually do not reach for tissue collection in an early ARDS, especially when no previous pulmonary pathology is known and usually an infectious cause might be assumed. In ARDS or AHRF tissue acquisition with open lung biopsy alone or in combination with BAL and lung forceps biopsy was reported to have a relevant impact to the diagnostic work up and change the treatment in up to 73% of the patients. It is however connected to a relevant number of severe adverse events and procedure related deaths . In this particular patient cohort this is difficult to compare. Time to rapidly find an exact diagnosis is limited and usually does not allow several attempts of interventional methods. When tissue collection seems necessary the balance between a method with high diagnostic yield and expectable complication rate at the lowest possible level, TBCB should be considered, when surgical lung biopsy is not consented or not warranted for any reason and skills with TBCB are already established.
Because of the need for diagnostic precision on the one hand and manageable complications on the other hand, we decided not to perform TBFB regularly prior to TBCB. The TBFB prior to TBCB performed in one single patient did not reveal any relevant diagnostic information.
However, there is still debate on the procedural settings in TBCB . Further studies have to contribute to this discussion. Transbronchial biopsy, even TBCB, has never been reported under ECMO. As this seems to be a situation with high clinical need, we could show that TBCB might be feasible with an acceptable risk profile. Also, open lung biopsy during ECMO treatment has never been reported before.
We acknowledge the relevant risk profile in our patients, but the side effects could be handled consecutively. However, complications need to be effectively monitored and treated, if necessary. Prophylaxis of endobronchial haemorrhage with inserted blocking utensils should be done especially when effective anticoagulation cannot be withdrawn. We did not work with a prophylactic balloon blockade, that is especially recommended when experience with the procedure is lacking or general endotracheal intubation is not performed . However as “experience” cannot be defined more specifically this should be decided by the individual operator. As we experienced two severe complications in the patients where fluoroscopy was logistically impossible we postulate that this item should be mandatory to increase the periprocedural safety. When fluoroscopy is impossible to provide, TBCB especially in ARDS patients should not be performed.
Surveillance and treatment of procedure related side effects are essential. TUS has been reported to be an excellent tool for either exclusion of pneumothorax directly or delayed after a broad range of bronchoscopic interventions  or but also with exclusive focus on TBCB [12, 13], and is recommended to be used as first method for pneumothorax exclusion after procedures with increased risk for pneumothorax in the intensive care unit setting when compared to delayed chest X-ray . In the one patient with pleural defect that absence of pneumothorax might be explained due to stiffness of the lung tissue but is not generalizable.
We scheduled the biopsies quite late in the patients’ clinical course. The earlier cited studies reported to do TBCB earlier in diagnostic workup / clinical course. This was however not possible in our patients since they were partially referred for treatment to our center. Whether an earlier transbronchial biopsy would have changed the clinical course remains speculation. This should be considered when even the initial presentation cannot be explained by infection or other common causes of ARDS. We used TBCB to evaluate the prognosis of the pulmonary damage. The suggested and reasonable diagnostic workflow describes tissue collection when previous steps including BAL could not illuminate the cause of the unexplained ARDS . But it is reasonable that the earliest possible chance to secure the diagnosis and get an idea of the patients’ prognosis will help in difficult therapeutic decisions and canalize limited ICU resources.
Limitations of this report are due to the small number of patients and the missing control group. Results are not generalizable, prospective clinical studies should be scheduled to increase knowledge about the value of TBCB in this group of patients with enormous clinical need for the right decision.