Evaluation of Nickel Release from Endobronchial Valves as a Possible Cause of Hypersensitivity Pneumonitis in a Patient Treated with Bronchoscopic Lung Volume Reduction

Abstract

Background: Endobronchial valve (EBV) placement is an established lung volume reduction procedure aiming to improve lung function and exercise capacity in patients with severe emphysema. As EBVs consist of silicone and nitinol (a metal alloy of nickel and titanium), there are concerns that nickel ions might be released and could have a clinical impact in patients with a contact allergy to nickel. Based on a case with hypersensitivity pneumonitis (HP) after treatment with EBVs, we aimed to evaluate the in vitro nickel release from EBVs using inductively coupled plasma mass spectrometry (ICP-MS) and scanning electron microscopy (SEM). Methods: Six EBVs were immersed in artificial saliva for a period of 7 days. At 24-h intervals, the nickel ion concentration was measured using ICP-MS. Results: There was evidence of a significant nickel release from EBV during the first 48 h, which is possibly due to an incomplete silicone layer detected by SEM. The concentration of released nickel was below the toxic limit. Conclusions: To the best of our knowledge, we report the first case of HP after EBV treatment. Our finding of in vitro release of nickel ions from EBVs may contribute to the current understanding on hypersensitivity reactions after nitinol implants in patients with nickel contact allergy. However, it did not confirm a causative relationship.

Endobronchial Valve Treatment Does Not Cause Significant Nickel Deposition in Lung Tissue

“…To date, only one in vitro study has assessed the release of nickel ions from EBVs. This study found a significant release of nickel in the first 48 hours, which did remain below the toxic level (for oral intake of nickel) [7]. However, it remains unknown if these results resemble the in vivo situation, especially because the implantation environment can influence the amount of nickel that can leach from nitinol devices.…”

“…Furthermore, the nitinol frame of EBVs is mostly covered by silicone, preventing nickel ion release, which is not the case with Amplatzer septal occluders. However, it has been shown that the surface area of the EBV is not always completely covered with silicone [7,8].…”

Identification of damage associated molecular patterns and extracellular matrix proteins as major constituents of the surface proteome of lung implantable silicone/nitinol devices

“…Endobronchial valves are composed of a duck-bill unidirectional valve attached to a nitinol frame. All components are either composed of, or covered by silicone [29] . Silicone and nitinol have good biocompatibility profiles [ 5 , 30 ].…”

Complications after bronchoscopic lung volume reduction

“…However, care providers must be aware of potentially fatal complications, such as post-valvular pneumonia with septic shock (Figure 1) or severe hemoptysis with subsequent respiratory failure ( Figure 2). Recently, a case of severe hypersensitivity pneumonitis in a patient with Nickel allergy treated with endobronchial valves (15). In addition, the authors detected loss of Nickel ions from valves in in vitro experiments.…”