Sickle cell disease (SCD) can cause severe pain called vaso-occlusive pain crisis (VOC) and sometimes lead to a dangerous lung problem called acute chest syndrome (ACS). When someone has VOC, their red blood cells get stuck and block blood flow. To help, doctors often give oxygen to keep oxygen levels in the blood at 95%. This study is testing a new way to give more oxygen through a device called **high-flow nasal oxygen (HFNO)**, which might help stop the pain and prevent ACS.

HFNO delivers humidified air at a high rate and can provide up to 100% oxygen. This may improve breathing and comfort better than the usual oxygen therapy. The study will use a special design called **multi-arm multi-stage (MAMS)** to check how safe and effective HFNO is for people with VOC. The device will be used in hospitals.

• The study is for adults aged 18 and older with sickle cell disease experiencing VOC.
• Participants must not have other serious conditions like primary ACS or heart disease.
• The study will be conducted in a hospital setting using the AIRVO 2 device.