Abstract

IntroductionChronic respiratory diseases are a major global health burden, and oxygen therapy remains a cornerstone treatment for chronic hypoxemia. However, the effectiveness of long-term oxygen therapy (LTOT) depends not only on indication but also on the interaction between device performance, patient physiology, and real-world use. Variability in delivery systems, inadequate titration, and poor adherence often lead to mismatches between prescribed and delivered oxygen doses.Areas coveredThis review synthesizes current evidence on LTOT as a drug-delivery system, focusing on device characteristics, delivery performance, and patient-device matching across rest, exertion, and sleep. It examines stationary and portable systems, as well as home high-flow nasal cannula (HFNC). Key challenges such as pulse-dose variability, device limitations, adherence, and safety are addressed. Evidence from clinical trials, physiological studies, registries, and guidelines is integrated to show how delivery systems and patient factors influence effectiveness.Expert opinionLTOT should be reframed as a precision drug delivery system rather than a simple flow-based prescription. Device-specific titration, confirmation of adequate oxygenation with the prescribed device under the intended conditions of use, and individualized matching are essential. Future strategies should prioritize objective monitoring, advanced technologies, and scalable education to reduce the gap between prescription and real-world effectiveness.