NOTT (1980)

Prior to NOTT, the role of long-term oxygen therapy (LTOT) in COPD was debated, particularly regarding its impact on survival. This study aimed to determine if continuous oxygen therapy improved survival compared to nocturnal oxygen therapy in patients with chronic obstructive pulmonary disease and severe hypoxemia.

This was a randomized controlled trial conducted in the US, enrolling patients with stable COPD and severe resting hypoxemia (PaO2 < 55 mmHg or PaO2 55-59 mmHg with cor pulmonale/polycythemia). Patients were randomized to receive either continuous oxygen (at least 18 hours/day) or nocturnal oxygen (12 hours/day) for an average follow-up of 19 months. The primary endpoint was all-cause mortality.

Continuous oxygen therapy significantly improved survival compared to nocturnal oxygen therapy. The 3-year survival rate was 68% in the continuous oxygen group versus 49% in the nocturnal oxygen group (p < 0.005). Patients receiving continuous oxygen also showed improvements in pulmonary hemodynamics, including a decrease in pulmonary artery pressure. The benefits were dose-dependent, with greater survival observed in those receiving oxygen for more hours per day.

The NOTT study established that continuous long-term oxygen therapy (at least 15 hours/day) significantly improves survival in hypoxemic COPD patients and remains a cornerstone of management.

The study was conducted prior to modern COPD management strategies, and the oxygen delivery methods were less refined. The relatively small sample size and specific inclusion criteria limit generalizability to all hypoxemic COPD patients.