High-flow nasal oxygen therapy (HFNOT) is a cornerstone treatment modality in severe acute hypoxemic respiratory failure, with benefits in improving oxygen deficit while normalizing breathing rate and having an effect on airway humidification. These physiological effects indicate a potential benefit in end-stage chronic respiratory failure. We aimed to assess the clinical impact of home HFNOT in reducing both exacerbation rates and overall disease burden in end-stage chronic respiratory disease. We designed a retrospective study including patients followed in the pulmonology department of a tertiary center who started home HFNOT until June 2023. Pre- and post-home HFNOT exacerbations and hospital admissions were registered, and each patient served as their own control for the statistical analysis. In total, 36 patients were included in the study: 24 patients (66.7%) with interstitial lung disease and 12 (33.3%) with obstructive lung disease. Overall, the median titrated fraction of inspired oxygen was significantly lower in obstructive patients
no significant differences were found between groups regarding titrated airflow. Obstructive patients had a significantly higher number of pre-treatment exacerbations and hospital stays. Both clinical subgroups presented less median overall post-treatment exacerbations and hospital admissions vs. pre-treatment start. Although mortality was high, home treatment was well tolerated by most patients, with only one patient interrupting high-flow therapy due to intolerance. Home HFNOT proved to be an overall feasible treatment strategy for patients with end-stage respiratory disease. Obstructive lung disease patients benefited the most from the treatment, possibly due to hypercapnia correction.