Long-Term Oxygen Therapy in Patients with Pulmonary Artery Hypertension

DISCUSSION

Two randomized controlled trials (RCTs) in chronic obstructive pulmonary disease (COPD) showed survival benefits when LTOT was used for 15 h/day.^[3,4] An RCT on nocturnal oxygen therapy trial (NOTT) included 203 patients at six centers and they were randomly allocated to receive nocturnal oxygen therapy and continuous oxygen therapy. Baseline parameters such as arterial oxygen and carbon dioxide tensions (PaO₂ and PaCO₂), SpO₂, and demographics were recorded. Oxygen was administered by nasal prongs with a flow rate of 1-4 L/min. This trial reported a decrease in mortality rate after using LTOT and they concluded that continuous oxygen therapy was associated with lower mortality rates than nocturnal oxygen therapy.^[3]

Cooper et al.^[5] conducted a 12-year retrospective survival study in patients with hypoxic cor pulmonale prescribing LTOT as cor pulmonale is a maladaptive response to pulmonary hypertension. They included 72 patients in their study, 22 of whom were using oxygen concentrator and the rest cylinders. Baseline parameters were recorded before the therapy. The 1-year survival with oxygen therapy was found to be 88% and the overall 5-year survival was 62%. These study reports were considered to be better than the earlier report of 5-year survival without oxygen therapy, i.e., 40%. Weitzenblum et al. found out that LTOT for 15-18 h/day can reverse the progression of pulmonary hypertension in a high percentage of patients with severe COPD. The rationale behind the study was to report survival benefit with the use of oxygen therapy and to identify which group of PAH with their subtypes will be benefited with oxygen therapy.^[6] Many researches related to oxygen therapy in COPD and cor pulmonale are available, but the effect of LTOT has not been explored in PAH patients.

Of the 332 patients with pulmonary hypertension enrolled in this study, 32 were prescribed LTOT. Two-thirds of the patients were women. The mean (±SD) age of men was 65 (±10) years and 54 (±14) years in women. Studies by Walker et al.^[7] and Badesch et al.^[8] showed that PAH is more prevalent among females with a ratio of 4.3:1. Up-to-date registries of PAH report older populations ranging from 50 ± 17 years to 65 ± 15 years.^[9–12] In our study, 75% of participants who underwent LTOT were diagnosed as Group III which included asthma 6 (18%), COPD 12 (37.5%), bronchiectasis 3 (9.4%), tuberculosis 2 (6.3%), and obstructive sleep apnea 1 (3.1%). Chaouat et al. and Andersen et al. in their researches on the Global Initiative for Chronic Obstructive Lung Disease Stage IV revealed that most of these patients (90%) had PAH indicated by (mean pulmonary arterial pressure [mPAP]) >25 mmHg with most ranging between 20 and 35 mmHg and very few ranging between 3% and 5% with mPAP >35-45 mmHg.^[13,14] Asthma and PAH are essentially separate diseases, but these two diseases have important pathological features in common which are inflammation, smooth muscle contraction, and remodeling.^[15] In patients with COPD, chronic hypoxemia is a major reason for the development of pulmonary hypertension. Therefore, correction of alveolar hypoxia with supplemental oxygen appears suitable for treating pulmonary hypertension in COPD. The administration of LTOT has been shown to improve survival in COPD patients with chronic hypoxemia. Two major studies that reported the survival benefits of LTOT are Medical Research Council and the NOTT ^[3,4]

Our study showed significant improvement of oxygenation, respiratory rate, and hemoglobin in patients who used LTOT. The mean (±SD) duration of oxygen usage in our study was 15.22 (±1.963) hours during follow-up; at 1 year, 26 (81.3%) participants survived, 3 (9.4%) expired, and 3 (9.4%) dropped to follow-up. Sliwinski et al. suggested that the long-term use of oxygen may significantly improve survival, despite the lack of an acute oxygen effect on reducing pulmonary artery pressures.^[16]

Weitzenblum et al.^[6] suggested that LTOT for 15-18 h/day resulted in a small reduction in pulmonary hypertension after the first 2 years followed by a return to initial values and subsequent stabilization of PAPs over 6 years. In our study, patients who used LTOT had reduced hospital admission when compared to the patients who did not use LTOT.

A study by Ringbaek et al. shows that in hypoxemic COPD patients, LTOT is associated with a reduction in hospitalization.^[17] Short-term readmission is common after PAH hospitalization. Patients admitted to high-volume PAH hospitals have lower rates of 30 days' readmission.^[18] In the REVEAL Registry, PAH-related hospitalization was associated with relatively more re-hospitalization and worse survival at 3 years.^[19] Our findings are similar to the findings in the literature. This study also calls for improvement in protocols, which lead to prescription of LTOT based on eligibility criteria, which aid to select the patients that might benefit most from such intervention. However, this study has not looked at the adverse effects of LTOT. The findings of this study should not be generalized due to its limitations.

This study has a few limitations: first, this was done on participants who were diagnosed by physicians seeking oxygen therapy. Therefore, it may not be generalized to the general population. Second, the diagnosis was not based on invasive measurements and 6-min walk test, and the study did not have a control group for comparison. Third, during follow-up, no vital sign parameters were measured as the patients were not visited by the research team. The values were recorded from the medical records available. Finally, the sample size was small.