Background:Oxygen inhalation therapy is essential for the treatment of patients with chronic mountain sickness (CMS),but the efficacy of oxygen inhalation for populations at high risk of CMS remains unknown.This research investigated whether oxygen inhalation therapy benefits populations at high risk of CMS.Methods:A total of 296 local residents living at an altitude of 3658 m were included;of which these were 25 diagnosed cases of CMS,8 cases dropped out of the study,and 263 cases were included in the analysis.The subjects were divided into high-risk (180 ≤ hemoglobin (Hb) ＜210 g/L,n =161) and low-risk (Hb ＜180 g/L,n =102) groups,and the cases in each group were divided into severe symptom (CMS score ≥6) and mild symptom (CMS score 0-5) subgroups.Severe symptomatic population of either high-or low-risk CMS was randomly assigned to no oxygen intake group (A group) or oxygen intake 7 times/week group (D group);mild symptomatic population of either high-or low-risk CMS was randomly assigned to no oxygen intake group (A group),oxygen intake 2 times/week group (B group),and 4 times/week group (C group).The courses for oxygen intake were all 30 days.The CMS symptoms,sleep quality,physiological biomarkers,biochemical markers,etc.,were recorded on the day before oxygen intake,on the 15th and 30th days of oxygen intake,and on the 15th day after terminating oxygen intake therapy.Results:A total of 263 residents were finally included in the analysis.Among these high-altitude residents,CMS symptom scores decreased for oxygen inhalation methods B,C,and D at 15 and 30 days after oxygen intake and 15 days after termination,including dyspnea,palpitation,and headache index,compared to those before oxygen intake (B group:Z =5.604,5.092,5.741;C group:Z =4.155,4.068,4.809;D group:Z =6.021,6.196,5.331,at the 3 time points respectively;all P ＜ 0.05/3 vs.before intake).However,dyspnea/palpitation (A group:Z =5.003,5.428,5.493,both P ＜ 0.05/3 vs.before intake) and headache (A group:Z =4.263,3.890,4.040,both P ＜ 0.05/3 vs.before intake) index decreased significantly also for oxygen inhalation method A at all the 3 time points.Cyanosis index decreased significantly 30 days after oxygen intake only in the group of participants administered the D method (Z=2.701,P =0.007).Tinnitus index decreased significantly in group A and D at 15 days (A group:Z =3.377,P =0.001,D group:Z =3.150,P =0.002),30 days after oxygen intake (A group:Z =2.836,P =0.005,D group:Z =5.963,P ＜ 0.0001) and 15 days after termination (A group:Z =2.734,P =0.006,D group:Z =4.049,P =0.0001),and decreased significantly in the group B and C at 15 days after termination (B group:Z=2.611,P =0.009;C group:Z =3.302,P =0.001).In the population at high risk of CMS with severe symptoms,oxygen intake 7 times/week significantly improved total symptom scores of severe symptoms at 15 days (4 [2,5] vs.5.5 [4,7],Z =2.890,P =0.005) and 30 days (3 [1,5] vs.5.5 [2,7],Z=3.270,P =0.001) after oxygen intake compared to no oxygen intake.In the population at high risk of CMS with mild symptoms,compared to no oxygen intake,oxygen intake 2 or 4 times/week did not improve the total symptom scores at 15 days (2 [1,3],3 [1,4] vs.3 [1.5,5];χ2 =2.490,P =0.288),and at 30 days (2 [0,4],2 [1,4.5] vs.3 [2,5];χ2 =3.730,P =0.155) after oxygen intake.In the population at low risk of CMS,oxygen intake did not significantly change the white cell count and red cell count compared to no oxygen intake,neither in the severe symptomatic population nor in the mild symptomatic population.Conclusions:Intermittent oxygen inhalation with proper frequency might alleviate symptoms in residents at high altitude by improving their overall health conditions.Administration of oxygen inhalation therapy 2-4 times/week might not benefit populations at high risk of CMS with mild CMS symptoms while administration of therapy 7 times/week might benefit those with severe symptoms.Oxygen inhalation therapy is not recommended for low-risk CMS populations.