1. The Evidence for Long-Term Oxygen Therapy
Greg Spratt BS, RRT, CPFT Chief Clinical Officer Rotech Healthcare Inc.

2. Objectives Understand benefits of LTOT in chronic hypoxemia
Discuss use of oxygen for nocturnal desaturations
Discuss benefits of oxygen during activity
Discuss desaturations while using oxygen
Discuss compliance with oxygen

3. LTOT in Chronic Hypoxemia
Chronic Hypoxemia – PaO2 < 55 mm Hg or SpO2 < 88% at rest
PaO mm Hg or SpO2 89% with evidence of:
P pulmonale (EKG)
Hematocrit > 55%
Clinical Evidence of Right Heart Failure
Only therapy widely accepted to improve survival in COPD

4. LTOT in COPD Medical Research Council (MRC)

5. MRC Study
Compared hypoxaemic patients receiving oxygen for 15 hr/day, including the hours of sleep, with patients receiving no oxygen. This trial demonstrated that oxygen was associated with a significant reduction in mortality
Lancet 1981; 1:

6. Survival with LTOT in COPD Nocturnal Oxygen Therapy Trial (NOTT)

7. NOTT Study
Comparing continuous oxygen therapy (average 19 hr/day) with therapy for 12 hr/day, including the hours of sleep, demonstrated a further reduction in mortality using continuous oxygen.
Ann Intern Med 1980; 93:

8. Survival Response is ‘Dose Dependent’

9. Benefits of LTOT
The mechanism for improved survival has yet to be completely delineated, but improved pulmonary hemodynamics appear to play a role
Pulmonary vascular resistance may be decreased
Weitzenblum et al. Am Rev Respir Dis 1985; 131:
Oswald-Mammosser et al. Chest 1995; 107:
Zielinski et al. Chest 1998; 113:
MacNee et al. Am Rev Respir Dis 1988; 137:
Timms et al. Ann Inter Med 1985; 102:

10. Benefits of LTOT
Continuous oxygen therapy reverses secondary polycythemia, improves cardiac function during rest and exercise [8, 9]
Balter et al. Chest 1992; 102:
Zielinski J. Curr Opin Pulm Med 1999; 5: 81-87
Reduces the oxygen cost of ventilation, and improves exercise tolerance
Mannix et al. Chest 1992; 101:
Dean et al. Am Rev Respir Dis 1992; 146:
Somfay et al. Eur Respir J 2001; 18:

11. Benefits of LTOT
Improves neuropsychiatric deficits in abstract thinking, motor skills and perceptual motor abilities
Krop et al. Chest 1973; 64:
Heaton et al. Arch Intern Med 1983; 143:
Petty TL, ed. Chronic Obstructive Pulmonary Disease. pp

12. LTOT and HRQL 43 COPD patients
Measured by CRQ and Hospital Anxiety and Depression Scale
Low HRQL by CRQ at baseline
28 (67%) and 26 (68%) ‘responders at 2 and 6 months in LTOT group
Non-LTOT showed progressive decline in HRQL
Eaton et al. Resp Med 2004; 98:285-93

13. LTOT and Hospitalizations
246 patients
125 started COT during hospitalization
37 started COT as outpatient
58 started non-COT (< 15 h/day) in hospital
26 started non-COT as outpatient
Hospitalizations reduced by 23.8%, 43.5%, and 31.2% repectively
Trend was better when started as OP
Ringbaeck et al. ERJ 2002; 20:38 – 42

14. Desaturations During Sleep
Nocturnal Oxygen Desaturation (NOD) occurs in ~ 30% of COPD patients
Defined as
Fletcher- Desats to SpO2 < 90% for 5 minutes with a nadir SpO2 < 85%
Chest 1987; 92:604-8
International Oxygen Club- Desats SpO2 < 88% for at 30% of the night

15. Fletcher Studies More end organ evidence of hypoxemia
More abnormal cardiopulmonary hemodynamics
Chest 1984; 85:6-14
Chest 1987; 92:604-8
Chest 1989; 95:157-66
Decreased survival in NOD group
Chest 1992; 101:

16. Pulmonary Artery Pressure in NOD
Pulmonary artery mean pressure was significantly higher in NOD (19.1 +/- 4.7 vs /- 1.9 mmHg, p less than 0.05)
All patients with Pulmonary Hypertension (6 out of 40) belonged to NOD group.
Levi-Valensi P et al. Eur Respir J 1992 May;5(5):645.

17. Treating NOD with Nocturnal O2
Downward trend in pulmonary artery pressure (-3.7 mm Hg) compared with desaturating patients treated with room air (+3.9)” in patients treated with long-term oxygen (ie, 36 months).[i]
Increase in PCWP in patents not treated with oxygen.
There was a trend toward increased survival in oxygen treated vs. non-oxygen treated NOD subjects.
Am Rev Repir Dis 1992; 145:
Chest 1992; 101:

18. Studies Not Favoring O2 for NOD
64 patients (35 w/NOD by IOC definition, 29 wo NOD)
2 year study
The mean changes in PAP were similar
Rates of death were similar
Similar need for LTOT (by ATS criteria) during follow-up of up to 6 yrs
Chaouat et al. Eur Respir J May;17(5):848-55

19. To Treat or Not to Treat?
May be subgroups that benefit and those that don’t
Some suggest only when evidence of damage from hypoxemia (e.g., RVH, polycythemia)
Studies may be too short (survival curve doesn’t separate for 3 years)
Need for more studies

20. Benefits of Oxygen During Activity
Increases capacity for activity (distance and endurance)
Decreased Dyspnea
Improves HRQL
Reduces Increase in PAP during activity

21. Oxygen and Exercise Performance
75 patients seperated by mild, moderate, and severe obstruction w/mild resting hypoxemia (> 60 mm Hg)
Significant improvement in 6MWT
Significantly reduced elevations in PAP and P Occlusion Pressure during activity
Fujimoto et al. Chest 2002; 122:

22. Oxygen and Exercise Performance
20 stable COPD patients, DBR design
Patients classified as desaturators (5% and <90%) vs non-desats, and O2 responders (10% inc in WD or decrease of 3 in Borg) vs non-respon.
With O2, WD increased 22% and dyspnea decreased by 36% in DS and dyspnea decreased by 47% but WD did not change
No significant difference between BWT and compressed air
Jolly et al. Chest 2001; 120:

23. Oxygen and Activity
12 patients DB RC using 40% O2 or CA w/mild hypoxemia at rest
Measured Walk Time, Dyspnea Onset, and Right Ventricular Systolic Pressure (RVSP)
With O2, significant improvements in walk time, dyspnea onset, rise in RVSP, and mean RVSP at max exercise
No improvement with CA group
Dean et al. Am Rev Respir Dis. 1992; 146:941-5

24. Exercise Response Dose Dependent
10 severe COPD and 7 healthy subjects
Mild hypoxemia(SpO2 at rest > 92% and during exercise > 88%)
Compared walk endurance, dyspnea and hyperinflation at varying % of O2 (21, 30, 50, 75, and 100%)
Measured walk endurance of 4.2 minutes (21%) 7.8 (30%), and 10.3 (50%)
Significant improvements with oxygen in exercise endurance (92% at 30% and 157% at 50%)
Dyspnea and hyperinflation improved (EELV, EILV)
Improvements in dyspnea and hyperinflation
Somfay et al. Eur Respir J 2001; 18: 77–84

25. Oxygen and Activity 159 patients 75 given concentrators only
84 given concentrators and LOX or Small Cylinder/OCD portable
Oxygen use is significantly longer w/port
No difference between LOX and tank
Improved activity with port
Only 60% of those with port used them
Vergeret et al. ERJ 1989; 2:20-25

26. Ambulatory Oxygen and HRQL
41 patients
DB, RC Design using tanks filled with O2 vs Compressed Air
Using CRQ, HAD, and SF-36
Significant difference in improvement in HRQL in O2 vs CA groups
Eaton T et al. Eur Respir J 2002; 20:

27. Desaturations During LTOT
LTOT patients with a resting PaO2 of > 60 mm Hg on oxygen, SpO2 was > 90% for an average of 78% of the time.
In patients with a daytime PaO2 of < 60 mm Hg, SpO2 was > 90% for an average of 69% of the 24-hour period.
Morrison D et al. Respir Med 1997; 91:

28. Desaturation During LTOT
Average SpO2 of 94% at the beginning of the recording,
Patients on oxygen spent an average of 6.9 hours below a SpO2 of 90% with a minimum SpO2 of 61%.
Most desaturations came during sleep and naps.
“The oxygen flow rate prescribed, based on blood gas measurements at rest, did not protect 85% of the patients studied from deep falls in SpO2 during daily life.”
Sliwinski P et al. Eur Respir J 1994; 7:

29. Desaturation During LTOT
82 COPD patients
47.6% spent > 30% of the night with an SaO2 of < 90% while breathing supplemental oxygen
Mean overnight SaO2 while breathing oxygen was 87.1%
Time spent with an SaO2 of < 90% was 66.1% of the recording time
Plywaczewski et al. Chest 2000;117:

30. Desaturation During LTOT
27 COPD patients
25% of time below SpO2 of 90%
Time below 90% was a wide range of 3 – 67%
Pilling et al. Chest 1999; 116:

31. Improving Compliance with LTOT
Formal training (45 patients) at onset vs none (41 patients)
Need for oxygen, disease process, oxygen safety, and smoking habit
82% w/training were using oxygen > 15 h/d
44% w/o training were using oxygen > 15 h/d
Peckham et al. Resp Med 1998; 92:1203-6

32. Compliance with LTOT 930 COPD Patients 45% use LTOT 15 h/d
Factors associated with increased compliance included:
Education
Smoking Cessation
Pepin et al. Chest 1996; 109:

33. Summary
LTOT has many benefits in chronic hypoxemia and during activity desats
May benefit patients with nocturnal desats
Recognize that many patients are not optimally managed with a single liter flow
Compliance with oxygen can be improved with education