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

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

LTOT in Chronic Hypoxemia Chronic Hypoxemia – PaO2 < 55 mm Hg or SpO2 < 88% at rest PaO2 56 -59 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

LTOT in COPD Medical Research Council (MRC)

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: 681-685

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

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: 391-398

Survival Response is ‘Dose Dependent’

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: 493-498. Oswald-Mammosser et al. Chest 1995; 107: 1193-1198. Zielinski et al. Chest 1998; 113: 65-70. MacNee et al. Am Rev Respir Dis 1988; 137: 1289-1295. Timms et al. Ann Inter Med 1985; 102: 29-36.

Benefits of LTOT Continuous oxygen therapy reverses secondary polycythemia, improves cardiac function during rest and exercise [8, 9] Balter et al. Chest 1992; 102: 482-485 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: 910-915. Dean et al. Am Rev Respir Dis 1992; 146: 941-945. Somfay et al. Eur Respir J 2001; 18: 77-84.

Benefits of LTOT Improves neuropsychiatric deficits in abstract thinking, motor skills and perceptual motor abilities Krop et al. Chest 1973; 64: 317-322. Heaton et al. Arch Intern Med 1983; 143: 1941-1947. Petty TL, ed. Chronic Obstructive Pulmonary Disease. pp. 355-373.

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

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

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

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; 101:649-655

Pulmonary Artery Pressure in NOD Pulmonary artery mean pressure was significantly higher in NOD (19.1 +/- 4.7 vs 16.8 +/- 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.

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; 145:1070-76 Chest 1992; 101:649-655

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. 2001 May;17(5):848-55

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

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

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; 122:457-463

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; 120:437-443

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

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

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

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: 306-312

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; 91:287-291

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; 7:274-278

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;117:679-683.

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: 314-321

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

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; 109:1144-50

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