The Evidence for Long-Term Oxygen Therapy

Greg Spratt BS, RRT, CPFTChief Clinical Officer

Rotech Healthcare Inc.

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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

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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

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LTOT in COPDMedical Research Council (MRC)

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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

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Survival with LTOT in COPDNocturnal Oxygen Therapy Trial

(NOTT)

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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

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Survival Response is ‘Dose Dependent’

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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.

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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.

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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.

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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

HRQLEaton et al. Resp Med 2004; 98:285-93

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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

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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

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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 groupChest 1992; 101:649-655

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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.

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

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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

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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

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Benefits of Oxygen During Activity

• Increases capacity for activity (distance and endurance)

• Decreased Dyspnea

• Improves HRQL

• Reduces Increase in PAP during activity

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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

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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

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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

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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

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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

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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

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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

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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

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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.

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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

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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

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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

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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