Treatment of Advanced Disease
Beyond bronchodilators, corticosteroids, antibiotics and ancillary
pharmacologic agents, additional technologically oriented care is
appropriate for selected patients with advanced stages of disease. The
strategies include pulmonary rehabilitation, long-term home oxygen (LTOT),
definition of pulmonary rehabilitation by the committee of the American
College of Chest Physicians 1974 was as follows:
“Pulmonary rehabilitation may be defined as an art of
medical practice wherein an individually tailored, multi-disciplinary
program is formulated, which through accurate diagnosis, therapy,
emotional support and education, stabilizes or reverses both the physio
and psychopathology of pulmonary diseases and attempts to return the
patient to the highest possible functional capacity allowed by the
pulmonary handicap and overall life situation.”
Since that time, other definitions have been offered, but none have
a better foundation than the above. Text books have been written to
summarize the technologies and therapeutic approaches to pulmonary
rehabilitation, and one is cited in the references at the end of this
The components of pulmonary rehabilitation include patient and
family education, the strategic use of pharmacologic agents, (which are
covered in another section), breathing retraining and breathing exercises,
physical reconditioning, oxygen (in selected patients), and patient
A new publication for COPD patients gives a state of the art review
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patients and their families in layman’s language. (See Frontline Advice
for COPD Patients).
Most experts believe that pulmonary rehabilitation should
be considered earlier in the disease process than it has been
traditionally thought of (i.e., moderate COPD), not waiting until the
patient has severe disease.
Numerous studies have shown that pulmonary rehabilitation increases
exercise tolerance, provides a better quality of life, and reduces anxiety
and depression. There is a variable effect upon hospitalizations, but, in
general, hospitalizations are also reduced.
The systemic nature of advanced COPD has received appropriate emphasis.
The spiraling dyspnea and inactivity pathway must be stopped. For some
reason, patients with only mild to moderate stages of COPD cannot achieve
an age-predicted target heart rate of maximum oxygen consumption. Why this
is must have something to do with oxygen delivery or oxygen utilization.
The consequences of hypoxemia in advanced stages of COPD are reactive
pulmonary hypertension, increased airflow resistance and expanded red cell
mass, reduced tissue oxygen transport and combinations. The scientific
basis for oxygen administration for at least 15 hours per day has been
established by the nocturnal oxygen therapy trial (NOTT) and the British
MRC trial. In both trials, the survival difference was seen between
continuous ambulatory oxygen and stationary oxygen, and stationary oxygen
versus no oxygen.
Why nearly continuous oxygen therapy in the NOTT study prolonged
survival in COPD patients remains unexplained. It could be the duration of
oxygen therapy or, more likely, the ability to ambulate with oxygen. The
ability to ambulate would improve tissue oxygen transfer, and perhaps
restore energy production at the tissue level. Ambulation provides
physical reconditioning and has known psychosocial value. The NOTT study
showed that continuous oxygen improved brain function more than nocturnal
Table 6 lists the USA prescribing criteria for long term oxygen therapy
(LTOT). These criteria were used in the NOTT.
Prescribing Criteria for Long Term
criteria specified by the Medicare program, which must be met in order for
the costs of the oxygen to be reimbursed, are as follows:
Qualification on the
basis of hypoxemia alone:
55 mmHg, or
- Sa02 88%
(breathing room air)
requiring additional clinical evidence of hypoxia, Pa02 56-59
mmHg or Sa02 89% plus one or more of the
- P-pulmonale (P
waves 3 mm or more in lead II, III, or a VF of electrocardiogram)
right-sided heart failure (dependent edema)
(hematocrit over 55%)
New developments in oxygen therapy include the use of transtracheal
oxygen and concealing oxygen cannula in ordinary eye glasses.
New light-weight systems such as the Helios (weighing only 3.75 lbs.)
filled with a conserver providing an 8-hour supply of oxygen at 2 liters
per minute make ambulation and participation in the full activities of
daily living a reality. Light-weight, battery powered oxygen concentrators
are on the horizon. One unit weighs less than 10 lbs. and has just been
introduced to the marketplace, the Essential Life
The mechanisms of improved survival from all LTOT include improved
hemodynamics from reduced right ventricular afterload or increased right
ventricular function, improved tissue oxygen transport, and improved
cellular oxygen utilization.
Lung transplantation is available for only a select few patients.
Although the quality of life is improved through lung transplantation,
rejection through bronchiolitis obliterans is a major limiting factor. The
length of life in advanced stages of COPD is not greatly increased with
lung transplantation as compared with pulmonary rehabilitation therapy
alone. The National Emphysema Therapy Trial (NETT), which evaluated lung
volume reduction surgery, has recently reported that surgery was superior
to ordinary pulmonary rehabilitation. Selection of ideal patients is key.
Eliminating patients with an FEV1of less than 20% of predicted,
a DCO of less than 20% of predicted, and homogenous distribution of
emphysema, seem critical.
New techniques may make lung volume reduction surgery less traumatic
and more accessible to selected individuals. The goal of lung volume
reduction surgery is to improve elastic recoil and restore the
length-tension relationships in the diaphragm. Ventilation profusion
distribution is also improved. The clinical counterpart is reduced
dyspnea, improved exercise tolerance and improved oxygenation. A limited
number of patients can be freed from the use of LTOT, at least for a
period of time.
Beeh KM, Kornmann O, Lill J, et al: Induced
sputum cell profiles in lung transplant recipients with or without chronic
rejection: correlation with lung function. Thorax 2001;56:557-560.
Increased sputum neutrophils relate to rejection in lung transplant
Butland RJ, Pang J, Gross ER, et al: Two-,
six- and 12 minute walking tests in respiratory disease. BMJ
1982;284:1607-1608. The original report that gave evidence that the 6
minute walk test correlated well with the twelve minute walk test.
Casaburi R, Petty
TL (eds): Principles and Practice of Pulmonary Rehabilitation. WB
Saunders, Philadelphia PA, 1993. A comprehensive text book on pulmonary
rehabilitation with a historical perspective.
Christopher KL, Spofford BT, Petrun MD, et
al: A program for transtracheal oxygen delivery. Assessment of safety and
efficacy. Ann Intern Med 1987;107:802-808. An early report on the
advantages of transtracheal oxygen (TTO) delivery in selected patients
Continuous or nocturnal oxygen therapy in
chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen
Therapy Trial Group (Petty TL, Chairman) Ann Intern Med 1980;93:391-398.
The original report of the NOTT which showed a significant survival
benefit for ambulatory oxygen used for more hours than stationary
nocturnal oxygen (17.4 hours versus 11.8 hours).
Good JT Jr., Petty TL: Frontline Advice for
COPD Patients. Snowdrift Pulmonary Conference, Inc., Denver CO – 94 p. A
comprehensive monograph written for patients.
Heaton RK, Grant I, McSweeny AJ, et al:
Psychologic effects of continuous and nocturnal oxygen therapy in
hypoxemic chronic obstructive pulmonary disease. Arch Intern med
1983;143:1941-1947. Showed that ambulatory oxygen improved brain function
more than in nocturnal stationary oxygen.
Hudson LD, Tyler ML, Petty TL:
Hospitalization needs during an outpatient rehabilitation program for
severe chronic airways obstruction. Chest 1976;70:606-610. Evidence of
reduced hospitalizations following institution of a pulmonary
Long-term domiciliary oxygen therapy in
chronic hypoxic cor pulmonale complicating chronic bronchitis and
emphysema. Report of the Medical Research Council Working Party. Lancet
1981;1:681-686. Showed a survival benefit with oxygen delivered for 15
hours per day compared with no oxygen. Survival effect did not occur until
after 500 days of treatment.
Mueller RE, Petty TL, Filley GF: Ventilation
and arterial blood gas changes induced by pursed lips breathing. J Appl
Physiol 1970;28:784-789. Pursed lips breathing resulted in slower, deeper
breathing and improved arterial oxygenation.
Petty TL, Bliss PL: Ambulatory oxygen
therapy, exercise, and survival with advanced chronic obstructive
pulmonary disease (the Nocturnal Oxygen Therapy Trial revisited). Resp
Care 2000;45:204-211. A retrospective analysis of the NOTT study. Survival
with ambulatory oxygen was superior to survival with stationary oxygen in
persons able to increase their exercise. Hospitalizations also reduced
with ambulatory oxygen.
Petty TL: Pulmonary rehabilitation of early
COPD. COPD as a systemic disease. Chest 1994;105: 1636-1637. An editorial
comment about why COPD must be considered a systemic disease.
Ries AL, Kaplan RM, Limberg TM, et al:
Effects of pulmonary rehabilitation on physiologic and psychosocial
outcomes in patients with chronic obstructive pulmonary disease. Ann
Intern Med 1995;122:823-832. A controlled trial showing advantages of
pulmonary rehabilitation over standard care.
The National Emphysema Treatment Trial
Group. Rationale and design of the National Emphysema Treatment Trial. J
Cardiopulmonary Rehabil 2000;20:24-36. A detailed review of study design
The National Emphysema Treatment Trial
Group. Patients at high risk of death after lung-volume-reduction surgery.
N Engl J Med 2001;345:1075-1083. Evidence of high mortality in patients
with extremely poor ventilatory and diffusion function.