COPD Maintenance Management of Symptomatic

The Early Recognition and
Management of Chronic Obstructive Pulmonary Disease

Index:

 Introduction

COPD
Definitions and Pathogenesis

The
National Lung Health Education Program

Methods
of Smoking Cessation

Maintenance
Management of Symptomatic COPD

Treatment
of Advanced Disease

The
New Era

Maintenance Management of Symptomatic COPD

During the evolution of COPD, patients go through stages in which they
are unaware of the effects of the damage to their lungs. Then, depending
upon whether they primarily experience damage to their airways (“chronic
bronchitis”), or their distal air space units (“emphysema”), they
typically experience various combinations of cough, excess mucus, dyspnea
and exercise limitation.

Principles of Symptomatic Therapy

Treatment of COPD patients usually involves the elements identified in
Table 2. The great majority of symptomatic COPD patients will benefit from
management of airflow limitation and enhancement of physical conditioning.
Management of hypoxemia and surgical measures to improve lung mechanics
are reserved for those with more advanced disease.

Reversible
elements of airflow limitation
Mucosal edema/congestion
Mucus
hypersecretion
Smooth muscle bronchoconstriction
Leukocyte
mediated inflammation
Physiological deconditioning
Hypoxemia

Abnormal lung mechanics

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Major Components of Therapy

The primary components of a COPD treatment program are noted in Tables
3 and 4. Obviously all of these interventions are not appropriate for all
patients with COPD; their deployment in relation to severity of disease is
depicted in Table 5.

• Smoking cessation
  
• BronchodilationBeta-agonists:short- (i.e., albuterol) and long-
  (i.e.,formoterol, salmeterol) acting
  Anticholinergics:
  short- (i.e.,ipratropium)and long- (i.e.,tiotropium) acting

  Theophylline

• Corticosteroids
  Inhaled/Systemic
  
• Mucolytics/Expectorants
• Mechanical
  hygiene
  Airway agitators: Flutter®, Pep®, or Acapella®
  Valves
  Postural drainage/clapping or vibrating
• Supplemental
  oxygen
  Continuous
  Nocturnal
  With
  exercise
• Preventing
  infection
  Streptococcus pneumoniae
  vaccination
  Influenza vaccination
  Influenza anti-viral
  agents
• Pulmonary
  Rehabilitation
• Assessment for
  sleep-disordered breathing
• Management of
  gastro-esophageal reflux disease (GERD)
• Surgical relief of
  abnormal lung mechanics
  Lung volume reduction
  surgery
  Bullectomy
  Lung transplantation

Table 4

COMMENTS:   Evidence suggests that the
500/50 dose of Advair is efficacious in COPD – 500 ug bid of fluticasone
in several studies, including ISOLDE, was used for efficacy. * Evidence of
benefit from lower doses of inhaled corticosteroids is lacking. In the
Lung Health Study of triamcinolone, evidence of a reduction in bone
density was found. Thus long term surveillance for developing osteoporosis
and preventive therapy is strongly suggested. *Pending FDA approval for use in
moderate to advanced COPD, i.e., FEV₁ <50% of predicted.

Table 5

Bronchodilation is the first line therapy
for treatment of symptoms in COPD patients. Long-acting beta-agonists,
such as salmeterol or formoterol given twice daily, establish a platform
of enhanced airflow throughout the day and night. In addition,
beta-agonists may accelerate ciliary beat activity, possibly aiding with
mucus clearance. The bronchodilator effect may be strengthened in most
patients by the addition of an anticholinergic agent which effects
bronchodilation via different pathways than beta- agonists. Ipratropium is
currently available in the U.S. and a longer acting agent, tiotropium (now
available in many countries), may soon be available here as well. Early
clinical experience suggests that inhaled tiotropium may be more effective
than salmeterol in improving a variety of parameters of lung function.
Neither the long-acting beta-agonists nor the anti-cholinergic agents have
sufficiently rapid onset of action to relieve acute bronchospasm; a
short-acting beta-agonist, such as albuterol, plus or minus a short-acting
anticholinergic (ipratropium) should be used for relief of episodic
breathlessness. These agents (anti-cholinergics or beta-agonists) can be
used alone, but many studies show that their combined use leads to greater
bronchodilation than that observed with either agent alone. This is
because these agents work by different mechanisms to bronchodilate.
Therefore, this leads to additive, or greater than additive (synergistic)
bronchodilator effect.

The role of theophylline in COPD management
is somewhat controversial today. Although this drug has demonstrated
bronchodilation capacity, it is less effective than either the
beta-agonist or anticholinergic agents. Additionally, the risk of
toxicity, possibly related to altered hepatic elimination associated with
drug-drug interactions, has created further reluctance to use the drug.
However, for patients who do not enjoy consistently satisfactory control
of their symptoms on beta-agonists, anticholinergics and inhaled steroids,
a trial of theophylline is justified. By introducing the drug slowly in
escalating dosage, some of the troublesome gastrointestinal or central
nervous system side effects may be minimized. In addition to
bronchodilation, other potential benefits of theophylline include improved
mucociliary clearance, reinforcement of respiratory drive, and
augmentation of diaphragmatic contractility/endurance. Theophylline may
also help to combat inflammation, but evidence-based studies are limited
on the anti-inflammatory effect in COPD.

Corticosteroids may be helpful in the
management of selected COPD patients. Used commonly in the management of
acute exacerbations of chronic bronchitis (AECB), chronic use of systemic
steroids only results in substantial improvements in the FEV₁
for about 1 in 5 COPD patients. And, a modest additional number of
COPD patients will report subjective improvement while receiving oral
steroids, despite a lack of improvement on spirometry. However, given the
predictable and formidable sequelae of long-term systemic steroids, such
treatment should be employed cautiously.

There has been recent interest in the use of newer, more potent inhaled
steroids, to learn whether the beneficial effects can be achieved without
the morbid complications.

Available data suggest that inhaled corticosteroids may both improve
airflow and reduce the frequency and severity of exacerbations for
moderate to severe COPD patients. Thus, it has become common practice to
utilize inhaled agents to complement beta-agonists and anti-cholinergic
drugs. However, the benefits of the inhaled steroids should be weighed
against their potential complications and expenses. It should be noted
that the benefits of inhaled steroids in COPD are only observed using
high-range dosing. Long-term use of potent steroids, even inhaled, may
entail risks for cataracts, osteoporosis, and adrenal suppression. Indeed,
for the patient on long-term high dose inhaled steroids, it is prudent to
consider ”stress” dose steroid replacement therapy if the patient must
undergo general anesthesia/surgery.

The highest combination dose of salmeterol fluticasone will likely
receive FDA approval for use in the maintenance management of severe COPD,
but it has not received FDA approval as of the time of this printing.
(6/03)

The more common problems related to inhaled steroids, especially the
more potent varieties, are oral-pharyngeal or esophageal thrush and
laryngeal myopathy. To lessen deposition of steroids on these proximal
structures, use of spacers with MDI devices and post-inhalation rinsing
after use of all steroid-delivering devices is strongly encouraged.
Purpuric lesions, especially around the wrists, are seen commonly, most
prominently in women.

An occasional patient will enjoy symptomatic and physiologic benefit
from oral corticosteroids that cannot be duplicated with inhaled products.
In these cases, it is incumbent upon the clinician to establish the
minimal dosage required, usually by a gradual wean over weeks to months.
In some cases, benefits can be maintained even with alternate day dosing.

Clinical research is underway to identify agents other than
corticosteroids that are directed more specifically against inflammation
particularly related to COPD.

Mucolytics or expectorants may be of modest
benefit in patients with COPD. N-acetylcysteine (NAC) is the prototypic
mucolytic agent, but due to its cost and limited utility, NAC use in its
inhaled formulation in COPD is generally discouraged in the United States.
However, reviews of the clinical experience in the United States and
Europe suggest that there may be modest benefits from the use of oral NAC
therapy among patients with symptomatic but stable COPD [see Stey]. Note
that these trials, done outside the U.S., involved oral administration of
MAC (total doses 400 to 600 mg/day given b.i.d. or t.i.d.). Oral tablets
are not available in the U.S. Thus, one would be forced to employ the
inhaled form as an oral agent, which has not been systematically studied.
If inhaled NAC were to be used, logically it might be attempted in those
with difficulty in clearing secretions.

By contrast, recombinant human DNAase (Dornase®), which has proven
utility in patients with CF, has not resulted in benefit for patients with
non-CF-related bronchial disorders.

Guaifenesin (glyceryl guaiacolate) may lessen the tenacity of
respiratory secretions, aiding in their elimination. For patients who
continue to have difficulty due to chronic congestion despite optimal
inhaled therapy and mechanical hygiene, a trial is warranted. This
medication is available in a variety of compounds, and pseudoephedrine is
commonly added. To lessen side-effects, a simple formulation is generally
preferable.

Mechanical hygiene involves techniques
employing manual percussion or devices to augment mucus clearance, with or
without postural positioning. Historically, “PD&C,” (postural drainage
and clapping) was practiced in hospitals and recommended for home care.
But due to inconvenience and time constraints, such recommendations were
rarely adhered to after discharge. By contrast, the more user-friendly
devices, such as the Flutter®, Pep®, or Acapella® valves have been
received much more enthusiastically. These devices all work by generating
an intermittent, vibrating energy to the airways, helping to mobilize
tenacious secretions. Used after inhaled bronchodilator therapy, these
devices help clear congested airways. Patients report that although they
cough heavily during and shortly after such treatment, they are less
likely to experience embarrassing, disruptive paroxysms of cough at work
or social occasions.

To use these devices optimally, patients should be instructed in their
use by respiratory therapists or other qualified healthcare professionals.

Preventing lower respiratory tract
infections is an important element of COPD care. All patients
should receive Pneumovax, and if they have not been vaccinated in the past
10 years, they should be revaccinated to both boost immunity and take
advantage of the additional serotypes included in recent vaccines.

Persons with COPD should receive the ‘flu” vaccine every fall when it
first becomes available. If they miss the vaccine and are exposed to
someone with presumed influenza, they should take prophylactic
anti-influenza therapy with agents such as amantadine, rimantadine,
zanamivir (Relenza ®) or oseltamivir (Tamiflu®). Or, if they have been
vaccinated but nevertheless are coming down with an illness presumed to be
influenza, such therapy may lessen the severity and duration of the
illness.

Finally, persons with COPD should be cautioned to avoid unnecessary
contact with persons known to be infected or at very high risk of viral
respiratory infections (e.g., grandchildren in primary school or large
gatherings during “flu season”).

Long term oxygen therapy (LTOT), pulmonary rehabilitation and surgery
are discussed in the next section.

Sleep disordered breathing may complicate
the health of persons with COPD. Individuals who report daytime
somnolence, snoring, restless sleep, or spouse-described apneas should be
considered for evaluation. Other warning signs include new onset
hypertension and/or erythrocytosis.

Nutritional issues may also be important for
persons with COPD. Typically, with advancing COPD—commonly with
emphysema-dominant disease—patients begin to lose weight. In some
respects, this may be seen as a physiological adjustment to diminished
lung capacity. But, in extreme cases, the weakness which ensues may be
deleterious. Nutritional counseling and special enriched diets may be
beneficial.

At the other extreme, some patients with bronchitis-dominant disease
may suffer from obesity which compromises their mobility and endurance.
Weight loss may prove beneficial.

Depression is common among persons whose
lives have been compromised by COPD. Psychological counseling and
sex-education may prove helpful. However, in a substantial portion of
cases, pharmacotherapy may be essential to relieve the pall of
depression.

Gastro-esophageal reflux disease (GERD)
becomes increasingly common among persons with progressive COPD. Over half
of those with advanced COPD (FEV₁ < 50% predicted) have GERD
and/or disordered esophageal motility. This is relevant in terms of the
differential diagnosis of retrosternal chest pain (i.e., is it cardiac
ischemia or GERD?). It is also important to remember that several commonly
used COPD medications, including beta-agonists, theophylline, and
corticosteroids, can exacerbate GERD.

Osteoporosis is typically found in persons
with advanced COPD. Special risk factors include female gender and slender
body habitus. Additional hazards secondary to chronic use (systemic or
inhaled) include diminished exercise capacity and compromised
nutrition.

Summary

Patients who are symptomatic with stable COPD require a variety of
interventions to optimize their life styles and survival. Depending on
their particular circumstances, they may benefit from maximizing airflow,
reducing and clearing secretions, physical rehabilitation, preventing
infections, and assuring adequate oxygenation. The various elements can be
introduced over time with careful observation to determine which
intervention has favorable (or unfavorable) effects. Awareness of other
disorders that are common among those with COPD will aid in early
recognition, treatment, or prevention. Prompt recognition and effective
management of acute exacerbations of chronic bronchitis are essential.

References

Barnes PJ: Chronic obstructive pulmonary
disease. N Engl J Med 2000;343:269-280. A state of the art review of all
aspects of COPD including conventional and future novel therapies.

Barnes PJ: Theophylline: new perspectives on
an old drug. Am J Respir Crit Care Med 2003;167;813-818. A review on the
mechanisms of action of theophylline. It may promote steroid action in
COPD.

Brus R. Effects of high-dose inhaled
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exposure to beclomethasone triamcinolone, budesonide and fluticasone
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Donohue, JF, van Noord, JA, Bateman, ED, et
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the risk of AECB.

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