MEDICAL CARE IN PULMONARY REHABILITATION
MEDICAL CARE
The goal of treatment is to preserve optimal lung function, thereby preventing symptoms and recurrence of exacerbations and, as a result, improving function in daily living, as well as QOL. Once the diagnosis of chronic obstructive pulmonary disease (COPD) has been established, educate the patient about the disease. Encourage the patient to actively participate in therapy.
Smoking cessation continues to be the most important therapeutic intervention. Many patients with COPD have a history of smoking, and many currently smoke. A smoking cessation plan is an essential part of a comprehensive management strategy.
The success rates of smoking cessation plans are low because of the addictive potential of nicotine, the conditioned response of individuals who smoke to smoking-associated stimuli, forceful promotional campaigns by the tobacco industry, poor education, and psychological problems faced by patients who attempt to quit smoking, including depression. Any smoking cessation program must involve multiple interventions.
In patients with stable disease, oral and inhaled medications are used to reduce dyspnea and improve exercise tolerance. Most of the medications employed are directed at 4 potentially reversible causes of airflow limitation in a disease state with largely fixed obstruction.
The following factors may be present:
Bronchial smooth muscle contraction
Bronchial mucosal congestion and edema
Airway inflammation
Increased airway secretion
SMOKING CESSATION AND PHYSICAL INTERVENTION
The transition from smoking to abstention from smoking occurs in the following 5 stages:
1) Precontemplation
2) Contemplation
3) Preparation
4) Action
5) Maintenance
Smoking intervention programs include self-help, group, physician-delivered, workplace, and community programs. Setting a quit date may be helpful. Physicians and other health care providers should participate in setting the target date and should follow up with respect to maintenance.
Successful cessation programs usually employ such tools as patient education, establishment of a quit date, follow-up support, relapse prevention, advice for healthy lifestyle changes, social support systems, and adjuncts to treatment (eg, pharmacologic agents).
SMOKING CESSATION AND PHARMACOLOGIC INTERVENTION
Nicotine replacement therapy
Supervised use of pharmacologic agents is an important adjunct to self-help and group smoking cessation programs.
Nicotine is the ingredient in cigarettes that is primarily responsible for addiction. Withdrawal from nicotine may cause adverse effects, including anxiety, irritability, difficulty concentrating, anger, fatigue, drowsiness, depression, and sleep disruption. These effects usually occur during the first several weeks of any attempt at smoking cessation.
Nicotine replacement therapies after smoking cessation reduce withdrawal symptoms. A smoker who requires his/her first cigarette within 30 minutes of waking up is most likely to be highly addicted and could benefit from nicotine replacement therapy.
Several nicotine replacement therapies are available. Nicotine polacrilex is a chewing gum with better quit rates than counseling alone. Transdermal nicotine patches are available readily for replacement therapy. Long-term success rates range from 22-42%, compared to 2-25% with a placebo. These agents are well tolerated, and the adverse effects are limited to localized skin reaction.
Nicotine replacement therapy patches are sold under the trade names NicoDerm, Nicotrol, and Habitrol. The usual drug-dosing schedule is the same for all 3 brands. Individuals who smoke more than 1 pack per day initially need a 21-mg patch, followed by 14-mg and 7-mg patches.
Nicotine replacement therapy chewing pieces are marketed in 2 strengths (ie, 2 mg, 4 mg). An individual who smokes 1 pack per day should use 4-mg pieces. The 2-mg pieces are to be used by individuals who smoke less than 1 pack per day. Instruct patients to chew hourly, as well as at the time of their initial cravings for 2 weeks. Gradually reduce the amount chewed over the next 3 months.
The use of an antidepressant medication (eg, bupropion) also is effective for smoking cessation. A study recorded sustained cessation at 1 year for 23% of smokers using bupropion (which enhances central nervous system nonadrenergic function), as opposed to sustained cessation for 12% of smokers using a placebo. Bupropion also is effective in patients who have not succeeded with nicotine replacement therapy.
The most recent drug to receive approval for smoking cessation is varenicline (Chantix). It is a partial agonist selective for alpha 4 beta 2 nicotinic acetylcholine receptors. Action is thought to result from activity at a nicotinic receptor subtype, where its binding produces agonist activity while simultaneously preventing nicotine binding. Agonistic activity is significantly lower than that of nicotine. Gradually titrate the dose upward within 1 wk before the quit date to 1 mg twice a day orally after meals. Decrease the dose with severe renal impairment or end-stage renal disease.
Serious neuropsychiatric symptoms have been reported during postmarketing surveillance and may include changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide; these adverse events have been exhibited in patients without preexisting psychiatric illness, and patients with preexisting psychiatric illness have reported worsening symptoms during varenicline treatment.
Anti-inflammatory agents (inhaled steroids)
The minority of patients who respond to oral corticosteroids could be maintained on long-term inhaled steroids.
Despite a lack of conclusive evidence to support the role of inhaled corticosteroids in the management of COPD, the use of these agents is widespread. Researchers have completed 3 large, placebo-controlled trials investigating the use of these agents in severe, mild, and very mild disease. Based on the rate of decline in the forced expiratory volume in 1 second (FEV1), results from these 3 trials suggest that inhaled corticosteroids do not slow the decline in lung function but do decrease the frequency of exacerbations and improve disease-specific and health-related QOL.
Inhaled corticosteroids have fewer adverse effects than do oral agents. Although effective, these agents improve expiratory flows less than oral preparations do, even at high doses. These agents may be beneficial in slowing the rate of progression in a subset of COPD patients who demonstrate rapid decline in pulmonary function.
Bronchodilators
Inhaled beta 2–agonist bronchodilators activate specific B2-adrenergic receptors on the surface of smooth muscle cells; this raises levels of intracellular cyclic adenosine monophosphate (AMP) and increases smooth muscle relaxation. Patients, even those who have no measurable increase in expiratory flow, benefit from treatment using beta 2 agonists.
Methylxanthines have decreased in popularity because of their narrow therapeutic range and frequent toxicity. Their mechanism of action may involve increased intracellular calcium transport, adenosine antagonism, and inhibition of prostaglandin E2. Additionally, methylxanthines may improve diaphragm muscle contractility.
Beta-2 agonists
Beta-2 agonists produce less bronchodilation in patients with COPD than they do in patients with asthma. Furthermore, spirometric changes may be insignificant, despite symptomatic benefit. Patients primarily use beta-2 agonists for relief of symptoms of COPD. Inhaled beta-2 agonists are the initial treatment of choice for acute exacerbations of COPD.
In stable patients, beta-2 agonists have an additive effect when used with an anticholinergic agent (eg, ipratropium bromide). Although oral preparations of beta-2 agonists are available, the preferred route of administration is inhalation. Use a spacer, if indicated, to improve aerosol delivery and reduce adverse effects.
Long-acting bronchodilators
Two long-acting beta-2 agonists (ie, formoterol, salmeterol) are available.
They improve symptoms and morning peak flows and may be useful when bronchodilators are used frequently.
More studies should establish the best role for these agents.
Anticholinergic agents
Treatment with aerosolized anticholinergic agents (eg, ipratropium bromide) may be more effective than a beta-2 agonist would be in patients with COPD. Ipratropium bromide has bronchodilatory activity with minimum adverse effects and is administered by a metered dose inhaler.
Studies in patients with stable COPD have shown that ipratropium bromide has equivalent or superior activity when compared with a beta-2 agonist. In combination with a beta-2 agonist, there is an additional 20-40% bronchodilation. This medication has slower onset and a longer duration than a beta-2 agonist and is less suitable for use as needed.
Inhaled anticholinergic bronchodilators do not influence the long-term decline of FEV1. Initiate regular therapy with an ipratropium at 2-4 puffs 4 times a day and add a beta-2 agonist as needed.
Anticholinergic drugs compete with acetylcholine for postganglionic muscarinic receptors; these agents thereby inhibit cholinergically mediated bronchomotor tone, resulting in bronchodilation. They block vagally mediated reflex arcs that cause bronchoconstriction. The onset of action is slower (eg, 30-60 min).
Long-acting bronchodilators
Theophylline improves respiratory muscle function, stimulates the respiratory center, and promotes bronchodilation, in addition to demonstrating anti-inflammatory effects.
Adding theophylline to the combination of bronchodilators can be of further benefit to patients with stable COPD. The response to theophylline therapy may vary among patients with severe COPD.
Patients metabolize theophylline primarily with the hepatic enzyme system, in a process that is affected by age, as well as by heart and liver abnormalities. Because of theophylline's potential for toxicity, monitor serum levels of theophylline during therapy. Adverse effects include anxiety, tremors, insomnia, nausea, cardiac arrhythmia, and seizures.
Oral steroids
The use of corticosteroids requires a careful evaluation for individual patients who, despite being on adequate bronchodilator therapy, develop an exacerbation or fail to improve sufficiently. Most studies suggest that 10-20% of patients with COPD improve if given chronic oral steroid therapy. Carefully document the effectiveness of such therapy (>20% improvement in FEV1) before giving a patient prolonged daily or alternate-day treatment.
Researchers found a positive correlation between bronchial eosinophilia and bronchodilator response in patients who had mild to moderate airflow obstruction. Outpatients have successfully used oral steroids to treat acute exacerbations; however, after stabilization, gradually wean the patient off oral corticosteroids because of the potential adverse effects of these agents.
In a meta-analysis of 16 controlled trials in patients with stable COPD, researchers found that approximately 10% of these patients responded to these drugs. Carefully identify recipients. An increase in FEV1 of more than 20% has been used as a surrogate marker for steroid response. In acute exacerbation of COPD, use steroids routinely to improve symptoms and lung function.
Antibiotics
In patients with COPD, chronic infection or colonization of the lower airways is common from Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. The goal of antibiotic therapy in COPD is not to eliminate the organisms, but to treat acute exacerbations.
Exacerbations are indicated by increased sputum purulence and volume, as well as by the development of dyspnea along with other features, including fever, leukocytosis, or infiltrate on a chest radiograph.
The first-line treatment choices include amoxicillin, cefaclor, and trimethoprim/sulfamethoxazole. Second-line antibiotic regimens are the more expensive antibiotics, including azithromycin, clarithromycin, and fluoroquinolones.
The use of antibiotics in patients with COPD is supported by the results of a meta-analysis showing that patients who receive oral antibiotic therapy have a small, but clinically significant, improvement in peak expiratory flow rate and a rapid resolution of symptoms.
Patients who benefit most are those whose exacerbations are characterized by increases in at least 2 of the Winnipeg criteria (ie, dyspnea, sputum production, sputum purulence).
Mucolytic agents
Mucolytic agents reduce sputum viscosity and improve secretion clearance. Viscous lung secretions in patients with COPD consist of mucus-derived glycoproteins and leukocyte-derived deoxyribonucleic acid (DNA).
The oral agent N -acetylcysteine has antioxidant and mucokinetic properties; it is used to treat patients with COPD.
Oxygen therapy
COPD commonly is associated with progressive hypoxemia. Oxygen reduces mortality rates in patients with advanced COPD because of the favorable effects on pulmonary hemodynamics.
Two landmark trials (ie, The British Medical Research Council [MRC study] and the National Heart, Lung, and Blood Institute's Nocturnal Oxygen Therapy Trial [NOTT]) showed that long-term oxygen therapy improves survival 2-fold or more in hypoxemic patients with COPD. Hypoxemia is defined as PaO2 of less than 55 mm Hg or as oxygen saturation of less than 90%. Oxygen was used from 15-19 hours per day.
Specialists therefore recommend long-term oxygen therapy for patients with a PaO2 of less than 55 mm Hg and a PaO2 of less than 59 mm Hg with evidence of polycythemia or cor pulmonale. Reevaluate these patients 1-3 months after initiating therapy, because some patients may not require long-term oxygen.
The condition of many patients with COPD who are not hypoxemic at rest worsens during exertion. Even though studies designed to determine the long-term benefit of oxygen solely for exercise have not been conducted yet, home supplemental oxygen commonly is prescribed for these patients.
Oxygen supplementation during exercise can reduce dyspnea, improve exercise tolerance, and prevent increases in pulmonary artery pressure.
Oxygen therapy generally is safe. Oxygen toxicity from high-inspired concentrations (more than 60%) is well recognized. Little is known about the long-term effects of low-flow oxygen.
The increased survival and QOL benefits of long-term oxygen therapy outweigh the possible risks. PaCO2 retention from depression of hypoxic drive has been overemphasized. PaCO2 retention is more likely a consequence of ventilation/perfusion mismatching rather than of respiratory center depression. Although this complication is not common, it is best avoided by titration of oxygen delivery in order to maintain PaO2 at 60-65 mm Hg.
The major physical hazards of oxygen therapy are fires and explosions. Patients, family members, and other caregivers must be warned not to smoke. Overall, however, major accidents are rare and can be avoided by good patient and family training.
OXYGEN SYSTEMS
The continuous flow nasal cannula is the standard means of oxygen delivery for the stable hypoxemic patient. This means of oxygen delivery is simple, reliable, and generally well tolerated. Each liter of oxygen flow adds 3-4% to the fractional inspired oxygen (FIO2). Nasal oxygen delivery is also beneficial for most mouth-breathing patients.
Oxygen-conserving devices function by delivering all of the oxygen during early inhalation. These devices improve the portability of oxygen therapy and reduce overall costs. Three distinct oxygen-conserving devices exist (ie, reservoir cannulas, demand pulse delivery devices, transtracheal oxygen delivery systems).
Transtracheal oxygen delivery involves the insertion of a catheter percutaneously between the second and third tracheal interspaces. Transtracheal oxygen delivery is invasive and requires special training by the physician, the patient, and the caregiver. The procedure has risks as well as medical benefits, but it also has limited application. Humidification generally is not beneficial when the patient receives oxygen by nasal cannula at flows of less than 5 L/min.
PREVENTATIVE THERAPY
Influenza vaccine
Influenza is an acute respiratory illness caused by influenza A or B viruses that occur in outbreaks and in epidemics worldwide almost every year. Influenza viruses that affect humans are classified into 2 antigenic subtypes: hemagglutinin (H) and neuraminidase (N). Three subtypes of hemagglutinin (H1, H2, H3) and 2 subtypes of neuraminidase (N1, N2) are recognized.
The influenza vaccines are inactivated preparations of the virus or the split products. Several studies have examined the efficacy of influenza vaccine in different populations. A meta-analysis of 20 cohort studies in elderly persons had a pooled estimate of vaccine efficacy at 56%. These studies have found that in patients with chronic lung disease, administration of influenza vaccine substantially decreases mortality, hospitalization for influenza and pneumonia, exacerbation of chronic lung disease, and physician visits for respiratory complaints.
Present recommendations for the administration of influenza vaccines include the provision of these vaccines to the following populations:
Persons aged 65 years or older
Residents of nursing homes and chronic care facilities
Adults and children who have chronic disorders of the pulmonary or cardiovascular systems
Adults and children who required regular medical follow-up or hospitalization during the previous year because of chronic diseases such as diabetes mellitus, renal dysfunction, or immune suppression
The adverse effects of influenza vaccine are seen in fewer than 5% of cases and include low-grade fever and mild systemic symptoms. Vaccine is not recommended for people who are allergic to egg products. A small risk of Guillain-Barré syndrome (approximately 1 case per million vaccine recipients) may exist.
Pharmacologic agents such as zanamivir (Relenza), an inhaled compound, and oseltamivir (Tamiflu), an orally ingested compound, have been demonstrated to be effective in the prophylaxis and therapy of influenza A and B infections. Both of these medications, if taken within 36 hours of the infection, have been shown to decrease the duration and severity of influenza symptoms.
Oseltamivir resistance emerged in the United States during the 2008-2009 influenza season. Revised interim recommendations for antiviral treatment and prophylaxis of influenza were issued by the US Centers for Disease Control and Prevention (CDC). Preliminary data from a limited number of states indicated a high prevalence of influenza A (H1N1) virus strains that were resistant to oseltamivir. Because of this, zanamivir has been recommended as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure is suspected. A second-line alternative is a combination of oseltamivir and rimantadine rather than oseltamivir alone. Local influenza surveillance data and laboratory testing can assist the physician with regard to the choice of antiviral agent.
Influenza A viruses (including subtypes H1N1 and H3N2) and influenza B viruses currently circulate worldwide, but the prevalence of each can vary among and within communities over the course of an influenza season. In the United States, 4 prescription antiviral medications (oseltamivir, zanamivir, amantadine, rimantadine) have been approved for the treatment and chemoprophylaxis of influenza. Since January 2006, the neuraminidase inhibitors (oseltamivir, zanamivir) have been the only recommended influenza antiviral drugs because of widespread resistance to the adamantanes (amantadine, rimantadine) among influenza A (H3N2) virus strains. The neuraminidase inhibitors have activity against influenza A and B viruses, while the adamantanes have activity against only influenza A viruses.
In 2007-2008, a significant increase in the prevalence of oseltamivir resistance was reported among influenza A (H1N1) viruses worldwide. During the 2007-2008 influenza season, 10.9% of H1N1 viruses tested in the United States were resistant to oseltamivir.
Pneumococcal vaccine
Ninety different capsular types of pneumococcus are known, making it impossible to manufacture a comprehensive vaccine. Thus, vaccines representing a subgroup of highly prevalent types have been formulated. The currently available pneumococcal vaccines include 23 purified capsular polysaccharide antigens, representing 85-90% of the types that cause invasive disease in the United States.
The Centers for Disease Control and Prevention have demonstrated a 57% overall protective effectiveness of this vaccine against invasive disease; however, many trials have shown no efficacy against pneumonia or other invasive diseases in vaccinated populations. The vaccine presently is recommended for patients at risk of pneumococcal infection. These at-risk patients include the following groups:
Elderly individuals (aged 65 years or more) who have chronic cardiovascular conditions
Patients with chronic pulmonary disease or diabetes mellitus
Persons with alcoholism
Patients with chronic liver disease or who are living in chronic care facilities
Immunocompromised patients receiving immunosuppressive therapy or chemotherapy
Patients who have asplenia or who recently have undergone organ transplantation
The vaccine is administered intramuscularly as a single 0.5 mL dose. In rare cases, a second dose may be administered 5 years later. Mild, local adverse effects may develop; rare systemic reactions, such as fever and myalgias, also have been seen.