Medical Care: The goal of treatment is to improve the activities of daily living and the quality of life by preventing symptoms and recurrence of exacerbations and by preserving optimal lung function. Once the diagnosis of COPD is established, the patient should be educated about the disease and should be encouraged to participate actively in therapy. Smoking cessation is the most important therapeutic intervention.
Smoking cessation
Many patients with COPD have a history of smoking and are current smokers. A smoking cessation plan is an essential part of a comprehensive treatment plan. The success rates for smoking cessation are low because of the addictive potential of nicotine, the conditioned response to smoking-associated stimuli, psychosocial problems (eg, depression, poor education), and forceful promotional campaigns by the tobacco industry. The process of smoking cessation must involve multiple interventions.
Smoking cessation, physician intervention
The transition from smoking to nonsmoking status involves 5 stages. These stages are (1) precontemplation, (2) contemplation, (3) preparation, (4) action, and (5) maintenance. Smoking intervention programs include self-help, group, physician-delivered, workplace, and community programs. Setting a target date to quit may be helpful. Physicians and other healthcare providers should participate in setting the target date and should follow up with respect to maintenance. Successful cessation programs usually employ the following resources and tools:
" Patient education
" A target date to quit
" Follow-up support
" Relapse prevention
" Advice for healthy lifestyle changes
" Social support systems
" Adjuncts to treatment (ie, pharmacological agents)
Smoking cessation, pharmacologic intervention
Supervised use of pharmacologic agents is an important adjunct to self-help and group smoking cessation programs. Nicotine is the ingredient in cigarettes primarily responsible for the addiction of smoking. Withdrawal from nicotine may cause unpleasant adverse effects (eg, anxiety, irritability, difficulty concentrating, anger, fatigue, drowsiness, depression, sleep disruption). These effects usually occur during the first weeks after quitting smoking. Nicotine replacement therapies after smoking cessation reduce withdrawal symptoms. A person who smokes and who requires the first cigarette within 30 minutes of waking, is likely to be highly addicted and would benefit from nicotine replacement therapy. Several nicotine replacement therapies are available.
Nicotine polacrilex is a chewing gum and produces better quit rates than counseling alone. Transdermal nicotine patches are available readily for replacement therapy. Long-term success rates have been 22-42%, compared to 2-25% with placebos. These agents are well tolerated, and the adverse effects are limited to localized skin reactions. The use of an antidepressant medication, Zyban (150 mg bid) has been shown to be effective for smoking cessation and may be used in combination with nicotine replacement therapy.
The most recent drug to receive approval for smoking cessation is varenicline (Chantix). It is a partial agonist selective for alpha4, beta2 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 nicotine.
Alpha1-antitrypsin deficiency
The treatment strategies for AAT deficiency involve reducing the neutrophil elastase burden, primarily by smoking cessation, and augmenting the levels of AAT. Augmentation strategies include the following:
" Available augmentation strategies include pharmacologic attempts to increase endogenous production of AAT by the liver (eg, danazol, tamoxifen) or administration of purified AAT by periodic IV infusion or by inhalation.
" Gene therapy represents another augmentation strategy, but this approach has been confined to animal models.
" Tamoxifen can increase endogenous production of AAT to a limited extent, so this may be beneficial in persons with the PISZ phenotype. IV augmentation therapy is the only available approach that can increase serum levels above 11 mmol/L, the protective threshold. Studies show that the infusions can maintain levels of more than 11 mmol/L, and replacement is administered weekly (60 mg/kg), biweekly (120 mg/kg), or monthly (250 mg/kg). The ability of IV AAT augmentation to alter the clinical course of patients with AAT deficiency has not been demonstrated. Uncontrolled observations of patients suggest that the FEV1 may fall at a slow rate in patients who receive AAT replacement.
Emphysema associated with hypocomplementemic vasculitis urticaria syndrome
Therapy for the emphysema associated with HVUS generally includes bronchodilators and corticosteroids, which have been reported to relieve bronchospasm. Cytotoxic therapy (eg, cyclophosphamide, azathioprine) has been used with variable success, and administration of dapsone has resulted in improvement in a small number of patients.
Pharmacologic therapy of emphysema
Bronchodilators
In COPD, beta2 agonists produce less bronchodilatation compared to asthma. Furthermore, spirometric changes may be insignificant despite symptomatic benefits.
Beta2 agonists are used primarily for relief of symptoms of COPD. Inhaled beta2 agonists are the initial treatment of choice for acute exacerbations of COPD. In stable patients, beta2 agonists have an additive effect when used with an anticholinergic agent (eg, ipratropium bromide). Although oral preparations of beta2 agonists are available, the preferred route of administration is inhalation. A spacer should be used, if indicated, to improve aerosol delivery and reduce adverse effects.
Treatment with aerosolized anticholinergic agents (eg, ipratropium bromide) may be more effective than beta2 agonists in patients with COPD. Ipratropium bromide has bronchodilatory activity with minimum adverse effects and is administered via metered-dose inhaler. Studies in patients with stable COPD have shown that ipratropium bromide has equivalent or superior activity when compared with a beta2 agonist. In combination with a beta2 agonist, an additional 20-40% bronchodilation occurs. This medication has slower onset and longer duration than beta2 agonists, and it is less suitable for use as needed. Appropriate dosage is 2-4 puffs 3-4 times a day, but some patients require a larger dose (eg, 4-6 puffs 4-6 times per d). Therefore, regular therapy with ipratropium at 2-4 puffs 4 times a day is initiated, and a beta2 agonist is added as needed. Inhaled anticholinergic bronchodilators do not influence the long-term decline of FEV1.
Long-acting bronchodilators (eg, theophylline) improve respiratory muscle function and stimulate the respiratory center in addition to bronchodilatation. Anti-inflammatory effects also may occur. Adding theophylline to the combination of bronchodilators can result in further benefit in patients with stable COPD. The response to theophylline therapy also may vary among patients with severe COPD. Theophylline is metabolized primarily by the hepatic enzyme system and is affected by age, heart abnormalities, and liver abnormalities. Serum levels of theophylline should be monitored during therapy because of the drug's potential for toxicity. Adverse effects include anxiety, tremors, insomnia, nausea, cardiac arrhythmia, and seizures.
Anti-inflammatory therapy
The use of corticosteroids requires a careful evaluation in patients on adequate bronchodilator therapy who do not improve sufficiently or who develop an exacerbation. Most studies suggest that 20-30% of patients with COPD improve if administered long-term oral steroid therapy. Carefully document the effectiveness of such therapy (>20% improvement in FEV1) before administering prolonged daily or alternate-day treatment.
A positive correlation was found between bronchial eosinophilia and bronchodilator response in patients who had mild-to-moderate airflow obstruction.
Oral steroids have been used with success to treat outpatients with acute exacerbations; however, after stabilization, oral corticosteroids should be weaned gradually because of the potential for adverse effects. A minority of patients who respond to oral corticosteroids can 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. Three large placebo-controlled trials investigating the use of these agents in severe, mild, and very mild disease have been completed. Based on the rate of decline in FEV1, results from these 3 trials suggest that inhaled corticosteroids do not slow the decline in lung function but decrease the frequency of exacerbations and improve disease-specific, health-related quality of life. Furthermore, because 2 of these 3 studies included patients who smoked during the study; these results may not truly reflect the efficacy of inhaledcorticosteroids in favorably altering the natural history of emphysema.
Phosphodiesterase IV inhibitors
Cilomilast and roflumilast are systemically available, second-generation, selective phosphodiesterase-4 inhibitors. They cause a reduction of the inflammatory process (macrophages and CD8+ lymphocytes) in patients with COPD. Cilomilast is completely absorbed following oral administration and its elimination half-life is approximately 6.5 hours. A dose of 15 mg twice daily has been found to be clinically effective. Nausea, presumably of central origin, is the principal adverse reaction. The preliminary clinical studies suggest a favorable clinical effect in COPD.
Antibiotics
In patients with COPD, chronic infection or colonization of the lower airways is common with S pneumoniae, H influenzae, and Moraxella catarrhalis. The goal of antibiotic therapy in COPD is not to eliminate organisms, but to treat acute exacerbations. The exacerbations are indicated by increased sputum purulence and volume and development of dyspnea with other features (eg, fever, leukocytosis, infiltrate on chest radiograph).
The first-line treatment choices include amoxicillin, cefaclor, and trimethoprim/sulfamethoxazole. Second-line antibiotic regimens include antibiotics that are more expensive (eg, azithromycin, clarithromycin, fluoroquinolones).
The use of antibiotics in patients with COPD is supported by the results of a meta-analysis showing that patients who received oral antibiotic therapy had a small but clinically significant improvement in peak expiratory flow rate and a rapid resolution of symptoms. The patients who benefited most from antibiotic therapy were those with exacerbations that were characterized by at least 2 of the following: increases in dyspnea, sputum production, and sputum purulence (ie, Winnipeg criteria).
Mucolytic agents
These agents reduce sputum viscosity and improve secretion clearance. Viscous lung secretions in patients with COPD consist of mucus-derived glycoproteins and leukocyte-derived DNA. The use of mucolytic agents in clinical practice currently is not recommended because of the lack of evidence for their benefit.
" Pharmacologic treatment of COPD is targeted to symptom reduction. With the exception of smoking cessation and continuous long-term oxygen treatment, drug therapy does not modify the natural history of COPD. Recent long-term pharmacologic studies in COPD have evaluated prevention of exacerbations and/or hospitalization as the primary outcome. Tiotropium, a long-acting anticholinergic agent, reduces the frequency of exacerbations and the use of health care resources in patients with moderate-to-severe COPD. Inhaled steroids may also reduce the frequency and severity of exacerbations in patients with severe COPD. Whether the combination of inhaled steroids and long-acting bronchodilators has additive effects on lung function and/or exacerbations is still unclear.
Surgical Care: Over the past 50-75 years, various surgical approaches to improve symptoms and restore function in patients with emphysema have been described. Only giant bullectomy and, possibly, lung volume reduction surgery (LVRS) are useful.
" Bullectomy for giant bullae
o Removal of giant bullae has been a standard approach in selected patients for many years.
o The bullae in patients with emphysema generally range from 1-4 cm in diameter; however, on occasion, bullae known as giant bullae can occupy more than one third of the hemithorax. Giant bullae may compress adjacent lung tissue, reducing the blood flow and ventilation to the relatively normal lung. Removal of these bullae may result in expansion of compressed lungs and improvement of function.
o Patients who are symptomatic and have an FEV1 of less than 50% of the predicted value have a better outcome after bullectomy. Bullectomy is performed through either midline sternotomy or a lateral incision, with or without video-assisted thoracoscopy. Postoperative leaks are the major potential complications.
o Giant bullectomy can produce subjective and objective improvement in selected patients, ie, those who have bullae that occupy at least 30%-and preferably 50%-of the hemithorax that compress adjacent lung, with an FEV1 of less than 50% of predicted and relatively preserved lung function otherwise.
" Lung volume reduction surgery
o Nearly 40 years ago, Brantigan et al first reported resectional surgery for diffuse emphysema in 33 patients. They resected 20-30% of the portion of each lung that appeared most diseased. The hypothesis suggested that removal of a portion of the emphysematous lung increased the radial traction on the airways in the remaining lung, improving expiratory airflow and mechanical function of the respiratory system, thereby reducing symptoms.
o LVRS has gained considerable momentum recently, after a marked improvement in the FEV1 (ie, +82%) and forced vital capacity ([FVC] +27%), improvement in 6-minute walk distance, and improvement in quality of life indices were observed in one randomized controlled trial. Functional and physiologic improvements can be detected following the procedure, including improvement in subjective dyspnea, exercise tolerance, and quality of life. Improvement generally is observed within the first 6 months after surgery and continues for as long as 3 years.
o In one study, at 4 years after LVRS, improved FEV1 over baseline and decreased oxygen dependence were observed in 27% and 22% of patients, respectively. Although palliation of symptoms of end-stage emphysema is an important benefit of the procedure, improvement in patient survival would be a major finding to support wider application of lung reduction surgery. In the United States and Canada, large prospective studies to evaluate the effectiveness of LVRS are being undertaken.
o The indications and patient selection criteria for LVRS have not been defined rigorously. Generally, candidates for LVRS have symptoms secondary to severe emphysema, marked hyperinflation (defined as elevated respiratory volume [RV]-to-total lung capacity [TLC] ratio), and evidence of heterogeneous emphysema on a CT scan. Patients who are hypercapnic or have pulmonary hypertension or other cardiac risk factors are excluded.
o The surgical approach uses a midline sternotomy with stapling of the resected lung margins. Resection of 20-30% of each lung from the upper zones generally is performed.
o The LVRS procedure has a mortality rate ranging from 0-18%. Several complications, including pneumonia and prolonged air leaks, have been observed.
o Criteria for LVRS candidates are still being evaluated in clinical trials. Until further information is available, the following criteria may provide some guidance. Inclusion criteria are as follows: severe emphysema with hyperinflation, FEV1 10-40% of predicted, residual volume greater than 180% of predicted, and TLC over 110% of predicted.
o Relative contraindications and/or exclusion criteria to the procedure are numerous and include the following:
" General - Age older than 75 (80) years, obesity, current smoking, bronchiectasis, malignancy, active ischemia or severe heart disease, prior median sternotomy or lung resection, significant pleural abnormalities, 6-minute walk less than 250 feet (after rehabilitation), disease likely to limit survival to less than 5 years, mental incompetency or active psychiatric illness, and associated interstitial lung disease (these patients are directed to transplant)
" Pulmonary - A PaCO2 greater than 50 mm Hg, DLCO less than 25% of predicted, patient requiring either invasive or noninvasive ventilatory support, supplemental oxygen requirement over 6 L/min (for arterial oxygen saturation [SaO2] >87%), more than 1 cup of sputum production per day, or pulmonary arterial hypertension
" Lung transplantation
o Lung transplantation is a relatively new therapy for advanced lung disease.
o Patients with COPD make up the largest single category of patients who undergo lung transplantation. The timing of transplant is difficult; the patients selected to receive transplants should have a life expectancy of 2 years or less.
o With lung transplantation, the profound dyspnea and limited lifestyle is exchanged for improved quality of life at the risk of worsening survival.
Diet: Inadequate nutritional status associated with low body weight in patients with COPD is associated with impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity, and higher mortality rates. Nutritional support is an important part of their comprehensive care.
DRUG TREATMENT :
1. BRONCHODILATORS :
- ALBUTEROL
- METAPROTERENOL
- IPRATROPIUM
- THEOPHYLLINE
- SALMETEROL
- FORMOTEROL
2. CORTICOSTEROIDS :
- FLUTICASONE
- BUDESONIDE
- PREDNISONE
3. SMOKING CESSATION THERAPY :
- NICOTINE TRANSDERMAL PATCH
- BUPROPION
4. ANTIBIOTICS :