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Chronic%20obstructive%20pulmonary%20disease Treatment
Principles of Therapy
- Goals of therapy
- Prevention and control of symptoms
- Reduction of the frequency and severity of exacerbations
- Improvement of health status
- Improvement of exercise tolerance
- Drug therapy for COPD is determined by individualized assessment of symptoms and exacerbation risk
- Based on studies, the existing pharmacotherapy for COPD do not modify the long-term decline in lung function; however, limited evidence suggests that regular treatment with long-acting beta2-agonists, inhaled corticosteroid and its combination can decrease the rate of decline in lung function
Initial Treatment
- The following table summarizes treatment recommendations by patient category of COPD:
|
Patient Category |
Recommended Initial Treatment* |
|
A |
Short-acting anticholinergic or short-acting beta2-agonist monotherapy |
|
B |
Long-acting anticholinergic or long-acting beta2-agonist monotherapy |
|
C |
Long-acting anticholinergic monotherapy |
|
D |
Long-acting anticholinergic or Long-acting anticholinergic+ long-acting beta2-agonist or Inhaled corticosteroid + long-acting beta2-agonist |
*Adapted from: Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2020 report.
Follow-up Treatment
- Should be based on the predominant symptom, either for dyspnea or persistent exacerbations, irrespective of the patient's GOLD grouping
- Inhaler technique and treatment adherence should be investigated in every follow-up
- Patients may be considered for an additional long-acting bronchodilator if breathlessness or exercise limitation is still present despite inhaled bronchodilator monotherapy
- Dual combination therapy with 2 long-acting inhaled bronchodilators or long-acting beta2-agonist plus an inhaled corticosteroid should be considered in patients previously given short-acting bronchodilators or long-acting inhaled bronchodilator monotherapy who show disease progression
- Triple combination therapy should be offered to patients with disease progression despite treatment with a bronchodilator and corticosteroid combination therapy
- Roflumilast or Azithromycin may be given to patients suffering from persistent exacerbations previously given bronchodilator combination therapy and with eosinophil count of <100 cells/μL
- Roflumilast should be considered in patients with FEV1 <50% predicted and chronic bronchitis
- Azithromycin may be added for patients who are ex-smokers
|
|
|
| Initial Therapy | Follow-up Therapy |
| Long-acting anticholinergic or long-acting beta2-agonist | Long-acting anticholinergic + long-acting beta2-agonist |
| Long-acting anticholinergic + long-acting beta2-agonist |
|
| Long-acting beta2-agonist + inhaled corticosteroid |
|
1For patients with adverse effects (eg pneumonia) or unresponsive to inhaled corticosteroids, or if initial indication is unclear
Recommended Follow-up Regimens After Initial Therapy Based on Predominant Symptom: Exacerbations or Both Dyspnea and Exacerbations
|
|
|
| Initial Therapy | Follow-up Therapy |
| Long-acting anticholinergic or long-acting beta2-agonist |
|
| Any dual-agent combination therapy |
|
| Triple therapy |
|
1Consider in patients with blood eosinophil count ≥300 cells/microliter or with ≥100 cells/microliter and ≥2 moderate exacerbations per year or 1 severe exacerbation requiring hospitalization
2For patients with adverse effects (eg pneumonia) or unresponsive to inhaled corticosteroids, or if initial indication is unclear
Pharmacotherapy
Bronchodilators
- Classes (listed alphabetically): Anticholinergics, beta2-agonists, methylxanthines
- All bronchodilators increase exercise capacity
- Inhaled bronchodilators are recommended for all symptomatic patients with stable COPD with FEV1 of <60%
- May also be used for symptomatic stable COPD patients with predicted FEV1 of 60-80%
- Inhaled therapy is preferred to oral, because of better efficacy, faster onset and decreased likelihood of adverse effects
- Short-acting bronchodilators are given on a “when required” basis for immediate relief of symptoms and long-acting bronchodilators are administered on a regular basis to prevent or reduce symptoms
- Regular treatment with long-acting bronchodilators is more effective and convenient but can be more expensive
- When possible, therapy should be via the inhaled route but if cost is a barrier, then oral bronchodilators (beta2-agonists) can be considered
- Inhaled bronchodilators are preferred to Theophylline because of the latter’s low bronchodilating effect and high potential for toxicity
- Combination therapy with inhaled long-acting anticholinergics, long-acting beta2-agonists, or corticosteroids are recommended for symptomatic patients with stable COPD & FEV1 of <60% predicted
- Combining drugs with different mechanisms of action may increase bronchodilatation with less side effects compared to simply increasing the dose of a bronchodilator
- Combination therapy with long-acting beta2-agonist and long-acting anticholinergic can decrease exacerbation rates and are significantly with lower cost compared to intranasal corticosteroid/long-acting beta2-agonist combination therapy
- Choice of drugs will depend on the patient’s response and preference, together with drug’s side effects and cost
Anticholinergics
- Eg Long-acting: Aclidinium, Glycopyrronium, Tiotropium, Umeclidinium; Short-acting: Ipratropium, Oxitropium
- Block the effects of acetylcholine on M2 and M3 (short-acting), and M1 and M3 (long-acting) receptors
- Long-acting inhaled anticholinergics are recommended for symptomatic patients with FEV1 of <60% predicted
- Short-acting anticholinergics generally have a longer duration of bronchodilatation than short-acting beta2-agonists
- Based on a large, long-term, randomized, controlled study in patients with moderate to very severe COPD, Tiotropium with concurrent respiratory medication other than another inhaled anticholinergic agent, resulted in the following benefits:
- Positive effects on quality of life
- Reduced risk of exacerbations and exacerbation-related hospitalizations
- Reduced respiratory morbidity including respiratory failure and cardiac morbidity
- Have been shown to be very safe at a wide range of doses
- Based on short-term, clinical studies in patients with moderate to severe COPD, combination of short-acting anticholinergic and short-acting beta2-agonist may provide superior bronchodilatation than either medication alone
- Aclidinium and Glycopyrronium have effects on lung function and breathlessness comparable to that of Tiotropium but further studies are needed
Beta2-agonists
- Eg Long-acting: Arformoterol, Formoterol, Indacaterol, Olodaterol, Salmeterol, Tulobuterol, Vilanterol (given as combination therapy); Short-acting: Fenoterol, Levalbuterol, Salbutamol (Albuterol), Terbutaline
- Long-acting inhaled beta2-agonists are recommended for symptomatic patients with FEV1 of <60% predicted
- Relax airway smooth muscle by stimulating beta2-adrenergic receptors
- Salmeterol and Formoterol significantly improves FEV1, lung function, dyspnea, quality of life and exacerbation rate
- Vilanterol, in combination with Umeclidinium or Fluticasone, showed improved lung function and slower decline in FEV1
- Based on several clinical trials, combination of long-acting beta2-agonists (eg Salmeterol) and inhaled corticosteroids (eg Fluticasone) may reduce COPD exacerbation and may improve lung function and quality of life better than when each drug is used alone
- Inhaled beta2-agonists have a faster onset of action and less side effects than oral preparations
Methylxanthines
- Eg Aminophylline, Theophylline
- May act as non-selective inhibitor of phosphodiesterase, but have also been observed to exert a range of non-bronchodilator actions
- Though have modest effect in COPD, inhaled bronchodilators are preferred to Theophylline, owing to the latter’s poor bronchodilating property and potential toxicity
- Combination of a beta2-agonist, an anticholinergic and Theophylline may produce additional improvements in health status and lung function
- All studies that have shown efficacy of Theophylline in COPD made use of slow-release preparations
Corticosteroids
- Eg Inhaled: Beclomethasone, Budesonide, Fluticasone; Systemic: Prednisolone, Methylprednisolone
- Regular treatment with inhaled corticosteroids alone does not change the long-term decline of FEV1
- Regular treatment with inhaled corticosteroids is appropriate in patients with FEV1 <50% predicted or ≥2 exacerbations/year and repeated exacerbations (eg 3 exacerbations in the last 3 years)
- May reduce airway hyper-reactivity in these patients and decrease symptoms of COPD including exacerbations
- Inhaled corticosteroid in combination with 1 or 2 long-acting bronchodilators is recommended in patients with:
- History of hospitalizations for COPD exacerbations despite appropriate maintenance therapy with long-acting bronchodilator
- ≥2 moderate COPD exacerbations per year despite appropriate maintenance therapy with long-acting bronchodilator
- History of, or concomitant asthma
- Blood eosinophil count >300 cells/microliter
- In patients with more advanced COPD and repeated exacerbation, treatment with inhaled corticosteroids can be beneficial
- Dose-response relationships and long-term safety of inhaled corticosteroids in COPD are not known
- On a 3-year period treatment in COPD patients with high prevalence of osteoporosis, therapy with high-dose Fluticasone alone or in combination with Salmeterol was not associated with decreased bone mineral density (BMD) compared with placebo
- Previous long-term trials investigating BMD in COPD patients produced conflicting results
- The use of combination therapy with inhaled corticosteroids and long-acting beta2-agonist is more effective in reducing exacerbations and improving pulmonary function than either medication alone; however, the combination produces a small increased risk of non-fatal pneumonia
- In patients with FEV1 <60%, treatment with long-acting beta2-agonist, inhaled corticosteroids and its combination have been shown to reduce the rate of decline of pulmonary function; addition of the combination to an anticholinergic (eg Tiotropium) appears to provide additional benefits
- Addition of a long-acting anticholinergic to combination therapy of inhaled corticosteroid and long-acting beta2-agonist (triple inhaled therapy) has been shown to improve lung function, symptoms and health status, and reduce exacerbations compared to combination therapy of inhaled corticosteroid and long-acting beta2-agonist, long-acting beta2-agonist and long-acting anticholinergic, or monotherapy with a long-acting anticholinergic
- Long-term use of oral corticosteroids is not recommended
- Short-course trials of oral corticosteroids may not reliably predict which patients will respond to inhaled corticosteroids
Phosphodiesterase-4 Inhibitor
- Eg Roflumilast
- Reduce inflammation through inhibition of the breakdown of intracellular cyclic AMP
- Has no direct bronchodilator effects but has been shown to improve FEV1 in patients treated with Tiotropium or Salmeterol
- Roflumilast has been shown to reduce exacerbations in patients with severe to very severe COPD (FEV1 <50% predicted) with chronic bronchitis treated with oral corticosteroids
- Same effect on exacerbation reduction has been noted when added to long-acting bronchodilators
- Roflumilast can not be administered with Theophylline
- Has more side effects compared to inhaled medications
Other Pharmacologic Agents
Alpha-1 Antitrypsin Augmentation Therapy
- May help halt the development and progression of pulmonary disease in patients with AATD
- Studies demonstrated a reduction in spirometric progression with alpha-1 antitrypsin augmentation therapy in patients with FEV1 35-49% predicted
- Especially recommended for nonsmoking patients or those who stopped smoking with FEV1 35-60% predicted
- Further studies are needed to prove the efficacy versus cost of this treatment
Antibiotics
- Not recommended except for treatment of infectious bacterial exacerbations
- Treatment with macrolides (eg Azithromycin) may be considered for previous smokers with moderate to severe exacerbations despite inhaled bronchodilator therapy
Cough and Cold Preparations
- Eg Ambroxol, Carbocysteine, Erdosteine, N-acetylcysteine
- Antitussives are not recommended because cough has a protective effect in COPD
- Expectorants and mucolytics were seen to have benefits in few patients with viscous mucous, but overall benefits seem to be very small
- May be considered in patients with chronic cough productive of sputum
- Therapy may be continued if there is a decrease in the frequency of cough and sputum production
- N-acetylcysteine may help reduce exacerbations in COPD patients without inhaled corticosteroid treatment
Vaccines
Influenza Vaccine
- May decrease morbidity and mortality rates due to influenza
- Should be given yearly, 1-2 months prior to anticipated peak influenza season, because of new antigens and waning immunity from the previous years
- Associated with reduced risk of all-cause mortality
Pneumococcal Vaccines
- Eg 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23)
- Recommended in COPD patients ≥65 years old and in younger patients with significant comorbidities (eg cardiac disease, chronic pulmonary disease)
- PPSV23 reduces occurrence of community-acquired pneumonia (CAP) in patients <65 years old with FEV1 <40% predicted or comorbidities
- Studies showed that PCV13 exhibited significant efficacy for both CAP and vaccine-type invasive pneumococcal disease in adults ≥65 years old with efficacy lasting for at least 4 years
- Possesses comparable or even greater efficacy when compared to the immunogenicity of PPSV23
- Generally given only once, but revaccination may be considered in 5-10 years
Inhalation Devices
- Effective drug delivery and training in inhaler technique should be emphasized and re-checked as necessary
- Choice of device depends on price, availability, the prescribing doctor, and the skills and ability of the patient
- Metered dose inhaler (MDI)
- COPD patients may have poorer coordination and experience more difficulty with MDI use
- Use of spacers with the MDI may be advised for patients who find it hard to master MDI inhaler technique
- Dry powder inhaler (DPI)
- Breath-activated and may therefore require less hand-and-mouth coordination
- May be more convenient and may provide improved deposition of the drug
- Nebulizer
- Not recommended for routine use because of greater cost of treatment
- Assessment of inhaler technique should be done prior to modifying current therapy
ACUTE EXACERBATION OF COPD
Bronchodilators
- Long-acting selective beta2-agonist bronchodilators include Arformoterol, Bambuterol, Formoterol, Indacaterol,Olodaterol, Salmeterol and Tulobuterol
- Short-acting selective beta2-agonist bronchodilators include Clenbuterol, Fenoterol, Hexoprenaline,Levalbuterol, Orciprenaline, Procaterol, Salbutamol (Albuterol), Terbutaline and Trimetoquinol
- Long-acting anticholinergic bronchodilators: Aclidinium, Glycopyrronium, Tiotropium, Umeclidinium
- Short-acting anticholinergic bronchodilators: Ipratropium, Oxitropium
Hospital Management
- Short-acting inhaled beta2-agonists, with or without short-acting anticholinergics are typically preferred for treating acute COPD exacerbations
- An anticholinergic may be added if the patient does not respond immediately to short-acting inhaled beta2-agonists
- Long-acting bronchodilators can be used with or without inhaled corticosteroids during exacerbation or as a maintenance therapy that should be started as soon as possible before hospital discharge
Home Management
- The dose and/or frequency of ongoing bronchodilator treatment should be increased
- An anticholinergic, if not yet in use, may be added until improvement is noted
- High-dose nebulized therapy may be given when required for several days
- Long-term use of nebulizer therapy after an exacerbation is not recommended
Corticosteroids
- Improves oxygenation and lung function, and reduces risk for relapse, treatment failure and length of hospital stay
Hospital Management
- Oral or IV corticosteroids are recommended as an addition to bronchodilator therapy, in the absence of significant contraindications
- Oral route is preferred, as no significant difference in efficacy was seen when compared to parenteral administration
- IV route may be used in patients with severe exacerbation and with contraindications for oral medications
- Shorten recovery time and help hasten restoration of lung function
- Duration of therapy with oral corticosteroid must not exceed 5-7 days, as there is no advantage to prolonged therapy and the risk of side effects is increased
Home Management
- Addition of oral corticosteroid to existing bronchodilator therapy may be considered if patient’s baseline FEV1 is <50% predicted
- Nebulized Budesonide alone or in combination with Formoterol may be used as an alternative to oral corticosteroids; may cause significant reduction of complications (eg hyperglycemia)
Antibiotics
- Given in patients who presents with increased purulence of sputum together with increase in dyspnea and sputum volume or in patients who need mechanical ventilation
- May reduce recovery time, interval to relapse, treatment failure, and duration of hospital stay
- Local antibiotic sensitivity patterns for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis must be taken into account when choosing an antibiotic agent
- Recommended oral antibiotic agents include:
- 1st-line: Amoxicillin, Doxycycline and Clarithromycin
- 2nd-line: Co-amoxiclav, Levofloxacin, Co-trimoxazole, Azithromycin, Cefuroxime axetil
- Given if no improvement seen or with clinical deterioration after 72 hours of treatment initiation
- Recommended IV antibiotic agents include Co-amoxiclav, Clarithromycin, Piperacillin/tazobactam
- Recommended duration of antibiotic therapy is 5-7 days
Heparin (SC/Low Molecular Weight)
- Consider administration of SC/LMW Heparin to reduce the risk of pulmonary embolism in patients with polycythemia or dehydration, with or without a history of thromboembolic disease
Non-Pharmacological Therapy
Pulmonary Rehabilitation
- Multidisciplinary program for patients with chronic respiratory impairment that is individually designed to maximize a patient’s physical and social performance and autonomy
- In regions with limited resources, simplified pulmonary rehabilitation programs are useful and are recommended
- Includes exercise training, nutrition counseling, education and psychological support
- Recommended for symptomatic patients with FEV1 of <50% predicted
- May also be considered in symptomatic patients with FEV1 of >50% predicted with exercise limitations, patients with mMRC >1, and following acute exacerbations
- Program should last 6-8 weeks to be effective; no additional benefit is seen in extending the program to 12 weeks
Site of Care
Please refer to the Symptom and Risk Evaluation of COPD table for characteristics per patient category
- Patients belonging to category A or B may be managed on an outpatient basis during exacerbations
- Patients belonging to category C or D may require hospitalization and more aggressive management during exacerbations
Indications for Hospital Treatment for Chronic Obstructive Pulmonary Disease Exacerbations
- Significant increase in signs and symptoms (eg sudden development of resting dyspnea, SaO2 <90%, changes in chest X-ray, arterial pH <7.35, arterial PaO2 <7 kPa, <53 mmHg)
- Acute lung failure
- Onset of new symptoms (eg cyanosis, peripheral edema, impaired level of consciousness)
- Absence of response to initial medical treatment
- Significant comorbidities (eg heart failure or newly occurring arrhythmias)
- Frequent exacerbations
- Older age
- Lack of home support
