chronic%20obstructive%20pulmonary%20disease
CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) is an inflammatory respiratory disease characterized by reversible airflow limitation.

The patient usually have chronic cough, sputum production or dyspnea with or without history of risk factors for the disease.

The chronic airflow limitation is caused by a combination of small airways disease and parenchymal destruction.

It is a preventable & treatable disease.

Principles of Therapy

General Therapeutic Principles

  • Pharmacotherapy is highly valuable for the following:
    • Prevention & control of symptoms
    • Reduction of the frequency & severity of exacerbations
    • Improvement of health status
    • Improvement of exercise tolerance
  • Drug therapy for COPD is determined by individualized assessment of symptoms & 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 & its combination can decrease the rate of decline in lung function
  • The following table summarizes treatment recommendations by patient category of COPD:

  • Patient Category

    Recommended treatment

    A

    • Short-acting anticholinergic or short-acting beta2-agonist as required (1st choice)
    • Long-acting anticholinergic or long-acting beta2-agonist or short-acting beta2-agonist & short-acting anticholinergic (2nd choice)
    • Theophylline (alternative choice*)

    B

    • Long-acting anticholinergic or long-acting beta2-agonist (1st choice)
    • Long-acting anticholinergic & long-acting beta2-agonist (2nd choice)
    • Short-acting beta2-agonist &/or short-acting anticholinergic or Theophylline (alternative choice*)

    C

    • Inhaled corticosteroid + long-acting beta2-agonist or long-acting anticholinergic (1st choice)
    • Long-acting anticholinergic & long-acting beta2-agonist or

      Long-acting anticholinergic & phosphodiesterase-4 inhibitor or

      Long-acting beta2-agonist & phosphodiesterase-4 inhibitor (2nd choice)

    • Short-acting beta2-agonist &/or short-acting anticholinergic or Theophylline (alternative choice*)

    D

    • Inhaled corticosteroid + long-acting beta2-agonist &/or long-acting anticholinergic (1st choice)
    • Inhaled corticosteroid + long-acting beta2-agonist & long-acting anticholinergic or

      Inhaled corticosteroid + long-acting beta2-agonist & phosphodiesterase-4 inhibitor or

      Long-acting anticholinergic & long-acting beta2-agonist or

      Long-acting anticholinergic & phosphodiesterase-4 inhibitor (2nd choice)

    • Carbocysteine or short-acting beta2-agonist &/or short-acting anticholinergic or Theophylline or N-acetylcysteine (alternative choice*)

Adapted from Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2017 report.
* May be used alone or in combination with the 1st or 2nd choice medication options

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 decreased likelihood of adverse effects
  • Given on a “when required” basis for immediate relief of symptoms or on a regular basis to prevent or reduce symptoms
  • Regular treatment with long-acting bronchodilators is more effective & 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, Theophylline) can be considered
    • Inhaled bronchodilators are preferred to Theophylline because of the latter’s potential 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
  • Choice of drugs will depend on the patient’s response & preference, together with drug’s side effects & cost

Anticholinergics

  • Eg (long-acting) Aclidinium, Glycopyrronium, Tiotropium, Umeclidinium, (short-acting) Ipratropium, Oxitropium
  • Block the effects of acetylcholine on M2 & M3 (short-acting), & M1 & 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 & exacerbation-related hospitalizations
    • Reduced respiratory morbidity including respiratory failure & 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 & short-acting beta2-agonist may provide superior bronchodilatation than either medication alone
  • Aclidinium & Glycopyrronium have effects on lung function & breathlessness comparable to that of Tiotropium but further studies are needed

Beta2-agonists

  • Eg Arformoterol, Fenoterol, Formoterol, Indacaterol, Levalbuterol, Olodaterol, Salbutamol (Albuterol), Salmeterol, Terbutaline, Tulobuterol
  • 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 & Formoterol significantly improves FEV1, lung function, dyspnea, quality of life & exacerbation rate
  • Based on several clinical trials, combination of long-acting beta2-agonists (eg Salmeterol) & inhaled corticosteroids (eg Fluticasone) may reduce COPD exacerbation & may improve lung function & quality of life better than when each drug is used alone
  • Inhaled beta2-agonists have a faster onset of action & 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 effective in COPD, inhaled bronchodilators are preferred to Theophylline, owing to the latter’s potential toxicity
  • Combination of a beta2-agonist, an anticholinergic &/or Theophylline may produce additional improvements in health status & 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 & repeated exacerbations (eg 3 exacerbations in the last 3 years)
    • May reduce airway hyper-reactivity in these patients & decrease symptoms of COPD including exacerbations
  • In patients with more advanced COPD & repeated exacerbation, treatment with inhaled corticosteroids can be beneficial
  • Dose-response relationships & 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 & long-acting beta2-agonist is more effective in reducing exacerbations & 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 & 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
  • 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

Inhalation Devices

  • Effective drug delivery & training in inhaler technique should be emphasized & re-checked as necessary
  • Choice of device depends on price, availability, the prescribing doctor, & the skills & ability of the patient
  • Metered dose inhaler (MDI)
    • COPD patients may have poorer coordination & 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 & may therefore require less hand-&-mouth coordination
    • May be more convenient & 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

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 & 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 may be considered for previous smokers

Cough & Cold Preparations

  • Eg Ambroxol, Carbocysteine, Erdosteine, N-acetylcysteine
  • Antitussives are not recommended because cough has a protective effect in COPD
  • Expectorants & 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 & sputum production
  • N-acetylcysteine may help reduce exacerbations in COPD patients without inhaled corticosteroid treatment

Vaccines

Influenza Vaccine

  • May decrease morbidity & mortality rates due to influenza
  • Should be given yearly, 1-2 months prior to anticipated peak influenza season, because of new antigens & waning immunity from the previous years
  • Associated with reduced risk of all-cause mortality

Pneumococcal Polysaccharide Vaccine [Pneumococcal conjugate vaccine (PCV13) & 23-valent pneumococcal polysaccharide vaccine (PPSV23)] 

  • Recommended in COPD patients ≥65 years & in younger patients with significant comorbidities (eg cardiac disease, chronic pulmonary disease)
  • PPSV23 reduces occurrence of community-acquired pneumonia (CAP) in patients <65 years with FEV1 <40% predicted or comorbidities
  • Studies showed that PSV13 exhibited significant efficacy for both CAP & vaccine-type invasive pneumococcal disease in adults ≥65 years 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

Bronchodilators

Hospital Management

  • Short-acting inhaled beta2-agonists 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
  • Oral or IV Theophylline & other methylxanthines should only be used as adjunctive treatment, when the response to inhaled bronchodilators is insufficient
    • May be considered in more severe exacerbations
    • Should be used with caution because of the increased likelihood of drug interactions & toxic effects
    • Close monitoring of serum Theophylline levels is recommended

Home Management

  • The dose &/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

Hospital Management

  • Oral or IV corticosteroids are recommended as an addition to bronchodilator therapy, in the absence of significant contraindications
  • Shorten recovery time & help hasten restoration of lung function
  • As much as possible, a course of oral corticosteroid must not exceed 14 days as there is no advantage to prolonged therapy & 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 & sputum volume or in patients who need mechanical ventilation
  • Local antibiotic sensitivity patterns for Streptococcus pneumoniae, Haemophilus influenzae & Moraxella catarrhalis must be taken into account when choosing an antibiotic agent

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

SELECTIVE BETA2-AGONISTS BRONCHODILATORS

Long-Acting

Short-Acting

Arformoterol

Clenbuterol

Bambuterol1

Fenoterol

Formoterol

Hexoprenaline

Indacaterol

Levalbuterol

Olodaterol

Orciprenaline2

Salmeterol

Procaterol

Tulobuterol

Salbutamol (Albuterol)3

Terbutaline3

Trimetoquinol

1Prodrug of Terbutaline.
2Less selective than Salbutamol.
3Long-acting extended-release oral preparations are available

Non-Pharmacological Therapy

Pulmonary Rehabilitation

  • Multidisciplinary program for patients with chronic respiratory impairment that is individually designed to maximize a patient’s physical & social performance & autonomy
    • In regions with limited resources, simplified pulmonary rehabilitation programs are useful & are recommended
  • Includes exercise training, nutrition counseling, education & 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, & following acute exacerbations
  • Program should last ≥2 months to be effective; the longer it continues, the better the results

Site of Care

Please refer to the Symptom and Risk Evaluation for 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 & more aggressive management during exacerbations

Indications for Hospital Treatment for Chronic Obstructive Pulmonary Disease Exacerbations:

  • Significant increase in symptoms (eg sudden development of resting dyspnea)
  • Severe underlying COPD
  • Onset of new symptoms (eg cyanosis, peripheral edema)
  • Absence of response to initial medical treatment
  • Significant comorbidities (eg heart failure or newly occurring arrhythmias)
  • Frequent exacerbations
  • Older age
  • Lack of home support
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