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JereReijula
TimoHelin

Chronic Obstructive Pulmonary Disease (COPD)

Essentials

  • The possibility of chronic obstructive pulmonary disease (COPD) should be considered in any smoker with a productive cough. The majority of smokers do not notice even this symptom themselves.
  • The diagnosis is based on history of exposure, symptoms and bronchial constriction observed in post-bronchodilator spirometry. FEV1/FVC after bronchodilation is below 0.70 (GOLD 2020 http://goldcopd.org/gold-reports/). The severity of the disease is classified by symptoms, exacerbations and FEV1 z score.
  • The most important differential diagnosis is asthma. Asthma and COPD may occur concurrently, and many people with asthma smoke.
  • Smoking cessation and physical exercise form central parts of treatment.
  • The choice of medication depends on the severity of symptoms, occurrence of exacerbations and results of lung function tests.
  • Medication is used to reduce symptoms, such as dyspnoea on exertion, and to prevent exacerbations.

Definitions

  • Chronic obstructive pulmonary disease (COPD) is a common, preventable disease characterized by persistent respiratory symptoms, progressive airway obstruction and chronic inflammation as a reaction to respiratory exposure to harmful particles or gases.
  • In chronic bronchitis, sputum occurs for at least 3 months during 2 consecutive years.
  • In bronchial obstruction, expiratory flow is reduced due to bronchial obstruction and, associated with emphysema, decreased elastic forces of the lung.

Aetiology

  • Smoking is the most important aetiology of COPD. Half of those who smoke have symptoms of chronic bronchitis. Gradually progressing airway obstruction is detected in more than 25% of long-term smokers.
  • A non-smoker may also develop COPD as a result of outdoor or indoor air pollution and passive exposure to smoke.
  • The attributable fraction for occupational aetiology of COPD is estimated to be about 14%.
  • Alpha1-antitrypsin deficiency is a rare cause of COPD/emphysema in young patients. If a patient develops COPD before the age of 45 or after an exceptionally short period of smoking (less than 20 pack years), serum alpha1-antitrypsin levels should be determined.

Symptoms

  • Cough and sputum production are the most common symptoms.
  • Patients with progressive disease suffer from gradually increasing dyspnoea on exertion.
  • The symptoms are usually aggravated in association with respiratory tract infections.
  • General symptoms may include weight loss and fatigue.
  • Symptoms can be assessed by the CAT test (COPD Assessment Test™) http://www.catestonline.org or mMRC scale (modified Medical Research Council dyspnoea scale)http://www.mdcalc.com/mmrc-modified-medical-research-council-dyspnea-scale.

Findings

  • Most patients only seek medical help when the disease is already severe. In mild disease, auscultation findings may be normal and no signs of obstruction may be found.
  • The following symptoms indicate severe COPD (their absence does not exclude mild COPD).
    • Because of airway obstruction, wheezing is heard at the end of forced expiration.
    • A patient with emphysema may have a barrel-chested appearance. On auscultation reduced breath sounds are heard, and on percussion the sound is hyperresonant.
    • There may be cyanosis associated with hypoxaemia.
    • In severe cases, the respiration rate is increased, accessory respiratory muscles are in use and muscle mass is reduced. Additionally, signs of increased workload of the right heart may occur.

Diagnosis

  • Spirometry is the cornerstone of diagnosis, always combined with bronchodilation test http://www.dynamed.com/condition/copd#PULMONARY_FUNCTION_TESTS. In mild cases biological fluctuation often occurs and spirometry should be repeated.
  • The level of obstruction is measured by determining forced expiratory volume in one second (FEV1). International (see Global Lung Function Initiative http://www.ers-education.org/guidelines/global-lung-function-initiative.aspx http://erj.ersjournals.com/content/53/2/1802277) and local reference values are available. Find out about the appropriate values in your setting.
    • Clinical severity is defined by FEV1, symptoms, exacerbations and by the need for pharmacotherapy.
  • A reduced ratio of forced expiratory volume to forced vital capacity (FEV1/FVC < 0.7 or according to the new reference values z < -1.65) in post-bronchodilator spirometry is consistent with COPD. For bronchodilation, use a beta2-agonist (e.g. salbutamol 400 µg inhalation aerosol).
  • Significant response to bronchodilation (12%, and an increase of at least 200 ml in FEV1) is usually observed in patients with asthma but may also occur in 25 to 50% of patients with COPD.
  • Chest x-ray is of minor value in the diagnosis of COPD http://www.dynamed.com/condition/copd#CHEST_X_RAY. Nevertheless, it should be performed for differential diagnosis (particularly to exclude lung cancer).
  • Blood eosinophil count should be determined, since it has an impact on choosing drugs http://www.dynamed.com/condition/copd#BLOOD_TESTS.
  • If the patient is young (below 45 years) and the level of smoking low (less than 20 pack years), it is worthwhile to check alpha1-antitrypsin concentration.
  • The following examinations may be performed as considered necessary:
    • Pulse oximetry and blood gas analysis
      • Pulse oximetry can be used to assess the need for consulting a specialist when considering oxygen therapy. If the oxygen saturation rate is below 90% at rest in a non-smoker, the patient may be referred for assessment of the need for oxygen therapy. At a late stage of COPD, the partial pressure of oxygen (arterial pO2) will decrease and the partial pressure of carbon dioxide (arterial pCO2) may increase.
    • Diffusion capacity
      • Diffusion capacity is usually decreased in COPD with emphysema.
  • Asthma and COPD often coexist.
  • The most important diseases to consider in differential diagnosis are asthma, chronic bronchitis, respiratory infections and cardiac diseases.

Comorbidities

  • Moderately severe and severe COPD, especially, are often associated with comorbidities, the most important being cardiovascular diseases, metabolic syndrome, diabetes, osteoporosis, depression and numerous types of cancer.

Complications

  • Acute
    • Recurring and prolonged lower respiratory tract infections
    • Acute respiratory failure
    • Pneumothorax (rupture of emphysematic bullae)
  • Chronic
    • Chronic respiratory failure, cardiopulmonary disease (cor pulmonale)

Treatment Self-Management for Patients with Chronic Obstructive Pulmonary Disease, Telehealthcare for Chronic Obstructive Pulmonary Disease

Smoking cessation Smoking Cessation for People with Chronic Obstructive Pulmonary Disease

Nutrition Nutritional Supplementation in Stable Chronic Obstructive Pulmonary Disease

  • 25% of patients are underweight, some overweight. A BMI below 21 is considered to represent undernutrition. Calorie- and protein-dense additional nutrients should be considered if nutrition cannot be otherwise corrected.

Pharmacotherapy Combined Corticosteroid and Long-Acting Beta-Agonist in One Inhaler for Chronic Obstructive Pulmonary Disease, Oral Corticosteroids for Stable COPD, Inhaled Corticosteroids Versus Long-Acting Beta(2)-Agonists for Chronic Obstructive Pulmonary Disease, Tiotropium, Inhaled Steroids and Long-Acting Beta2-Agonists Alone or in Combinations for Chronic Obstructive Pulmonary Disease, Long-Acting Beta2-Agonist in Addition to Tiotropium Versus Either Agent Alone for Chronic Obstructive Pulmonary Disease, Oral Theophylline for Chronic Obstructive Pulmonary Disease, Phosphodiesterase 4 Inhibitors for Chronic Obstructive Pulmonary Disease, Tiotropium Versus Ipratropium for COPD, Anti-Cholinergic Bronchodilators Versus Beta2-Sympathomimetic Agents for Acute Exacerbations of Chronic Obstructive Pulmonary Disease, Cardioselective Beta-Blockers for Chronic Obstructive Pulmonary Disease, Short-Acting Beta2-Agonists for Chronic Obstructive Pulmonary Disease, Inhaled Corticosteroids in COPD, Long-Acting Beta-2 Agonists for Chronic Obstructive Pulmonary Disease, Tiotropium for Stable Chronic Obstructive Pulmonary Disease

  • So far, no medication has been proved with certainty to affect the progress of the disease (annual decrease of FEV1) or associated mortality. Medication is useful in alleviating subjective symptoms and in treating and shortening acute exacerbations. The aim of preventing or reducing exacerbations is to affect the course of the disease.
  • Treatment is chosen according to the patient's phenotype. The degree of obstruction and severity of symptoms also affect the choice of treatment http://www.dynamed.com/condition/copd#GLOBAL_INITIATIVE_FOR_CHRONIC_OBSTRUCTIVE_LUNG_DISEASE__GOLD__RECOMMENDATIONS.

Drugs used for the treatment of COPD

Group of drugsActive ingredient
Short-acting bronchodilator ("attack medication")
  • Short-acting beta2-agonists (SABA)
Salbutamol, terbutaline, fenoterol*
  • Short-acting anticholinergic / muscarinic antagonist (SAMA)
Ipratropium bromide
Long-acting bronchodilator
  • Long-acting beta2-agonists (LABA)
  • Duration of action about 12 h:formoterol, salmeterol
  • Duration of action about 24 h:indacaterol, olodaterol, vilanterol*
  • Long-acting anticholinergic /muscarinic antagonists (LAMA)
  • Duration of action about 12 h: acclidinium bromide
  • Duration of action about 24 h: tiotropium bromide, glycopyrronium bromide, umeclidinium bromide
Inhaled glucocorticoids (ICS) Beclomethasone, budesonide, fluticasone propionate, fluticasone furoate*, mometasone**, ciclesonide**
OralPhosphodiesterase inhibitor (theophylline, roflumilast)
Combination products
  • Short-acting bronchodilator (SABA and SAMA)
Salbutamol-ipratropium bromide, fenoterol-ipratropium bromide
  • Long-acting bronchodilator (LABA and LAMA)
Indacaterol-glycopyrronium bromide, vilanterol-umeclidinium bromide, formoterol-acclidinium bromide
  • Glucocorticoid and beta2-agonist
Beclomethasone-formoterol, budesonide-formoterol, fluticasone-salmeterol, fluticasone-vilanterol
  • Glucocorticoid and beta2-agonist and anticholinergic
Fluticasone-vilanterol-umeclidinium bromide, beclomethasone-formoterol-glycopyrronium bromide
* In combination preparations only
** COPD not an official indication (in Finland)
Regular medication is warranted in all COPD patients if the patient has
  • COPD symptoms on a regular basis (usually CAT score 10) or
  • a high risk of later developing exacerbations (at least 2 exacerbations during the previous year or even one that required hospital care).
  • If at the time of diagnosis the patient has plenty of symptoms or exacerbations, LAMA, LABA or LAMA+LABA therapy is selected.
  • If blood eosinophil count is > 0.3 × 109 or the patient presents with features suggestive of asthma-COPD phenotype, an ICS is added to the treatment. Such features include
    • asthma or symptoms of asthma
    • earlier history of IgE-mediated allergy causing symptoms of asthma
    • strong fluctuation in the level of obstruction:
      • FEV1 improves 15% and 400 ml
      • FEV1 improves repeatedly 12% and 200 ml
      • Significant 24-hour variation observed in PEF monitoring at least 3 times during a 2-week period.

Other drug alternatives

  • Roflumilast
    • Can be added to other medication (at least to long-acting bronchodilating drugs) if the patient also has chronic bronchitis, poor lung function (FEV1< 50%) and recurrent exacerbations.
    • Roflumilast reduces exacerbations of COPD and improves lung function Phosphodiesterase 4 Inhibitors for Chronic Obstructive Pulmonary Disease but it has significant adverse effects, such as gastrointestinal symptoms, headache and weight loss.
    • In Finland a separate medical statement detailing the patient's health status is needed for its prescription.
  • Theophylline
    • Can be combined with an inhaled glucocorticoid and/or long-acting bronchodilating drugs. It adds to the efficacy of bronchodilating drugs even at low doses.
    • Theophylline has a slow onset of effect, its therapeutic range is narrow, and it is associated with numerous adverse effects. In addition, it has interactions with other drugs.
    • It is recommended to use theophylline only as an additional drug in patients with severe symptoms.

Poor response to pharmacotherapy

  • If the response to drugs is poor
    • ensure treament compliance
    • ensure that the patient has quit smoking
    • check correct use of the dispensing device and change, if necessary, the inhalator
    • re-evaluate the phenotype of the patient's disease, as necessary

Treatment of mucus production

  • Bottle PEP (positive expiratory pressure) is suitable for self-initiated mucus drainage. The patient exhales through a plastic tube into water in a bottle and then coughs up the mucus.
  • Mucolytic agents may reduce exacerbations of COPD Mucolytic Agents for Chronic Bronchitis without significant adverse effects but will not improve lung function.

Long-term use of antimicrobial drugs

  • Continuous use of macrolides (erythromycin, clarithromycin, azithromycin, roxithromycin) will reduce exacerbations of COPD Prophylactic Antibiotic Therapy for Chronic Obstructive Pulmonary Disease but their extensive use is restrained by the fear of increased bacterial resistance to macrolides. The treatment of patients with recurrent exacerbations should be assessed in specialized care.

Oral glucocorticoid therapy

An acute exacerbation and its treatment Action Plans for Chronic Obstructive Pulmonary Disease, Hospital at Home for Acute Exacerbations of Chronic Obstructive Pulmonary Disease

  • The diagnosis of an exacerbation of COPD is clinical.
    • Increased dyspnoea
    • Cough
    • Possibly purulent sputum
  • Examinations
    • Status (respiratory rate, skin tone, use of auxiliary breathing muscles, peripheral oedema, auscultation of the heart and lungs, blood pressure)
    • Oxygen saturation
    • Chest x-ray
    • Basic blood count with platelet count, CRP, creatinine, electrolytes, ECG
  • The severity of the exacerbation has an effect on the selection of pharmacotherapy and treatment location.
    • Mild: can be treated in outpatient care; medication consists of short-acting bronchodilators
    • Moderately severe: can be treated in outpatient care; medication consists of bronchodilators, oral glucocorticoids or an antimicrobial drug
    • Severe: requires hospital care; in addition to the aforementioned treatments often oxygen therapy and support for respiration
  • Treatment
    • Oxygen by nasal catheter or by venturi mask. Caution should be exercised when dosing if the result of arterial blood gas analysis is not available, but oxygen saturation of 88 to 92% should be attempted.
      • Nasal catheter flow should not exceed 2 l/min or the concentration of venturi mask oxygen 28% in patients above the age of 50 years.
      • Administration of oxygen is also well-founded due to the fact that patients with COPD often have concomitant heart disease.
    • Bi-level positive pressure ventilation improves recovery from severe acute exacerbation of COPD Noninvasive Positive-Pressure Ventilation for Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
    • Inhaled beta2-agonist
      • 5-10 mg salbutamol, often combined with 0.5 mg ipratropium, or a combination of 0.5 mg ipratropium and 2.5 mg salbutamol or of 0.5 mg ipratropium and 1.25 mg fenoterol
      • Administration of an aerosol with propellant (200-300 µg salbutamol) using a spacer is probably at least as effective as its administration as a continuous spray (nebulizer).
      • Inhaled bronchodilators can be given every 4 to 6 hours.
    • Theophylline infusions are of no use Theophylline for Exacerbations of COPD.
    • The patient's condition permitting, a course of oral glucocorticoids should be started. The recommended dose is 30-40 mg prednisolone/day for 5 days Systemic Corticosteroids for Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Oral administration is as effective as intravenous administration.
      • If the patient's general status is impaired, he cannot swallow or keeps vomiting, the course can be started intravenously (40 mg methyl prednisolone every 6 to 8 hours). Alternatively, the patient can be given an inhaled glucocorticoid: 1 mg budesonide 2 to 4 times daily through a nebulizer.
  • If the response is poor, the patient should be admitted to the in-patient ward at a health centre or to a hospital. Confusion, instable haemodynamics, oxygen saturation below 90%, pneumonia or other severe disease (e.g. diabetes, heart disease or renal failure) suggest a need for hospital treatment.

Symptoms of acute infection

  • The significance of antimicrobial treatment in exacerbations of COPD has been shown in a number of studies Antibiotics for Exacerbations of Chronic Obstructive Pulmonary Disease. Factors that are an indication for starting antimicrobial treatment include
    • increased dyspnoea
    • increased sputum
    • purulent sputum.
  • If the patient exhibits two of the three symptoms listed above, antimicrobial medication is usually indicated.
  • Options for antimicrobial treatment include amoxicillin, amoxicillin-clavulanic acid, doxycycline and sulpha-trimethoprim, and in recurrent exacerbations moxifloxacin can be considered.

Home oxygen therapy Ambulatory Oxygen for Improving Exercise Capacity in Patients with COPD, Oxygen Therapy during Exercise Training in Chronic Obstructive Pulmonary Disease, Symptomatic Oxygen for Chronic Obstructive Pulmonary Disease, Domiciliary Oxygen in Chronic Obstructive Pulmonary Disease

Principles

  • Oxygen therapy at home can be used to prevent elevation of pulmonary arterial pressure in advanced COPD and to prolong survival Domiciliary Oxygen in Chronic Obstructive Pulmonary Disease.
  • The effect of home oxygen therapy on symptoms (e.g. shortness of breath) is quite limited.
  • Home oxygen therapy is monly indicated in patients with chronic hypoxaemia, i.e. arterial desaturation.
  • Treatment decisions should be made after critical consideration.
  • When initiating home oxygen therapy, appropriate monitoring of the treatment must be ensured. Treatment decisions and implementation of treatment and monitoring should be the responsibility of the local pulmonary clinic.

Criteria for initiating home oxygen therapy

  • Chronic, advanced pulmonary disease (FEV1< 1.5 l)
  • The partial pressure of oxygen in arterial blood, measured with the patient in a stable phase of the disease breathing room air is < 7.3 kPa in two samples taken with an interval of at least three weeks.
  • The partial pressure of oxygen can also be 7.3-8.0 kPa if one of the following criteria is fulfilled:
    • signs of increased pulmonary arterial pressure (e.g. oedema)
    • secondary polycythaemia (haematocrit > 55)
    • significant nocturnal hypoxaemia established by oximetry and reversible by oxygen therapy that is not due to concomitant sleep apnoea syndrome
    • significant neuropsychological symptoms reversible by oxygen therapy.
  • Oxygen therapy gives the desired response (PaO2> 8.0 kPa) without unfavourable increase in the partial pressure of carbon dioxide in arterial blood.
  • The patient does not smoke and is sufficiently co-operative.
  • Due to the risk of explosion, no open fire devices (wood-burning stove, fireplace, tiled stove, etc.) must be used in the household.

Implementation of treatment

  • An electric oxygen concentrator is most often used for home oxygen therapy. The oxygen concentrator removes nitrogen from room air and provides the patient with over 90% pure oxygen.
  • Portable liquid oxygen is suitable for certain patients, those in working life and/or who are motivated for rehabilitation through physical exercise.
  • Home calls made by a rehabilitation instructor are an essential part of the monitoring of patients receiving oxygen therapy at home.

Noninvasive ventilation Nocturnal Positive Pressure Ventilation for COPD, Noninvasive Positive-Pressure Ventilation for Acute Exacerbation of Chronic Obstructive Pulmonary Disease

  • Nocturnal noninvasive ventilation (NIV; with or without oxygen therapy) can be considered if the patient has any of the following during appropriate therapy:
    • hypercapnia (PaCO2 exceeding 7 kPa), corrected by at least 20% with NIV
    • recurrent exacerbations, during which noninvasive or invasive ventilation is needed, or
    • marked hypercapnia during oxygen therapy, and symptoms of nocturnal hypoventilation.

Surgical treatment

  • Can be considered in carefully selected patients with severe COPD.
  • Requires at least 6 months of not smoking.
  • Lung volume reduction surgery will benefit appropriately chosen patientsLung Volume Reduction Surgery (LVRS) in Diffuse Emphysema. In the operation, the most badly destroyed regions of the lungs of a patient with severe emphysema are resected.
  • Lung transplantation may be indicated in some patients.
  • Endoscopic lung volume reduction, with the help of, for example, endobronchial valves, may be a treatment alternative in severe emphysema.

References

Evidence Summaries

Related Keywords

ATC Code:

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Primary/Secondary Keywords