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Chronic Obstructive Pulmonary Disease (COPD)

Essentials

  • The possibility of chronic obstructive pulmonary disease (COPD) should be considered in any smoker with dyspnoea or a productive cough. The majority of smokers do not notice these symptoms themselves or have become accustomed to them.
  • The diagnosis is based on history of exposure, symptoms and permanent bronchial constriction. In spirometry, FEV1/FVC after bronchodilation is below 0.70 (GOLD 2023 http://goldcopd.org/2023-gold-report-2/). The severity of the disease is classified by symptoms, exacerbations and FEV1 z score.
  • Smoking cessation and physical exercise form central parts of treatment.
  • The most important differential diagnosis is asthma. Asthma and COPD may also occur concurrently, and many people with asthma smoke.
  • Other concomitant diseases worsen the prognosis, and diagnosis of such diseases and their treatment according to recommendations form a part of a comprehensive approach.
  • 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 and to improve the prognosis.

Definitions

  • Chronic obstructive pulmonary disease (COPD) is a common, preventable, heterogeneous lung disease that should be treated. It is characterized by chronic respiratory symptoms (dyspnoea, cough, sputum production and/or exacerbations) due to dysfunction of either airways (chronic bronchitis, bronchiolitis) or alveoli (emphysema) resulting in permanent and often progressive airway obstruction (Current Care Guideline 2020 [in Finnish http://www.kaypahoito.fi/hoi06040] and GOLD 2023 http://goldcopd.org/2023-gold-report-2/).
  • In chronic bronchitis, sputum production is present for at least 3 months during 2 consecutive years unassociated with any other lung disease (such as bronchiectasis i.e. bronchial dilatation).
  • In bronchial obstruction, expiratory flow is reduced due to bronchial obstruction and, when there is emphysema, decreased elastic forces of the lung.
  • COPD is associated with a number of extrapulmonary comorbidities that should be considered when planning treatment.

Prevalence

Aetiology and pathogenesis

  • COPD is caused by dynamic, repetitive and cumulative interaction between genetic and environmental factors damaging or disturbing the normal developmental/ageing process of the lungs.
  • 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. In low income countries, most cases of COPD occur in non-smokers. Air pollution and domestic biomass burning increase the risk significantly.
  • 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 a relatively short period of smoking (less than 20 pack years), serum alpha1-antitrypsin levels should be determined.
  • Previously diagnosed asthma will increase the prevalence and incidence of COPD.

Symptoms

  • Cough, dyspnoea and sputum production are the most common symptoms.
  • Other commonly described symptoms include wheezing or rhoncus, a feeling of pressure in the chest, fatigue or exhaustion, reduced activity, weight loss and recurrent episodes of bronchitis.
  • Patients may not actively report the symptoms, and some have adapted to them by reducing physical activity, for example.
  • The symptoms are usually aggravated in association with respiratory tract infections.
  • 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

  • The diagnosis is based on history of exposure, symptoms and bronchial constriction (obstruction) observed in post-bronchodilator spirometry.
  • Spirometry Pulmonary Function Tests is the cornerstone of diagnosis, always combined with a bronchodilation test . In mild cases (FEV1/FVC 0.6-0.8) physiological 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.ersnet.org/science-and-research/ongoing-clinical-research-collaborations/the-global-lung-function-initiative/ 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) in post-bronchodilator spirometry is consistent with COPD. For bronchodilation, use a beta2-agonist (e.g. salbutamol 400 µg inhalation aerosol). It should be noted, however, that FEV1/FVC may be < 0.7 even in the absence of COPD.
  • Significant response to bronchodilation Pulmonary Function Tests (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. Nevertheless, it should be performed for differential diagnosis (particularly to exclude lung cancer).
  • The blood eosinophil count should be determined, since it has an impact on choosing drugs.
  • If the patient is young (below 45 years) and the level of smoking exposure low (less than 20 pack years), it is worthwhile to check alpha1-antitrypsin concentration.
  • The following examinations should 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.
  • In COPD, spirometry is used primarily at the time of diagnosis. During follow-up, spirometry may be useful if there is a need to assess the progression or severity of the disease or the efficacy of treatment, or if the cause of new symptoms in not clear.
    • In such cases, spirometry is normally done using a bronchodilation test and with the patient's normal medication but preferably without the patient taking short-acting bronchodilators (symptomatic medication or medication to be taken as necessary) before the examination (12-h break, if possible). Long-acting bronchodilators (so-called regular medication) should not be paused if they are being used.
    • Spirometry should generally always be done using a bronchodilator in order to see any bronchodilator response.

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

  • The most essential factor for the prognosis
  • Does not normalize lung function, but the progressive deterioration of FEV1 slows down to the same pace as in non-smokers.
  • See Smoking Cessation.

Physical exercise Pulmonary Rehabilitation for Chronic Obstructive Pulmonary Disease, Pulmonary Rehabilitation Following Exacerbations of Chronic Obstructive Pulmonary Disease, Water-Based Exercise Training for Chronic Obstructive Pulmonary Disease, Oxygen Therapy during Exercise Training in Chronic Obstructive Pulmonary Disease, Breathing Exercises for Chronic Obstructive Pulmonary Disease

  • Insufficient attention has been paid to the significance of physical exercise and muscle condition. Their importance should be emphasized at all stages of disease. Physical activity will improve performance and reduce symptoms and exacerbations.

Nutrition Nutritional Supplementation in Stable Chronic Obstructive Pulmonary Disease

  • As many as 25% of patients are underweight while some are overweight. A BMI below 21 is considered to represent undernutrition. Calorie- and protein-dense nutritional supplements 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

  • Pharmacotherapy should always be combined with non-pharmacological forms of treatment, of which smoking cessation is the most important.
  • Triple therapy (ICS + LABA + LAMA) appears to reduce exacerbations requiring hospital treatment and mortality in patients with moderately severe to severe COPD with exacerbations despite dual bronchodilation (LABA + LAMA).
  • Medication is useful in alleviating subjective symptoms and in treating and preventing acute exacerbations. The aim of preventing or reducing exacerbations is to influence the course of the disease.
  • Treatment is chosen according to the patient's phenotype. The degree of obstruction and symptoms also influence the choice of treatment.

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 (SAMA)
Ipratropium bromide
Long-acting bronchodilator
  • Long-acting beta2-agonists (LABA)
  • Long-acting anticholinergic (LAMA)
Inhaled glucocorticoids (ICS)Beclomethasone
Budesonide
Fluticasone propionate
Fluticasone furoate*
Mometasone**
Ciclesonide**
OralPhosphodiesterase inhibitors (theophylline, roflumilast)
Combination products
  • Short-acting bronchodilator (beta2-agonist and anticholinergic)
Salbutamol-ipratropium bromide
Fenoterol-ipratropium bromide
  • Long-acting bronchodilator (beta2-agonist and anticholinergic)
Indacaterol-glycopyrronium bromide
Vilanterol-umeclidinium bromide
Formoterol-acclidinium bromide
Olodaterol-tiotropium bromide
Formoterol-glycopyrronium bromide
  • Glucocorticoid and beta2-agonist
Beclomethasone-formoterol
Budesonide-formoterol
Fluticasone-salmeterol
Fluticasone-vilanterol
Formoterol-fluticasone
Indacaterol-mometasone
  • Glucocorticoid and beta2-agonist and anticholinergic
Fluticasone-vilanterol-umeclidinium bromide
Beclomethasone-formoterol-glycopyrronium bromide
Indacaterol-glycopyrronium bromide-mometasone
Formoterol-glycopyrronium bromide-budesonide
* In combination preparations only
** COPD not an official indication (check local situation)
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 numerous symptoms or exacerbations, LAMA+LABA therapy should be selected primarily.
  • If the blood eosinophil count is > 0.3 × 109 or the patient presents with features suggestive of asthma-COPD phenotype, an inhaled glucocorticoid (ICS) should be 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.
    • May require separate medical certificate for reimbursement.
  • Azithromycin
    • 250-500 mg azithromycin on 3 days a week for one year (combined with inhaled medication) may reduce the risk of exacerbations in patients with recurrent exacerbations despite other medication.
    • When using azithromycin, the risk of bacterial resistance, prolonged QT time and hearing loss must be considered.
    • Azithromycin gives less benefit in smokers.
  • 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.
    • Use of theophylline for the treatment of COPD is recommended only as an additional drug in patients with severe symptoms.
    • Any use of theophylline should be restricted to oral (tablet) medication.

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, if necessary, change the inhalaler
    • 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. Provide the patient with patient education materials.
  • 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

Oral glucocorticoid therapy

Workup and treatment of acute exacerbations 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 affects 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 respiratory support
  • Treatment
  • 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

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 only 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, 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)
  • 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 at 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 additional 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 and 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, open fire devices (wood-burning stove, fireplace, tiled stove, etc.) must not 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, for example with the help of endobronchial valves, may be a treatment alternative in severe emphysema.

COPD and driving health

  • Advanced COPD may restrict the patient's driving ability.
  • A pulmonary specialist should assess whether the requirements for driving fitness are fulfilled if, in a stable phase, SpO2 is < 90% at rest or FEV1< 30% of the expected level.
  • To assess driving fitness, an arterial blood gas sample should be taken with the patient sitting. If there is clinical suspicion of cognitive decline, neuropsychological tests should be considered. The targets of pO2> 7.3 kPa and pCO2< 6.7 kPa must be achieved (with the help of nocturnal bi-level positive pressure ventilation or treatment with an oxygen concentrator, as necessary).
  • Health-based assessment of driving ability may be indicated. The test should be long enough (max. 90 min) for any decline in oxygen saturation (SpO2< 90%) to be detected by pulse oximetry.
  • Check also local regulations concerning driving health.

    References

    • Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for Prevention, Diagnosis and Management of COPD: 2023 Report. http://goldcopd.org/2023-gold-report-2/
    • [Chronic obstructive pulmonary disease]. A Current Care Guideline. Working group appointed by the Finnish Medical Society Duodecim and the Finnish Respiratory Society. Helsinki: Finnish Medical Society Duodecim 2020 (accessed 20 Nov 2023). Available in Finnish at http://www.kaypahoito.fi/hoi06040.

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