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Flashcards in Respiratory Therapeutics - COPD Deck (32)
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1
Q

What is COPD

A

COPD is characterised by airflow obstruction that is not fully reversible. The airflow obstruction is usually progressive in the long term. COPD is predominantly caused by smoking. Other factors, particularly occupational exposures, may also contribute to the development of COPD. Exacerbations often occur which are a rapid and sustained worsening of symptoms beyond normal day‐to‐day variations. COPD produces symptoms, disability and impaired quality of life which may respond to pharmacological and other therapies that have limited or no impact on the airflow obstruction. COPD is the preferred term for conditions in patients with airflow obstruction who were previously diagnosed as having chronic bronchitis or emphysema

2
Q

Main risk factors for COPD

A
  • Tobacco smoking
  • Indoor air pollution (such as biomass fuel used for cooking and heating)
  • Outdoor air pollution
  • Occupational dusts and chemicals (vapours, irritants, and fumes)
3
Q

Aetiology

A

COPD is caused by long term exposure to toxic particles and gases. Cigarette smoking accounts for over 90% of cases in developed countries. In developing countries, inhalation of smoke from biomass fuels used in heating and cooking in poorly ventilated areas are also implicated. In addition, pollution and climate can be implicated. There is some individual susceptibility to developing COPD. Patients who have Alpha1 Antitrypsin deficiency may develop COPD.

4
Q

Pathophysiology

A

An increase in numbers of mucus‐secreting goblet cells of the bronchial mucosa occur with COPD. Microscopically, there is infiltration of the walls of the bronchi and bronchioles with acute and chronic inflammatory cells. Lymphoid follicles may develop in severe disease. The epithelial layer may become ulcerated and with time, squamous epithelium replaces the columnar cells. Inflammation is followed by scarring and thickening of the walls which narrows the small airways. The small airways are particularly affected in the disease and initially this may be in the absence of any significant breathlessness.

Squamous cell metaplasia and fibrosis of bronchial walls develops with further progression of the disease.

5
Q

Symptoms can include:

A

Symptoms can include:
Chronic cough productive / non-productive
Smoker’s cough
Wheeze (not always present)
Breathlessness
Infective exacerbations with purulent sputum
Cardiovascular function can be affected
Other systems can be affected e.g. hypertension, osteoporosis and metabolic problems can occur

Symptoms can be worsened by:

  • Cold
  • Foggy weather
  • Atmospheric pollution
  • In advanced disease – even mild exercise
6
Q

Signs In severe disease:

A

Tachypnoea
Prolonged expiration
Intercostal indrawing on inspiration
Pursing of lips on expiration
Poor chest expansion
Hyperinflated lungs
Loss of normal cardiac and hepatic dullness
Carbon dioxide – responsive / insensitive
Heart failure and oedema – rare features and in terminal cases.

7
Q

Signs in mild cases

A

in mild cases there may be no signs or a quiet wheeze throughout the chest

8
Q

Diagnosis

A

This is based on several factors. There is no single diagnostic test for COPD. A clinical judgement is made on the basis of a combination of history, physical examination and spirometry to confirm airflow obstruction. Examples include the following:

Age > 35 years who have a risk factor (generally smoking) and who present with one or more symptoms
Exertional breathlessness
Chronic cough
Regular sputum production
Frequent winter `bronchitis’
Wheeze
Ask about other factors (see NICE guidance)

Further investigations that should be carried out include:

Post-bronchodilator spirometry
Chest X-ray
FBC
Calculate the  patient’s BMI
Other additional investigations (see NICE guidance)

The Medical Research Council Dyspnoea Scale is used which grades breathlessness according to level of exertion. There are five grades, 1 – 5, 5 being the most breathless.

9
Q

Spirometry

A

Airflow obstruction should be measured at the time of diagnosis of COPD or, if reconsidering diagnosis. Post-bronchodilator spirometry should be carried out to confirm the diagnosis of COPD.
Parameters measured when spirometry is carried out include:

FEV1
FVC
FEV1/FVC ratio
Severity of airflow obstruction can be graded according to the reduction in patient’s FEV1 (see table in NICE guidance).

10
Q

Types of respiratory failure

A

There are two main types of respiratory failure which can be classified as follows:

Type 1 – low PaO2, normal or low PaCO2
Type 2 – low PaO2, high PaCO2
Persistence of chronic alveolar hypoxia and hypercapnia leads to constriction of pulmonary arterioles and subsequent pulmonary arterial hypertension. Cardiac output can be normal or increased but salt and fluid retention occur as a result of renal hypoxia.

11
Q

Patients with advanced COPD may develop ..

A

Patients with advanced COPD may develop Cor pulmonale

12
Q

COPD drug therapy all

A

Beta 2 agonists inhaled
Antimuscarinics
Xanthines
PDE 4 Inhibitors

13
Q

COPD drug therapy - Antimuscarinics

A

Antimuscarinics

Short acting - ipratropium

Long acting – tiotropium, aclidinium bromide (NICE ESNM 8), glycopyrronium bromide (NICE ESNM 9)

14
Q

Combined inhalers

A

note: Ultibro Breezhaler® 85/43 micrograms (Indacaterol/glycopyrronium) was the first long-acting beta2 agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination inhaler to be approved for chronic obstructive pulmonary disease (COPD). It was launched in December 2014 (see NICE ESNM 33). Please note further products: Anoro/Ellipta® (Umeclidinium/vilanterol) received a European marketing authorisation in June 2014, which is now licensed in the UK as a maintenance treatment to relieve symptoms in adults with COPD (see NICE ESNM 49); Duaklir Genair® (aclidinium/formoterol) received a European marketing authorisation for maintenance bronchodilator treatment to relieve symptoms in adults with COPD in December 2014 (ESNM 57). Spiolto Respimat® 2.5micrograms olodaterol /dose and 2.5micrograms of Tiotropium /dose solution for inhalation cartridge with device (Boehringer Ingelheim Ltd) approved in 2015

15
Q

COPD drug therapy - Xanthines

A

Xanthines

Aminophylline, theophylline

Theophylline is not generally effective in exacerbations of COPD. Theophylline is metabolised by the liver. Theophylline can be given orally. Aminophylline can be given orally or by intravenous infusion. They have a narrow therapeutic index.

Plasma-theophylline concentration is measured 5 days after starting oral treatment and at least 3 days after any dose adjustment. A blood sample should usually be taken 4–6 hours after an oral dose of a modified-release preparation (sampling times may vary—consult local guidelines).

Patients receiving aminophylline or theophylline therapy should have their theophylline plasma concentration measured. A plasma-theophylline concentration of 10 – 20mg/litre (55 – 110 micromol/litre) is required for satisfactory bronchodilation (a lower plasma concentration may be effective). Theophylline plasma concentration is increased in patients with heart failure, hepatic impairment, viral infections, in the elderly and by drugs that inhibit its metabolism. Plasma concentration is decreased in smokers, by alcohol consumption and by drugs that induce its metabolism. Aminophylline and theophylline can interact with many medications. It is imperative that pharmacokinetic calculations are performed to avoid sub-therapeutic levels or toxic effects.

16
Q

COPD Drug therapy - PDE 4 Inhibitors

A

Phosphodiesterase type-4 inhibitor

Roflumilast is licensed as an adjunct to bronchodilators for the maintenance treatment of severe COPD associated with chronic bronchitis with a history of frequent exacerbations as add on to bronchodilator treatment PJ article and NICE article

It may need to be taken for several weeks to achieve its effect. Before commencing treatment, patients should be issued with a patient card and should be informed of the risks and precautions associated with roflumilast. Patients should be advised to record their body-weight at regular intervals.

17
Q

COPD drug therapy - Beta 2 agonists inhaled

A

Beta 2 agonists inhaled

Short-acting - terbutaline, salbutamol

Long acting - formoterol, salmeterol, indacaterol, olodaterol (ESNM 54)

Inhaled combined preparations with corticosteroid e.g. Seretide®, Symbicort®, Fostair®

18
Q

Clinical features differentiating COPD and asthma

A

COPD / ASTHMA

Smoker or ex-smoker: Nearly all / Possibly

Symptoms under age 35: Rare / Often

Chronic productive cough: Common / Uncommon

Breathlessness: Persistent and progressive / Variable

Night time waking with breathlessness and/or wheeze: Uncommon / Common

Significant diurnal or day-to-day variability of symptoms: Uncommon / Common

Exacerbations:
Oxygen: Asthma high.. COPD usually low concentration (carbon dioxide retainers)
Prednisolone: note different doses and durations.
Bronchodilators – generally the same
Aminophylline – not so much in asthma
Magnesium Sulphate – only asthma (acute severe)
Antibiotics – often in COPD not necessarily in asthma

Maintenance:
Different sequence: Asthma have ICS before LABA (see how NICE differs)
COPD LABA can be first – see CHM warnings
Asthma – not ipratropium usually or tiotropium – although recently TIO (Spiriva respimat licensed)

Newer COPD drugs: roflumilast, indacaterol, glycopyrrolate, aclidinium

ASTHMA – leukotrienes eg montelukast – momentasone, ciclesonide, ICS

COPD – no ICS licensed alone

ASTHMA – stepwise (note new guidance that beta 2 agonists should RARELY be used alone to treat asthma in BTS SIGN guidance)

COPD – not stepwise management, but can discontinue treatment if not effective e.g. mucolytic
ASTHMA – cromones.

19
Q

The severity of airflow obstruction should be assessed according to the reduction in FEV1

A

Post-bronchodilator FEV1/FVC, FEV1 % predicted - Severity of airflow obstruction

< 0.7, ≥ 80% Stage 1 – Mild

< 0.7, 50–79% Stage 2 – Moderate

< 0.7, 30–49% Stage 3 – Severe

< 0.7, < 30% Stage 4 - Very Severe

20
Q

What is chronic bronchitis?

A

Clinically defined as persistent cough with sputum production for at least 3 months of the year for 2 consecutive years. Cigarette smoke causes hyperplasia and hypertrophy of mucus secreting glands. Hyperplasia of goblet cells, less ciliated cells on epithelium. Small airways obstructed: mucus plugs, mucosal oedema, smooth muscle hypertrophy, peribronchial fibrosis. Secondary bacterial colonisation of retained products, airflow obstruction, impaired gas exchange

21
Q

What is emphysema?

A

permanent enlargement of the air spaces distal to terminal bronchiole, alveolar septal destruction due to protease-antiprotease imbalance. As distal airways held
open by alveolar septa – airways collapse therefore obstruction. Bullae form rupture causing pneumothorax.

22
Q

Summarise the working definition of COPD according to the NICE guideline 101.

A

Airflow obstruction is defined as a reduced FEV1/FVC ratio (where FEV1 is forced expired volume in 1 second and FVC is forced vital capacity), such that FEV1/FVC is less than 0.7

If FEV1 is ≥ 80% predicted normal a diagnosis of COPD should only be made in the presence of respiratory symptoms, for example breathlessness or cough.

23
Q

What is the Medical Research Council Dyspnoea Scale? How is it used in relation to COPD?

A

Gives an indication of breathlessness – Grades 1 – 5, this is available online

24
Q

Outline the mode of action of bronchodilators used to treat COPD. How would you monitor their effectiveness? What are their common side effects? What steps could be taken to minimise some of these side effects? Are
there any additional counselling points?

A

Beta2 agonists – beta receptors (detail in lecture notes/ pharmacology text). Side effects: tachycardia, hypokalaemia, fine tremor, nervous tension.

Antimuscarinics – parasympathetic system – muscarinic receptors. Side effects: dry mouth, urinary retention, constipation, angle-closure glaucoma. Protect eyes, use mouthpiece (in preference to mask) for nebuliser. Protect eyes from dry powder- NB glaucoma. Tiotropium respimat – care with cardiac rhythm disorders.

Theophylline/aminophylline – inhibit phosphodiesterase, prevents breakdown of cAMP – side effects: nausea, vomiting, GI irritation, arrhythmias, CNS stimulation. Narrow therapeutic index – ensure levels are taken.

Monitoring effectiveness:
Acute situation: Respiratory rate, Oxygen Sats, CO2, pH
PEF
Chronic situation: spirometry, QOL, exercise tolerance etc

Olodaterol (Striverdi Respimat) is a new a long-acting beta-2 agonist (LABA) for COPD

Aclidinium, Umeclidinium, glycopyrronium, and tiotropium are licensed for the maintenance treatment of patients with chronic obstructive pulmonary disease. They are
not suitable for the relief of acute bronchospasm.
Incruse received a European marketing authorisation in April 2014 and was launched in the UK in October 2014.

Seebri Breezhaler® (Novartis) (NICE ESNM 9)
Inhalation powder, hard capsule, (for use with Seebri Breezhaler® device), orange, glycopyrronium (as glycopyrronium bromide) 50 micrograms, net price 30-cap pack with Seebri Breezhaler® device = £27.50, 6-cap pack with Seebri Breezhaler® device = £5.50.
Counselling, administration: Dose by inhalation of powder, adult over 18 years, 50 micrograms (1 capsule) once daily
Equivalence Each 50 microgram capsule of glycopyrronium delivers 44 micrograms of glycopyrronium

Eklira Genuair® (Almirall) (NICE ESNM 8) Inhalation powder, aclidinium bromide 400 micrograms/metered inhalation, net price 60- dose unit = £28.60. Counselling, administration. Dose by inhalation of powder, adult over 18 years, 1 inhalation twice daily Equivalence Each 400 microgram metered inhalation of aclidinium bromide delivers 322micrograms of aclidinium

Combination products:
EU approval has also been granted for a new once-daily inhaled corticosteroid/LABA combination —Relvar Ellipta (fluticasone furoate/vilanterol) — delivered via a new dry
powder device and licensed for both asthma and COPD. Note: doses that are licensed for COPD

Ultibro Breezhaler 85/43 micrograms (Indacaterol/glycopyrronium) is the first LABA/LAMA combination inhaler to be approved COPD. It is expected to be launched in the UK in quarter 2, 2014 (see NICE) ESNM 33.

Please note a further product: Anoro/Ellipta (Umeclidinium/vilanterol) received a European marketing authorization in June 2014, which is now licensed in the UK as a maintenance treatment to relieve symptoms in adults with COPD.

Tiotropium/olodaterol (Spiolto Respimat) was launched in the UK in June 2015 and is the fourth LAMA/LABA combination inhaler to be available in the UK.

Fostair® (see ESNM 47). Note in the BNF, doses that are licensed for COPD.
CHECK REGARDING UP TO DATE LICENSING OF PRODUCTS IN UK

25
Q

deficiency of.. may cause COPD

A

Patients who have Alpha1 Antitrypsin deficiency may develop COPD.

26
Q

What is COPD

A

COPD is characterised by limitations to airflow in the lungs that are not fully reversible. The disease if progressive

27
Q

2 chronic conditions that are encompassed by COPD

A

Bronchitis - inflammation of airways

Emphysema - destruction of alveoli

28
Q

Main cause of COPD

A

Exposure to cigarette smoke. Toxic particles and gases in smoke cause inflammation of small airways. over time the repeated release of inflammatory mediators causes the release of proteases by neutophils. These proteases cause mucus hyper-secretion (chronic bronchitis) and alveolar wall destruction (emphysema)

29
Q

β2-agonists - mech of action, example of drug and dose

A

Short-acting β2-agonists have been shown to improve lung function, although they do not prevent the overall deterioration of lung function over time that occurs in COPD. Long-acting β2-agonists are used if the short acting drugs fail to achieve control of airway function. Stimulation of β2-adrenoceptors in the lungs results in relaxation of smooth muscle and hence bronchodilation. This is useful for the treatment of breathlessness associated with COPD. Stimulation of β2-adrenoceptors in the lungs also inhibits the release of histamine from mast cells and so reduces the inflammatory response.
Long-acting β2-agonists are useful in controlling this inflammation.
Short-acting examples include: salbutamol, terbutaline. Long-acting examples include: formoterol, salmeterol

30
Q

Anti-muscarinics

A

Acetylcholine is produced by the parasympathetic nervous system in response to the effects of noxious substances such as cigarette smoke. Acetylcholine produces bronchoconstriction and also stimulates the exocrine glands in the respiratory tract resulting in hypersecretion of mucus. Anticholinergic drugs block the action of acetylcholine on bronchial smooth muscle and also decrease the production of mucus. Short-acting anticholinergics can be used for the relief of breathlessness, but their onset of action is slower than that of short-acting β2-agonists. Long-acting anticholinergics are useful for slowing the progression of COPD.
Short-acting example is ipratropium.
Long-acting example is tiotripium

31
Q

Glucocorticoids - third line

A

These are only introduced when a long-acting B2-agonist and/or a long-acting antimuscarinic have failed to control the progression of COPD. They are only licensed for use in a combination inhaler with a long-acting B2-agonist.
They have some anti-inflammatory action but inflammation in COPD is less responsive than in asthma.
Glucocorticoids suppress the activity of cytokines produced in the inflammatory response and so decrease the release of histamine from mast cells and the release of other inflammatory markers.

32
Q

maintenance treatment of COPD

A

indacterol