Asthma

 

• Background

  Pathophysiology

  • Airway hyper-responsiveness, leading to (a) bronchospasm – constriction of smooth muscle in small airways (bronchi and bronchioles) – and (b) airway inflammation, leading to mucus secretion.
  • Reversible
  • No gold standard definition.

  Epidemiology

  • Affects 15% of children.
  • Not usually diagnosed in those under 2 years old, due to the difficulty of distinguishing from viral-induced wheeze and frequent URTIs.

• Presentation

  Symptoms:

  • SOB and dry cough, which often has diurnal variation, being worse at night and in the morning.

  Signs:

  • Wheeze
  • Hyperinflation
  • Pulsus paradoxus in a severe attack.
  • Reduced air entry due to mucous plug in attack.

  Features which suggest asthma:

  • Reversibility to bronchodilators (>12% change in PEFR or FEV1).
  • Episodic time course.
  • Triggers: exercise, stress, pets, viral URTIs, cold air, and tobacco smoke.
  • Eczema or hay fever may also be present.

  Features which suggest it is not asthma:

  • Dizziness and tingling (suggests panic attack).
  • Symptoms only with colds.
  • Productive cough without wheeze.
  • Voice disturbances.
  • Smoking. However, if someone has pre-existing asthma, don't assume it has become COPD just because they later start smoking.

• Risk factors

  • Atopy
  • Family history of atopy or asthma.

• Investigations

  Diagnosis with lung function testing:

  • Spirometry: FEV1/FVC ratio <0.7 confirms obstructive airway disease.
  • Then do bronchodilator reversibility (BDR) test, with ≥12% improvement in FEV1 +ve for asthma.
  • In adults, diagnosis should be confirmed with fractional exhaled nitric oxide test (FeNO), with ≥40 ppb +ve for asthma. Use in kids (5-16) only if diagnosis uncertain.
  • If spirometry, BDR, or FeNO -ve, consider 2-4 weeks of peak flow monitoring. >20% variability is +ve for asthma.
  • Specialist referral if these tests are -ve but symptoms continue.

  Who to test:

  • NICE advise formal testing for all ≥5 years old.
  • British Thoracic Society advise formal testing for those ≥5 years old with low or intermediate probability based on clinical history, but go straight to treatment if high probability (and then only test formally if there is a poor response).

  In children who cannot perform spirometry – generally those <5 years old – use clinical diagnosis and trial of treatment.

  Other tests:

  • CXR in adults to rule out other causes. May show hyperinflation in asthma.
  • Allergy testing – skin prick testing or allergen-specific IgE in blood – can identify a specific trigger if it is suspected, but is not routinely recommended.

• Management

  Overview:

  • Aim to achieve patient control over management including an asthma action plan, PEFR monitoring, and symptom diary.
  • Teach inhaler technique as many patients have trouble.
  • Inhaled steroids reduce nocturnal symptoms quickly, but wider effects takes months, so users need to know to be patient.

  In addition to inhalers:

  • Remove any identified allergens.
  • Annual flu vaccine, which is via nasal spray in kids.
  • Smoking cessation. Among its many harms, smoking weakens the effectiveness of steroids.
  • Routine antibiotics are not recommended, even if there is purulent sputum as this can be part of normal inflammation. Of course, clinical judgement can override this.

  Stepwise medical treatment

  • Most people are at steps 1-2.
  • Start at a level appropriate to disease severity.
  • Remember: you can move down as well as up!

  1. Inhaled short acting β2 agonist (SABA) as required:

  • Salbutamol 100 μg/puff. Use 2 puffs before exercise if likely to bring on symptoms.
  • Move to step 2 if using >3 times/week, waking at night, or has acute asthma exacerbation.

  2. Add inhaled corticosteroid (ICS):

  • Fluticasone, beclometasone, or budesonide.
  • Start at low dose.

  3. Add leukotriene receptor antagonist (LTRA):

  • Montelukast or zafirlukast.

  4. Add inhaled long-acting β2 agonist (LABA):

  • Salmeterol or formoterol, in combination inhaler with ICS.
  • Continue LTRA if felt to be effective.
  • If remains uncontrolled, switch ICS/LABA combo to maintenance and reliever therapy (MART), a combo which includes a fast-acting LABA (e.g. formoterol) and is used as both maintenance and reliever.

  5. Increase ICS dose until effective or trial further drug (theophylline or long-acting muscarinic antagonist).

  6. Refer to specialist for consideration of systemic immunomodulators such as:

  • Prednisolone PO.
  • Monoclonal antibodies: omalizumab (anti IgE); mepolizumab, reslizumab, or benralizumab (anti IL5).

  5-16 years old

  As for >16 years, except:

  • If LTRA insufficient, switch to (don't add) LABA.

  0-4 years old

  As for 5-16 years, except:

  • Stop ICS after 8 weeks to confirm response (and diagnosis), restarting if symptoms recur.
  • Don't add LABA; just refer to specialist after step 3.

  Drug cautions in asthma

  β-blockers:

  • Contraindicated in asthma as they lead to bronchospasm.
  • Non-cardioselective β-blockers especially problematic: propranolol, timolol.

  NSAIDs and ASA:

  • Can trigger bronchospasm, either in existing patients or as a standalone cause of new asthma.
  • Affects <10% of asthma patients.
  • OK to use if previously taken, but probably avoid if never taken, and use clopidogrel instead.
  • Can occur as Samter's triad: aspirin sensitivity, polyps ± rhinitis, and asthma.

  Management in pregnancy

  • ⅓ ↑symptoms, ⅓ ↓symptoms, and ⅓ no change.
  • Monitor closely if moderate or severe asthma as there is a risk of pregnancy complications if poorly-controlled.

• β2 agonists

  Can be short-acting (SABA) or long-acting (LABA).

  Mechanism

  Stimulate β2 adrenergic receptors in smooth muscle of airways → ↑cAMP → ↓Ca2+ intracellular → smooth muscle relaxation.

  Side effects

  • Fine tremor.
  • ↑HR and palpitations
  • Anxiety
  • Headache
  • Muscle cramps: common SE of LABAs.
  • ↓K+

• Corticosteroids

  Drugs

  Glucocorticoids:

  • Hydrocortisone is simply cortisol, the most important endogenous human glucocorticoid. Also has mineralocorticoid activity. Cortisone is an inactive metabolite of cortisol, but can be converted back into cortisol, so it can be used therapeutically.
  • Prednisolone is a synthetic glucocorticoid with a longer half life than cortisol, while prednisone is an inactive delayed-release version which is metabolised to active prednisolone. There is little evidence that prednisone has any benefits over the active prednisolone.
  • Dexamethasone is a more potent synthetic glucocorticoid, often used in oncology and intracranial conditions.
  • Others: methylprednisolone, fluticasone, beclometasone, and budesonide

  Mineralocorticoids:

  • Fludrocortisone: has strong mineralocorticoid activity, in addition to some glucocorticoid activity. Used to replace aldosterone in Addison's and congenital adrenal hyperplasia.

  Mechanism

  • Lipophilic molecule which passes through phospholipid bilayer of cell membrane, and binds to nuclear glucocorticoid or mineralocorticoid receptors, leading to altered synthesis of many proteins.
  • Anti-inflammatory effects due to ↑lipocortin-1 → ↓phospholipase A2 → ↓eicosanoid production, which includes prostaglandins, thromboxanes, and leukotrienes.

  Side effects

  Inhaled corticosteroids (ICS):

  • Oral candidiasis. Treat with nystatin or miconazole.
  • Dysphonia

  Oral glucocorticoids cause Cushing's syndrome and other symptoms:

  • Metabolic: ↑appetite, ↑weight, ↑glucose, ↑lipids.
  • GI: ulcers, acute pancreatitis.
  • Psych: mood changes, insomnia, psychosis.
  • Osteoporotic fractures.
  • Cushing appearance: moon face, striae.
  • Eyes: glaucoma, cataracts.
  • ↑BP
  • Infection
  • ↑WBC due to neutrophils being detached from vessel endothelium (demargination). Distinguished from infectious causes by absence of ↑CRP.

  Mineralocorticoids:

  • Fluid retention and ↑BP.

  Withdrawal:

  • Can cause an Addisonian crisis.
  • Courses >2 weeks require tapering and not sudden cessation.

• Theophylline

  Mechanism

  • A methylxanthine drug. Others include caffeine.
  • Phosphodiesterase inhibition → ↓Ca2+ intracellular → airway smooth muscle relaxation.
  • Aminophylline is a compound of theophylline and ethylenediamine, making it more water soluble and shorter-acting.

  Side effects

  • Nausea and vomiting.
  • Arrhythmias
  • Seizures
  • ↓K+

  Monitoring

  To ensure therapeutic levels, check plasma theophylline concentration 5 days after starting oral therapy or 4-6 hours after starting IV aminophylline.

  Interactions

  Clarithromycin and ciprofloxacin are enzyme inhibitors → ↑theophylline level. So lower the theophylline dose or avoid the combination.

• Teaching inhaler technique

  Basics

  • First ask what they broadly know about asthma and inhaler use.
  • Detach metal canister to show and check the date on the drug.
  • Ensure lips and teeth are around mouthpiece.
  • Ensure slow breath.
  • Praise correct behaviour.
  • Advise them to follow a steroid inhaler with mouthwash (e.g. Canestan [fluconazole]) to prevent thrush.

  Metered dose inahler

  1. Remove inhaler cap and shake inhaler.
  2. Breath out gently.
  3. Place mouthpiece in mouth, start breathing in, then press canister and continue slow, deep inhalation.
  4. Hold breath 10 seconds, then breath out slowly.
  5. Wait 30 seconds, then repeat all steps including the shake.

  Volumatic spacer technique

  • Needed if <8 years old, or if older and having difficulty with MDI.
  • Pick one of the techniques below and stick with it. Multiple breath is easiest.
  • Maintain spacer by washing frequently, allowing it to drip dry (cloth drying would create static). Replace every 6 months.
  • 'Prime it' when new or after each wash, by giving 2 puffs without mouth on. These puffs can stick to the sides, ensuring subsequent puffs don't stick and are delivered properly.

  Single breath technique:

  1. Remove inhaler cap, shake, insert into device.
  2. Place mouthpiece in mouth between teeth (but without biting) and with lips forming a seal. For children under 3, use a mask and ensure it forms a tight seal over the nose and mouth. Tilt spacer upwards at 30-45 degrees.
  3. Press canister once.
  4. Take deep, slow breath in, and hold for 10 seconds, then breath out.
  5. Breath in again but do not press canister.
  6. Remove MDI from spacer, keeping the device in/over the mouth. Repeat as needed, including shaking again.

  Multiple breath technique. Same as single breath, but change steps 3-6 with:

  1. Start breathing in/out normally, which should cause valve clicks. 10 breaths for an older child, or 30 seconds if very young.
  2. Once breathing pattern established, depress canister, then keep device in place and continue tidal breathing 5-10 times.
  3. Repeat all steps, including removal and shake of inhaler.

• Peak flow rate (PEFR) measurement and symptom diaries

  Basics

  • First check they know what asthma is and why it's important to monitor their symptoms.
  • Explain the steps below, demonstrate yourself, and then have them demonstrate to you.
  • They should check and record PEFR every morning and evening, and when they have an attack.

  PEFR measurement technique

  1. Set marker to zero.
  2. Stand or sit up.
  3. Take as deep a breath as you can.
  4. Place mouth on mouthpiece and breath out as hard as you can.
  5. Note the reading.
  6. Do it 3 times, recording the best one in a symptom diary.

  Acute asthma plan

  All patients should have an acute asthma plan, which may include advise such as:

  • Give up to 10 puffs of salbutamol in an attack.
  • If they don't get better, they need urgent medical care.
  • It they get better but need 10 puffs again within 4 hours, they should see their GP.