Mednotes

L15 Clinical Pharmacology Anti-inflammatories

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tagsclinicalpharmacology, lecture
aliasesL15 Clinical Pharmacology Anti-inflammatories

26 min read

Overview

This lecture covers the anti-inflammatory “preventer” medications used in obstructive airways disease, principally the glucocorticoids given by inhalation (fluticasone, budesonide, beclomethasone) and orally (prednisone). It starts from the inflammatory chemistry the drugs act on, the arachidonic acid cascade released from mast cell membranes, then works through the steroid receptor mechanism and the genes glucocorticoids switch on and off, their cellular and clinical effects in asthma, and their metabolic, regulatory and systemic adverse effects. The second half is about controlling those adverse effects through route of delivery: the pharmacokinetics of inhaled steroids, aerosol deposition, local and systemic toxicity, and safe tapering and switching. It closes with how the guidelines (GINA 2024, GOLD, COPD-X) position ICS in asthma versus COPD versus asthma-COPD overlap, and the unsettled question of ICS in cystic fibrosis.

Definitions and disease framing

  • Asthma (GINA): a heterogeneous disease, usually characterised by chronic airway inflammation. Defined by a history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation.
  • COPD (GOLD): a heterogeneous lung condition characterised by chronic respiratory symptoms (dyspnoea, cough, sputum production and/or exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction.
  • Asthma-COPD overlap / “asthma + COPD”: a descriptive term, not a single disease entity, for patients with persistent airflow limitation plus clinical features of both asthma and COPD. It covers several clinical phenotypes reflecting different underlying mechanisms.
  • Evidence base cited: GINA 2023/2024 guidelines, GOLD 2023 report, and bpac NZ guidance on pharmacological management of asthma and of COPD.

The arachidonic acid cascade: the target of preventer therapy

Ordered pathway as given in the lecture:

  1. Allergen encounter activates the mast cell (IgE receptors on its surface).
  2. Injury to the phospholipid cell membrane.
  3. Phospholipases liberate arachidonic acid from membrane phospholipids.
  4. Arachidonic acid branches down two routes.

5-lipoxygenase pathway (leukotrienes)

  • Leukotriene B4: chemotaxis.
  • Leukotrienes C4, D4, E4 (the slow-reacting substance of anaphylaxis, SRSA): bronchoconstriction, vasodilation and increased microvascular permeability. The annotated version of the diagram lists their effects as increased permeability, vasoconstriction and bronchoconstriction.

Cyclooxygenase pathway (prostanoids)

  • Prostacyclin: vasodilation.
  • Prostaglandin E1: vasodilation.
  • Thromboxane A2: vasoconstriction, plus bronchoconstriction.
  • PGD2: vasodilation and bronchoconstriction.

Preventers: what they are

Anti-inflammatory compounds used as preventers are the corticosteroids (glucocorticoids):

  • Inhaled: fluticasone, budesonide, beclomethasone.
  • Oral: prednisone.

Corticosteroids divide into glucocorticoids (cortisol) and mineralocorticoids (aldosterone); mineralocorticoids are covered in the cardiovascular and renal modules, not here.

Steroid receptor mechanism

Steps of glucocorticoid action:

  1. The glucocorticoid, being lipophilic, crosses the cell membrane.
  2. It binds an intracellular steroid receptor complex, held with the chaperone proteins Hsp56, Hsp70 and Hsp90.
  3. The receptor-hormone complex crosses the nuclear membrane.
  4. It binds the hormone response element on DNA (the glucocorticoid response element, GRE/HRE).
  5. Transcription is induced: DNA to mRNA to protein, giving altered cellular function.

The primary action of glucocorticoids is therefore regulation of gene expression, which produces both their metabolic effects (control of carbohydrate, fat and protein metabolism) and their anti-inflammatory effects (preventing phospholipid release, decreasing eosinophil recruitment and action). Glucocorticoids are highly effective at suppressing inflammatory cytokines and immune cells.

Genes up- and down-regulated

  • Up-regulated, phospholipase inhibitors: lipocortin-1 (annexin-1).
  • Up-regulated, anti-inflammatory mediators: IL-10, IL-12, and the IL-1 receptor antagonist.
  • Down-regulated, pro-inflammatory targets: IL-2, IL-3, IL-4, IL-5, IL-6, IL-11, IL-13, IL-15, TNFα, GM-CSF, endothelial adhesion molecules, COX, phospholipase A2, iNOS and others.

Where this bites on the cascade

  • Lipocortin-1 inhibits the phospholipases, so arachidonic acid is not released from membrane phospholipids in the first place.
  • Glucocorticoid also directly down-regulates PLA2 and decreases COX.
  • Net effect: reduced production of leukotrienes and of prostaglandins/thromboxane downstream.

Cellular effects of corticosteroids

Inflammatory cells

  • Eosinophil: decreased numbers, apoptosis.
  • T lymphocyte: decreased cytokines.
  • Mast cell: decreased numbers.
  • Macrophage: decreased cytokines.
  • Dendritic cell: decreased numbers.

Structural cells

  • Epithelial cell: decreased cytokines and mediators.
  • Endothelial cell: decreased leak.
  • Airway smooth muscle: increased β2 receptors, decreased cytokines.
  • Mucus gland: decreased mucus secretion.

Pertinent effects in asthma

  • Reduce recruitment and number of inflammatory cells, and consequently reduce damage to the airway epithelium.
  • Inhibit macrophage function, reducing the antigen response.
  • Reduce vascular permeability, and decrease histamine release from basophils and mast cells.
  • No bronchodilator effect, although over time they may decrease airway hyper-responsiveness.
  • They cannot reverse airway remodelling in poorly managed asthma.

Systemic adverse effects of glucocorticoids

High dose oral steroids generally have adverse systemic effects.

Metabolic actions

  • Carbohydrate: decreased glucose uptake and utilisation in skeletal muscle (conserving energy), increased hepatic gluconeogenesis to boost glucose levels.
  • Protein: increased catabolism, decreased anabolism.
  • Fat: redistribution.
  • Overall the patient gains fat and wastes muscle. Glucocorticoids are not anabolic steroids.

Regulatory actions

  • Osteoporosis: inhibits vitamin D-mediated Ca2+ absorption and suppresses osteoblast function.
  • HPA axis suppression: switches off endogenous glucocorticoid production, giving adrenal/HPA suppression.
  • Inflammation and immune reactions: decreased chronic inflammation, but immunosuppression permitting infections such as pulmonary aspergillosis, and decreased wound healing.

Clinical picture (Cushingoid habitus): euphoria (though sometimes depression, psychotic symptoms or emotional lability), benign intracranial hypertension, cataracts, moon face with plethoric cheeks, buffalo hump, hypertension, increased abdominal fat, avascular necrosis of the femoral head, thinning of skin, easy bruising, thin arms and legs from muscle wasting, poor wound healing. Also osteoporosis, tendency to hyperglycaemia, increased appetite and obesity, negative nitrogen balance and increased susceptibility to infection. Illustrated clinically by buffalo hump, abdominal striae and poorly healing skin tears.

The HPA axis and adrenal suppression

Ordered axis: stress stimulates the hypothalamus, which releases CRH (corticotropin releasing hormone), which drives the anterior pituitary to release ACTH (adrenocorticotropin hormone), which stimulates the adrenal cortex to produce cortisol, which exerts its metabolic effects and feeds back negatively on both the pituitary and the hypothalamus. Synacthen (ACTH) given intravenously is an exogenous input used to stimulate the adrenal cortex.

A high systemic dose of glucocorticoid amplifies that negative feedback chronically, suppressing the HPA axis: adrenal suppression.

Comparative potency of corticosteroids

Glucocorticoids (glucocorticoid potency / mineralocorticoid effect / duration of action on HPA; S = short, I = intermediate, L = long):

  • Cortisol (hydrocortisone): 1 / 1 / 12 h (S), the index level.
  • Cortisone: 0.8 / 0.8 / 12 h (S).
  • Hydrocortisone: 1 / 0.8 / 12 h (S).
  • Prednisone-prednisolone: 3.5-4 / 0.8 / 12-36 h (I).
  • Methylprednisolone: 5 / 0.5 / 12-36 h (I).
  • Betamethasone: 25 / 0 / >48 h (L).
  • Dexamethasone: 30 / 0 / >48 h (L).

Mineralocorticoids (glucocorticoid potency / mineralocorticoid potency / duration):

  • Fludrocortisone: 10 / 125-200 / 12-36 h (I).
  • Deoxycorticosterone: 0 / 20.
  • Aldosterone: 0 / 200-1000.

Principle: enhancing glucocorticoid activity improves anti-inflammatory action while reducing mineralocorticoid-related Na+ and H2O retention. Glucocorticoid potency and anti-inflammatory potency track together. Budesonide has a 200-fold higher affinity for the glucocorticoid receptor and a 1000-fold higher topical anti-inflammatory potency than cortisol.

Inhaled glucocorticoids: pharmacokinetics and delivery

The inhalation route minimises ADRs by avoiding the systemic circulation.

  • Key examples: fluticasone propionate; the combination inhaler Seretide (fluticasone with salmeterol, a LABA); beclomethasone dipropionate.
  • Metered dose inhalers contain microcrystalline drug preparations (fluticasone, budesonide, beclomethasone) and allow delivery at roughly 1/100 of the concentration needed for a similar systemic anti-inflammatory effect from an oral drug.
  • Typical dosing: 1-2 puffs once or twice daily, depending on severity, choice of steroid and inhaler device.
  • Metabolism: in lung and liver by the CYP3A family (CYP3A4, 3A5, 3A7). Very little active drug reaches the systemic circulation, reducing the potential for ADRs.
  • Interpatient variability in metabolism of inhaled glucocorticoids could contribute to steroid resistance and insensitivity.
  • Most glucocorticoids induce CYP enzymes, increasing their own metabolism.

Deposition of aerosols

Three mechanisms, with their share of deposition:

  1. Inertial impaction: 90% (large particles hitting airway branch points).
  2. Sedimentation: 9% (medium particles settling out).
  3. Diffusion: 1% (small particles moving by Brownian motion).

Relevant particle size for inhaled drug aerosols is 1-10 µm; particles under 1 µm are not applicable.

Disposition of inhaled fluticasone

  • About 90% is swallowed, less than 10% reaches the lungs, and only about 1% enters the systemic circulation.
  • Particle size determines fate: >10 µm deposits in the mouth; 1-5 µm reaches the small airways; <0.5 µm is exhaled.
  • The low pH of the GI tract and first-pass metabolism (gut wall and liver, via the portal vein) greatly reduce the drug entering the systemic circulation.

Adverse effects of inhaled glucocorticoids

Systemic

With chronic high dose use, enough drug may be absorbed from the GI tract and pulmonary epithelium to cause systemic effects, and poor inhaler use worsens this. Long-term inhalation of potent steroids such as fluticasone can result in:

  • Infection and immunosuppression.
  • Poor wound healing in trauma.
  • Osteoporosis.
  • Delayed growth in children.
  • Secondary adrenal insufficiency: systemic glucocorticoid presence suppresses endogenous cortisol, leaving insufficient adrenal reserve to respond to stress when the glucocorticoid is discontinued.

Risk table for systemic toxicity of inhaled glucocorticoids:

  • HPA axis suppression: no significant risk until high chronic doses are used.
  • Bone resorption: modest but significant increase seen even at low doses (400 µg/day beclomethasone).
  • Candidiasis: incidence <5%, reduced by use of a spacer device.
  • Growth retardation: difficult to separate the effect of the disease from the effect of treatment when all studies are considered.

ICS in children: assessment of future risk

Height should be checked at least yearly, because poorly controlled inhaler use in asthma can affect growth (Pedersen 2001), and growth velocity may be further reduced in the first 1-2 years of ICS treatment (Loke 2015). Consider referral if there is growth delay.

Local, and how to mitigate

  • Oropharyngeal candidiasis: local immunosuppression of the oral and pharyngeal mucosa allows infection by Candida albicans (white plaques on the tongue and oral mucosa).
  • Dysphonia: hoarse voice from laryngeal deposition of drug particles, more with pMDIs than with DPIs.

To reduce these ADRs:

  • Rinse after use, or gargle with an antifungal mouthwash.
  • Use a large volume spacer to reduce travel of large droplets.
  • Reduce dose frequency according to pulmonary function tests, symptom presentation and FENO.

Oral corticosteroids

  • Prednisone tablets or prednisolone suspension.
  • Used early during acute asthma exacerbations if the patient is unresponsive to bronchodilators. Mnemonic SOS: Salbutamol, Oxygen, Steroids.
  • Prednisone is a prodrug: converted to prednisolone by hepatic 11-β hydroxysteroid dehydrogenase 1, which then binds glucocorticoid receptors.
  • Short course, high dose: prednisone 40-60 mg once daily for about 5 days, then stop.
  • Longer courses need gradual reduction of systemic levels, using dose tapering to avoid exacerbating asthma and suppressing pituitary/adrenal function.

Chronic oral steroids and withdrawal

Chronic supra-physiological oral glucocorticoid levels may induce a Cushingoid symptomatology, involving a suppressed HPA axis and adrenal atrophy, so withdrawal needs great care.

Tapering rule where therapy has been chronic (>7 days): rapidly reduce the therapeutic dose to a physiological level (for example prednisone 5-7.5 mg/day), then proceed with slower withdrawal to permit HPA axis recovery. Check the cortisol response if needed. Resume the patient on the ICS as soon as oral dose reduction occurs.

Important

Black box warning on switching asthmatics from chronic systemic steroids to inhalation delivery: it takes months for the HPA axis to recover, so the patient may have adrenal insufficiency. Inhaled steroids will control the asthma, but during recovery the rest of the body remains deficient in endogenous glucocorticoid (hydroxycortisone). Recognise the risk of immunosuppression, taper according to the individual and the length of glucocorticoid exposure, and if the patient is stressed, resume oral/systemic steroids as soon as possible.

Guideline placement of preventers

GINA 2024, adults and adolescents 12+ years

Personalised asthma management follows a cycle of assess, adjust, review for individual patient needs.

Track 1, preferred controller and reliever (ICS-formoterol). Using ICS-formoterol as the reliever reduces exacerbation risk compared with a SABA reliever and is a simpler regimen.

  • Steps 1-2: as-needed-only low dose ICS-formoterol.
  • Step 3: low dose maintenance ICS-formoterol.
  • Step 4: medium dose maintenance ICS-formoterol.
  • Step 5: add-on LAMA, refer for phenotype assessment, consider high dose maintenance ICS-formoterol, with or without anti-IgE, anti-IL5/5R, anti-IL4Rα, anti-TSLP.
  • Reliever throughout: as-needed low dose ICS-formoterol.

Track 2, alternative controller and reliever. Before choosing a SABA-reliever regimen, check whether the patient is likely to adhere to daily controller treatment.

  • Step 1: take ICS whenever SABA is taken.
  • Step 2: low dose maintenance ICS.
  • Step 3: low dose maintenance ICS-LABA.
  • Step 4: medium/high dose maintenance ICS-LABA.
  • Step 5: add-on LAMA, refer for phenotype assessment, consider high dose maintenance ICS-LABA, with or without the biologics above.
  • Reliever throughout: as-needed ICS-SABA, or as-needed SABA.

Other controller options (limited indications, or less evidence for efficacy or safety): low dose ICS whenever SABA taken, or daily LTRA, or add HDM SLIT; medium dose ICS, or add LTRA, or add HDM SLIT; add LAMA or LTRA, or switch to high dose ICS-only; add azithromycin (adults) or add LTRA. As a last resort consider adding low dose OCS, weighing side effects.

Stepwise management of stable COPD (COPD-X Plan, NZ/Aus 2022)

Severity bands:

  • Mild: few symptoms, breathless on moderate exertion, little or no effect on daily activities; FEV1 approximately 60-80% predicted.
  • Moderate: breathless walking on level ground, increasing limitation of daily activities, recurrent chest infections, exacerbations requiring oral corticosteroids and/or antibiotics; FEV1 approximately 40-59% predicted.
  • Severe: breathless on minimal exertion, daily activities severely curtailed, exacerbations of increasing frequency and severity; FEV1 <40% predicted.

Confirm the diagnosis with post-bronchodilator airflow limitation on spirometry, FEV1/FVC <0.70. Any pattern of cough with or without chronic sputum production may indicate COPD. The overall aims are to optimise function, prevent deterioration and develop a plan of care.

Non-pharmacological interventions: reduce risk factors (avoid tobacco smoke and air pollution, support smoking cessation, annual influenza and pneumococcal vaccine); optimise function (regular exercise, nutrition, GP action plan); optimise treatment of co-morbidities (cardiovascular disease, anxiety, depression, lung cancer, osteoporosis); refer symptomatic patients to pulmonary rehabilitation; initiate advanced care planning (moderate/severe); manage advanced lung disease with domiciliary oxygen, long-term non-invasive ventilation, surgery and bronchoscopic interventions if indicated (severe).

Pharmacological interventions, in order:

  1. Start with short-acting relievers as needed (SABA or SAMA).
  2. Add long-acting bronchodilators (LAMA or LABA), considering combination LAMA/LABA depending on symptomatic response.
  3. Consider adding ICS; single inhaler triple therapy ICS/LABA/LAMA may be suitable in patients with at least one severe exacerbation requiring hospitalisation or at least two moderate exacerbations in the previous 12 months plus significant symptoms despite LAMA/LABA or ICS/LABA, or in patients already stabilised on a combination of LAMA, LABA and ICS.

Assess and optimise inhaler device technique at every visit, and minimise inhaler device polypharmacy.

Warning

The transcript flags that the bottom edge of the COPD-X stepwise management table appears cut off in the render, so content below the transcribed rows is not confirmed.

Key safety summary: asthma versus COPD

The labels “asthma” and “COPD” remain clinically important because the evidence supports safety-based differences in treatment.

  • Asthma: never treat with bronchodilators alone, because of the risk of death, hospitalisation and severe exacerbations.
  • COPD: start treatment with LABA and/or LAMA without ICS.
  • Patients with both diagnoses are more likely to die or be hospitalised if treated with LABA alone rather than ICS-LABA (Gershon et al, JAMA 2014; Kendzerska et al, Annals ATS 2019).
  • High dose ICS may be needed for severe asthma but should not be used in COPD, because of pneumonia risk.

Warning

The transcript flags this summary slide as not rendered, transcribed from pdftotext only, so its layout and any diagram are not confirmed. The same flag applies to the ICS-in-children slide above.

Patients with features of both asthma and COPD (GINA/GOLD)

Clinical phenotype: adults with chronic respiratory symptoms (dyspnoea, cough, chest tightness, wheeze). Three columns of the decision table:

Highly likely to be asthma, treat as asthma. History: symptoms vary over time and in intensity; triggers may include laughter, exercise, allergens, seasonal exposures; onset before age 40; symptoms improve spontaneously or with bronchodilators (minutes) or ICS (days to weeks); current asthma diagnosis or asthma diagnosed in childhood. Lung function: variable expiratory airflow limitation; persistent airflow limitation may be present.

Features of both asthma and COPD, treat as asthma. History: symptoms intermittent or episodic, may have started before or after age 40; may have a history of smoking or other toxic exposures, low birth weight, or respiratory illness such as tuberculosis; plus any of the asthma features listed at left. Lung function: persistent expiratory airflow limitation, with or without bronchodilator reversibility.

Likely to be COPD, treat as COPD. History: dyspnoea persistent on most days, onset after age 40, limitation of physical activity, possibly preceded by cough and sputum, bronchodilator gives only limited relief; history of smoking or other toxic exposure, low birth weight, or respiratory illness such as tuberculosis; no past or current asthma diagnosis. Lung function: persistent expiratory airflow limitation, with or without bronchodilator reversibility.

Initial pharmacological treatment (alongside treating comorbidities and risk factors):

  • Asthma: ICS-containing treatment is essential to reduce the risk of severe exacerbations and death; as-needed low dose ICS-formoterol may be used as reliever; do not give LABA and/or LAMA without ICS; avoid maintenance OCS.
  • Both: ICS-containing treatment is essential to reduce risk of severe exacerbations and death; add-on LABA and/or LAMA usually also needed; additional COPD treatments as per GOLD; do not give LABA and/or LAMA without ICS; avoid maintenance OCS.
  • COPD: treat as COPD per the GOLD report, initially LAMA and/or LABA; add ICS per GOLD for patients with hospitalisations, at least 2 exacerbations per year requiring OCS, or blood eosinophils ≥300/µl; avoid high dose ICS; avoid maintenance OCS; a reliever containing ICS is not recommended.

Review the patient after 2-3 months, and refer for expert advice if there is diagnostic uncertainty or inadequate response.

Inhaler combination compatibility

A green tick indicates therapies that can be used together.

  • SABA (salbutamol: Ventolin, Airomir, Asmol; terbutaline: Bricanyl): combinable with SAMA, LAMA, LABA, LABA/LAMA, ICS/LABA and ICS/LAMA/LABA, but not with itself.
  • SAMA (ipratropium: Atrovent): combinable with SABA, LABA, ICS/LABA.
  • LAMA (tiotropium: Spiriva; glycopyrronium: Seebri; aclidinium: Bretaris; umeclidinium: Incruse): combinable with SABA, LABA, ICS/LABA.
  • LABA (salmeterol: Serevent; formoterol: Oxis, Foradile; indacaterol: Onbrez): combinable with SABA, SAMA, LAMA.
  • LABA/LAMA (indacaterol/glycopyrronium: Ultibro; umeclidinium/vilanterol: Anoro; tiotropium/olodaterol: Spiolto; aclidinium/formoterol: Brimica): combinable with SABA.
  • ICS/LABA (fluticasone propionate/salmeterol: Seretide and SalplusF/Cipla; budesonide/formoterol: Symbicort and DuoResp; fluticasone furoate/vilanterol: Breo): combinable with SABA, SAMA, LAMA.
  • ICS/LAMA/LABA (fluticasone furoate/umeclidinium/vilanterol: Trelegy): combinable with SABA.

ICS in cystic fibrosis

  • A clear benefit of ICS in CF patients has not been established, and there is no benefit to chronic ICS use in CF.
  • Delivering inhaled drugs in sufficient quantities to airways blocked by viscous mucus may be ineffective, and poor inhaler technique, especially in children, adds to the problem.
  • The airway inflammation in CF is predominantly neutrophilic, and where neutrophils predominate (for example in severe asthma and acute bronchiolitis) corticosteroids are not particularly effective (Green 2002; Patel 2004).
  • The role of neutrophils in the pathology is unclear, beneficial versus deleterious.
  • Fluticasone has been shown to prolong neutrophil survival by inhibiting apoptosis, so ICS might actually promote inflammation in CF airways. The benefit remains unclear.

Self-test

  1. Define asthma as GINA defines it, and state how the GOLD definition of COPD differs in its stated causes and course.
  2. Explain what “asthma-COPD overlap” means and why the lecture stresses it is not a definition of a single disease entity.
  3. Describe the steps of the arachidonic acid cascade from allergen encounter to mediator release, naming the two branching enzymes.
  4. List the leukotriene and prostanoid products of the cascade with the physiological effect of each.
  5. Describe the steps by which a glucocorticoid molecule alters cellular function after crossing the cell membrane.
  6. Name the phospholipase inhibitor whose transcription glucocorticoids up-regulate, and explain the two other ways glucocorticoids reduce flux through the cascade.
  7. Distinguish the cytokines glucocorticoids up-regulate from those they down-regulate.
  8. List the effects of corticosteroids on the inflammatory cells and on the structural cells of the airway.
  9. Explain why a glucocorticoid preventer does not relieve an acute attack, and state the two things the lecture says glucocorticoids cannot and can do to airway responsiveness over time.
  10. Describe the metabolic actions of high dose oral glucocorticoids on carbohydrate, protein and fat, and predict the resulting change in body composition.
  11. Explain the mechanism by which chronic glucocorticoid use causes osteoporosis.
  12. Describe the steps of the HPA axis from stress to cortisol, and predict what happens to it during chronic high dose systemic glucocorticoid therapy.
  13. Rank cortisol, prednisone, dexamethasone and fludrocortisone by glucocorticoid potency, and state which of them has essentially no mineralocorticoid effect.
  14. Explain why increasing glucocorticoid potency relative to mineralocorticoid potency is pharmacologically desirable.
  15. Describe the fate of an inhaled dose of fluticasone, giving the approximate percentage swallowed, reaching the lungs and reaching the systemic circulation.
  16. List the three mechanisms of aerosol deposition with their approximate contributions, and state the useful particle size range for inhaled drug aerosols.
  17. Which enzyme family metabolises inhaled glucocorticoids, and what two consequences does the lecture draw from that?
  18. List the four major systemic adverse effects of inhaled glucocorticoids in the risk table, with the risk statement attached to each.
  19. Distinguish oropharyngeal candidiasis from dysphonia as ICS adverse effects, by mechanism, and list three measures that reduce them.
  20. A child on regular ICS attends for review. What should be monitored at least yearly, and why?
  21. Describe the regimen for oral prednisone in an acute asthma exacerbation, including the dose, duration and the activation step prednisone must undergo.
  22. Explain the rule for tapering oral glucocorticoids after more than seven days of therapy, and why tapering is done in two phases.
  23. Predict what happens if an asthmatic on chronic systemic steroids is switched abruptly to an inhaled steroid and then suffers a major physiological stress, and state the correct management.
  24. Distinguish GINA Track 1 from Track 2 by reliever, and state the reason given for preferring Track 1.
  25. State the spirometric criterion that confirms COPD and the FEV1 bands defining mild, moderate and severe disease.
  26. State the conditions under which ICS should be added in stable COPD.
  27. Distinguish the initial pharmacological treatment of asthma from that of COPD in a patient with chronic respiratory symptoms, and state what should be done for a patient with features of both.
  28. Explain why high dose ICS is acceptable in severe asthma but not in COPD.
  29. Explain why ICS have not been shown to benefit patients with cystic fibrosis, giving both a delivery reason and an immunological one.
  30. Integrative: a 55 year old with a childhood asthma diagnosis, a smoking history and persistent airflow limitation is currently on a LABA/LAMA inhaler alone. Using the definitions, the safety summary and the overlap table, explain what is wrong with this regimen and what should change.

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