Asthma-COPD Overlap Syndrome: an Overview of the New GINA/GOLD Guidelines

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Asthma-COPD overlap syndrome: An overview of the new GINA/GOLD guidelines

Item Type Article

Authors Morrow, Ruth

Publisher Nursing in General Practice

Journal Nursing in General Practice

Download date 05/10/2021 18:20:56

Link to Item http://hdl.handle.net/10147/559070

Find this and similar works at - http://www.lenus.ie/hse nursingingeneralpractice clinical review

Asthma-COPD Overlap Syndrome: An overview of the new GINA/GOLD guidelines

RUtH MORROW, CLiNiCAL EDiTor, NUrSiNG iN GENErAL PrACTiCE

Background GiNA/GOLD GUiDELiNES FOR AStHMA, COPD AND This article explores a new syndrome, ACoS – Asthma-CoPD AStHMA-COPD OVERLAP SyNDROME (ACOS)1 overlap Syndrome and presents the new GiNA/GoLD Guidelines. The diagnosis and management of ACoS will be addressed with Step-wise approach to ACOS recommendations for onward referral should the patient’s condi- GiNA/GoLD (2014) recommend a step-wise approach to diagno- tion warrant it. sis, management, and onward referral of the patient presenting Asthma-CoPD overlap Syndrome (ACoS) is “characterised with ACoS. The Guidelines ask: by persistent airfl ow obstruction with several features usually associated with asthma and several features associated with Step 1: Does the patient have chronic airways disease? CoPD. ACoS is therefore identifi ed by the features that it shares Step 2: The syndromic diagnosis of asthma, CoPD and ACoS in with both asthma and CoPD”.1 an adult patient ACoS occurs in people that have asthma, are over 40 and who Step 3: Spirometry smoke or non-smokers with long standing asthma who progress Step 4: Commence initial therapy to CoPD. in 2014, GiNA & GoLD published a joint guidance on the Step 5: referral for specialised investigations (if necessary) diagnosis and management of ACoS. The prevalence of ACoS was demonstrated in a screening Diagnosis questionnaire carried out by Marco et al,2 which showed 1.6% Step 1: Does the patient have chronic airways disease? in 20-44 age group, 2.1% in 45-64 age group and 4.5% in A fi rst step in diagnosing these conditions is to identify patients 65-84 age group. it has been documented that patients with at risk of, or with signifi cant likelihood of having chronic airways ACoS experience more frequent and severe exacerbations and disease, and to exclude other potential causes of respiratory experience longer hospital stays than patients with either asthma symptoms. This is based on a detailed medical history, physical or CoPD alone.3 examination, and other investigations.

25 clinical review nursingingeneralpractice

Clinical history • Abnormalities on chest X-ray or CT scan (performed for Features that should prompt consideration of chronic airways other reasons such as screening for lung cancer), including disease include: hyperinflation, airway wall thickening, air trapping, • History of chronic or recurrent cough, sputum production, hyperlucency, bullae or other features of emphysema dyspnoea, or wheezing; or repeated acute lower respiratory • May identify an alternative diagnosis, including bronchiectasis, tract infections evidence of lung infections such as tuberculosis, interstitial • Report of a previous doctor diagnosis of asthma or COPD lung diseases or cardiac failure. • History of prior treatment with inhaled medications • History of smoking tobacco and/or other substances Screening questionnaires • Exposure to environmental hazards, e.g. occupational or Many screening questionnaires have been proposed to help the domestic exposures to airborne pollutants. clinician identifying subjects at risk of chronic airways disease, based on the above risk factors and clinical features. Examples Physical examination are the Asthma Control Test and the COPD Assessment Test. • May be normal • Evidence of hyperinflation and other features of chronic lung STEP 2. The syndromic diagnosis of asthma, COPD and ACOS in disease or respiratory insufficiency an adult patient • Abnormal auscultation (wheeze and/or crackles). Given the extent of overlap between features of asthma and COPD, the approach proposed focuses on the features that Radiology are most helpful in distinguishing asthma and COPD (Table • May be normal, particularly in early stages 1a).

Table 1a. Usual features of asthma, COPD and ACOS (GINA and GOLD, 2014) Feature Asthma COPD ACOS Age of onset Usually childhood but can Usually > 40 years of age Usually age ≥40 years, but may have commence at any age had symptoms in childhood or early adulthood Pattern of respiratory Symptoms may vary over time Chronic usually continuous Respiratory symptoms including symptoms (day to day, or over longer symptoms, particularly exertional dyspnoea are persistent periods), often limiting activity. during exercise, with ‘better’ but variability may be prominent Often triggered by exercise, and‘worse’ days emotions including laughter, dust or exposure to allergens. Lung function Current and/or historical FEV1 may be improved by Airflow limitation not fully reversible, variable airflow limitation, e.g. therapy, but post-BD FEV1/ but often with current BD reversibility, AHR FVC <0.7 persists Lung function between May be normal between Persistent airflow Persistent airflow limitation symptoms symptoms limitation Past history or family history Many patients have allergies History of exposure to Frequently a history of doctor- and a personal history of noxious particles and gases diagnosed asthma (current or asthma in childhood, and/or (mainly tobacco smoking and previous), allergies and a family family history of asthma biomass fuels) history of asthma, and/or a history of noxious exposures Time course Often improves spontaneously Generally, slowly progressive Symptoms are partly but significantly or with treatment, but may over years despite treatment reduced by treatment. Progression is result in fixed airflow limitation usual and treatment needs are high Chest x-ray Usually normal Severe hyperinflation & other Similar to COPD changes of COPD Exacerbations Exacerbations occur, but the Exacerbations can be reduced Exacerbations may be more common risk of exacerbations can be by treatment. If present, than in COPD but are reduced considerably reduced by comorbidities contribute to by treatment. Comorbidities can treatment impairment contribute to impairment Typical airway inflammation Eosinophils and/or neutrophils Neutrophils in sputum, Eosinophils and/or neutrophils in lymphocytes in airways, may sputum. have systemic inflammation

26 NEW COMBINATION Rapid onset* and ** 50/5 µg 125/5 µg 250/10 µg long lasting ef cacy Asthma maintenance treatment

INNOVATION Modern aerosol device with a patient-facing dose counter1

* Open label study, signi cant increase in FEV1 5 mins after dosing (p=o.oo1) (Aalbers et al: Onset of Bronchodilation with uticasone/formoterol combination versus uticasone/salmeterol in an open-label, randomised study; Adv Ther 2012) ** 6-12 month open label study, signi cant improvement in spirometric secondary endpoints vs baseline (Mansur et al, Long Term Safety and Ef cacy of uticasone/formoterol combination therapy in Asthma; JAMP -Vol 25, No0, 2012 p1-10)

utiform is indicated for the regular treatment of asthma in adults and adolescents (12 years and over), fluticasone propionate/formoterol where use of a combination product (inhaled corticosteroid [ICS] and long-acting ß2-agonist [LABA]) is appropriate. utiform 250/10µg indicated in adults only.

utiform® (FLUTICASONE PROPIONATE AND FORMOTEROL FUMARATE) PRESSURISED INHALATION SUSPENSION. impairment. Prolonged treatment with high doses of corticosteroids may result in adrenal suppression and acute adrenal crisis, particularly in Prescribing Information Ireland. Please read the Summary of Product Characteristics before prescribing. adolescents and children or potentially as a result of trauma, surgery, infection or rapid dose reduction. Patients should be advised that utiform Presentation: Pressurised inhalation suspension, in a pressurised metered dose inhaler (pMDI), containing uticasone propionate and contains a small amount of ethanol; however this negligible amount does not pose a risk to patients. utiform is not recommended in children formoterol fumarate dihydrate at strengths of 50 µg/5 µg, 125 µg/5 µg or 250 µg/10 µg per actuation. Indications: Regular treatment of asthma under 12 years of age. Interactions: Caution is advised in long-term co-administration with strong CYP3A4 inhibitors (e.g. ritonavir, atazanavir,

where the use of a combination product (inhaled corticosteroid and long-acting ß2-agonist) is appropriate: For patients not adequately controlled clarithromycin, indinavir, itraconazole, nel navir, saquinavir, ketoconazole and telithromycin); co-administration should be avoided if possible. with inhaled corticosteroids and ‘as required’ inhaled short-acting ß2-agonist (SABA), or for patients already adequately controlled on both an Ritonavir in particular should be avoided, unless the bene ts outweigh the risks of systemic side-effects. Caution is advised with use of non- inhaled corticosteroid and a long-acting ß2-agonist (LABA). utiform 50 µg/5 µg and 125 µg/5 µg per actuation are indicated for use in adults potassium sparing diuretics (e.g. loop or thiazide), xanthine derivatives, glucocorticosteroids, L-Dopa, L-thyroxine, oxytocin, alcohol or other and adolescents 12 years and above. utiform 250 µg/10 µg per actuation is only indicated for use in adults. Dosage and administration: adrenergic drugs. There is an increased risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons. For inhalation use. The patient should be shown how to use the inhaler correctly by a physician or other healthcare professional. Patients should Hypokalaemia may increase the risk of arrhythmias in patients being treated with digitalis glycosides. Concomitant use of ß-adrenergic drugs can be given the strength of utiform containing the appropriate uticasone propionate dose for their disease severity (note that utiform 50 µg/5 have a potentially additive effect. Extreme caution should be taken when using formoterol fumarate with drugs known to prolong the QTc interval, µg per actuation is not appropriate in patients with severe asthma). The appropriate strength should be taken as two inhalations, twice-daily such as tricyclic antidepressants or MAOIs (and for two weeks following their discontinuation), as well as antipsychotics (including phenothiazines), (normally in the morning and evening) and used every day, even when asymptomatic. utiform should not be used in children under 12 years. quinidine, disopyramide, procainamide and antihistamines. Concomitant use of an MAOI or a similar agent, such as furazolidone or procarbazine, Prescribers should be aware that in asthmatics, uticasone propionate is as effective as some other inhaled steroids when administered at may precipitate hypertensive reactions. ß-blockers and formoterol fumarate may inhibit the effect of each other. ß-blockers may produce severe approximately half the total daily microgram dose. Total daily dose can be increased if asthma remains poorly controlled by administering a higher bronchospasm in asthma patients, and they should not normally be treated with ß-blockers including those that are used as eye drops to treat

strength inhaler. Appropriate doses of the ß2-agonist and inhaled corticosteroid (ICS) in separate inhalers, or the ICS alone, should be prescribed glaucoma. Under certain circumstances, e.g. as prophylaxis after myocardial infarction, cardioselective ß blockers could be considered with caution if a patient requires doses outside the recommended dose regimens. Patients should be assessed regularly and once asthma is controlled, Pregnancy and lactation: utiform is not recommended during pregnancy. It should only be considered if bene ts to the mother outweigh treatment should be reviewed and stepped down to the lowest effective dose, or an ICS alone. It is extremely important to regularly review risks to the foetus. It is not known whether uticasone propionate or formoterol are excreted in breast milk; a risk to the breast feeding infant patients as their treatment is stepped down. ICSs alone are rst line treatment for most patients. utiform is not intended for initial treatment cannot be excluded. A decision should be made on whether to discontinue breastfeeding or discontinue/abstain from utiform. Side-effects: of mild asthma. For patients with severe asthma the ICS therapy should be established before prescribing a xed-dose combination product. Potentially serious side-effects: hyperglycaemia; depression; aggression; behavioural changes (predominantly in children); paradoxical Patients on utiform must not use an additional LABA. An inhaled SABA should be taken for immediate relief of asthma symptoms arising bronchospasm; agitation; vertigo; palpitations; ventricular extrasystoles; angina pectoris; tachycardia; hypertension; dyspnoea; peripheral oedema; between doses. The AeroChamber Plus® spacer device is recommended in patients who nd it dif cult to use inhalers; re-titration should always Cushings Syndrome; adrenal suppression; growth retardation; cataract and glaucoma; hypersensitivity reactions and QTc interval prolongation. follow the introduction of a spacer device. Patients should be advised to contact their prescriber when the utiform dose indicator is getting near Please consult the SPC for details of non-serious side-effects and those reported for the individual molecules. Legal category: POM Package zero.Contra-indications: Hypersensitivity to any of the active substances or excipients. Precautions and warnings: utiform should not be quantities: One inhaler containing 120 actuations 50 µg/5 µg, 125 µg/5 µg, 250 µg/10 µg Marketing Authorisation numbers: PA used for the rst treatment of asthma, to treat acute asthma symptoms or for prophylaxis of exercise-induced asthma. It should not be initiated 1688/13/1-3 Marketing Authorisation holder: Mundipharma Pharmaceuticals Limited, Millbank House, Arkle Road, Sandyford, Dublin 18, during an exacerbation, during signi cantly worsening or acutely deteriorating asthma, and should not be stopped abruptly. Patients should use Ireland. Member of the Mundipharma Pharmaceutical Group. For medical information enquiries, please contact [email protected] their utiform maintenance treatment as prescribed, even when asymptomatic. If a patient experiences serious asthma-related adverse events Date of preparation: January 2013 or exacerbations, they should continue treatment but also seek medical advice. Patients should be reviewed as soon as possible if there is any Reference: indication of deteriorating asthma control. In the case of sudden and progressive deterioration, which is potentially life-threatening, an urgent 1. utiform Summary of Product Characteristics medical assessment should be carried out. Use with caution in patients with: pulmonary tuberculosis; quiescent tuberculosis; fungal, viral or other infections of the airway; thyrotoxicosis; pheochromocytoma; diabetes mellitus (consider additional blood sugar controls); uncorrected ® FLUTIFORM is a registered trademark of Jagotec AG, and is used under licence. hypokalaemia; predisposition to low levels of serum potassium; impaired adrenal function (monitor HPA axis function regularly) ; hypertrophic ® AEROCHAMBER and AEROCHAMBER PLUS are registered trade marks of Trudell Medical International. obstructive cardiomyopathy; idiopathic subvalvular aortic stenosis; severe hypertension; aneurysm or other severe cardiovascular disorders. There © 2012 Mundipharma Pharmaceuticals Limited.

is risk of potentially serious hypokalaemia with high doses of ß2-agonists or concomitant treatment with ß2-agonists and drugs that can induce or potentiate a hypokalaemic effect. Particular caution is recommended in unstable or acute severe asthma and other conditions when the Adverse events should be reported. Reporting forms and information can be found at likelihood for hypokalemia adverse effects is increased. Monitoring of serum potassium levels is recommended during these circumstances. http://www.imb.ie/EN/Safety--Quality/Online-Forms/Human-Medicine-Adverse-Drug-Reaction.aspx. Formoterol may induce prolongation of the QTc interval. Caution must be observed when treating patients with existing prolongation of QTc Adverse events should also be reported to Mundipharma Pharmaceuticals Limited on 01 206 3800/1800 991830 interval. utiform should be discontinued immediately if there is evidence of paradoxical bronchospasm. Systemic effects with an ICS may occur, (outside of ce hours). particularly at high doses for prolonged periods or when combined with potent CYP3A4 inhibitors, but are less likely than with oral corticosteroids. Date of preparation: March 2014 Use of a spacer device may also cause an increased systemic exposure. Increased exposure can be expected in patients with severe hepatic IRE/FL-12042(1)

2010939 Flutiform product ad 340x245 IPharm.indd 1 15/04/2014 12:12 clinical review nursingingeneralpractice

Table 1b assists the clinician in determining if the patient has asthma or CoPD. if three or more boxes are checked for either asthma or CoPD, that diagnosis is suggested. it there are similar number of boxes checked in each column, the diagnosis of ACoS should be considered.

Step 3: Spirometry Spirometry is essential for the assessment of patients with spirometry at a single suspected chronic disease of the airways in order to confi rm or exclude the diagnosis. it should be performed at either the initial or a subsequent visit in order to avoid unnecessary trials of vari- visit is not always ous therapies. Spirometry confi rms chronic airfl ow limitation but is of more limited value in distinguishing between asthma with confi rmatory of a fi xed airfl ow obstruction, CoPD and ACoS (GiNA & GoLD, 2014) Measurement of peak expiratory fl ow (PEF), although not an alternative to spirometry, if performed repeatedly on the diagnosis, and results same meter over a period of 1–2 weeks may help to confi rm the diagnosis of asthma by demonstrating excessive variability, but a must be considered normal PEF does not rule out either asthma or CoPD. A high level of variability in lung function may also be found in ACoS. After the results of spirometry and other investigations are in the context of the available, the provisional diagnosis from the syndrome-based assessment must be reviewed and, if necessary, revised. As clinical presentation shown in Table 2, spirometry at a single visit is not always confi rmatory of a diagnosis, and results must be considered in the context of the clinical presentation, and whether treatment has been commenced. inhaled corticosteroids and long-acting bronchodilators infl uence results, particularly if a long withhold period is not used prior to performing spirometry. Further tests might therefore be necessary either to confi rm the diagnosis or to assess the response to initial and subsequent treatment.

Table 1b: Features that favour Asthma or COPD GINA and GOLD, 2014 Features asthma COPD Age of onset onset before age 20 years onset after age 40 years Pattern of Variation in symptoms over minutes, hours or days Persistence of symptoms despite treatment respiratory Symptoms worse during the night or early Good and bad days but always daily symptoms and symptoms morning exertional dyspnoea Symptoms triggered by exercise, emotions Chronic cough and sputum preceded onset of dyspnoea including laughter, dust or exposure to allergens unrelated to triggers Lung function record of variable airfl ow limitation (spirometry, record of persistent airfl ow limitation (post-bronchodilator p e a k fl o w) FEV1/FVC < 0.7) Lung function Lung function normal between Lung function abnormal between symptoms between symptoms symptoms Past history or Previous doctor diagnosis of asthma Previous doctor diagnosis of CoPD, chronic bronchitis or family history Family history of asthma, and emphysema other allergic condition Heavy exposure to a risk factor: tobacco smoke, biomass fuels Time course No worsening of symptoms over time. Symptoms Symptoms slowly worsening over time (progressive course vary either seasonally, or from year to year over years) May improve spontaneously or rapid-acting bronchodilator treatment provides only have an immediate response to limited relief. BD or to iCS over weeks Chest x-ray Normal Severe hyperinfl ation

28 Improvement in early morning, daily and night-time COPD symptoms.1* *compared to placebo Twice daily administration1

Eklira Genuair 322 micrograms inhalation powder Abbreviated Prescribing Information Please consult the Summary of Product Characteristics (SPC) for the full prescribing information. Presentation: Inhalation powder in a white inhaler with an integral dose indicator and a green dosage button. Each delivered dose contains 375 µg aclidinium bromide equivalent to 322 µg of aclidinium. Also, contains lactose. Use: Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Dosage: For inhalation use. Recommended dose is one inhalation of 322 µg aclidinium twice daily. Patients should be instructed on how to administer the product correctly. No dose adjustments are required for elderly patients, or those with renal or hepatic impairment. No relevant use in children and adolescents. Contraindications: Hypersensitivity to aclidinium bromide, atropine or its derivatives, including ipratropium, oxitropium or tiotropium, or to any of the excipients. Warnings and Precautions: Do not use in asthma. Stop use if paradoxical bronchospasm occurs and consider other treatments. Do not use for the relief of acute episodes of bronchospasm. Use with caution in patients with myocardial infarction in the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, or hospitalisation within the previous 12 months for heart failure functional classes III and IV. Dry mouth, observed with anticholinergic treatment, may be associated with dental caries in the long term. Use with caution in patients with symptomatic prostatic hyperplasia or bladder-neck obstruction or with narrow-angle glaucoma. Do not use in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. Interactions: Do not administer with other anticholinergic-containing medicinal products. No other interactions expected. Please consult the SPC for more details. Fertility, pregnancy and lactation: No data on use in pregnancy. Consider risk-benefit before using during lactation. Unlikely to affect fertility at the recommended dose. Side-effects: Common (1-10%): Sinusitis, nasopharyngitis, headache, cough, diarrhoea. Uncommon (0.1- 1%): Blurred vision, tachycardia, palpitations, dysphonia, dry mouth, rash, pruritus, urinary retention. Rare (0.01-0.1%): hypersensitivity. Not known: angioedema. Pack sizes: Carton containing 1 inhaler with 60 unit doses. Legal category: POM Marketing Authorisation Number: EU/1/12/778/002 Marketing Authorisation holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden. Marketed by: A. Menarini Pharmaceuticals Ireland Ltd., Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin. Further information is available on request to A. Menarini Pharmaceuticals Ireland Ltd. or may be found in the SPC. Last updated: March 2015 Reference: 1. Eklira® Genuair® Summary of Product Characteristics, last updated February 2015.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions to: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra.ie, e-mail: [email protected]. Date of Item: March 2015 Adverse events should also be reported to A. Menarini Pharmaceuticals Ireland Ltd. Phone no: 01 284 6744. IR-Ekl-03-2015 clinical review nursingingeneralpractice

Management of ACOS • Smoking cessation STEP 4: Commence initial therapy • Pulmonary rehabilitation Faced with a diff erential diagnosis equally balanced between • Vaccinations asthma and CoPD (i.e. ACoS), it is recommended that treatment • Treatment of comorbidities, as advised in the respective should be started accordingly for asthma. This recognizes the GiNA (2015) and GoLD (2015) reports. important role of inhaled corticosteroids (iCS) in preventing • in a majority of patients, the initial management of asthma morbidity and even death in patients with uncontrolled and CoPD can be satisfactorily carried out at primary care asthma symptoms, for whom even seemingly ‘mild’ symptoms level. However, both the GiNA (2015) and GoLD (2015) strategy (compared to those of moderate or severe CoPD) might indicate reports make provision for referral for further diagnostic signifi cant risk of a life-threatening attack procedures at relevant points in patient management (see • if the syndromic assessment suggests asthma or ACoS, or Step 5). This may be particularly important for patients there is signifi cant uncertainty about the diagnosis of CoPD, with suspected ACoS, given that it is associated with worse it is prudent to start treatment as for asthma until further outcomes and greater health care utilisation.1,4,5 investigation has been performed to confi rm or refute this initial position. STEP 5: Referral for specialised investigations (if necessary) • Treatments will include an iCS (in a low or moderate dose, referral to a respiratory expert and further evaluation is depending on level of symptoms). necessary in the following situations: • A long-acting beta2-agonist (LABA) should also be • Patients with persistent symptoms and/or exacerbations continued (if already prescribed), or added. However, it is despite treatment. important that patients should not be treated with a LABA • Diagnostic uncertainty, especially if an alternative diagnosis without an iCS (often called LABA monotherapy) if there are (e.g. bronchiectasis, post-tuberculosis scarring, bronchiolitis, features of asthma. pulmonary fi brosis, pulmonary hypertension, cardiovascular • if the syndromic assessment suggests CoPD, appropriate diseases and other causes of respiratory symptoms) needs to symptomatic treatment with bronchodilators or combination be excluded. therapy should be commenced, but not iCS alone (as • Patients with suspected asthma or CoPD in whom atypical or monotherapy) additional symptoms or signs (e.g. haemoptysis, signifi cant • Treatment of ACoS should also include advice about other weight loss, night sweats, fever, signs of bronchiectasis or therapeutic strategies including: other structural lung disease) suggest an additional pulmonary • inhaler technique diagnosis. This should prompt early referral, without • Education including self-management strategies necessarily waiting for a trial of treatment for asthma or CoPD.

Table 2: Spirometric measures in asthma, COPD and ACOS (GINA/GOLD, 2014) sPIrOmetrIC VarIaBLe asthma COPD aCOs Normal FEV1/FVC pre – or post Compatible with diagnosis Not compatible with Not compatible unless BD diagnosis other evidence of chronic airfl ow limitation Post-BD FEV1/FVC <0.7 indicates airfl ow limitation required for diagnosis (GoLD) Usually present but may improve spontaneously or on treatment FEV1 ≥80% predicted Compatible with diagnosis Compatible with GoLD Compatible with diagnosis of (good asthma control or classifi cation of mild airfl ow mild ACoS interval between symptoms) limitation (categories A or B) if post – BD FEV1/FVC <0.7 FEV1 <80% predicted Compatible with diagnosis. An indicator of severity of An indicator of severity of risk factor for asthma airfl ow limitation and risk of airfl ow limitation and risk of exacerbations future events (e.g. mortality future events (e.g. mortality and CoPD exacerbations) and exacerbations) Post-BD increase in FEV1 >12% Usual at some time in course Common and more likely when Common and more likely when and 200 ml from baseline of asthma, but may not be FEV1 is low, but ACoS should also FEV1 is low, but ACoS should (reversible airfl ow limitation) present when well controlled be considered or on controllers also be considered Post-BD increase in High probability of asthma Unusual in CoPD Consider ACoS FEV1 >12% and 400ml Compatible with diagnosis from baseline (marked of ACoS reversibility)

30 Symbicort® Turbohaler® (budesonide/formoterol)

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ABRIDGED PRESCRIBING INFORMATION psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression Refer to full Summary of Product Characteristics (SmPC) before prescribing (particularly in children). Height of children should be monitored. Potential effects on bone should be considered especially Symbicort® Turbohaler® 100/6; 200/6; 400/12; Inhalation Powder in patients on high doses for prolonged periods that have co-existing risk factors for osteoporosis. Prolonged treatment with (budesonide/formoterol fumarate dihydrate) high doses of inhaled corticosteroids, particularly higher than recommended doses, may also result in clinically significant adrenal suppression. Additional systemic corticosteroid cover should be considered during periods of stress e.g. severe Indication Asthma: Treatment of asthma where the use of a combination (inhaled corticosteroid and long acting β2 infections or elective surgery. Transfer from oral steroid therapy to Symbicort may result in the appearance of allergic or adrenoceptor agonist) is appropriate. Symbicort 100/6 is not appropriate for patients with severe asthma. COPD (Symbicort arthritic symptoms which will need treatment. In rare cases, tiredness, headache, nausea and vomiting can occur due to 200/6; 400/12): Symptomatic treatment of patients with severe COPD (FEV1 <50% predicted normal) and a history of insufficient glucocorticosteroid effect and temporary increase in the dose of oral glucocorticosteroids may be necessary. repeated exacerbations, who have significant symptoms despite regular therapy with long-acting bronchodilators. To minimise risk of oropharyngeal candida infection patients should rinse mouth with water. Observe caution in patients Presentation Inhalation powder. Each metered dose contains Symbicort Turbohaler 100/6: 100mcg budesonide/ with thyrotoxicosis, phaeochromocytoma, diabetes mellitus, untreated hypokalaemia, or severe cardiovascular disorders. inhalation and 6mcg formoterol fumarate dihydrate/inhalation. Symbicort Turbohaler 200/6: 200mcg budesonide/inhalation Re-evaluate need for Symbicort in patients with active or quiescent pulmonary tuberculosis, fungal and viral infections in and 6mcg formoterol fumarate dihydrate/inhalation. Symbicort Turbohaler 400/12: Each metered dose contains 400mcg the airways. Hypokalaemia may occur at high doses. Particular caution recommended in unstable or acute severe asthma. budesonide/inhalation and 12mcg formoterol fumarate dehydrate/inhalation. Refer to the SmPC for information on the Monitor serum potassium levels. In diabetic patients consider additional blood glucose monitoring. The small amounts of milk method of administration. proteins present may cause allergic reactions. Dosage and Administration Asthma Not intended for the initial management of asthma. Dose should be individualised. Drug Interactions Concomitant treatment with potent CYP3A4 inhibitors should be avoided. If this is not possible the If a patient requires dosages outside recommended regimen appropriate doses using individual inhalers should be time interval between administration should be as long as possible. Symbicort maintenance and reliever therapy is not prescribed. When long-term symptoms are controlled, titrate to the lowest effective dose, which could include a once daily recommended in these patients. Not recommended with beta adrenergic blockers (including eye drops) unless compelling dosage. Symbicort maintenance therapy – regular maintenance treatment with a separate rescue medication: reasons. Concomitant administration with quinidine, disopyramide, procainamide, phenothiazines, antihistamines Adults (≥18 years including elderly) 100/6 and 200/6: 1-2 inhalations twice daily (maximum of 4 inhalations twice (terfenadine) and TCAs can prolong the QTc-interval and increase the risk of ventricular arrhythmias. L-Dopa, L-thyroxine, daily); 400/12: 1 inhalation twice daily (maximum 2 inhalations twice daily). Adolescents (12-17 years) 100/6 and 200/6: oxytocin and alcohol can impair cardiac tolerance. Concomitant administration with MAOIs, including agents with similar 1-2 inhalations twice daily; 400/12: 1 inhalation twice daily. Children (6-11 years) 100/6 only: 2 inhalations twice daily. properties such as furazolidone and procarbazine, may precipitate hypertension. Elevated risk of arrhythmias in patients Symbicort is not recommended for children under 6 years. Symbicort 400/12 is not recommended for children receiving anaesthesia with halogenated hydrocarbons. Hypokalaemia may increase the disposition towards arrhythmias in under 12 years. Asthma (Symbicort maintenance and reliever therapy – regular maintenance treatment and as patients taking digitalis glycosides needed in response to symptoms) for Symbicort 100/6 and 200/6 only (NOT recommended with 400/12 strength): Fertility, Pregnancy and Lactation No data available on the potential effect on fertility. During pregnancy, use only when especially consider for (i) patients with inadequate asthma control and in frequent need of reliever medication (ii) patients the benefits outweigh the potential risks. Budesonide is excreted in breast milk, however at therapeutic doses no effects on with asthma exacerbations in the past requiring medical intervention. Close monitoring for dose-related adverse effects the child are anticipated. is needed in patients who frequently take high numbers of Symbicort as-needed inhalations. Adults (including elderly) 100/6 & 200/6: 1 inhalation twice daily or as 2 inhalations once daily. For some patients a dose of 2 inhalations twice daily Undesirable effects Common: headache, palpitations, tremor, candida infections in the oropharynx, coughing, mild may be appropriate (200/6 strength only). Patients should take 1 additional inhalation as needed in response to symptoms. irritation in the throat, hoarseness. Uncommon: tachycardia, nausea, dizziness, bruises, aggression, psychomotor If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations should be hyperactivity, anxiety, sleep disorders. Rare: hypokalaemia, cardiac arrhythmias including atrial fibrillation, supraventricular taken on any single occasion. A total daily dose of >8 inhalations is not normally needed; however, up to 12 inhalations a tachycardia and extrasystoles, bronchospasm and immediate and delayed hypersensitivity reactions including exanthema, day could be used for a limited period. Patients using >8 inhalations daily should be strongly recommended to seek medical urticaria, pruritus, dermatitis, angioedema and anaphylactic reaction. Very Rare: psychiatric disorders including depression, advice. Patients should be advised to always have Symbicort for reliever use. Children and adolescents under 18 years behavioural changes (predominantly in children), angina pectoris, prolongation of QTc-interval, hyperglycaemia, taste of age: not recommended. COPD (200/6): Adults: 2 inhalations twice daily. (400/12): 1 inhalation twice daily. disturbance, Cushing’s syndrome, adrenal suppression, growth retardation, decrease in bone mineral density, cataract and glaucoma and variations in blood pressure. As with other inhalation therapy, paradoxical bronchospasm may occur in very Contraindications Hypersensitivity to active substances or excipient. rare cases Warnings and Precautions If treatment is ineffective, or exceeds the highest recommended dose therapy should be Package Quantities Each Symbicort Turbohaler 100/6 or 200/6 contains 120 inhalations. Each Symbicort Turbohaler reassessed. Sudden and progressive deterioration in control requires urgent medical assessment. Treatment should not 400/12 contains 60 inhalations. Legal Category Prescription Only Medicine (POM). Marketing Authorisation Numbers be stopped abruptly. Patients should have their appropriate rescue medication available at all times i.e. either Symbicort PA 970/28/1-3. Marketing Authorisation Holder (MAH) AstraZeneca UK Limited, 600 Capability Green, Luton, LU1 3LU, or a separate reliever. If needed before exercise a separate reliever should be used. Therapy should not be initiated during UK. Further product information available on request from The MAH (address above), Freephone -1800 800 899. an exacerbation. Serious asthma-related adverse events and exacerbations may occur. If asthma symptoms remain uncontrolled or worsen patients should continue treatment but seek medical advice. If paradoxical bronchospasm occurs Abridged Prescribing Information prepared 12/14. Symbicort should be discontinued. It responds to a rapid-acting inhaled bronchodilator and should be treated straightaway. Symbicort and Turbohaler are Trade Marks of the AstraZeneca group of companies. Systemic effects may occur, particularly at high doses prescribed for long periods e.g. Cushing’s syndrome, Cushingoid Approval ID: 680320.011 features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely a range of Date of preparation: February 2015.

ASTR2694_Puzzle_Ad_BLUE_fullpage_395hx273h_MedIndo_v1.indd 1 23/02/2015 10:38 clinical review nursingingeneralpractice

Source: GINA/GOLD Guidelines for Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS).

32 1 THE FIRST ONCE-DAILY DUAL BRONCHODILATOR1 Once-Daily ® ® Dual Bronchodilator ULTIBROBREEZHALER START A NEW CHAPTER IN COPD2-4

85mcg indacaterol maleate/43mcg glycopyrronium bromide inhalation powder

Once-daily ULTIBRO BREEZHALER is indicated as maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).1

Ultibro Breezhaler ▼This medicinal product is subject to additional monitoring. This will allow quick identifi cation of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions. ABBREVIATED PRESCRIBING INFORMATION Please refer to Summary of Product Characteristics (SmPC) before prescribing. Presentation: Ultibro Breezhaler 85mcg / 43mcg inhalation powder hard capsules containing indacaterol maleate and glycopyrronium bromide respectively and separate Ultibro Breezhaler inhaler. Indications: A maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Dosage and administration: Recommended dose is the inhalation of the content of one capsule once daily, administered at the same time of the day each day, using the Ultibro Breezhaler inhaler. Capsules must not be swallowed. No dose adjustment required in elderly patients, for patients with mild and moderate hepatic impairment or for patients with mild to moderate renal impairment. No data available for use in patients with severe hepatic impairment and should only be used in patients with severe renal impairment or end-stage renal disease requiring dialysis if the expected benefi t outweighs the potential risk. No relevant use in the paediatric population. Contraindications: Hypersensitivity to the active substances or to any of the excipients. Warnings/Precautions: Not to be administered concomitantly with medicinal products containing other LABA’s or LAMA’s. Asthma: ♦ ULTIBRO BREEZHALER SHOULD NOT BE USED FOR TREATMENT OF ASTHMA. Acute use: ♦ Not indicated for treatment of acute episodes of bronchospasm. Hypersensitivity: ♦ Immediate hypersensitivity reactions have been reported after administration of indacaterol or glycopyrronium. If signs suggesting allergic reactions occur (in particular, angioedema, diffi culties in breathing or swallowing, swelling of the tongue, lips and face, urticaria or skin rash), treatment should be discontinued immediately and alternative therapy instituted. Paradoxical bronchospasm: ♦ If paradoxical bronchospasm occurs, Ultibro Breezhaler should be discontinued immediately and alternative therapy instituted. Anticholinergic e ects related to glycopyrronium: ♦ To be used with caution in patients with narrow-angle glaucoma and in patients with urinary retention. Patients with severe renal impairment: ♦ Should only be used in patients with severe renal impairment, including those with end-stage renal disease requiring dialysis, if the expected benefi t outweighs the potential risk. These patients should be monitored closely for potential adverse reactions. Cardiovascular e ects: ♦ To be used with caution in patients with cardiovascular disorders (coronary artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension), in patients with known or suspected prolongation of the QT interval or patients treated with medicinal products affecting the QT interval and in patients with unstable ischaemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding chronic stable atrial fi brillation), a history of long QT syndrome or whose QTc (Fridericia method) was prolonged. ♦ LABA’s may produce a clinically signifi cant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms, ECG changes. In case such effects occur, treatment may need to be discontinued. Hypokalaemia: ♦ LABA’s may produce signifi cant hypokalaemia in some patients, which has the potential to produce cardiovascular effects. In patients with severe COPD, hypokalaemia may be potentiated by hypoxia and concomitant treatment which may increase the susceptibility to cardiac arrhythmias. Hyperglycaemia: ♦ Inhalation of high doses of LABA’s may produce increases in plasma glucose. Upon initiation of treatment with Ultibro Breezhaler plasma glucose should be monitored more closely in diabetic patients. ♦ Ultibro Breezhaler has not been investigated in patients for whom diabetes mellitus is not well controlled. General disorders: ♦ To be used with caution in patients with convulsive disorders or thyrotoxicosis, and in patients who are unusually responsive to LABA’s. Excipients: ♦ Patients with rare hereditary problems of galactose intolerance, the Lapp lactase defi ciency or glucose-galactose malabsorption should not take this medicine. Pregnancy and Lactation: ♦ Ultibro Breezhaler should only be used during pregnancy if the expected benefi t to the patient justifi es the potential risk to the foetus. ♦ Not known whether indacaterol, glycopyrronium and their metabolites are excreted in human milk. Use of Ultibro Breezhaler by breast-feeding women should only be considered if the expected benefi t to the woman is greater than any possible risk to the infant. Interactions: ♦ Concomitant use is not recommended with beta- adrenergric blockers, anticholinergics or sympathomimetic agents. ♦ Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids, or non-potassium-sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists, therefore use with caution. ♦ Inhibition of the key contributors of indacaterol clearance, CYP3A4 and P-gp, does not raise any safety concerns given the safety experience of treatment with indacaterol. ♦ No clinically relevant drug interaction is expected when glycopyrronium is co-administered with cimetidine or other inhibitors of the organic cation transport. Adverse reactions: ♦ Very common: upper respiratory tract infection. ♦ Common: nasopharyngitis, urinary tract infection, sinusitis, rhinitis, dizziness, headache, cough, oropharyngeal pain including throat irritation, dyspepsia, dental caries, gastroenteritis, musculoskeletal pain, pyrexia, chest pain. ♦ Uncommon: hypersensitivity, angioedema, diabetes mellitus and hyperglycaemia, insomnia, paraesthesia, glaucoma, ischaemic heart disease, atrial fi brillation, tachycardia, palpitations, paradoxical bronchospasm, epistaxis, dry mouth, pruritus / rash, muscle spasm, myalgia, pain in extremity, bladder obstruction and urinary retention, peripheral oedema and fatigue. ♦ Please refer to SmPC for a full list of adverse events for Ultibro Breezhaler. Legal Category: POM Pack sizes: Cartons containing 6 capsules (1x6 capsule blister strips) and one Ultibro Breezhaler inhaler or 30 capsules (5x6 capsule blister strips) and one Ultibro Breezhaler inhaler. Marketing Authorisation Holder: Novartis Europharm Limited, Frimley Business Park, Camberley GU16 7SR, United Kingdom. Marketing Authorisation Numbers: EU/1/13/862/001 & 003. Full prescribing information is available on request from Novartis Ireland Ltd, Beech Hill Offi ce Campus, Clonskeagh, Dublin 4. Tel: 01 2601255 or at www.medicines.ie Date of Revision of API Text: 26 Jan 2015 References: 1.Ultibro Breezhaler SmPC. www.medicines.ie , accessed on May 2015. 2. Vogelmeier CF, Bateman ED, Pallante J, et al. Effi cacy and safety of once-daily QVA149 compared with twice-daily salmeterol/fl uticasone in patients with COPD (ILLUMINATE): a randomised, double-blind, prallel group study. Lancet Respir Med. 2013;1:51-60. 3. Bateman ED, Ferguson GT, Barnes et al. Dual bronchodilation with QVA149 vs single bronchodilatot therapy: the SHINE study. EUR Respir J. Published online May 2013 as doi: 10.1183/0931936.00200212. 4. Wedzicha JA, Decramer M, Ficker JH, et al. Analysis of chronic obstructive pulnmonary disease exacerbations with the dual bronchodilator therapy QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel group study. Lancet Respir Med. 2013;1:199-209.

IE02/ULT14-CNF098b(1) Date of Preparation: May 2015 clinical review nursingingeneralpractice

• When chronic airways disease is suspected but syndromic chronic condition, nurses are in a privileged position to assist features of both asthma and COPD are few. patients attain and obtain an optimal quality of life. • Patients with comorbidities that may interfere with the assessment and management of their airways disease. References • Referral may also be appropriate for issues arising during on- 1. Global Initiative for Asthma & Global Initiative for COPD, 2014, going management of asthma, COPD or ACOS, as outlined in Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, the GINA4 and GOLD5 strategy reports.1 COPD and Asthma-XCOPD Overlap Syndrome. 2. Dr Marco R., Pesce G., Maron A, et al, 2013, The coexistence of Conclusion asthma and chronic obstructive pulmonary disease (COPD): This article has explored the new syndrome, ACOS, its diagnosis prevalence in risk factors in young, middle-aged and elderly and management and has presented the GINA/GOLD Guidelines people from the general population. PLoS One2013;8:e62985 for same. ACOS can be managed in primary care with the practice 3. Papaiwannoy A., Zarogoulidis P, Porpodis K., et al, 2014, nurse being an integral part of supporting and educating these Asthma-chronic obstructive pulmonary disorder overlap syn- patients. These patients require on-going education in relation drome (ACOS): current literature review. Journal of Thoracic to inhaler technique, adherence to medication regimes, non- Disease, 6 (S1), S146-S151 pharmacological interventions such as vaccinations, breathing 4. GINA, 2015, Global Initiative for Management and Prevention exercises and self-management. As these patients tend to have of Asthma poorer outcomes than patients with either asthma or COPD 5. Global Initiative for Chronic Obstructive Pulmonary Disease alone, it is imperative, that they are adequately assessed and (GOLD), 2015, Global Strategy for Diagnosis, Management treated using the new guidance from GINA & GOLD1. As with any and Prevention of COPD.

MCQS

Q1 ACOS can be diagnosed in: Q5 Patients should be referred to a a) adults under 20 who have asthma respiratory specialist: b) adults over 40 who have asthma and smoke a) when there is no improvement in condition with c) adults with long-standing asthma who go on to treatment develop COPD b) when the patient has multiple co-morbidities d) adults with emphysema c) patient has haemoptysis d) all of the above Q2 There are 6 steps recommended by GINA/GOLD (2014) in the diagnosis and Q6 Patients who have ACOS are more likely to management of ACOS have: True or false a) more prolonged hospital stays than patients who have asthma or COPD alone Q3 In ACOS, on spirometry testing, the FEV1/ b) shorter hospital stays than patients who have FVC ratio will be: asthma or COPD alone a) >80% c) the same length of stay as patients who have b) 100% asthma or COPD alone c) <70% pre bronchodilator d) more attendances to the emergency department

d) <70% post bronchodilator

Q6: a Q6:

Q4 Patients with a diagnosis of ACOS should d; Q5:

be treated with: b; Q4:

a) inhaled bronchodilator therapy (SABA) alone d; Q3:

b) combined inhaled LABA and ICS False; Q2: c; and b Q1:

c) inhaled LAMA alone ANSWERS: MCQ d) oral steroids