Berkshire East Respiratory Guidelines

Berkshire East Respiratory Guidelines This is an update of guidelines which had previously have been drawn up following discussions at the East Berkshire Respiratory Group. This multidisciplinary group consisted of consultants, respiratory nurses, pharmacists, prescribing advisors, GPs and practice nurses representing both primary and secondary care across East Berkshire. The purposes of the guidelines are to ensure: 1. The management of Asthma is in accordance with the British Guideline on the Management of Asthma 2012 and the management of Chronic Obstructive Pulmonary Disease (COPD) is in accordance with the NICE COPD guidelines 2010 following expert advice from consultants at Heatherwood and Wexham Park Hospitals. 2. Drug choices are based on evidence of clinical effectiveness in consultation with local experts. 3. Drug choices are cost effective for both primary and secondary care. 4. Seamless care is promoted with the same drugs being used in primary and secondary care. 5. Clinicians have the opportunity to gain experience with a small number of drugs. It is expected these guidelines will cover 70% plus of patients for whom respiratory drugs are prescribed in primary and secondary care. The agents of choice are the preferred drugs and devices for initiation of therapy. Alternative choices are given to guide prescribers. It is expected that the alternative choices will be prescribed for patients experiencing problems with the first drug or device. For asthmatic patients GPs should consider seeking specialist opinion at any stage, especially for patients at or above Stage 4. The management of COPD is based on the NICE COPD Guidelines 2010. The management of asthma is based on the British Guidelines on the Management of Asthma SIGN/BTS 2012. The British Guideline on the Management of Asthma and NICE COPD guidelines emphasise a patient focused approach to management thus drug device choices should be carefully considered. Developed & produced by the East Berkshire Respiratory Group 2005 Reviewed & Updated: May 2011 Reviewed and Updated: March 2014 Prices from BNF 66 September 2013, MIMS October 2013 Drug Tariff Online October 2013. Data sources include BNF 66 September 2013, Individual Product SPCs, and National Drug Information Reviews. BTS/ SIGN Management of Asthma 2012 NICE COPD Guidelines 2010T Whilst every effort has been made to ensure all information in these guidelines is accurate prescribers are Page 1 of 49

a Berkshire East Respiratory Guidelines - Asthma Table of Contents Page Number Introduction 1 Section 1: Asthma 1.1 Diagnosis and Assessment 3 2. Management of Asthma 9 3. Drug Therapy 12 4. Review 25 5. Acute Asthma in Primary Care: Management and Drug Choices 26 Section 2: Chronic Obstructive Pulmonary Disease (COPD) 1.Diagnosis and Severity Assessment 30 2.Smoking Cessation 33 3. Pulmonary Rehabilitation 34 4. Management of COPD 35 5. Drug Delivery 37 6. Drug Therapy 38 7. Review 42 8. Referral to Secondary Care 42 9. Exacerbations of COPD in Primary Care: Management and Drug 43 Choices 10. Appendices: I Self Management Plans II Rescue Packs Contributors 49 References 50 47 48 Whilst every effort has been made to ensure all information in these guidelines is accurate prescribers are Page 2 of 49

Section 1: Asthma 1.1 Diagnosis and assessment in adults Management and Drug Choices - The following guidance is based on the British Guideline on the Management of Asthma Revised Edition June 2012. www.sign.ac.uk/guidelines/fulltext/101/index.html 1. Symptoms suggestive of asthma include: Wheeze. Shortness of breath. Chest tightness. Cough. These symptoms tend to be: Variable. Intermittent. Worse at night and early morning. Provoked by triggers including exercise, environmental and occupational exposures. 2. Additional information: Personal or family history (often maternal) of asthma or atopy (eczema, allergic rhinitis) Recognised triggers including pollens, dust, animals, exercise, viral infections, chemicals, cigarette smoke and irritants, cold or damp air, environmental and occupational exposures History of worsening after use of aspirin/nsaid or Beta Blockers. 3. Objective Measurements: Variability of Peak Expiratory Flow (PEF) and forced expiratory volume in one second (FEV 1 ) in response to therapy is a feature of asthma. If they are repeatedly normal in the presence of symptoms a diagnosis of asthma should be challenged. Objective tests should be used to confirm a diagnosis of current asthma before long term therapy is started. Either one of the following methods can be used: Either 20% diurnal variation on 3 days when recording peak flow measurements (best of three attempts) QDS for two weeks: or FEV 1 15 % (and 200 ml) increase after short acting β2 agonist. or or or (e.g. salbutamol 400 microgram by pmdi + spacer or 2.5 mg by nebuliser). FEV 1 15% (and 200 ml) increase after trial of steroid tablets (prednisolone 30 mg/day for 14 days). FEV 1 15% decrease after six minutes of exercise (running). Only in difficult cases histamine or methacholine challenge (requires referral to secondary care). Trials of treatment withdrawal, with weekly monitoring of spirometry and recording of QDS PEFR along with symptoms may be helpful where there is doubt. Whilst every effort has been made to ensure all information in these guidelines is accurate prescribers are Page 3 of 49

Calculation of Peak Flow Diurnal Variability 20% or greater variation on 3 or more days per week demonstrates poor control To calculate: subtract the lower Peak Flow reading from the higher on any one day; divide by the highest figure and multiply by 100 = % variability e.g. morning peak flow: 450 afternoon peak flow: 350 % variability = 450 350/ 450 x 100 =100/ 450 x 100 = 22% Further information on peak flow and interpretation of readings is available on www.peakflow.com 4. Asthma can but not always, be differentiated from COPD based mainly on history (see COPD section P.18). Whilst every effort has been made to ensure all information in these guidelines is accurate prescribers are Page 4 of 49

Berkshire East Respiratory Guidelines - Asthma Presentation with suspected asthmas in adults (adapted from British Guideline on the Management of Asthma 2012) Presentation with suspected asthma Clinical assessment with spirometry and/or 2 weeks of PEFR diary HIGH PROBABILITY: Diagnosis of asthma likely INTERMEDIATE PROBABILITY: Diagnosis uncertain LOW PROBABILITY: Other diagnosis likely FEV 1/FVC <70% FEV 1/FVC >70% Trial of treatment Investigate/ treat other condition Response? Response? Yes No No Yes Continue treatment Assess compliance and inhaler technique. Consider further investigation and/or referral Further investigation. Consider referral Continue treatment Whilst every effort has been made to ensure all information in these guidelines is accurate prescribers are Page 5 of 49

Diagnosis and Assessment in children Focus the initial assessment of children suspected of having asthma on: Presence of key features in the history and clinical examination Careful consideration of alternative diagnosis. Record the basis on which the diagnosis of asthma is suspected. Using a structured questionnaire may produce a more standardized approach to the recording of presenting clinical features and the basis for a diagnosis of asthma. 1 In children with a high probability of asthma: Move straight to a trial of treatment. Reserve further testing for those with a poor response. 2 In children with a low probability of asthma: Consider more detailed investigation and specialist referral. 3 In children with an intermediate probability of asthma who can perform spirometry and have evidence of airways obstruction, offer a reversibility test and / or a trial of treatment for a specified period: If there is reversibility, or if treatment is beneficial, treat as asthma. If there is insignificant reversibility, and / or treatment trial is not beneficial, consider tests for alternative conditions. 4 In children with an intermediate probability of asthma who can perform spirometry, and have no evidence of airways obstruction, consider testing for atopic status, bronchodilator reversibility and, if possible, bronchial hyper-responsiveness using methacholine or exercise. 5 In children with an intermediate probability of asthma, who cannot perform spirometry, consider testing for atopic status and offering a trial of treatment for a specified period: If treatment is beneficial, treat as asthma. If treatment is not beneficial, stop asthma treatment, and consider tests for alternative conditions and specialist referral. The label of asthma in a child should only be given when objective features of asthma are found. This label can affect future career choices. Indications for specialist referral in children Diagnosis unclear or in doubt. Symptoms present from birth or perinatal lung problem. Excessive vomiting or posseting. Severe upper respiratory tract infection. Persistent wet or productive cough. Family history of unusual chest disease. Failure to thrive. Whilst every effort has been made to ensure all information in these guidelines is accurate prescribers are Page 6 of 49

Nasal polyps. Unexpected clinical findings e.g. focal signs, abnormal voice or cry, dysphagia, inspiratory stridor. Failure to respond to conventional treatment (particularly inhaled corticosteroids above 400 microgram / day or frequent use of steroid tablets). Parental anxiety or need for reassurance. Whilst every effort has been made to ensure all information in these guidelines is accurate prescribers are Page 7 of 49

Berkshire East Respiratory Guidelines Asthma Presentation with suspected asthma in children (Adapted from British Guideline on the Management of Asthma 2012) Clinical assessment with spirometry and two weeks of recording qds PEFR HIGH PROBABILITY: Diagnosis of asthma likely INTERMEDIATE PROBABILITY: Diagnosis uncertain or poor response to asthma treatment LOW PROBABILITY: Other diagnosis likely Consider referral Positive Test Supports Diagnosis Negative Test Does Not Support Trial of asthma treatment for 2-4 weeks Consider tests* of lung function and atopy Investigate/ treat other condition Response? Response? Yes No No Yes Continue treatment and find minimum effective dose Assess compliance and inhaler technique. Consider further investigation and/or referral Further investigation. Consider referral Continue treatment Lung function tests include spirometry before and after bronchodilator (test of airway reversibility) and possible exercise or methacholine challenge (tests of airway responsiveness). Most children over the age of 5 years can perform lung function tests. Whilst every effort has been made to ensure all information in these guidelines is accurate prescribers are Page 8 of 49

2. Management of Asthma Berkshire East Respiratory Guidelines Asthma Summary of Stepwis Management in Adults (taken from British Guideline on the Management of Asthma 2012) advised to check the BNF or product SPCs for full prescribing information Page 9 of 49

Berkshire East Respiratory Guidelines Asthma Summary of stepwise management in children aged 5-12 years (taken from the British Guideline on the Management of Asthma 2012 advised to check the BNF or product SPCs for full prescribing information Page 10 of 49

Berkshire East Respiratory Guidelines Asthma Summary of stepwise management in children less than 5 years (taken from the British Guideline on the Management of Asthma 2012 advised to check the BNF or product SPCs for full prescribing information Page 11 of 49

3. Drug Therapy 3.1 Choice of Inhaler Device in Asthma Technique and Training 1. Prescribe inhalers only after patients have received training in the use of the device and have demonstrated satisfactory technique. 2. Inhaler technique should be checked at every review and prior to any changes in medication. Beta Agonist Delivery Acute Asthma Children and adults with mild and moderate exacerbations of asthma should be treated by pressurised Metered Dose Inhaler (pmdi) + spacer with doses titrated according to clinical response. Stable Asthma In children aged 5-12 years, pmdi + spacer is as effective as any other hand held inhaler. In adults, pmdi + spacer is as effective as any other hand held inhaler, but patients may prefer some types of dry powder inhaler (DPI). Choice of reliever inhaler for stable asthma should be based on patient preference and assessment of correct use. Many patients will not be prepared to carry a spacer. This group should be offered and trialled on a dry powder inhaler. Inhaled Steroids for Stable Asthma In children aged 5-12 years, pmdi + spacer is as effective as any DPI. In adults, a pmdi + spacer is as effective as any DPI. CFC Propellant PMID vs HFA Propellant PMDI Salbutamol HFA can be substituted for salbutamol CFC at 1:1 dosing. HFA Beclametasone (BDP) pmdi (Clenil ) may be substituted for CFC BDP pmdi at 1:1 dosing. This ratio does not apply to HFA BDP pmdi (Qvar ) which may be substituted for CFC BDP pmdi at 1:2 ratio. Prescribing Devices The choice of device may be determined by the choice of drug. If the patient is unable to use a device satisfactorily an alternative should be found. The patient should have their ability to use an inhaler device assessed annually by a Healthcare Professional who has had training in and can demonstrate competency in this field. The medication needs to be titrated against clinical response to ensure optimum efficacy. Reassess inhaler technique as part of structured clinical review. Page 12 of 49

In children aged 0-5 years, pmdi and spacer are the preferred method of delivery of β 2 agonists or inhaled steroids. A face mask is required until the child can breathe reproducibly using the spacer mouthpiece. Where this is ineffective a nebuliser may be required. 3.2 Use and Care of Spacers The spacer should be compatible with the pmdi being used. The drug should be administered by a single actuation of the metered dose inhaler into the spacer, each followed by inhalation and repeated if required or prescribed. There should be minimal delay between pmdi actuation and inhalation. Tidal breathing is as effective as single breaths. Spacers should be cleaned monthly rather than weekly as per manufacturer s recommendations or performance is adversely affected. They should be washed in detergent, not rinsed and allowed to dry in air. The mouthpiece should be wiped clean of detergent before use. Volumatic spacers must be washed as described before initial use. Drug delivery may vary significantly due to static charge. Metal and other antistatic spacers are not affected in this way. Plastic spacers should be replaced at least every 12 months but some may need changing at six months. Cost Comparison of Spacer Devices* Universal Spacer Device Standard Infant Child Adult with mask Able Spacer (small volume) 4.20 6.86 6.86 Aerochamber Plus (medium 4.75 7.92 7.92 7.92 volume) Optichamber 4.49 7.49 7.49 7.49 Pocket Chamber 4.18 9.75 9.75 9.75 Volumatic (for GSK devices only) 3.81 6.70 6.70 - *Costs taken from Drug Tariff Online October 2013 online accessed October 2013 Page 13 of 49

3.3 Choice of Drugs and Devices in the Treatment of Asthma Short acting β 2 agonists These are indicated for the relief of mild to moderate symptoms of asthma at Step 1 of the British Guideline for the Management of Asthma. Unless individual patients are shown to benefit from regular use of inhaled short-acting β 2 agonists then as required use is recommended. Excessive β 2 agonist use is a marker of poorly controlled asthma. These patients should have their asthma management reviewed by a Respiratory Nurse Practitioner or Doctor. Using two or more canisters of β 2 agonists per month or >10-12 doses/day is a marker of poorly controlled asthma that puts patients at risk of fatal or near-fatal asthma. Short acting β 2 agonist Adults and Children over 5 years: 1 st Choice Salbutamol pmdi CFC free (spacer device should be given to all patients) Alternative Salbutamol Easyhaler Salamol Easi-Breathe Ventolin Accuhaler Or Bricanyl Turbohaler* (Dry Powder Inhaler) * only use if unable to tolerate other devices Children Under 5 years: 1 st Choice Salbutamol pmdi CFC free with spacer device Recommended dose (1 dose = 1 puff) 100-200microgram (1-2 doses) up to four times a day or as required 100-200 microgram (1-2 doses) up to four times a day or as required 200 micrograms up to four times a day or as required 500microgram (1 dose) up to four times a day or as required 100-200 microgram (1-2 doses) up to four times a day or as required Cost per equivalent 200 dose of 100 micrograms Salbutamol ( )* 1.50 3.31 6.30 10.00 13.84 1.50 * Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 Page 14 of 49

3.4. Inhaled Corticosteroids For steps 2, 3, and 4 of the British Guideline on the Management of Asthma, treatments have been judged on their ability to improve symptoms, improve lung function and prevent exacerbations, with an acceptable safety profile. There is no good evidence of clinically important differences in efficacy at equivalent doses between the inhaled corticosteroids. Inhaled steroids are the recommended preventer drug for adults and children for achieving overall treatment goals. Inhaled steroids should be considered for patients with any of the following asthma-related features: Exacerbations of asthma in the last two years (no evidence to recommend for children <5 years). Using inhaled β 2 agonists three times a week or more. Symptomatic three times a week or more. Waking one night a week. Starting dose of inhaled steroid Start patients at a dose of inhaled steroids appropriate to the severity of disease. In adults, a reasonable starting dose will usually be 400 microgram Beclometasone per day and in children 200 microgram Beclometasone per day. In children under five years, higher doses may be required if there are problems in obtaining consistent drug delivery. Titrate the dose of inhaled steroid to the lowest dose at which effective control of asthma is maintained. Steroid dose should be reviewed every three months until good asthma control is achieved. Control should then be monitored at each asthma review and dose adjusted as necessary, Step down the dose and use of ICS where clinically appropriate. Decrease the dose by 25 to 50% each time, where clinically appropriate. Review patients every three months as they step down. 2. Frequency of dosing of inhaled steroids Give inhaled steroids initially twice daily, except ciclesonide which is given once daily. Once a day inhaled steroids at the same total daily dose can be considered if good control and monitoring is established and maintained (e.g. PEFs, patient diary). Safety of inhaled steroids in adults Titrate the dose of inhaled steroid to the lowest dose at which effective control of asthma is maintained. In practice it should rarely be necessary to increase the steroid dose above the standard recommended dose as detailed in Step 2 of British Respiratory Guideline for Management of Asthma. At higher doses there is an increased risk of side effects with minimal improvement in response*. *Current problems in Pharmacovigilance CSM warnings (Vol 28 Oct 2002 Adrenal suppression in children; Vol 27 Aug 2001 High dose Fluticasone) If a patient, despite demonstrating good technique, does not respond to adequate doses of inhaled steroid +/- long acting β 2 agonist then referral to a specialist should be considered. Page 15 of 49

Provide steroid cards routinely for patients receiving: systemic steroids of more than 3 weeks duration. long-term maintenance steroids. prolonged treatment with high doses of ICS (beclometasone 1600 micrograms, fluticasone 800 micrograms, budesonide 1600 micrograms. multiple courses of short bursts of steroids (3 or more per year). Inform all patients (and their carers) about the important benefits and safety issues of ICS emphasising the need to practice good oral care after ICS use. Oropharyngeal Thrush: some patients cannot tolerate inhaled corticosteroids due to severe mouth soreness or thrush. These patients can be tried on Ciclesonide (Alvesco ) once a day (dose 40 160micrograms od) instead of the other ICS medications. Ciclesonide is inactive in the mouth and so has a reduced incidence of side effects. 3. Safety of inhaled steroids in children Monitor height and weight of children on high doses of inhaled steroids on an annual basis. The lowest dose of inhaled steroids compatible with maintaining disease control should be used. 4. Safety of inhaled steroids in children treated with 800 micrograms Beclometasone per day or equivalent: Specific written advice about steroid replacement (e.g. Steroid Alert Card) in the event of a severe intercurrent illness or surgery should be part of the management plan. The child should be under the care of a specialist paediatrician for the duration of the treatment. Smoking Clinicians should be aware that higher doses of inhaled steroids may be needed in patients who are smokers or ex-smokers. Page 16 of 49

Berkshire East Respiratory Guidelines Asthma Corticosteroids Standard Dose Adults: Steps 2 & 3 Children 5-12 years: Steps 2,3, & 4 Adults and children aged 5-12 years: High Dose Adults: Step 4 Children: N/A Cost per 28 days Standard High dose ( )* 1 st choice Beclometasone pmdi with a spacer device Beclometasone Easyhaler (Adults ONLY) Beclometasone (Qvar ) Easi- Breathe (Adults ONLY) Becometasone (Qvar ) Autohaler (Adults ONLY) 100 400 micrograms twice a day 200 400 micrograms bd (Adults ONLY) 50 200 micrograms bd 400 1000 micrograms twice a day 200 400 micrograms bd 2.08-18.25 4.18-20.90 2.17-18.98 2.20-19.28 Qvar is NOT interchangeable with other pressurised MDIs and is approximately twice as potent as Clenil Modulite. Beclometasone pressurised MDIs should be prescribed by brand name. Alternative Budesonide Easyhaler (Child ONLY if >6 years) Budesonide turbohaler* (Dry Powder) *only if unable to use pmdi 100 400 micrograms twice a day 400 800micrograms twice a day 2.48-19.84 3.32-31.05 Alternative Fluticasone MDI with a spacer device Or Fluticasone Accuhaler (Dry Powder) 50 200 micrograms Twice a day 200 500 micrograms twice a day 2.54-33.73 5.96-33.73 N.B A spacer device should be used with inhaled corticosteroids delivered via MDI. This is particularly important in children, if a patient has poor technique or if dose is greater than 800 micrograms daily for Budesonide or Beclometasone or 400 microgram daily for Fluticasone. Ciclesonide can be used if oropharyngeal side effects are severe. Page 17 of 49

Standard Dose Children under 5 years: Step 2 Cost per 28 days with spacer ( )* Children under 5 years: 1 st Choice Beclometasone pmdi 100 200 micrograms twice a day 2.08-4.53 N.B A Spacer device should be added in children Maximum recommended doses of inhaled corticosteroids Maximum adult dose: Maximum child dose: Beclometasone 1000 micrograms twice a day 400 micrograms twice a day (5-12 years) Budesonide 800 micrograms twice a day 400micrograms twice a day (5-12 years) Fluticasone 500 micrograms twice a day 200 micrograms twice a day (5-12 years) * Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 The MHRA has advised (July 2008) that beclometasone diproprionate CFC-free inhalers should be prescribed by brand name. Page 18 of 49

3.5 Initial Add-On Therapy Before initiating a new drug therapy practitioners should recheck compliance, inhaler technique and eliminate trigger factors where possible If trigger factors are considered to be within the work environment a specialist referral should be made. The duration of a trial of add-on therapy will depend on the desired outcome. If there is no response to treatment the drug should be discontinued. The first choice as add-on therapy to inhaled steroids in adults and children (5-12 years) is an inhaled long-acting β 2 agonist (LABA), which should be considered before going above a dose of 400 microgram Beclometasone or equivalent per day and certainly before going above 800 microgram Beclometasone. Improves lung function and symptoms, and decreases exacerbations. The first choice as add-on therapy to inhaled steroids in children under five years old is leukotriene receptor antagonists. If asthma control remains suboptimal after the addition of an inhaled long-acting β 2 agonist (LABA) then the dose of inhaled steroids should be increased to 800 micrograms/day in adults or 400 micrograms/day in children (5-12 years), if not already on these doses. Leukotriene receptor antagonists may provide improvement in lung function, a decrease in exacerbations, and an improvement in symptoms (Adults, 5-12 years, and <5 years). Theophyllines may improve lung function and symptoms, but side effects occur more commonly (Adults and children 5-12 years only). Slow-release β 2 agonist tablets may also improve lung function and symptoms, but side effects occur more commonly (>12 years only). Page 19 of 49

3.6 Combination steroid / long acting β 2 agonists (LABA) Flow diagram taken from British Asthma Guidelines 2011 There is no difference in efficacy in giving inhaled steroid and long-acting β 2 agonist in combination or in separate inhalers. Once a patient is on stable therapy, combination inhalers have the advantage of guaranteeing that the long-acting β 2 agonist is not taken without inhaled steroid. Where a combination inhaler exists containing the same steroid as the patient has already been established on then transfer may be made to that combination at the appropriate dose and careful monitoring should take place until good control is established. For equivalent doses of Beclometasone, budesonide and fluticasone please see the inhaled corticosteroid section. Budesonide/formoterol rescue therapy o In selected adult patients at step 3 who are poorly controlled or in selected adult patients at step 2 (above Beclometasone 400 microgram/day who are poorly controlled) the use of budesonide / formoterol in a single inhaler as rescue medication instead of a short-acting β 2 agonist in addition to its regular use as controller therapy has been shown to be an effective treatment regimen. When this management option is introduced the total regular dose of daily inhaled corticosteroids should not be decreased. The regular maintenance dose of inhaled steroids may be budesonide 200 micrograms twice daily or budesonide 400 microgram twice daily. Patients taking rescue budesonide/formoterol once a day or more should have their treatment reviewed. Careful education of patients about the specific issues around this management strategy is required. See Self Management Plan in Appendix I. Page 20 of 49

Combination steroid/ long acting β 2 agonist NB Fostair has extra-fine particles and is more potent than traditional beclometasone dipropionate CFC-free inhalers Fostair licensed with Aerochamber Plus Standard dose Adults and Children 5-12 years: Step 3 1 dose = 1 puff High dose Adults: Step 4 Children N/A 1 dose = 1 puff Cost per 28 days treatment ( )* Adults and children over 5 years: Dose Cost Fostair (over 18 years only) Beclometasone 100 Beclometasone 100 Std 13.68 microgram / Formoterol 6 microgram / Formeterol microgram 6 microgram High 27.37 1-2 doses twice a day 2 doses twice a day Fostair 100/6 can be prescribed for patients already using beclometasone diproionate 250micrograms in another CFC-free inhaler; dose of Fostair should be adjusted according to response Alternative Seretide Accuhaler (Dry Powder Inhaler) Fluticasone 100 microgram / Salmeterol 50 microgram 1 dose twice a day Fluticasone 500 microgram/salmeterol 50 microgram 1 dose twice a day Std 16.80 High 38.19 Alternative Symbicort Turbohaler (Dry Powder Inhaler) Alternative Seretide Evohaler (MDI) * Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 Budesonide 200 microgram / Formoterol 6 microgram 1 dose twice a day Fluticasone 50 microgram/ Salmeterol 25 microgram 2 doses twice a day Budesonide 400 microgram / Formoterol 12 microgram 2 doses twice a day Fluticasone 250 microgram/ Salmeterol 25 microgram 2 doses twice a day Std 17.73 High 70.93 Std 16.80 High 55.52 NB A spacer device should be used with inhaled corticosteroids via MDI Children under 5 years: N/A Long acting β 2-agonist not indicated in children under 5 years in the British Guideline on the Management of Asthma Page 21 of 49

3.7. Other Add on drugs (doses specified are recommended adult doses) Leukotriene Receptor Antagonists: May provide an improvement in lung function, a decrease in exacerbations and an improvement in overall symptoms. May be of benefit in patients with exercise induced asthma and in those with concomitant rhinitis, but they are less effective in those with severe asthma who are also receiving high doses of other drugs. Page 22 of 49

1 st Choice: Montelukast Cost per 28 days ( )* Adult and Child over 15 years: 10mg daily 2.66 Child 6 months 6 years: 4mg daily 2.35 (sachets) 3.88 (tablets) Child 6 15 years: 5mg daily 2.66 Costs taken from Drug Tariff Online October 2013 Theophyllines: May improve lung function and symptoms, but side effects occur more commonly. Narrow margin between the therapeutic and toxic dose. Plasma concentration for optimum response is 10-20mg/litre. Plasma concentration is altered by cytochrome P450 enzyme inhibitors or inducers (See Appendix 1: Interactions, BNF). Maintenance therapy should be guided by serum measurements when there is a suspicion of either toxicity or sub-therapeutic levels, when increasing the dose or when adding other interactive medicines. Must be prescribed using the brand name to ensure bioequivalence. 1 st Choice: Uniphyllin Continus Cost per 28 days ( )* Adult: 200mg 400mg every 12 hours 2.96-5.65 Child: 9mg/kg (up to 200mg) every 12 hours 2.96 Alternative: Slo-Phyllin Cost per 28 days ( )* Adult: 250 500mg every 12 hours 4.34-8.68 Child 2-6 years: 60 120mg every 12 hours 2.76-5.52 Child 6-12 years: 125 250mg every 12 hours 3.48-4.34 * Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 3.8 Long term oral steroids (daily oral steroid or regular booster courses) For the small number of patients not controlled at step 4, use daily steroid tablets in the lowest dose providing adequate control. Long term oral steroids should only be considered following secondary care referral. The aim of treatment is to control the asthma using the lowest possible dose or, if possible, to stop long term steroid tablets completely. Inhaled steroids are the most effective drug for decreasing requirement for long term steroid tablets. In adults, the recommended method of eliminating or reducing the dose of steroid tablets is inhaled steroids, at doses of up to 2,000 microgram/day, if required. In children aged 5-12, consider very carefully before going above an inhaled steroid dose of 800 microgram/day. There is a role for a trial of treatment with long acting β 2 agonists, leukotriene receptor antagonists, and theophyllines for about six weeks. They should be stopped if no improvement in steroid dose, symptoms or lung function is detected. There is no evidence that other formulations of prednisolone offer any advantage. Page 23 of 49

Patients on long term steroid tablets (e.g. longer than three months) or requiring frequent courses of steroid tablets (e.g. three or more per year) will be at risk of systemic side effects. o Blood pressure should be monitored. o Urine or blood sugar and cholesterol should be checked. Diabetes mellitus and hyperlipidaemia may occur. o Bone mineral density should be monitored. When a significant reduction occurs, treatment with a long-acting bisphosphonates should be offered (see British Osteoporosis Society guidelines, www.nos.org.uk). o Growth (height and weight) should be monitored in children. o Cataracts may be screened for in children through community optometric services. 1 st choice: Prednisolone 5mg tablets at the lowest dose providing adequate control. Peak flow meters Measurement of peak flow is particularly helpful for patients who are poor perceivers and hence slow to detect deterioration in their asthma, and for those with moderate or severe asthma. Peak flow records should be interpreted with caution and with regard to the clinical context. To get maximum information the patient needs to be highly motivated, have good technique and the task must be logistically possible. With careful use the meters should be expected to last at least two years Only peak flow meters conforming to European Union Standard EN 13826 are recommended for use. Readings from the new peak flow meters are often lower than those obtained from old Wright-scale peak flow meters and the correct recording chart should be used. The type of peak flow meter used should be documented in patient notes to enable accurate comparisons to be made. Calculation of Peak Flow Diurnal Variability 20% or greater variation on 3 or more days per week demonstrates poor control To calculate: subtract the lower Peak Flow reading from the higher on any one day; divide by the highest figure and multiply by 100 = % variability e.g. morning peak flow: 450 afternoon peak flow: 350 % variability = 450 350/ 450 x 100 =100/ 450 x 100 = 22% Further information on peak flow and interpretation of readings is available on www.peakflow.com 1 st Choice Cost ( )* Mini Wright Standard 60 800 litres/minute 6.86 Low Range 30 400 litres/ minute 6.90 * Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 Page 24 of 49

4. Review In primary care patients with asthma should be reviewed regularly, at least on an annual basis, by a nurse or doctor with appropriate training in asthma management. Inhaler technique should be observed, measured and any necessary corrections made All patients should be offered self-management education which should focus on individual needs. Patients should have their own peak flow meter and be encouraged to monitor and record their peak flow twice daily as reflected in their Personal Asthma Management Plan. Patients should know when to increase their medication and when to seek medical assistance Patients should know when and how to step down treatment. See Appendix I Self Management Plan. Appendix II Rescue Packs See Asthma UK Peak Flow Link. A variety of Apps are available, such as My Asthma Log. Page 25 of 49

5. Acute Asthma in Primary Care Management And Drug Choices Please refer to the British Guideline for the Management of Asthma for detailed guidance on the management of acute asthma and for detailed definitions of levels of severity of acute asthma exacerbations. Assessment Assessment of the patient will include the following observations: Peak expiratory flow or spirometry. Respiratory rate. Heart rate. Ability to complete sentences in one breath. Oxygen saturation (if available). Frequency of recent reliever inhaler use. Criteria for Admission Adults Admit patients with any feature of: A life threatening or near fatal attack Severe attack persisting after treatment Peak Expiratory Flow measurement of 50% or below of either predicted or usual best. Children Admit children with: Severe or life threatening asthma. Acute asthma which has not improved after receiving up to 10 doses (puffs) of β 2 agonist (further doses should be given while awaiting transfer). Drug Therapy Failure to respond adequately at any time requires immediate referral to hospital. Please refer to the British Guideline on the Management of Asthma for detailed guidance on the management of acute asthma and for detailed definitions of levels of severity of acute asthma exacerbations. Page 26 of 49

5.1 Adults Oxygen Give supplementary oxygen to all hypoxaemic patients with acute severe asthma to maintain a SpO 2 level of 94-98%. Lack of pulse oximetry should not prevent the use of oxygen. Oximetry should be interpreted in the context of the clinical situation and inspired oxygen concentration. In hospital, ambulance and primary care, nebulised β 2 agonist bronchodilators should preferably be driven by oxygen. Bronchodilators In acute asthma without life threatening features, short acting β 2 agonists can be administered by repeated activations of a pressurised metered dose inhaler via an appropriate large volume spacer; give 1-10 puffs of salbutamol 100 micrograms/metered inhalation each inhaled separately, one minute apart and repeat at 10-20 minute intervals if necessary. May be given by nebuliser (oxygen-driven) if available. Use high-dose inhaled β 2 agonists as first line agents in acute asthma and administer as early as possible. Reserve intravenous β 2 agonists for those patients in whom inhaled therapy cannot be used reliably but these patients need close monitoring in a hospital setting. In acute asthma with life threatening features and in severe asthma (PEF or FEV1 <50% of their best) the nebulised route (oxygen-driven if available) is recommended and urgent admission to A&E should be arranged. Add nebulised ipratropium bromide (0.5mg every 4-6 hours) to β 2 agonist treatment for patients with acute severe or life threatening asthma or those with a poor initial response to β 2 agonist therapy. Steroid Therapy Steroid tablets reduce mortality, relapses and subsequent hospital admission and requirement for β 2 agonist therapy. The earlier they are given in the acute attack the better the outcome. Give steroids in adequate doses in all cases of acute asthma. Continue high dose prednisolone (0.5mg/kg) daily for at least five days or until recovery. Titrate upwards any regular dose of steroid. It is not known if inhaled steroids provide further benefit in addition to systemic steroids. Inhaled steroids should however be started, or continued as soon as possible to commence the chronic asthma management plan. Page 27 of 49

5.2 Children Over 2 years β 2 agonists should be given as first line treatment. Children with acute asthma at home and symptoms not controlled by up to 10 puffs of salbutamol via pressurised Metered Dose Inhaler and spacer, or 2.5-5mg of nebulised salbutamol, should see urgent medical attention. Additional doses of bronchodilator should be given as needed whilst awaiting medical attention if symptoms are severe. Paramedics attending to children with acute asthma should administer nebulised salbutamol driven by oxygen if symptoms are severe whilst transferring the child to the emergency department. Children with severe or life threatening asthma should be transferred to hospital urgently. Oxygen Children with life threatening asthma or SpO2 <94% should receive high flow oxygen via a tight fitting face mask or nasal cannula at sufficient flow rates to achieve normal saturations. Inhaled β 2 agonists (Salbutamol / Terbutaline) Inhaled β 2 agonists are the first line treatment for acute asthma. A pressurised metered dose inhalers + spacer (with face mask for children < 3 years) is the preferred option in mild to moderate asthma. Inhalers should be actuated into the spacer in individual puffs and inhaled immediately by tidal breathing (for five breaths). Individualise drug dosing according to severity and adjust according to the patient s response. Increase β 2 agonist dose by two puffs every two minutes according to response up to ten puffs. Children with severe or life threatening asthma (SpO2 <92%) should receive frequent doses of nebulised bronchodilators driven by oxygen (2.5-5mg salbutamol or 5-10mg terbutaline). Discontinue long-acting β 2 agonists when short-acting β 2 agonists are required more often than four-hourly. Ipratropium Bromide There is good evidence for the safety and efficacy of frequent doses of ipratropium bromide (every 20-30 minutes) used in addition to β 2 agonists for the first two hours of a severe asthma attack. Benefits are more apparent in the most severe patients. Steroid Therapy Steroid tablets Give prednisolone early in the treatment of acute asthma attacks. Use a dose of 20mg prednisolone for children aged 2-5 years and a dose of 30-40mg for children >5 years. Those already receiving maintenance steroid tablets should receive 2mg/kg prednisolone up to a maximum dose of 60mg. o Repeat the dose of prednisolone in children who vomit and consider intravenous steroids in those who are unable to retain orally ingested medication. o Treatment for up to three days is usually sufficient, but the length of course should be tailored to the number of days necessary to bring about recovery. Weaning is unnecessary unless the course of steroids exceeds 14 days. Page 28 of 49

Inhaled steroids Do not initiate inhaled steroids in preference to steroid tablets to treat children with acute asthma. Leukotriene Receptor Antagonists Initiating oral montelukast in primary care settings, early after the onset of acute asthma symptoms, can result in decreased asthma symptoms and the need for subsequent healthcare attendances in those with mild exacerbations. There is no clear evidence to support the use of leukotriene receptor antagonists for moderate to severe acute asthma. 5.3 Children Aged Less Than 2 Years β2 agonists Bronchodilators For mild to moderate acute asthma, a pressurised metered dose inhaler + spacer (with face mask) is the optimal drug delivery device. Oral β2 agonists are not recommended for acute asthma in infants. Steroid Therapy Consider steroid tablets in infants early in the management of severe episodes of acute asthma in the hospital setting Steroid tablet therapy (10mg of soluble prednisolone for up to three days) is the preferred steroid preparation for use in this age group. Ipratropium Bromide Consider inhaled ipratropium bromide in combination with an inhaled β2 agonist for more severe symptoms. Failure to respond adequately at any time requires immediate referral to hospital. Patient should be monitored, informed of possibility of relapse and given patient information leaflet. If unresponsive to above within 30 minutes or relapse within 3-4 hours. Immediately refer to hospital. Give nebulised β2 agonist with nebulised ipratropium. Give high flow oxygen via a face mask. Further Management Monitor symptoms and peak flow. Review in surgery in 24 hours. Modify treatment at review. Control should be monitored and medication adjusted as necessary. Page 29 of 49

Berkshire East Respiratory Guidelines COPD Section 2: Chronic Obstructive Pulmonary Disease Management and Drug Choices The following guidance is based on the NICE COPD Guidelines 2010 http://www.nice.org.uk/nicemedia/live/13029/49398/49398.doc 1. Diagnosis and Severity Assessment A diagnosis of COPD should be considered in patients over the age of 35 who have a risk factor (generally smoking) and who present with one or more of the following symptoms: Exertional breathlessness Chronic cough Regular sputum production Frequent winter bronchitis Wheeze N.B. Patients may not necessarily be symptomatic Spirometry should be performed: At the time of diagnosis. To reconsider the diagnosis, if patients show an exceptionally good response to treatment. Measure post-bronchodilator spirometry to confirm the diagnosis of COPD The following should be used as a definition of COPD: Airflow obstruction is defined as FEV 1 /FVC is less than 0.7. If FEV 1 is 80% predicted normal a diagnosis of COPD should only be made in the presence of respiratory symptoms, for example breathlessness or cough. Consider alternative diagnoses or investigations in: Older people without typical symptoms of COPD where the FEV 1 /FVC ratio is <0.7l Younger people with symptoms of COPD where the FEV 1 /FVC ration is 0.7l Reversibility testing is not part of the new NICE guidelines and is of no value in the diagnosis of COPD. However, reversibility testing may be an aid in excluding a diagnosis of asthma. Page 30 of 49

Asthma can be differentiated from COPD based mainly on history: COPD ASTHMA Smoker or ex-smoker Nearly all Possibly Symptoms under 35 Uncommon 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 Severity of airflow limitation is measured by spirometry: Post-bronchodilator FEV 1 /FVC FEV 1 % predicted NICE clinical guideline 101 (2010) Severity of airflow obstruction Post-bronchodilator <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** *Symptoms should be present to diagnose COPD in people with mild airflow obstruction **or FEV1 <50% with respiratory failure 5. Assessment of breathlessness: Medical Research Council (MRC) dyspnoea scale Grade Degree of breathlessness related to activities 1. Not troubled by breathlessness except on strenuous exercise 2. Short of breath (SOB) when hurrying or walking up a slight hill 3. Walks slower than contemporaries on the level because of breathlessness, or has to stop for breath when walking at own pace 4. Stops for breath after about 100m or a few minutes on the level 5. Too breathless to leave the house, or breathless when dressing and undressing Measures of daily living should also be recorded: Walking distance Time taken on stairs Page 31 of 49

Time taken to wash and dress 6. The following measurements should also be made for nutritional assessment, a key component of COPD care. Patient s weight and height. BMI. Page 32 of 49

Berkshire East Respiratory Guidelines COPD 2. Smoking Cessation Smoking cessation is the most effective therapy for COPD and is the most cost effective medical intervention. The top two most cost effective interventions are flu vaccination and smoking cessation. Ensure patients receive their annual flu vaccination. Unless contraindicated, offer NRT, varenicline or bupropion, as appropriate, to people who are planning to stop smoking combined with an appropriate support programme to optimise smoking quit rates for people with COPD. Ensure patients are aware of local Stop Smoking services. Patients can self-refer or be referred by their GP for NRT products and support. NRT provision and local community-based support is detailed on Smokefreelife Berkshire Details of clinics can be found at www.smokefreelifeberkshire.com. The COPD Value Pyramid Page 33 of 49

Triple therapy in COPD is not cost effective and provides least value. Consider the safety of high dose inhaled corticosteroids in COPD; inhaled corticosteroids only benefit some COPD patients through reduction of exacerbations. Rescue packs (antibiotics and steroids) can reduce hospital admissions due to exacerbations. 3. Pulmonary Rehabilitation Pulmonary Rehabilitation is a 6 week course (twice weekly sessions) of supervised high intensity exercise. 94% of patients who complete the course leave walking both further and faster Referral criteria include a confirmed respiratory diagnosis, shortness of breath with activities of daily living, stable co-morbidities and cognitive independence Page 34 of 49

4. Management of stable COPD (Algorithm 2 taken from NICE Clinical Guideline 101, COPD, June 2010) The overall aims of management are to stop smoking, control symptoms, prevent exacerbations and address nutritional status Algorithm 2: Management of stable COPD Patient with COPD Assess symptoms/problems Manage those that are present as below Patients with COPD should have access to the wide range of skills available from a multidisciplinary team Smoking Breathlessness and exercise limitation Frequent exacerbations Respiratory failure Cor pulmonale Abnormal BMI Chronic productive cough Anxiety and depression Offer help to stop smoking at every opportunity Combine pharmacotherapy with appropriate support as part of a programme Optimise inhaled therapy using the algorithm (2a) below If still symptomatic consider adding theophylline Offer pulmonary rehabilitation to all patients who consider themselves functionally disabled (usual MRC grade 3 and above) including those who have had a recent hospitalisation for an exacerbation Consider referral for surgery: bullectomy, LVRS, transplantation Offer annual influenza vaccination Offer pneumococcal vaccination Give self-management advice Optimise bronchodilator therapy using the algorithm (2a) below Assess for appropriate oxygen: - LTOT - ambulatory - short burst Consider referral for assessment for long-term domiciliary NIV Assess need for oxygen Use diuretics Refer for dietetic advice Refer to Nutrition support in adults (NICE clinical guideline 32) Give nutritional supplements if the BMI is low Consider trial of mucolytic therapy Continue if symptomatic improvement Be aware of anxiety and depression and screen for them in those most physically disabled Refer to Depression in Adults with a Chronic Physical Health Problem (NICE clinical guideline 91) Palliative care Opiates should be used when appropriate for the palliation of breathlessness in patents with end-stage COPD unresponsive to other medical therapy Use benzodiazepines, tricyclic antidepressants, major tranquillisers and oxygen when appropriate Involve multidisciplinary palliative care teams advised to check the BNF or product SPCs for full prescribing information Page 35 of 49

Use of inhaled therapies (Algorithm 2a taken from NICE Clinical Guideline 101, COPD, June 2010) Algorithm 2a: Use of inhaled therapies Please note: This algorithm should be used within the wider context of the management of COPD, including algorithms 1, 2 and 3 Breathlessness and exercise limitation Exacerbations or persistent breathlessness SABA or SAMA as required* FEV1 50% FEV1 < 50% LABA LAMA Discontinue SAMA ------------------------- Offer LAMA in preference to regular SAMA four times a day LABA + ICS in a combination inhaler ------------------------ Consider LABA + LAMA if ICS declined or not tolerated LAMA Discontinue SAMA ------------------------- Offer LAMA in preference to regular SAMA four times a day Persistent exacerbations or breathlessness LABA + ICS in a combination inhaler -------------------------- Consider LABA + LAMA if ICS declined or not tolerated LAMA + LABA + ICS in a combination inhaler Abbreviations: SABA Short-acting beta agonist SAMA Short-acting muscarinic antagonist LABA Long-acting beta agonist LAMA Long-acting muscarinic antagonist ICS Inhaled corticosteroid * SABA (as required) may continue at all stages Offer therapy (strong evidence) Consider therapy (less strong evidence) advised to check the BNF or product SPCs for full prescribing information Page 36 of 49

5. Drug Delivery 1. Patients should be treated with the device that they have shown to consistently use in the most effective manner. 2. Inhaler technique should be checked at every review and prior to any changes in medication. Choice of Inhaler Device in COPD Poor co-ordination in this group of patients can significantly impair the patient s ability to use an pressurised Metered Dose Inhaler. A spacer or alternative inhaler device should usually be considered. If a patient is unable to use a particular device satisfactorily, it is not suitable for him or her, and an alternative should be found. Inhalers should be prescribed only after patients have received training in the use of the device and have demonstrated satisfactory technique. Pressurised Metered Dose Inhalers and dry powder devices require a certain amount of inspiratory effort for activation. This should be assessed before prescribing these devices. A device such as an in-check dial can be used to measure inspiratory effort. However, this does not cover all types of inhaler and an alternative would be to assess ability to use the device followed by assessment of symptoms. Inhaler devices other than pressurised metered dose inhalers should be prescribed by brand name to minimise confusion and optimise drug therapy. Pressurised metered dose inhalers should be prescribed generically where possible. Nebuliser Solutions in COPD Selected patients with severe COPD may derive benefit from very high doses of bronchodilators that can be more conveniently delivered using a nebuliser. Nebulised therapy for a stable patient is not routinely appropriate unless it is demonstrably more effective than conventional inhaled therapy. Ongoing assessment and confirmation of this should be carried out (see MRC Dyspnoea Scale). Those in whom nebulised therapy may be considered should be assessed by a respiratory consultant. If hypercapnic or acidotic the nebuliser should be driven by compressed air, not oxygen. Nebulisers are not prescribable on the NHS. Details of Nebuliser suppliers are available from Berkshire East Chest Clinic based at King Edward VII Hospital, Windsor. Page 37 of 49

6. Drug Therapy Short acting bronchodilators Do not modify decline in lung function or alter the natural course of the disease. Are given either on an as needed basis for relief of symptoms or on a regular basis to prevent or reduce symptoms. All categories of bronchodilators may modestly increase exercise capacity in COPD, without necessarily changing FEV 1. A short acting inhaled β 2 agonist combined with an anti-muscarinic bronchodilator increases FEV 1 and other measures of airway calibre more than single drug therapy. Indication: if symptomatic and with spirometric abnormality* *FEV 1 <80% predicted and FEV 1 /FVC <0.7 Short acting Bronchodilator of Choice Cost for 28 days treatment ( )* 1 st Choice Salbutamol inhaler (spacer device should be considered) Or Ipratropium aerosol inhaler (spacer device should be considered) Salbutamol 100 microgram 2 puffs as required or four times a day Ipratropium 20 microgram 1-2 puffs as required or three to four times a day 1.50-3.36 2.12-5.66 Nebules of Choice Nebules should only be prescribed after full assessment by a respiratory consultant and considered if the patient is unable to use pressurised metered dose inhaler + spacer. Advice on Nebulisers is available from the Chest Clinic based at King Edward VII Hospital, Windsor Severe COPD Compound bronchodilator nebules Ipratropium bromide with Salbutamol (nebules) (Ipratropium bromide 500 micrograms, salbutamol 2.5mg/2.5ml vial) 1 vial (2.5ml) three to four times a day or as required 33.74-44.99 *Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 Long acting bronchodilators and inhaled combination therapy There are two classes of long acting bronchodilator licensed for use in COPD. Response to either class of drugs is not exclusive and sequential trial of both types of bronchodilator may be appropriate. Page 38 of 49

The drug should be used for a trial period of 3 months and discontinued if there is an inadequate response. Response should be measured by using the MRC Dyspnoea Scale and assessment of daily activities. Other inhaled or nebulised antimuscarinic agents should be stopped when tiotropium is prescribed o Offer once-daily long-acting muscarinic antagonist (LAMA) in preference to four-timesdaily short-acting muscarinic antagonist (SAMA) to people with stable COPD who remain breathless or have exacerbations If FEV 1 50% predicted: either long-acting β 2 agonist (LABA) or LAMA o If FEV 1 <50% predicted: either LABA with an inhaled corticosteroid (ICS) in a combination inhaler, or LAMA. LABAs should be used in patients who have two or more exacerbations per year. In people with stable COPD and an FEV 1 50% who remain breathless or have exacerbations despite maintenance therapy with a LABA. o Consider LABA + ICS in a combination inhaler. o Consider LAMA in addition to LABA where ICS is declined or not tolerated. Offer LAMA in addition to LABA + ICS to people with COPD who remain breathless or have exacerbations despite taking LABA+ICS, irrespective of their FEV 1. Consider LABA+ICS in a combination inhaler in addition to LAMA for people with stable COPD who remain breathless or have exacerbations despite maintenance therapy with LAMA irrespective of their FEV 1. All LAMAs should be reviewed after first three months of initiation to check effectiveness and stopped if no clinical improvement. Document date and outcome of review. The choice of drug(s) should take into account the person s symptomatic response and preference, and the drug s potential to reduce exacerbations, it s side effects and cost. Indication: if still symptomatic on short acting muscarinic antagonist (SAMA) Use for a trial period of 3 months only and withdraw if there is an inadequate response Long acting β2 agonist (LABA) Recommended Dose (1 dose = 1 puff) 1 st Choice Easyhaler Formoterol Breath Actuated dry powder inhaler Alternative Salmeterol Accuhaler (dry powder inhaler) Alternative Salmeterol MDI (spacer should be considered) OR 12 microgram 1 dose twice a day 50 microgram 1 blister twice a day 25 microgram 2 doses twice a day Cost for 28 days treatment ( )* 11.08 27.31 27.31 Long acting muscarinic antagonist Recommended Dose Cost for 28 days (LAMA) treatment ( )* 1 st Choice Tiotropium 18 microgram HandiHaler 18 microgram 1 dose once daily 32.55 Tiotropium 2.5microgram Respimat 5 microgram 2 doses once daily 33.85 Aclidinium bromide 400microgram Inhaler 322microgram [Aclidinium] 1 dose bd 29.69 * Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 Page 39 of 49

Inhaled combination therapy (ICS/LABA) Prolonged treatment with inhaled corticosteroids (ICS) does not modify the long term decline in FEV 1 however long term studies of ICS demonstrate an improvement in health related quality of life and a decrease in exacerbation rate in patients with moderate to severe COPD. The aim of treatment is to reduce the exacerbation rates and slow the decline in health status, not to improve lung function. Oral corticosteroid reversibility tests should not be used to predict response to ICS. Clinicians should be aware of the potential risk of developing osteoporosis and other side effects (including non-fatal pneumonia) in patients treated with high dose ICS and discuss this risk with patients. Combination Steroid/Long acting β 2 agonist inhaler devices should be prescribed at the licensed doses as recommended in these guidelines. Combination Steroid/Long acting β 2 agonist Alternative Licensed Dose (1 dose = 1 puff) Cost / 28 days treatment ( )* Symbicort Turbohaler 400/12 (Dry Powder Inhaler) Alternative Budesonide 400 microgram / Formoterol 12 microgram 1 dose twice a day 35.47 Seretide 500 Accuhaler (Dry Powder Inhaler) Fluticasone 500 microgram / Salmeterol 25 microgram 1 blister twice a day 38.19 NB. These are the licensed doses and devices for the combination inhalers The licensed dose of Symbicort represents half the equivalent steroid dose which is licensed for Seretide. Please consider this when comparing cost of treatment. * Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 Theophyllines The term theophyllines is used to mean slow-release formulations of this drug. A combination of a β 2 agonist, an muscarinic antagonist and / or theophyllines may produce additional improvements in lung function and health status in COPD. There is a narrow margin between the therapeutic and toxic dose. Serum measurements should be taken when clinically indicated. Plasma concentrations are increased by cytochrome P450 enzyme inhibitors, including some antibiotics and reduced by smoking (See Appendix 1: Interactions, BNF). Must be prescribed by the brand name to ensure bioequivalence. Response should be measured by using the MRC Dyspnoea Scale and assessment of daily activities (see MRC Scale). Page 40 of 49

Indication: only use after a trial of short-acting bronchodilators and long-acting bronchodilators, or in patients who are unable to use inhaled therapy Recommended Dose Cost / 28 days treatment ( )* Uniphyllin Continus 200mg twice a day 2.96 OR Slo-Phyllin Continus 250mg twice a day 4.34 - Use for a trial period of 2 months only then withdraw if inadequate response Oral Steroids Long term treatment with oral glucocorticosteroids is not recommended in COPD. There is no evidence of long term benefit with this treatment. Oral Mucolytics Regular use of mucolytics may be of some benefit in patients with severe exacerbations of COPD and/ or a chronic productive cough. They are indicated for reduction of sputum viscosity Do not routinely use mucolytic drugs to prevent exacerbations in people with stable COPD Indication: Consider as a trial in patients with excessive mucus production and exacerbations. Discontinue if there is no benefit after 4 weeks. Carbocisteine 375mg Capsules Or 250mg/5ml oral liquid * Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 Long Term Oxygen Therapy Recommended Dose Cost / 28 days treatment ( )* 750mg three times a day initially Caps 26.57 Liquid 29.36 then 1.5g daily in divided doses Caps 17.72 Liquid 19.57 This should be prescribed following full assessment by the Home Oxygen Service Assessment & Review. Assess the need for oxygen therapy in patients with very severe airflow obstruction (FEV 1 <30% predicted), cyanosis, polycythaemia, peripheral oedema, raised jugular venous pressure or oxygen saturations 92% breathing air. Consider assessment for patients with severe airflow obstruction (FEV 1 30-49% predicted). Practices should have a pulse oximeter to ensure all patients needing LTOT are identified Ambulatory oxygen should be considered for patients already on LTOT who want to continue with therapy outside the home. Short-burst oxygen therapy should only be considered for episodes of intermittent hypoxia. See end of document for local oxygen guidance. Page 41 of 49

Influenza Vaccination and Pneumococcal Vaccination All patients should be offered a pneumococcal vaccination and an annual flu vaccination. Nutritional Supplements and Advice BMI > 26: BMI <19: refer to dietician and provide advice on weight loss. refer to dietician, provide nutritional advice and consider nutritional interventions including food supplements. 7. Review Patients with mild or moderate COPD should be reviewed in primary care at least once per year. Patients with severe COPD should be reviewed in primary care at least twice per year. For most patients with stable severe disease regular hospital review is not necessary, but access to hospital assessment is available when necessary. 8. Referral to Secondary Care May be appropriate at any stage of disease and includes the following criteria: Rapidly progressing disease (a loss of 500ml or more measured by spirometry over 5 years) Severe disease requiring interventions such as Oxygen therapy, long-term nebuliser therapy, non-invasive ventilation, pulmonary rehabilitation or referral to the hospital-at-home scheme and community COPD service. Aged under 40 years or with a family history of alpha -1 antitrypsin deficiency. Onset of cor pulmonale. Symptoms disproportionate to lung function deficit. Page 42 of 49

9. Exacerbations of Chronic Obstructive Pulmonary Disease Management and Drug Choices Exacerbations Causes and definition The causes of exacerbations of COPD are not understood. Many factors can trigger them and they are a major cause of morbidity, mortality and hospital admission. Patients at risk of having an exacerbation of COPD should be given self-management advice that encourages them to respond promptly to the symptoms of an exacerbation. Exacerbations are defined as: A sustained worsening of the patient s symptoms from their usual stable state which is beyond normal day to day variations, and is acute in onset Commonly reported symptoms are: Worsening breathlessness, cough, increased sputum production and change in sputum colour. The change in these symptoms often necessitates a change in medication. Assessment Assessment of the patient will include the following: Pulse Blood Pressure Oxygen saturation Respiratory rate Chest examination Checking for ankle oedema and cor pulmonale Drug Therapy Bronchodilators Increased inhaled bronchodilator therapy with the use of additional short acting bronchodilators on an as required basis. Systemic Corticosteroids In the absence of significant contraindications oral corticosteroids should be considered in patients who have an exacerbation with a significant increase in breathlessness which interferes with daily activities. Selected patients at risk of having an exacerbation of COPD should be given a Rescue pack (Appendix II) containing a course of corticosteroid tablets and antibiotics to keep at home for use as part of a self-management strategy. Rescue pack patients should be informed about how to increase inhaled bronchodilator therapy and when more urgent care is required. Osteoporosis prophylaxis should be considered in patients requiring frequent courses of oral corticosteroids. Page 43 of 49

Corticosteroid Recommended Dose Cost/7 days treatment ( )* Prednisolone 5mg tablets 30mg daily for 7 days 1.81 (non-enteric coated) Antibiotics Antibiotics should be used to treat exacerbations of COPD associated with a history of more purulent sputum or clinical signs of pneumonia. Selected patients at risk of having an exacerbation of COPD should be given a course of antibiotics to keep at home for use as part of a self-management strategy. Recommended Cost/28 days Recommended Cost/28 days Dose treatment ( )* Dose treatment ( )* Infective Exacerbation of COPD CAP 1 st Choice Amoxicillin 500mg three times a day for 5 days 1.15 500mg 1g three times a day for 7 10 days 1.61-4.60 Alternative Doxycycline Penicillin allergy Clarithromycin 200mg stat/ 100mg once a day for 5 day course 500mg twice a day for 5 days 83p 2.01 200mg stat/ 100mg once a day for 7 10 days 500mg twice a day for 7 10 days 1.11-1.52 2.81-4.02 If resistant risk factors Co-amoxiclav 625mg three times a day for 5 days 1.77 N/A N/A * Costs taken from Drug Tariff Online October 2013 accessed October 2013 and MIMS October 2013 Taken from Management of Infection Guidance for Primary Care June 2013 - Berkshire East Further Management Arrange appropriate review. Establish optimal therapy. Arrange multi-disciplinary assessment if necessary. Consider referral to the COPD Admission Avoidance team. Page 44 of 49

Algorithm 3, Taken from NICE Clinical Guideline 101, Chronic Obstructive Pulmonary Disease, June 2010 Algorithm 3: Managing exacerbations of COPD Exacerbations of COPD can be associated with increased: Dyspnoea/sputum purulence/sputum volume/cough Initial management Increase frequency of bronchodilator use - consider giving via a nebuliser Oral antibiotics if purulent sputum Prednisolone 30 mg daily for 7 14 days for all patients with significant increase in breathlessness, and all patients admitted to hospital, unless contraindicated Decide where to manage (see table below) Hospital Investigations Chest X-ray Arterial Blood gases (record inspired oxygen concentration) ECG Full blood count and urea and electrolytes Theophylline level if patient on theophylline at admission Sputum microscopy and culture if purulent Further management If necessary, oxygen should be given to keep the SaO2 within the individualised target range* Assess need for noninvasive ventilation: - consider respiratory stimulant if NIV not available - assess need for intubation Consider intravenous theophyllines if poor response to nebulised bronchodilators Consider hospital-at-home or assisted-discharge scheme Before discharge Establish on optimal therapy Arrange multidisciplinary assessment if necessary *Readers should refer to local protocols for oxygen therapy Factors to consider when deciding where to manage patient Factor Able to cope at home Breathlessness General condition Level of activity Cyanosis Worsening peripheral oedema Level of consciousness Already receiving LTOT Social circumstances Favours treatment at home Yes Mild Good Good No No Normal No Good Favours treatment in hospital No Severe Poor - deteriorating Poor/ confined to bed Yes Yes Impaired Yes Living alone/ Not coping Acute confusion No Yes Rapid rate of onset Significant comorbidity (particularly cardiac and insulin dependent diabetes) Changes on the chest radiograph No No No Yes Yes SaO2 < 90% No Yes Present Arterial ph level 7.35 < 7.35 Arterial PaO2 7kPa < 7kPa Home Investigations Sputum culture not normally recommended Pulse oximetry if severe exacerbation Further management Arrange appropriate review Establish on optimal therapy Arrange multidisciplinary assessment if necessary Abbreviations: LTOT long-term oxygen therapy SaO2 oxygen saturation of arterial blood PaO2 partial pressure of oxygen in arterial blood Page 45 of 49

Local Oxygen Guidance Adult Home Oxygen Service Assessment & Review (HOS-AR) Pre-referral Pathway (Oximetry Monitoring). Referral to the Home Oxygen Service Assessment and Review (HOS-AR). Home Oxygen Service Assessment and Review (HOS-AR). Page 46 of 49

10. Berkshire East Respiratory Guidelines - Appendices Appendix I Self Management Plans For further information on Self Management Plans see Asthma UK website. A variety of Apps are available, such as My Asthma Log For further information for COPD refer to Chest Clinic based at King Edward VII Hospital, Windsor. The service offers a variety of support methods including a Staying Healthy Leaflet and a selfmanagement plan on how to deal with future COPD exacerbations. Page 47 of 49

Appendix II - Rescue Packs The contents of Asthma and COPD Rescue packs listed below. Review is required during the course of Rescue medication, as duration of treatment may need to be extended beyond the minimum time period indicated. Asthma Prednisolone Daily Dose Age Duration Asthma 40mg Adult and Children > 12 5 days Don't stop 30mg 5-12 years 3 days steroids before full 20mg 2-5 years 3 days recovery 10mg 2 years 3 days Antibiotics Dose CAP Amoxicillin 500mg - 1g tds 7-10 days Clarithromycin 500mg bd 7-10 days Doxycycline 200mg STAT / 100mg od 7-10 days COPD Prednisolone Daily Dose Age Duration COPD 30mg N/A 7 days Antibiotics Dose Infective exacerbation of COPD Amoxicillin 500mg 5 days Clarithromycin 500mg bd 5 days Doxycycline 200mg STAT / 100mg 5 days od *Co-amoxiclav 625mg tds 5 Days * if resistant risk factors Page 48 of 49

Contributions gratefully received from: Asthma UK Sally Clarke Geoff Francis Carina Joanes Angela Jones Jo King Maureen Maul Medicines Optimisation Pharmacists Cathy O Brien Richard Russell Helen Rutherford Kirsty Scott Fiona Wyles Prescribing Support Pharmacist, Medicines Optimisation Team, WAM CCG G.P., Maidenhead Medicines Information Manager, HWPH Consultant Asthma Lead, HWPH COPD Advanced Nurse Practitioner, HWPH P.A., Medicines Optimisation Team, WAM CCG Medicines Optimisation Team, WAM CCG Respiratory Lead Nurse, Datchet H.C. Consultant COPD Lead, HWPH G.P., Gainsborough Practice Directorate Pharmacist Manager, HWPH Asthma Advanced Practitioner, HWPH Page 49 of 49