1 New Approaches for Severe Adult AsthmaHuffing and Puffing? New Approaches for Severe Adult Asthma

2 Planning Committee J. Mark FitzGerald MD FRCPCAlan Kaplan MD CCFP(EM) FCFP Jacques Bouchard MD, CCFP Kenneth Bayly MD, MCFP This program has been reviewed and co-developed by the Family Physicians Airways Group of Canada.

3 Presenter Disclosure Relationships with commercial interests: [TBD]Faculty: [INSERT NAME + CREDENTIALS] Relationships with commercial interests: [TBD] Grants/Research Support: [TBD] Speakers Bureau/Honoraria: [TBD] Consulting Fees: [TBD] Other: [TBD]

4 Disclosure of Commercial SupportThis program has received financial support from Boehringer Ingelheim in the form of an unrestricted educational grant. Potential for conflicts of interest: [Presenter name] has received [payment/funding] from [insert].

5 Mitigating Potential Bias[Explain how potential sources of bias identified in the presenter disclosure and commercial support slides have been mitigated.]

6 Accreditation This program has been accredited by the College of Family Physicians of Canada and the ______________ Chapter for up to ____ Mainpro-M1 credit(s).

7 Abbreviations used in this programACOS = asthma-COPD overlap syndrome COPD = chronic obstructive pulmonary disease CTS = Canadian Thoracic Society FABA = fast acting beta2-agonist FEV1 = forced expiratory volume in 1 second FLAP = 5-lipoxygenase-activating protein ICS = inhaled corticosteroid IL = interleukin GINA = Global Initiative for Asthma LAAC = long-acting anticholinergic (LAACs are also called long acting muscarinic antagonists (LAMAs)) LABA = long-acting beta2-agonist LTRA = leukotriene receptor antagonist PEF = peak expiratory flow PDE4 = phosphodiesterase-4 SABA = short-acting beta2-agonist SABD = short-acting bronchodilator WHtR = waist-to-height ratio

8 Learning Objectives Recognize patients whose asthma is not controlled.Assess reasons for poor asthma control. Identify options for maintenance treatment in severe uncontrolled asthma. Adjust therapy for optimal current and future control of asthma. Learning Objectives After completion of the program, the participant will be able to: Recognize patients whose asthma is not controlled. Assess reasons for poor asthma control. Identify options for maintenance treatment in severe uncontrolled asthma. Adjust therapy for optimal current and future control of asthma.

9 Uncontrolled Asthma Despite the range of currently available treatments, more than half of asthma patients continue to have uncontrolled asthma and remain at risk of future exacerbations.1–5 Uncontrolled asthma is associated with significant morbidity and mortality. Poor asthma control accounts for most asthma-related healthcare costs.6–8 Despite the range of currently available treatments, more than half of asthma patients continue to have uncontrolled asthma and remain at risk of future exacerbations.1–5 Uncontrolled asthma is associated with significant morbidity and mortality. Poor asthma control accounts for most asthma-related healthcare costs.6–8

10 Associated with … Reliever medication use Risk of exacerbationsRisk of hospitalization Healthcare costs Risk of death (~250 deaths annually in Canada) 9–12 Uncontrolled asthma is associated with reduced functioning and quality of life, and with increased:9–12 Reliever medication use Risk of exacerbations Risk of hospitalization Healthcare costs Risk of death (~250 deaths annually in Canada)

11 Asthma Control The Asthma In Canada (AIC) survey (1999) The Reality of Asthma Control (TRAC) study (2004) The Control of Asthma and Side Effect (CASE) study (2005) Asthma control in Canada is low. While asthma-related mortality has declined over the past two decades, levels of asthma control in Canada have remained largely unchanged and unacceptably low, as shown by three major surveys conducted between 1999 and 2005 (see slide).13–15 AIC = Asthma in Canada; TRAC = The Reality of Asthma Control; CASE = Control of Asthma and Side Effects Chapman KR, et al. Can Respir J 2001;8(SA):35A-40A; FitzGerald JM, et al. Can Respir J 2006;13(5):253-9; FitzGerald JM, et al. Can Respir J 2008;15(1):27-32.

12 Current and Future ControlPatients with current symptoms are at 6 times greater risk of an exacerbation in coming weeks Reduced quality of life Presence of symptoms may be underestimated, by both patients and practitioners Current symptom control in asthma is a predictor of future risk. Poor control predicts future reduction in lung function, increased risk of exacerbations, and increased risk of side effects due to oral corticosteroid use.9 Patients with uncontrolled asthma experience more potentially life-threatening exacerbations, and have significantly increased use of medical services.16 People with asthma symptoms: - are at about six times greater risk of an exacerbation over the next few weeks than those with minimal-to-no daytime symptoms.17 experience reduced quality of life; they are affected physically, socially, and professionally.18 The presence of symptoms may be underestimated, by both patients and practitioners.

13 Discussion How often do you reassess your asthma patients for control?How do you efficiently assess asthma control in your patients?

14 Key Points The goal of asthma management is to control symptoms and minimize risk, especially the risk of exacerbations. Poor control predicts future reduction in lung function, increased risk of exacerbations, and increased risk of side effects due to oral corticosteroid use. Poor asthma control increases the risk of exacerbations, hospitalization, and death. Current control in asthma is a predictor of future risk, and risk of exacerbation. The goal of asthma management is to control symptoms and minimize risk, especially the risk of exacerbations. Current symptom control in asthma is a predictor of future risk. Poor control predicts future reduction in lung function, increased risk of exacerbations, and increased risk of side effects due to oral corticosteroid use. Poor asthma control increases the risk of exacerbations, hospitalization, and death. Current control in asthma is a predictor of future risk, and risk of exacerbation.

15 Robert 45 years old Never-smoker Works as a machinist2 exacerbations in 10 months Symptoms interfering with work, sleep, sports 250 mcg fluticasone in combination with LABA, one inhalation twice daily salbutamol inhaler prn, currently 4 times per week Robert is a 45-year-old patient with asthma who is visiting you for his follow-up appointment. Robert experienced an acute exacerbation 21 days ago – his second in 10 months. He required a short course of oral corticosteroids for each exacerbation. A lifetime non-smoker, at a healthy body weight, Robert’s asthma symptoms continue to interfere with his work as a machinist, and with his sleep. He tells you he also has not been participating in his usual Saturday bike ride with his friends. You have managed Robert’s asthma for the past 9 months with 250 mcg fluticasone in combination with LABA, given as one inhalation twice daily. Robert also has a salbutamol inhaler for symptom-relief as-needed. Robert tells you he uses his reliever inhaler 4 times per week. When you ask him to demonstrate to you how he administers his asthma medications, he does so correctly. You review Robert’s pre- and post-bronchodilator spirometry results to reconfirm the diagnosis.

16 Discussion Is Robert’s asthma controlled?Robert’s asthma is not controlled. See asthma control criteria on next slide.

17 Asthma Control Criteria (CTS 2012)Characteristic Frequency or Value Daytime symptoms <4 days/week Night-time symptoms <1 night/week Physical activity Normal Exacerbations Mild, infrequent Absence from work or school due to asthma None Need for a FABA** <4 doses/week FEV1 or PEF ≥90% personal best PEF diurnal variation* <10%–15% Sputum eosinophils† <2%–3% Asthma control should be assessed regularly (see the CTS criteria for asthma control in Table). Standard assessment now includes symptoms, spirometry, the need for rescue medication, and where available may include the use of sputum eosinophil count (but this measure is not often used in primary care).19 Lougheed, M. D. et al. Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Can. Respir. J. J. Can. Thorac. Soc. 19, 127–164 (2012). *Diurnal variation is calculated as the highest PEF minus the lowest divided by the highest peak flow multiplied by 100 for morning and night (determined over a two-week period). ; **(SABA or use of ICS/LABA) fewer than 4 times per week; † Consider in adults with uncontrolled moderate to severe asthma who are assessed in specialist centres. Lougheed, M. D. et al. Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Can. Respir. J. J. Can. Thorac. Soc. 19, 127–164 (2012).

18 GINA Update 2015: SABA OveruseHigh usage of SABA is a risk factor for exacerbations. Very high usage (e.g. >200 doses/month) is a risk factor for asthma-related death. Reliever use 4 or more times per week indicates UNCONTROLLED ASTHMA. (CTS criteria) About GINA: The Global Initiative for Asthma (GINA) works with health care professionals and public health officials around the world to reduce asthma prevalence, morbidity, and mortality.

19 What should be your next step?Increase the prescription for salbutamol to ensure Robert has enough to relieve symptoms on demand? Step-up Robert’s controller treatment to help him achieve symptom control? Assess possible reasons for Robert’s poor asthma control? Other? Discuss the options for next step. Best Answer: c) assess possible reasons for Robert’s poor asthma control When asthma is uncontrolled, reconfirm the diagnosis and assess possible reasons for poor control *before* stepping up therapy.

20 Reasons for Poor ControlPoor adherence to medications Poor inhaler technique Smoking/exposure Trigger exposure Comorbidities Incorrect diagnosis Reconfirm the diagnosis in patients with poorly controlled asthma. Reasons for poor asthma control should then be assessed prior to making medication adjustments. This includes: Check factors affecting adherence to medication with open-ended, non-judgmental questions Ask about drug side effects or concerns Ask about drug or device cost coverage Assess the patient’s understanding of the chronic nature of asthma Check inhaler technique Ask the patient to demonstrate their inhaler technique Encourage review of inhaler technique with collaborating care providers (e.g., pharmacist, asthma educator) Assess smoking history and second-hand smoke exposure Offer smokers assistance with quitting at every interaction Ensure patients understand the importance of avoiding second hand smoke Emphasize that cigarette smoke not only triggers asthma but reduces the effect of asthma medications as well Assess exposure to other triggers Discuss the settings and situations in which symptoms or exacerbations occur Review common triggers with the patient, and discuss the importance of their avoidance Consider occupational triggers Assess for any effect of comorbidities Common comorbidities with asthma include allergic rhinitis, gastro-esophageal reflux disease, obesity, obstructive sleep apnea, depression and anxiety, and more11,20–22,12,23 Review health and immunization history, comorbidities, and current therapies Review the Action Plan and ensure understanding

21 Adherence is Poor in AsthmaAsk patients regularly about satisfaction or ‘concerns’ with treatment Review inhaler technique Check prescription refills Simplify treatment regimens Memory aids and reminders – physician-delivered or electronic Studies show drug adherence rates of less than 50% in people with asthma.24–26 Ask patients regularly about their satisfaction with treatment and whether they have any troubles with the medications, so that barriers to adherence can be addressed. A recent study found that brief physician-delivered or electronic reminders improved adherence to controller treatment and improved asthma control.28,29

22 Check Triggers Triggers might go unrecognizedExercise, temperature, humidity, smog, wood smoke, scents, emotional upset, anxiety, smoking and second hand smoke Allergens such as trees, pollen, grasses, animals Consider occupational triggers – Robert works as a machinist. Could there be triggers in his workplace? Common asthma triggers include:30 exercise cold air or hot, humid air smog, wood smoke scents emotional upset, anxiety smoking and second hand smoke allergens such as trees, pollen, grasses, animals occupational triggers

23 Patient Education Asthma changes, e.g., in response to triggers or seasons Importance of identifying triggers Review the action plan Review role of medications: controllers vs relievers Track reliever use Patient Education The following talking points can help patients understand and adhere to their asthma management plan:31 Help patients understand that their asthma is not static; it is a variable condition that will change in response to triggers or seasons. Explain the importance of identifying and avoiding personal triggers. Together with your patient, make a written action plan Recommend regular follow-up for monitoring and treatment adjustment. Help patients understand the role of each of their medications and the importance of adherence: Explain that controller medications are for prevention, and need to be taken every day, even if symptoms are absent. They treat the cause of asthma (airway inflammation). Explain that relievers help alleviate symptoms immediately if coughing or wheezing. However, reliever medications (with the exception of single maintenance and reliever therapy) do not treat the underlying cause of asthma. Ask patients to track how often they use their reliever. Increased use over time means they should make an appointment to see you.

24 This is one example of the Asthma Action PlanThis is one example of the Asthma Action Plan. This one is provided by the FPAGC and can be downloaded from their website. It uses colour-coding: Green = control Yellow = control is lost Red = urgent loss of asthma control From the Family Physicians Airway Group of Canada. Available from:

25 Key Points Despite the range of currently available treatments, more than half of asthma patients remain uncontrolled and at risk of future exacerbations. Asthma control should be regularly assessed, at 1-3 months after treatment started, then every months.  During step-up therapy for uncontrolled asthma, assess control at least every 2-3 months. When asthma symptoms are uncontrolled despite correct diagnosis, adherence to management, treatment, and other reasons for poor control have been ruled out, therapy should be adjusted to achieve optimal symptom control.   Review the Action Plan to ensure patient understanding. Despite the range of currently available treatments, more than half of asthma patients remain uncontrolled and at risk of future exacerbations. Asthma control should be regularly assessed, at 1-3 months after treatment started, then every 3-12 months.  During step-up therapy for uncontrolled asthma, assess control at least every 2-3 months. When asthma symptoms are uncontrolled despite correct diagnosis, adherence to management, treatment, and other reasons for poor control have been ruled out, therapy should be adjusted to achieve optimal symptom control.

26 After ruling out other reasons for poor asthma control, you conclude that Robert’s asthma severity level is now: Mild? Moderate? Severe? Discuss the severity level. Answer: severe Robert’s asthma has remained uncontrolled at a medium-to-high dose of ICS/LABA. His asthma would now be classified as severe.

27 GINA Categories of Asthma SeverityMild asthma: well-controlled with Steps* 1 or 2 (as-needed SABA or low dose ICS) Moderate asthma: well-controlled with Step 3 (low-dose ICS/LABA) Severe asthma: requires Step 4/5 (moderate or high dose ICS/LABA ± add-on), or remains uncontrolled despite this treatment GINA Categories of Asthma Severity Mild asthma: well-controlled with Steps 1 or 2 (as-needed SABA or low dose ICS) Moderate asthma: well-controlled with Step 3 (low-dose ICS/LABA) Severe asthma: requires Step 4/5 (moderate or high dose ICS/LABA ± add-on), or remains uncontrolled despite this treatment Asthma severity is based on the level of treatment required to control symptoms and exacerbations. Severity changes over time, and should be assessed after several months of treatment with controller medications. Importantly, uncontrolled asthma does not always indicate increasing asthma severity. Assess reasons for poor asthma control before stepping up treatment. *Steps are outlined on next slide

28 Asthma Management (GINA 2015)The GINA report was updated in Steps 4 and 5 address severe asthma. (About GINA: The Global Initiative for Asthma (GINA) provides a regularly updated strategy for asthma management and prevention worldwide. The GINA report is not a guideline, but is a clinically-oriented and evidence-based, practical approach to managing asthma in clinical practice that is relevant to both low- and high-resource countries.) Notes for graphic on slide: * For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS ** For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy # Tiotropium by soft-mist inhaler is indicated as add-on treatment for adults (≥18 yrs) with a history of exacerbations LAAC = long-acting anticholinergic; SABA = short-acting beta2-agonist; SABD = short-acting bronchodilator; LTRA = leukotriene receptor antagonist From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) Available from: From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) Available from:

29 Management of Severe asthma: (top right of slide) The CTS guidelines for asthma management were last updated in 2012 (see slide). Note: A new option for add-on to ICS/LABA is the long-acting anticholinergic (LAAC) tiotropium. Management of Severe asthma: (top right of slide) For asthma patients already receiving low-dose inhaled corticosteroids (ICS), and who remain uncontrolled the evidence based option is the addition of a long-acting β2-agonist (LABA) - assuming possible reasons for poor control have been addressed. Additional options for add-on for patients who remain uncontrolled include:19,32 LTRA tiotropium the anti-IgE monoclonal antibody omalizumab Other less evidence-based interventions include: an increased dose of ICS , theophylline and oral glucocorticosteroids,.19,32,33 Lougheed, M. D. et al. Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Can. Respir. J. J. Can. Thorac. Soc. 19, 127–164 (2012).

30 ICS Dose Levels Inhaled corticosteroid Low Medium High beclometasone >200–400 >400 budesonide > >800 ciclesonide 80-160 > >320 fluticasone > >500 mometasone > >440 From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2015. Available from:

31 Treatment Options Relievers Controllers SABA salbutamol terbutalineICS beclomethasone budesonide ciclesonide fluticasone mometasone

32 Key Points Sustained step-up in treatment is recommended if asthma is poorly controlled, despite confirming diagnosis, and proper adherence to medications and all other aspects of management ICS are the foundation therapy for all patients with asthma SABA as-needed reliever medication is indicated for all patients Sustained step-up in treatment is recommended if asthma is poorly controlled, despite confirming diagnosis, and proper adherence to medications and all other aspects of management. ICS are the foundation therapy for all patients with asthma SABA as-needed reliever medication is indicated for all patients (unless they are using a budesonide/formoterol formulation as single maintenance and reliever therapy).

33 LABA Treatment Options After ICSControllers LABA (adjunctive to ICS) formoterol salmeterol ICS/LABA formulations available as combinations budesonide + formoterol* fluticasone + salmeterol mometasone + formoterol fluticasone + vilanterol Note that budesonide/formoterol can be used as single maintenance and reliever therapy Can be used as reliever + controller therapy

34 Treatment Options (Add-on to ICS/LABA)Controllers LAAC Tiotropium (NEW) LTRA montelukast zafirlukast Anti-IgE omalizumab Oral Corticosteroids prednisolone prednisone dexamethasone Xanthine-derivative theophylline

35 Tiotropium: New Asthma Indication in CanadaAs add-on to ICS/LABA (dose equivalent to >500 mcg fluticasone or >800 mcg budesonide/day) For patients uncontrolled on high-dose ICS/LABA and who have had one or more exacerbations in the previous year Recommended dose of tiotropium is 2 inhalations of 2.5 mcg once daily from the inhaler at the same time of day, every day Tiotropium is now approved in Canada, as add-on maintenance bronchodilator treatment in adult patients with asthma who remain symptomatic on a combination of inhaled corticosteroid (equivalent to, but not limited to ≥500 mcg fluticasone/day or ≥800 mcg budesonide/day) and a long acting β2 agonist and who experienced one or more severe exacerbations in the previous year. Tiotropium is not indicated as rescue medication for the relief of acute bronchospasm in COPD or asthma. The recommended dose of tiotropium is 2 inhalations of 2.5 micrograms once daily at the same time of day, every day.

36 Tami 36 years old Non-smoker BMI = 49 kg/m2Exacerbation 2 weeks ago (fall, previous one in spring) Seasonal allergies, allergic rhinitis, dermatitis 200 mcg budesonide/LABA; two inhalations twice daily +2 inhalations daily prn relief Failed trial of LTRA Tami is a 36-year-old non-smoker with asthma who experienced a moderate exacerbation 2 weeks ago. Tami has seasonal allergies, allergic rhinitis, and dermatitis. It is currently autumn and Tami’s previous acute exacerbation was in the spring. With a BMI of 49 kg/m2, Tami is obese, which contributes to her daily breathlessness, as does her anxiety. The extra weight and difficulty breathing contribute to her difficulty exercising. You currently prescribe asthma maintenance therapy budesonide in combination with LABA, given as two inhalations of (200 mcg budesonide) twice daily. Tami tells you she is also administering about 2 additional inhalations per day for on-demand relief of symptoms. You ask Tami to demonstrate to you how she administers her medication and she does so correctly. You previously initiated a trial of LTRA for Tami, which she had to discontinue due to headaches. You reconfirm Tami’s diagnosis of asthma, and review other possible reasons for poor asthma control, none of which appear to be factors.

37 What agent(s) are options for stepping-up Tami’s asthma therapy?Increase the dose of ICS/LABA Switch to a different ICS/LABA Add-on LAAC (tiotropium) Add-on LTRA (a second trial) Add-on theophylline Add-on anti-IgE therapy Tami should be referred for discussion of adjusting therapy. Any of the listed options are possible next steps for stepping up Tami’s Increase the dose of ICS/LABA – maintenance dose is already at maximum but prn doing can be increased. But the need for increased reliever medication signals inadequate controller effect… Switch to a different ICS/LABA – a different combination may or may not work better for Tami. You would have to prescribe a new reliever medication as well, since only one ICS?LABA combination is indicated for reliever use in Canada. Add-on LAAC (tiotropium) – new option Add-on LTRA (a second trial) – but this has already been tried Add-on theophylline – discuss this option Add-on anti-IgE therapy – discuss this option therapy

38 Severe Asthma (GINA 2015) GINA 2015: Severe Asthma Add-on treatment for severe asthma (Step 5): Step-up strategies for severe asthma at GINA step 5 may include higher-dose ICS/LABA, oral* corticosteroids, phenotype-specific or non-specific treatments, or non-pharmacological interventions. (Non-pharmacological interventions are also indicated for other severity levels.) “Add-on controller medications such as theophylline and LTRAs, although suggested for severe asthma, appear in the small number of available studies to be of limited benefit. In patients with ongoing uncontrolled symptoms and persistent airflow limitation despite moderate-high dose ICS and LABA, add-on treatment with the long-acting anti-cholinergic bronchodilator, tiotropium41, showed improved lung function and decreased reliever use.” ― GINA 2015 From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) Available from:

39 Discussion What factors do you feel are barriers to stepping up therapy in patients with moderate-to-severe asthma who remain uncontrolled at high doses of ICS/LABA?

40 Reviewing Response General: 1-3 months after treatment started, then every months During pregnancy, every 4-6 weeks After an exacerbation, within 1 week Reviewing Response and Adjusting Treatment (GINA)32 How often should a patient with asthma be reviewed? 1-3 months after treatment started, then every 3-12 months During pregnancy, every 4-6 weeks After an exacerbation, within 1 week

41 Reviewing Response While stepping up asthma treatmentSustained step-up, for at least 2-3 months if asthma poorly controlled Important: first check for common causes (symptoms not due to asthma, incorrect inhaler technique, poor adherence) Short-term step-up, for 1-2 weeks, e.g. with viral infection or allergen exposure May be initiated by patient with written asthma action plan Day-to-day adjustment For patients prescribed budesonide/formoterol maintenance and reliever regimen How often should a patient with asthma be reviewed? Stepping up asthma treatment Sustained step-up, for at least 2-3 months if asthma poorly controlled Important: first check for common causes (symptoms not due to asthma, incorrect inhaler technique, poor adherence) Short-term step-up, for 1-2 weeks, e.g. with viral infection or allergen May be initiated by patient with written asthma action plan Day-to-day adjustment For patients prescribed budesonide/formoterol maintenance and reliever regimen GINA 2015; Pocket Guide, p.17

42 Stepping Down (GINA) When symptoms have been well controlled and lung function stable for ≥3 months, and No respiratory infection, patient not travelling, not pregnant Step down ICS doses by 25–50% at 3 month intervals Stopping ICS is not recommended in adult asthma GINA 2015 Recommendations for Stepping Down Controller Treatment:32 Aim To find the lowest dose that controls symptoms and exacerbations, and minimizes the risk of side-effects When to consider stepping down When symptoms have been well controlled and lung function stable for ≥3 months No respiratory infection, patient not travelling, not pregnant Prepare for step-down Record the level of symptom control (include spirometry) and consider risk factors Make sure the patient has a written asthma action plan Book a follow-up visit in 1-3 months Step down based on available dose formulations for the maintenance treatment Stepping down ICS doses by 25–50% at 3 month intervals is feasible and safe for most patients Stopping ICS is not recommended in adults with asthma

43 Reviewing Response While stepping down asthma treatment:Consider step-down after good control maintained for 3 months Find each patient’s minimum effective dose, that controls both symptoms and risk of exacerbations How often should a patient with asthma be reviewed? Stepping down asthma treatment Consider step-down after good control maintained for 3 months Find each patient’s minimum effective dose, that controls both symptoms and risk of exacerbations

44 Key Points Tiotropium is now approved in Canada, as add-on maintenance treatment in adult patients with asthma who remain symptomatic on a combination of inhaled corticosteroid (equivalent to, but not limited to ≥500 mcg fluticasone/day or ≥800 mcg budesonide/day) and a long acting β2 agonist and who experienced one or more severe exacerbations in the previous year.

45 Key Points Step-up strategies for severe asthma (Step 5, GINA 2015) include:19,32 LTRA tiotropium the anti-IgE monoclonal antibody omalizumab Other less evidence-based interventions include: an increased dose of ICS, theophylline, and oral glucocorticosteroids.19,32,33 To find the lowest dose of medication that controls symptoms and prevents exacerbations, and minimizes the risk of side-effects.

46 Thank you for your participation!

47 Interpreting Spirometry (GINA 2015)Spirometry plays a key role in the diagnosis of asthma, and can also be helpful in assessing asthma control.19 Spirometry also helps differentiate asthma from chronic obstructive pulmonary disease (COPD), and the asthma-COPD overlap syndrome (ACOS) (see Table). (Asthma-COPD overlap syndrome (ACOS) is characterized by persistent airflow limitation with several features of both asthma and COPD.) 34 In adults, asthma is probable when there is a post-bronchodilator increase in FEV1 of >12% and >200 mL from baseline, minutes after mcg salbutamol or equivalent. This is the commonly used criteria for diagnosis. Probability is greater if the increase is >15% and >400mL but consider the possibility of ACOS (see slide).34 In the absence of reversibility ideally the diagnosis should be confirmed with a methacholine challenge test. From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) Available from:

48 References 1. Barnes, P. J. New therapies for asthma: is there any progress? Trends Pharmacol. Sci. 31, 335–343 (2010). 2. Canonica, G. W. et al. Unmet needs in asthma: Global Asthma Physician and Patient (GAPP) Survey: global adult findings. Allergy 62, 668–674 (2007). 3. Bateman, E. D. et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am. J. Respir. Crit. Care Med. 170, 836–844 (2004). 4. Adams, R. J., Fuhlbrigge, A., Guilbert, T., Lozano, P. & Martinez, F. Inadequate use of asthma medication in the United States: results of the asthma in America national population survey. J. Allergy Clin. Immunol. 110, 58–64 (2002). 5. Partridge, M. R., van der Molen, T., Myrseth, S.-E. & Busse, W. W. Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm. Med. 6, 13 (2006). 6. Accordini, S. et al. Poor control increases the economic cost of asthma. A multicentre population- based study. Int. Arch. Allergy Immunol. 141, 189–198 (2006). 7. Haughney, J. et al. Achieving asthma control in practice: Understanding the reasons for poor control. Respir. Med. 102, 1681–1693 (2008). 8. Sadatsafavi, M. et al. The preventable burden of productivity loss due to suboptimal asthma control: a population-based study. Chest 145, 787–793 (2014). 9. Bateman, E. D. et al. Stability of asthma control with regular treatment: an analysis of the Gaining Optimal Asthma controL (GOAL) study. Allergy 63, 932–938 (2008). 10. Guilbert, T. W. et al. Asthma that is not well-controlled is associated with increased healthcare utilization and decreased quality of life. J. Asthma Off. J. Assoc. Care Asthma 48, 126–132 (2011).

49 References 11. Government of Canada, P. H. A. of C. Life and Breath: Respiratory Disease in Canada (2007) - Public Health Agency of Canada. (2007). at 12. Vila, G. et al. Psychopathology and quality of life for adolescents with asthma and their parents. Psychosomatics 44, 319–328 (2003). 13. Chapman, K. R., Ernst, P., Grenville, A., Dewland, P. & Zimmerman, S. Control of asthma in Canada: failure to achieve guideline targets. Can. Respir. J. J. Can. Thorac. Soc. 8 Suppl A, 35A–40A (2001). 14. FitzGerald, J. M., Boulet, L.-P., McIvor, R. A., Zimmerman, S. & Chapman, K. R. Asthma control in Canada remains suboptimal: the Reality of Asthma Control (TRAC) study. Can. Respir. J. J. Can. Thorac. Soc. 13, 253–259 (2006). 15. Fitzgerald, J. M., Chan, C. K., Holroyde, M. C. & Boulet, L.-P. The CASE survey: patient and physician perceptions regarding asthma medication use and associated oropharyngeal symptoms. Can. Respir. J. J. Can. Thorac. Soc. 15, 27–32 (2008). 16. McIvor, R. A., Boulet, L.-P., FitzGerald, J. M., Zimmerman, S. & Chapman, K. R. Asthma control in Canada: no improvement since we last looked in Can. Fam. Physician Médecin Fam. Can. 53, 672– 677 (2007). 17. Bateman, E. D. et al. Overall asthma control: the relationship between current control and future risk. J. Allergy Clin. Immunol. 125, 600–608, 608.e1–608.e6 (2010). 18. Braman, S. S. The global burden of asthma. Chest 130, 4S–12S (2006). 19. Lougheed, M. D. et al. Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Can. Respir. J. J. Can. Thorac. Soc. 19, 127–164 (2012). 20. Boulet, L.-P. Influence of comorbid conditions on asthma. Eur. Respir. J. 33, 897–906 (2009).

50 References 21. Boulet, L.-P. Asthma and obesity. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 43, 8–21 (2013). 22. Gershon, A. S., Wang, C., Guan, J. & To, T. Burden of comorbidity in individuals with asthma. Thorax 65, 612–618 (2010). 23. Moullec, G. et al. Interaction effect of psychological distress and asthma control on productivity loss? Eur. Respir. J. 45, 1557–1565 (2015). 24. Yeung, M., O’Connor, S. A., Parry, D. T. & Cochrane, G. M. Compliance with prescribed drug therapy in asthma. Respir. Med. 88, 31–35 (1994). 25. Spector, S. L. et al. Compliance of patients with asthma with an experimental aerosolized medication: implications for controlled clinical trials. J. Allergy Clin. Immunol. 77, 65–70 (1986). 26. Mawhinney, H. et al. As-needed medication use in asthma usage patterns and patient characteristics. J. Asthma Off. J. Assoc. Care Asthma 30, 61–71 (1993). 27. Boulet, L.-P., Vervloet, D., Magar, Y. & Foster, J. M. Adherence: the goal to control asthma. Clin. Chest Med. 33, 405–417 (2012). 28. Foster, J. M. et al. Inhaler reminders improve adherence with controller treatment in primary care patients with asthma. J. Allergy Clin. Immunol. 134, 1260–1268.e3 (2014). 29. Chan, A. H. Y. et al. The effect of an electronic monitoring device with audiovisual reminder function on adherence to inhaled corticosteroids and school attendance in children with asthma: a randomised controlled trial. Lancet Respir. Med. 3, 210–219 (2015). 30. The Lung Association. Asthma: Treatment. At https://www.lung.ca/lung-health/lung- disease/asthma/treatment 31. Asthma Society of Canada. Treatment - The Asthma Society of Canada. At 32. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention (2014). At

51 References 33. Boehringer Ingelheim Canada Ltd. Spiriva Respimat Product Monograph. (2015). at ingelheim.ca/content/dam/internet/opu/ca_EN/documents/humanhealth/product_monograph/SpirivaRespimat PMEN.pdf 34. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: Updated (2015). at 35. AstraZeneca Canada Inc. SYMBICORT TURBUHALER (budesonide and formoterol fumarate dihydrate Dry Powder Inhalers for Oral Inhalation). (2014). At Products-AZ 36. Bateman, E. D. et al. Overall asthma control: the relationship between current control and future risk. J. Allergy Clin. Immunol. 125, 600–608, 608.e1–608.e6 (2010). 37. GlaxoSmithKline Inc. ADVAIR DISKUS (salmeterol xinafoate/fluticasone propionate dry powder for inhalation). (2014). at 38. Merck Canada Inc. ZENHALE (mometasone furoate / formoterol fumarate dihydrate Inhalation aerosol) Product Monograph. (2014). at 39. GlaxoSmithKline Inc. Breo Ellipta Product Monograph. (2015). at pdf/product-monographs/Breo%20Ellipta.pdf 40. Global Initiative for Asthma (GINA). GINA Pocket Guide at 41. Kerstjens, H. A. M. et al. Tiotropium in asthma poorly controlled with standard combination therapy. N. Engl. J. Med. 367, 1198–1207 (2012). 42. Coates, A. L. et al. Spirometry in primary care. Can. Respir. J. J. Can. Thorac. Soc. 20, 13–22 (2013).