CAPA 2012 Deborah Hellyer MD

 Review Asthma – what is it  Control is possible  What is new? CTS 2012 Guidelines  Special considerations  ASA Triad  Occupational Asthma  Asthma in Pregnancy  Emergency treatment

 An inflammatory disorder of the airways characterized by paroxysmal or persistent symptoms such as dyspnea, chest tightness, wheezing, sputum production and cough, associated with variable airflow limitation and a variable degree of hyperresponsiveness of airways to endogenous or exogenous stimuli

Asthma Prevalence and Mortality Source: Masoli M et al. Allergy 2004

 2.7 million Canadians have asthma  13% of Ontarians have asthma, 21% of Ontario children aged 0-14 have asthma  39% of people with asthma report limitation in physical activity  Asthma is the # 1 reason for children being hospitalized

Pathology of Asthma Source: “What You and Your Family Can Do About Asthma” by the Global Initiative For Asthma Created and funded by NIH/NHLBI, 1995 Normal Asthma Asthma involves inflammation of the airways

Inducers Allergens, chemical sensitizers Air pollution, viruses, occupational exposures Inflammation Airway Hyperresponsiveness Airflow Limitation Symptoms Cough, Wheeze, Chest tightness Dyspnea Triggers Allergens, exercise, cold air, SO 2 particulates

Source: Peter J. Barnes, MD Asthma Inflammation: Cells and Mediators

Source: Peter J. Barnes, MD Asthma Inflammation: Cells and Mediators

 Frequent episodes of breathlessness, chest tightness, wheezing or cough  Symptoms worse at night or the early morning  Symptoms develop with a viral respiratory tract infection, after exercise, or to exposure to alloallergens or irritants  Symptoms develop in young children after playing or laughing  Symptoms improve with bronchodilators or corticosteroids

 Post infectious Cough  Post Nasal Drip  COPD  Heart Failure  Angina  Lung Cancer  Hyperventilation Syndrome  Vocal Cord Dysfunction

 Predisposing Factors  Atopy  Genetics  Gender  Causal Factors  Indoor Allergens  Occupational Sensitizers  Outdoor Allergens  Contributing Factors  Air Pollution  Diet  Low Birth Weight  Respiratory Infections  Smoking

 Supplement history with objective measures in lung function in children over six years of age  Reversible airway obstruction after bronchodilator or  Variable airflow limitation over time or  Airway hyperresponsiveness  Assessing Allergic Status

 Spirometry Testing: lung volumes in/out, lung flow of air in/out  Peak Flow Monitoring: lung flow of air in/out

Pulmonary Function MeasurementChildren (> 6 years)Adults Preferred spirometry showing reversible airway obstruction Reduced FEV 1 /FVC AND Increase in FEV 1 after bronchodilator or after a course of controller therapy Less than lower limit of normal based on age, height and ethnicity AND ≥ 12% Less than lower limit of normal based on age, sex, height, ethnicity (< ) AND ≥ 12% (minimum ≥ 200 ml) Alternative PEF variability Increase after bronchodilator or course of controller therapy OR Diurnal Variation ≥ 20% OR Not recommended 60L/min OR  8% based on twice daily readings  > 20% based on multiple daily readings Alternative Positive Challenge test Methacholine OR Exercise Challenge PC 20 < 4 mg/ml 4 mg/ml – 16 mg/ml borderline OR ≥ 10-15% decrease in FEV1 post exercise

1 Time (sec) 2345 FEV 1 Volume Normal Subject Asthmatic (After Bronchodilator) Asthmatic (Before Bronchodilator) Note: Each FEV 1 curve represents the highest of three repeat measurements

Measuring Airway Responsiveness

 Confirm diagnosis  Self management education including: environmental trigger avoidance, inhaler technique, adherence, action plan  Reliever therapy  Daily Controller therapy  Regular assessment of asthma control, including spirometry and PEF

Asthma Management and Prevention Program Goals of Long-term Management Achieve and maintain control of symptoms Maintain normal activity levels, including exercise Maintain pulmonary function as close to normal levels as possible Prevent asthma exacerbations Avoid adverse effects from asthma medications Prevent asthma mortality Achieve and maintain control of symptoms Maintain normal activity levels, including exercise Maintain pulmonary function as close to normal levels as possible Prevent asthma exacerbations Avoid adverse effects from asthma medications Prevent asthma mortality

Reducing Exposure to Environmental Tobacco Smoke Evidence suggests an association between environmental tobacco smoke exposure and exacerbations of asthma among school-aged, older children, and adults. Evidence shows an association between environmental tobacco smoke exposure and asthma development among pre-school aged children.

Reducing Exposure to House Dust Mites  Use bedding encasements  Wash bed linens weekly  Avoid down fillings  Limit stuffed animals to those that can be washed  Reduce humidity level (between 30% and 50% relative humidity per EPR-3) Source: “What You and Your Family Can Do About Asthma” by the Global Initiative For Asthma Created and funded by NIH/NHLBI, 1995

Reducing Exposure to Mold Eliminating mold and the moist conditions that permit mold growth may help prevent asthma exacerbations.

Reducing Exposure to Cockroaches Remove as many water and food sources as possible to avoid cockroaches.

Exercise can cause asthma symptoms … BUT Asthma should not usually prevent you from exercising if you:  Keep your asthma under control  Warm-up before and cool-down after exercise  Take a “reliever” medicine 5–10 minutes before exercising, if needed

 Air pollution comes from many sources, including vehicles and industry  Highest pollution levels tend to be during the hot humid days of summer  To reduce exposure to air pollution, the following may help: Reduce outdoor activity when pollution levels are high Keep windows and doors closed when there are high pollution levels(air conditioning may be needed when it gets hot)

 Moulds can be indoors in damp basements and bathrooms, and outdoors in damp weather  The following can help: Clean mouldy areas well Keep humidity around 35-45% A de-humidifier can help, especially in damp basements Get rid of clutter in the basement, to allow air to move freely Ensure proper water drainage around your home Keep bathroom dry and use fan to remove humidity Seek professional help if indoor mould doesn’t go away or if there is a lot of mould Limit outdoor activity when outdoor mould levels are high

 Pollens are tiny particles that come off trees, grass and weeds  If you are allergic to pollens, the following may help: Keep windows and doors closed in home and car during pollen seasons (air conditioner is often needed when it’s hot outside) After being outside for a long time during pollen season, shower and change clothes Person with allergies should not mow the lawn

 If a pet is making your asthma worse, the best option by far is to find it a new home  If it is not possible to find it a new home: Keep pet out of bedroom always Wash pet twice a week Encase pillows and mattress in allergy-proof covers Remove carpeting if possible Use a large HEPA* filter air cleaner in bedroom Vacuum furniture regularly with vacuum equipped with a HEPA* filter, or central vacuum system with exhaust outside the house *HEPA = High Efficiency Particulate Air

Reliever Medications  Rapid-acting inhaled β 2 -agonists  Systemic glucocorticosteroids  Anticholinergics  Theophylline  Short-acting oral β 2 -agonists

Controller Medications Inhaled glucocorticosteroids Leukotriene modifiers Long-acting inhaled β 2 -agonists in combination with inhaled glucocorticosteroids Systemic glucocorticosteroids Theophylline Cromones Anti-IgE

Estimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by Age Drug Low Daily Dose (  g) Medium Daily Dose (  g) High Daily Dose (  g) > 5 y Age 5 y Age 5 y Age < 5 y Drug Low Daily Dose (  g) Medium Daily Dose (  g) High Daily Dose (  g) > 5 y Age 5 y Age 5 y Age < 5 y Beclomethasone > > >1000 >400 Budesonide > >1000 >400 Budesonide-Neb Inhalation Suspension >1000 Ciclesonide 80 – > > > >320 Flunisolide > > >2000 >1250 Fluticasone > > >500 >500 Mometasone furoate > > > >400 Triamcinolone acetonide > > >2000 >1200

 Control  Spirometry or PEF  Inhaler Technique  Adherence  Triggers and new exposures  Medications  Environment – home and work  Comorbidities  Sputum eosinophils

60% of Canadians with asthma do not have it under control Why do so many people let asthma affect them so much?

 Do not know what good asthma control is  Do not realize that you can get good control of asthma  May not think that their asthma is bad enough to need treatment (even mild asthma often needs daily medicines)  Worried about taking medicines every day, about side effects, and costs  It may be hard to avoid triggers (eg. pets, smoke, dust mites in the bed, carpets, moulds, pollen) Possible reasons …

Medication Usage Difficulties associated with inhalers Complicated regimens Fears about, or actual side effects Cost Distance to pharmacies Medication Usage Difficulties associated with inhalers Complicated regimens Fears about, or actual side effects Cost Distance to pharmacies Non-Medication Factors Misunderstanding/lack of information Fears about side-effects Inappropriate expectations Underestimation of severity Attitudes toward ill health Cultural factors Poor communication Non-Medication Factors Misunderstanding/lack of information Fears about side-effects Inappropriate expectations Underestimation of severity Attitudes toward ill health Cultural factors Poor communication

CharacteristicFrequency or Value Daytime Symptoms< 4 days/week Night time symptoms< 1 night/week Physical ActivityNormal ExacerbationsMild, infrequent Absence from work/schoolNone Need for fast acting beta 2 agonist< 4 doses/week FEV 1 or PEF≥ 90% personal best PEF diurnal variation< 10-15% Sputum eosinophils<2-3%

Warning SignsWhat to Do Green Light  I feel Good!  I am not coughing!  I sleep well!  I have lots of energy!  Green Zone  Take my regular controller  Carry my blue reliever  Exercise /play everyday Yellow Light  I am coughing/wheezing  I use my reliever 3 or more times  I don’t feel good!  Yellow Zone  Follow my action plan  Use my controller  Get lots of rest  Go get help! Red Light  I am breathing fast  I have trouble walking/ talking  I am coughing lots  Red Zone  Asthma is dangerous!!!  Take my reliever!  Go Get Help from an adult or call 911!

Step 1 – As-needed reliever medication  Patients with occasional daytime symptoms of short duration  A rapid-acting inhaled β 2 -agonist is the recommended reliever treatment (Evidence A)  When symptoms are more frequent, and/or worsen periodically, patients require regular controller treatment (step 2 or higher) Treating to Achieve Asthma Control

Step 2 – Reliever medication plus a single controller  A low-dose inhaled glucocorticosteroid is recommended as the initial controller treatment for patients of all ages (Evidence A)  Alternative controller medications include leukotriene modifiers (Evidence A) appropriate for patients unable/unwilling to use inhaled glucocorticosteroids Treating to Achieve Asthma Control

Step 3 – Reliever medication plus one or two controllers  For adults and adolescents, combine a low-dose inhaled glucocorticosteroid with an inhaled long- acting β 2 -agonist either in a combination inhaler device or as separate components (Evidence A)  Inhaled long-acting β 2 -agonist must not be used as monotherapy  For children, increase to a medium-dose inhaled glucocorticosteroid (Evidence A) Treating to Achieve Asthma Control

Additional Step 3 Options for Adolescents and Adults  Increase to medium-dose inhaled glucocorticosteroid (Evidence A)  Low-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A)  Low-dose sustained-release theophylline (Evidence B) Treating to Achieve Asthma Control

Step 4 – Reliever medication plus two or more controllers  Medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β 2 -agonist (Evidence A)  Medium- or high-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A)  Low-dose sustained-release theophylline added to medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β 2 -agonist (Evidence B) Treating to Achieve Asthma Control

Step 5 – Reliever medication plus additional controller options  Addition of oral glucocorticosteroids to other controller medications may be effective (Evidence D) but is associated with severe side effects (Evidence A)  Addition of anti-IgE treatment to other controller medications improves control of allergic asthma when control has not been achieved on other medications (Evidence A)

Treating to Maintain Asthma Control Stepping up treatment in response to loss of control  Rapid-onset, short-acting or long- acting inhaled β2-agonist bronchodilators provide temporary relief.  Need for repeated dosing over more than one/two days signals need for possible increase in controller therapy

Treating to Maintain Asthma Control Stepping up treatment in response to loss of control  Use of a combination rapid and long-acting inhaled β 2 -agonist (e.g., formoterol) and an inhaled glucocorticosteroid (e.g., budesonide) in a single inhaler both as a controller and reliever is effecting in maintaining a high level of asthma control and reduces exacerbations (Evidence A)  Doubling the dose of inhaled glucocortico- steroids is not effective, and is not recommended (Evidence A)

Treating to Maintain Asthma Control Stepping down treatment when asthma is controlled  When controlled on medium- to high-dose inhaled glucocorticosteroids: 50% dose reduction at 3 month intervals (Evidence B)  When controlled on low-dose inhaled glucocorticosteroids: switch to once-daily dosing (Evidence A)

Treating to Maintain Asthma Control Stepping down treatment when asthma is controlled  When controlled on combination inhaled glucocorticosteroids and long-acting inhaled β 2 -agonist, reduce dose of inhaled glucocorticosteroid by 50% while continuing the long-acting β 2 -agonist (Evidence B)  If control is maintained, reduce to low- dose inhaled glucocorticosteroids and stop long-acting β 2 -agonist (Evidence D)

Assess Patient Risk Features that are associated with increased risk of adverse events in the future include:  Poor clinical control  Frequent exacerbations in past year  Ever admission to critical care for asthma  Low FEV 1, exposure to cigarette smoke, high dose medications

Assessment of Future Risk Risk of exacerbations, instability, rapid decline in lung function, side effects Features that are associated with increased risk of adverse events in the future include:  Poor clinical control  Frequent exacerbations in past year  Ever admission to critical care for asthma  Low FEV 1, exposure to cigarette smoke, high dose medications Any exacerbation should prompt review of maintenance treatment

 Exacerbations of asthma are episodes of progressive increase in shortness of breath, cough, wheezing, or chest tightness  Exacerbations are characterized by decreases in expiratory airflow that can be quantified and monitored by measurement of lung function (FEV 1 or PEF)  Severe exacerbations are potentially life- threatening and treatment requires close supervision  Exacerbations of asthma are episodes of progressive increase in shortness of breath, cough, wheezing, or chest tightness  Exacerbations are characterized by decreases in expiratory airflow that can be quantified and monitored by measurement of lung function (FEV 1 or PEF)  Severe exacerbations are potentially life- threatening and treatment requires close supervision

Primary therapies for exacerbations:  Repetitive administration of rapid-acting inhaled β 2 -agonist  Early introduction of systemic glucocorticosteroids  Oxygen supplementation Closely monitor response to treatment with serial measures of lung function Primary therapies for exacerbations:  Repetitive administration of rapid-acting inhaled β 2 -agonist  Early introduction of systemic glucocorticosteroids  Oxygen supplementation Closely monitor response to treatment with serial measures of lung function

 Role of noninvasive measurements of airway inflammation for the adjustment of anti- inflammatory therapy  The initiation of adjunct therapy to ICS for uncontrolled asthma  The role of single inhaler ICS/long acting beta 2 agonist as a reliever  Escalation of controller for acute loss of asthma control as a part of self management

 Sputum Eosinophils are not normally present in healthy, nonatopic  Increased in asthmatics exposed to aeroallergens  Decline within 3-7 days of ICS  Normal sputum eosinophilic counts <2-3% of a differential sputum count  Maybe useful in guiding treatment  Recommendation – monitoring sputum eosinophils in adults in addition to  Standard methods of control

 Biological mediator produced in the airways  Produced through a reaction catalyzed by inducible NO synthetase  Upregulated in the presence of airway inflammation  Correlates with eosinophilic airway inflammation  Confounding effect of atopic status, smoking and concomitant ICS treatment  Recommendation cannot be endorsed – insufficient evidence

 Initiation of adjunct therapy with uncontrolled asthma despite adherence to low dose ICS in adults and medium dose ICS in children  In adults with asthma not achieving control with low dose ICS, addition of a LABA; alternative increase ICS to medium or start LTRA  In children not achieving control on medium ICS add in LABA or LTRA; also should be referred to a specialist

 Do not recommend use as a reliever in lieu of FABA in adults with no maintenance therapy  Use of a SABA as a reliever in individuals with mild asthma on ICS monotherapy  In exacerbation prone individuals >12 yrs with moderate asthma on a fixed ICS/LABA; use of budesonide/formoterol as a reliever

 Recommend daily ICS in lieu of starting intermittent ICS at the onset of an acute loss of asthma control  Safest and minimal effective ICS dose be prescribed to minimize side effects in all age groups

 Children and adults on maintenance ICS monotherapy do not routinely double their dose of ICS as part of the written action plan at the onset of an episode of acute loss of asthma control  Trial increasing ICS maintenance dose by 4-5 fold for 7-14 days (history of severe exacerbations in past requiring systemic steroids

 Prednisone dose and duration in adults should be individualized based on previous response  Dose of mg/day for at least 5 days

Special considerations are required to manage asthma in relation to:  Pregnancy  Surgery  Rhinitis, sinusitis, and nasal polyps  Occupational asthma  Respiratory infections  Gastroesophageal reflux  Aspirin-induced asthma  Anaphylaxis and Asthma Special considerations are required to manage asthma in relation to:  Pregnancy  Surgery  Rhinitis, sinusitis, and nasal polyps  Occupational asthma  Respiratory infections  Gastroesophageal reflux  Aspirin-induced asthma  Anaphylaxis and Asthma

 Aspirin Exacerbated Respiratory Disease  Asthma, Nasal Polyposis, ASA sensitivity  5%-20% asthmatics; symptoms occur 30 mins to 3 hours after ingestion  Perturbations of the arachidonic acid metabolism and a resulting imbalance between proinflammatory and antiinflammatory mediators, leading to chronic airway inflammation  Leukotriene modifying agents

 Think occupation in a newly diagnosed adult asthmatic or difficult to control asthma  If diagnosed early and removed from exposure asthma resolves  If remains in exposure loss of lung function

Previous severe exacerbation (eg, intubation or ICU admission) Two or more hospitalizations for asthma in the past year Three or more emergency department visits for asthma in the past year Hospitalization or emergency department visit for asthma in the past month Use of more than two canisters of short-acting beta agonist per month Difficulty perceiving asthma symptoms or severity of exacerbations Low socioeconomic status, inner city residence, illicit drug use, major psychosocial problems Comorbidities, such as cardiovascular, chronic lung, or psychiatric disease

 Clinical Findings  Pulsus Paradoxus  Accessory muscle usage  Diaphoresis  Breathlessness when supine  Peak Flow  < 200  Gas Exchange  Hypoxemia  Hypercapnea

 Inhaled Beta agonists  Inhaled anticholinergics  Glucocorticosteroids  Magnesium Sulfate  Nonconventional therapies  Helium Oxygen  Leukotriene receptor antagonists  Ineffective therapies  Methylxantines –theophylline  Inhaled glucocorticosteroids  Empiric antibiotics

 Worse 35%, improve 28%, unchanged 33%  FVC, FEV 1, PEF do not change  RV, FRC decrease; TLC decrease 3 rd trimester  MV, TV increase circulating progesterone  PaO mmHg; PaCO mmHg – compensated respiratory alkalosis  Exacerbations 20-36% middle trimester  Small but statistically significant perinatal mortality, preterm delivery, LBW  Need to control asthma

 Asthma control is achievable  Patient education and self management is the key  Aim for the lowest medications, keep it simple  Monitor, monitor and monitor  Resources – CTS guidelines, GINA guidelines

Characteristic Controlled (All of the following) Partly controlled (Any present in any week) Uncontrolled Daytime symptoms Twice or less per week More than twice per week 3 or more features of partly controlled asthma present in any week Limitations of activities NoneAny Nocturnal symptoms / awakening NoneAny Need for rescue / “reliever” treatment Twice or less per week More than twice per week Lung function (PEF or FEV 1 ) Normal < 80% predicted or personal best (if known) on any day Assessment of Future Risk (risk of exacerbations, instability, rapid decline in lung function, side effects)

controlled partly controlled uncontrolled exacerbation LEVEL OF CONTROL maintain and find lowest controlling step consider stepping up to gain control step up until controlled treat as exacerbation TREATMENT OF ACTION TREATMENT STEPS REDUCEINCREASE STEP 1 STEP 2 STEP 3 STEP 4 STEP 5 REDUCE INCREASE

Shaded green - preferred controller options TO STEP 3 TREATMENT, SELECT ONE OR MORE: TO STEP 4 TREATMENT, ADD EITHER