1. Just Breathe: Clinical Updates in the Treatment of Asthma and COPD
Margaret Miklich, PharmD, BCACP Clinical Assistant Professor

2. I have no conflicts of interest to disclose.

3. Pharmacist Objectives
Construct a comprehensive asthma treatment plan consistent with current GINA guidelines.
Construct a comprehensive COPD treatment plan consistent with current GOLD guidelines.
Compare and contrast drug delivery devices for inhaled asthma and COPD medications.

4. Technician Objectives
Describe two goals of asthma treatment.
Describe two goals of COPD treatment.
Differentiate between “rescue” and “controller” medications.

5. Abbreviations
GINA= Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention.
EPR= National Heart, Lung, and Blood Institute (NHLBI). National Asthma Education and Prevention Program (NAEPP). Expert Panel Report (EPR): Guidelines for the Diagnosis and Management of Asthma
SABA= Short-acting beta agonist
ICS= Inhaled corticosteroid
LTRA= leukotriene receptor antagonist
LABA= long-acting beta agonist
SAMA= short-acting muscarinic antagonist
LAMA= long-acting muscarinic antagonist
COPD= chronic obstructive pulmonary disease
IgE= immune-globulin E
IL= interleukin
GOLD= global initiative for chronic obstructive lung disease
FEV1= forced expiratory volume in one second
mMRC= modified medical research council dyspnea scale
CAT= COPD assessment test
HFA= hydrofluoroalkane
DPI= dry powder inhaler

6. Asthma

7. U.S. Children U.S. Adults 8.4% 6,188,000 7.6% 18,445,000
Asthma Epidemiology
U.S. Children
U.S. Adults
7.6% 18,445,000
8.4% 6,188,000
2015 National Health Interview Survey (NHIS) Data

8. 10.5 million 1.6 million 3,615 $56 billion Asthma Epidemiology
Physician office visits with asthma as primary diagnosis
1.6 million
ED visits with asthma as primary diagnosis
3,615
Deaths with asthma as underlying cause
$56 billion
Cost of asthma in the U.S.
National Ambulatory Medical Care Survey; 2010 National Hospital Discharge Survey (NHDS) datahttps://wonder.cdc.gov/

9. Asthma Guidelines 2002 Focused update of EPR-2
2011 EPR-3 quick-reference guide updated
1991 EPR-1
1989 1st expert panel convened
2007 EPR-3
1997 EPR-2
1995 1st GINA guideline
2006 GINA
guideline major revision
2014 GINA
guideline major revision
2002 Focused update of GINA
guideline
1993 GINA founded
GINA= Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention.
EPR= National Heart, Lung, and Blood Institute (NHLBI). National Asthma Education and Prevention Program (NAEPP). Expert Panel Report (EPR): Guidelines for the Diagnosis and Management of Asthma

10. Asthma Definition
“….a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable airflow limitation”

11. Asthma Goals of Therapy
Reduce Impairment
Prevent and control symptoms (e.g. SOB, coughing)
Reduce use of SABA for quick-relief of symptoms
Maintain near normal pulmonary function
Maintain normal activity levels
Reduce Risk
Prevent acute exacerbations
Prevent ED visits and hospitalizations
Prevent progressive loss of lung function
Minimize adverse effects of pharmacotherapy

12. Stepwise Therapy: EPR-3

13. Stepwise Therapy- GINA 2017

14. Summary of Preferred Controllers
Step 1
Step 2
Step 3
Step 4
Step 5
Step 6
EPR-3
None
Low-dose ICS
Medium-dose ICS
-or-
Low-dose ICS plus LABA
Medium-dose ICS plus LABA
High-dose ICS plus LABA
-and-
consider omalizumab
High-dose ICS plus LABA plus OCS
GINA
Medium or high-dose
ICS plus LABA
Alternative: add tiotropium
Refer for add-on treatment: omalizumab
mepolizumab reslizumab
tiotropium
EPR-3;

15. Stepwise Therapy- GINA 2017
Before stepping up, check:
Diagnosis
Adherence
Inhaler technique
Modifiable risk factors
Stepping up is a “Therapeutic Trial”
Sustained step up (2-3 months)
Short-term step up (1-2 weeks)
Day-today adjustment

16. Tiotropium FDA approvals
2004: Handihaler® for COPD 2014: Respimat® for COPD 2015: Respimat® for asthma in ≥ : Respimat® for asthma in ≥6
GINA 2017 Guidelines In Steps 4 & 5:
Add-on therapy for adults/adolescents with a history of exacerbations

17. New Biologic Agents: Anti-IgE
Omalizumab (Xolair)
MOA: inhibits IgE binding on mast cells, limiting release of allergen inflammatory mediators
$$$
Dosing: subQ q2-4 weeks; based on weight and baseline IgE level
Role in Therapy: add-on to ICS/LABA for patients (age ≥6) with mod/sev allergic asthma not controlled on Step 4
BBW: Anaphylaxis
Xolair (omalizumab) [prescribing information]. San Francisco, CA: Genentech Inc; July 2016

18. New Biologic Agents: IL-5 Antagonists
MOA: inhibits IL-5 signaling to ↓ production and survival of eosinophils
$$$
Mepolizumab (Nucala)
Reslizumab (Cinqair)
SubQ q4 weeks
Dosing
IV q4 weeks; weight based
Add-on to ICS/LABA for patients (age ≥ 12) with severe eosinophilic asthma not controlled on Step 4
Role in Therapy
Add-on to ICS/LABA for adults with severe eosinophilic asthma not controlled on Step 4
None
BBW
Anaphylaxis
Benralizumab: pending FDA approval
Cinqair (reslizumab) [prescribing information]. Frazer, PA: Teva; March 2016 Nucala (mepolizumab) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; February 2017

19. In the Pipeline IL-4 and IL-13 Antagonists
Lebrikizumab, Tralokinumab, Anrukinzumab, Dupilumab
Soluble Guanylate Cyclase (sGC) Stimulators
Riociguat, Cinaciguat
Sensitive Glucocorticoid Receptor Agonists and Modulators (SEGRAMs)
Syndecan-4
Calcialytics
Images via Creative Commons

20. Assessment Question 1: Pharmacists
CG is a 31yo woman with a PMH of asthma who presents to your respiratory clinic. She is not controlled on Step 3 therapy (low-dose ICS plus LABA). She needs to be stepped up to Step 4. What is an option for therapy per GINA guidelines?
Change to medium-dose ICS
Change to medium-dose ICS plus LABA
Add tiotropium to current therapy
Add reslizumab to current therapy

21. Assessment Question 1: Technicians
Which of the following are goals of asthma treatment? [Select all that apply]
Decrease exacerbations
Increase rescue inhaler use
Decrease symptoms
Increase lung function

22. COPD

23. COPD Epidemiology
U.S. Adults
6.4% 15,700,000
Wheaton. MMWR

24. 15,694 $1.05 billion COPD Epidemiology
Medicare hospitalizations for COPD as primary diagnosis (PA)
$1.05 billion
Annual cost for Medicare COPD readmissions (US)
Medicare reimbursement!
Ford. Chest AHRQ Statistical Brief #196

25. COPD GOLD Guidelines 2011 GOLD Major Revision
(ABCD multimodal grading)
1998 GOLD formed
2017 GOLD Major Revision (refined ABCD grading)
2001 1st GOLD report
(spirometric grading)
GOLD = Global Initiative for Chronic Obstructive Lung Disease

26. COPD Goals of Therapy Reduce Symptoms Reduce Risk Relieve symptoms
Improve exercise tolerance
Improve health status
Reduce Risk
Prevent disease progression
Prevent and treat exacerbations
Reduce mortality
GOLD 2017

27. COPD Definition
“….a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases”
Underlies importance of symptoms. Removes inflammatory response. Distinguishes airway involvement from alveolar involvement.

28. Assessment of COPD: GOLD 2001

29. Assessment of COPD: GOLD 2011

30. Assessment of COPD: GOLD 2017
"Spirometry remains a key diagnostic feature and an important modality in defining severity of airflow obstruction," Dr Martinez
told Medscape Medical News. "Therapeutically, it has limited relevance for pharmacotherapeutic options

31. Treatment of COPD: GOLD 2017
GOLD Grade
Preferred Treatment
For Continued Symptoms or Exacerbations A
PRN SABA or LABA or SAMA or LAMA
Use alternative class B
LABA or LAMA
LAMA + LABA C
LAMA
LAMA + LABA* [or] LABA + ICS D
LAMA + LABA + ICS [or] LABA + ICS
*preferred
GOLD 2017

32. Assessment Question 2: Pharmacists
SD is a 74 yo man who presents to your internal medicine clinic for follow up of COPD. He has GOLD Grade C (treated with LAMA). He just had another exacerbation. What is the most appropriate therapy for him now?
Remain on LAMA
Switch to LABA + ICS
Add LABA to current therapy
Add LABA and ICS to current therapy

33. Assessment Question 2: Technicians
Which of the following is a goal of COPD treatment?
Decrease exacerbations
Decrease exercise tolerance
Decrease health status
All of the above

34. Inhaled Drugs and Drug-Delivery Devices

35. Role of the Pharmacist Safe and effective pharmacotherapy Adherence
Inhaler Technique
Self-Management

36. Short Acting Beta Agonists (SABAs)* Long-Acting Beta Agonists (LABAs)+
Albuterol (Proventil, Ventolin, Proair)
HFA, DPI, Nebs, Respiclick
PRN
Available in combo with SAMA
Levalbuterol (Xopenex)
HFA, Nebs -
Long-Acting Beta Agonists (LABAs)+
Salmeterol (Serevent)++
Diskus
BID
Available in combo with ICS
Formoterol (Performist)++
Nebs
Available in combo with
ICS, LAMA
Indacaterol (Arcapta)
Neohaler
QDAY
Olodaterol (Striverdi)
Respimat
Available in combo with LAMA
Arformoterol (Brovana)
Vilanterol++
ONLY available in combo with ICS, LAMA
* “Rescue” inhaler for asthma approved in COPD; BBW for ↑ risk of asthma-related death approved for use in asthma ONLY in used in combination with ICS

37. Muscarinic Antagonist
Short Acting Muscarinic Antagonists(SAMAs)
Ipratropium (Atrovent)
HFA, Nebs
PRN
Available in combo with SABA
Long-Acting Muscarinic Antagonists (LAMAs)*
Tiotropium (Spiriva)**
Handihaler, Respimat
QDAY
Available in combo with LABA
Aclidinium (Tudorza)
Pressair
BID
Umeclidinium (Incruse)
Ellipta
Glycopyrrolate (Seebri)
Neohaler
*approved in COPD; **approved in asthma

38. Inhaled Corticosteroids
Inhaled Corticosteroids (ICS)
Beclomethasone (QVAR)
HFA
BID -
Budesonide (Pulmicort)
Flexhaler, Nebs
Available in combo with LABA
Ciclesonide (Alvesco)
Flunisolide (Aerospan)
Fluticasone furoate (Arnuity)
Ellipta
QDAY
Fluticasone proprionate (ArmonAir, Flovent)
HFA, Respiclick, Diskus
Mometasone (Asthmanex)
HFA, Twishaler

39. Combination Products LABA/LAMA Indacaterol/Glycopyrrolate (Utibron)
Neohaler
BID
Olodaterol/Tiotropium (Stiolto)
Respimat
QDAY
Vilanterol/Umeclidinium (Anoro)
Ellipta
LABA/ICS
Budesonide/Formoterol (Symbicort)
HFA
BID
Mometasone/Formoterol (Dulera)
Fluticasone/Salmeterol (Advair)
Diskus, HFA
Fluticasone/Vilanterol (Breo)
Ellipta
QDAY
SABA/SAMA
Ipratropium/Albuterol (Combivent)
HFA, Nebs
PRN

40. Delivery Devices Metered dose inhalers Slow deep inhalation
HFA
Slow deep inhalation
Spacer improves delivery
Requires priming
Images via Creative Commons

41. Delivery Devices Soft mist inhaler Slow deep inhalation
Respimat
Slow deep inhalation
Excellent delivery to lung
Requires priming
Image via Creative Commons

42. Delivery Devices Dry powder multidose inhaler
Diskus, Ellipta, Respiclick, Pressair, Twisthaler
Quick forceful inhalation
May require “activation” of next dose
Images via Creative Commons

43. Delivery Devices Dry powder capsule/piercing device inhaler
Handihaler, Neohaler
Quick forceful inhalation
Requires manual loading and piercing of capsule
Images via Creative Commons

44. Assessment Question 3: Pharmacists
Which of the following inhaler(s) is/are dry powder multidose inhalers? [select all that apply]
Respimat
Respiclick
Twisthaler
Handihaler

45. Assessment Question 3: Technicians
Which of the following inhalers is a “rescue” medication for asthma?
Inhaled Corticosteroid (ICS)
Long-Acting Muscarinic Antagonist (LAMA)
Long-Acting Beta Agonist (LABA)
Short-Acting Beta Agonist (SABA)

46. References
2015 National Health Interview Survey (NHIS) Data
2012 National Ambulatory Medical Care Survey; 2010 National Hospital Discharge Survey (NHDS) datahttps://wonder.cdc.gov/
Food and Drug Administration Approved Drug Products.
Bottrell J. New, Exciting, Asthma Treatments On The Horizon. Asthma.net. treatments-horizon/
AHRQ Statistical Brief #196: Trends in Hospital Readmissions for Four High-Volume Conditions,
National Asthma Education and Prevention Program (NAEPP). Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma. Clinical Practice Guidelines, National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No , prepublication Available at 
Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA).
Global Initiative for Chronic Obstructive Lung Disease (GOLD): Global Strategy for the Diagnosis, Management, and Prevention of COPD
Ford ES, Croft JB, Mannino DM, Wheaton AG, Zhang X, Giles WH. COPD Surveillance—United States,  Chest ;144(1): doi: /chest

47. Just Breathe: Clinical Updates in the Treatment of Asthma and COPD
Margaret Miklich, PharmD, BCACP Clinical Assistant Professor