acos update - association of pas in allergy asthma & immunology · 2019-08-01 · asthma-copd...

ACOS UpdateAsthma COPD Overlap Syndrome

AAPA-AAI Seattle

Brian Bizik MS PA-CAsthma and Allergy of Idaho and Nevada

Terry Reilly Health Services

DisclosuresINDUSTRY AFFILIATIONSGrifols Pharmaceutical - speaker, consultantBoehringer Ingelheim Pharmaceuticals – media consultant, consultant, speakerMeda Pharmaceuticals – speaker, consultantCircassia Pharmaceuticals – advisory panelGSK – advisory panel

CLINICAL RESEARCH2017 – Sub-I, Genetech Zenyatta Severe Asthma Study2016 – Sub-I, Biota Human Rhinovirus Study2015 – Sub-I, Sanofi Traverse Severe Asthma Study2015 – Sub-I, Sanofi Liberty Severe Asthma Study2013 – Study Coordinator: MediVector Influenza Study

Brian Bizik does not intend to discuss the use of any off-label use/unapproved use of drugs or devices

Why ACOS?• 10,000 foot view of the topic• Why might we care?• Dx and thoughts about Tx• Where next?

Hardin M, et al, Respir Res 2011;12:127.

Poorer quality of life (SGRQ)

Higher probability of exacerbation in past year

More frequent exacerbations

OR 3.55 (95% CI: 2.19-5.75) p<0.001

More rapid lung function decline

More refractory to ICS and OCS

Higher OCS requirement

A first look at where GOLD 2019 has us. . .

Chronic Obstructive Pulmonary Disease (COPD)

► COPD is currently the fourth leading cause of death in the world.1

► COPD is projected to be the 3rd leading cause of death by 2020.2

► More than 3 million people died of COPD in 2012 accounting for 6% of all deaths globally.

► Globally, the COPD burden is projected to increase in coming decades because of continued exposure to COPD risk factors and aging of the population.

1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2095-128.2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11): e442.

COPD Definition

►Chronic Obstructive Pulmonary Disease (COPD) is 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.

© 2019 Global Initiative for Chronic Obstructive Lung Disease

Definition of asthmaAsthma is a heterogeneous disease, usually characterized by chronic airway inflammation (no longer primarily bronchoconstriction).

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 expiratory airflow limitation.

Pathology, pathogenesis & pathophysiology

► Pathology Chronic inflammation Structural changes

► Pathogenesis Oxidative stress Protease-antiprotease imbalance Inflammatory cells Inflammatory mediators Peribronchiolar and interstitial fibrosis

► Pathophysiology Airflow limitation and gas trapping Gas exchange abnormalities Mucus hypersecretion Pulmonary hypertension

Diagnosis and Initial Assessment

OVERALL KEY POINTS:

► COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors for the disease.

► Spirometry is required to make the diagnosis; the presence of a post-bronchodilator FEV1/FVC < 0.70 confirms the presence of persistent airflow limitation.

► The goals of COPD assessment are to determine the level of airflow limitation, the impact of disease on the patient’s health status, and the risk of future events (such as exacerbations, hospital admissions, or death), in order to guide therapy.


►Symptoms of COPD

Chronic and progressive dyspnea Cough Sputum productionWheezing and chest tightnessOthers – including fatigue, weight loss, anorexia,

syncope, rib fractures, ankle swelling, depression, anxiety.

Post-bronchodilator FEV1

Choice of evaluations

►COPD Assessment Test (CATTM)►Chronic Respiratory Questionnaire (CCQ® )►St George’s Respiratory Questionnaire (SGRQ)►Chronic Respiratory Questionnaire (CRQ)►Modified Medical Research Council (mMRC)

questionnaire


Assessment of Exacerbation Risk

► COPD exacerbations are defined as an acute worsening of respiratory symptoms that result in additional therapy.

► Classified as: Mild (treated with SABDs only) Moderate (treated with SABDs plus antibiotics and/or oral corticosteroids) or Severe (patient requires hospitalization or visits the emergency room). Severe

exacerbations may also be associated with acute respiratory failure.

► Blood eosinophil count may also predict exacerbation rates (in patients treated with LABA without ICS).


ABCD assessment tool

Pharmacological therapy


► Pharmacological therapy for COPD is used to reduce symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance and health status.

► To date, there is no conclusive clinical trial evidence that any existing medications for COPD modify the long-term decline in lung function.

► The classes of medications commonly used to treat COPD are shown on the next two slides.

► The choice within each class depends on the availability and cost of medication and favourable clinical response balanced against side effects.

► Each treatment regimen needs to be individualized as the relationship between severity of symptoms, airflow limitation, and severity of exacerbations can differ between patients.

Pharmacological therapy


Management of stable COPD

OVERALL KEY POINTS:

► The management strategy for stable COPD should be predominantly based on the individualized assessment of symptoms and future risk of exacerbations.

► All individuals who smoke should be strongly encouraged and supported to quit.

► The main treatment goals are reduction of symptoms and future risk of exacerbations.

► Management strategies are not limited to pharmacologic treatments, and should be complemented by appropriate non-pharmacologic interventions.

Management of Stable COPD

► Once COPD has been diagnosed, effective management should be based on an individualized assessment to reduce both current symptoms and future risks of exacerbations.

Treatment of stable COPD

Definition of abbreviations: eos: blood eosinophil count in cells per microliter; mMRC: modified Medical Research Council dyspneaquestionnaire; CAT™: COPD Assessment Test™.

Treatment of stable COPD

► Following implementation of therapy, patients should be reassessed for attainment of treatment goals and identification of any barriers for successful treatment (Figure 4.2).

► Following review of the patient response to treatment initiation, adjustments in pharmacological treatment may be needed.

© Global Initiative for Asthma

Definitions

AsthmaAsthma is 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 expiratory airflow limitation. [GINA 2014]

COPDCOPD is a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with enhanced chronic inflammatory responses in the airways and the lungs to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. [GOLD 2015]

Asthma-COPD overlap syndrome (ACOS) [a description]

Asthma-COPD overlap syndrome (ACOS) is characterized by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD. ACOS is therefore identified by the features that it shares with both asthma and COPD.

GINA 2014, Box 5-1

Features of both asthma and COPD

Asthma Overlap syndromes COPD

Atopy / allergies / family history

Eosinophilia (sputum)

Chronic airflow obstruction

Recurrent exacerbations / frequent exacerbator

Corticosteroid insensitivity

Chronic bronchitis

Alpha 1-AT deficiency

Non-eosinophilic / neutrophilic (sputum)

Occupational asthma

Smoke / biomass /occupational exposure

FEV1 reversibility tests

Childhood onset atopic asthma

Systemic inflammation

Multimorbidity

Atopy / allergies / family history Atopy / allergies / family history






Chronic bronchitis



Occupational asthma


FEV1 reversibility tests / AHR



Multimorbidity

Atopy / allergies / family history 100% 64% 25%

Gibson P, et al, Thorax 2009; 74:728

De Marco R, et al, PLOS ONE 2013;8:e62985.

Allergic rhinitis 59% 55% 24%







Chronic bronchitis



Occupational asthma





Multimorbidity

100% >80% 66%

Tashkin D, et al, ERJ 2008; 31:742




Eosinophilic (sputum)




Chronic bronchitis



Occupational asthma

Smoking / biomass /occupational exposure




Multimorbidity

1.27 3.161.70

De Marco R, et al, PLOS ONE 2013;8:e62985.







Chronic bronchitis



Occupational asthma




Multimorbidity


?60% ?20%?40%



Eosinophilic (sputum)




Chronic bronchitis



Occupational asthma





Multimorbidity

?15% 80%>80%

Gibson P, et al, Thorax 2009; 74:7285x higher neutrophils in ACOS

Fabbri LM, et al. AJRCCM 2003;167:418-424.

ASTHMACOPD

Unexpected mild emphysema in non-smoking asthma with persistent AFO

72-year-old women non-smoker, lifelong asthma• Mild centrilobular emphysema, fractured alveolar

septae• Neutrophils predominate


Usual features of asthma, COPD and ACOS

Feature Asthma COPD ACOS

Pattern of respiratorysymptoms

Symptoms vary over time(day to day, or over longerperiod), often limitingactivity. Often triggered byexercise, emotionsincluding laughter, dust, orexposure to allergens

Chronic usually continuoussymptoms, particularlyduring exercise, with ‘better’and ‘worse’ days

Respiratory symptomsincluding exertional dyspneaare persistent, but variabilitymay be prominent

Lung function Current and/or historicalvariable airflow limitation, e.g. BD reversibility, AHR

FEV1 may be improved bytherapy, but post-BDFEV1/FVC <0.7 persists

-Airflow limitation not fullyreversible, but often withcurrent or historicalvariability

Lung functionbetween symptoms

May be normal Persistent airflow limitation Persistent airflow limitation

Age of onset Usually childhood but cancommence at any age

Usually >40 years Usually ≥40 years, but mayhave had symptoms aschild/early adult


Usual features of asthma, COPD and ACOS (continued)

Feature Asthma COPD ACOS

Past history orfamily history

Many patients haveallergies and a personalhistory of asthma in childhood and/or familyhistory of asthma

History of exposure tonoxious particles or gases(mainly tobacco smoking orbiomass fuels)

Frequently a history ofdoctor-diagnosed asthma(current or previous),allergies, family history ofasthma, and/or a history ofnoxious exposures

-

Time course Often improvesspontaneously or withtreatment, but may result in fixed airflow limitation

Generally slowly progressiveover years despite treatment

Symptoms are partly butsignificantly reduced bytreatment. Progression isusual and treatment needsare high.

Chest X-ray- Usually normal Severe hyperinflation andother changes of COPD

Similar to COPD

Exacerbations Exacerbations occur, butrisk can be substantiallyreduced by treatment

Exacerbations can bereduced by treatment. Ifpresent, comorbiditiescontribute to impairment

Exacerbations may be morecommon than in COPD but are reduced by treatment. Comorbidities can contributeto impairment.


Features that (when present) favor asthma or COPD

Feature Favors asthma Favors COPDAge of onset Before age 20 years After age 40 years

Lung function Record of variable airflow limitation (spirometry, peak flow)

Normal between symptoms

Record of persistent airflow limitation (post-BD FEV1/FVC <0.7)

Abnormal between symptomsPast history or family history

Previous doctor diagnosis of asthmaFamily history of asthma, and other allergic

conditions (allergic rhinitis or eczema)

Previous doctor diagnosis of COPD, chronic bronchitis or emphysema

Heavy exposure to a risk factor: tobacco smoke, biomass fuels

Chest X-ray Normal Severe hyperinflation

Time course No worseningof symptoms over time. Symptoms vary seasonally, or from year to year

May improve spontaneously, or respond immediately to BD or to ICS over weeks

Symptomsslowly worsening over time (progressive course over years)

Rapid-acting bronchodilator treatment provides only limited relief

Pattern of respiratorysymptoms

Symptoms vary overminutes, hours or daysWorse during night or early morningTriggered by exercise, emotions including

laughter, dust, or exposure to allergens

Symptoms persist despite treatmentGood and bad days, but always daily

symptoms and exertional dyspneaChronic cough and sputum preceded

onset of dyspnea, unrelated to triggersSyndromic diagnosis of airways diseaseThe shaded columns list features that, when present, best distinguish between asthma and COPD. For a patient, count the number of check boxes in each column. If 3 or more boxes are checked for either asthma or COPD, that diagnosis is

suggested. If there are similar numbers of checked boxes in each column, the diagnosis

of ACOS should be considered.


Stepwise approach to diagnosis and initial treatment

For an adult who presents with respiratory symptoms:1. Does the patient have chronic

airways disease?

2. Syndromic diagnosis of asthma, COPD and ACOS

3. Spirometry4. Commence initial therapy

5. Referral for specialized investigations (if necessary)

GINA 2014, Box 5-4 (1/6)


Step 1 – Does the patient have chronic airways disease?

GINA 2014, Box 5-4 (2/6)


Step 3 - Spirometry

Spirometric Asthma COPD ACOS

Normal FEV1/FVC pre- or post-BD

Compatible with asthma Not compatible with diagnosis (GOLD)

Not compatible unless other evidence of chronic airflow limitation

FEV1 =80% predicted Compatible with asthma (good control, or interval between symptoms)

Compatible with GOLD category A or B if post-BD FEV1/FVC <0.7

Compatible with mild ACOS

Post-BD increase in FEV1 >12% and 400mL from baseline

High probability ofasthma

Unusual in COPD. Consider ACOS

Compatible with diagnosis of ACOS

Post-BD FEV1/FVC <0.7 Indicatesairflow limitation; may improve

Required for diagnosis by GOLDcriteria

Usual in ACOS

Post-BD increase in FEV1 >12% and 200mL from baseline (reversible airflow limitation)

Usual at some time in courseof asthma; not always present

Common in COPD and more likely when FEV1 is low, but consider ACOS

Common in ACOS, and more likely when FEV1 is low

FEV1 <80% predicted Compatible with asthma. A risk factor for exacerbations

Indicates severity of airflow limitation and risk of exacerbations and mortality

Indicates severity of airflow limitation and risk of exacerbations and mortality

GINA 2014, Box 5-3


Investigation Asthma COPDDLCO Normal or slightly elevated Often reducedArterial blood gases Normal between

exacerbationsIn severe COPD, may be abnormal between exacerbations

Airway hyperresponsiveness

Not useful on its own in distinguishing asthma and COPD. High levels favor asthma

High resolution CT scan

Usually normal; may show air trapping and increased airway wall thickness

Air trapping or emphysema; may show bronchial wall thickening and features of pulmonary hypertension

Tests for atopy (sIgEand/or skin prick tests)

Not essential for diagnosis; increases probability of asthma

Conforms to background prevalence; does not rule out COPD

FENO If high (>50ppb) supports eosinophilic inflammation

Usually normal. Low in current smokers

Blood eosinophilia Supports asthma diagnosis May be found during exacerbations

Sputum inflammatory cell analysis

Role in differential diagnosis not established in large populations

Step 5 – Refer for specialized investigations if needed

GINA 2014, Box 5-5


Stepwise approach to diagnosis and initial treatment

Case Study67 YO Male, long standing hx of asthma. Diagnosed with asthma as a child. Smoked for 15 years total.

On a dual agent (budesonide and formoterol)Has 3-4 exacerbations per yearNot sure the steroid bursts help

Went without his dual agent inhaler last year for 1 months while in the Medicare black hole and did not notice any differenceThoughts?

GINA 2014, Box 5-4 (1/6)


Summary

Be thinking about your COPD patients who might have asthma and your asthma patients that might have fixed airway disease

1. Assess their status and history2. Decide if the tx they are on makes sense3. Consider a trial going the other way. . . Asthma to

COPD or COPD to asthma

4. Keep the regular meds on hand5. Evaluate their progress

GINA 2014, Box 5-4 (1/6)

ACOS UpdateAsthma COPD Overlap Syndrome

AAPA-AAI SeattleBrian Bizik MS PA-C

Asthma and Allergy of Idaho and NevadaTerry Reilly Health Services

[email protected]

mailto:[email protected]

acos update - association of pas in allergy asthma & immunology · 2019-08-01 · asthma-copd...

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