Asthma 2018

Are We Making A

Meaningful Impact ?

Kenneth Miller, MEd, MSRT, RRT-ACCS, NPS, AE-C, FAARC

Clinical Educator

Wellness Champion

Lehigh Valley Health Network

Allentown, Penna.

Presentation Objectives

• Describe the pathophysiology associated with the asthmatic patient.

• Define what is asthma and describe the epidemiological prevalence.

• Define clinical end-points when treating the asthmatic patient.

• Explain the current ventilatory management of the asthmatic patient.

• Review alternative strategies in the management of severe asthma.

What is Asthma??

Historical Perspectives

The term Asthma comes from the Greek verb aazein, meaning to pant, to exhale with the open mouth, sharp breath. In The Iliad, a Greek epic poem (attributed to Homer) describing the siege of Troy, the expression asthma appeared for the first time.

The Corpus Hippocraticum, by Hippocrates, is the earliest text where the

word asthma is found as a medical term. We are not sure whether Hippocrates (460-360 BC) meant asthma as a clinical entity or as merely a symptom. Hippocrates said spasm linked to asthma were more likely to occur among anglers, tailors and metalworkers. Galen (130-200 AD), an ancient Greek physician, he described asthma as bronchial obstructions and treated it with owl's blood in wine.

Moses Maimonides (1135-1204 AD), the rabbi and philosopher who lived in Spain, Morocco and Egypt, was also a physician who practiced medicine in the court of Sultan Saladin of Egypt and Syri. Among many medical texts, Maimonides wrote Treatise of Asthma for Prince Al-Afdal, a patient of his. Moses revealed that his patient's symptoms often started as a common cold during the wet months. Eventually the patient gasped for air and coughed until phlegm was expelled. He noted that the dry months of Egypt helped asthma sufferers. He also suggested avoidance of strong scents, plenty of sleep, fluids, moderation of sexual activity, and chicken soup.

Bernardino Ramazzini (1633-1714 AD), known to some as the father of sports medicine, detected a link between asthma and organic dust. He also recognized exercise-induced asthma. At the beginning of the 20th century asthma was seen as a psychosomatic disease - an approach that probably undermined any medical breakthroughs at the time. During the 1930s to 1950s, asthma was known as one of the holy seven psychosomatic illnesses. Asthma was described as psychological, with treatment often involving, as its primary component, psychoanalysis and other 'talking cures'. A child's wheeze was seen as a suppressed cry for his or her mother. Psychoanalysts thought that patients with asthma should be treated for depression. This psychiatric theory was eventually refuted and asthma became known as a physical condition. Asthma, as an inflammatory disease, was not really recognized until the 1960s when anti-inflammatory medications started being used.

What is Asthma 2017?? • Asthma is a chronic (long-lasting) inflammatory

disease of the airways.

• In those susceptible to asthma, this inflammation causes the airways to spasm and swell periodically so that the airways narrow. The individual then must wheeze or gasp for air.

• Obstruction to air flow either resolves spontaneously or responds to a wide range of treatments, but continuing inflammation makes the airways hyper-responsive to stimuli such as cold air, exercise, dust mites, pollutants in the air, and even stress and anxiety.

Teenager’s view Of Asthma

Asthma Epidemiology

• Prevalent in 10% of the world’s population

• Increase noted by 20-30% over the last two decades

• More common in males, but more severe in females

• Approximately 2,000 death per year in the United States

• Death rates higher in patients >55 years old

• Death rates higher in lower social-economic groups

Asthma Overview: Prevalence, Morbidity and Mortality in the USA

Centers for Disease Control and Prevention National Center for Health Statistics, National Health Statistics Report: Asthma

Prevalence, Health Care Use, and Mortality: United States, 2009–2013: http://www.cdc.gov/nchs/data/nhsr/nhsr032.pdf

∙ 24.6 million

People diagnosed with asthma

∙ 12.8 million

People experience asthma attacks

∙ 1.8 million

Emergency room visits

∙ 456,000

Hospitalizations

∙ 3,447

Asthma-related deaths

Approximately 9 People Die From Asthma Each Day in the U.S.

Annual incidence, based on 2016 data

Children

Adults

Male

Female

White

Black

Hispanic

Non-Hispanic

Northeast

Midwest

South

West

0 5 10 15 20 25

Rate per 100 persons with asthma

95% confidence interval. NOTES: Crude (unadjusted) risk-based rates are presented. See Table 15 for underlying data.

SOURCE: CDC/NCHS, National Hospital Ambulatory Medical Care Survey.

Hospital Outpatient Department Visits by Selected Characteristics

30

2

5

2

0

1

5

1

0

5

0

95% confidence interval. NOTES: Crude (unadjusted) risk-based rates are presented. See Table 15 for underlying data.

SOURCE: CDC/NCHS, National Hospital Ambulatory Medical Care Survey.

ED Visits by Age Group

0–4 5–14 15–19 20–24 25–34 35–64 65 years years years years years years years or over

0–4 5–14 15–19 20–24 25–34 35–64 65 years years years years years years years or over

Deaths by Age

Mild

Moderate Severe

$12,800

$4,800

$2,200

Co

st/P

atie

nt/

Year

Cisternas M, et al., A comprehensive study of the direct and indirect costs of an adult with asthma. J Allergy

Clin Immunol 2013;111(6):1212-1218.

$4,000

$2,000

$6,000

$8,000

$10,000

$12,000

Increased Healthcare Utilization

ER Visits

Hospitalizations

Impact of Asthma

Annual Cost by Asthma Severity

16

Est. $20.7B annual

healthcare costs

PA Asthma Partnership 2010-2015

PA Asthma Partnership 2005-2010

Asthma Pathophysiology

• Airway inflammation

• Airway hyperresponsiveness

• Airway obstruction

Mucus Plugging in Asthma

Role of Pollution in Asthma

Thunderstorm Asthma

on the Rise

Recently in the Journal of Allergy and Clinical Immunology, Dr Gennaro D’Amato and colleagues explored the nature of this phenomenon and implications for the future. The authors point out that although rare, these events are expected to occur more often with anticipated climate change. According to the authors, the evidence for this so far is limited to pollen and outdoor mold seasons—but even in the northeastern United States, that is about three quarters of the year

How Do We

Diagnosis

Asthma?

Classification of Asthma

In ancient times, “Album graecum” – or more colloquially known as dog poo – was a popular treatment for a Asthma. In these days, feces was usually mixed with honey and was believed to treat inflamed airways!

Treatment?

Owl’s Blood mixed with tree nectars

Treatment In the Past Three

Centuries

• 1812-Smoking of Datura Stramonium or

inhalation of HCL acid

• 1912-Avoid irritants, injectable adrenaline

and PO Ephedrine

• 2012-Inhaled steroids and LABA

Photo with permission Felix Kudish.

Asthma Nectar

Short-acting Beta2-agonists

Low-dose Inhaled Corticosteroids (ICS)

Low-dose ICS + Long-acting Beta2-agonists (LABA)

or Medium-dose ICS

Medium-dose ICS + LABA

High-dose ICS + LABA and Consider Omalizumab

High-dose ICS + LABA + Oral Corticosteroids

and Consider Omalizumab

Adapted from National Asthma Education and Prevention Program (NAEPP) Guidelines. Expert Panel Report 3: Guidelines for the

Diagnosis and Management of Asthma. National Heart, Lung, and Blood Institute, NIH Publication No. 07-4051, Revised August 2010.

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2

3

4

5

6

Alternatives

Needed

2017 Stepwise Approach for Managing Asthma

Treatment of Asthma

Beta-agonist

Inhaled steroids

Leukotriene Receptor Antagonists (LTRAs)

Montelukast (sold as Singulair®) Zafirlukast (sold as Accolate®)

Theophyilline

While the mechanisms of action of Theophylline are not totally known with

certainty, studies in animals suggest

that bronchodilation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV

Omalizumab (Xolair, Genentech)

*Is a recombinant humanized IgG1

monoclonal anti-IgE antibody that binds to

the IgE molecule

*Omalizumab is not anaphylactogenic, since

it cannot interact with IgE that is already

bound to cell surfaces and thus cannot

induce degranulation of mast cells or

basophils.

*Instead, omalizumab binds to circulating IgE,

regardless of allergen specificity, forming

small, biologically inert IgE–anti-IgE

complexes without activating the

complement cascade thus causing edema.

Administration Of Xolair

*Omalizumab is administered subcutaneously once every 2

or 4 weeks.

*For each patient, the dosing schedule (2 vs 4 weeks

between injections; and the amount of omalizumab, in

milligrams, for each injection) is determined according to

the serum IgE level and the body weight of the patient.

*The product label of Xolair initially approved by FDA

covers patients with serum IgE in the range of 30 to about

700 IU/ml (international units per milliliter).] A clinical

development effort is on-going to expand the coverage of

patients with serum IgE up to 1500 IU/ml.

Cost of Xolair

A one-month supply of Xoliar will

cost patients

between $541 and $2,706,

depending on the dosage. This price

is much higher than the cost of

conventional treatments for asthma.

Side Effects of Xolair

•itching, mild rash;

•joint pain, bone fractures;

•arm or leg pain;

•nausea;

•dizziness, tired feeling;

•ear pain; or.

•cold symptoms such as stuffy nose,

sneezing, sinus pain, cough, sore

throat.

Alternative methods

Garlic Herbs

Ginger Ginger is a well-known natural treatment for various ailments including asthma. Researchers have found that it can help reduce airway inflammation and inhibit airway contraction.

Mustard Oil When having an asthma attack, massaging with mustard oil can help clear the respiratory passages and restore normal breathing. Heat some mustard oil with a little camphor. Transfer it in a bowl and when it is comfortably warm, gently rub it on the chest and upper back and massage. Do this several times a day until the symptoms subside.

Figs

Honey

Honey is one of the oldest natural cures for asthma. The alcohol and ethereal oils in honey help reduce asthma symptoms. •Just inhaling the smell of honey produces positive results for some people. •You can also mix one teaspoon of honey into a glass of hot water and drink it slowly about three times a day. •Before going to bed, swallow one teaspoon of honey with one-half teaspoon of cinnamon powder. •This will help remove phlegm from your throat and allow you to sleep better.

Role of Vitamin D

• High doses of V-D have demonstrated a

reduction in airway responsiveness

• May increase the immune system and

prevent Mast Cell release of histamine like

enzymes

Cannabis and Asthma?

*It’s known that cannabis is a powerful anti-inflammatory.

*One of the main ways cannabis treats asthma symptoms is by

discouraging inflammation and opening the passages of the respiratory

system. This, in turn, decreases coughing and shortness of breath. While

many people may imagine the effects of smoking marijuana and smoking

cigarettes to be similar, the effects of marijuana on the bronchial passages

are actually the opposite of tobacco cigarettes - which constrict the

passages of the airway, causing asthma symptoms to worsen.

*A 2012 study published in The Journal of the American Medical

Association found that people who suffered from asthma and smoked

marijuana on a moderate basis actually increased their lung function,

without suffering the lung damage associated with tobacco cigarettes.

*These results have surprised almost everyone, from consumers to

doctors who specialize in the diagnosis and treatment of asthma. It's clear

the effectiveness of medical marijuana on asthma symptoms has the

potential to revolutionize how the condition is treated in the future.

Breast feeding and

Asthma

Experts say that asthma patients facing cold weather can cut their chances of an asthma

attack if they wear a scarf over their nose and mouth.

Breathing in cold, damp air can make the airways tighten and trigger an attack

in three out of four people, charity Asthma UK says. This can leave people

coughing, wheezing and gasping for breath.

“…cold weather is impossible to avoid over winter, but if people have asthma,

simply wrapping a scarf around their nose and mouth can warm up the air

before they breathe it in, reducing their risk of having an asthma attack,”

experts say.

Women with asthma who only use short-acting asthma relievers take longer to become pregnant than other women, according to research published in the European Respiratory Journal. However, the study of more than 5,000 women in Australia, New Zealand, the United Kingdom and Ireland also shows that women with asthma who use long-acting asthma preventers conceive as quickly as other women. Several studies have identified a link between asthma and female infertility, but the impact of asthma treatments on fertility has been unclear. “Studying the effect of asthma treatments in women who are pregnant or trying to get pregnant is important as women often express concerns about exposing their unborn babies to potentially harmful effects of medications.”

Cleaner Ship Fuels Will Reduce Childhood Asthma by 3.6% Globally

Published on February 12, 2018

A new study in Nature Communications quantifies global health benefits and finds cleaner shipping fuels will result in a 3.6% reduction of childhood asthma globally.

The study was led by University of Delaware’s James Corbett, and included an international team of researchers from the Finnish Meteorological Institute (FMI), Rochester Institute of Technology (RIT) in New York and Energy and Environmental Research Associates.

The team studied the impacts of sulfur emitted by ships using current marine fuels, which produce air pollution particles that are small enough to be breathed deeply into the lungs and are considered harmful to human health.

Challenges in Managing Severe Asthma

• Prevalence of severe asthma (NAEPP) = 5-10%

• Many patients remain symptomatic despite standard of care medications

• Medications are limited, require adherence, and can have serious side effects

• Additional therapeutic treatment options are needed…

Asthmatic Airway

Role of Airway Smooth Muscle on Asthma

Normal Airway Asthma Attack

Reduce Airway Smooth Muscle (ASM)

Reduce Bronchoconstriction

Reduce Asthma Exacerbations

Improve Asthma Quality of Life

69

Bronchial Thermoplasty – Reduces ASM

69

What is Bronchial Thermoplasty?

• Safe, outpatient bronchoscopic procedure:

• Delivers controlled energy to the airway walls in the lungs

• Reduces excess airway smooth muscle, which limits the muscle’s ability

to constrict the airways (asthma exacerbations)

• Demonstrated to increase asthma control and improve

asthma-related quality of life in patients with severe asthma

• Complementary treatment to current asthma reliever and

controller medications - not a cure or replacement for current

asthma medications

70

The Alair® Bronchial Thermoplasty System

• Alair Catheter – a flexible tube with an expandable wire array at the tip (introduced into the lungs through a standard bronchoscope)

• Alair Radiofrequency (RF)

Controller – supplies energy via

the Catheter to the airway wall

Application of RF Energy

• Temperature controlled energy (650

C-180F) is delivered to airway wall

for 10 seconds per activation – no

permanent damage to epithelium

Canine Model: Airway on left treated with bronchial

thermoplasty. Airway on right was not treated.

Cox et al. Eur Respir Journal. 2004;24: 659-663

Airway Responsiveness to

Local Methacholine Challenge

Three Treatment Sessions

74

Bronchial thermoplasty is performed in 3 separate treatment sessions each scheduled approximately 3 weeks apart

Classification of Life-

threatening Asthma

• Gradual deterioration over an extended period

of time

• often associated with an infection

• A mild attack that turns into a severe attack

(asphyxia asthma)

• often associated with an event or reaction

• can occur with any asthmatic!!!!!

Hospitalization ICU Admission

Duration and severity of

symptoms

Drowsy or confused

Severity of airflow Paradoxical thoraco-

abdominial movement

Severity of prior

exacerbations

Absence of wheezing

Medication utilization at time

of exacerbation

Bradycardia

Access to medical care and

medications

PEPR<25%

Presence of psychiatric illness SpO2<90%

Home support and conditions Pulsus paradoxus

Important considerations of hospitalization vs. ICU admission

Gradual Onset Sudden Onset

Course Days Hours-asphyxic

Incidence 10-33% 45-88%

Airway pathology Mucus plugging None

Inflammatory cell Eosinophil Neutrophil

Response to

treatment

Slow Quicker

Hospitalization

course

Long Short

Prevention Possible Underdetermined?

Phenotypes of Acute Severe Asthma

Flatten Diagrams

Pulse Paradoxes

BP varies more than 10 mm/hg between inspiration and exhalation Reflective of airway obstruction and air trapping

inspiration

exhalation

Indications for Mechanical

Ventilation

• PaCO2>40 mm Hg

• Refractory hypoxemia

• PaO2<60 on FIO2>50%

• Mental status deterioration

• Loss of breath sounds

• Excessive accessory muscle work

Goal of Mechanical Ventilation

• Provide acceptable gas exchange

while avoiding ventilator induced

trauma secondary to hyper-

inflation and baro-trauma

Ventilator Management

• Sedation? Pharmcalogically paralyze?

• Utilize assisted spontaneous mode of ventilation

• Minimize airway pressures and allow long

expiratory time

• Usually minimize FIO2 requirements

• Administer continous bronchodilators via ventilator

Ventilator Parameters

• Mode of ventilation

• PCV vs Volume targeted

• Tidal volume

• 6-8cc/kg IBW

• PEEP

• 3-8cmh20

• Monitor PLt

• I/E ratio

• 1:3-4

• Rate

• <12

Using Ventilator Graphics

Severe Bronchospasm with Air Trapping

Auto PEEP via the Pressure/time curve

Auto-PEEP Measurements

• Advantages

• trend values

• est. of airway

obstruction

• easily performed

• Disadvantages

• under-estimate

• can lead to more

air-trapping

• ventilator

limitations

• incorrect

interpretation

Auto-PEEP Measurements

Ventilatory Management

• Usually short term if solely airway problem

• PCMV--PSV---SBT---extubation

• Longer duration if secondary infection-retained secretions

• Complications:

• pneumonia

• lung collapse

• pneumothorax

• muscle weakness

Clinical Interventions to Aid

With Mechanical Ventilation

• Continuous beta-agonist therapy

• IV steroids

• CPT?

• IPV

• Active humidification

• Sedation

• Reassurance and controlled breathing

Alternative Interventions

• Permissive hypoventilation

• Isoflurane

• Heliox

• ECMO

• BIPAP

• Magnesium Sulfate

• High Flow Oxygen

Permissive Hypercapnia

• Allow PaC02 to rise in order protect the

lung for injury from high PIP/PLT

• Maintain pH > 7.25

• Buffer pH with THAM or HCO3

• May cause cardiac ischemia

• Not to be used in head injured patients

Isoflurane

• Inhaled anesthetic agent

• Sustained bronchodilation secondary by blocking

airway reflex and direct relaxation of smooth

muscle.

• 10-20% mixture for airway dilation.

• May reduce systemic blood pressure

Delivery of Isoflurane

Heliox

• Lower density than oxygen

• Produces a lower Reynolds Number

• Clinical studies have demonstrated a reduced of

WOB by 35%

• Decreases pulses paradoxes

• Reduction in PaCO2

• ?reliable ventilator monitoring

Heliox

Pre Heliox Raw

Settings P-CMV 38/12 I/E 1:3.3

Post heliox administration 70/30

V-V ECMO

• Utilized in severe situations often

associated with mucus plugging

• Plt>35cm

• PaCO2>90 and pH<7.20

• Ability to allow the lung to rest

• Associated with many hazards and

complications

Oxygenated blood reinfused

Drainage lumen

Oxygenated blood directed across TV

Dual Lumen Cannula for VV ECMO

High Flow Oxygen

Approximately 1 cm/h20 of “back pressure CPAP” per every

ten liters of flow

Advantages of High Flow

Oxygen

• May produce some back pressure

PEEP to help split airways

• Provides high molecular humidity

• Will meet patients flow demands

Magnesium Sulfate

• The mechanism of action includes

blocking of calcium-channel pathway and

release of histamine

• Administered IV 30/70mg/kg over a 30

minutes

• Side effects facial flushing, muscle

weakness, and tachycardia

Conclusion

• Asthma can be life threatening

• Asthma mortality is increasing

• Invention must be quick

• Have lots of weapons in your treatment arsenal

• Despite all our interventions Asthma continues

to rise

QUESTIONS!