Bronchial asthma

Mohammed Alageel

Bronchial asthma

Goals

• Review burden of disease
• Review pathophysiology of airway obstructive disease
• Review the subtypes of asthma disease

Entomology

• Greek “ασυμα”, signifying panting, and was used initially as a synonym for “breathlessness.”
• Subsequent definitions of asthma highlight concepts of airway hyper-responsiveness, bronchospasm, and reversible airway obstruction.

CONTENTS

BRONCHIAL
ASTHMA

• INTRODUCTION
• CLASSIFICATION
• RISK FACTORS
• Diagnosis
• Treatment & Prevention

Introduction

• Asthma is a chronic inflammatory disorder of the airways that is characterized: syndrom

clinically by recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night/early morning.

physiologically by widespread, reversible narrowing of the bronchial airways and a marked increase in bronchial responsiveness. ↑ secretions, edema many cells and cellular elements play a role. With variable reversibility

Pathology

• Permanent structural airway changes (airway remodeling) may contribute to increased airway obstruction and hyper-responsiveness and decrease the response to therapy.
  • This is routinely used to assess asthma and monitor the disease.
• Nitric oxide (NO) produced by airway epithelial cells in the large and small airways and alveoli is a reflection of ongoing airway inflammation.
• The American Thoracic Society (ATS) guidelines recommend FeNO as part of the initial diagnosis of asthma and for monitoring of airway inflammation. FeNO has also been shown to be a predictive factor for asthma exacerbations, with higher levels being associated with a greater number of exacerbations.
• Most asthma begins in childhood and resolves with age.

Burden of Disease

• In 2015, 358 million people globally had asthma, up from 183 million in 1990.
• It caused about 397,100 deaths in 2015, most of which occurred in the developing world.
• Asthma impacts patients, their families, and the community as a whole in terms of lost work and school days, poor quality of life, frequent emergency department (ED) visits, and hospitalizations

Age and race distribution

• Despite the advancements in the contemporary medicine, there are 40–70% of patients who have uncontrolled asthma
• Asthma impacts patients, their families, and the community in terms of lost work and school days, poor quality of life, frequent emergency department (ED) visits, and hospitalizations
• Asthma is more prevalent in children than adults, in females more than males and in African descent more than Caucasians and Hispanics
• Developed nations have higher rates of asthma, which suggests that urbanization and westernization are correlated with increased asthma prevalence.

KSA asthma burden

• Asthma affects more than 2 million Saudis, and recent studies suggest that majority of them have uncontrolled asthma with their quality of life adversely being impacted
• prevalence of asthma to a host of factors including change in lifestyle, socioeconomic status, dietary habits and allergens, dust, tobacco smoke, sandstorms, and industrial and vehicular pollutants
• According to Ministry of Health, SA, the prevalence of asthma ranges from 15 to 25%

CLASSIFICATION

Classification

■ A heterogeneous disorder.

► Atopic /extrinsic /allergic ( 70%):

• Most common type
• Environmental agent: dust, pollen, food, animal dander → Cause Histamen release
• Family history - present
• Serum IgE levels - increased
• Skin test with offending agent - wheal flare

Classification

• Non-atopic/ intrinsic /non-allergic( 30%)
  • Triggered by respiratory tract infection
  • Viruses - most common cause
  • Family history uncommon
  • IgE level normal
  • No associated allergy
  • Skin tests NEGATIVE
  • Cause- hyperirritability of bronchial tree

Classification

most of Asthmatic will not get worse with NSAIDs

Drug induced asthma aka Aspirin-exacerbated respiratory disease (AERD)

• Several pharmacologic agents
• Aspirin sensitive asthma
  • Increased bronchoconstrictor leukotrienes.
  • sensitive to small doses of aspirin.
  • Inhibits COX pathway, without affecting LPO pathway

Pathophysiology

I. Chronic inflammation

II. Airway Hyperresponsiveness

asthma is not a single disease but a syndrome with various phenotypes.

Pathophysiology

I. Inflammation

• Chronic inflammatory state

• Involves respiratory mucosa from trachea to terminal bronchioles, predominantly in the bronchi. so there’s thickning of Airway

• Activation of mast cell, infiltration of eosinophils & T-helper type 2 (Th2) lymphocytes

• Exact cause of airway inflammation is unknown.

• Thought to be an interplay between endogenous and environmental factors.

□ Endogenous factors

► Atopy

• Genetic predisposition to IgE mediated type I hypersensitivity
• The major risk factor for asthma

► Genetics

Environmental factors

• Viral infections: RSV, Mycoplasma, Chlamydia
• Air pollution
• Allergens :house dust mite

II. Airway Hyperresponsiveness (AHR)

• The excessive bronchoconstrictor response to multiple inhaled triggers that would have no effect on normal airways.
• Characteristic physiologic abnormality of asthma.

*Reversible disease
if we don’t treat it we’ll become Chronic

Pathophysiology

Risk factors

► Host factors:

• predispose individuals to, or protect them from, developing asthma

i. Genetic non-modifiable factor

• o Atopy Same modifiable and the others non-modifiable

• o Airway hyperresponsiveness

i i. Gender non-modifiable factor

iii. Obesity modifiable factor

Risk factors

➤ Environmental factors: Very Important to ask if it. the prevention could be the treatment.

• influence susceptibility to development of asthma in predisposed individuals, precipitate asthma exacerbations, and/or cause symptoms to persist
• Indoor allergens, Outdoor allergens
• Occupational sensitizers
• Tobacco smoke, Air Pollution
• Respiratory Infections
• Diet

Triggers

Asthma Triggers

• Allergens
• Virus Infections
• Drugs
• Exercise
• Food
• Air pollutants
• Physical factors
• GERD
• Stress
• Occupational factors

DIAGNOSIS

Clinical manifestations

➤ Symptoms

• Wheezing, dyspnea and cough.
• Variable – both spontaneously and with therapy.
• Symptoms worse at night.
• Nonproductive cough
• Limitation of activity

► Signs Hyperresonant

• ↑ respiratory rate, with use of accessory muscles
• Hyper-resonant percussion note
• Expiratory rhonchi abnormal lung Sound
• No findings when asthma is under control or b/w attacks

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Classification for asthma severity

Grade	Symptoms	Night-time Symptoms
Mild intermittent	Symptoms ≤ 2 times/week	≤ 2 times/month
Mild persistent	Symptoms ≥ 2 times/week but ≤ 1/day	≥ 2 times/month
Moderate persistent	Daily Symptoms	≥ 1/week
Severe persistent	Continued Symptoms Limited physical activity	Frequent

Clinical manifestations

Dyspnea

Weakness

Cough

Night cough

Wheezing

Headache

Tachycardia

Allergy

Shortness of breath

Laboratory diagnosis

Gold standard

Pulmonary function

tests: For diagnosis and evaluation of treatment responsiveness

• Using Spirometry
• estimate degree of obstruction
• $\downarrow$ FEV1, $\downarrow$ FEV1/FVC, $\downarrow$ PEF.

Laboratory diagnosis

Recently not needed we do it only if we think that it isn’t Asthma

➤ CXR: as well as Blood test

■ hyperinflation, emphysema

➤ Arterial blood-gas not Indicated
analysis(not useful generally)

■ hypoxia & hypocarbia

➤ Skin hypersensitivity test

➤ Sputum & blood eosinophilia

➤ Elevated serum IgE levels

monitoring
the disease

TREATMENT

Management

I. Non-Pharmacological

II. Pharmacological

Non-Pharmacological

• Reduce exposure to indoor allergens - SMR to avoid triggers
• Avoid tobacco smoke
• Avoid vehicle emission
• Identify irritants in the workplace
• Explore role of infections on asthma development, especially in children and young infants

Non-Pharmacological

Influenza Vaccination

• should be provided to patients with asthma when vaccination of the general population is advised
• routine influenza vaccination of children and adults with asthma does not appear to protect them from asthma exacerbations or improve asthma control

Prophylaxis

• Preservation of the environment, healthy life-style (smoking cessation, physical training) – are the basis of primary asthma prophylaxis. for weight loss
• These measures in combination with adequate drug therapy are effective for secondary prophylaxis.

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Pharmacological treatment

Classification of drugs

-Bronchodilators : rapid relief, by relaxation of airway smooth muscle

• β2 Agonists
• Anticholinergic Agents
• Methylxanthines
• -Controllers : inhibit the inflammatory process
• Glucocorticoids
• Leukotrienes pathway inhibitors
• Cromones
• Anti-IgE therapy

in ER

β2 Agonists in asthma

• Potent bronchodilators.
• Usually given by inhalation route.
  or mask
• Effects: may cause tachycardia

Relaxation of airway smooth muscle

• Inhibition of mast cell mediator release
• Reduction in plasma exudation
• Increased mucociliary transport
• Inhibition of sensory nerve activation

No effect on airway inflammation

That’s why we don’t use it alone.
add Corticosteroid

a) Short-Acting ${\beta }_2$ Agonists E.g 2-3h salbutamol, terbutaline

Convenient, rapid onset, without significant systemic side effect

• Bronchodil. of choice in acute severe asthma
• Used for symptomatic relief
• Only treatment required for mild, intermittent asthma.

Use >2 times a week indicates need of a regular controller therapy. “Prophylactic therapy”

b) Long-Acting ${\beta }_2$ Agonists

• E.g salmeterol, formoterol
• Duration of action - >12 hrs.
• Used in combination with inhaled corticosteroid therapy.
• Improve asthma control and reduce frequency of exacerbations.
• Should not be used as monotherapy (increased mortality).
• Not effective for acute bronchospasm.

Instructions for Metered-Dose Inhaler (MDI) Use

make sure that pit is using it well

Box 73-3

1. Remove cap from the MDI container.
2. Assemble the MDI and hold it upright.
3. Shake the canister.
4. Place the mouthpiece loosely between the teeth (or hold it 3-4 cm in front of the open mouth).
5. Exhale fully (to functional residual capacity).
6. Actuate the inhaler at the beginning of a slow and full inhalation (as if sipping hot soup) lasting 5 or 6 seconds.
7. Hold breath for at least 10 seconds.
8. Wait 1 minute before reuse.

► Anticholinergic agents

not at home use only in hospital because of its side effect:

• Dysgeusia
• urine retention
• Myopia

E.g. Ipratropium bromide, tiotropium.

Prevent cholinergic nerve induced bronchoconstriction.

Less effective than ${\beta }_2$ agonists.

Response varies with existing vagal tone.

Use in asthma (not regular)

• Intolerance to inhaled ${\beta }_2$ agonist.
• Status asthmaticus – additive effect with ${\beta }_2$ agonist

■ Ipratropium:

• slow, bitter taste
• precipitate glaucoma
• paradoxical bronchoconstriction(rare)

■ Tiotropium:

• longer acting, approved for treatment of COPD.
• Dryness of mouth

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► Methylxanthines use in refractory asthma pit

• Medium potency bronchodilator
• E.g Theophylline, theobromine, caffeine
• Recently interest has declined in this class of drugs:
  • Side effects
  • Need for plasma drug levels(toxicity)
  • Pharmacokinetics
  • Availability of other effective drugs
  • Still widely used drugs especially in developing countries due to their lower cost.

■ Adverse effects

• Anorexia, nausea, vomiting, abdominal discomfort
• headache, and anxiety
• Seizures or arrhythmias
• Diuresis

■ Doxylphylline

• long acting, oral

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> Corticosteroids in asthma

• Effective drugs for treatment of asthma.

• Development of inhaled corticosteroids is a major advance in asthma therapy.

• Used prophylactically as a controller therapy.

• Reduce the need for rescue ${\beta }_2$ agonist.

• Benefit starts in 1 week but continues up to several months.

• If asthma not controlled at low dose of ICS then addition of long acting ${\beta }_2$ agonist is more effective than doubling steroid dose.

• Effects: Broad anti-inflammatory effects: by

• Marked inhibition of infiltration of airways inflammatory cells.

• Modulation of cytokine and chemokine production

• Inhibition of eicosanoid synthesis

• Decreased vascular permeability.

• Potentiate effect of ${\beta }_2$ agonist.

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■ Inhaled corticosteroids (ICS)

✗ Use of ${\beta }_2$ Agonists >2 times a week indicates need of a ICS

○ E.g Beclomethasone, Budesonide, Fluticasone

- Adverse effects:

• Oropharyngeal candidiasis, dysphonia
• Decreased bone mineral density.
• Skin thinning, purpura
• Growth retardation in children

change in Voice

only in exacerbation

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Systemic(oral/IV) steroids in asthma

Indication

1. Acute exacerbation (lung function $<30\%$ predicted)
2. Chronic severe asthma
   • A 5-10 day course of prednisolone 30-45mg/d is used.
   • 1% of patients may require regular maintenance therapy.

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> Leukotrienes pathway inhibitors

1. Inhibition of 5-lipoxygenase, thereby preventing leukotriene synthesis. Zileuton.
2. Inhibition of the binding of LTD4 to its receptor on target tissues, thereby preventing its action. E.g. Zafirlukast, montelukast.
   • Oral route.
   • Adverse effects
     • Liver toxicity
     • vasculitis with eosinophilia

• They are less effective than ICSs in controlling asthma
• Use in asthma
  • Patients unable to manipulate inhaler devices.
  • Aspirin induced asthma.
  • Mild asthma – alternative to ICS.
  • Moderate to severe asthma – may allow reduction of ICS dose

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> Cromones

• E.g Cromolyn sodium & nedocromil sodium
• On chronic use (four times daily) reduce the overall level of bronchial reactivity.
• have no effect on airway smooth muscle tone and are ineffective in reversing asthmatic bronchospasm; they are only of value when taken prophylactically.
• Inhalation route
• May act by stabilization of Mast cells with inhibition of mediator release

Uses

• Asthma - Prevention of asthmatic attacks in mild to moderate asthma

Adverse effects

• Well tolerated drugs
• Minor side effects- throat irritation, cough, and mouth dryness, rarely, chest tightness, and wheezing

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► Anti-IgE therapy: if fit take it means he has bad disease

• Omalizumab

• recombinant humanized monoclonal antibody targeted against IgE.

• Action:

  • IgE bound to omalizumab cannot bind to IgE receptors on mast cells and basophils, thereby preventing the allergic reaction at a very early step in the process.

• Use in asthma

• Persons >12 years of age with moderate-to-severe persistent asthma.

• Omalizumab is not an acute bronchodilator and should not be used as a rescue medication or as a treatment of status asthmaticus.

• Expensive drug

• Has to be given under direct medical supervision due to the risk of anaphylaxis

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In the Emergency departmentFactors related to poor outcomes

• Inadequate patient and physician assessment of an acute episode resulting in undertreatment

• Overuse of prescribed or over-the-counter medications leading to delays in seeking treatment

• Failure of physicians to consider previous ED visits, hospitalizations, or life-threatening episodes of asthma

• Failure to initiate corticosteroid therapy early during an exacerbation.

ACUTE exacerbations of asthma classified by severity

Mild, moderate or severe (Status asthmaticus)

• Reflected by the degree of airway obstructions and acute response to bronchodilators
• Also assessed by degree of physiological response and hemodynamic compromise

Table 73-1 Objective Findings in Asthma Assessment Y

FACTOR	SEVERE ASTHMA ( $FE{V}_1<1.0$ L)
Pulse rate (beats/min)	$\ge 120$ but may be less with equally severe asthma
Respiratory rate (breaths/min)	$\ge 40$ but most are $>20$ , therefore nondiscriminating
Pulsus paradoxus (mm Hg)	$\ge 10$ but may be absent with equally severe asthma in 50% of cases
Pulse rate $\ge 120$ , respiratory rate $\ge 20$ , pulsus paradoxus $\ge 10$	If all three abnormal, 90% with severe asthma, but only 40% with $FE{V}_1<1.0$ L have all three abnormal
Use of accessory muscles of respiration	If present, may indicate severe asthma; if absent, may have equally severe asthma in 50% of cases
ABG analysis (mm Hg)	$Pa{o}_2\le 60$ or $Pac{o}_2\ge 42$ indicates severe asthma; all other values difficult to interpret unless $PEFR$ or $FE{V}_1$ known
Pulmonary function studies	$PEFR$ and $FE{V}_1$ measure directly the degree of airflow obstruction; most useful in assessing severity and guiding treatment decisions

ABG, arterial blood gas; $FE{V}_1$ , forced expiratory volume in 1 second; $Pac{o}_2$ , partial pressure of carbon dioxide in arterial blood; $Pa{o}_2$ , partial pressure of oxygen in arterial blood; $PEFR$ , peak expiratory flow rate.

Box 73-2 The Differential Diagnosis of Asthma z

• Cardiac conditions
  • Valvular heart disease
  • Congestive heart failure in old age
• COPD exacerbation
  • Pulmonary infection
  • Pneumonia
  • Allergic bronchopulmonary aspergillosis
  • Löffler’s syndrome
  • Chronic eosinophilic pneumonia
• Upper airway obstruction
  • Laryngeal edema
  • Laryngeal neoplasm
  • Foreign body
  • Vocal cord dysfunction
• Endobronchial disease
  • Neoplasm
  • Foreign body
  • Bronchial stenosis
• Pulmonary embolus
• Carcinoid tumor
• Allergic or anaphylactic reaction in children
• Miscellaneous conditions
  • GERD
  • Noncardiogenic pulmonary edema
  • Addison’s disease
  • Invasive worm infection

not all wheeze
mean asthma

COPD, chronic obstructive pulmonary disease; GERD, gastroesophageal reflux disease.

Trx algorithm

	MILD TO MODERATE	SEVERE
FEV 1 or PEFR (% predicted/personal best)	≥40%	Unable or <40%
Oxygen therapy	Maintain SaO 2 ≥90%	Maintain SaO 2 ≥90%
Nebulized albuterol solution
Levalbuterol (optimal)	1.25 mg q20min for up to three doses	1.25 mg q20min for three doses
Racemic albuterol	2.5 mg q20min for up to three doses	Continuous for 1 hr if severe 5.0 mg q20min for three doses Continuous for 1 hr if severe
Albuterol MDI with VHC
Levalbuterol (45 µg/puff) (optimal)	6-12 puffs q20min for up to three doses WS	Same for three doses (if able to do), WS
Racemic albuterol (90 µg/puff)	6-12 puffs q20min for up to three doses WS	Same for three doses (if able to do), WS
Ipratropium therapy
Nebulized solution	If previous response (same dose as for severe)	0.5 mg q20min for three doses (may mix with albuterol solution)
MDI (18 µg/puff) with VHC	If previous response (same dose as for severe)	8 puffs q20min for three doses
Systemic corticosteroids
Oral (preferred)	40-80 mg of prednisone or prednisolone per day if no immediate response to albuterol	40-80 mg of prednisone or prednisolone per day
Intravenous (unable to take orally or absorb)	40-80 mg of methylprednisolone per day	40-80 mg of methylprednisolone per day
Intravenous magnesium sulfate	Not indicated	2-3 g over 20 min (or at rates of up to 1 g/min) if FEV 1 ≤ 25% predicted

FEV₁, forced expiratory volume in 1 second; MDI, metered-dose inhaler; PEFR, peak expiratory flow rate; SaO₂, oxygen saturation in arterial blood; VHC, valved holding chamber; WS, with supervision.

Pearls

• Most patients suffering asthma are poorly controlled
• If B agonists are used more than twice a week, then controlling therapy should be initiated
• Long-acting B agonists should not be used in isolation to treat asthma
• Magnesium plays a therapeutic role in moderate to severe asthma

Doesn’t work in asthma nowadays

• * give IV B agonist in severe asthma - we may use ephedrine
  (when contraindicated put Pit in BIPAP)