Bronchial Asthma

• Asthma is a chronic lung disease that inflames and narrows the airways (tubes that bring air into and out of an individual’s lungs).
• Asthma is the most common chronic disease among children.
• The word – asthma – (aazein) – “to breath with open mouth or to pant”
• Estimated 300 million people live with asthma

No single universally agreed definition of asthma

Why?

Not a single entity, but a term used to describe a set of symptoms that results from the action of a number of incompletely understood mechanisms;

DEFINITION

Bronchial asthma is a chronic inflammatory disorder of the airway associated with airway hyperresponsiveness and bronchoconstriction, which presents with wheezing, breathlessness, chest tightness, and cough.

The airway obstruction is reversible either spontaneously or with treatment.

GINA:

‘A chronic inflammatory disorder of the airways. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, coughing, chest tightness, and difficult breathing. Inflammation makes the airways sensitive to stimuli such as allergens, tobacco smoke, cold air, exercise, and chemical irritation. When exposed to stimuli, the airway may become swollen, constricted, filled with mucus, and hyperresponsive to a variety of stimuli. The resulting airflow limitation is reversible (although not completely so in some patients), either spontaneously or with treatment. When asthma therapy is adequate, inflammation can be reduced over the long term, symptoms can be controlled, and most asthma-related problems prevented’.

COMPONENTS OF THE DEFINITION

1. Chronic inflammatory nature of the disease.
2. Increase in airway hyper-responsiveness.
3. Resultant broncho-constriction as evidenced by recurrent episodes of wheezing, dyspnoea, cough, and chest tightness.
4. Symptoms disappear spontaneously or as a result of treatment.
5. The disease may also take a Chronic cause with a change in airway symmetry and leading to persistent symptoms.

• Annual worldwide death has been put at 250,000, most of them vastly preventable.
• In Nigeria, about 15 million people may be asthmatic.
• A major cause of school/work absence.
• An overall increase in severity of asthma increases the pool of patients at risk for death.
• Various studies have been done on the prevalence of asthma in Nigeria. Reported prevalence ranges between 5% – 18%.
• Desalu et al in Ilorin reported a prevalence of 15.2%.

Natural History of Asthma

• Prevalence increases again during later adulthood to 7-9%.
• Often stated, most patients with asthma during childhood will outgrow it by early adulthood.
• Statistics show this to be true only in 30-50% of children.
• Usually more likely in male patients.

INCREASED PREVALENCE

• Parental history of asthma or atopy
• Parental Smoking-
  • Maternal smoking in pregnancy (Tucson’s Cheloris study; British longitudinal study)
• Sensitization to allergies (dust mite)
• Widespread use of antibiotics
• Western diet
• CD4 TH2 mediated

DECREASED PREVALENCE

• Farm environment (First year of life)
• Presence of older siblings
• Early attending of day-care during first 6 months of life
• Tuberculosis viral infection
• CD4 TH1 mediated

Risk Factors for Asthma

Host factors: Predispose individuals to, or protect them from, developing asthma.

Environmental factors: Influence susceptibility to the development of asthma in predisposed individuals, precipitate asthma exacerbations, and/or cause symptoms to persist.

The critical role of inflammation in asthma has been further substantiated. However, there is considerable variability in the pattern of inflammation, indicating phenotypic differences that may influence treatment responses.

Among environmental factors, allergic reactions remain important. There is also evidence suggesting a key and expanding role for viral respiratory infections.

The onset of asthma for most patients begins early in life, with the pattern of disease persistence determined by early, recognizable risk factors including atopic disease, recurrent wheezing, and a parental history of asthma.

The pathophysiology of asthma is complex and involves the following components:

• Airway inflammation
• Intermittent airflow obstruction
• Bronchial hyperresponsiveness

Airway inflammation

The inflammation in asthma can be acute, subacute, or chronic, and it involves airway edema and mucus secretion, which contribute to airflow obstruction and bronchial reactivity.

The inflammation involves varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling.

Principal cells identified in airway inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes regulate airway inflammation through the release of numerous cytokines.

The presence of airway hyperresponsiveness in asthma is an exaggerated response to numerous stimuli. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

A study reported changes in airway resident mast cell populations, with a greater proportion of chymase-positive mast cells in the airways and increased prostaglandin D2 levels being important predictors of severe asthma.

Chronic inflammation of the airways is associated with increased bronchial hyperresponsiveness, leading to bronchospasm and typical symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants, viruses, cold air, or exercise.

Airway inflammation in asthma may represent a loss of normal balance between two “opposing” populations of Th lymphocytes: Th1 and Th2. Th1 cells produce IL-2 and IFN-α, critical in cellular defense mechanisms in response to infection. Th2 generates a family of cytokines (IL-4, IL-5, IL-6, IL-9, and IL-13) that can mediate allergic inflammation.

The current “hygiene hypothesis” of asthma suggests that the immune system of the newborn is skewed toward Th2 cytokine generation. Following birth, environmental stimuli such as infections activate Th1 responses and bring the Th1/Th2 relationship to an appropriate balance. However, unequivocal support for the “hygiene hypothesis” has not been demonstrated.

Airflow Obstruction

Airflow obstruction in asthma can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling.

Acute bronchoconstriction is the consequence of immunoglobulin E-dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response.

Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic response.

Chronic mucous plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve.

Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction.

Airway obstruction causes increased resistance to airflow and decreased expiratory flow rates, leading to a decreased ability to expel air and may result in hyperinflation. The resulting overdistention helps maintain airway patency, thereby improving expiratory flow; however, it also alters pulmonary mechanics and increases the work of breathing.

Bonchial Hyperresponsiveness

Hyperinflation compensates for the airflow obstruction, but this compensation is limited when the tidal volume approaches the volume of the pulmonary dead space, resulting in alveolar hypoventilation.

Uneven changes in airflow resistance, uneven distribution of air, and alterations in circulation from increased intra-alveolar pressure due to hyperinflation all lead to ventilation-perfusion mismatch. Vasoconstriction due to alveolar hypoxia also contributes to this mismatch.

In the early stages, when ventilation-perfusion mismatch results in hypoxia, hypercarbia is prevented by the ready diffusion of carbon dioxide across alveolar capillary membranes. Thus, patients with asthma in the early stages of an acute episode have hypoxemia in the absence of carbon dioxide retention.

Hyperventilation triggered by the hypoxic drive also causes a decrease in PaCO2. An increase in alveolar ventilation in the early stages of an acute exacerbation prevents hypercarbia.

With worsening obstruction and increasing ventilation-perfusion mismatch, carbon dioxide retention occurs. In the early stages of an acute episode, respiratory alkalosis results from hyperventilation.

Later, the increased work of breathing, increased oxygen consumption, and increased cardiac output result in metabolic acidosis. Respiratory failure leads to respiratory acidosis due to retention of carbon dioxide as alveolar ventilation decreases.

• History and patterns of symptoms
• Measurements of lung function
  • Peak Expiratory Flow (PEF)
  • Spirometry
• Measurement of airway hyperresponsiveness
  • Pharmacological
  • Non-pharmacological
• Measurements of allergic states to identify risk factors

HISTORY

• Symptoms vary over time and in severity:
• Cough, wheeze, breathlessness
• Chest tightness
• Symptoms occur or worsen at night or after exposure to triggers
• Colds "go to the chest" or take more than 10 days to clear

COMMON TRIGGERS

Symptoms can occur or worsen in the presence of:

• Allergens
  • Animal dander
  • Dust mites
  • Pollen
  • Fungi, moulds
  • Cockroaches
• Others
  • Exercise
  • Viral infection
  • Smoke
  • Changes in temperature
  • Strong emotional expression
  • Aerosol chemicals
  • Drugs (NSAIDs, ß-blockers)

PHYSICAL SIGNS

• Tachypnoea, tachycardia – universal features of acute asthma
• Average respiratory rate is 25-30 breaths/min
• Rates >30 breaths/min or HR > 120 beats/min are not uncommon
• Sinus tachycardia tends to improve rather than worsen with use of sympathomimetics as airway function improves
• Diffuse musical wheezes are characteristic
• Presence or intensity of wheezes does not reliably predict the severity of asthma

INVESTIGATIONS

• Spirometry
• Peak Expiratory Flow
• Allergy Skin Testing
• Bronchoprovocative Test
• Blood and Sputum Eosinophils
• Serum Immunoglobulin E
• Exhaled Nitric Oxide Investigations
• Arterial Blood Gas
• Pulse Oximetry Assessment
• Chest Radiography
• Chest CT Scanning
• MRI
• ECG
• Nuclear Imaging
• Pulmonary Function Testing
• Sinus CT Scanning

SPIROMETRY

Spirometry measures the amount and rate of air a person breathes in order to diagnose illness or determine progress in treatment.

Spirometry measures the amount and rate of air a person breathes in order to diagnose illness or determine progress in treatment.

• Reversibility- >12% improvement in FEV1 (or FVC) and an absolute improvement of >0.2 L
• Calculation of reversibility=
  [FEV1 (post-bronchodilator) - FEV1 (baseline)x100]/FEV1 (baseline)
• The absence of reversibility does not exclude asthma because it is variable condition

Reversible and Variable Airflow Limitation

• Reversibility of Airways’ Obstruction
  • Increased FEV1 >12% (200mls) 15-20 minutes after inhaling ß2-agonist
• Variability of Airways’ Obstruction
  • PEF varies between morning and evening:
    • >20% in patients taking bronchodilator
    • >10% in patients not taking bronchodilator
• Exercise-induced Airways’ Obstruction
  • Decreased PEF >15% after 6 minutes of exercise

Consider especially if unusual features in the history, or poor correlation between objective measures and symptoms, or poor treatment response:

• Chronic Obstructive Pulmonary Disease (COPD)
• Upper Airway Obstruction
• Foreign Body Aspiration
• Tumour, especially Tracheal
• Congestive Cardiac Failure
• Vocal Cord Dysfunction
• Hyperventilation Syndrome
• Chronic Thromboembolic Disease or Primary Pulmonary Hypertension
• Interstitial Lung Disease
• Churg–Strauss Syndrome
• Bronchiolitis
• Gastro-oesophageal Reflux Disease

• ATOPIC ASTHMA
  • Also known as extrinsic asthma
  • Most common
  • Commonly childhood onset
  • Systemic production of IgE
• NON-ATOPIC ASTHMA
  • Also known as intrinsic asthma
  • Commonly adult onset
  • Local IgE within the airways

Asthma Clinical Types
Asthma	Some Characteristic Features
Fatality-prone asthma	History of 2 or more emergency visits to hospital for the past one year. Intubation and mechanical ventilation in the previous year. History of extreme and rapid progression of symptoms. History of sensitivity to certain foods as nuts, or shrimps.
Steroid resistant asthma	Failure of two weeks treatment with 40mg of methyl prednisolone to cause 15% improvement in FEV1
Brittle Asthma	Asthma prone to recurrent severe attacks
Steroid dependant asthma	Require frequent and continuous treatment with oral steroids
Extrinsic asthma	Allergic sensitization, positive skin test,↑ IgE
Intrinsic Asthma	Non-allergic asthma
Adult-Onset Asthma	Diagnosed after 20 years of age
Seasonal Asthma	Symptoms worsen during high allergen seasons (grass pollen)
Exercise-Induced Asthma	Triggered by exercise- almost a sine qua non asthma
Nocturnal Asthma	Expression of asthma, not a discrete subcategory
Drug-induced asthma	Aspirin, NSAIDs, Beta-blockers, ACE inhibitors
Asthmatic bronchitis	Asthma/COPD in a cigarette smoker
Allergic bronchopulmonary aspergillosis	Eosinophilia, positive skin test, IgE, infiltrates in chest x-ray, may develop bronchiectasis
Occupational asthma	Exposure to irritants at workplace or environment
Cough-variant asthma	Presents only with cough, usually excessive cough. More common in children (13%) and adults above 50 years old.
Aspirin-sensitive asthma	Development of bronchoconstriction in asthmatics following the ingestion of aspirin, associated with nasal polyps (acetylsalicylic acid).
Asthma with Gastroesophageal reflux disease (G.E.R.D.)	Asthma exacerbated by Gastroesophageal reflux disease (G.E.R.D.). More common in children.

Principles of Management

Periodic assessment and monitoring

• Symptoms and signs
• Pulmonary function
• Quality of life
• Asthma exacerbation
• Compliance with therapy
• Inhalation technique, adverse effect

Avoidance of trigger factors

• Study your asthma
• Find out environmental triggers
• Treat co-morbidities – GERD, obesity, viral infectious

Patient Education

• Basic asthma education
• Inhalation technique
• Action plan – emergency
• Self management plans

Medications

• Self care approach
• Focus on anti-inflammatory (preventative therapy)
• Plan for acute exacerbation

Treatment

Three main types of medications

1. Preventer (controllers)
2. Relievers (bronchodilators)
3. Combination drugs (preventers and relievers)

PREVENTER (CONTROLLERS)

• Reduce inflammation
• Make airways less reactive to triggers
• Should be administered twice daily (regulatory)
• • Steroid inhalers e.g. Becotide
  • Non-steroid controllers e.g. anti-leukotrienes, cromoglycate

RELIEVERS (BRONCHODILATORS)

• Relax the muscles of the wall of the airways during attack e.g. salbutamol
• Should be taken only when symptoms occur.
• Not regularly.

Relievers

• Inhaled fast-acting β2 agonists
• Inhaled anticholinergics
• Systemic glucocorticosteroids
• Theophylline
• Short-acting oral β2 agonist

Preventers/Controllers

• Inhaled corticosteroids
• Inhaled long-acting β2 agonists
• Inhaled cromones
• Oral anti-leukotrienes
• Oral theophyllines
• Oral corticosteroids
• Systemic glucocorticosteroids
• Anti IgE (Omalizumab)
• Anti TNFα (etanercept)
• Interferon-α
• Anti-interleukin 5, 13

Combination Drugs (Preventers and Relievers)

Combine both functions. They reduce the burden of taking lots of drugs e.g.

• Seretide (combination of fluticasone and salmeterol)
• Symbicort (combination of budesonide and formoterol)

Non-pharmacological Treatment

• Homeopathy
• Yoga
• Hypnosis
• Acupuncture
• Chiropractic
• Bronchial thermoplasty

Goals of Asthma Management

The long-term goals of asthma management are:

1. Symptom control: to achieve good control of symptoms and maintain normal activity levels
2. Risk reduction: to minimize future risk of exacerbations, fixed airflow limitation, and medication side effects

Levels of Asthma Control

Levels of Asthma Control
Characteristic	Controlled- all of the following	Partly controlled- any present in any week	Uncontrolled
Daytime symptoms	None (2 or less / week)	More than twice / week	3 or more features of partly controlled asthma present in any week
Limitations of activities	None	Any
Nocturnal symptoms / awakening	None	Any
Need for rescue / "reliever" treatment	None (2 or less / week)	More than twice / week
Lung function (PEF or FEV1)	Normal	< 80% predicted or personal best (if known) on any day
Exacerbation	None	One or more / year	1 in any week

The control-based asthma management cycle

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The control-based asthma management cycle

Stepwise management – additional components

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Stepwise management – additional components

Step 1 – as-needed inhaled short-acting beta2-agonist (SABA)

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Step 1 – as-needed inhaled short-acting beta2-agonist (SABA)

Step 2 – low-dose controller + as-needed inhaled SABA

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Step 2 – low-dose controller + as-needed inhaled SABA

Step 3 – one or two controllers + as-needed inhaled reliever

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Step 3 – one or two controllers + as-needed inhaled reliever

Step 4 – two or more controllers + as-needed inhaled reliever

×

Step 4 – two or more controllers + as-needed inhaled reliever

Step 5 – higher level care and/or add-on treatment

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Step 5 – higher level care and/or add-on treatment

Steps 1-5

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Steps 1-5

SYMPTOMS	SIGNS	LUNG FUNCTION TEST (PEF)	BLOOD GAS
Increasing breathlessness Speaking in monosyllables Increasing night-time symptoms Increased use of bronchodilators and additional medication Irritable, Agitation Decreased exercise tolerance	Use of accessory muscles of respiration Cyanosis Drowsy (life-threatening) Respiratory rate >25 breath/min Pulse rate >110 bpm Chest Auscultation: widespread and loud polyphonic wheezes	PEF <50% of patient’s best or predicted PEF <200 L/min Non-improvement in PEF after ≥20 –30 mins of inhaled bronchodilators	Decreased arterial partial pressure of Carbon dioxide Decrease partial pressure of oxygen Pulse oximetry <90%

Features of Life-Threatening Asthma

• Confusion
• Exhaustion
• Cyanosis
• Bradycardia
• Feeble respiratory effort
• Silent chest
• Peak expiratory flow <33% of predicted

Drugs	Examples	Actions
Life-savers
S	Salbutamol (in form of nebulizer)	Bronchodilator
O	Oxygen (high dose)	Enhances breathing and improves ventilation
S	Systemic steroids (prednisolone)	Anti-inflammatory

Stepcare Approach to Management in Acute Severe Asthma

Initial assessment:

1. History of predisposition to acute severe asthma as earlier stated
2. Physical examination, PEF, O2 saturation, arterial blood gases.
3. Initial short-acting beta 2 agonists given by a nebulizer or metered dose inhaler with volumatic
4. Moderate dose of Oxygen (40-60%) to achieve O2 saturation of 90%
5. Systemic steroid (oral prednisolone 30- 60mg if patient can tolerate, IV hydrocortisone 100-200mg, if not)
6. Do not sedate.

Continuous monitoring:

• PEF, O2 saturation, or arterial blood gases

If no improvement after 30 minutes to 1 hour, continue above management:

1. Add inhaled anticholinergic (ipratropium bromide)
2. Or intravenous aminophylline

Continue monitoring, if no improvement in 1-2 hours:

1. Continue Oxygen and initial management
2. Consider intravenous magnesium sulphate
3. Or intravenous beta 2 agonists
4. Or subcutaneous beta 2 agonists.

If no improvement:

• Patient becomes drowsy or comatose, PEF <30%, worsening hypoxemia, hypercapnia:
• Admit ICU
• Continue O2, inhaled beta 2 agonists, intravenous glucocorticosteroids, and anticholinergics
• Consider IV beta 2 agonist or IV theophylline
• Possible intubation and mechanical ventilation.

Criteria for Discharge:

• PEF >75% of predicted or best
• On discharge medication for 24hrs
• Inhaler technique checked and taught
• PEF variability <25%
• Treatment with oral and inhaled steroid
• Own PEF meter and self-management plan
• Patient education
• Written action plan
• Follow-up at the clinic