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ASTHMA Eosinophilic infiltration  characteristic feature of

Jessamine C. Dacanay, MD, FPCP, DPCCP asthmatic airway. Eosinophils are linked to the
development of acute hypersensitivity reaction through
Asthma release of basic protein and ROS.
• A chronic inflammatory disorder of the airways
• This chronic inflammation is associated with Structural Cells  includes epithelial cells, fibroblasts and
airway hyperresponsiveness that leads to smooth muscle cells are sources of inflammatory
recurrent episodes of wheezing, breathlessness, mediators.
chest tightness, and coughing
• There is widespread, variable, and often Inflammatory mediators promotes bronchoconstriction,
reversible airflow limitation microvascular leakage, airway mucus secretion, and
• Associated with widespread but variable airflow attract other inflammatory cells.
obstruction
• Reversible with treatment or spontaneously Neutrophils, Eosinophils, mast cells,and dendritic cells, are
• Inflammation of the bronchioles cause recruited into the bronchial airways followed by mucus
hyperresponsiveness to variable stimuli hypersecretion and goblet cell hyperplasia.

Prevalence Other findings:

 mucus hypersecretion
• 10-12% in adults  angiogenesis d/t vasodilatation
• 15% in children  subepithelial fibrosis
• Childhood  Males > Females  bronchoconstriction d/t cholinergic stimulation
• Adult  Equal sex ratio  hypertrophy and hyperplasia of airways

Mortality increases when...

• poorly controlled disease

• frequent use of bronchodilators
• lack of ICS use
• history of prior near fatal asthma
 ex. episodes that need to be intubated

Figure 2. Inflammation in the airways of asthmatic patient

leads to airway hyperresponsiveness and symptoms.

Risk factors

1. Atopy
• Strongest risk factor: family history of atopic
Figure 1. Asthma Inflammation, Cells, and Mediators. disease ( 3x-4x)
• House dust mites
The allergen is taken up by the macrophage or dendritic • cat and dog fur
cells and migrate to the local lymph nodes where they • cockroaches (KAKRAAACH!)
present the allergenic peptides to uncommitted T • grass and tree pollens
lymphocytes to program production of allergen specific T 2. Production of specific IgE antibodies
cells. Dendritic cells produce chemokines that attract TH2
cells into the airways. 3. Infections  are common triggers of exacerbations;
their roles in etiology is still unknown.
Mast cells  activated by allergen by IgE mediated • RSV- development of asthma
mechanism and binding of specific IgE renders them more • Mycoplasma/Chlamydia – found in airways of
sensitive to activation by physical stimuli. patients with severe asthma

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4. Environmental Factors • Production of inflammatory mediators such as:

• Increasing incidence of asthma in developing - IL5  eosinophilic inflammation
countries - IL-4/IL-13  increased IgE formation

5. Viral respiratory infection Effects of Inflammation

• Epithelial Shedding
“Hygiene hypothesis” • Fibrosis
• exposure to infections early in life influences the • Hypertrophy and hyperplasia of airway smooth
development of a child’s immune system along a muscle
non-allergic pathway leading to a reduced risk of • Increase mucosal blood flow (because of
asthma and other allergic diseases. vasodilatation and angiogenesis)
• Mucus hypersecretion
6. Diet
• Though still not proven, there is increased Asthmatic Triggers
incidence of asthma in:
Triggers Examples
- Vitamins A and C Allergens Activate mast cells
- magnesium Release of mediators
- selenium Viral infection Rhinovirus
- omega 3 (most common RSV
- Vitamin D deficiency trigger) Coronavirus

7. Obesity independent risk factor (most asthmatic patients would have

8. Air pollution exacerbations after a cold)
9. Occupational Exposure Pharmacologic Beta-blockers (bronchoconstriction)
agents Aspirin
Pathology Exercise Typically begins after exercise has ended
(Prevented by Resolves spontaneously after 30 mins
• Increase numbers of activated eosinophils, T regular Worse in cold dry climates
lymphocytes and mast cells treatment with
• Thickening of the BM seen as: ICS)
o subepithelial collagen deposition Food
Air pollution
Inflammation Occupation
• Found in the upper airways such as the trachea to Hormonal Fall in progesterone
the terminal bronchioles Premenstrual worsening
• predominance in the cartilaginous bronchi
GERD
• Inflammation leads to airway
hyperresponsiveness leading to variable airflow
Pathophysiology
obstruction
• Increased number of different cells
Findings:
1. Mast cells
 Airflow limitation
• Initiates the acute bronchoconstrictor responses
o mainly due to bronchoconstriction
to allergens
 Reduction in:
• Activated by allergens thru IgE dependent
o FEV1
mechanisms
o FEV1/FVC Ratio
• Produces: Histamine, prostaglandins and
o Peak Expiratory Flow rate
cysteinyl-leukotrienes
Forced Vital Capacity (FVC)- forceful expiration after
2. Macrophages and Dendritic Cells
inhaling maximally.
• Initiate inflammatory response thru activation
of certain cytokines
Forced Expiratory Volume (FEV1) – Volume of air exhaled
after 1 second.
3. Eosinophils
• Characteristic of asthmatic airways
FEV1/FVC Ratio = 70% (normal)
• Associated with airway hyperresponsiveness
This means that 70% of the vital capacity is exhaled in 1
second. For asthmatic patients, the FEV1/FVC ratio is
4. T Lymphocytes
decreased, <70%
• TH 2 predominant immune response
PULMO – ASTHMA (DR. DACANAY) CASTILLO, N.P. 3F
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Peak Expiratory Flow Rate (PEF)  air is blown in to a 2. Methacholine/Histamine Challenge Test or
tube where we get the average flow to determine if the Bronchoprovocation Test
patient has bronchial asthma.
• Determines if there is an increase in airway
hyperresponsiveness especially in asymptomatic
 Early closure of peripheral airway – leads to: asthma
o Hyperinflation – determined via CXR • Provocation with either metacholine or histamine
o Air trapping - CXR or hypertonic saline
o Increased residual volume • (+) bronchoprovocation test: provocative
concentration of metacholine lead to a 20%
Clinical Features decrease in FEV1

• Wheezing, dyspnea and coughing Imaging

• Symptoms can be variable
• Resolves spontaneously or with treatment Chest radiograph
• Worse at night and typically awake in the wee  usually normal
hours of the morning due to frequent coughing  Hyperinflated lungs in exacerbations
and/or dyspnea  rule out co- existing conditions – to exclude other
• Increased mucus production causes of dyspnea
• Inspiratory and expiratory rhonchi
• Wheezes – high pitch; caused by Treatment
bronchoconstriction
• Rhonchi – low pitch; caused by movement 1. Relievers (Bronchodilators)
of the secretions upon breathing o rapid relief of symptoms
• Hyperinflation o relaxation of smooth muscles
• Some patients present with nonproductive cough
• Absence of physical findings in controlled asthma 2. Controllers
o inhibit underlying inflammatory response
Diagnosis
RELIEVERS/ BRONCHODILATORS
1. Pulmonary Function Test (PFT)
 Reverses bronchoconstricion
 Spirometry  Little or no effect on inflammation
o We first get a baseline spirometer  B2 agonists, anticholinergics and theophyllines
readings then we nebulize with
bronchodilators and read again for post- 1. B2 Agonists
bronchodilator results o Stimulates adenyl cyclase
o reduced FEV1, FEV1/FVC ration and PEF o increased intracellular CAMP
o relaxes smooth muscles
 Reversibility o inhibits certain inflammatory cells
o >12% and 200 ml increase in FEV1 post particularly mast cells
bronchodilator
SABA LABA
 Measurement of PEF >3 to 6 hours >12 hours duration
o diurnal variation of asthma
o we check the difference of peak flow in >rapid onset (15-20 >should not be used as
the morning and evening to determine mins) a monotherapy
hyperresponsiveness of airway (without ICS)
>increased use
 Increased airway resistance, TLC and RV – due to uncontrolled asthma >improve control and
bronchoconstriction reduce exacerbations
>nebulizer/MDI when added to ICS
 Diffusing Capacity for Carbon Monoxide (DLCO) is
usually normal >muscles tremors and
palpitations

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o can be given in controlled asthma (5-10

2. Anticholinergics mg/day)
o prevents cholinergic nerve induced o Prednisone/Prednisole 30-45 mg/day
bronchoconstriction and mucus secretion upto 60 mg once daily for 5-10 days and
o less effective than b2 agonists no tapering needed for exacerbations
o only used as an additional medication in o 1% of asthmatics may require
uncontrolled asthma maintenance treatment with OCS
o Adverse effects: dry mouth and urinary o Systemic side effects: Trucal obesity,
retention bruising, osteoporosis, diabetes,
o Used more on COPD hypertension, gastric ulceration,
depression and cataract
3. Theophylline
o Oral bronchodilator 3. Anti-Leukotrienes
o Inhibition of phophodiesterases increases  Leukotrienes  products of Arachidonic
CAMP acid that are potent bronchoconstrictors
o Narrow Therapeutic range high chances of
developing adverse effects o Less effective than ICS
o Given only in intermittent mild asthma
o At low doses anti-inflammatory effects o Add on therapy
o Slow release preparation: OD/BID o Less effective than LABA as add on
o Add- on medication in poorly controlled o Oral, OD/BID
asthma
o Adverse effects: Nausea, vomiting and Cysteinyl Leukotrienes
headaches o potent bronchoconstrictors
o At high doses  Arrhythmias and seizures
Montelukast/Zafirlukast
CONTROLLERS o LT 1 receptor blockers

1. Inhaled Corticosteroids 4. Cromones

o most effective controller o Cromolyn Na/Nedocromil Na
o reduces inflammatory numbers and their o Inhibit mast cell degranulation
activation o Effective in Exercise Induced
o reduction of Airway hyperresponsiveness Asthma/Allergen induced asthma
o Not available in PH
Mode of Action
• Inhibition of NF- KB 5. Omaluzimab
• Recruitment of histone deacetylase 2
• Increase expression of B2 receptors o Anti IgE monoclonal antibody
• Given BID o Reduces number of exacerbations  dec
inflammation
Effects o Subcutaneous injection every 2-4 weeks
• Rapidly improve symptoms and lung function o Side Effect: Anaphylaxis
• Prevents exacerbations, Exercise Induced Asthma,
AirwayHyperresponsiveness Chronic Asthma
• Maximal improvement may take several months o Managed by a stepwise approach
• Prevents irreversible changes in airway function
• 1st line therapy for persistent asthma Table 1. GINA Levels of Asthma Control
• Added to a LABA if still uncontrolled with ICS
alone

Adverse Effects
• Hoarseness and oral candidiasis
• Reduced by a large volume spacer device
• Minimal systemic side effects compared to oral
corticosteroids (OCS)

2. Oral Corticosteroids
o used for treatment of acute severe asthma
(exacerbations)

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Refractory Asthma
o Difficult to control despite maximal medications
o 5% of asthmatics
o Require maintenance OCS
o Make sure to rule out : non compliance with
medications
• Some patients exacerbate not because
they are uncontrolled but because they
are non compliant
o Allergic rhinitis
o GERD
o Drugs

Steroid Resistant Asthma

o Failure to respond to a high dose of oral
prednisone/prednisolone (40md OD over 2 weeks)
o Reduction in response of circulating
monocytes/lymphocytes

Special Considerations

Pregnancy
1/3 rule
o 1/3 will improve
o 1/3 will exacerbate
o 1/3 will remain the same

 same treatment as non pregnant

 OCS: Prednisone better than prednisolone

Breastfeeding
First, determine whether patient is controlled, partly  Same treatment as non pregnant
controlled, or uncontrolled. For instance, if the patient is
controlled, we start with Step 1: as needed SABA. If the Aspirin-Sensitive Asthma
patient is still unresponsive, we move the treatment to o preceded by rhinitis and nasal polyps
Step 2: as needed SABA + low dose ICS or LT modifier. If o provokes rhinorrhea, conjunctival irritation, facial
patient seem to improve for 2-3 months, we can now step flushing and wheezing
down.
Note: if the patient started on low dose ICS (step 2  Non selective COX should be avoided
onwards) we maintain the ICS even if the patient is  Respond to ICS and Anti-leukotrienes
controlled.
Cigarette Smoking
Management o interferes with anti-inflammatory actions of
corticosteroids
Acute Severe Asthma (Acute Exacerbations) o require higher doses of steroids
o High o2 particularly if the patient is hypoxemic o cessation improves lung function and reduces
o SABA via nebulizer/MDI with spacer steroid resistance
o SAMA
o IV Steroids Surgery
o IV Aminophylline o if well controlled: No contraindication to General
o IM Magnesium Sulfate – last option Anesthesia and intubations
o Acute Severe Asthma o FEV1 < 80%: Should be given a boost of OCS prior
o Watch out impending Respiratory Failure to surgery to decrease exacerbation
• Hypercapnia o High doses of steroids: Contraindicated
• Unresponsive o Steroids impair wound healing
o Avoid sedation
• Sedation may precipitate hypercapnia
o Give antibiotics if signs and symptoms of
pneumonia develops
PULMO – ASTHMA (DR. DACANAY) CASTILLO, N.P. 3F