Pathophysiology of Asthma:

Pathophysiology of Asthma – It is a diffuse airway inflammation caused by triggering stimuli resulting in partially or completely reversible bronco-constriction.

The chronic inflammation is associated with airway hyper‐responsiveness that leads to recurrent episodes of wheezing , breathlessness, chest tightness and coughing particularly at night or early morning.

Types of Asthma:

Mild persistent Asthma – low dose inhaled corticosteroids or Theophylline or Montelukast.

Moderate persistent Asthma – medium dose inhaled corticosteroids or low dose inhaled corticosteroids + long acting beta 2 agonists or low dose inhaled corticosteroids + Theophylline

Severe persistent Asthma  – high dose inhaled corticosteroids + long acting beta 2 agonista later if it continues oral corticosteroids.

Seasonal Asthma – This type occurs in response to allergens that are only in the surrounding environment at certain times of year, such as cold air in the winter or pollen during hay fever season.

Pathophysiology of Asthma:

• Inflammation in asthma is characterized by eosinophils, CD4+ T-lymphocytes, macrophages and mast cells
• Prominent pathological features of asthma include:
  • airway hyper-responsiveness
  • episodic bronchospasm in the large airways
  • vasodilation and angiogenesis
• Severe asthma can be classified into two sub-types: eosinophil (+) and eosinophil (-)
• Neutrophils are found in severe, corticosteroid- dependent asthma

Causes for Asthma:

1. Genetic susceptibility and Gene – Environment interaction.
2. Perinatal Factors
3. Indoor and Outdoor Allergens like Smoking and Environmental Tobacco Smoke
4. Other Pollutants
5. Race/Ethnicity and Socioeconomic Status
6. Obesity
7.  Respiratory Illnesses

Diagnosis in Pathophysiology of Asthma:

• Typical history
• Intermittent symptoms (reversible)
• Association of symptoms to weather changes, dust, smoke, exercise, viral infection, animals with fur or feathers, house-dust mites, mold, pollen, strong emotional expression (laughing or crying hard), airborne chemicals or dust
• Diurnal variation
• Family history
• Presence of atopy, allergic rhinitis, skin allergies.
• Spirometry should be done at the time of initial assessment and after treatment is initiated and symptoms and peak expiratory flow (PEF) have been stabilized at least every 1 to 2 years to assess the maintenance of airway function.

Goals of Asthma Therapy:

• Prevent recurrent exacerbations and minimize the need for emergency department visits or hospitalizations
• Maintain (near‐) “normal” pulmonary function
• Maintain normal activity levels (including exercise and other physical activity)
• Provide optimal pharmacotherapy with minimal or no adverse effects

Treatment of Asthma:

Beta2-adrenergic agonists are used to treat symptoms associated with asthma and chronic obstructive pulmonary disease (COPD).

Short-acting beta2-adrenergic agonists include:

• albuterol (systemic, inhalation)
• levalbuterol (inhalation)
• metaproterenol (inhalation)
• pirbuterol (inhalation)
• terbutaline (systemic).

Long-acting beta2-adrenergic agonists include:

• formoterol (inhalation)
• salmeterol (inhalation).

Albuterol

Inhaler – 90 mcg / puff, 2 puffs every 4 – 6 hrs as needed and 2 puffs before exercise

Nebulizer – children below 5 yrs – 0.63 to 2.5 mg in 3 ml saline every 4 – 6 hrs as needed, children above 5 yrs – 1.25 to 2.5 mg in 3 ml saline every 4 – 6 hrs as needed and in adults – 1.25 to 5 mg in 3 ml saline every 4 – 6 hrs as needed.

Levalbuterol

Inhaler – 45 mcg / puff, 2 puffs every 4 -6 hrs as needed

Nebulizer – 0.31 to 1.25 mg in 3 ml every 6 – 8 hrs as needed.

Pirbuterol

MDI – 200 mcg / puff, 1 – 2 puffs every 4 – 6 hrs as needed

LA Beta 2 agonists – Not be used as monotherapy.

Salmeterol

Inhaler — 21 to 50 mcg / puff, 1 – 2 puffs every 12 hrs.

Anticholinergics:

Inhaled ipratropium, an anticholinergic, is a bronchodilator used primarily in the patient suffering from COPD, but it may also be used as an adjunct to beta2-adrenergic agonists.

Ipratropium (SA)

MDI – 18mcg / puff, 2 puffs every 6 hrs as needed

Nebulizer – 500 mcg (0.02%) solution, 500 mcg every 6 – 8 hrs as needed

Tiotropium (LA)

DPI – 18mcg / capsule, 1 capsule / day.

Leukotriene modifiers:

They are used for the prevention and long-term control of mild asthma. Leukotriene receptor antagonists include:

Montelukast – 4, 5, 10 mg tablets, once a day in the evening

Zafirlukast – 10 , 20 mg tablets, once a day in the evening

Mast cell stabilizers:

They are used to prevent asthma attacks, especial- ly in a child or a patient with mild disease. They’re also used in an adult or child with mild to moderate persistent asthma. Drugs in this class include: cromolyn

Corticosteroids:

Corticosteroids are anti-inflammatory drugs available in inhaled and systemic forms for the short- and long-term control of asthma symptoms. Many products with differing potencies are available.

Beclomethasone

MDI – 40 – 80 mcg / puff, 1 – 2 puffs every 12 hrs

Budesonide

DPI – 90 or 180 mcg / inhalation, 360 mcg twice a day

Nebulizer – 0.5 mg / day or 0.25 mg twice a day for children below 8 yrs, not indicated for adults

Fluticasone

MDI – 44,110,220 mcg / inhalation, children – 88 – 176 mcg twice a day, adults – 88 – 220 mcg twice a day

DPI – 50, 100, 250 mcg / inhalation, children – 50 mcg twice a day, adults – 100 – 250 mcg twice a day

Mometasone

DPI – 110 or 220 mcg / inhalation, children – 110 mcg once a day in evening, adults – 220 mcg once a day in evening

Oral:

Methylprednisolone – 2,4,8,16,32 mg tablets

Prednisolone – 5 mg tablets or 5 mg / 5 ml or 15 mg / 5 ml solution

Prednisone – 1,2.5, 5, 10, 20, 50 mg tablets or 5 mg / ml or 5mg / 5ml solution

children – 1 – 2 mg / kg per day for 3 – 10 days, adults – 7.5 – 60 mg / day in the morning or every other morning for Prednisolone and for Prednisone – 40 – 60 mg once a day or 20 – 30 mg twice a day.

Combination drugs:

Ipratropium / Albuterol – 2 puffs 4 times a day or 3 ml vial 4 times a day

Fluticasone / Salmeterol – 1 inhalation twice a day

Budesonide / Formoterol – 2 inhalations twice a day

Mometasone / Formoterol – 2 inhalations twice a day

Counselling on side effects:

Beta 2 agonists – dizziness, headache, palpitations, tachycardia

Leukotriene antagonists – headaches, GI disturbances, sleep disorders

Corticosteroids – decreased ability to respond, physical stress, fatigue, joint pains, muscle tenderness, severe withdrawal syndrome, susceptible to infections, GI tract problems(ulcers), thinning of bones, weight gain, insomnia, mood changes, elevated bp, fluid restriction, elevated sugar, can cause glaucoma, worsen cataract condition, atherosclerosis, aseptic necrosis(death of parts of bone). Elderly patients using corticosteroids having risk factors for osteoporosis must use calcium and vitamin D supplements.

Treat asthma aggressively during pregnancy

• Aspirin induced asthma – Avoid use of NSAIDS
• Controlling triggering factors in Asthma – It is important to control triggering factors
• Use of synthetic fiber pillows, impermeable mattress covers, frequent washing of bed sheets / pillow covers with hot water
• Upholstered furniture, soft toys, carpets should be removed
• Dehumidifiers should be use in basements and house cleaning
• Aspirin induced should use paracetamol,choline magnesium salicylate etc.

Environmental factors for Asthma

• Avoid exposure to allergens (dust, mite, cockroach, pets)
• Diet low in vitamin C,E and omega 3 fatty acids
• Obesity
• Perinatal factors (young mothers, poor maternal nutrition, premature birth, low birth weight, lack of breast feeding)

Other factors in Pathophysiology of Asthma:

• Infections, cold viruses
• Exercises – specially in cold and dry environment
• Inhaled irritants – smoke, air pollution
• Emotions – anxiety, anger, excitement
• Aspirin – severe asthma upto 30% in older patients
• GERD induces asthma because of bronchoconstriction

Counselling on diet,exercise,lifestyle management:

• Eat food rich in vitamin C, E, Omega 3 fatty acids
• Bell Pepper, Guava, Citrus fruits, Papaya, Strawberries for vitamin C
• Tofu, Spinach, Nuts, Sunflower seeds, Fish for vitamin E
• Flax seeds, Walnuts, Fish, Tofu, Soybean for Omega 3 fatty acids.

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