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It is characterized by recurrent episodes of dyspnoea Q, dry cough Q, and wheeze Q caused by reversible airways Q obstruction.


(Reversible airway obstruction is the most important criteria & is the most characteristic feature)


Three factors contribute to airway narrowing: Both large & small airways)

  1. Bronchial muscle contraction Q: Triggered by a variety of stimuli;
  2. Mucosal swelling Q
  3. Mucosal inflammation Q, caused by mast cell and basophil degranulation resulting in the release of inflammatory mediators; increased mucus production.

Recent Advances: Exhaled NO (Ref. Hari. 18th ed., Pg - 2109)

  1. Exhaled NO is now being used as a noninvasive test to measure eosinophilic airway inflammation.
  2. The typically elevated levels in asthma are reduced by ICS (Inhaled Corticosteroid), so this may be a test of compliance with therapy. 

Asthma (Intrinsic Asthma)


Difference between (= Extrinsic Asthma / Allergic asthma/ Atopic Asthma/Intermittent Asthma) & Intrinsic Asthma (= Idiosyncratic Asthma)



Extrinsic asthma

Intrinsic asthma

1. H/o atopy



2. Attack related to environment exposure



3. IgE level



4. Age of onset

Young, Early

Adult, late

5. Severity

Less severe

More severe




6. Response to bronchodilator



8. % of total patient



9. Sensitivity to aspirin



10. Associated feature


Nasal polyp


Important points

  1. Reversible Airflow obstruction is a characteristic feature
  2. Asthma involves both large and small airways
  3. Intermittent asthma responds better to bronchodilator therapy than persistent asthma
  4. Asthma is best diagnosed by demonstration of reversible obstruction. 

Basic Physiology


Criteria of reversibility: Increase FEV1 of > 12% or > 200 ml after 15 minutes of inhaled Beta-2 agonist or 2 to 4 weeks of prednisolone therapy. (Ref. Hari. 18th ed., Pg- 2109)



  1. Cold air, exercise, emotion, allergens (house dust mite, pollen, animal fur), infection, drugs (eg aspirin, NSAIDs, beta blockers).
  2. Diurnal variation in symptoms or peak flow. Marked morning dipping of peak flow is common and can dip the balance into a serious attack, despite having normal peak flow at other times.
  3. Exercise: Quantify the exercise tolerance.
  4. Acid reflux: This has a known association with asthma.
  5. Other atopic disease: Eczema, hay fever, allergy, or family history
Recent Advances:

Vitamin D deficiency may also predispose to the development of asthma

Extra Edge: 

Aspirin associated asthma usually begins with perennial vasomotor rhinitis that is followed by a hyperplastic rhinosinusitis with nasal polyps.



  1. State of persistent subacute inflammation of the large and small airways.
  2. Cells – Mast cells, eosinophils, lymphocytes & epithelial cells.
  3. Mediators – Histamine, bradykinin, Leukotrines, D,E, PG E2, F2α, D2 & PAF, IL – 3, IL – 4, IL – 13.
  4. Response – Bronchoconstriction, vascular congestion, edema formation, increase mucus production & impaired mucociliary function. 


The most striking pathological feature in bronchial asthma is bronchial inflammation & occlusion of bronchi and bronchioles (both large & small airway) by thick tenacious mucus plugs.


Features of Asthma:

  1. Chronic inflammatory disorder
  2. Hyperresponsiveness of airways (AHR)
  3. Airway epithelial shedding
  4. Subepithelial fibrosis and thickening of basement membrane
  5. Hypertrophy and Hyperplasia of airway smooth muscle
  6. Microvascular leakage resulting in airway edema and plasma exudation into airway lumen
  7. Mucus Hypersecretion and formation of viscid mucus plugs that occlude airways
  8. Defects in autonomic neural control

The microscopically identifiable features described in sputum are three ‘C’s

  1. Charcot Leyden crystals : Derived from granules of eosinophils and found only in Asthma
  2. Curshmann spirals : Curiously twisted casts of airways: Whorls of shed epithelium
  3. Creola bodies : Clumps of cells or isolated metaplastic cells


Symptoms (Triad)

  1. Intermittent dyspnea,
  2. Wheeze, (is the pathognomic feature Q).
  3. Cough (often nocturnal) Dry cough is the earliest feature Q


  1. Tachypnea;
  2. Audible wheeze;
  3. Hyperinflated chest:
  4. Widespread, polyphonic rhonchi

Feature of Severe attack:

  1. Inability to speak complete sentence in one breath Q
  2. Pulse > 120 per minute
  3. Respiratory rate >25/min
  4. Pulsus paradoxus of > 10 mmHg Q
  5. FEV1 between 33 to 50% of predicted

Feature of Life-threatening attack: (LQ 2012)

  1. Silent chest Q    (LQ 2012) 
  2. Cyanosis Q
  3. Bradycardia Q
  4. Confusion Q  (altered sensorium)
  5. FEV1 <33% of predicted Q
  6. Respiratory acidosis
  7. Hypercapnia

Particles of size <2.5 μ can be carried to the lower airways.

  1. Particles with size above 10-15 μ in diameter, because of their settling velocities in air, do not penetrate beyond the upper airways.
  2. Particle of size 2.5-10 μ deposit relatively high in the tracheobronchial tree.
  3. Particles of size <2.5 μ can be carried to the lower airways. 

Management of chronic asthma

  1. Beta 2 adrenoceptor agonists relax bronchial smooth muscle (cAMP), acting within minutes.
    1. Short acting Beta 2 agonist - Salbutamol is best given by inhalation (aerosol, nebulizer), but may also be given per oral or IV.
      i. Tachyarrhythmias,
      ii. Hypokalemia Q,
      iii. Tremor Q,
      iv. Anxiety Q,
    2. Long. Acting inhaled beta 2-agonist (eg salmeterol. formoterol) can help nocturnal symptoms and reduce morning dips.
      They may be an alternative to steroid dose when symptoms are uncontrolled. Salmeterol are not given in acute attack
      SE: as salbutamol. Paradoxical bronchospasm Q (salmeterol). Tolerance and arrhythmias can occur.
  2. Corticosteroids are best inhaled to minimize systemic effects, eg beclomethasone via spacer (or powder), but may be given PO or IV. They act over days to reduce bronchial mucosal inflammation.
Extra Edge: Asthma is characterized by hyperresponsiveness of airways
  1. Asthma is an allergic disease of the airways
  2. Inhaled corticosteroids are the mainstay of treatment
  1. Aminophylline (metabolized to theophylline) may act by inhibiting phosphodiesterase, thus reduce bronchoconstriction by increasing cAMP levels.
  2. Anticholinergics (eg ipratropium, tiotropium) may reduce muscle spasm synergistically with beta 2-agonists.
  3. Cromoglycate May be used as prophylaxis Q in mild and exercise-induced Q asthma (always inhaled), especially in children.
  4. Leukotriene receptor antagonists (eg montelukast, zafirlukast Q) block the effect of cysteinyl leukotrienes in the airways. Not effective in acute attack.

Step-wise approach to asthma therapy
according to the severity of asthma and ability to control symptoms. ICS, inhaled corticosteroid; LABA, long-acting Beta2-agonists; OCS, oral corticosteroid. (Ref. Hari. 18th ed., fig.254.7, Pg - 2113)


Status asthmaticus (acute severe asthma)


Severe obstruction persisting for days to weeks.


Acute Severe Asthma: Treatment (Ref. Hari. 18th ed., Pg - 2113)

  1. A high concentration of oxygen should be given by face mask to achieve oxygen saturation of >90%.
  2. The mainstay of treatment is high doses of short-acting inhaled Beta2-agonists that are given either by nebulizer or via a metered dose inhaler with a spacer.
  3. In severely ill patients with impending respiratory failure, intravenous Beta2-agonists may be given.
  4. Corticosteroids are used intravenously (hydrocortisone or methylprednisolone) for the treatment of acute severe asthma.
  5. An inhaled anti-cholinergic may be added if there is not a satisfactory response to Beta2-agonists alone, as there are additive effects.
  6. In patients who are refractory to inhaled therapies, a slow infusion of aminophylline may be effective.
  7. Magnesium sulfate given intravenously.
  8. Prophylactic intubation may be indicated for impending respiratory failure, when the PaCO2 is normal or rises.
  9. These patients may benefit from an anesthetic, such as halothane, if they have not responded to conventional bronchodilators.
  10. Sedatives should never be given as they may depress ventilation.
  11. Antibiotics should not be used routinely unless there are signs of pneumonia.

Important Points: In severe acute asthma sedative and montelukast are not given.


Recent advances - Tiotropium bromide (anticholinergic) is used in COPD


Recent Advance: New Drugs

  1. Anti-IgE monoclonal antibody Omalizumab is a new drug Q be of use in highly selected patients with persistent allergic asthma (PQ) It is an IgE blocker.
  2. MgSO4 is used in severe asthma.
  3. Bambuterol is a long acting beta-adrenoceptor agonist (LABA) used in the treatment of asthma; it also is a prodrug of terbutaline. It is a new drug, not given in Harrison 18th edition also !!! 
Recent Advances:

Refractory Asthma: Treatment


Definition: Asthma which is difficult to control is called as refractory asthma.

  1. Low doses of theophylline may be helpful in some patients, and theophylline withdrawal has been found to worsen many patients.
  2. Most of these patients require maintenance treatment with oral corticosteroids.
  3. Steroid-sparing therapies are rarely effective.
  4. Omalizumab (Anti-TNF therapy) is effective, particularly when there are frequent exacerbations.
  5. A few patients may benefit from infusions of beta 2-agonists.


Recent Advances: Newer types of asthma (Ref. Hari. 18th ed., Pg- 2114)

Brittle asthma

  1. Some patients show chaotic variations in lung function despite taking appropriate therapy. 
  2. Some show a persistent pattern of variability and may require oral corticosteroids or, at times, continuous infusion of Beta2-agonists (type I brittle asthma).
  3. Whereas others have generally normal or near-normal lung function but precipitous, unpredictable falls in lung function that may result in death (type 2 brittle asthma).
  4. These latter patients are difficult to manage as they do not respond well to corticosteroids, and the worsening of asthma does not reverse well with inhaled bronchodilators.
  5. The most effective therapy is subcutaneous epinephrine, which suggests that the worsening is likely to be a localized airway anaphylactic reaction with edema.
  6. In some of these patients, there may be allergy to specific foods.

Extra Edge:
Uses of Various Monoclonal antibodies


Main category Type Application

Anti- inflammatory


♦ Rheumatoid Arthritis

♦ Crohn's disease

♦ Ulcerative Colitis


♦ Rheumatoid Arthritis

♦ Crohn's disease

♦ Ulcerative Colitis


♦ Rheumatoid Arthritis


♦ Acute rejection of kidney transplants


♦ Acute rejection of kidney transplants


♦ Moderate-to-severe allergic asthma



♦ Relapsed acute myeloid leukaemia


♦ B cell leukemia


♦ Non-Hodgkin's Lymphoma, CLL


♦ Breast cancer with HER2/neu overexpression


♦ Approved in squamous cell carcinomas, Glioma


♦ Squamous Cell Carcinomas, colorectal carcinoma


♦ Anti-angiogenic cancer therapy



♦ RSV infections in children


♦ PREVENT coagulation in coronary angioplasty



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