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It is a syndrome characterized by airflow obstruction that varies markedly, both spontaneously and with treatment.
Symptoms-wheezing, breathlessness, cough, chest tightness
Prevalence-10-12% adults, 15% children Developed country>Developing countries

Risk Factors
Endogenous Factors
Genetic predisposition Atopy
Ethnicity? Obesity?
Viral infections
Environmental Factors
Indoor allergens Outdoor allergens occupational sensitizers Passive smoking Respiratory infections
Allergens-Dermatophagoides species(dust mite), environmental exposure, grass pollen, ragweed, tree pollen, fungal spores, pets furs, cockroaches etc
Virus infection-upper respiratory tract virus such as rhinovirus, respiratory syncytial virus, coronavirus etc
Pharmacological agents-beta blockers, ACE inhibitors, aspirin
Exercise(may exacerbate )
Physical factors-cold air, hyperventilation
Air pollutants-sulfur dioxide, irritant gases
Irritants-household sprays paint fumes
Occupational factors
Hormonal factors-fall in progesterone thyrotoxicosis
Gastrointestinal reflex
Types of asthma-
Atopic asthma-classical type I IgE mediated hypersensitivity, allergen sensitization, seen from childhood, +ve history of asthma in family, skin test +ve
Non-atopic asthma-no allergen sensitization, no
such history, skin test –ve, virus infection?
Drug induced asthma-sensitive to certain drugs like aspirin, NSAIDS etc
Occupational asthma-stimulants such as fumes, organic and chemical dusts(wood, cotton), gas(toluene), penicillin products etc
Exercise induced asthma-begins after exercise and stops after 30 minutes, worsen in cold and dry climate
Inflammatory mediators
Effects of inflammation
Airway remodeling
Chronic inflammation of lower airways
Mucosal infiltration of activated eosinophils and T lymphocytes
Thickening of basement membrane
Goblet cell metaplasia
Smooth muscle hypertrophy and thickening
Shedding of epithelium
Occlusion of airway by mucosal plug
Allergic type of inflammation occurs
From trachea to terminal bronchiole
Predominantly in bronchi
Airway hyperresponsiveness
Cells involved in inflammation-mast cell macrophages dendritic cell eosinophils neutrophils T lymphocytes and structural cells
Early phase reaction-mediated by granules release from mast cell, bronchoconstriction, vasodilation and increase permeability
Late phase reaction-inflammation with recruitment of eosinophils, T lymphocytes, neutrophils, macrophages etc and subsequent release of mediators.
Mast cell-activated by IgE dependant mechanism, initiate acute bronchoconstriction action by releasing histamine, prostaglandinD2,leukotrienes etc
Macrophage-activated by low affinity IgE receptor, produce various inflammatory mediators
Dendritic cell-macrophage like major APC in airways, TSLP(Thymic stromal lymphopoietin) by epithelial cell induced chemokine release for TH2 cells
Eosinophils-infiltration is characteristic feature of asthma, activated by IL-5, causes exacerbation of asthma by producing mediators
Neutrophil-activated and infiltration
T cell-release cytokines, causes recruitment of eosinophils, also causes maintenance of mast cells, in asthma TH2 cell produce IL- 5(eosinophil recruitment) IL-4, IL-13(increase IgE production and mucus secretion).CD4+ cell also involved
Structural cells-epithelial cells(TSLP),
fibroblasts etc
Inflammatory mediators-
Histamine, prostaglandin D2, cysteinly leukotrienes-cause smooth muscle contraction, increased microvascular leakage, increased mucus secretion, act as chemoattractant for inflammatory cells
Cytokines- IL-4, IL-5, IL-13-causes allergic inflammation, IL-1beta, TNF-alpha-amplification of inflammation, TSLP(Tymic stromal lmphopoietin)- from epithelial cells act as chemoattractant for TH2 cells, IL-10, IL-12-anti inflammatory
Chemokines-attract inflammatory cells, Eotaxin(CCL11) attract eosinophil via CCR3 receptor, TARC(CCL17) and MDC (CCL 22) from epithelial cell attract TH2 cell via CCR4.
Oxidative stress-increase in ROS production
NO-act as relaxant but mainly causes
vasodilatation leading to leakage
Transcription factor-NF-kB, activator protein-

Effects of inflammation-
-dysfunction, damage, loss of enzyme, loss of relaxant factors, loss of barrier functio
Fibrosis- subepithelial fibrosis, basement membrane thickening, deposition of III and V collagen(by factors release from eosinophil)
Smooth muscle- increased responsiveness to constrictor mediators, in chronic cases hypertrophy/hyperplasia by growth factors released by inflammatory mediators
Vascular response-vasodilation, angiogenesis, microvascular leakage
Mucus hypersecrection- by goblet cell hyperplasia, increase in mucus plug, leading to blocking of airway
Neural effect-reflex cholinergic bronchoconstriction by increased muscarinic action

Airway remodeling
Several changes can be seen
Irreversible narrowing of lumen
Decline in lung function
Smooth muscle hyperplasia

Asthma is chronic inflammatory disorder with airway hyperresponsiveness and airway obstruction.
various risk factors and triggers
Types-atopic and non-atopic
Eosinophilic infiltration and thickening of B.M.
Hyperplasia of gland and vasodilatation
IgE dependant mast cell activation and release of
various mediators
Early and late phase reactions with dendritic cell and TH2 cell
Various mediators-cytokine, chemokines, PGs etc
Epithelium shedding, fibrosis, hypertrophy of muscle
and increased permeability
Airway remodeling

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