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High Cor)cal Center Afferent pathway Central por-on Brain Stem Efferent pathway ganglion

High Cor)cal Center Afferent pathway Rapidly adap-ng receptor Bronchial /Pulmonary C- fiber Central por-on Brain Stem Efferent pathway ganglion AirwaySmooth muscle Respiratory muscle: Diaphragm Accessory muscle

High Cor)cal Center Afferent pathway Rapidly adap-ng receptor Bronchial /Pulmonary C- fiber Central por-on Brain Stem Efferent pathway ganglion Excessive s)mula)on Receptor threshold AirwaySmooth muscle Respiratory muscle: Diaphragm Accessory muscle

High Cor)cal Center Afferent pathway Rapidly adap-ng receptor Bronchial /Pulmonary C- fiber Central por-on Brain Stem Efferent pathway ganglion Lessen filtering effect Excessive s)mula)on Receptor threshold AirwaySmooth muscle Respiratory muscle: Diaphragm Accessory muscle

High Cor)cal Center Modula)on Afferent pathway Rapidly adap-ng receptor Bronchial /Pulmonary C- fiber Central por-on Brain Stem Enhanced reflex Efferent pathway ganglion Lessen filtering effect Excessive s)mula)on Receptor threshold AirwaySmooth muscle Respiratory muscle: Diaphragm Accessory muscle

Where? S"mula"on sites What? Mechanical, physical (temp. ph, osmolarity): RAR Chemical (inflammatory, vapour, acid, alkali): C- fiber How? Excessive s"mula"on Impaired modula"on (psychological) Lowering threshold Enhanced reflex (Familiar sensory hyper- reflex, inflamma"on

Where? S"mula"on sites What? Mechanical, physical (temp. ph, osmolarity): RAR Chemical (inflammatory, vapour, acid, alkali): C- fiber How? How? Excessive s)mula)on s"mula"on Impaired modula)on modula"on (psychological) Lowering threshold Enhanced reflex reflex (Familiar sensory hyper- reflex, inflamma)on inflamma"on

Excessive s-mula-on Impaired modula-on psychological Cough receptor threshold Cough reflex enhancement

Cause Increased Cough Reflex Normal cough reflex Decreased cough reflex All respiratory disorders Use of ACE inhibitors Inhaled of irritant substances Psychogenic cough Throat clearing Cerebrovascular injury Decreased ac-vi-es of daily living An-phsycho-c drugs Sleep Vitamin B12 and folate deficeincy Anaesthe-cs Coma Disturbance of conciuosness Cerebrovascular diseases

Hyperresponsiveness Underlying inflamma)on Drugs Upper airways GERD Pharynx, larynx Post- infec)ous Familial sensory hyperreflex Mucosa atrophic Mouth breathing Environmental factors Saliva secre9on Lower airways Cough variant Asthma Eosinophilic bronchi)s Asthma/ COPD Bronchioli)s/pneumoni)s Non- hyperresponsiveness Excessive triggers Upper airways Postnasal drip (irrita)ng) Sinusi)s Acid regurgita)on Environmental / occupa)onal Lower airways Lung/endobronchial tumor Endobronchial TB, foreign body Lung edema, fibrosis Lung infiltrates (e.g. PCP, eosinophilic) Others (air, fluid, tumor) Pleural disease Middle or inner ear Medias)num Diaphragm

Cough Challenge Test Citric acid Capsaicin Cough Receptors (sensory nerves) Depolariza*on Hypertonic saline Low chloride pause 1 10 40 seconds

Cough Challenge Test

Posi)ve Cough Challenge Test Citric acid: C2 <100 mm C5<250mM Inflamma-on H+ Osmolarity

Posi)ve Cough Challenge Test Citric acid: C2 <100 mm C5<250mM Inflamma-on H+ Osmolarity Denuded epithelium

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(Nega*ve Cough Challenge test) Mechanical Endobronchial lesions: tumor Foreign body Fluid (post- nasal drip, pleural, pulmonary edema) Air (pneumothorax, inters))al emphysema) Irritants (environmental, occupa)onal) Flow (phona)on, snoring, hyperven)la)on) Physical Temperature ph (acid regurgita)on, bile regurgita)on)