1. Acid stress in the pathology of asthma
Fabio L.M. Ricciardolo, MD, PhD, Benjamin Gaston, MD, John Hunt, MD 
Journal of Allergy and Clinical Immunology 
Volume 113, Issue 4, Pages (April 2004)
DOI: /j.jaci

2. Fig 1
Overview: acid stress and the asthmatic phenotype. Esophageal acid is sensed and triggers airway reflexes through the vagus nerve. Acid can be inhaled as liquid or vapor during gastroesophageal reflux episodes and from ambient acid fog. Disturbance in endogenous airway pH homeostatic mechanisms may occur. Sensory nerves convey the presence of a low airway lining fluid pH to the central nervous system and also act through local axonal reflexes. Efferent nerves then trigger bronchoconstriction and cough and initiate neurogenic inflammation. Acidification of airways leads to pronounced disturbance in airway cell biology. Volatile acids in the lung are readily exhaled, and this acidopnea can be quantified. AE1, Anion exchange protein 1; BK2, bradykinin receptor 2; NHE1, Na+/H+ exchange protein 1; NOS, nitric oxide synthase; VR-1, vanilloid receptor 1.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )

3. Fig 2
Nerve pathways of acid-induced effects in the airways. In the esophagus protons activate sensory neurons that convey signals through sensory ganglia to neurons in the medulla oblongata that stimulate efferent vagus responses. Esophageal afferents of the sensory neurons may project axons to the airways, releasing neuropeptides and modulating the excitability of the parasympathetic neuronal ganglia and increasing secretions and smooth muscle constriction. Protons in the airways directly excite capsaicin-sensitive sensory nerves, leading to reflex bronchosconstriction and promoting neurogenic inflammation.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )

4. Fig 3
Acidity in the airway. Acidic loading in the airway may occur because of inhaled or aspirated acid or a deviation in the airway pH homeostatic processes. Disturbance in airway pH homeostatic mechanisms may occur through alterations in the activities of epithelial anion and cation exchange proteins and ammonia (NH3) and bicarbonate (HCO3–)–producing glutaminase. Protons (H+) sensitize vanilloid receptor 1 on the capsaicin-sensitive sensory nerves, producing local axonal reflexes with the subsequent release of tachykinins (NKA and substance P). Low pH also favors bradychinin production that, together with tachykinins, trigger bronchoconstriction and cough. Acidic airways lead to abnormal enzyme and protein function, encourage eosinophilic necrosis-inflammation, inhibit ciliary motility, alter mucous viscosity and fluid production, and affect nitric oxide production and chemistry. AE1, Anion exchange protein 1; BK2, bradykinin receptor 2; NHE1, Na+/H+ exchange protein 1; NOS, nitric oxide synthase; VR-1, vanilloid receptor 1.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )