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Acid stress in the pathology of asthmaā˜†

https://doi.org/10.1016/j.jaci.2003.12.034Get rights and content

Abstract

Although alteration of airway pH may serve an innate host defense capacity, it also is implicated in the pathophysiology of obstructive airway diseases. Acid-induced asthma appears in association with gastroesophageal reflux after accidental inhalation of acid (fog, pollution, and workplace exposure) and in the presence of altered airway pH homeostasis. Endogenous and exogenous exposures to acids evoke cough, bronchoconstriction, airway hyperreactivity, microvascular leakage, and heightened production of mucous, fluid, and nitric oxide. Abnormal acidity of the airways is reflected in exhaled breath assays. The intimate mechanisms of acid-induced airway obstruction are dependent on activation of capsaicin-sensitive sensory nerves. Protons activate these nerves with the subsequent release of tachykinins (major mediators of this pathway) that, in conjunction with kinins, nitric oxide, oxygen radicals, and proteases, modulate diverse aspects of airway dysfunction and inflammation. The recognition that acid stress might initiate or exacerbate airway obstructive symptomatology has prompted the consideration of new therapies targeting pH homeostasis.

Section snippets

Exogenous airways acidification (inhalation of acid)

The effects of inhaled acids are primarily related to the titratable acidity as opposed to the pH of the fluid inhaled.1 A weak acid (ie, acetic acid) at a pH of 4.6 could have a greater effect on the airway than a strong acid (ie, hydrochloric acid) at the same pH because the concentration of acetic acid is much greater than the concentration of hydrochloric acid required to achieve a given pH.

Several epidemiologic studies invoke acid fogs as important risk factors for asthma and bronchitis,2.

Acid and release of tachykinins

Capsaicin-sensitive primary sensory neurons belong to a subpopulation of neurons with thinly myelinated or unmyelinated fibers of the AĪ“ and C types that contain neuropeptides.41 These neurons are named for their ability to be stimulated by capsaicin, the pungent ingredient contained in a variety of red peppers of the genus Capsicum, and express neuropeptide transmitters in their central and peripheral terminals. In 1878, A. Hƶgyes noted that the irritant action of an extract of Capsicum

Conclusions

Regulation of pulmonary lumenal pH, like that of gastrointestinal and renal tubular pH, is of physiologic importance and involves complex biochemistry. Acidification appears to represent an innate immune response and host defense mechanism that might be dysregulated in a broad spectrum of pulmonary diseases, including asthma. Although toxic to certain airway pathogens, this endogenous acidification, like exogenous acidification, also can contribute to pulmonary pathology through diverse

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    ā˜†

    Dr Ricciardolo was supported by the Italian Ministry of Health (Ricerca Corrente 2001), and Drs Gaston and Hunt were supported by the United States National Institutes of Health/National Heart Lung and Blood Institute and The American Academy of Allergy, Asthma and Immunology Education and Research Trust. Dr Hunt is a Parker B. Francis Fellow in Pulmonary Research.

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