Prostaglandin E<sub>2</sub>Inhalation Increases the Sensation of Dyspnea during Exercise

Taguchi, Osamu; Kikuchi, Yoshihiro; Hida, Wataru; Iwase, Nobuhisa; Okabe, Shinichi; Chonan, Tatsuya; Takishima, Tamotsu

doi:10.1164/ajrccm/145.6.1346

Cited by 35 publications

(25 citation statements)

References 10 publications

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“…Conversely, drugs known to stimulate airway nociceptors have been shown to cause dyspnea in humans without affecting airway resistance. Drugs in this category include prostaglandin E 2 and adenosine (52,53).…”

Section: Dyspneamentioning

confidence: 99%

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

Undem

Kollárik

2005

Proceedings of the American Thoracic Society

104

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Circumstantial evidence supports the hypothesis that the vagal nervous system is dysregulated in chronic obstructive pulmonary disease. This dysregulation can lead to an increased sensitivity of the cough reflex such that the coughing becomes, at times, "nonproductive" or inappropriate. Vagal dysregulation can also lead to an increase in the activity of the parasympathetic reflex control of the airways, which contributes to greater mucus secretion and bronchial smooth muscle contraction. Indirect evidence indicates that lung disease is accompanied by substantive changes to the entire reflex pathways, including enhanced activity of the primary afferent nerves, increases in synaptic efficacy at secondary nerves in the central nervous system, and changes in the autonomic nerve pathways. Drugs aimed at normalizing neuronal activity may, therefore, be beneficial in chronic obstructive pulmonary disease.

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Section: Dyspneamentioning

confidence: 99%

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

Undem

Kollárik

2005

Proceedings of the American Thoracic Society

104

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“…PGE 2 is also known to activate sensory endings in the lung. For example, inhalation of aerosolized PGE 2 elicits coughs and retrosternal soreness without significant change in baseline airway resistance (31,32) and augments the dyspneic sensation during exercise (31) in healthy human subjects. Inhalation of PGE 2 aerosol also induces reflex bronchoconstriction in asthmatic patients, despite its potent direct dilating effect on airway smooth muscles (27).…”

Section: Excitability Of Airway Afferents Modulated By Inflammatory Mmentioning

confidence: 99%

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Lee

Widdicombe

2001

Environ Health Perspect

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Among the three major types of sensory receptors innervating the airways and lungs, C-fiber endings and rapidly adapting pulmonary receptors (RARs or irritant receptors) are believed to be primarily responsible for eliciting the reflex responses in defending the lungs against inhaled irritants and toxins (1-3). The third type, slowly adapting pulmonary receptors (SARs or stretch receptors), plays an important role in regulating the respiratory volume-timing relationship (4), and is considered to be pure mechanoreceptor and relatively insensitive to chemical irritants. Several recent studies have attempted to uncover the mechanisms underlying the interaction between the pulmonary C fibers and RARs in the overall regulation of the defense reflex responses. Inhalation of cigarette smoke, a common inhaled irritant in human airways, has been shown to elicit irregular breathing pattern, cough reflex, and bronchoconstriction in a number of species including humans (5-9). Although it is believed that most of these responses are mediated through the activation of these two types of vagal afferents, the relative contributions of these two types of afferents to the emergence of these reflex responses are not known. In anesthetized animals (dogs, cats, or rats), spontaneous inhalation of one to two tidal breaths of cigarette smoke into the lungs via a tracheal cannula immediately elicited pulmonary chemoreflexes, characterized by apnea, bradycardia, and hypotension, known to be elicited by activation of pulmonary C fibers (1-3,6). After perineural capsaicin treatment of both cervical vagi to selectively block the conduction of capsaicin-sensitive C fibers, inhaled cigarette smoke no longer evoked any inhibitory effect on breathing (9). Conversely, an augmented inspiration, a reflex effect of activating RARs, was triggered within the first three breaths from the onset of cigarette smoke inhalation in > 85% of the rats studied (Figure 1). When the temperature of the vagus nerve was cooled progressively to 6-7 °C to block the conduction of myelinated afferents, as indicated by the ablation of the apneic response to lung inflation, the augmented breaths evoked by the cigarette smoke inhalation were also abolished (9). Both the apnea and augmented breath evoked by inhaled cigarette smoke were completely abolished by bilateral cervical vagotomy. Similarly, augmented breaths were also elicited when other chemical irritants such as sulfur dioxide (SO 2 ) (9), ammonia (NH 3 ) (9), acrolein (10), and wood smoke (11) were inhaled after the perineural capsaicin treatment of both vagi in anesthetized rats.It is interesting to note that augmented breaths were consistently elicited by inhaled irritants only after the conduction in bronchopulmonary C-fiber afferents are blocked by perineural capsaicin treatment of both vagi but were rarely seen when the same irritants were inhaled in the same animals with intact C fibers (9-11). These results suggest that both vagal bronchopulmonary C-fiber afferents and RARs are stimulated by these inhale...

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“…Different stimuli may have different effects on the pulmonary receptors. Prostaglandin E2, a mediator that increases sensory nerve excitability, exacerbates the dyspnea associated with exercise, despite the fact that it is a bronchodilator (49). Histamine inhalation leads to a more profound dyspnea than methacholine, despite a similar degree of bronchoconstriction (50,51).…”

Section: Dyspneamentioning

confidence: 99%

Diagnosis of asthma – a new approach

Löwhagen

2012

Allergy

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Current definition of asthma involves four cornerstones: inflammation, hyperresponsiveness, bronchoconstriction, and symptoms. In research, the symptoms have had the slightest attention. According to international guidelines, the asthma symptoms are episodic breathlessness, wheeze, cough, tightness of the chest, and shortness of breath. As there are several symptoms, a primary question is how they are related to bronchoconstriction, the main clinical feature of asthma. Symptoms and lung function tests are regularly used for the evaluation of clinical health status and effect of treatment. However, there is no or poor correlation between these two variables, which means that they represent different mechanisms. Reduced lung function, such as a low FEV 1 , represents bronchial constriction, what do the symptoms represent? Some symptoms such as breathlessness and shortness of breath seem not to be evidence-based asthma symptoms. Focusing on bronchial obstruction is important in view of the potential risk of asthma attacks, but nonobstructive symptoms occur frequently and may also cause severe discomfort and poor quality of life. Interpreting all symptoms as signs of bronchoconstriction (asthma) may lead to misinterpretation when assessing health status and effect of treatment. Although a 'soft' variable, the strength of symptoms is that they are representing various mechanisms. The physiological preconditions for control and defense of respiration must be considered in the diagnostic process, regardless of inflammation, allergy, psychology, or other etiological factors. Based on studies on dyspnea in cardiopulmonary diseases, including asthma and asthma-like disorders, there seems to be a continuous spectrum of symptoms and mechanisms integrated in a single asthma syndrome.

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Prostaglandin E₂Inhalation Increases the Sensation of Dyspnea during Exercise

Cited by 35 publications

References 10 publications

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Diagnosis of asthma – a new approach

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Prostaglandin E2Inhalation Increases the Sensation of Dyspnea during Exercise

Cited by 35 publications

References 10 publications

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Diagnosis of asthma – a new approach

Contact Info

Product

Resources

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Prostaglandin E₂Inhalation Increases the Sensation of Dyspnea during Exercise