Allergen challenge increases capsaicin-evoked cough responses in patients with allergic asthma

Satia, Imran; Watson, Richard M.; Scime, Tara; Dockry, Rachel; Sen, Shilpi; Ford, J Webber; Mitchell, Patrick; Fowler, Stephen J.; Gauvreau, Gail M.; O'Byrne, Paul M.; Smith, Jaclyn A.

doi:10.1016/j.jaci.2018.11.050

Cited by 41 publications

(33 citation statements)

References 32 publications

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“…These observations were demonstrated by studies on the same animal model showing that inhibition of the TRPV1 mRNA and protein expression using various antagonists including capsazepine caused an improvement in pulmonary function, decreased airway hyperresponsiveness, and reduced cytokine concentrations in aggravated asthma ( 145 , 147-149 ). In addition, the use of allergens to induce bronchoconstriction seems to increase the TRPV1 response to capsaicin, increasing cough reflex sensitivity, as demonstrated in a recent clinical trial ( 150 ). The effects of stimulating TRPV1 receptors with capsaicin are increased in mice with atopic dermatitis to the extent that asthmatic-like inflammation of the airways is produced while compliance of the lungs is decreased ( 151 ).…”

Section: Capsaicin In Asthmamentioning

confidence: 90%

Comparative effects of capsaicin in chronic obstructive pulmonary disease and asthma (Review)

et al. 2021

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Chronic obstructive pulmonary disease (COPD) and asthma are chronic respiratory diseases with high prevalence and mortality that significantly alter the quality of life in affected patients. While the cellular and molecular mechanisms engaged in the development and evolution of these two conditions are different, COPD and asthma share a wide array of symptoms and clinical signs that may impede differential diagnosis. However, the distinct signaling pathways regulating cough and airway hyperresponsiveness employ the interaction of different cells, molecules, and receptors. Transient receptor potential cation channel subfamily V member 1 (TRPV1) plays a major role in cough and airway inflammation. Consequently, its agonist, capsaicin, is of substantial interest in exploring the cellular effects and regulatory pathways that mediate these respiratory conditions. Increasingly more studies emphasize the use of capsaicin for the inhalation cough challenge, yet the involvement of TRPV1 in cough, bronchoconstriction, and the initiation of inflammation has not been entirely revealed. This review outlines a comparative perspective on the effects of capsaicin and its receptor in the pathophysiology of COPD and asthma, underlying the complex entanglement of molecular signals that bridge the alteration of cellular function with the multitude of clinical effects.

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Section: Capsaicin In Asthmamentioning

confidence: 90%

Comparative effects of capsaicin in chronic obstructive pulmonary disease and asthma (Review)

et al. 2021

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“…In a study of human asthmatics, the number of airway and blood eosinophils correlated with the length of airway nerves and the number of nerve branch points [ 42 ]. In addition, in another study of allergic asthmatics, allergen inhalation challenge significantly increased capsaicin cough responses and also spontaneous coughs over 24 hours in allergic asthmatics, compared to diluent inhalation (negative control) [ 43 ]. Cigarette smoke extracts or particulate matter 2.5 may also provoke similar changes in the airway nervous systems, although precise effects may differ between stimuli [ 44 - 46 ].…”

Section: Insights From Recent Mechanistic Studiesmentioning

confidence: 99%

Recent progress in the management of chronic cough

Song

McGarvey

2020

Korean J Intern Med

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Chronic cough is a common clinical condition with significant impact on quality of life and for which effective therapy remains an unmet clinical need. Over the past decade, there has been a major shift in how we approach this problem, driven by better appreciation of the clinical manifestation of chronic cough and an improved understanding of the associated neurobiology. "Cough hypersensitivity syndrome" has been proposed as a new diagnostic term for chronic cough, encompassing different phenotypes of the condition. Accumulating evidence suggests that this new concept is clinically relevant. However, while it is gaining widespread endorsement within the allergy and respiratory community, raising its profile in routine clinical practice is a priority. Thus, the present paper reviews recent progress in our understanding and management of chronic cough, with focus on mechanistic and clinical studies. It also provides detail on knowledge gaps and future research directions.

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“…Previous observational data from subjects with mild/moderate asthma showed no relationship between capsaicin cough responses or 24-hour cough counts and blood (9) or sputum (12) eosinophil counts at baseline. However, after allergen challenge, an increase in sputum eosinophils after 24 hours was associated with increased capsaicin-evoked cough responses (13). This implies that inducing eosinophilic airway inflammation sensitizes the airway nerves.…”

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confidence: 99%

Identifying a Neurophenotype in Severe Asthma

Satia

O’Byrne

2020

Am J Respir Crit Care Med

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Understanding why excessive symptoms and frequent exacerbations are poorly controlled in patients with severe asthma is a major unmet need. Uncontrolled daily symptoms despite high-dose inhaled (or oral) corticosteroids with or without bronchodilators impose a major burden on the lives of patients, with implications for their work and social and family life, and exacerbations are costly for healthcare systems (1-4). Symptoms are difficult to measure because they are highly subjective and can be confounded by anxiety or depression. Cough is a common troublesome asthma symptom that can be experimentally evoked by inhaled cough stimuli (5) and objectively quantified by 24-hour cough monitoring (6). Capsaicin is a commonly used cough challenge agent that is known to activate TRPV1 (transient receptor potential vanilloid-1), which is found predominantly on unmyelinated c-fibers (7). Hence, capsaicin cough challenge can be used as an experimental model to investigate functional nerve responses in patients with asthma. In a study presented in this issue of the Journal, Kanemitsu and colleagues (pp. 1068-1077) investigated the associations of capsaicin cough reflex sensitivity, as measured by the concentration of capsaicin causing two or five coughs (C2/C5), with clinical, physiological, and inflammatory features in patients with severe asthma (8). The clinical features were divided into two groups based on a combination of the degree of asthma control as measured by Asthma Control Questionnaire (.1.5) or Asthma Control Test (,20), exacerbation frequency (>2 burst of oral steroids for >3 d), and hospitalizations (>1). In a univariate analysis, heightened cough reflex sensitivity (lower C2/C5) and higher absolute serum neutrophil counts (.5,000/ml) were associated with poor asthma control, frequent exacerbations, and hospitalizations. However, this was confined mainly to nonatopic patients, where the mechanisms of clinical features remain poorly understood. In a multivariate analysis, heightened C5 increased the odds of poor asthma control (odds ratio [OR], 4.83), exacerbations (OR, 2.83), and a trend toward hospitalization (OR, 3.43). When compared with other variables, poor asthma control (Asthma Control Test , 20) was most strongly influenced by heightened cough reflex sensitivity (C5), followed by FEV 1 , 80% predicted, with some borderline significant contributions from being a nonatopic, ex-smoker with higher serum neutrophil counts. In contrast, greater exacerbation frequency (>2) was most strongly influenced by FEV 1 , 80% predicted, followed by heightened cough reflex sensitivity and a borderline significant contribution from being female (OR, 3.34). Finally, hospitalizations were influenced most strongly by patients who were ex-smokers, with a FEV 1 , 80% predicted, raising the possibility these patients had chronic airflow limitation.

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Allergen challenge increases capsaicin-evoked cough responses in patients with allergic asthma

Cited by 41 publications

References 32 publications

Comparative effects of capsaicin in chronic obstructive pulmonary disease and asthma (Review)

Comparative effects of capsaicin in chronic obstructive pulmonary disease and asthma (Review)

Recent progress in the management of chronic cough

Identifying a Neurophenotype in Severe Asthma

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