Tiotropium Attenuates Refractory Cough and Capsaicin Cough Reflex Sensitivity in Patients with Asthma

Fukumitsu, Kensuke; Kanemitsu, Yoshihiro; Asano, Tomohiko; Takeda, Norihisa; Ichikawa, Hiroya; Yap, Jennifer Maries; Fukuda, Satoshi; Uemura, Takashi; Takakuwa, Osamu; Ohkubo, Hirotsugu; Maeno, Ken; Ito, Yutaka; Oguri, Tetsuya; Nakamura, Atsushi; Takemura, Masashi; Niimi, Akio

doi:10.1016/j.jaip.2018.01.016

Cited by 48 publications

(27 citation statements)

References 46 publications

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“…Some reports have indicated that the use of anticholinergic agents, such as tiotropium, improves refractory cough in asthma patients and augments the threshold to this substance during the challenge. This suggests that tiotropium suppresses the neuronal activity of TRPV1, a mechanism independent of the muscarinic type 3 (M3) receptor blockade ( Fukumitsu et al, 2018 ).…”

Section: Bronchial Airwaymentioning

confidence: 99%

Neuroimmune Pathophysiology in Asthma

Pavón-Romero

Serrano-Pérez

García-Sánchez

et al. 2021

Front. Cell Dev. Biol.

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Asthma is a chronic inflammation of lower airway disease, characterized by bronchial hyperresponsiveness. Type I hypersensitivity underlies all atopic diseases including allergic asthma. However, the role of neurotransmitters (NT) and neuropeptides (NP) in this disease has been less explored in comparison with inflammatory mechanisms. Indeed, the airway epithelium contains pulmonary neuroendocrine cells filled with neurotransmitters (serotonin and GABA) and neuropeptides (substance P[SP], neurokinin A [NKA], vasoactive intestinal peptide [VIP], Calcitonin-gene related peptide [CGRP], and orphanins-[N/OFQ]), which are released after allergen exposure. Likewise, the autonomic airway fibers produce acetylcholine (ACh) and the neuropeptide Y(NPY). These NT/NP differ in their effects; SP, NKA, and serotonin exert pro-inflammatory effects, whereas VIP, N/OFQ, and GABA show anti-inflammatory activity. However, CGPR and ACh have dual effects. For example, the ACh-M3 axis induces goblet cell metaplasia, extracellular matrix deposition, and bronchoconstriction; the CGRP-RAMP1 axis enhances Th2 and Th9 responses; and the SP-NK1R axis promotes the synthesis of chemokines in eosinophils, mast cells, and neutrophils. In contrast, the ACh-α7nAChR axis in ILC2 diminishes the synthesis of TNF-α, IL-1, and IL-6, attenuating lung inflammation whereas, VIP-VPAC1, N/OFQ-NOP axes cause bronchodilation and anti-inflammatory effects. Some NT/NP as 5-HT and NKA could be used as biomarkers to monitor asthma patients. In fact, the asthma treatment based on inhaled corticosteroids and anticholinergics blocks M3 and TRPV1 receptors. Moreover, the administration of experimental agents such as NK1R/NK2R antagonists and exogenous VIP decrease inflammatory mediators, suggesting that regulating the effects of NT/NP represents a potential novel approach for the treatment of asthma.

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Section: Bronchial Airwaymentioning

confidence: 99%

Neuroimmune Pathophysiology in Asthma

Pavón-Romero

Serrano-Pérez

García-Sánchez

et al. 2021

Front. Cell Dev. Biol.

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“…A study in rabbits showed that acid-sensing ion channels and mechanoreceptors might mediate LAMA-induced downregulation of cough (Mutolo et al, 2016). Furthermore, modulation of cough reflex sensitivity, but not bronchodilation, is the mechanism by which tiotropium bromide may alleviate asthmatic cough refractory to LABA/ICS (Fukumitsu et al, 2018), although mAChR antagonists do not inhibit ozone-induced hypertussive responses at doses that are bronchodilatory (Clay et al, 2016). Results from phase III studies suggest that aclidinium bromide (400 mg) taken twice-a-day may improve cough by reducing, in particular, night-time cough frequency and severity (McGarvey et al, 2016).…”

Section: B Bronchodilators and Comorbiditiesmentioning

confidence: 99%

Pharmacology and Therapeutics of Bronchodilators Revisited

et al. 2019

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“…They do exert antitussive effects, but unlikely to modulate CRS (19). Treatment options of CRS in asthma may include LTRAs, tiotropium, and bronchial thermoplasty despite very preliminary (19,(29)(30)(31)(32).…”

Section: Review Article On the 3rd International Cough Conferencementioning

confidence: 99%

“…It is very important to note that the presence of chronic cough (33,34), increase of objective cough frequency (35), and heightened CRS to hypertonic saline/isocapnic hyperpnea (36) and capsaicin (37,38) in individuals with asthma are all associated with poor control or prognosis and more severe disease phenotype (Figure 3) (38). The treatment strategy of cough or CRS is therefore essential in asthma, especially those with nonatopic disease (31,37,38) and daytime coughing that is often refractory (39), despite night-time cough is characteristic of asthma (40). Eosinophils play important roles in the pathogenesis of cough of asthma (41), but ICSs Figure 2 Prevalence of classic asthma and CVA patients in two novel phenotypes of asthma defined by the predominant cite of eosinophilic airway inflammation (19,22).…”

Section: Review Article On the 3rd International Cough Conferencementioning

confidence: 99%

Narrative Review: how long should patients with cough variant asthma or non-asthmatic eosinophilic bronchitis be treated?

Niimi

2021

J Thorac Dis

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The causes of chronic cough can be categorized into eosinophilic and noneosinophilic disorders, and approximately 30% to 50% of people with chronic cough have eosinophilic airway inflammation, the presence of which can be confirmed by sputum eosinophilia or elevated exhaled nitric-oxide levels. Cough variant asthma (CVA) is a phenotype of asthma which lacks wheezing or dyspnea, and consistently one of the most common causes of chronic cough worldwide. CVA and non-asthmatic eosinophilic bronchitis (NAEB) shares common feature such as chronic dry cough, eosinophilic inflammation, and development of chronic airflow obstruction (CAO) and asthma in a subset of patients. The distinctive characteristic of these conditions is the presence of airway hyperresponsiveness in CVA but not in NAEB. Coughing is responsive to bronchodilators such as beta-agonists in CVA, but such feature has not been clarified in NAEB. Inhaled corticosteroids (ICSs) are the first-line treatment, and leukotriene receptor antagonists are also effective, in patients with both CVA and NAEB. This review will give an outline of clinical and physiological features, and prognosis and its determinants of CVA and EBNA. Further, the rationale and evidence, despite limited, for the need of long-term treatment will be discussed. The development of airway remodeling due to mechanical stress to the airways exerted by long-standing coughing will also be discussed.

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Tiotropium Attenuates Refractory Cough and Capsaicin Cough Reflex Sensitivity in Patients with Asthma

Cited by 48 publications

References 46 publications

Neuroimmune Pathophysiology in Asthma

Neuroimmune Pathophysiology in Asthma

Pharmacology and Therapeutics of Bronchodilators Revisited

Narrative Review: how long should patients with cough variant asthma or non-asthmatic eosinophilic bronchitis be treated?

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