Cough and dyspnea during bronchoconstriction: comparison of different stimuli

Suguikawa, T R; Garcia, Clécia Aparecida; Martinez, Edson Zangiacomi; Vianna, Elcio Oliveira

doi:10.1186/1745-9974-5-6

Cited by 14 publications

(11 citation statements)

References 33 publications

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“…Directly inhaled bradykinin causes a potent bronchoconstriction in asthmatic patients, but even in high concentrations has no effect in healthy individuals (Barnes, 1992). Thus, bradykinin has occasionally been suggested as a marker, more sensitive than methacholine, for demonstrating AHR (Berman et al, 1995;Suguikawa et al, 2009).…”

Section: Bradykinin and Related Kininsmentioning

confidence: 99%

Nicotine Exaggerates LPS-Induced Airway Hyperreactivity via JNK-Mediated Up-regulation of Toll-Like Receptor 4

Zhang²,

Cardell³

2014

Am J Respir Cell Mol Biol

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Tobacco smokers often display increased airway hyperreactivity (AHR) when faced with bacterial infections. The present study uses a murine organ-culture model to dissect the mechanisms involved in this exaggerated smooth muscle response. Nicotine simulates the effects of smoking, and LPS represents bacterial infection. Contractile responses of isolated murine tracheal segments were analyzed in myographs after organ culture with increasing concentrations of LPS and/or nicotine for 4 days with or without specific MAPK inhibitors. Nicotine's effect on the expression of cell surface Toll-like receptors (TLRs), MCP-1, COX-2, and TNF-α were examined by real-time PCR. Increased protein expression was verified by immunohistochemistry. LPS concentration-dependently increased contractile responses to bradykinin and des-Arg(9)-bradykinin. A combination of nicotine and low-dose LPS caused powerful synergistic contractions along with increased kinin receptor expression. Specific kinin B1 and B2 receptor inhibitors blocked this reaction. Nicotine increased mRNA and protein expression of TLR4 and -6 in the epithelium and smooth muscle layer, with MCP-1 and COX-2 mRNA increasing in parallel. Specific inhibition of JNK attenuated nicotine's effects. In conclusion, long-term exposure to nicotine up-regulated the expression of TLR4 and -6 via a JNK-related pathway, causing an exaggeration of the LPS-induced local airway inflammation and increased AHR. This might offer a mechanistic explanation to the increased AHR seen in tobacco smokers confronted with bacterial infections.

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Section: Bradykinin and Related Kininsmentioning

confidence: 99%

Nicotine Exaggerates LPS-Induced Airway Hyperreactivity via JNK-Mediated Up-regulation of Toll-Like Receptor 4

Zhang²,

Cardell³

2014

Am J Respir Cell Mol Biol

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“…No such contraction can be induced in healthy controls . Thus, bradykinin has been suggested as a more sensitive marker for airway hyperreactivity than methacholine . To assess the potential relationship between various neutrophil subsets and asthmatic hyperactivity, neutrophil subsets were co‐cultured with murine trachea, and bradykinin‐induced smooth muscle contractions were evaluated in myographs.…”

Section: Discussionmentioning

confidence: 99%

“…Bradykinin has been proposed as a sensitive indicator for AHR, found to be increased in bronchoalveolar lavage (BAL) fluid from asthmatic patients as a result of allergen challenge . In the presented paper, we have investigated the role of activated neutrophils, produced by LPS in vitro stimulation, on Bradykinin‐induced AHR.…”

Section: Introductionmentioning

confidence: 99%

Dividing neutrophils in subsets reveals a significant role for activated neutrophils in the development of airway hyperreactivity

Ekstedt

Säfholm

Georén

et al. 2018

Clin Experimental Allergy

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Background: Previous research has emphasized the importance of eosinophils in allergic asthma, while paying less attention to neutrophils. The known functionality of neutrophils in the inflammatory process has recently changed and knowledge about subsets of neutrophils, as characterized by their expression of CD16 and CD62L, has surfaced. Their specific roles in asthma are still unknown.Objective: To study the functional differences between subsets of neutrophils by characterizing the impact of individual subsets on airway smooth muscle reactivity. Methods:The direct effect of neutrophils on airway hyperresponsiveness was assessed by co-culturing different subsets of neutrophils (produced by LPS in vitro stimulation) with human isolated small airways or murine tracheae with subsequent evaluation of smooth muscle reactivity to bradykinin in myographs. Supernatants and tissue were saved for ELISA and immunohistochemistry.Results: The CD16 high CD62L dim neutrophils were found to enhance the response to bradykinin in both human isolated small airways and murine tracheae. No such effects were obtained for the other subsets. The response is due to an upregulation of bradykinin receptor 2 through release of TNFα from the neutrophil.Conclusions and Clinical Relevance: The present study introduces a new concept regarding the role of neutrophils and defines a novel direct link between a specific activated neutrophil subset and airway smooth muscle, establishing neutrophils as important players in the development of asthmatic airway hyperactivity.

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“…Nowadays, evidence to support their use to measure other symptoms, such as dyspnoea and fatigue, is mounting (19,20). In clinical trials of patients with COPD, asthma, CF or BE, breathlessness or dyspnoea is frequently measured by means of a visual analogue scale (VAS) (21)(22)(23)(24)(25)(26). VAS scores have also been applied to measure sputum volume, cough frequency and fatigue in patients with a variety of chronic respiratory diseases (22,25,27,28).…”

Section: Discussionmentioning

confidence: 99%