Airway oxidative stress in chronic cough

Koskela, Heikki; Purokivi, Minna

doi:10.1186/1745-9974-9-26

Cited by 6 publications

(4 citation statements)

References 57 publications

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“…Exhaled breath condensate (EBC) concentration of 8-isoprostane reflects airway oxidative stress. It is higher in patients with chronic cough than in healthy subjects and, among the cough patients, correlates with the impairment in the cough-related quality of life [88]. In asthma, high concentration of 8-isoprostane in EBC is associated with poor cough-related quality of life and with the degree of cough responsiveness to dry air hyperpnoea.…”

Section: The Ability Of Cpthas To Differentiate Subjects With Asthma mentioning

confidence: 98%

Cough-provocation tests with hypertonic aerosols

2020

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Recent advances in cough research suggest a more widespread use of cough-provocation tests to demonstrate the hypersensitivity of the cough reflex arc. Cough-provocation tests with capsaicin or acidic aerosols have been used for decades in scientific studies. Several factors have hindered their use in everyday clinical work: i.e. lack of standardisation, the need for special equipment and the limited clinical importance of the response. Cough-provocation tests with hypertonic aerosols (CPTHAs) involve provocations with hypertonic saline, hypertonic histamine, mannitol and hyperpnoea. They probably act via different mechanisms than capsaicin and acidic aerosols. They are safe and well tolerated and the response is repeatable. CPTHAs can assess not only the sensitivity of the cough reflex arc but also the tendency of the airway smooth muscles to constrict (airway hyper-responsiveness). They can differentiate between subjects with asthma or chronic cough and healthy subjects. The responsiveness to CPTHAs correlates with the cough-related quality of life among asthmatic subjects. Furthermore, the responsiveness to them decreases during treatment of chronic cough. A severe response to CPTHAs may indicate poor long-term prognosis in chronic cough. The mannitol test has been stringently standardised, is easy to administer with simple equipment, and has regulatory approval for the assessment of airway hyper-responsiveness. Manual counting of coughs during a mannitol challenge would allow the measurement of the function of the cough reflex arc as a part of clinical routine.

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Section: The Ability Of Cpthas To Differentiate Subjects With Asthma mentioning

confidence: 98%

Cough-provocation tests with hypertonic aerosols

2020

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“…On the other hand, the increased oxidative stress pathways at baseline and induced by poly(I:C) in ASMC from chronic cough patients is of interest. It has been previously reported that increased airway oxidative stress is associated with chronic cough [ 24 ]. Recent work has indicated that oxidative stress, in particular downstream of mitochondrial dysfunction, activates airway nociceptive sensory nerves that may contribute to an excessive cough reflex [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Impaired innate immune gene profiling in airway smooth muscle cells from chronic cough patients

et al. 2017

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Chronic cough is associated with airway inflammation and remodelling. Abnormal airway smooth muscle cell (ASMC) function may underlie mechanisms of chronic cough. Our objective was to examine the transcriptome and focused secretome of ASMCs from chronic cough patients and healthy non-cough volunteers. ASMC gene expression profiling was performed at baseline and/or after stimulation with polyinosinic:polycytidylic acid (poly(I:C)) to mimic viral infection. Supernatants were collected for multiplex analysis. Our results showed no significant differentially expressed genes (DEGs, false discovery rate (FDR) <0.05) between chronic cough and healthy non-cough ASMCs at baseline. Poly(I:C) stimulation resulted in 212 DEGs (>1.5 fold-change, FDR <0.05) in ASMCs from chronic cough patients compared with 1674 DEGs in healthy non-cough volunteers. The top up-regulated genes included chemokine (C–X–C motif) ligand (CXCL) 11 (CXCL11), CXCL10, chemokine (C–C motif) ligand (CCL) 5 (CCL5) and interferon-induced protein 44 like (IFI44L) corresponding with inflammation and innate immune response pathways. ASMCs from cough subjects had enhanced activation of viral response pathways in response to poly(I:C) compared with healthy non-cough subjects, reduced activation of pathways involved in chronic inflammation and equivalent activation of neuroregulatory genes. The poly(I:C)-induced release of inflammatory mediators, including CXCL8, interleukin (IL)-6 and CXCL1, from ASMCs from cough patients was significantly impaired compared with healthy non-cough subjects. Addition of fluticasone propionate (FP) to poly(I:C)-treated ASMCs resulted in greater gene expression changes in healthy non-cough ASMCs. FP had a differential effect on poly(I:C)-induced mediator release between chronic cough and healthy non-cough volunteers. In conclusion, altered innate immune and inflammatory gene profiles within ASMCs, rather than infiltrating cells or nerves, may drive the cough response following respiratory viral infection.

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“…Additionally, it facilitates comparison of epidemiological results. Recent population-based studies and clinical trials utilise one of the aforementioned testing methods each: Sovij€ arvi [30][31][32][33][34][35][36][37], Malmberg [38][39][40][41] or Nieminen [14,[42][43][44]; the reference table may serve the purpose of offering comparisons in these example studies and others, or in future studies. Nowadays, the supply of histamine as a challenge test substance is very limited, therefore, a comparison to other challenge methods was also needed.…”

Section: Utilitymentioning

confidence: 99%

Measurement of bronchial hyperreactivity: comparison of three Nordic dosimetric methods

Lassmann-Klee

Sundblad

Malmberg

et al. 2020

Scandinavian Journal of Clinical and Laboratory Investigation

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Clinical testing of bronchial hyperreactivity (BHR) provides valuable information in asthma diagnostics. Nevertheless, the test results depend to a great extent on the testing procedure: test substance, apparatus and protocol. In Nordic countries, three protocols predominate in the testing field: Per Malmberg, Nieminen and Sovij€ arvi methods. However, knowledge of their equivalence is limited. We aimed to find equivalent provocative doses (PD) to obtain similar bronchoconstrictive responses for the three protocols. We recruited 31 patients with suspected asthma and health care workers and performed BHR testing with methacholine according to Malmberg and Nieminen methods, and with histamine according to Sovij€ arvi. We obtained the individual response-dose slopes for each method and predicted equivalent PD values. Applying a mixed-model, we found significant differences in the mean (standard error of mean) response-dose (forced expiratory volume in one second (FEV 1 )%/mg): Sovij€ arvi 7.2 (1.5), Nieminen 13.8 (4.2) and Malmberg 26 (7.3). We found that the earlier reported cutpoint values for moderate BHR and marked BHR between the Sovij€ arvi (PD 15 ) and Nieminen (PD 20 ) methods were similar, but with the Malmberg method a significant bronchoconstrictive reaction was measured with lower PD 20 values. We obtained a relationship between slope values and PD (mg) between different methods, useful in epidemiological research and clinical practice.

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Airway oxidative stress in chronic cough

Cited by 6 publications

References 57 publications

Cough-provocation tests with hypertonic aerosols

Cough-provocation tests with hypertonic aerosols

Impaired innate immune gene profiling in airway smooth muscle cells from chronic cough patients

Measurement of bronchial hyperreactivity: comparison of three Nordic dosimetric methods

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