Publications by authors named "Plevkova Jana"

22 Publications

  • Page 1 of 1

The effect of the voltage-gated sodium channel Na1.7 blocker PF-05089771 on cough in the guinea pig.

Respir Physiol Neurobiol 2022 05 31;299:103856. Epub 2022 Jan 31.

Department of Pathophysiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. Electronic address:

Cough in chronic respiratory diseases is a common symptom associated with significant comorbidities including visceral pain. Available antitussive therapy still has limited efficacy. Recent advances in the understanding of voltage-gated sodium channels (Nas) lead to the rational hypothesis that subtype Na1.7 is involved in initiating cough and thus may present a promising therapeutic target for antitussive therapy. We evaluated the antitussive effect of Na1.7 blocker PF-05089771 administered systemically and topically in awake guinea pigs using capsaicin cough challenge. Compared to vehicle, peroral or inhaled PF-05089771 administration caused about 50-60 % inhibition of cough at the doses that did not alter respiratory rate. We conclude that the Na1.7 blocker PF-05089771 inhibits cough in a manner consistent with its electrophysiological effect on airway C-fibre nerve terminals.
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http://dx.doi.org/10.1016/j.resp.2022.103856DOI Listing
May 2022

Animal models of cough.

Respir Physiol Neurobiol 2021 08 26;290:103656. Epub 2021 Mar 26.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathophysiology, Martin, Slovakia. Electronic address:

Cough is a vital airway reflex that keeps the respiratory tract wisely protected. It is also a sign of many diseases of the respiratory system and it may become a disease in its own right. Even though the efficacy of antitussive compounds is extensively studied in animal models with promising results, the treatment of pathological cough in humans is insufficient at the moment. The limited translational potential of animal models used to study cough causes, mechanisms and possible therapeutic targets stems from multiple sources. First of all, cough induced in the laboratory by mechanical or chemical stimuli is far from natural cough present in human disease. The main objective of this review is to provide a comprehensive summary of animal models currently used in cough research and to address their advantages and disadvantages. We also want to encourage cough researchers to call for precision is research by addressing the sex bias which has existed in basic cough research for decades and discuss the role of specific pathogen-free (SPF) animals.
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http://dx.doi.org/10.1016/j.resp.2021.103656DOI Listing
August 2021

Changes of Motile Ciliary Phenotype in Patients with Primary Ciliopathies.

Adv Exp Med Biol 2021 ;1335:79-85

Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.

Primary ciliopathies are a group of disorders associated with abnormal formation and function of primary cilia. Many cilia-associated proteins found in primary cilia are also present in motile cilia. Such proteins are important for the ciliary base, such as the transition zone or basal bodies, and the intraflagellar transport. Their exact role in the respiratory motile cilia is unsettled. In this prospective clinical single-center study, we investigated the hypothesis that these proteins regulate the function of motile cilia. We addressed the issue by defining the motile cilia beat frequency in the respiratory tract of patients with primary ciliopathies accompanied by chronic kidney disease and comparing it in those without kidney involvement. Ciliary beat frequency in the nasal mucosa samples was evaluated by the ciliary analysis software LabVIEW. Both children and their parents with primary ciliopathies and kidney involvement had significantly lower median airway ciliary beat frequencies than those without kidney involvement who have normal ciliary motility. Further, the ciliary beat frequency is inversely associated with the serum creatinine level. These findings strongly suggest that kidney involvement in patients with primary ciliopathy may underlie the development of motile cilia dysfunction in the respiratory tract, potentially increasing respiratory morbidity.
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http://dx.doi.org/10.1007/5584_2021_617DOI Listing
November 2021

Volume feedback during cough in anesthetized cats, effects of occlusions and modulation summary.

Respir Physiol Neurobiol 2021 01 14;283:103547. Epub 2020 Sep 14.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Medical Biophysics, Mala Hora 4, 03601, Martin, Slovakia.

The study investigates the effects of 6 occlusion conditions on the mechanically induced cough reflex in 15 anesthetized (pentobarbital) spontaneously breathing cats (14♂, 1♀). Esophageal pressure and integrated EMG activities of inspiratory (I) diaphragm and expiratory (E) abdominal muscles were recorded and analyzed. Occlusions: inspiratory (Io), continual I (cIo), during I and active E (I+Eo) cough phase, during I and then E phase with short releasing of airflow before each phase (I-Eo), and E occlusion (Eo) had little influence on cough number. Only continual E occlusion (cEo) reduced the number of coughs by 19 % (to 81 %, p < 0.05). Cough I esophageal pressure reached higher amplitudes under all conditions, but only Eo caused increased I diaphragm motor drive (p < 0.05). Cough E efforts (abdominal motor drive and E amplitudes of esophageal pressure) increased during Eo, decreased during I+Eo (p  < 0.05), and did not change significantly under other conditions (p > 0.05). All I blocks resulted in prolonged I cough characteristics (p < 0.05) mainly cough I phase (incrementing part of the diaphragm activity). Shorter I phase occurred with cEo (p < 0.05). Cough cycle time and active E phase (from the I maximum to the end of cough E motor drive) prolonged (p < 0.05) during all occlusions (E phase duration statistically non-significantly for I+Eo). Airflow block during cough (occlusions) results in secondary changes in the cough response due to markedly altered function of cough central pattern generator and cough motor pattern produced. Cough compensatory effects during airflow resistances are more favorable compared to occlusions. Volume feedback represents significant factor of cough modulation under various pathological obstruction and/or restriction conditions of the respiratory system.
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http://dx.doi.org/10.1016/j.resp.2020.103547DOI Listing
January 2021

Retrospective Study of Factors Potentially Influencing Occurrence of Cough in Slovak Patients with Sarcoidosis.

Can Respir J 2019 2;2019:3808206. Epub 2019 Jun 2.

Department of Pathophysiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.

Introduction: Sarcoidosis is a multisystem granulomatous disease of unknown aetiology, commonly involving the lungs.  Cough is a frequent and troublesome symptom of sarcoidosis that reduces patients' quality of life.

Aim: Retrospective analysis of different factors-smoking history, Scadding stage, results of lung function testing, calcium metabolism, endobronchial finding, CD4+/CD8+ T-cell ratio in bronchoalveolar lavage fluid (BALF), and other sarcoidosis symptoms in relationship to presence/absence of cough in sarcoidosis patients.

Methods: We retrospectively studied sarcoidosis patients diagnosed at the Clinic of Pneumology and Phthisiology of Martin University Hospital between 1998 and 2018. Patients with a history of cough-relevant comorbidities were excluded from the study. GraphPad Prism 7.0 software was used to perform statistical analysis.

Results: 101 sarcoidosis patients were included to the study: 65 patients reporting from cough and 36 without cough. The cough was slightly more frequent in nonsmokers (=0.166) and in women (=0.688). Cough was associated with dyspnoea (=0.0007), fever (=0.0324), and chest pain (=0.0206) and did not associate with arthralgia (=0.317) and erythema nodosum (=0.505). Patients with cough had significantly a lower average value of calciuria (=0.0014) and lower MEF25 (=0.0304), MEF50 (=0.0061), FEV1 (=0.0025), and FVC (=0.0025) in % of predicted values, and more often positive endobronchial finding (=0.0206), compared to patients without cough. Calcemia, FEV1/FVC, DLCO, and CD4+/CD8+ T-cell ratio in BALF and occurrence of cough did not differ between different stages of the disease.

Conclusions: We found significant differences between sarcoidosis patients with/without cough regarding symptoms, results of lung function tests, endobronchial finding, and calcium metabolism. Further research is needed to understand the etiopathogenesis of cough in sarcoidosis patients.
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http://dx.doi.org/10.1155/2019/3808206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589189PMC
April 2020

Cough and airway defence - Special issue of respiratory physiology and neurobiology.

Respir Physiol Neurobiol 2018 11 13;257:1-4. Epub 2018 Apr 13.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathophysiology, Slovakia.

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http://dx.doi.org/10.1016/j.resp.2018.04.004DOI Listing
November 2018

Sensitivity of airway cough-related afferents is influenced by female sex hormones.

Respir Physiol Neurobiol 2018 11 8;257:12-17. Epub 2018 Jan 8.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathophysiology, Slovak Republic; Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Biomedical Center, Division of Neuroscience, Slovak Republic; Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Simulation Education Center, Slovak Republic. Electronic address:

Chronic hypersensitivity cough syndrome affects mainly postmenopausal women; however, the pathogenesis of cough hypersensitivity in this demographic is not entirely understood. The role of sex hormones in cough has never been studied in detail; however, sex hormones seem to play an important role in the lung health of women. Our study was aimed to analyse the effect of female sex hormones (oestrogen - E2 and progesterone - Pg) on cough sensitivity measured by inhalation of capsaicin in follicular and luteal phases of menstrual cycle, characterized by significantly different concentrations of sex hormones. These data were compared with a matched group of women taking oral contraceptives. Cough sensitivity to capsaicin increased in luteal phase in subjects with normal menstrual cycle, and this functional change was not present in group with contraceptive pills. The cough sensitivity correlates with the Pg/E2 ratio, and relative lack of oestrogen in luteal phase is associated with higher cough sensitivity to capsaicin.
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http://dx.doi.org/10.1016/j.resp.2018.01.006DOI Listing
November 2018

Cough in sarcoidosis patients.

Respir Physiol Neurobiol 2018 11 4;257:18-24. Epub 2018 Jan 4.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathophysiology, Slovakia; Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Biomedical Center, Division of Neuroscience, Slovakia; Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Simulation Education Center, Slovakia.

Sarcoidosis is a multi-system disease of unknown aetiology characterized by presence of non-caseating granulomatous inflammation. Cough is a common and significant symptom in sarcoidosis, reducing quality of life. Objective 24 h cough monitoring proved that sarcoidosis patients have significantly higher cough frequency compared to controls and their cough has diurnal variation, it is gender-specific and shows racial differences. It correlates with the presence of inflammation in the airways, but is not influenced by the X-ray staging of the disease, nor the degree of airway obstruction. Subjects with sarcoidosis have heightened cough reflex sensitivity, which is a result of interaction between the airway cough sensors and consequences of pathological process, detailed pathogenesis of cough in this demographic is unclear. The airway hyperresponsiveness, sarcoidosis of the upper airways and sensitivity to biomechanical forces play a role. More studies should be performed to understand pathogenesis of cough in sarcoidosis patients to improve the management of this troublesome symptom.
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http://dx.doi.org/10.1016/j.resp.2018.01.004DOI Listing
November 2018

Cough modulation by upper airway stimuli in cat - potential clinical application?

Open J Mol Integr Physiol 2016 Aug 22;6(3):35-43. Epub 2016 Aug 22.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Medical Biophysics.

The modulation of mechanically induced tracheobronchial cough was tested by applying various stimuli and the elicitation of other airway protective behaviors in pentobarbital anesthetized cats. Capsaicin and histamine were injected in the nose, and mechanical nylon fiber and / or air puff stimulation was applied to the nose and nasopharynx. Reflex responses of cough, sneeze, aspiration reflex and expiration reflex were induced mechanically. Swallow was initiated by the injection of water into oropharynx. Subthreshold mechanical stimulation of nasopharyngeal and nasal mucosa, as well as water stimulation in the oropharynx and larynx, with no motor response, had no effect on rhythmic coughing. Cough responsiveness and excitability increased with capsaicin and air puff stimuli delivered to the nose. Vice versa, the number of cough responses was reduced and cough latency increased when aspiration reflexes (>1) occurred before the cough stimulus or within inter-cough intervals (passive E2 cough phase). The occurrence of swallows increased the cough latency as well. Cough inspiratory and / or expiratory motor drive was enhanced by the occurrence of expiration reflexes, swallows, and sneezes and also by aspiration reflex within the inspiratory phase of cough and by nasal air puff stimuli. Complex central interactions, ordering and sequencing of motor acts from the airways may result in the disruption of cough rhythmic sequence but also in the enhancement of cough. Our data confirm that number of peripheral stimuli and respiratory motor responses significantly alters cough performance. We propose developing and testing stimulation paradigms that modify coughing and could be employed in correcting of inappropriate or excessive coughing.
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http://dx.doi.org/10.4236/ojmip.2016.63004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606332PMC
August 2016

Role of gender in basic cough research.

Respir Physiol Neurobiol 2017 11 21;245:53-56. Epub 2016 Dec 21.

Department of Pathophysiology JFM CU, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin (JFM CU), Slovak Republic.

Cough hypersensitivity affects mainly postmenopausal women. Pathogenesis remains unknown in their case; therefore, an optimal treatment is unavailable. Only male guinea pigs are used in basic cough research and exclusion of females leads to gender bias. Nowadays, the efforts of grant agencies aim to support projects which take gender into account and involve both sexes to reduce gender bias. The aim of our pilot study is to assess the suitability of female guinea pig model in cough research. Cough response to citric acid (0.4M) was obtained in female and male guinea pigs (n=12 each). Reproducibility of cough response was tested four times a week apart. The cough was detected from the airflow traces and cough sound analysis. Our initial results show that cough response of female guinea pigs is higher than in males. Variability of females is also higher than in males. Further investigations are necessary to validate this model in different conditions to achieve gender equality in cough studies.
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http://dx.doi.org/10.1016/j.resp.2016.12.006DOI Listing
November 2017

TRPV4 antagonist GSK2193874 does not modulate cough response to osmotic stimuli.

Respir Physiol Neurobiol 2017 02 29;236:1-4. Epub 2016 Oct 29.

Jessenius Faculty of Medicine in Martin, Biomedical Center Martin JFM CU, Comenius University in Bratislava, Slovakia; Jessenius Faculty of Medicine in Martin, Department of Pathophysiology JFM CU, Comenius University in Bratislava, Slovakia; Jessenius Faculty of Medicine in Martin, Simulation Education Center JFM CU, Comenius University in Bratislava, Slovakia.

Osmolarity changes of airway superficial fluid are associated with cough and are used in research. TRPV4 is calcium channel initially described as osmosensor. In the airways, it can play role in increasing cough reflex sensitivity. The aim of our study was to test whether cough to osmotic stimuli is mediated via TRPV4 channel. Cough response was measured in 12 male guinea pigs by inhalation of saline, distilled water, hypertonic solution and citric acid for 10min in whole-body plethysmograph. Data were obtained in naïve animals and after pre-treatment with selective TRPV4 antagonist GSK2193874 in doses 300μg/kg (GSK300) and 900μg/kg (GSK900). Cough response to all tested aerosols was significantly higher than to saline. Pre-treatment with GSK300 did not influence response to osmotic stimuli - only reduced cough to citric acid. GSK900 reduced cough response to hypotonic stimuli and citric acid. TRPV4 mediated activation of airway afferents does not seem to be the exclusive mechanism responsible for cough to osmotic stimuli.
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http://dx.doi.org/10.1016/j.resp.2016.10.010DOI Listing
February 2017

The course of lung inflation alters the central pattern of tracheobronchial cough in cat-The evidence for volume feedback during cough.

Respir Physiol Neurobiol 2016 07 25;229:43-50. Epub 2016 Apr 25.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Medical Biophysics, Mala Hora 4, 03601 Martin, Slovakia.

The effect of volume-related feedback and output airflow resistance on the cough motor pattern was studied in 17 pentobarbital anesthetized spontaneously-breathing cats. Lung inflation during tracheobronchial cough was ventilator controlled and triggered by the diaphragm electromyographic (EMG) signal. Altered lung inflations during cough resulted in modified cough motor drive and temporal features of coughing. When tidal volume was delivered (via the ventilator) there was a significant increase in the inspiratory and expiratory cough drive (esophageal pressures and EMG amplitudes), inspiratory phase duration (CTI), total cough cycle duration, and the duration of all cough related EMGs (Tactive). When the cough volume was delivered (via the ventilator) during the first half of inspiratory period (at CTI/2-early over inflation), there was a significant reduction in the inspiratory and expiratory EMG amplitude, peak inspiratory esophageal pressure, CTI, and the overlap between inspiratory and expiratory EMG activity. Additionally, there was significant increase in the interval between the maximum inspiratory and expiratory EMG activity and the active portion of the expiratory phase (CTE1). Control inflations coughs and control coughs with additional expiratory resistance had increased maximum expiratory esophageal pressure and prolonged CTE1, the duration of cough abdominal activity, and Tactive. There was no significant difference in control coughing and/or control coughing when sham ventilation was employed. In conclusion, modified lung inflations during coughing and/or additional expiratory airflow resistance altered the spatio-temporal features of cough motor pattern via the volume related feedback mechanism similar to that in breathing.
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http://dx.doi.org/10.1016/j.resp.2016.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369651PMC
July 2016

Impact of Air Pollution on Age and Gender Related Increase in Cough Reflex Sensitivity of Healthy Children in Slovakia.

Front Physiol 2016 23;7:54. Epub 2016 Feb 23.

Department of Pathophysiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava Bratislava, Slovakia.

Background: Numerous studies show higher cough reflex sensitivity (CRS) and cough outcomes in children compared to adults and in females compared to males. Despite close link that exists between cough and environment the potential influence of environmental air pollution on age- and gender -related differences in cough has not been studied yet.

Purpose: The purpose of our study was to analyse whether the effects of exposure to environmental tobacco smoke (ETS) from parental smoking and PM10 from living in urban area are implied in age- and gender-related differences in cough outcomes of healthy, non-asthmatic children. Assessment of CRS using capsaicin and incidence of dry and wet cough was performed in 290 children (mean age 13.3 ± 2.6 years (138 females/152 males).

Results: CRS was significantly higher in girls exposed to ETS [22.3 μmol/l (9.8-50.2 μmol/l)] compared to not exposed girls [79.9 μmol/l (56.4-112.2 μmol/l), p = 0.02] as well as compared to exposed boys [121.4 μmol/l (58.2-253.1 μmol/l), p = 0.01]. Incidence of dry cough lasting more than 3 weeks was significantly higher in exposed compared to not exposed girls. CRS was significantly higher in school-aged girls living in urban area [22.0 μmol/l (10.6-45.6 μmol/l)] compared to school-aged girls living in rural area [215.9 μmol/l (87.3-533.4 μmol/l); p = 0.003], as well as compared to teenage girls living in urban area [108.8 μmol/l (68.7-172.9 μmol/l); p = 0.007]. No CRS differences were found between urban and rural boys when controlled for age group. No CRS differences were found between school-aged and teenage boys when controlled for living area.

Conclusions: Our results have shown that the effect of ETS on CRS was gender specific, linked to female gender and the effect of PM10 on CRS was both gender and age specific, related to female gender and school-age. We suggest that age and gender related differences in incidence of cough and CRS might be, at least partially, ascribed to the effect of environmental pollutants. The role of age and gender in the effect of air pollution on cough strongly suggest some interplay of development with biological and behavioral factors.
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http://dx.doi.org/10.3389/fphys.2016.00054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763033PMC
March 2016

Defining Chronic Cough: A Systematic Review of the Epidemiological Literature.

Allergy Asthma Immunol Res 2016 Mar 18;8(2):146-55. Epub 2015 Sep 18.

Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Castle Hill Hospital, University of Hull, Cottingham, East Yorkshire, United Kingdom.

Purpose: Recent evidence suggests a global burden of chronic cough in general populations. However, the definitions vary greatly among epidemiological studies, and none have been validated for clinical relevance. We aimed to examine previous epidemiological definitions in detail and explore the operational characteristics.

Methods: A systematic review was conducted for epidemiological surveys that reported the prevalence of chronic cough in general adult populations during the years 1980 to 2013. A literature search was performed on Pubmed and Embase without language restriction. Epidemiological definitions for chronic cough were classified according to their components, such as cutoff duration. Meta-analyses were performed for the male-to-female ratio of chronic cough prevalence to explore operational characteristics of epidemiological definitions.

Results: A total of 70 studies were included in the systematic review. The most common epidemiological definition was identified as 'cough ≥3 months' duration without specification of phlegm (n=50); however, it conflicted with the cutoff duration in current clinical guidelines (cough ≥8 weeks). Meta-analyses were performed for the male-to-female ratio of chronic cough among 28 studies that reported sex-specific prevalence using the most common definition. The pooled male-to-female odds ratio was 1.26 (95% confidence interval 0.92-1.73) with significant heterogeneity (I²=96%, P<0.001), which was in contrast to clinical observations of female predominance from specialist clinics. Subgroup analyses did not reverse the ratio or reduce the heterogeneity.

Conclusions: This study identified major issues in defining chronic cough in future epidemiological studies. The conflict between epidemiological and clinical diagnostic criteria needs to be resolved. The unexpected difference in the gender predominance between the community and clinics warrants further studies. Clinical validation of the existing definition is required.
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http://dx.doi.org/10.4168/aair.2016.8.2.146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713878PMC
March 2016

The global epidemiology of chronic cough in adults: a systematic review and meta-analysis.

Eur Respir J 2015 May 5;45(5):1479-81. Epub 2015 Feb 5.

Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Castle Hill Hospital, University of Hull, Cottingham, UK Both authors contributed equally; S-H. Cho and A.H. Morice are joint lead authors of this article.

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http://dx.doi.org/10.1183/09031936.00218714DOI Listing
May 2015

Interactions of mechanically induced coughing and sneezing in cat.

Respir Physiol Neurobiol 2015 Jan 28;205:21-7. Epub 2014 Sep 28.

Institute of Medical Biophysics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4, 036 01 Martin, Slovak Republic.

Mutual interactions of cough and sneeze were studied in 12 spontaneously breathing pentobarbitone anesthetized cats. Reflexes were induced by mechanical stimulation of the tracheobronchial and nasal airways, respectively. The amplitude of the styloglossus muscle EMG moving average during the sneeze expulsion was 16-fold higher than that during cough (p<0.01). Larger inspiratory efforts occurred during coughing (p<0.01) vs. those in sneeze. The number of reflexes during simultaneous mechanical stimulation of the nasal and tracheal airways was not altered significantly compared to controls (p>0.05) and there was no modulation in temporal characteristics of the behaviors. When both reflexes occurred during simultaneous stimuli the responses were classified as either sneeze or cough (no hybrid responses occurred). During simultaneous stimulation of both airway sites, peak diaphragm EMG and inspiratory esophageal pressures during sneezes were significantly increased. The expiratory maxima of esophageal pressure and amplitudes of abdominal EMGs were increased in coughs and sneezes during simultaneous mechanical stimulation trials compared to control reflexes.
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http://dx.doi.org/10.1016/j.resp.2014.09.011DOI Listing
January 2015

What is chronic cough in children?

Front Physiol 2014 28;5:322. Epub 2014 Aug 28.

Service D'explorations Fonctionnelles Pédiatriques, Hôpital D'enfants Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France ; EA 3450 DevAH - Laboratoire de Physiologie, Faculté de Médecine, Université Lorraine Vandoeuvre, France.

The cough reflex is modulated throughout growth and development. Cough-but not expiration reflex-appears to be absent at birth, but increases with maturation. Thus, acute cough is the most frequent respiratory symptom during the first few years of life. Later on, the pubertal development seems to play a significant role in changing of the cough threshold during childhood and adolescence resulting in sex-related differences in cough reflex sensitivity in adulthood. Asthma is the major cause of chronic cough in children. Prolonged acute cough is usually related to the long-lasting effects of a previous viral airway infection or to the particular entity called protracted bacterial bronchitis. Cough pointers and type may orient toward specific etiologies, such as barking cough in croup or tracheomalacia, paroxystic whooping cough in Pertussis. Cough is productive in protracted bacterial bronchitis, sinusitis or bronchiectasis. Cough is usually associated with wheeze or dyspnea on exertion in asthma; however, it may be the sole symptom in cough variant asthma. Thus, pediatric cough has particularities differentiating it from adult cough, so the approach and management should be developmentally specific.
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http://dx.doi.org/10.3389/fphys.2014.00322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148026PMC
September 2014

Control of coughing by medullary raphé.

Prog Brain Res 2014 ;212:277-95

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Pathophysiology, Martin, Slovakia.

The medullary raphé nuclei participate in the regulation of breathing and airway defensive reflexes. Our focus was to analyze the effects of codeine and kainic acid within the medullary raphé on coughing, sneezing, solitary expulsions, and concomitant breathing changes using models of anesthetized cats (n=12) and rabbits (n=15) and microinjection techniques. Our findings are consistent with (1) involvement of neurons within the medullary raphé in the generation of the cough motor pattern by a codeine-sensitive and -insensitive mechanisms, (2) a contribution of raphé nuclei to the control of expiratory efforts, (3) limited contribution of the medullary raphé to the cough-gating mechanism, (4) minor contribution of respiration/coughing neuronal network, including the portion within raphé nuclei and the respiratory/cough central pattern generator, to the production of the sneeze reflex motor pattern.
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http://dx.doi.org/10.1016/B978-0-444-63488-7.00014-8DOI Listing
April 2015

Chronic cough in subjects with upper airway diseases - analysis of mechanisms and clinical applications.

Asia Pac Allergy 2013 Apr 26;3(2):127-35. Epub 2013 Apr 26.

Department of Pathophysiology & Simulation Centre, Jessenius Faculty of Medicine, Comenius University, Martin 036 01, Slovak Republic.

Cough is the commonest respiratory symptom leading to a medical consultation. Although acute cough which is usually associated with respiratory viral infection is not a problem to manage, chronic cough is frequently a diagnostic and therapeutic challenge as it does not respond to usual treatments. Specific group of chronic coughers are considered to have upper airway diseases, lately categorized as having upper airway cough syndrome. There is an increasing pool of evidence that upper airway diseases have significant involvements in the regulation of cough reflex, indicating that they must be taken into considerations as major triggers of coughing in the patients. Here we summarize current literature and experiences on the pathogenesis of upper airway cough syndrome, and discuss further clinical applications.
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http://dx.doi.org/10.5415/apallergy.2013.3.2.127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3643059PMC
April 2013

Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels.

Cough 2012 Dec 3;8(1):11. Epub 2012 Dec 3.

Department of Pathophysiology, Comenius University, Jessenius Faculty of Medicine Martin, Sklabinska Str, 26, Martin, 036 01, Slovak Republic.

Unlabelled:

Background: Cough, the most important airways defensive mechanism is modulated by many afferent inputs either from respiratory tussigenic areas, but also by afferent drive from other organs. In animal models, modulation of cough by nasal afferent inputs can either facilitate or inhibit the cough response, depending on the type of trigeminal afferents stimulated.

Methods: In this study we addressed the question of possible bidirectional modulation of cough response in human healthy volunteers by nasal challenges with TRPA1 and TRPM8 agonists respectively. After nasal challenges with isocyanate (AITC), cinnamaldehyde, (-) menthol and (+) menthol (all 10-3 M) nasal symptom score, cough threshold (C2), urge to cough (Cu) and cumulative cough response were measured).

Results: Nasal challenges with TRPA1 relevant agonists induced considerable nasal symptoms, significantly enhanced urge to cough (p<0.05) but no statistically significant modulation of the C2 and cumulative cough response. In contrast, both TRPM8 agonists administered to the nose significantly modulated all parameters including C2 (p<0.05), Cu (p<0.01) and cumulative cough response (p <0.01) documenting strong anti irritating potential of menthol isomers.

Conclusions: In addition to trigeminal afferents expressing TRP channels, olfactory nerve endings, trigemino - olfactoric relationships, the smell perception process and other supramedullar influences should be considered as potential modulators of the cough response in humans.
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http://dx.doi.org/10.1186/1745-9974-8-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546011PMC
December 2012

Fractionated irradiation-induced altered spatio-temporal cell distribution in the rat forebrain.

Acta Histochem 2013 May 12;115(4):308-14. Epub 2012 Oct 12.

Institute of Histology and Embryology, Jessenius Faculty of Medicine in Martin, Comenius University, Malá Hora 4, 036 01 Martin, Slovak Republic.

Ionizing radiation as one of the strongest cytogenetic factors can induce significant injury to the adult brain. In the present study, adult male Wistar rats were exposed to whole-body irradiation with fractionated doses of gamma rays (a total dose of 3Gy). Seven, 14 and 21 days after irradiation the cell types located in the neurogenic anterior subventricular zone (SVZa) were labeled using immunohistochemistry for SVZa-derived young neurons and astrocytes. Cell counting was performed in four anatomical parts along the pathway known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm of the RMS. A considerable increase was seen in the number of neuroblasts in the SVZa, vertical arm and elbow on day 7 after irradiation. Until days 14 and 21 there was a marked decline in the density of young neurons, mostly in the horizontal arm of the RMS. In contrast, the number of astrocytes gradually increased in the caudal parts of the RMS until day 14 after irradiation. Strong enhancement was replaced by a steep decline within the RMS up to 21 days after treatment. Our results showed that the radiation response of proliferating cells originating from the SVZa may play a contributory role in the development of more adverse late radiation-induced effects.
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http://dx.doi.org/10.1016/j.acthis.2012.09.001DOI Listing
May 2013

Mechanisms of the cough associated with rhinosinusitis.

Pulm Pharmacol Ther 2009 Apr 10;22(2):121-6. Epub 2008 Dec 10.

Department of Pathophysiology, Jessenius Medical School, Comenius University, Martin, Slovakia.

The diseases of the nose and paranasal sinuses (rhinosinusitis) often in combination with asthma and gastroesophageal reflux are common causes of chronic cough in patients with normal chest radiograph. The relationships between rhinosinusitis and cough are incompletely understood. We investigated modulation of the cough reflex by the inputs from the nose. We demonstrate that the cough reflex is sensitized by the intranasal administration of sensory nerve activators in animal models and in humans. Cough reflex is also sensitized in the guinea pig model of allergic nasal inflammation and in patients with allergic rhinitis. In patients with allergic rhinitis the cough sensitization is augmented during the allergen season. We conclude that the cough reflex can be sensitized from the nose. Our data indicate that this sensitization is mediated by nasal sensory nerves. We speculate that by inducing the cough reflex sensitization rhinosinusitis contributes to chronic cough. If combined with environmental or endogenous cough triggers, the cough reflex sensitization is predicted to cause excessive coughing. The potential endogenous cough triggers may be associated with rhinosinusitis (postnasal drip, aspiration of nasal secrets) or secondary to a coexistent disease such as asthma or gastroesophageal reflux.
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http://dx.doi.org/10.1016/j.pupt.2008.11.014DOI Listing
April 2009
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