Obesity is characterized by chronic, low-grade systemic inflammation. Obesity may also be associated with chronic cough. The aim of this pilot study was to clarify relation of cough reflex sensitivity and body mass index (BMI) in children with chronic cough. Altogether 41 children having symptoms of chronic cough were submitted to cough reflex sensitivity measurement. We assessed the relation of cough reflex sensitivity (CKR) due to BMI. Cough reflex sensitivity was defined as the lowest capsaicin concentration which evoked two (C2) or five (C5) coughs. Capsaicin aerosol in doubling concentrations (from 0.61 to 1250 micromol/l) was inhaled by a single breath method (KoKo DigiDoser; nSpire heath Inc, Louisville, CO, USA), modified by the addition of an inspiratory flow regulator valve (RIFR; nSpire heath Inc, Louisville, CO, USA). BMI was calculated. Pulmonary function was within normal range. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Children (22 boys and 19 girls, mean age 6.8 years) cough reflex sensitivity (median, with the Inter-Quartile Range) for C2 was 19.5 (73.4) micromol/l; for C5 it was 78.1 (605.5) micromol/l. We have noticed statistically significant relation of the cough reflex sensitivity (C5) and body mass index (P<0.0001); however, the effect size was small, R2=0.03. Increase of body mass index in one unit is associated with -34.959 micromol/l decrease of C5. We did not find a statistically significant relation between C2 and BMI (P=0.41). The median value of CKR (C2) in boys is not statistically significantly different than the median value of CKR (C2) in girls (P-value 0.5). The median value of CKR (C5) in boys is not statistically significantly different than the median value of CKR (C5) in girls (P-value 0.5). Increase of body mass index in children suffering from chronic cough relates to decrease of cough reflex sensitivity (C5 value).

• MeSH
• alergie patofyziologie   MeSH
• chronická nemoc MeSH
• dítě MeSH
• index tělesné hmotnosti MeSH
• kapsaicin škodlivé účinky   MeSH
• kašel chemicky indukované   patofyziologie   MeSH
• látky ovlivňující senzorický systém škodlivé účinky   MeSH
• lidé MeSH
• mladiství MeSH
• pilotní projekty MeSH
• předškolní dítě MeSH
• reflex fyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kapsaicin MeSH
• látky ovlivňující senzorický systém MeSH

Laboratory research of cough reflex utilizes almost exclusively male guinea pigs - a practice that represents a significant obstacle in the successful translation of results into clinical practice. Chronic hypersensitivity cough syndrome affects mostly postmenopausal women and it represents significant decrease in patient's quality of life. No cause for such exaggerated cough can be found, therefore this condition cannot be treated appropriately. One of the reasons leading to the lack of relevant data about mechanisms responsible for hypersensitivity of cough related pathways is nowadays widely discussed gender bias, which is present in nearly all branches of biomedical research. Since gender differences in cough reflex physiology do exist in humans, it would be reasonable to study cough-related phenomena on both sexes of laboratory animals. In this study, we focused on detailed characterization of cough response of female guinea pigs to aerosols of commonly used tussive agents (capsaicin, distilled water, allyl isothiocyanate, cinnamaldehyde, citric acid). In pooled data from multiple challenges we found no statistical difference in number of cough and cough latency between sexes. Based on our results we conclude that the utilization of female guinea pigs model does not lead to messy data and can be used in basic cough research.

• MeSH
• akrolein analogy a deriváty   toxicita   MeSH
• kapsaicin toxicita   MeSH
• kašel chemicky indukované   patofyziologie   MeSH
• kyselina citronová toxicita   MeSH
• modely nemocí na zvířatech * MeSH
• morčata MeSH
• pohlavní dimorfismus * MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akrolein MeSH
• cinnamaldehyde MeSH Prohlížeč
• kapsaicin MeSH
• kyselina citronová MeSH

New knowledge about the neural aspects of cough has revealed a complex network of pathways that initiate cough. The effect of inflammation on cough neural processing occurs at multiple peripheral and central sites within the nervous system. Evidence exists that direct or indirect neuroimmune interaction induces a complex response, which can be altered by mediators released by the sensory or parasympathetic neurons and vice versa. The aim of this study was to clarify changes of cough reflex sensitivity - the activity of airway afferent nerve endings - in asthmatic children.25 children with asthma and 15 controls were submitted to cough reflex sensitivity measurement - capsaicin aerosol in doubling concentrations (from 0.61 to 1250 µmol/l) was inhaled by a single breath method. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Asthmatic children' (11 boys and 14 girls, mean age 9 ± 1 yrs) cough reflex sensitivity (geometric mean, with the 95 % CI) for C2 was 4.25 (2.25-8.03) µmol/l vs. control C2 (6 boys and 9 girls, mean age 8 ± 1 yrs) was 10.61 (5.28-21.32) µmol/l (p=0.024). Asthmatic children' C5 was 100.27 (49.30-203.93) µmol/l vs. control C5 56.53 (19.69-162.35) µmol/l (p=0.348). There was a statistically significant decrease of C2 (cough threshold) in the asthmatic patients relative to controls (p-value for the two-sample t-test of log(C2) for the one-sided alternative, p-value = 0.024). The 95 % confidence interval for the difference of the mean C2 in asthma vs. control, [1.004, 6.207]. For C5, the difference was not statistically significant (p-value = 0.348). There was a statistically significant decrease of cough reflex sensitivity (the activity of airway afferent nerve endings) - C2 value in the asthmatic children relative to controls.

• MeSH
• aferentní nervové dráhy účinky léků   patofyziologie   MeSH
• bronchiální astma chemicky indukované   diagnóza   patofyziologie   MeSH
• dítě MeSH
• kapsaicin škodlivé účinky   MeSH
• kašel chemicky indukované   diagnóza   patofyziologie   MeSH
• látky ovlivňující senzorický systém škodlivé účinky   MeSH
• lidé MeSH
• prospektivní studie MeSH
• reflex účinky léků   fyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kapsaicin MeSH
• látky ovlivňující senzorický systém MeSH

Since the recognition of angiotensin-converting enzyme inhibitors (ACEIs)-induced cough, drug has been considered as a potential cause of chronic cough. This review presents recent knowledge on drug-induced coughs in patients with chronic cough. The focus is placed on ACEIs, for which there are a multitude of studies documenting their associations with cough. Additional drugs are discussed for which there are reports of cough as a side effect of treatment, and the potential mechanisms of these effects are discussed.

• MeSH
• blokátory kalciových kanálů škodlivé účinky   MeSH
• chronická nemoc MeSH
• fentanyl škodlivé účinky   MeSH
• inhibitory ACE škodlivé účinky   MeSH
• kašel chemicky indukované   diagnóza   patofyziologie   MeSH
• lidé MeSH
• opioidní analgetika škodlivé účinky   MeSH
• reflex účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• blokátory kalciových kanálů MeSH
• fentanyl MeSH
• inhibitory ACE MeSH
• opioidní analgetika MeSH

Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subservepruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Adelta nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.

• MeSH
• agonisté histaminu škodlivé účinky   MeSH
• histamin škodlivé účinky   MeSH
• kapsaicin škodlivé účinky   MeSH
• kašel chemicky indukované   patofyziologie   MeSH
• látky ovlivňující senzorický systém škodlivé účinky   MeSH
• lidé MeSH
• nervová vlákna myelinizovaná účinky léků   fyziologie   MeSH
• nervová vlákna nemyelinizovaná účinky léků   fyziologie   MeSH
• nervové receptory účinky léků   fyziologie   MeSH
• neurony aferentní účinky léků   fyziologie   MeSH
• periferní nervy účinky léků   patofyziologie   MeSH
• pruritus chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• agonisté histaminu MeSH
• histamin MeSH
• kapsaicin MeSH
• látky ovlivňující senzorický systém MeSH

Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing.Upper airway cough syndrome (UACS) - previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.

• MeSH
• chronická nemoc MeSH
• kapsaicin škodlivé účinky   MeSH
• kašel chemicky indukované   patofyziologie   MeSH
• kationtové kanály TRPV agonisté   fyziologie   MeSH
• kationtový kanál TRPA1 agonisté   fyziologie   MeSH
• lidé MeSH
• nervové receptory účinky léků   fyziologie   MeSH
• nervus vagus účinky léků   patofyziologie   MeSH
• nosní sliznice účinky léků   patofyziologie   MeSH
• syndrom MeSH
• trachea účinky léků   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kapsaicin MeSH
• kationtové kanály TRPV MeSH
• kationtový kanál TRPA1 MeSH
• TRPA1 protein, human MeSH Prohlížeč
• TRPV1 protein, human MeSH Prohlížeč

The aim of this study was to investigate the effects of melatonin on oxidative stress, the expression of transient receptor potential melastatin-2 (TRPM2) in guinea pig brains, and the influence of melatonin on oxidative stress in lungs and airway inflammation induced by particulate matter 2.5 (PM2.5). A particle suspension (0.1 g/ml) was nasally administered to the guinea pigs to prepare a PM2.5 exposure model. Cough frequency and cough incubation period were determined through RM6240B biological signal collection and disposal system. Oxidative stress markers, including malondialdehyde (MDA), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px), in the medulla oblongata were examined through spectrophotometer. Reactive oxygen species (ROS) were detected in the hypoglossal nucleus, cuneate nucleus, Botzinger complex, dorsal vagal complex, and airway through dihydroethidium fluorescence. Hematoxylin-eosin (HE) staining and substance P expression via immunohistochemistry revealed the inflammatory levels in the airway. TRPM2 was observed in the medulla oblongata through immunofluorescence and Western blot. The ultrastructure of the blood-brain barrier and neuronal mitochondria was determined by using a transmission electron microscope. Our study suggests that melatonin treatment decreased PM2.5-induced oxidative stress level in the brains and lungs and relieved airway inflammation and chronic cough. TRPM2 might participate in oxidative stress in the cough center by regulating cough.

• MeSH
• antioxidancia terapeutické užití   MeSH
• hematoencefalická bariéra účinky léků   patologie   MeSH
• kašel chemicky indukované   farmakoterapie   patologie   MeSH
• kationtové kanály TRPM metabolismus   MeSH
• látky znečišťující vzduch škodlivé účinky   MeSH
• medulla oblongata účinky léků   metabolismus   MeSH
• melatonin terapeutické užití   MeSH
• morčata MeSH
• mozek - chemie účinky léků   MeSH
• oxidační stres účinky léků   MeSH
• pevné částice škodlivé účinky   MeSH
• plíce účinky léků   MeSH
• velikost částic MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• kationtové kanály TRPM MeSH
• látky znečišťující vzduch MeSH
• melatonin MeSH
• pevné částice MeSH

Single-agent dacetuzumab has demonstrated antitumor activity in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Preclinical data demonstrated improved dacetuzumab antitumor activity in combination with rituximab, ± chemotherapy. We designed a phase 2b, double-blind, placebo-controlled trial to compare rituximab, ifosfamide, carboplatin and etoposide (R-ICE) + dacetuzumab with R-ICE + placebo in patients with DLBCL who relapsed after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) (ClinicalTrials.gov #NCT00529503). The primary endpoint was complete response (CR); additional endpoints included failure-free survival and overall survival (OS). Overall, 151 patients were randomized (75 dacetuzumab, 76 placebo). No notable differences between arms in demographics or subsequent treatment parameters were observed. Cytopenias, cough and infection were more frequent with dacetuzumab. Futility analysis failed to demonstrate higher CR rates with dacetuzumab (36% dacetuzumab, 42% placebo); consequently, enrollment was stopped. Unplanned post hoc analysis showed that patients who underwent subsequent autologous stem cell transplant experienced improvement in OS (hazard ratio = 0.195, p = 0.004), which may be explained by potential immunomodulatory effects of dacetuzumab on antigen-presenting cells.

• Klíčová slova
• Dacetuzumab, R-ICE, diffuse large B-cell lymphoma, salvage therapy, stem cell transplant,
• MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• difúzní velkobuněčný B-lymfom farmakoterapie   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• dvojitá slepá metoda MeSH
• etoposid aplikace a dávkování   škodlivé účinky   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• ifosfamid aplikace a dávkování   škodlivé účinky   MeSH
• indukce remise MeSH
• Kaplanův-Meierův odhad MeSH
• karboplatina aplikace a dávkování   škodlivé účinky   MeSH
• kašel chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• prednisolon aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři MeSH
• trombocytopenie chemicky indukované   MeSH
• vinkristin aplikace a dávkování   MeSH
• výsledek terapie MeSH
• záchranná terapie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• cyklofosfamid MeSH
• dacetuzumab MeSH Prohlížeč
• doxorubicin MeSH
• etoposid MeSH
• humanizované monoklonální protilátky MeSH
• ifosfamid MeSH
• karboplatina MeSH
• prednisolon MeSH
• rituximab MeSH
• vinkristin MeSH

BACKGROUND: Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, is approved for the treatment of patients with cystic fibrosis aged 6 years or older with Gly551Asp-CFTR. We assessed the safety and efficacy of ivacaftor during 96 weeks of PERSIST in patients with cystic fibrosis who completed a previous 48-week, placebo-controlled trial of the drug (STRIVE or ENVISION). METHODS: In this phase 3, open-label extension study, patients received ivacaftor 150 mg every 12 h in addition to their prescribed cystic fibrosis therapies. Patients who received placebo in their previous study initiated ivacaftor in this extension study. Patients were eligible if they had a Gly551Asp-CFTR mutation on at least one allele. The primary objective was to assess the long-term safety profile of ivacaftor as assessed by adverse events, clinical laboratory assessments, electrocardiograms, vital signs, and physical examination; secondary measures included change in forced expiratory volume in one second (FEV1), weight, and pulmonary exacerbations. This study is registered with ClinicalTrials.gov, number NCT01117012 and EudraCT, number 2009-012997-11. FINDINGS: Between July 8, 2010, and April 8, 2013, 144 adolescents/adults (≥12 years) from STRIVE and 48 children (6-11 years) from ENVISION were enrolled. Across both trials, 38 (20%) patients had a serious adverse event during the first 48 weeks and 44 (23%) during the subsequent 48 weeks. Two adults (1%) and one child (<1%) discontinued because of adverse events. The most common adverse events were pulmonary exacerbation, cough, and upper respiratory tract infection. Patients previously treated with ivacaftor had sustained improvements in FEV1, weight, and rate of pulmonary exacerbations for up to 144 weeks of treatment. Among adolescents/adults and children who previously received ivacaftor, absolute change in FEV1 at week 96 (144 weeks ivacaftor) was 9·4 and 10·3 % points and absolute increase in weight was 4·1 kg and 14·8 kg, respectively. For adolescents/adults only, the pulmonary exacerbation rate remained suppressed compared with that of patients who received placebo in the placebo-controlled study. INTERPRETATION: At 144 weeks of treatment, ivacaftor was well tolerated, with no new safety concerns. Ivacaftor also provided durable effects for 144 weeks in patients who had received active treatment in the placebo-controlled study. Those patients who previously received placebo had improvements comparable to those of patients treated with ivacaftor in the placebo-controlled study. FUNDING: Vertex Pharmaceuticals Inc.

• MeSH
• aminofenoly škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• chinolony škodlivé účinky   terapeutické užití   MeSH
• cystická fibróza farmakoterapie   genetika   patofyziologie   MeSH
• dítě MeSH
• dospělí MeSH
• hmotnostní přírůstek účinky léků   MeSH
• infekce dýchací soustavy chemicky indukované   MeSH
• kašel chemicky indukované   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• progrese nemoci MeSH
• protein CFTR genetika   MeSH
• usilovný výdechový objem účinky léků   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminofenoly MeSH
• CFTR protein, human MeSH Prohlížeč
• chinolony MeSH
• ivacaftor MeSH Prohlížeč
• protein CFTR MeSH

Cough is a common and important symptom of asthma and allergic rhinitis. Previous experimental evidence has shown enhanced cough sensitivity during early phase of experimental allergic rhinitis in guinea pigs. We hypothesized that airway inflammation during the late phase response after repeated nasal antigen challenge may affect the afferent sensory nerve endings in the larynx and tracheobronchial tree and may also modulate cough response. In the present study we evaluated the cough sensitivity during a period of early and late allergic response in sensitized guinea pigs after repeated nasal antigen challenges. Forty-five guinea pigs were sensitized with ovalbumin (OVA). Four weeks later 0.015 ml of 0.5 % OVA was intranasally instilled to develop a model of allergic rhinitis that was evaluated from the occurrence of typical clinical symptoms. Animals were repeatedly intranasally challenged either by OVA (experimental group) or by saline (controls) in 7-day intervals for nine weeks. Cough was elicited by inhalation of citric acid aerosols. Cough was evaluated at 1 or 3 h after the 6th nasal challenge and 17 or 24 h after the 9th nasal challenge. The cough reflex was significantly increased at 1 and 3 h after repeated nasal challenge in contrast to cough responses evoked at 17 and 24 h after repeated nasal challenge. In conclusion, enhanced cough sensitivity only corresponds to an early allergic response after repeated nasal challenges.

• MeSH
• alergeny imunologie   MeSH
• časové faktory MeSH
• celoroční alergická rýma imunologie   patologie   patofyziologie   MeSH
• dýchací soustava imunologie   patologie   patofyziologie   MeSH
• imunizace * MeSH
• kašel chemicky indukované   imunologie   patofyziologie   MeSH
• kýchání imunologie   MeSH
• kyselina citronová aplikace a dávkování   MeSH
• modely nemocí na zvířatech MeSH
• morčata MeSH
• nosní provokační testy MeSH
• ovalbumin imunologie   MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alergeny MeSH
• kyselina citronová MeSH
• ovalbumin MeSH