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Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the most effective first-time treatment in allergic rhinitis. In this study we evaluated the cough sensitivity during the early and late allergic responses in guinea pigs with experimental allergic rhinitis. Another aim of the study was to follow up the effect of inhaled beclomethasone dipropionate on the cough in guinea pigs with allergic rhinitis. 31 guinea pigs were sensitized with ovalbumin (OA). Animals were intranasally challenged with OA (experiment) or saline (control) in 7-day intervals for 9 weeks. Cough was induced by inhalation of citric acid aerosols in gradually increasing concentrations for 30 s and was evaluated 1 h after the 8th nasal challenge (NCH) and 17 h after the 9th NCH. Cough was significantly increased only during an early allergic response, 1 h after repeated NCH [18 (14-23) vs. 8 (3-10); P<0.001]. Five experimental animals were inhaling aerosol of beclomethasone dipropionate seven days between the 8th and the 9th NCH and cough was evaluated 1 h after the 9th NCH. Inhaled corticosteroids significantly inhibited the enhanced allergic rhinitis related cough [4 (1-9) vs.19 (9-37) vs. 6 (3-9); P<0.05].
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In the present study we investigated the effects of nasal histamine on the intensity of coughing and the effects of intensified nasal breathing following nasal histamine on cough sensitivity (CS) in 14 subjects with seasonal allergic rhinitis. The study consisted of two parts performed one week apart. First, baseline CS to capsaicin was determined, followed by intranasal histamine challenge (4mg/ml, 0.1 ml) and the count of the number of coughs to inhaled capsaicin on the background of most intensive nasal symptoms (sneezing, itching, rhinorrhea, and nasal blockage) evoked by histamine. In the second part, CS was determined after intranasal histamine followed by 10 min of intensified nasal breathing through the nose or mouth in a randomized order at 2-day intervals. The number of coughs induced after intranasal histamine was significantly higher, compared with intranasal saline, [9 (7-12) vs. 4.5 (4-6), P<0.001]. CS also was significantly increased after nasal histamine, but nasal intensified breathing failed to cause any changes in CS. We conclude that stimulation of nasal mucosa with histamine enhanced the cough response in subjects with allergic rhinitis.
Cough associated with upper respiratory tract disorders is a common and troublesome problem in children and little is known about the etiology of this type of cough. This study examined the capsaicin cough sensitivity (CS) in children suffering from allergic rhinitis (AR) and upper respiratory tract infection (URI), comparing it with that in healthy children taken as controls (C). CS to capsaicin, spirometry, skin prick tests, and nose-throat examination were performed in 61 children grouped by the diagnosis of AR, URI, and C. The results, in order of C vs. AR vs. URI, expressed as a geometric mean (±95% CI) log10 µM of capsaicin for C2 (the lowest concentration of capsaicin in µmol/l required to induce 2 coughs) were: 1.8 (1.6-1.9) vs. 1.0 (0.8-1.2) vs. 0.48 (0.2-0.8), P<0.001 and for C5 (the lowest concentration of capsaicin in µmol/l required to induce 5 coughs) 2.9 (2.8-2.9) vs. 2.6 (2.5-2.6) vs. 2.1 (2.0 –2.3), P<0.05. We found that CS in children with AR, even when tested out of pollen season, was significantly heightened compared with controls. CS in children with URI was extremely high compared with both C and AR groups. We conclude that pathological processes in the nose of any etiology could cause a sensitization of the cough reflex with decreased cough threshold during asymptomatic period of AR. Cough also is enhanced by acute inflammation in the upper airways in nonatopic children.
Preparations from rhizomes of Petasites hybridus (L.) Gaertn., B. Mey. & Scherb. (common butterbur) have a long history of use in folk medicine in treatment of several diseases as anti-inflammatory and spasmolytic drugs. Extracts from this species are of interest to researchers in the field of phytopharmacology due to their biologically active compounds, particularly two eremophilane sesquiterpenes (petasin and isopetasin), which are contained not only in rhizomes and roots, but also in leaves. Moreover, P. hybridus contains pyrrolizidine alkaloids, which showed hepatotoxic, carcinogenic and mutagenic properties. Hence, special extracts devoid of alkaloids obtained by sub- and super-critic carbon dioxide extraction were used in the preclinical, clinical studies and phytotherapy. Our review aims to provide a literature survey of pharmacological as well as clinical trials of P. hybridus, carried out in 2000–2013. Also several studies of other species used in non-European countries have been included. Besides, the botanical description of Petasites genus and phytochemical characteristic of P. hybridus and toxicological studies of pyrrolizidine alkaloids as well as chemical profile of patented commercial extracts from rhizomes, roots and leaves of this species used in European phytotherapy have been performed. In this review, attention has also been paid to the promising and potential application of special extracts of P. hybridus not only in the prevention of migraine, treatment of allergic rhinitis symptoms, asthma and hypertension, but also in prevention and slowing the progression of neurodegenerative diseases developing with the inflammatory process in the CNS as a new therapeutic strategy. In fact, there is already an evidence of promising properties of P. hybridus extracts and sesquiterpens – decrease in the prostaglandins and leukotrienes release, inhibition of COX-1 and COX-2 activity, as well as antagonism of L-type voltage-gated calcium channels. In order to explain the new mechanisms of action of P. hybridus extracts in the CNS and their future application in phytotherapy of diseases with neuroinflammatory process, further studies should be performed.
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Antileukotriene treatment and allergic rhinitis-related cough in guinea pigs

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Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene receptor antagonists, as anti-inflammatory agents, have been effective in treatment of asthma and allergic rhinitis to inhibit the early and late allergic response. In the present study, we evaluated the effect of montelukast (Singulair, Merck, USA) on the cough reflex in an experimental model of allergen-induced rhinitis in guinea pigs. Guinea pigs (n=16) were sensitized with intraperitoneal ovalbumin (OVA). The animals were then used to develop a model of allergic rhinitis by repeated intranasal instillation of 0.5% OVA at weekly intervals for 8 weeks. Allergic rhinitis was evaluated from the occurrence of typical clinical symptoms including sneezing, conjuctival and nasal secretion, or nasal acoustic phenomenon. Between the 6th and 8th nasal challenge (NCh) the animals (n=8) were treated daily for 14 days with oral montelukast (10mg/kg). Cough was induced by citric acid aerosol inhalation in gradually increasing concentration (0.05-1.6 M) and was evaluated before sensitization and then after the 1st, 6th, and 8th nasal challenge when rhinitic symptoms were most conspicuous. The intensity of cough was significantly increased after the first and repeated nasal OVA challenges, and reduced after the 8th NCh that was preceded with montelukast treatment [9(6-14) vs. 16.5(14-22) vs. 25.5(23-42) vs. 8.5(8-13); P=0.0003]. We conclude that antileukotriene therapy suppresses the stimulating effect of experimental allergic rhinitis on the chemically-induced cough in awake guinea pigs.
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Cough sensitivity in allergic rhinitis

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The objective of this study was to evaluate capsaicin cough sensitivity in pollen sensitive patients with allergic rhinitis at the time of grass pollen season and out of it. Cough reflex sensitivity was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Capsaicin aerosol in doubled concentrations (from 0.02 to 200 µmol) was inhaled by a single breath. Two groups of pollen sensitive rhinitis subjects and a group of healthy controls were studied. The C2 for the 23 pollen sensitive patients of the first group, studied out of pollen season (January-February), was 0.22 µmol/l (0.06-0.76) (geometric mean + 95% CI), which was substantially lower than the 4.29 µmol/l (2.54-7.26) in 24 healthy volunteers (P=0.0001). In another group of 15 pollen sensitive patients, C2 was 0.84 µmol/l (0.14-5.20) out of pollen season and 0.11 µmol/l (0.03-0.33) during the pollen season (May-June) (P=0.04). We conclude that pollen-sensitive subjects who suffer of seasonal allergic rhinitis have significantly greater capsaicin cough sensitivity, regardles of them being in or out of pollen season. Subclinical inflammatory changes in the lower airways are probably responsible for this effect.
Some patients with allergic rhinitis and no clinical evidence of asthma exhibit bronchial hyperresponsiveness. In the present study, induced sputum and acetylcholine and capsaicin challenges were assessed in four groups of adult subjects: allergic rhinitis (AR), allergic rhinitis with lower airway symptoms (ARLA), mild stable asthma (BA), and healthy volunteers (C) to correlate lower airway inflammatory markers with bronchial and cough reactivity. Patients with AR (n = 13) and ARLA (n = 11) did not take any anti-inflammatory drugs. Those with BA (n = 9) used inhaled corticosteroids and C (n = 10) were respiratory symptoms free. The patients underwent capsaicin cough challenge and sputum induction with hypertonic saline during the first visit, and acetylcholine bronchial challenge on a separate day. We found that the percentage of eosinophils in induced sputum was significantly higher in patients with AR, ARLA, and BA than in C 14.5 ±1.8(SE) vs. 13.5 ±2.9 vs. 13.9 ±4.0 vs. 3.6 ±0.8 %, respectively (P=0.012). In contrast, acetylcholine PD20 in patients with AR, ARLA, and BA was significantly lower than in C 5.6 ±0.9 vs. 4.1 ±0.4 vs. 2.8 ±0.4 vs. 12.9 ±2.7 mg, respectively (P=0.0001). Neither the eosinophil percentage nor PD20, nor cough sensitivity appreciably differed across the patients groups. Sputum eosinophils correlated significantly with the acetylcholine PD20 (r=0.37, P=0.016). We conclude that eosinophilic inflammation of lower airways and increased bronchial reactivity were present in adult patients with allergic rhinitis.
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