scholarly journals Enhanced sensory nerve reactivity in non-eosinophilic asthma

Author(s):  
Hajar Ali ◽  
Collin Brooks ◽  
Julian Crane ◽  
Richard Beasley ◽  
Stephen Holgate ◽  
...  

ABSTRACT Background: Neural mechanisms may play an important role in non-eosinophilic asthma. This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic and non-eosinophilic asthma and non-asthmatics. Methods: Thirty-eight asthmatics and nineteen non-asthmatics (aged 14-21 years) underwent combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), atopy, and spirometry tests, followed by capsaicin challenge. Eosinophilic (EA) and non-eosinophilic asthma (NEA) were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity (AHR) was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs. Results: Non-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared to non-asthmatics (n=19) (geometric mean C5: 58.3μM, 95% confidence interval 24.1-141.5 vs 193.6μM, 82.2-456.0; p<0.05). There was a similar (but non-significant) difference in capsaicin sensitivity in NEA compared with EA (n=18), (58.3μM, 24.1-141.5 vs 191.0μM, 70.9-514.0; p=0.07). FEV1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control, or treatment were observed. Conclusion: Non-eosinophilic asthma, but not eosinophilic asthma, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of non-eosinophilic asthma.

2021 ◽  
Vol 8 (1) ◽  
pp. e000974
Author(s):  
Hajar Ali ◽  
Collin Brooks ◽  
Julian Crane ◽  
Richard Beasley ◽  
Stephen Holgate ◽  
...  

BackgroundNeural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics.MethodsThirty-eight asthmatics and 19 non-asthmatics (aged 14–21 years) underwent combined hypertonic saline challenge/sputum induction, fractional exhaled nitric oxide, atopy and spirometry tests, followed by capsaicin challenge. EA and NEA were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs.ResultsNon-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared with non-asthmatics (n=19) (geometric mean C5: 58.3 µM, 95% CI 24.1 to 141.5 vs 193.6 µM, 82.2 to 456.0; p<0.05). NEA tended to also have greater capsaicin sensitivity than EA, with the difference in capsaicin sensitivity between NEA and EA being of similar magnitude (58.3 µM, 24.1 to 141.5 vs 191.0 µM, 70.9 to 514.0) to that observed between NEA and non-asthmatics; however, this did not reach statistical significance (p=0.07). FEV1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control or treatment were observed.ConclusionNEA, but not EA, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of NEA.


1998 ◽  
Vol 5 (4) ◽  
pp. 261-268 ◽  
Author(s):  
Mark O Turner ◽  
Patrick R Johnston ◽  
Emilio Pizzichini ◽  
Marcia MM Pizzichini ◽  
Pat A Hussack ◽  
...  

BACKGROUND: Salmeterol is a potent long acting beta-agonist that is effective in relieving the symptoms and airflow limitation of asthma.OBJECTIVE: To determine whether the effect of salmeterol on clinical parameters in a mild eosinophilic exacerbation of asthma was similar to that of beclomethasone dipropionate (BDP) and, thus, is due to an anti-inflammatory property.PATIENTS AND METHODS: Thirty-four asthmatics with a persistent increase in symptoms for at least two weeks and an increase of sputum eosinophils of 4% or more were randomized in a double-blind fashion to one of three groups that received daily treatment with 100 µg salmeterol, 1 mg BDP or placebo in divided doses using identical pressurized inhalers. Patients were treated with study medications for three weeks, followed by one week of open label BDP (500 µg bid). Patients were seen at weekly intervals, and sputum and blood were obtained on each visit. The primary outcome measure was a change in sputum eosinophils, and secondary outcomes were changes in blood eosinophils, eosinophilic cationic protein (ECP) and clinical parameters. Three patients (one in each group) could not produce any sputum after randomization and were excluded from the analysis.RESULTS: Twelve patients received salmeterol, 10 received BDP and nine received placebo. Salmeterol treatment had no effect on sputum eosinophils geometric mean, (from 35.5 [24.9] to 26.9% [25.8]), blood eosinophils (from 7.6 [4.8] to 7.2% [3.9]) or ECP (from 33.1 [18.1] to 27.8 [16.3] mg/L) but improved morning peak expiratory flow (PEF) and diurnal variation of PEF, and decreased the use of rescue medication more than placebo (P<0.05 for all comparisons). In contrast, BDP improved both inflammatory indexes (sputum eosinophils from 22.5 [17.9] to 5.7% [6.8], blood eosinophils from 9.0 [5.5] to 2.1% 1.0, and serum ECP from 36.5 [22.0] to 16.1 [10.1] mg/L) as well as clinical parameters.CONCLUSIONS: These results show that salmeterol improves the symptoms and airway function of patients with asthma, but has no effect on eosinophilic airway infiltration. These findings support current asthma guidelines, which recommend the initial use of inhaled steroid to maximize clinical improvement. While salmeterol also produces clinical improvement, it does not suppress sputum eosinophilia. The analysis of induced or spontaneous sputum for inflammatory indexes may be a valuable clinical test to guide the use of inhaled steroid and/or a long acting beta-agonist.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
F. Schleich ◽  
S. Graff ◽  
F. Guissard ◽  
M. Henket ◽  
V. Paulus ◽  
...  

Abstract Background Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as compared to younger patients. Methods We conducted a retrospective analysis on a series of 758 asthmatics subdivided in three groups: lower than 40, between 40 and 70 and older than 70. All the patients who had a successful sputum induction were included in the study. Results Older patients had a higher Body Mass Index, had less active smokers and were more often treated with Long Acting anti-Muscarinic Agents. We found a significant increase in sputum neutrophil counts with ageing. There was no significant difference in blood inflammatory cell counts whatever the age group. Forced expiratory volume in one second (FEV1) and FEV1/FVC values were significantly lower in elderly who had lower bronchial hyperresponsiveness and signs of air trapping. We found a lower occurrence of the allergic component in advanced ages. Asthmatics older than 70 years old had later onset of the disease and a significant longer disease duration. Conclusion Our study highlights that asthmatics older than 70 years old have higher bronchial neutrophilic inflammation, a poorer lung function, signs of air trapping and lower airway variability. The role of immunosenescence inducing chronic low-grade inflammation in this asthma subtype remains to be elucidated.


Author(s):  
Sanjeev K. Singh ◽  
M. S. Muthu ◽  
Ravindran Revand ◽  
M. B. Mandal

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.


2018 ◽  
Vol 5 (10) ◽  
pp. 2726-2732
Author(s):  
Masoum Khoshfetrat ◽  
Sima Davarpanah ◽  
Aliakbar Keykha

Background: Co-administration of drugs with synergistic effects is considered as one of the methods to increase the effectiveness of intrathecal anesthesia and to reduce the need for injectable analgesics. The purpose of this study was to investigate the efficacy of intrathecal midazolam on enhancing the analgesic effect of fentanyl in patients undergoing lower limb surgery. Materials: The present double-blinded clinical trial was conducted on 90 candidate patients undergoing lower limb orthopedic surgery in 2017 at Khatam-Al-Anbiya Hospital in the city of Zahedan, Iran. To this end, the patients were selected via convenience sampling method and then randomly divided into three groups. Afterwards, 3 cc of 0.5% hyperbaric Marcaine was injected intrathecally in the first group, 3 cc of Marcaine + 25 ug of fentanyl was administered to the second group, and 3 cc of Marcaine + 25 ug of fentanyl + 1 mg of midazolam was administered to the third group (the final volume of all three syringes was brought up to 3.7 cc with normal saline). The duration of sensory nerve block and those of motor block and analgesia, as well as changes in vital signs, were then measured in these groups. Moreover, the data were analyzed using SPSS Statistics (Version 22.0) through Chi-square test and one-way analysis of variance (ANOVA). Results: The mean age and gender distribution of the patients in the three study groups did not differ significantly. The mean duration of sensory nerve block was equal to 98.6+/-11.1 min in the first group, 142.2+/-12.4 min in the second group, and 174.3+/-10.9 min in the third group; all showed a statistically significant difference (P=0.0001, P=0.001, P=0.000).The mean duration of analgesia was also reported to be 204.43+/-0.3 min in the first group, 323.62+/-7.4 min in the second group, and 526.22+/-0.9 min in the third group, indicating a statistically significant difference between the three study groups (P=0.0001, P=0.000, P=000). Conclusion: The results of this study demonstrated that adding midazolam to intrathecal fentanyl could significantly increase the duration of sensory nerve block and that of post-operative analgesia.  


2020 ◽  
Vol 58 (4) ◽  
pp. 421-430 ◽  
Author(s):  
Seungman Cha ◽  
Sung-Tae Hong ◽  
Jin-Su Lee ◽  
Hoo Gn Jeong ◽  
In-Sun Kwon ◽  
...  

This study aimed to investigate whether mass drug administration (MDA) intervention has an equivalent effect on reducing the prevalence and intensity of Schistosoma haematobium infection regardless of the baseline values. A repeated cross-sectional survey was performed targeting students of 12 primary schools in Al Jabalain and El Salam districts of White Nile State, Sudan, at both 1 week before and 8 months after the MDA. Prior to the baseline survey, school-aged children in Al Jabalain had received MDA interventions twice in 4 years, while those in El Salam had not. The baseline prevalence was 9.1% in Al Jabalain and 35.2% in El Salam, which were reduced to 1.8% and 5.5% at 8 months after the MDA, respectively. The corresponding reduction rates were 80.3% and 84.4%, not significant difference between both districts. However, changes in the geometric mean intensity (GMI) of egg counts were significantly different between both districts. The baseline GMIs were 14.5 eggs per 10 ml of urine (EP10) in Al Jabalain and 18.5 EP10 in El Salam, which were reduced to 7.1 and 11.2 EP10 after treatment, respectively. The corresponding reduction rates were 51.0% and 39.5%. In conclusion, MDA interventions were found to bring about similar relative reduction in prevalence regardless of the baseline value; however, the relative reduction in infection intensity was more salient in the district with a low baseline value for both prevalence and intensity. This clearly points to the importance of repeated MDA interventions in endemic areas, which will eventually contribute to schistosomiasis elimination.


Author(s):  
Marília Dalva TURCHI ◽  
Celina Maria Turchi MARTELLI ◽  
Maria Lúcia FERRAZ ◽  
Antonio Eduardo SILVA ◽  
Divina das Dores de Paula CARDOSO ◽  
...  

The study is a randomized trial using recombinant DNA vaccine to determine whether an intramuscular 10 µg dose or intradermal 2 µg induces satisfactory anti-HBs levels compared to the standard dose of intramuscular 20 µg. participants were 359 healthy medical and nurse students randomly allocated to one of the three groups: Group I - IM 20 µg; Group II - IM 10 µg; Group III - ID 2 µg at 0, 1 and 6 months. Anti-HBs titres were measured after complete vaccine schedule by ELISA/Pasteur. Baseline variables were similar among groups and side effects were mild after any dose. Vaccinees in the IM-10 µg group had seroconversion rate and geometric mean titre (GMT 2344 IU L-1), not significant different from the IM-20 µg group (GMT 4570 IU L-1). On the contrary, 21.4% of the ID - 2 µg recipients mount antibody concentration below 10 IU L1 and GMT of 91 IU L-1, a statiscally significant difference compared with the standard schedule IM-20 µg (p < 0.001). A three dose regimen of half dosse IM could be considered an appropriate schedule to prevent hepatitis B in young health adults which is of relevance to the expansion of hepatitis B vaccine programme


2019 ◽  
Vol 12 (3) ◽  
pp. 233-243 ◽  
Author(s):  
M.P. Dembedza ◽  
C. Chidewe ◽  
M.A. Benhura ◽  
B.M. Mvumi ◽  
L.R. Manema ◽  
...  

The longitudinal study assessed the effectiveness of hermetic storage technology in limiting aflatoxin exposure among women aged 15-45 years and children under five years of age from households in selected smallholder farming areas of Zimbabwe. Exposure levels were determined by measuring aflatoxin M1 (AFM1) in urine samples from women and children every three months during the 2015/2016 storage season for nine months. After extraction and immunoaffinity column clean up, AFM1 was determined by high performance liquid chromatography. Generally, the proportion of AFM1 positive urine samples from women increased throughout the grain storage season from 5.4% (n=23) (geometric mean (GM) 1.62 μg/l) at harvest to 75% (n=315) (GM 48.35 μg/l) nine months later (range <limit of quantification (LOQ)-217.29 μg/l). In urine samples from children, AFM1 positive samples increased from 2.2% (n=4) (GM 0.78 μg/l) at harvest to 72.5% (n=98) (GM 22.81 μg/l) nine months later (range <LOQ- 135.00 μg/l). Urinary AFM1 was significantly higher in samples from participants using conventional storage (GM 62.28 μg/l; range <LOQ-217.29 μg/l) compared with samples from participants using hermetic technology (GM 31.95 μg/l; range <LOQ-157.71 μg/l. There was no significant difference in AFM1 concentrations in urine samples from participants consuming grain from metal silos and hermetic bags (P>0.05) hence the two technologies are equally effective in limiting exposure to aflatoxins in humans. The study concluded that aflatoxin exposure levels among women and children from small-holder farming areas increase throughout the postharvest season and the use of hermetic storage technology resulted in up to 33.2% decrease in frequency of detection and 48.7% decrease in levels of AFM1 compared to conventional storage technologies. Thus hermetic grain storage can be an effective technology recommended for limiting aflatoxin exposure in smallholder farming populations.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
C. Q. Hoang ◽  
H. D. Nguyen ◽  
N. X. Ho ◽  
T. H. T. Vu ◽  
T. T. M. Pham ◽  
...  

Background. Scarce information exists about immunity to hand, foot, and mouth disease (HFMD) among household contacts of index cases in Vietnam and what that means for reducing ongoing HFMD transmission in the community. Methods. We analyzed neutralizing antibodies (NT) and the incidence of enterovirus (EVs) infection among household contacts of index cases in a province where HFMD remains endemic. Throat swab and 2 mL blood samples from household contacts were collected at enrollment, during and after 2 weeks follow-up. Results. The incidence of EV-A71 infection among household contacts was 40/84 (47.6%, 95% Cl: 36.9-58.3%), compared with 106/336 (31.5%, 95% Cl: 26.6-36.5%) for CV-A6 and 36/107 (33.6%, 95% Cl: 24.7-42.6%) for CV-A16. The incidence of CV-A6 infection was fairly constant across ages; in contrast, CV-A71 and CV-A16 had some variation across ages. At baseline, higher geometric mean titer (GMT) of EV-A71, CV-A6, and CV-A16 antibody titers was found for 25-34-year groups (range 216.3 to 305.0) compared to the other age groups. There was a statistically significant difference in GMT values of CV-A6 and CV-A16 between those who had an infection or did not have infection among households with an index case of these serotypes. Conclusions. Our results indicated that adults were becoming infected with HFMD and could be contributing to the transmission. There is, therefore, a need for considering the household setting as an additional target for intervention programs for HFMD.


Sign in / Sign up

Export Citation Format

Share Document