| 1. |
- Bjermer, Leif, et al.
(författare)
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The complex pathophysiology of allergic rhinitis : Scientific rationale for the development of an alternative treatment option
- 2019
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Ingår i: Allergy, Asthma and Clinical Immunology. - : Springer Science and Business Media LLC. - 1710-1492. ; 15, s. 24-
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Forskningsöversikt (refereegranskat)abstract
- Allergic rhinitis (AR) poses a global health problem and can be challenging to treat. Many of the current symptomatic treatments for AR have been available for decades, yet there has been little improvement in patient quality of life or symptom burden over the years. In this review, we ask why this might be and explore the pathophysiological gaps that exist within the various AR treatment classes. We focus on the benefits and drawbacks of different treatment options and delivery routes for AR treatments and consider how, given what is known about AR pathophysiology and symptomatology, patients may be offered more effective treatment options for rapid, effective, and sustained AR control. In particular, we consider how a new AR preparation, MP-AzeFlu (Dymista ® , Meda, Sweden), comprising a formulation of an intranasal antihistamine (azelastine hydrochloride), an intranasal corticosteroid (fluticasone propionate), and excipients delivered in a single spray, may offer benefits over and above single and multiple AR therapy options. We review the evidence in support of this treatment across the spectrum of AR disease. The concept of AR control is also reviewed within the context of new European Union and Contre les Maladies Chroniques pour un VIeillissement Actif-Allergic Rhinitis and its Impact on Asthma initiatives.
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| 2. |
- Bråbäck, Lennart, et al.
(författare)
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Confounding with familial determinants affects the association between mode of delivery and childhood asthma medication : a national cohort study
- 2013
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Ingår i: Allergy, Asthma & Clinical Immunology. - : BioMed Central. - 1710-1484 .- 1710-1492. ; 9:1, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mode of delivery may affect the risk of asthma but the findings have not been consistent and factors shared by siblings may confound the associations in previous studies. METHODS: The association between mode of delivery and dispensed inhaled corticosteroid (ICS) (a marker of asthma) was examined in a register based national cohort (n=199 837). A cohort analysis of all first born children aged 2-5 and 6-9 years was performed. An age-matched sibling-pair analysis was also performed to account for shared genetic and environmental risk factors. RESULTS: Analyses of first-borns demonstrated that elective caesarean section was associated with an increased risk of dispensed ICS in both 2-5 (adjusted odds ratio (aOR)=1.19, 95% confidence interval (CI) 1.09-1.29) and 6-9 (aOR=1.21, 1.09-1.34) age groups. In the sibling-pair analysis, the increased risk associated with elective caesarean section was confirmed in 2-5 year olds (aOR=1.22, 1.05-1.43) but not in 6-9 year olds (aOR=1.06, 0.78-1.44). Emergency caesarean section and vacuum extraction had some association with dispensed ICS in the analyses of first-borns but these associations were not confirmed in the sibling-pair analyses. CONCLUSIONS: Confounding by familial factors affects the association between mode of delivery and dispensed ICS. Despite this confounding, there was some evidence that elective caesarean section contributed to a modestly increased risk of dispensed ICS but only up to five years of age.
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| 3. |
- Dreborg, Sten, et al.
(författare)
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Do epinephrine auto-injectors have an unsuitable needle length in children and adolescents at risk for anaphylaxis from food allergy?
- 2016
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Ingår i: Allergy, Asthma & Clinical Immunology. - : Springer Science and Business Media LLC. - 1710-1484 .- 1710-1492. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Food allergy is the most common cause of anaphylaxis in children. Intramuscular delivery of epinephrine auto-injectors (EAI) is the standard of care for the treatment of anaphylaxis. We examined if children and adolescents at risk of anaphylaxis weighing 15-30 kg and >30 kg would receive epinephrine into the intramuscular space with the currently available EAI in North America and Europe. Methods: The distance from skin to muscle (STMD) and skin to bone (STBD) on the mid third anterolateral area of the right thigh was measured by ultrasound applying either high pressure ((max)) or slight pressure ((min)) in 102 children weighing 15-30 kg (group 1) and 100 children and adolescents, weighing more than 30 kg (group 2). Results: Using a high pressure EAI (HPEAI), Epipen Jr (R) and Auvi-Q (R)/Allerject (R) 0.15 mg, 11/102 (11 %) children in group 1 and 38/102 (38 %) using another HPEAI, Jext (R), had a STMDmax that showed a risk of intraosseous injection. There was a 1 % risk of subcutaneous injection with these devices. There was no risk of intraosseous injection using a low pressure EAI (LPEAI), Emerade (R). In group 2, the risk of intraosseous injection using a HPEAI was 3 % and no risk using a LPEAI. However, the risk of subcutaneous injection using HPEAI was 9 % and using LPEAI was 2 %. Conclusion: There is a risk of intraosseous injection using HPEAI (Epipen (R)/Epipen Jr (R), Auvi-Q (R)/Allerject (R) and especially Jext (R)) in children at risk of anaphylaxis. There was also a risk of subcutaneous injection using the currently available HPEAI in children and adolescents.
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| 4. |
- Dreborg, Sten, 1933-, et al.
(författare)
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Epinephrine auto-injector needle length : The impact of winter clothing
- 2020
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Ingår i: Allergy, Asthma & Clinical Immunology. - : BMC. - 1710-1484 .- 1710-1492. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epinephrine auto-injectors are expected to deliver the drug intramuscularly.Objective: To study whether injection through clothing influences the frequency of subcutaneous and intraosseous/periosteal deposition of epinephrine.Methods: Skin to muscle and skin to bone distances were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, with high or low pressure on the ultrasound probe. The risk/percentage of subcutaneous and intraosseous/periosteal injections was calculated using the lower and upper limits for the authority-approved length of EAI needles as provided by two high pressure EAI manufacturers and one low pressure EAI manufacturer. The addition winter clothing on the delivery of epinephrine was illustrated by comparing drug delivery fissue depth with no clothes. Furthermore, the riof non-intramuscular delivery for the shortest and longest approved needle length was calculated.Results: When using EpipenJr(R) in children < 15 kg the risk of intraosseous/periostal injection was reduced from 1% and 59% for the shortest and longest approved needle length to 0 and 15% with winter clothes. The Auvi-Q(R) 0.1 mg had no risk of intraosseous/periosteal injection. However, the subcutaneous deposition risk increased from 94% and 28% to 100% and 99% with winter clothes. The risk of subcutaneous injection using EpipenJr(R) in the youngest children increased from 13% and 0% to 81% and 1% with winter clothes, and with Epipen(R) in adults from 45% and 17% to 60% and 38%. Emerade(R), had a risk of subcutaneous injection in adults increasing from 14% and 10% to 28% and 21% adding winter clothes.Conclusion The risk of intraosseous/periosteal injections decreases and the risk of subcutaneous injection increases when injecting through winter clothes for all EAIs.
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| 5. |
- Dreborg, Sten, 1933-, et al.
(författare)
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International recommendations on epinephrine auto-injector doses often differ from standard weight-based guidance : a review and clinical proposals
- 2022
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Ingår i: Allergy, Asthma & Clinical Immunology. - : BioMed Central (BMC). - 1710-1484 .- 1710-1492. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Background: In anaphylaxis, the dosing of injectable epinephrine in medical settings has been arbitrarily recommended to be 0.01 mg/kg of body weight. For ethical reasons, there have been no dose-response studies or double-blind studies performed on patients with active anaphylaxis. Intramuscular delivery of epinephrine has been the standard. Auto-injectors for use in the treatment of anaphylaxis are available in four strengths (0.1, 0.15, 0.3, and 0.5 mg). However, in many countries, only the 0.15 and 0.3 mg strengths are available. Consequently, many adult, heavy patients are prescribed the 0.3 mg dose, which may result in only one-fifth to one-third of the recommended weight-based dose being administered in heavy patients experiencing anaphylaxis. Underdosing may have therefore contributed to mortality in anaphylaxis. Objective: To review the doses of epinephrine recommended for the treatment of anaphylaxis in the community, and assess whether recommendations should be made to increase dosing for heavy adult patients in hopes of avoiding future deaths from anaphylaxis. Methods: We reviewed multiple national and international recommendations for the dosing of epinephrine. We also reviewed the literature on adverse drug reactions from epinephrine, lethal doses of epinephrine, and epinephrine dose-finding studies. Results: The majority of national and regional professional societies and authorities recommend epinephrine delivered by auto-injectors at doses far lower than the generally accepted therapeutic dose of 0.01 mg/kg body weight. Furthermore, we found that the recommendations vary even within regions themselves. Conclusions: We suggest prescribing more appropriate doses of epinephrine auto-injectors based on weight-based recommendations. There may be some exceptions, such as for patients with heart disease. We hypothesize that these recommendations will lead to improved outcomes of anaphylaxis.
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| 6. |
- Dreborg, Sten, 1933-, et al.
(författare)
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The pharmacokinetics of epinephrine/adrenaline autoinjectors
- 2021
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Ingår i: Allergy, Asthma & Clinical Immunology. - : BioMed Central (BMC). - 1710-1484 .- 1710-1492. ; 17:1
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Forskningsöversikt (refereegranskat)abstract
- Background For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect. Objective To review the literature on pharmacokinetics of epinephrine autoinjectors. Results Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in C-max and AUC(0-20) when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster C-max. Two discernable C-max's were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies. Conclusions Intramuscular injection with higher doses of epinephrine appears to lead to a higher C-max. There is a dose dependent increase in plasma concentration and AUC(0-20). Most investigators found two C-max's with T-max 5-10 min and 30-50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.
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| 7. |
- Ekstedt, S, et al.
(författare)
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Effects of MP-AzeFlu enhanced by activation of bitter taste receptor TAS2R
- 2020
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Ingår i: Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. - : Springer Science and Business Media LLC. - 1710-1484. ; 16:1, s. 45-
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Tidskriftsartikel (refereegranskat)abstract
- MP-AzeFlu is relatively new a pharmaceutical drug used in the treatment of allergic rhinitis. It is comprised of azelastine hydrochloride (AZE), a potent histamine-H1-receptor antagonist and fluticasone propionate (FP), corticosteroid. It’s somewhat bitter taste (often considered a disadvantage) can be attributed to AZE. We here hypothesize that MP-AzeFlu may induce some of its beneficial effects through activation of bitter taste receptors (Tas2R), which have recently been described in human airways. In the nose Tas2Rs induce secretion of antimicrobial peptides and increase ciliary activity, while in the lung they cause airway smooth muscle relaxation. The mechanisms behind Tas2R-mediated effects are not yet fully known. In order to evaluate the role of Tas2R in the effects induced by MP-AzeFlu the dilatory response of pre-contracted isolated airways from Balb/c mice was investigated in tissue bath myographs in the presence or absence of various well-characterized pharmacological antagonists or their corresponding vehicles. MP-AzeFlu caused a potent dose-dependent relaxation of pre-contracted airways, an effect probably mediated by its AZE component. The dilatory effect of MP-AzeFlu and AZE both mimicked the response induced by the Tas2R agonist, chloroquine, but was independent of histamine receptor (H1-, H2- and H3-), prostaglandins, cAMP and cGMP involvement, all known to be common pathways for airway dilation. Other bitter-tasting antihistamines (i.e. olopatadine and desloratadine) also relaxed airway segments. These data support the notion that MP-AzeFlu has the ability to activate Tas2R in the same way as chloroquine. The effect appears to be mediated by AZE, but not via the histamine receptor. Activation of Tas2R by MP-AzeFlu may contribute to its superior efficacy over FP observed in controlled clinical trials in patients with moderate/severe allergic rhinitis.
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| 8. |
- Frykas, TLM, et al.
(författare)
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Mothers of children with food allergies report poorer perceived life status which may be explained by limited career choices
- 2021
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Ingår i: Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. - : Springer Science and Business Media LLC. - 1710-1484. ; 17:1, s. 12-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Pediatric food allergy is associated with direct, indirect and intangible costs. However, it remains unclear if intangible costs of pediatric food allergy influence parental career choices. Using data from 63 parents whose children had been diagnosed by a pediatric allergist with food allergy, we sought to (a) establish perceived life status of families with a food allergic child, and (b) to describe any career limitations viewed as attributable to food allergy. Compared to responding parents whose children had one to two food allergies, those with three or more food allergies had significantly poorer perceived life status (ß − 0.74; 95%CI − 1.41; − 0.07; p < 0.05). Overall, 14.3% of parents (all mothers) reported career limitations due to food allergy. Two of the 7 mothers (28.6%) who reported career limitations due to their child's food allergy fell below Statistics Canada cut-off for low-income, after tax dollars (LIM-AT). One of the three mothers who had changed jobs because of their child's food allergy was below the LIM-AT. No fathers reported food allergy-related career limitations. In conclusion, mothers of children with multiple food allergies reported worse perceived life status that may be partly explained by food allergy-related career limitations.
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