| 1. |
- Mårtensson, Anders, et al.
(författare)
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Nasal administration of a probiotic assemblage in allergic rhinitis: A randomised placebo-controlled crossover trial
- 2022
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 52:6, s. 774-783
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Tidskriftsartikel (refereegranskat)abstract
- Background: Topical probiotics have been suggested as a treatment option for allergic rhinitis, as they may skew the immune response towards a beneficial type-1 non-allergic profile. So far observations in man have exclusively involved oral intake. The aim of this study was to examine whether a topical/nasal administration of a probiotic assemblage (PA) affects quality of life, symptoms and signs of allergic rhinitis in a nasal allergen challenge (NAC) model.Methods: In a placebo-controlled and crossover design, 24 patients with seasonal allergic rhinitis were randomised to topical/nasal administration with a PA of Lactobacillus rhamnosus SP1, Lactobacillus paracasei 101/37 and Lactococcus lactis L1A or placebo for 3 weeks. Participants and investigators were blind to treatment allocation. The last week of each treatment period was combined with a NAC series. Efficacy variables were "Mini-Rhinoconjunctivitis Quality of Life Questionnaire" (Mini-RQLQ), "Total Nasal Symptom Score" (TNSS), "Peak Nasal Inspiratory Flow" (PNIF) and "Fractional Exhaled Nitric Oxide" (FeNO). In addition, to assess whether or not the PA produced any pro-inflammatory effect per se, soluble analytes were monitored in nasal lavage fluids. Finally, bacterial cultures, sampled using swabs from the middle nasal meatus, were assessed for the presence of the PA by MALDI-TOF analysis.Results: Administration of the PA did not produce any nasal symptoms (cf. placebo). An innate immune response was discerned within the PA run (cf. baseline), but no change in nasal lavage fluid levels of cytokines/mediators was observed cf. placebo except for IL-17/IL-17A (a minor increase in the PA run). Administration of the PA did neither affect Mini-RQLQ, TNSS, PNIF nor FeNO. No evidence of persistent colonization was observed.Conclusions: Topical/nasal administration of a PA comprising Lactobacillus rhamnosus SP1, Lactobacillus paracasei 101/37 and Lactococcus lactis L1A, while likely evoking a minor innate immune response yet being safe, does not affect quality of life, symptoms or signs of allergic rhinitis.
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| 2. |
- Mårtensson, Anders, et al.
(författare)
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Upper airway microbiome transplantation for patients with chronic rhinosinusitis
- 2023
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Ingår i: International Forum of Allergy and Rhinology. - : Wiley. - 2042-6976 .- 2042-6984. ; 13:6, s. 979-988
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic or recurrent rhinosinusitis without polyps (CRSsNP) is characterized by a persistent inflammation of the sinonasal mucosa. The underlying cause is unclear but increasing interest has been directed toward changes in the sinonasal microbiome as a potential driver. Methods: Twenty-two patients diagnosed with CRSsNP were treated with antibiotics for 13 days, followed by 5 consecutive days of nasal microbiome transplants from healthy donors. Outcome measures were 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire, total nasal symptom score (TNSS), endoscopic grading, 16S ribosomal RNA (rRNA) next generation sequencing (microbiome analysis), and nasal lavage fluid analysis of inflammatory cytokines. Patients were examined at the start of the study and after antibiotic treatment as well as 10 days and 3 months after the transplant series. Results: At the end of the study, patients reported significantly reduced SNOT-22 scores and microbiome analysis showed significantly increased abundance and diversity. No significant change was observed for TNSS or endoscopic scoring. Conclusion: Nasal microbiome transplants obtained from healthy individuals and administered as nasal lavages to patients with CRSsNP are feasible. The patients reported significant and lasting reduction of symptoms and these findings were associated with a lasting increase in abundance and diversity of the local bacterial flora. The observations, which need to be confirmed by randomized controlled trials, may constitute a new treatment avenue for these difficult to treat patients where antibiotics only provide short lasting symptom control.
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| 3. |
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| 4. |
- Greiff, Lennart, et al.
(författare)
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Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis
- 2012
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective: To evaluate the efficacy and safety of intranasal AZD8848. Methods: In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 mu g) was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779). In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 mu g) was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003). Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and alpha(2)-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results: AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30100 mu g produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and a2-macroglobulin were also reduced by AZD8848. Conclusions: Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis.
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| 5. |
- Mårtensson, Anders, et al.
(författare)
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Clinical efficacy of a topical lactic acid bacterial microbiome in chronic rhinosinusitis: A randomized controlled trial
- 2017
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Ingår i: Laryngoscope Investigative Otolaryngology. - : Wiley. - 2378-8038. ; 2:6, s. 410-416
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveA locally disturbed commensal microbiome might be an etiological factor in chronic rhinosinusitis (CRS) in general and in CRS without nasal polyps (CRSsNP) in particular. Lactic acid bacteria (LAB) have been suggested to restore commensal microbiomes. A honeybee LAB microbiome consisting of various lactobacilli and bifidobacteria have been found potent against CRS pathogens in vitro. Recently, we examined effects of single nasal administrations of this microbiome in healthy subjects and found it inert. In this study, we examined effects of repeated such administrations in patients with CRSsNP.Study DesignThe study was of a randomized, double-blinded, crossover, and sham-controlled design.MethodsTwenty patients received 2 weeks' treatment administered using a nasal spray-device. The subjects were monitored with regard to symptoms (SNOT-22 questionnaire, i.e., the primary efficacy variable), changes to their microbiome, and inflammatory products (IL-6, IL-8, TNF-, IL-8,a, and MPO) in nasal lavage fluids.ResultsNeither symptom scores, microbiological explorations, nor levels of inflammatory products in nasal lavage fluids were affected by LAB (c.f. sham).ConclusionTwo weeks' nasal administration of a honeybee LAB microbiome to patients with CRSsNP is well tolerated but affects neither symptom severity nor the microbiological flora/local inflammatory activity.Level of Evidence1b
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| 6. |
- Mårtensson, Anders, et al.
(författare)
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Effects of a honeybee lactic acid bacterial microbiome on human nasal symptoms, commensals, and biomarkers
- 2016
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Ingår i: International Forum of Allergy & Rhinology. - : Wiley. - 2042-6984 .- 2042-6976. ; 6:9, s. 956-963
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lactic acid bacteria (LAB) can restore commensal microbiomes and prevent infections. Arguably, nasal administrations of LAB may therefore be beneficial in chronic rhinosinusitis (CRS). Previous studies have examined effects of topical/nasal LAB in children with secretory otitis media, but little is as yet known about their effects on the human nasal airway. The aim of this pilot study was to examine effects on nasal symptoms and commensal bacteria in healthy subjects of nasal administration of a honeybee LAB microbiome; ie, a mixture of 9 Lactobacillus spp. and 4 Bifidobacterium spp. obtained from the honeybee Apis mellifera. Furthermore, we aimed to assess whether or not the honeybee LAB produced a local inflammatory response.METHODS: Twenty-two healthy subjects received a single administration of honeybee LAB in a sham-controlled, double-blinded, and crossover design. Using questionnaires, microbiological methods, and nasal lavages, they were assessed regarding symptoms, changes to commensal bacteria, and inflammatory products in nasal lavage fluids.RESULTS: The honeybee LAB did not produce any symptoms or other untoward effects. No changes were observed of commensal bacteria by the honeybee LAB, and no inflammatory response was detected (compared to sham); ie, unaffected nasal lavage fluid levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), monokine induced by interferon-γ (MIG), interleukin-15 (IL-15), epidermal growth factor (EGF), eotaxin, interferon gamma-induced protein-10 (IP-10), and interleukin-1 receptor antagonist (IL-1RA).CONCLUSION: A single human nasal administration of a honeybee LAB microbiome is well tolerated. Specifically, it does not affect commensal bacteria and does not produce an inflammatory response.
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| 7. |
- Valdemarsson, Stig, et al.
(författare)
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Evaluation of surgery for acromegaly: role of intraoperative growth hormone measurement?
- 2001
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 61:6, s. 459-470
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Intraoperative growth hormone (GH ) measurement has earlier been tried to improve surgery for acromegaly. We calculated GH half-life after adenomectomy and evaluated the possible role of this variable in predicting the final outcome of pituitary surgery in 28 consecutive patients with acromegaly. The sensitivity, specificity and predictive values were determined in relation to the results from GH suppression during an oral glucose load and IGF-1 3 months postoperatively. The GH half-life data were also compared to the corresponding results obtained from GH measurements between 60 min and 180 min after adenomectomy, and early, within 1 week, postoperatively. RESULTS: GH half-life < or =31 min was recorded in 8/13 cured patients but also in 2/15 unsuccessful cases. A mean GH concentration < or =4.4 mU/L between 60 min and 120 min after adenomectomy was found in 11/13 cured subjects but also in 3/15 not cured patients. A mean GH < or =4.0 mU/L between 90 min and 180 min was found in 11/13 cured and in 4/15 not cured patients. A mean early postoperative GH concentration < or =2.6 mU/L was noted in all 13 cured patients, but also in 2/13 unsuccessful cases. The specificity of early postoperative GH < or = 2.6 mU/L was 100% compared to 62% for a GH half-life < or =31 min (p<0.05) and 85% for the GH mean values between 60 min and 120 min and 90 min and 180 min, respectively. The sensitivity for persistent disease of values above the four cut-off limits used was between 73% and 87%. The positive predictive value for a mean early postoperative GH value >2.6 mU/L was 100%, and 72% for a GH half-life >31 min (n.s.). CONCLUSION: Although intraoperative GH half-life might be useful in some cases, it was not a reliable tool for predicting outcome of pituitary surgery in acromegaly. In cases with a 51% decrease of a basal GH concentration >5.5 mU/L, mean GH values < or =4 to < or =4.4 mU/L late intraoperatively were more informative but not as good as those obtained from the mean of a series of GH values drawn on one occasion within 1 week postoperatively, offering a 100% specificity for cure if < or =2.6 mU/L. Intraoperative GH half-life measurements should therefore be used with caution. The predictive values of the cut-off limits used in this study should be further evaluated before general application.
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| 10. |
- Balch, Graeme, et al.
(författare)
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Oral corticosteroids for painful acute otitis externa (swimmer's ear): A triple-blind randomised controlled trial.
- 2019
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Ingår i: Australian journal of general practice. - 2208-7958. ; 48:8, s. 565-572
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Tidskriftsartikel (refereegranskat)abstract
- Acute otitis externa is often painful. The aim of this study was to evaluate the efficacy of 10 mg oral prednisolone twice daily for four days in addition to conventional therapy.Patients attending general practice clinics in Far North Queensland, Australia, for acute painful otitis externa were given a study capsule with either 10 mg prednisone or placebo.Seventy-three patients were randomised. Results from 19 patients in the intervention group and 11 patients in the control group were analysed. Oral corticosteroids did not decrease the time to being completely pain-free but decreased the time for pain to reduce from more than 'moderate pain' to less than 'moderate pain', from 3.7 days to 2.4 days (P= 0.012, log rank test).Oral corticosteroids seem to be effective in reducing more than 'moderate pain' to less than 'moderate pain'. However, this result needs to be confirmed in a larger trial.
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