Upper airway microbiome transplantation for patients with chronic rhinosinusitis.

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.

Nasal administration of a probiotic assemblage in allergic rhinitis: A randomised placebo-controlled crossover trial.

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. TRIAL REGISTRATION: not registered.

Oral challenges with four apple cultivars result in significant differences in oral allergy symptoms.

BACKGROUND: We analyzed the hypoallergenic potential of a recently bred apple selection with unusually low content of Mal d 1, using an oral challenge model with three additional apple cultivars for comparison. METHODS: Sixty-six birch pollen-allergic individuals with a history of oral allergy syndrome after apple intake were subjected to a double-blind oral provocation with two apple cultivars (B:0654 and 'Discovery'). Thirteen also tested two other apple cultivars ('Ingrid Marie' and 'Gloster'). Three doses were given consecutively, 30 min apart: 10 g without peel, and 10 and 50 g with peel. A final assessment was conducted 30 min after the last intake. Oral symptoms were graded from 0 to 5. Total oral symptom score (TOS) included all scores for each cultivar at all time points. RESULTS: B:0654 induced significantly higher TOS than 'Discovery' when tested by 66 individuals, in spite of its lower Mal d 1 content. TOS values were higher in females and increased with increasing age of the individuals when challenged with 'Discovery'. Among the 13 individuals who tested all four cultivars, B:0654 produced a higher score after the second dose compared to 'Ingrid Marie'. This was also the case after the third dose compared to 'Ingrid Marie' and 'Gloster', and again 30 min after the last intake compared to each of the other three cultivars, as well as a higher TOS compared to each of the other three cultivars (all p < 0.01). CONCLUSIONS: Our test was safe and well tolerated, and produced significant differences among the apple cultivars. Contrary to expectations, B:0654 was less well tolerated than the other three cultivars.

Wine produced by ecological methods produces relatively little nasal blockage in wine-sensitive subjects.

CONCLUSION: Subjects with self-reported nasal symptoms following consumption of red wine may respond with less nasal blockage to a wine produced with ecological methods than to wine not labelled as ecologically produced. OBJECTIVE: To compare nasal symptoms following intake of three different wines--one that was ecologically produced and two that were traditionally produced. SUBJECTS AND METHODS: Individuals with self-reported nasal symptoms following consumption of red wine were subjected to controlled intake of three different wines in a double-blinded, randomized, and crossover design. Nasal symptoms and peak nasal inspiratory flow (PNIF) were monitored before and 15, 30, 45, and 60 min following intake of wine. RESULTS: All wines produced nasal symptoms, notably nasal blockage. While blockage scores did not differ between the two non-ecological wines, the ecological wine was associated with significantly lower blockage scores, as compared with both the other wines.

Effects of loratadine on red wine-induced symptoms and signs of rhinitis.

OBJECTIVE: Intake of red wine may produce nasal symptoms. Little is known about the pathophysiology and pharmacology of this condition. The aim of this study was to examine whether nasal symptoms produced by red wine are reproducible, associated with mucinous secretion or plasma exudation and affected by antihistamine treatment. MATERIAL AND METHODS: Twenty-eight subjects with a history of nasal symptoms associated with red wine intake received oral challenges with red wine and raspberry juice in a crossover design. Nasal symptoms and peak inspiratory flow (PIF) were assessed. Nasal lavages were performed and levels of fucose and alpha2-macroglobulin were determined as indices of mucinous secretion and plasma exudation, respectively. Twelve responders (according to preset criteria) were re-challenged 1 h after loratadine (10 mg) treatment, in a double-blind, placebo-controlled crossover design. Nasal symptoms and PIF were reassessed. Nasal lavages were performed and levels of fucose were redetermined. RESULTS: Red wine intake produced nasal symptoms (p < 0.05) and decreased nasal PIF (p < 0.01-0.05). A total of 54% of subjects were categorized as responders, and in this group red wine produced a slight increase in lavage fluid levels of fucose (p < 0.05). In contrast, levels of alpha2-macroglobulin were unaffected. A total of 83% of responders developed symptoms at re-challenge. Loratadine reduced post-challenge nasal secretion (p < 0.05). Also, red wine failed to reduce nasal PIF in patients receiving loratadine. CONCLUSION: Nasal symptoms associated with red wine intake can be reproduced by oral red wine challenges. This symptomatology may be associated with mucinous secretion, but not with plasma exudation. Loratadine may partially reduce nasal symptoms associated with intake of red wine.