Background: Current phenotyping of chronic rhinosinusitis (CRS) into CRS with nasal polyps and without nasal polyps may not adequately reflect the pathophysiologic diversity within CRS.

CD-sens seems to be very useful for the determination of a patient's allergen sensitivity and should be evaluated for the measurement and monitoring of anti-IgE treatment efficacy. CD-max, the conventional approach to basophil allergen challenge, which mirrors cell reactivity, gives incorrect information.

Secretion of outer membrane vesicles (OMV) is an intriguing phenomenon of Gram-negative bacteria and has been suggested to play a role as virulence factors. The respiratory pathogens Moraxella catarrhalis reside in tonsils adjacent to B cells, and we have previously shown that M. catarrhalis induce a T cell independent B cell response by the immunoglobulin (Ig) D-binding superantigen MID. Here we demonstrate that Moraxella are endocytosed and killed by human tonsillar B cells, whereas OMV have the potential to interact and activate B cells leading to bacterial rescue. The B cell response induced by OMV begins with IgD B cell receptor (BCR) clustering and Ca2+ mobilization followed by BCR internalization. In addition to IgD BCR, TLR9 and TLR2 were found to colocalize in lipid raft motifs after exposure to OMV. Two components of the OMV, i.e., MID and unmethylated CpG-DNA motifs, were found to be critical for B cell activation. OMV containing MID bound to and activated tonsillar CD19+ IgD+ lymphocytes resulting in IL-6 and IgM production in addition to increased surface marker density (HLA-DR, CD45, CD64, and CD86), whereas MID-deficient OMV failed to induce B cell activation. DNA associated with OMV induced full B cell activation by signaling through TLR9. Importantly, this concept was verified in vivo, as OMV equipped with MID and DNA were found in a 9-year old patient suffering from Moraxella sinusitis. In conclusion, Moraxella avoid direct interaction with host B cells by redirecting the adaptive humoral immune response using its superantigen-bearing OMV as decoys.

In Sweden, the cost of rhinitis is euro 2.7 billion a year in terms of lost productivity. A reduction in lost productivity of 1 day per individual and year would potentially save euro 528 million.

BackgroundAllergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases. We and others have previously demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, this has recently been disputed. The aim of this study was therefore to expand our previous trial, further assessing the safety and efficacy of ILIT.MethodsThirty-six patients with pollen-induced rhinoconjunctivitis were randomised to receive three intralymphatic inguinal injections of active allergen (1000 SQ-U birch- or grass-pollen) or placebo. Clinical effects, safety and circulating immunological markers were assessed before, 4 weeks after treatment and at the end of the consecutive pollen season.ResultsNo moderate or severe reactions were recorded following ILIT. Patients receiving active ILIT experienced a significant improvement in self-recorded seasonal allergic symptoms, as compared to placebo (p = 0.05). In a subgroup of these patients (“improved”), a reduction in nasal symptoms following nasal allergen provocation was also demonstrated. No changes in total IgE or IgG4 were found. However, the affinity of allergen specific IgG4 following active treatment was significantly increased, as compared to non-improved patients (p = 0.04). This could be correlated with clinical improvement, on an individual level.ConclusionsThis double-blinded placebo-controlled study confirms that ILIT is a safe and effective treatment for pollen-induced rhinoconjunctivitis, markedly reducing seasonal allergic symptoms.Trial registrationEudraCT: 2009-016815-39Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0324-9) contains supplementary material, which is available to authorized users.

Allergic rhinitis is a global illness with a well-recognised impact on quality of life and work performance. Comparatively little is known about the extent of its economic impact on society. The TOTALL study estimates the total cost of allergic rhinitis using a sample representing the entire Swedish population of working age. A questionnaire focused on allergic rhinitis was mailed out to a random population of Swedish residents, aged 18–65 years. Health-care contacts, medications, absenteeism (absence from work) and presenteeism (reduced working capacity at work) were assessed, and the direct and indirect costs of allergic rhinitis were calculated. Medication use was evaluated in relation to the ARIA guidelines. In all, 3,501 of 8,001 (44%) answered the questionnaire, and 855 (24%) of these reported allergic rhinitis. The mean annual direct and indirect costs because of allergic rhinitis were €210.3 and €750.8, respectively, resulting in a total cost of €961.1 per individual/year. Presenteeism represented 70% of the total cost. Antihistamines appear to be used in excess in relation to topical steroids, and the use of nasal decongestants was alarmingly high. The total cost of allergic rhinitis in Sweden, with a population of 9.5 million, was estimated at €1.3 billion annually. These unexpectedly high costs could be related to the high prevalence of disease, in combination with the previously often underestimated indirect costs. Improved adherence to guidelines might ease the economic burden on society.

Summary Toll‐like receptors (TLRs) recognize specific pathogen‐associated molecular patterns (PAMPs), which subsequently trigger innate immunity. Recent data also suggest a role for TLRs in the direct activation of adaptive immune cells. In the present study, the expression and function of TLR1–TLR10 were characterized in purified human tonsillar B cells, focusing on differences among CD19+ CD38– CD27– (naïve B cells), CD19+ IgD– CD27–[germinal centre (GC) B cells] and CD19+ CD38– CD27+ (memory B cells) cells. The study was also designed to compare the TLR expression in B cells obtained from infected and hyperplastic tonsils that served as controls. The results demonstrated a distinct repertoire of TLRs, in which TLR1, TLR2, TLR7, TLR9 and TLR10 predominated. No differences were found among naïve, GC and memory B cells. Tonsillar infection did not substantially alter the TLR expression profile in ex vivo‐isolated B‐cell subsets. Purified CD19+ B cells stimulated with Pam3CSK4, R‐837 and CpG oligodeoxynucleotide (ODN) 2006, via TLR1/TLR2, TLR7 and TLR9, respectively, showed an induction of interleukin‐6 secretion and an up‐regulated expression of human leucocyte antigen (HLA)‐DR. Collectively, the present study demonstrates that B cells exhibit constitutively high levels of specific TLRs, which are not developmentally regulated during the B‐cell differentiation process. Ongoing microbial infections, such as chronic tonsillitis, do not appear to affect the TLR profile in B cells. Furthermore, the distinct expression of TLRs allows B cells to respond directly to the cognate PAMPs. This further emphasizes the role of TLRs in directly activating adaptive immune cells.

103Sinusitis 104 105 Conflicts of interest 106Jan Lötvall has received consultancy and speaker fees from AstraZeneca, GlaxoSmithKline, MSD/Merck, 107Novartis, and Schering-Plough. 109Author contributions 110PT, RN, RH, and DJ analyzed the data and wrote the manuscript. WF, CB, PB and DJ conceived and supervised 111 the study. All authors collected data and critically revised the manuscript. 113Body word count: 2673 114Page 3 of 17 Allergy 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 118in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and 119validity of a symptom based definition of CRS using data from the GA2LEN European survey. 120Methods: On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, 121allergic rhinitis and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in 122prevalence of CRS between two study points, the standardized absolute repeatability and the chance corrected 123 repeatability (kappa) were determined. In two centers 342 participants underwent nasal endoscopy. The 124 association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. 125Results: There was a decrease in prevalence of CRS between the two study phases, and this was consistent 126across all centers (-3.0%, 95% CI: -5.0 to -1.0%, I 2 =0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 160Study design 161In a first cross-sectional phase (the GA²LEN Survey), 11 participating centers sent a questionnaire by mail to a 162 random sample of at least 3000 subjects aged 15 to 75 years, with up to three attempts to elicit a response. 163Samples were identified by random sampling from a population based local sampling frame. 164The questionnaire was newly developed for the diagnosis of chronic rhinosinusitis ( (Table 1); additionally, subjects were asked if a doctor had ever told whether the subject had CRS 167(further referred to as 'self-reported doctor-diagnosed CRS'). Asthma was defined as reporting 'having ever had 168 asthma' and at least one of the following symptoms in the last 12 months: 1) wheeze or whistling in the chest; or 1692) waking up with chest tightness, shortness of breath or an attack of coughing. Allergic rhinitis was defined by 170 the self reported history of 'nasal allergy'. 171In a second phase (the GA²LEN Survey Follow-Up), each center invited 120 randomly selected subjects with 172 asthma, 120 with CRS, 40 with asthma and CRS and 120 with neither asthma or CRS for a clinical study visit 173with further investigations among which a questionnaire including the same questions as those describ...