HealthSWEDE: costs with sublingual immunotherapy-a Swedish questionnaire study.

BACKGROUND: The aim of this cross-sectional survey was to compare the health-economic consequences for allergic rhinitis (AR) patients treated with sublingual Immunotherapy (SLIT) in terms of direct and indirect costs with a reference population of patients receiving standard of care pharmacological therapy. METHODS: Primary objective was to analyse the health-economic consequences of SLIT for grass pollen allergy in Sweden vs reference group waiting for subcutaneous immunotherapy (SCIT). A questionnaire was mailed to two groups of AR patients. RESULTS: The questionnaire was distributed to 548 patients, 307 with SLIT and 241 in reference group (waiting for SCIT). Response rate was 53.8%. Mean annual costs were higher for reference patients than SLIT group; € 3907 (SD 4268) vs € 2084 (SD 1623) p < 0.001. Mean annual direct cost was higher for SLIT-patients, € 1191 (SD 465) than for reference, € 751 (SD 589) p < 0.001. Mean annual indirect costs for combined absenteeism and presenteeism were lower for patients treated with SLIT, € 912 (SD 1530), than for reference, € 3346 (SD 4120) p < 0.001, with presenteeism as main driver. CONCLUSIONS: SLIT seems to be a cost-beneficial way to treat seasonal AR. This information might be used to guide future recommendations.

Aging-in-Place: Residents' Attitudes and Floor Plan Potential in Apartment Buildings From 1990 to 2015.

OBJECTIVES: We investigated apartment designs in apartment blocks built 1990-2015 in Gothenburg, Sweden. We investigated the residents' attitudes toward their previous, present, and future housing and their perceived possibilities for aging-in-place. We analyzed their apartments, focusing on the possibilities for aging-in-place in future care situations concerning bedroom capacity in a care situation; spatial proximity between bathroom, bedroom, storage, and entrance; and functional autonomy in a care situation without too much disturbance for a partner. BACKGROUND: Since the 2000s, the ambition in Sweden is to enable older people to remain in ordinary housing. The possibilities for aging-in-place should therefore be considered already in the design stage, also when producing standard apartments. METHODS: Semi-structured interviews were made with 30 households, with one or more resident 65 years or older. Floor plan analyses were made of their present apartments. RESULTS: The majority displayed a pragmatic attitude toward aging, high satisfaction with their present housing situation, and good chances for aging-in-place in future homecare scenarios. The floor plan analysis shows that the three concepts of bedroom capacity, spatial proximity, and functional autonomy can be used to determine the potential for aging-in-place. CONCLUSIONS: The results suggest that architectural qualities related to aging-in-place are not automatically connected to floor size or number of rooms. Small apartments can perform better than larger ones, depending on spatio-functional organization and connections between different functions. The residents' perceived chances for aging-in-place confirm this relation. Future studies should compare different locations, production periods, and relations between size, space efficiency, and accessibility.

The impact of the physical environment for caregiving in ordinary housing: Experiences of staff in home- and health-care services.

The strong driving forces for ageing in place demand sustainable solutions for the housing and care of older people and the health and safety of home- and health-care staff. The aim of the study was to elucidate staff experiences of providing home- and health-care to older people living in ordinary housing. This study was part of a larger project investigating the relation between home design and conditions for care in ordinary housing. The data were gathered through focus group interviews with staff in home- and health-care. Three main themes were found according to staff experiences of particular rooms' sizes and proportions, spatial configurations, and aspects to consider when designing new housing. This study contributes important knowledge about essential features of the physical environment for staff providing home- and health-care for older people in their own homes and to aid the development of functionally sustainable housing to minimise injuries to staff.

Allergome-wide peptide microarrays enable epitope deconvolution in allergen-specific immunotherapy.

BACKGROUND: The interaction of allergens and allergen-specific IgE initiates the allergic cascade after crosslinking of receptors on effector cells. Antibodies of other isotypes may modulate such a reaction. Receptor crosslinking requires binding of antibodies to multiple epitopes on the allergen. Limited information is available on the complexity of the epitope structure of most allergens. OBJECTIVES: We sought to allow description of the complexity of IgE, IgG4, and IgG epitope recognition at a global, allergome-wide level during allergen-specific immunotherapy (AIT). METHODS: We generated an allergome-wide microarray comprising 731 allergens in the form of more than 172,000 overlapping 16-mer peptides. Allergen recognition by IgE, IgG4, and IgG was examined in serum samples collected from subjects undergoing AIT against pollen allergy. RESULTS: Extensive induction of linear peptide-specific Phl p 1- and Bet v 1-specific humoral immunity was demonstrated in subjects undergoing a 3-year-long AIT against grass and birch pollen allergy, respectively. Epitope profiles differed between subjects but were largely established already after 1 year of AIT, suggesting that dominant allergen-specific antibody clones remained as important contributors to humoral immunity following their initial establishment during the early phase of AIT. Complex, subject-specific patterns of allergen isoform and group cross-reactivities in the repertoires were observed, patterns that may indicate different levels of protection against different allergen sources. CONCLUSIONS: The study highlights the complexity and subject-specific nature of allergen epitopes recognized following AIT. We envisage that epitope deconvolution will be an important aspect of future efforts to describe and analyze the outcomes of AIT in a personalized manner.

Is it possible to feel at home in a patient room in an intensive care unit? Reflections on environmental aspects in technology-dense environments.

This paper focuses on the patient's perspective and the philosophical underpinnings that support what might be considered optimal for the future design of the intensive care unit (ICU) patient room. It also addresses the question of whether the aspects that support at-homeness are applicable to ICU patient rooms. The concept of "at-homeness" in ICUs is strongly related to privacy and control of space and territory. This study investigates whether the sense of at-homeness can be created in an ICU, when one or more patients share a room. From an interdisciplinary perspective, we critically reflect on various aspects associated with conflicts surrounding the use of ICU patient rooms. Thus, from an architectural and a caring perspective, the significance of space and personal territory in ICU patient rooms is emphasized. Recommendations for further research are suggested. In conclusion, privacy and control are deemed to be essential factors in the stimulation of recovery processes and the promotion of well-being in situations involving severe illness or life-threatening conditions.

The SQ tree SLIT-tablet is highly effective and well tolerated: Results from a randomized, double-blind, placebo-controlled phase III trial.

BACKGROUND: The SQ tree sublingual immunotherapy (SLIT)-tablet (ALK-Abelló, Hørsholm, Denmark) is developed for treatment of tree pollen-induced allergic rhinoconjunctivitis (ARC). OBJECTIVE: The aim of this pivotal phase III trial was to demonstrate the efficacy and safety of the SQ tree SLIT-tablet. METHODS: This was a randomized, double-blind, placebo-controlled trial with 634 subjects (12-65 years) with moderate-to-severe ARC despite use of symptom-relieving medication. Eligible subjects were randomized 1:1 to active or placebo treatment. The primary end point was the average daily ARC total combined score (TCS) during the birch pollen season (BPS) analyzed for subjects with diary data during the BPS. Secondary end points included average daily symptom scores (DSS) during the BPS, average TCS and DSS during the tree pollen season (TPS), and average daily medication scores (DMS) in the BPS and TPS. RESULTS: The primary and key secondary end points demonstrated statistically significant and clinically relevant effects of the SQ tree SLIT-tablet compared with placebo. For the BPS, absolute (relative) differences from placebo were 3.02 (40%) for TCS, 1.32 (37%) for DSS, and 1.58 (49%) for DMS (all P < .0001). For the TPS, absolute (relative) differences from placebo were 2.27 (37%) for TCS, 0.99 (33%) for DSS, and 1.20 (47%) for DMS (all P < .0001). Treatment was well tolerated. The most frequently reported treatment-related adverse events were mild or moderate local reactions related to sublingual administration. CONCLUSION: The trial demonstrated the efficacy and safety of the SQ tree SLIT-tablet compared with placebo during the BPS and TPS in adolescents and adults with birch pollen-induced ARC (EudraCT 2015-004821-15).

PAP treatment in patients with OSA does not induce long-term nasal obstruction.

We hypothesized that positive airway pressure treatment would induce nasal obstruction and decrease nasal cavity due to mucosal swelling. We further hypothesized that subjective and objective nasal obstruction at baseline would negatively affect positive airway pressure adherence. A total of 728 patients with sleep apnea were investigated in the Icelandic Sleep Apnea Cohort at baseline and 2 years after starting positive airway pressure. Patients underwent home sleep apnea testing at baseline. Questionnaires were answered and acoustic rhinometry was completed at baseline and follow-up. The proportion of patients reporting subjective nocturnal nasal obstruction was reduced (baseline: 35% versus follow-up: 24%; p < 0.001). Small interior nasal dimensions increased (p < 0.001) independent of adherence to treatment. Small nasal volume at baseline was a determinant for becoming a non-user of positive airway pressure treatment (odds ratio 2.22, confidence interval 95% 1.35-3.67, p = 0.002). Subjective nasal obstruction decreased 2 years after initiating positive airway treatment in sleep apnea, and objectively small nasal dimensions increased. Small nasal volume at baseline was a negative predictor for positive airway pressure treatment adherence. Maybe most importantly, positive airway pressure treatment did not cause long-term objective or subjective nasal obstruction.

Nocturnal nasal obstruction is frequent and reduces sleep quality in patients with obstructive sleep apnea.

The prevalence and consequences of nasal obstruction in untreated obstructive sleep apnea patients are not known. The study objectives were to investigate the frequency of subjective and objective nasal obstruction in untreated sleep apnea patients and the associations with sleep and quality of life. Patients in the Icelandic Sleep Apnea Cohort were subjected to a type 3 sleep study, answered questionnaires and had their nasal dimensions measured by acoustic rhinometry. In total, 810 patients participated (including 153 females), aged 54.5 ± 10.6 years [mean ± standard deviation (SD)] with an apnea/hypopnea index 44.7 ± 20.7 h-1 . Nocturnal nasal obstruction (greater than or equal to three times per week) was reported by 35% of the patients. These patients had smaller nasal dimensions measured by the minimum cross-sectional area within the smaller nasal valve (0.42 ± 0.17 versus 0.45 ± 0.16 cm2 , P = 0.013), reported more daytime sleepiness (Epworth Sleepiness Scale score 12.5 ± 4.9 versus 10.8 ± 5.0; P < 0.001) and slightly lower mental quality of life than patients without nocturnal nasal obstruction. Nocturnal nasal obstruction is reported in one-third of the sleep apnea patients and they are more likely to suffer from daytime sleepiness and slightly reduced quality of life than other sleep apnea patients.

Treatment of idiopathic rhinitis with kinetic oscillations - a multi-centre randomized controlled study.

CONCLUSIONS: The potential effects of KOS are still uncertain regarding the most effective air pressure to be used as well as the physiological effects on the nasal mucosa. The results of the study do not support a convincing treatment effect by KOS on IR. OBJECTIVES: Idiopathic rhinitis (IR) is a common disorder, affecting ∼10-20% of the population. A new method for treating IR, Kinetic Oscillation Stimulation (KOS), has been reported to have beneficial effects on total vasomotor symptom scores (TVRSS). The primary objective with this study was to evaluate if a mean pressure of 65 mbar, pressure amplitude of 100 mbar, and 68 Hz treatment with KOS had a positive effect on total vasomotor symptom scores (TVRSS), as compared with a mean pressure of 65 mbar, pressure amplitude of 4 mbar, and 68 Hz treatment in patients with idiopathic rhinitis. METHODS: Two hundred and seven patients were randomized (Full Analysis Set, FAS) in the study, including five visits and lasting for ∼25 weeks. All patients had two treatment episodes, and all patients had at least one treatment, meant as active, with high amplitude pressure for 10 min in each nostril. Group 1 had two such treatments, and Group 2 had one treatment with low amplitude pressure, initially meant as placebo, on one occasion. Because of numerical improvements in these two groups, a new control group, Group 3, was introduced. They had one new control treatment where the balloon was inserted into the nose, without any air inflation and without oscillations. RESULTS: KOS treatment with high amplitude pressure did not have significant beneficial effects as compared to low amplitude pressure on TVRSS. Numerical improvements in TVRSS and SNOT 22 were found when comparing high and low amplitude pressure treatments with uninflated balloon treatment. However, this part of the study was initially single-blinded, and these results were secondary objectives.

Allergen-Specific Immunotherapy Alters the Frequency, as well as the FcR and CLR Expression Profiles of Human Dendritic Cell Subsets.

Allergen-specific immunotherapy (AIT) induces tolerance and shifts the Th2 response towards a regulatory T-cell profile. The underlying mechanisms are not fully understood, but dendritic cells (DC) play a vital role as key regulators of T-cell responses. DCs interact with allergens via Fc receptors (FcRs) and via certain C-type lectin receptors (CLRs), including CD209/DC-SIGN, CD206/MR and Dectin-2/CLEC6A. In this study, the effect of AIT on the frequencies as well as the FcR and CLR expression profiles of human DC subsets was assessed. PBMC was isolated from peripheral blood from seven allergic donors before and after 8 weeks and 1 year of subcutaneous AIT, as well as from six non-allergic individuals. Cells were stained with antibodies against DC subset-specific markers and a panel of FcRs and CLRs and analyzed by flow cytometry. After 1 year of AIT, the frequency of CD123+ DCs was increased and a larger proportion expressed FcεRI. Furthermore, the expression of CD206 and Dectin-2 was reduced on CD141+ DCs after 1 year of treatment and CD206 as well as Dectin-1 was additionally down regulated in CD1c+ DCs. Interestingly, levels of DNGR1/CLEC9A on CD141+ DCs were increased by AIT, reaching levels similar to cells isolated from non-allergic controls. The modifications in phenotype and occurrence of specific DC subsets observed during AIT suggest an altered capacity of DC subsets to interact with allergens, which can be part of the mechanisms by which AIT induces allergen tolerance.

TOTALL: high cost of allergic rhinitis-a national Swedish population-based questionnaire study.

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.

Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy.

BACKGROUND: Specific immunotherapy (SIT) is the only treatment with proved long-term curative potential in patients with allergic disease. Allergen-specific IgE is the causative agent of allergic disease, and antibodies contribute to SIT, but the effects of SIT on aeroallergen-specific B-cell repertoires are not well understood. OBJECTIVE: We sought to characterize the IgE sequences expressed by allergen-specific B cells and track the fate of these B-cell clones during SIT. METHODS: We used high-throughput antibody gene sequencing and identification of allergen-specific IgE with combinatorial antibody fragment library technology to analyze immunoglobulin repertoires of blood and the nasal mucosa from aeroallergen-sensitized subjects before and during the first year of subcutaneous SIT. RESULTS: Of 52 distinct allergen-specific IgE heavy chains from 8 allergic donors, 37 were also detected by using high-throughput antibody gene sequencing of blood samples, nasal mucosal samples, or both. The allergen-specific clones had increased persistence, higher likelihood of belonging to clones expressing other switched isotypes, and possibly larger clone size than the rest of the IgE repertoire. Clone members in nasal tissue showed close mutational relationships. CONCLUSION: In the future, combining functional binding studies, deep antibody repertoire sequencing, and information on clinical outcomes in larger studies might aid assessment of SIT mechanisms and efficacy.

Biological effects and clinical efficacy of a topical Toll-like receptor 7 agonist in seasonal allergic rhinitis: a parallel group controlled phase IIa study.

OBJECTIVE AND DESIGN: The purpose of the study was to examine effects of pre-treatment with a Toll-like receptor 7 (TLR7) agonist (AZD8848) in allergic rhinitis and to evaluate clinical effects of two dosing regimens. SUBJECTS: The study involved 83 patients with allergic rhinitis. Data on effects of AZD8848 on symptoms were analysed with data from a previous study (n = 68) of identical double blind, parallel group design (NCT00770003). TREATMENT: The treatment involved intranasal AZD8848 20 µg three times weekly, 60 µg once weekly, or placebo for 5 weeks. METHODS: Nasal lavage and plasma were analysed for proof-of-mechanism markers. Daily nasal allergen challenges were given for 7 days, starting 24 h after the final AZD8848 dose. Symptoms were monitored after each challenge and every morning and evening. RESULTS: Markers of TLR-activation increased following AZD8848 administration (CXCL10, TNFα, IL-6, IFNγ). Symptoms recorded soon after allergen challenge were reduced up to eight days after the final dose of AZD8848. Morning and evening symptoms were also reduced, and these changes reached statistical significance for morning observations. Adverse effects were more frequent in the 20 µg three times weekly group. CONCLUSIONS: Repeated administration of AZD8848 activated TLR7 and produced IFN-induced effects. This was associated with a sustained reduction in allergen responsiveness.

Topical dsRNA challenges may induce overexpression of airway antiviral cytokines in symptomatic allergic disease. A pilot in vivo study in nasal airways.

BACKGROUND: Airway challenge with dsRNA is of interest since this agent acts on TLR3 and mimics rhinoviral (RV) infection-induced interferons/cytokines. Contrasting frequent employment of dsRNA in epithelial cell cultures there is no information on effects of dsRNA administered to human airways in vivo. Here we explore effects of nasal dsRNA challenges in subjects with seasonal allergic rhinitis inside and outside Swedish birch pollen season. METHODS: We examined effects of dsRNA in seven patients with seasonal allergic rhinitis. By being studied both inside and outside of an active pollen season they served as their own controls. Based on pilot experiments a repeat dose regimen of dsRNA, 4 × 100 µg, was given daily into the right nostril on two consecutive days; left nostril received corresponding saline challenges. Airway cells for gene analyses were obtained by nasal brushing shortly before the first challenge and 48 h after challenges. RESULTS: Pollen counts and nasal symptoms indicated a significant season of allergic rhinitis. At the height of the pollen season, dsRNA challenges increased three antiviral proteins, interferons ß and λ1 and IL-32, compared to saline challenges. By contrast, outside the pollen season dsRNA did not increase the expression of these antiviral proteins. dsRNA did not cause any symptoms outside the season nor did it increase the allergic symptoms evoked by natural pollen exposure. CONCLUSION: These findings suggest the possibility that active mucosal inflammation, induced by natural allergen exposure in human airways, transiently increases in vivo antiviral responsiveness of airway surface cells.

Exploring the function and use of common spaces in assisted living for older persons.

OBJECTIVE: This exploratory study examines the function and use of common spaces in assisted living facilities (ALFs) from the residential and workplace perspectives. BACKGROUND: The impact of the physical environment on human activities in healthcare settings has been emphasized in many studies. Few studies, however, have explored the daily use of common spaces and the impact on the usability of ALFs. METHODS: Four explorative methods-observation, group interviews, individual interviews, and questionnaires-were used to investigate 14 ALFs in Sweden. The study involves residents, staff, relatives, architects, and people responsible for planning and construction of eldercare. This research strategy combines quantitative and qualitative methods to enhance the validity of the results. Method triangulation and data triangulation were used and the data were analyzed using Qualitative Content Analysis (QCA). RESULTS: The results show that residents and staff have different objectives for use and these differences affect usability, although explicit conflicts are rare. The residents, staff, and other stakeholders have different views about the demarcation of home and workplace and the role of common spaces as venues for social interaction. CONCLUSIONS: Both the residential and the workplace perspective must be considered when planning assisted living facilities. Otherwise, inherent conflicts between these perspectives will manifest as a result of the physical design. Common spaces have diverse functions that are reflected in their spatial organization. Therefore, ALFs should be designed so the intended function of a specific space is apparent to all users. KEYWORDS: Built environment, elderly, planning, satisfaction, staff.

Barrier-enforcing measures as treatment principle in allergic rhinitis: a systematic review.

BACKGROUND AND OBJECTIVES: Barrier-enforcing measures have been suggested as treatment options for allergic rhinitis. This review identifies and describes the literature on the subject. METHODS: Relevant publications were searched for in the PubMed database (search entries: 'allergic rhinitis' and 'treatment'). The evaluation comprised condition (seasonal or perennial allergic rhinitis), type of intervention, duration of treatment, study design, peer review status or not, number of test subjects, type of allergen exposure, and outcome in terms of effects or not on nasal symptoms of allergic rhinitis. RESULTS: Fifteen studies were either identified in the PubMed database search or from the reference lists of identified publications. Seven were placebo-controlled, randomized, and peer-reviewed, and symptom-reducing effects were reported by all of these reports. Limitations of this review reflect that the remainder of the studies had inferior designs, particularly lack of placebo control. CONCLUSIONS: Barrier-enforcing measures as achieved by nasal administrations of cellulose powder and microemulsions, respectively, have symptom-reducing effects in allergic rhinitis.

A topical microemulsion for the prevention of allergic rhinitis symptoms: results of a randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial (Nares study).

BACKGROUND: Since barrier protection measures to avoid contact with allergens are being increasingly developed, we assessed the clinical efficacy and tolerability of a topical nasal microemulsion made of glycerol esters in patients with allergic rhinitis. METHODS: Randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial in which adult patients with allergic rhinitis or rhinoconjunctivitis due to sensitization to birch, grass or olive tree pollens received treatment with topical microemulsion or placebo during the pollen seasons. Efficacy variables included scores in the mini-RQLQ questionnaire, number and severity of nasal, ocular and lung signs and symptoms, need for symptomatic medications and patients' satisfaction with treatment. Adverse events were also recorded. RESULTS: Demographic characteristics were homogeneous between groups and mini-RQLQ scores did not differ significantly at baseline (visit 1). From symptoms recorded in the diary cards, the ME group showed statistically significant better scores for nasal congestion (0.72 vs. 1.01; p = 0.017) and mean total nasal symptoms (0.7 vs. 0.9; p = 0.045). At visit 2 (pollen season), lower values were observed in the mini-RQLQ in the ME group, although there were no statistically significant differences between groups in both full analysis set (FAS) and patients completing treatment (PPS) populations. The results obtained in the nasal symptoms domain of the mini-RQLQ at visit 2 showed the highest difference (-0.43; 95% CI: -0.88 to 0.02) for the ME group in the FAS population. The topical microemulsion was safe and well tolerated and no major discomforts were observed. Satisfaction rating with the treatment was similar between the groups. CONCLUSIONS: The topical application of the microemulsion is a feasible and safe therapy in the prevention of allergic symptoms, particularly nasal congestion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01478425.

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.

Selective inhibition by simvastatin of IRF3 phosphorylation and TSLP production in dsRNA-challenged bronchial epithelial cells from COPD donors.

BACKGROUND AND PURPOSE: Statin treatment may ameliorate viral infection-induced exacerbations of chronic obstructive pulmonary disease (COPD), which exhibit Th2-type bronchial inflammation. Thymic stromal lymphopoietin (TSLP), a hub cytokine switching on Th2 inflammation, is overproduced in viral and dsRNA-stimulated bronchial epithelial cells from COPD donors. Hence, TSLP may be causally involved in exacerbations. This study tests the hypothesis that simvastatin inhibits dsRNA-induced TSLP. EXPERIMENTAL APPROACH: Epithelial cells, obtained by bronchoscopy from COPD (n = 7) and smoker control (n = 8) donors, were grown and stimulated with a viral infection and danger signal surrogate, dsRNA (10 µg·mL(-1) ). Cells were treated with simvastatin (0.2-5 µg·mL(-1) ), with or without mevalonate (13-26 µg·mL(-1) ), or dexamethasone (1 µg·mL(-1) ) before dsRNA. Cytokine expression and production, and transcription factor (IRF3 and NF-κB) activation were determined. KEY RESULTS: dsRNA induced TSLP, TNF-α, CXCL8 and IFN-ß. TSLP was overproduced in dsRNA-exposed COPD cells compared with control. Simvastatin, but not dexamethasone, concentration-dependently inhibited dsRNA-induced TSLP. Unexpectedly, simvastatin acted independently of mevalonate and did not affect dsRNA-induced NF-κB activation nor did it reduce production of TNF-α and CXCL8. Instead, simvastatin inhibited dsRNA-induced IRF3 phosphorylation and generation of IFN-ß. CONCLUSIONS AND IMPLICATIONS: Independent of mevalonate and NF-κB, previously acknowledged anti-inflammatory mechanisms of pleiotropic statins, simvastatin selectively inhibited dsRNA-induced IRF3 activation and production of TSLP and IFN-ß in COPD epithelium. These data provide novel insight into epithelial generation of TSLP and suggest paths to be exploited in drug discovery aimed at inhibiting TSLP-induced pulmonary immunopathology.

Long-term follow-up of patients operated with Uvulopalatopharyngoplasty from 1985 to 1991.

OBJECTIVES: Short-term outcome and side effects after Uvulopalatopharyngoplasty (UPPP) are well recognized. However, there is a lack of knowledge of the long-term outcome and side effects after this surgery. This study was completed to investigate the outcome and side effects 20 years after UPPP for snoring and obstructive sleep apnoea. METHODS: Medical records of patients who underwent UPPP surgery for sleep apnoea and snoring between 1985 and 1991 were investigated retrospectively. A specific questionnaire focusing on the present health profile, side effects of previous UPPP surgery and present sleeping patterns of patients was mailed out. RESULTS: UPPP patients, 186 (including 11 females) were identified. Of these, 35 (19%) had passed away and 7 (4%) were not located. 129 patients (mean: age 68 years, range 43-83) of the possible 144 patients answered the questionnaire (response rate 90%). At follow-up, 41 patients (32%) used continuous positive airway pressure (CPAP). 66 of the patients (52%) were satisfied with the result of the operation, but 61 (47%) were not satisfied. 49 patients (38%) reported persistent side effects (problems with nasal regurgitation 18 (14%), swallowing 26 (20%), changed voice 15 (12%), and pain in the oral cavity 15 (12%). CONCLUSION: Almost 50% of patients operated with UPPP were not satisfied with the result of the operation after about 20 years, and one third used CPAP at follow-up. A large proportion of patients still experienced side effects, which, after this time, are likely to be permanent.