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The importance of allergen immunotherapy (AIT) is multifaceted, encompassing both clinical and quality‐of‐life improvements and cost‐effectiveness in the long term. Key mechanisms of allergen tolerance induced by AIT include changes in memory type allergen‐specific T‐ and B‐cell responses towards a regulatory phenotype with decreased Type 2 responses, suppression of allergen‐specific IgE and increased IgG1 and IgG4, decreased mast cell and eosinophil numbers in allergic tissues and increased activation thresholds. The potential of novel patient enrolment strategies for AIT is taking into account recent advances in biomarkers discoveries, molecular allergy diagnostics and mobile health applications contributing to a personalized approach enhancement that can increase AIT efficacy and compliance. Artificial intelligence can help manage and interpret complex and heterogeneous data, including big data from omics and non‐omics research, potentially predict disease subtypes, identify biomarkers and monitor patient responses to AIT. Novel AIT preparations, such as synthetic compounds, innovative carrier systems and adjuvants, are also of great promise. Advances in clinical trial models, including adaptive, complex and hybrid designs as well as real‐world evidence, allow more flexibility and cost reduction. The analyses of AIT cost‐effectiveness show a clear long‐term advantage compared to pharmacotherapy. Important research questions, such as defining clinical endpoints, biomarkers of patient selection and efficacy, mechanisms and the modulation of the placebo effect and alternatives to conventional field trials, including allergen exposure chamber studies are still to be elucidated. This review demonstrates that AIT is still in its growth phase and shows immense development prospects. [ABSTRACT FROM AUTHOR]

Background: Allergen exposure chamber (AEC) is a clinical facility that allows exposure to allergenic airborne particles in controlled environment. Although AECs offer stable levels of airborne allergens, the validation of symptoms and other endpoints induced by allergen challenge is key for their recommendation as a plausible tool for the assessment of patients, especially in clinical research. This study aimed to demonstrate the reproducibility of defined clinical endpoints after AEC house dust mite (HDM) challenge under optimal conditions in patients with allergic rhinitis (AR). Method: HDM was distributed at different concentrations. The assessment was subjective by the patients: total nasal symptom score (TNSS), visual analog scale (VAS), and objective by the investigator: acoustic rhinometry, peak nasal inspiratory flow (PNIF), and nasal secretion weight. Safety was assessed clinically and by peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV1). Results: Constant environment: temperature, humidity, and carbon dioxide (CO2) concentration were maintained during all challenges. The concentration of HDM on average remained stable within the targeted values: 1000, 3000, 5000, 7000 particles (p)/m3. Most symptoms were observed at concentrations 3000 p/m3 or higher. The symptoms severity and other endpoints results were reproducible. 5000 p/m3, and challenge duration of 120 min were found optimal. The procedure was safe with no lung function abnormalities due to challenge. Conclusion: HDM challenge in ALL‐MED AEC offers a safe and reliable method for inducing symptoms in AR patients for the use in controlled clinical studies including allergen immunotherapy. [ABSTRACT FROM AUTHOR]

Loading of articular cartilage during motion squeezes the fluid from the cartilage, termed cartilage interstitial fluid (CIF), which was found to influence gene expression in synovial membrane cells. After crucial ligaments damage, these cells are exposed to synovial fluid containing factors released from articular cartilage; the aim of the present study was to establish the influence of CIF and factors present in CIF (CIF-like cocktails) on crucial ligament fibroblasts. CIF was squeezed from articular-epiphyseal cartilage complexes of newborn rats. Fibroblasts were obtained from crucial ligaments of adult rat knee joints. Cells were cultured in control medium, CIF and CIF-like cocktails, and the expression of selected genes was evaluated using quantitative PCR. CIF stimulated the expression of HAS1, HAS2, aggrecan, lubricin, MMP3, TIMP3 and TGFβ1. Expression of collagen type I, versican, MMP2, TIMP2, TNF and IL1β was inhibited. The CIF-like cocktail stimulated HAS1, HAS2, collagen type I, versican, aggrecan, lubricin, TIMP1, TGFβ1, IL1β, IL6 and inhibited of MMP3 and TNF expression. Both agents exerted similar effects on the expression of HAS2, aggrecan, lubricin, TGFβ1 and TNF. CIF contains inhibitory and stimulatory factors affecting gene expression in crucial ligament fibroblasts and some of them were not included in the CIF-like cocktail. Due to the powerful influence of CIF on crucial ligament fibroblasts and the synovial membrane, further studies on its composition are needed. An improved CIF like-cocktail could be applied in the treatment of various joint or tendon ailments. [ABSTRACT FROM AUTHOR]

Wstęp: Walidacja wiarygodnych biomarkerów klinicznych i laboratoryjnych ma ogromne znaczenie dla lepszej prospektywnej i retrospektywnej oceny skuteczności AIT (alergenowej immunoterapii swoistej). Obecnie do AIT kwalifikuje się pacjentów głównie na podstawie wywiadu chorobowego i spektrum uczuleń. Użytecznymi narzędziami stratyfikacji pacjentów są próby prowokacji alergenowej. Kabina Ekspozycji Środowiskowej (EEC - Environmental Exposure Chamber) zapewnia generowanie ekspozycji na alergen w dobrze kontrolowanych warunkach, stabilnych i niezależnych od czynników zewnętrznych. Cel: W badaniu oceniono skuteczność AIT u pacjentów uczulonych na alergeny roztoczy kurzu domowego (HDM - House Dust Mite) na podstawie poprawy klinicznej ocenianej „w terenie" za pomocą skali objawów i zużycia leków (CSMS - Combined Symptom Medication Score), a także po prowokacji alergenem donosowym (NAC - Nasal Allergen Challenge) i ekspozycji w EEC. Materiały i Metody: Do badania włączono 50 pacjentów z objawami alergicznego nieżytu nosa i spojówek wywołanego przez HDM, potwierdzonego za pomocą punktowych testów skórnych (SPT) oraz swoistych przeciwciał IgE (sIgE). Objawy oceniano za pomocą parametrów subiektywnych (skala objawów, skala zużycia leków, CSMS) i metod obiektywnych (rynometria akustyczna) zarówno podczas okresu wysokiego narażenia na HDM „w terenie", jak i poza sezonem dzięki NAC oraz EEC przed AIT i po 360 dniach AIT. Wyniki: Wykazano dodatnią korelację pomiędzy SPT z użyciem Dermatophagoides pteronyssinus (D.p.) i Dermatophagoides farinae (D.f.), p<0.05, r=0.65 oraz pomiędzy SPT D.f. a sIgE D.f. (p<0.05, r=0.73). Nie znaleziono statystycznie istotnych zależności pomiędzy SPT, sIgE a subiektywnymi lub obiektywnymi parametrami ocenianymi podczas NAC, ekspozycji w EEC lub CSMS „w terenie".Zarówno parametry subiektywne, jak i obiektywne wykazały znaczną poprawę po AIT w NAC i EEC. Objawy oceniane za pomocą CSMS w okresie wysokiego narażenia na HDM po 1 roku AIT był istotnie niższe (69%) w porównaniu do stanu sprzed leczenia (p<0.0001). Istotną statystycznie redukcję objawów po AIT zaobserwowano w NAC za pomocą metod subiektywnych (p<0.0001) oraz rynometrii akustycznej (p<0.0001, średnia redukcja MCA 32%, MID 13%). W EEC zaobserwowano 30% redukcję objawów ze strony nosa (p<0.005) i 58% redukcję objawów ze strony oczu (p<0.005) po AIT, natomiast nie zaobserwowano statystycznie istotnej różnicy w reakcji nosowej mierzonej w rynometrii akustycznej podczas ekspozycji w EEC. Nie stwierdzono statystycznie istotnej korelacji między CSMS ocenianym przed AIT a innymi parametrami ocenianymi w NAC lub EEC. Podsumowanie: Kliniczne punkty końcowe oceniane podczas ekspozycji w EEC i NAC znacząco odpowiadają analizie skuteczności AIT za pomocą CSMS podczas okresu wysokiego narażenia na alergen i mogą stanowić alternatywę dla tradycyjnych projektów badań naukowych i klinicznych. [ABSTRACT FROM AUTHOR]

Cartilage growth plate is a natural template from both a biochemical and structural point of view and allows osteoblasts migration, proliferation, differentiation, and ultimately, bone formation. It is evolutionary adjusted to support bone formation within strictly defined spatial framework serving as an interesting model for studying more mechanistically aspects which might be important for specific scaffold-based bone tissue engineering strategies. Surprisingly little is known about the geometric features of this physiological template. To this purpose we analyzed cartilage growth plate from rat, mouse, and human costochondral junction and tibia. High-resolution X-ray tomography showed that pore size in the zone of provisional calcification was within 20 to 30 µm range and in the metaphysis in 35 to 50 µm range. The thickness of calcified longitudinal septa in zone of provisional calcification was 3 to 5 µm and in metaphysis 7 to 12 µm. The porosity varied from 84 to 88%. We observed that numerical values characteristic for cartilage growth plate were not significantly influenced by the species of origin, by the type of bone, or by age. In addition, electron microscopy of calcified fragments of longitudinal septa showed that the calcium aggregates were globular, connected with each other, and formed a shell covering cartilage matrix located within longitudinal septa., (© 2015 Wiley Periodicals, Inc.)