Background: Patients with nonallergic irritant rhinitis (NAIR) have symptoms of nasal congestion, nasal irritation, rhinorrhea, and sneezing in response to nasal irritants. We currently have no reliable objective means to quantify these patients' subjective symptoms. In this study, we used the transient receptor potential vanilloid receptor (TRPV1) receptor agonist, capsaicin, as an intranasal challenge while comparing the changes in blood flow with optical rhinometry between subjects with NAIR and healthy controls (HCs). Methods: Six HCs and 6 NAIR subjects were challenged intranasally with saline solution followed by increasing concentrations of capsaicin (0.005 mM, 0.05 mM, and 0.5 mM) at 15-minute intervals. We recorded maximum optical density (OD) and numeric analog scores (NAS) for nasal congestion, nasal irritation, rhinorrhea, and sneezing for each subject after each challenge. Correlations between NAS and maximum OD were calculated. Results: Maximum OD increased with increasing concentrations of intranasal capsaicin in NAIR subjects. There were significant differences in maximum OD obtained for 0.05 mM and 0.5 mM capsaicin between NAIR subjects and HCs. Significant differences were found in the NAS for nasal irritation at 0.005 mM, 0.05 mM, and 0.5 mM, and nasal congestion at 0.5 mM. Correlation between maximum OD and mean NAS was most significant for 0.05 mM capsaicin. Conclusion: Optical rhinometry with intranasal capsaicin challenge could prove a viable option in the diagnosis of NAIR. Further studies will investigate its use to monitor a patient's response to pharmacologic therapy and provide further information about the underlying mechanisms of NAIR.

Background: Patients with nonallergic irritant rhinitis (NAIR) have symptoms of nasal congestion, nasal irritation, rhinorrhea, and sneezing in response to nasal irritants. We currently have no reliable objective means to quantify these patients' subjective symptoms. In this study, we used the transient receptor potential vanilloid receptor (TRPV1) receptor agonist, capsaicin, as an intranasal challenge while comparing the changes in blood flow with optical rhinometry between subjects with NAIR and healthy controls (HCs). Methods: Six HCs and 6 NAIR subjects were challenged intranasally with saline solution followed by increasing concentrations of capsaicin (0.005 mM, 0.05 mM, and 0.5 mM) at 15-minute intervals. We recorded maximum optical density (OD) and numeric analog scores (NAS) for nasal congestion, nasal irritation, rhinorrhea, and sneezing for each subject after each challenge. Correlations between NAS and maximum OD were calculated. Results: Maximum OD increased with increasing concentrations of intranasal capsaicin in NAIR subjects. There were significant differences in maximum OD obtained for 0.05 mM and 0.5 mM capsaicin between NAIR subjects and HCs. Significant differences were found in the NAS for nasal irritation at 0.005 mM, 0.05 mM, and 0.5 mM, and nasal congestion at 0.5 mM. Correlation between maximum OD and mean NAS was most significant for 0.05 mM capsaicin. Conclusion: Optical rhinometry with intranasal capsaicin challenge could prove a viable option in the diagnosis of NAIR. Further studies will investigate its use to monitor a patient's response to pharmacologic therapy and provide further information about the underlying mechanisms of NAIR.

Orientador: Ricardo de Lima Zollner / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T18:58:24Z (GMT). No. of bitstreams: 1 ZanellatoFabbri_Natalia_D.pdf: 35087770 bytes, checksum: d1d79dc3e2bc0a5a2a05b4261a363a74 (MD5) Previous issue date: 2014 / Resumo: Apesar das diversas terapias disponíveis para o tratamento da rinite alérgica (RA), muitos pacientes não obtêm alívio dos sintomas com uso de um único fármaco e apresentam frequentemente queixa da manutenção dos sintomas mesmo sob tratamento. Estudos clínicos aleatorizados compararam a eficácia de anti-histamínicos e corticoides intranasais, isolados e associados e demonstraram que as terapias com drogas combinadas apresentam melhores resultados. A RA é um fator de risco para o desenvolvimento de obstrução de VAI e estudos clínicos com pacientes asmáticos demostraram redução da responsividade brônquica e sintomas de asma apenas com tratamento tópico nasal. O objetivo do presente estudo foi avaliar (1) o efeito do tratamento tópico nasal com azelastina (AZE), budesonida (BUD) e combinação AZE/BUD na obstrução nasal e sintomas de RA; (2) o efeito do estímulo nasal inespecífico com histamina na função pulmonar; e (3) o efeito dos tratamentos tópicos nasais na função pulmonar de pacientes com RA. O desenho do presente trabalho foi aleatorizado, cruzado e cego composto por 3 tratamentos. 28 pacientes participaram do estudo, com tratamento tópico nasal de 30 dias e intervalo de 7 dias entre os tratamentos. Os pacientes foram submetidos ao protocolo de TPN com histamina, avaliado por escore de sintomas, rinometria acústica e espirometria. Nossos resultados mostraram que a terapia com AZE/BUD é mais efetiva na prevenção da obstrução nasal e sintomas da RA comparada ao tratamento com as drogas isoladas. Além disso, encontramos indivíduos com alterações na função pulmonar após estímulo nasal inespecífico e controle destas alterações após tratamento tópico nasal, sugerindo influência positiva do tratamento nasal na função pulmonar de indivíduos com hiperreatividade brônquica / Abstract: Despite the several therapies available for the treatment of allergic rhinitis (AR) many patients do not get relief of symptoms using a single drug and often have the maintenance of symptoms even under treatment. Randomized clinical trials comparing the efficacy of antihistamines and intranasal corticosteroids, isolated and associates, show that the combination drug therapies have better outcomes. The AR is a risk factor for the development of obstruction in lower airways and clinical studies with asthmatic patients demonstrated reduction of bronchial hyperresponsiveness and asthma symptoms after just nasal topical treatment. The aim of this study was to evaluate (1) the effect of treatment with topical nasal azelastine (AZE), budesonide (BUD) and combined drugs (AZE/BUD) in nasal obstruction and symptoms of RA; (2) the effect of non-specific nasal challenge with histamine in lung function; and (3) the effect of topical nasal treatment on lung function in patients with RA. The design of this study was randomized, crossover and blind consisting of 3 periods of treatment with nasal sprays. 28 patients participated in the study, composed for 3 periods of treatment (30 days) and 7-day interval between treatments. Patients underwent protocol nasal provocation test with histamine assessed by symptom scores, acoustic rhinometry and spirometry. Our results showed that therapy with AZE/BUD is more effective in preventing nasal obstruction and symptoms of RA compared to treatment with drugs isolated. Furthermore, we find individuals with changes in pulmonary function after nonspecific nasal stimulation and control of these changes after nasal topical treatment, suggesting a positive influence of nasal treatment on lung function in subjects with bronchial hyperreactivity / Doutorado / Clinica Medica / Doutora em Clínica Médica

In this investigation of immunotherapy (IT) children 6-16 years old with rhinoconjunctivitis due to birch polli­nosis were included. I. Methodological studies. To monitor IT a reliable provocation test is desirable. The conjunctival provocation test (CPT) was evaluated in 20 children with four repeated challenges. The test was found to have a good preci­sion, it was simple and appeared to be clinically safe. After repeated tests the levels of IgE antibodies against birch increased considerably in three children, indicating an immunological response. A pollen peak affects the symptoms of an atopic individual for several days. Thus pollen counts for previous days must be taken into account when relating symptom scores with the counts. A dynamic time series model was therefore developed by which groups of atopic patients could be compared when exposed to different amounts of pollens. II: Cross-reactivity between deciduous trees during IT. Immunotherapy with pollen allergen preparations made from either birch (B) or a mixture of birch, alder and hazel (M) were compared. As measured with symptom scores the children in the M group improved at least as much as those in the B group. In the B group but not in the M group the improvement correlated with immunochemical findings before IT or early during the treatment, probably an unsignificant finding. Otherwise there was little difference between the two groups. Analysis of sera with crossed radioimmunoelectrophoresis in 20 children revealed that 60% of the children below 13 years had de­veloped IgE antibodies during IT against allergens against which they had not been allergic before IT. This had no appearent clinical implications. III: Oral immunotherapy (OIT). A pilot study of 18 children treated with high doses of a birch pollen allergen preparation in enteric coated capsules and 8 untreated controls indicated that OIT was effective as shown by lower symptom scores, less conjuctival sensitivity and increased levels of IgE antibodies against birch. However, the gastrointestinal side-effects were pronounced. Therefore a second double-blind study, in 30 children, was performed reducing the side-effects through a different dose schedule. Compared with the placebo group, the ac­tively treated children had lower symptom scores (p = 0.04), reduced skin sensitivity (p = 0.01), increasing levels of IgE (p = 0.001) and IgG (p = 0.007) antibodies against birch before the birch pollen season and a suppression of the seasonal increase in levels of IgE antibodies against birch (p <0.001). After three months of OIT but not after ten months they also had a lower sensitivity in CPT than the controls (p = 0.01). The intestinal permeability as assessed by the urinary recovery of differently-sized polyethyleneglycols was studied in 24 of the children during IT. No changes were seen in the group of actively treated children. In two ad­ditional children openly treated with OIT small bowel biopsies were taken with normal morphological findings. Thus OIT did not result in a generalized inflammation of the small bowel. / digitalisering@umu

La compréhension de la biomécanique des structures articulaires est inhérente à l'amélioration de l'évaluation clinique de l'articulation coxo-fémorale. Cette articulation possède une capsule articulaire qui contient du liquide synovial et composée de ligaments capsulaires. Premièrement, le volume du liquide synovial peut être modifié en présence d'un problème articulaire. La pression intracapsulaire sera donc modifiée par ce changement de volume et par les mouvements articulaires effectués. Deuxièmement, les ligaments capsulaires s’allongent en fonction des différentes amplitudes articulaires. Les six degrés de liberté de mouvement de l'articulation coxo-fémorale rendent plus complexes l'évaluation et l'interprétation des pressions intracapsulaires et des allongements ligamentaires. À ce jour, les informations sur les pressions intracapsulaires et les allongements ligamentaires pendant les mouvements de l'articulation sont incomplètes ou limitées. La première étude visait à présenter les fluctuations des pressions intracapsulaires lors de cinq mouvements classiques au sein des compartiments capsulaire (latéral) et acétabulaire (médial). Latéralement, la pression est liée à l’amplitude articulaire. Médialement, la pression est beaucoup plus réactive aux mouvements. Cette première étude montre une variabilité importante entre les mouvements et les compartiments dans lesquels la pression est évaluée. La deuxième étude visait à rapporter les pressions dans les tests de provocation de flexion-abduction-rotation externe (FABER) et de flexion-adduction-rotation interne (FADIR). Lors du test de FABER, la pression intracapsulaire est négative dans les deux compartiments capsulaires. Pour le test de FADIR, la pression intracapsulaire est très élevée dans le compartiment latéral. Cette augmentation significative pourrait présenter une explication des problèmes de sensibilité et de spécificité du test de FADIR face à des modifications ostéologiques qui sont habituellement évaluées lors de son exécution. La troisième étude visait à présenter les allongements longitudinaux et transversaux du ligament iliofémoral lors de quatre mouvements articulaires soient l’abduction, la rotation externe et interne en extension et l’extension seule. Nos résultats montrent une hétérogénéité importante au sein des deux faisceaux du ligament iliofémoral lors de ces mouvements articulaires. La quatrième étude portait sur les allongements ligamentaires au sein du ligament iliofémoral lors du test de FABER. D’après nos résultats, il est possible d’observer des allongements significativement différents entre les faisceaux médial et latéral du ligament iliofémoral. Le faisceau latéral s’allonge dans sa globalité. L’allongement le plus important est observé dans la portion distale de ce faisceau. Médialement, le faisceau rétrécissait. Au regard de ces différents résultats entre les deux faisceaux, une distinction est nécessaire lors du test de FABER. En fait, ils auront des comportements complètement différents. En conclusion, ces quatre études portent sur l’analyse des pressions intracapsulaires et des allongements ligamentaires lors des mouvements classiques et des tests de provocation. Les différentes études montrent que la pression est dépendante du mouvement et du compartiment dans lequel elle est évaluée. Quant aux allongements, ceux-ci varient en regard du mouvement, de la portion et du faisceau dans lesquels ils sont évalués. Ces résultats soulignent l’importance de prendre en considération ces variations lors de l’évaluation clinique de la hanche. / Understanding tissue and joint biomechanics are inherent to improving the clinical evaluation of the coxofemoral joint. The coxofemoral joint has a joint capsule that contains synovial fluid and is composed of capsular ligaments. Firstly, the volume of synovial fluid can increase in the presence of a joint problem. The intra-articular pressure will therefore be modified by this change in volume and by the joint movements performed. Secondly, the capsular ligaments increase or decrease in length depending on the movement performed. The six degrees of freedom of movement of the coxofemoral joint make the assessment and interpretation of intra-articular pressures and ligament strains more complex. To date, information on intra-articular pressure and ligament strains during joint range of motion are incomplete or limited. The first study intended to present the fluctuations of intra-articular pressures during five classical movements within the capsular (lateral) and acetabular (medial) compartments. Laterally, the pressure is related to joint range of motion. Medially, the pressure is much more reactive. This study shows significant variability between movements and compartments in which the pressure is assessed. The second study aimed to report pressures in the flexion-abduction-external rotation (FABER) and flexion-adduction-internal rotation (FADIR) provocation tests. In the FABER test, the intra-articular pressure was negative in both capsular compartments. For the FADIR test, the intra-articular pressure was very high in the lateral compartment. This significant increase could present an explanation for the sensitivity and specificity problems of the FADIR test in the face of osteological changes. The third study aimed to present the longitudinal and transverse strains of the iliofemoral ligament during four joint movements, namely abduction, external and internal rotation in extension and extension alone. Our results show significant heterogenity within the two bands of the iliofemoral ligament during these joint movements. The fourth study looked at ligament strains within the iliofemoral ligament during the FABER test. According to our results, it is possible to observe significantly different strains between the medial and lateral bands of the iliofemoral ligament. The lateral band increase in length globally. The largest strain was observed in the distal portion of this band. Medially, the band decreases in length. In view of these different results between the two bands, it is important to distinguish them when performing the FABER test as they will have completely different behaviors. In conclusion, these four studies describe the analysis of intra-articular pressures and ligament strains during the classical movement and provocation test. They show that the pressure is dependent on the movement and the compartment in which it is assessed. As for ligament strains, they vary according to the movement, the portion, and the band in which they are evaluated. These results underline the importance of taking these variations into consideration during the clinical evaluation of the hip.