Title: Occurrence and Prevention of Asthma in Youth Division Cross-country Skiers Objectives: The aim of this thesis is to determine the incidence of asthma in youth division cross-country skiers and its prevention. Methods: This thesis will comprise the method of survey and content analysis of documents. Hypotheses: No.1 Assume that asthma will have lower prevalence in youth division cross- country skiers than in adult cross-country skiers. No.2 Assume that the majority of the surveyed cross-country skiing coaches met with asthmatic symptoms in their athletes. Results: We found that 12% of youth division athletes suffer from asthma and 24% from allergies. Keywords: cross country skiing, respiratory diseases, bronchial asthma, exercise-induced asthma, allergy prevention.

INTRODUÇÃO: A Asma Brônquica é caracterizada por obstrução ao fluxo aéreo, reversível ou não, e processo inflamatório pulmonar, caracterizado principalmente por eosinofilia. A persistência da inflamação pode induzir processo de reparo pulmonar associado à redução progressiva da função pulmonar. A recente descrição do sistema colinérgico anti-inflamatório, um mecanismo neural que suprime a resposta imune inata e controla a inflamação por inibição de citocinas proinflammatórias, e a detecção de alguns de seus componentes em células de vias aéreas sugerem uma importante participação deste sistema na fisiopatologia de doenças pulmonares. O principal mediador deste sistema é a acetilcolina (ACh), que é estocada em vesículas sinápticas pelo transportador vesicular de ACh (VAChT), proteína essencial para sua liberação. OBJETIVOS: Avaliar os efeitos da deficiência colinérgica por redução da VAChT nas alterações pulmonares observadas em modelo experimental de inflamação pulmonar induzida pela exposição crônica a ovoalbumina. METODOLOGIA: A redução colinérgica foi induzida pela modificação genética nos níveis de VAChT. Camundongos machos selvagens e mutantes foram submetidos ao protocolo de sensibilização subcutânea com ovoalbumina ou salina nos dias 0, 7 e 14. Após, foram submetidos a desafios inalatórios com ovalbumina a 1% ou inalações de salina por 20 minutos nos dias 26, 27 e 28. No dia 29, foi realizada a avaliação da mecânica pulmonar, da inflamação no lavado broncoalveolar e no tecido e análise histológica de remodelamento e expressão de MMP-9 e TIMP-1 por imunohistoquímica. Também foi quantificado por ELISA níveis de IL-4, IL-10 e de TNF-a no homogenato pulmonar. A análise estatística considerou um p<0,05 como significativo. RESULTADOS: Animais sensibilizados apresentaram hyperresponsividade brônquica, inflamação e edema peribrônquico e deposição de fibras colágenas e elásticas ao redor das vias aéreas comparado ao grupo salina (p<0,05). Além disso houve aumento de IL-4 no homogenato pulmonar e da expressão de MMP-9 e TIMP-1 nas células inflamatórias. Os animais mutantes, independente de serem ou não sensibilizados, apresentaram aumento de TNF-a no pulmão. Os animais mutantes que foram submetidos ao protocolo de sensibilização mostraram aumento da hiperresponsividade brônquica, do eosinófilos, do edema e da deposição de colágeno comparado aos animais selvagens que também foram sensibilizados com ovoalbumina. Estas alterações podem ser atribuídas ao aumento de IL-4 e de MMP-9/TIMP-1 que foi observado nos animais mutantes e sensibilizada em comparação com o os selvagens sensibilizados. Não houve diferença nos níveis de IL-10 nos grupos experimentais. Conclusão: A deficiência colinérgica piora a hiperresponsividade brônquica, a inflamação eosinofílica e o remodelamento, principalmente por interferir com a citocina pró-inflamatória IL-4 e na proporção de MMP-9 e TIMP-1. Estes dados sugerem que a via colinérgica antiinflamatória está envolvida na fisiopatogenia da asma e necessita ser mais investigada / BACKGROUND: Bronchial asthma is characterized by reversible or not airflow obstruction and pulmonary inflammation, mainly characterized by eosinophilia. The persistence of inflammation can induce lung repair process associated with progressive reduction in lung function. Recent evidence of the cholinergic anti-inflammatory system, a neural mechanism that suppresses the innate immune response and control inflammation by proinflammatory cytokines inhibition, and the detection of some of its components in airway cells suggest an important role of this system in pulmonary physiopathology. The main mediator of this system is acetylcholine (ACh), which is stored in synaptic vesicles by vesicular acetylcholine transporter (VAChT), an essential protein for ACh release. AIMS: To evaluate the effects of cholinergic deficiency by VAChT reduction on pulmonary alterations observed in an experimental model of pulmonary inflammation induced by chronic exposure to ovalbumin. METHODS: The cholinergic deficiency was induced by genetic modification on VAChT levels. Wild-type and mutant male mice were submitted to subcutaneous ovalbumin sensitization or saline protocol on days 0, 7 and 14. After, animals were submitted to inhalation challenge with ovalbumin 1% or saline for 20 minutes on days 26, 27 and 28. On day 29, we evaluated the pulmonary mechanics, inflammation in bronchoalveolar lavage and in airways, histological analysis of airway remodeling and the expression of MMP-9 and TIMP-1 by immunohistochemistry. It was also quantified by the levels of IL-4, IL-10 and TNF-a in lung homogenate. The statistical analysis were performed and a p<0.05 was considered significant. RESULTS: Sensitized animals presented bronchial hyperresponsividade, airway inflammation and edema and collagen and elastic fibers deposition of collagen and elastic fibers around the airways compared to saline group (p <0.05). Furthermore, there was an increase of IL-4 in lung homogenate and the expression of MMP-9 and TIMP-1 in inflammatory cells. The mutant animals, regardless the sensitization, showed an increase in lung content of TNF-a. The mutant and sensitized animals showed an increase in bronchial hyperresponsiveness, in eosinophils, edema and collagen deposition in airways compared to the wild type and sensitized animals. These changes can be attributed to increased IL-4 and MMP-9/TIMP-1 that were observed in mutant and sensitized animals. There was no difference in levels of IL-10 in the experimental groups. Conclusion: The cholinergic deficiency worsens bronchial hyperresponsiveness, eosinophilic inflammation, and airway remodeling mainly by interfering with the pro-inflammatory cytokine IL-4 and in MMP-9/TIMP-1 ratio. These data suggest that anti-inflammatory cholinergic pathway is involved in the asthma pathogenesis deserves further investigation

Erkrankungen das allergischen Formenkreises (Asthma bronchiale, Atopische Dermatitis, Allergische Rhino-Konjunktivitis) sind in ständiger Zunahme begriffen. Für den in der Klinik tätigen Pädiater stellt das allergische Asthma bronchiale die wichtigste Erkrankung aus dieser Gruppe dar. Asthma ist die häufigste chronische Atemwegs-Erkrankung im Kindesalter und verursacht durch Medikation und Hospitalisation enorme volkswirtschaftliche Kosten. Kardinale Symptome von Asthma sind reversibler Bronchospasmus nach Exposition mit z.B. Allergenen (Atemwegs-Obstruktion), eine funktionell abnorme glatte Atemwegsmuskulatur, die durch eine verstärkte Kontraktilität nach unspezifischer Stimulation gekennzeichnet ist (Bronchiale Hyperreagibilität oder Atemwegs-Hyperreaktivität, AHR), und das Vorliegen einer chronischen Entzündung der kleinen und mittleren Atemwege (Atemwegs-Inflammation, AI). Derzeitig finden für die Behandlung von Asthma bronchiale lediglich die symptomatische Therapie der Obstruktion mit muskelrelaxierenden Medikamenten (Bedarfstherapie) und die unspezifische anti-entzündliche Therapie mit steroidalen Antiphlogistika (Dauertherapie) regelmäßige und breite Anwendung. Während die Mehrzahl der Patienten hiermit relativ beschwerdefrei eingestellt werden kann, gibt es aber auch Asthmatiker, die unter den Nebenwirkungen einer hochdosierten, systemischen Steroid-Dauertherapie leiden (steroid-pflichtiges Asthma), oder trotz der intensiven Anwendung von Kortikoiden nicht symptomfrei bleiben (steroid-resistentes Asthma). Für diese Patientengruppe fehlt bislang eine effektive, nebenwirkungsarme und spezifisch anti-asthmatische Therapie. Grundlage für die Etablierung innovativer Strategien für die Behandlung von Asthma kann jedoch nur die genaue Kenntnis der pathophysiologischen Mechanismen sein, die zur Ausbildung der klinischen Symptome führen. Allergischen Erkrankungen liegt eine fehlgeleitete Immunreaktion gegen Umweltstoffe, wie z.B. Tierhaarepithelien, Blütenpollen oder Lebensmittel zugrunde. Mittlerweile gilt als gesichert, dass ein Ungleichgewicht in der Antwort von T-Lymphozyten auf diese Antigene die wesentliche Grundlage für die Ausbildung des allergischen Phänotyps darstellt. Bei allergischen Patienten überwiegt die Produktion von sog. Th2-Zytokinen. Diese sind von T-Zellen produzierte Botenstoffe, die für die Induktion und Regulierung der wesentlichen pathognomonischen Mechanismen bei der allergischen Immunreaktion verantwortlich sind. Durch Interleukin (IL)-4 und IL-13 kommt es zur gesteigerten Produktion von allergen-spezifischen IgE-Antikörpern, die Grundlage für die Aktivierung von Mastzellen und die Entwicklung der allergischen Frühreaktion (early asthmatic reaction). Durch IL-5, IL-3 und GM-CSF werden eosinophile Zellen aktiviert und wandern in die Atemwege ein. Hier entwickelt sich das Bild einer chronischen Atemwegs-Entzündung, und die Folge ist die allergische Spätreaktion (late asthmatic reaction). Der genaue Mechanismus und die Interaktion von T-Zell-Zytokinen, IgE-Produktion und eosinophiler AI ist nicht völlig geklärt und Gegenstand der vorliegenden Arbeit. Für die immunologischen Untersuchungen von AI und AHR wurde die Maus als Modell gewählt, die durch ihre gut definierte Immunologie und die Vielzahl von verfügbaren immunologischen "Werkzeugen" wie z.B. Antikörper und genetisch homogenen Stämmen entscheidende Vorteile bietet. Die in jüngerer Zeit entwickelten genetisch manipulierten Mausstämme ermöglichen darüber hinaus die genaue Analyse der Rolle einzelner Faktoren in der Pathogenese einer Erkrankung, da ihr vollständiges Fehlen (Defizienz) oder ihre Überexpression (Transgenität) direkte Rückschlüsse auf ihre Funktion erlauben. Zunächst wurden unterschiedliche Modelle der allergischen Sensibilisierung und Atemwegs-Provokation mit Allergen etabliert und miteinander verglichen. Das erste Modell, die Atemwegs-Sensibilisierung mit ausschließlicher Gabe von Allergen als Aerosol, imitiert den natürlichen Sensibilisierungsweg über die inhalative Route beim asthmatischen Patienten. Dieser Modus führt zu geringer allergen-spezifischer IgE-Produktion, einer marginalen inflammatorischen Reaktion in den Atemwegen und zu unspezifischer AHR, messbar in vitro durch elektrische Feldstimulation von trachealen Segmenten. Eine ausgeprägte inflammatorische Komponente oder die Ausbildung von in vivo AHR wie bei asthmatischen Patienten fehlen jedoch in diesem Modell. Als zweites wurde das Modell der passiven Sensibilisierung mit allergen-spezifischem IgE gefolgt von Allergen-Provokationen der Atemwege etabliert. Dieses Modell erlaubt im Gegensatz zum vorherigen die Unterscheidung des Einflusses von IgE und Allergen-Provokation der Atemwege. Auch hier entwickelt sich eine nur geringe, aber für die Ausbildung der AHR erforderliche eosinophile AI, die über die in vitro Bestimmung messbar ist. Als drittes Modell wurde die systemische Sensibilisierung mit Allergen gefolgt von Allergen-Provokationen der Atemwege etabliert. In diesem Modell kommt es zu hoher IgE-Produktion, und es herrscht eine ausgeprägte, eosinophile AI vor, die durch spezifische Immunohistochemie darstellbar und quantifizierbar ist. Für die Messung der AHR wurden zwei unterschiedliche in vivo Methoden entwickelt, die invasive Bestimmung des Atemwegswiderstandes und die Ganzkörper-Plethysmographie am nicht narkotisierten Tier. Durch den Einsatz von monoklonalen Antikörpern und genetisch alterierten Mausstämmen wurden in den drei unterschiedlichen Modellen der Einfluss und die Interaktion der wesentlichen Parameter der allergischen Immunreaktion für die Entwicklung von AI und AHR definiert. In den ersten beiden Modellen (Atemwegs- und passive Sensibilisierung) wurde anhand von T-Zell- und B-Zell-defizienten Mausstämmen und durch Einsatz von Antikörpern gegen T-Zellen oder Zytokine gezeigt, dass für die Entwicklung von eosinophiler AI die T-Zell-vermittelte Produktion von IL-5, für die Entwicklung von in vitro AHR das Zusammenspiel von allergen-spezifischer IgE-Produktion und eosinophiler AI notwendig ist. Im Modell der systemischen Sensibilisierung konnte in Mäusen, die genetisch defizient für B-Zellen oder Mastzellen oder mit anti-IgE Antikörpern behandelt waren, eine eosinophile AI und in vivo AHR wie bei normalen Tieren ausgelöst werden. Im Gegensatz hierzu kam es bei IL-4- oder IL-5-defizienten Mäusen oder nach Behandlung mit anti-IL-5 Antikörpern weder zu inflammatorischen Reaktionen noch zu funktionellen Veränderungen in den Atemwegen. Es kann hieraus gefolgert werden, dass bei allergen-induzierter AHR mit nur gering ausgeprägter AI ein gegen das erhöhte IgE gerichteter Ansatz (z.B. anti-IgE Antikörper) erfolgreich bei der Behandlung von Asthma sein kann. Bei Vorliegen von massiver AI scheint eine gegen die eosinophile Infiltration gerichtete Strategie (z.B. anti-IL-4/5 Antikörper) jedoch erfolgversprechender zu sein. / Allergic diseases such as bronchial asthma, atopic dermatitis and allergic rhino-conjunctivitis are steadily increasing. Asthma is the most common chronic airway disease in childhood, and leads to enormous socio-economic problems due to medication and hospitalisation. Cardinal symptoms of asthma are reversible bronchospasm after exposure with allergen (Airway Obstruction), a functional abnormality of the smooth muscles of the airways, that is characterized by increased contractility following unspecific stimulation (Bronchial Hyperreagibility or Airway Hyperreactivity, AHR), and the presence of a chronic inflammation in the small and middle-sized airways (Airway Inflammation, AI). Currently, treatment of asthma includes symptomatic therapy of airway obstruction with muscle relaxing medications (reliever) and unspecific anti-inflammatory therapy with cortico steroids (controller). Whereas the majority of patients lifes relatively safe and uncompromitted with this kind of treatment, a minority of asthmatic patients suffer either under the side-effects of continuous systemic high-dose steroids (steroid-dependent asthma), or stay symptomatic despite intensive treatment with steroids (steroid-resistent asthma). For this subgroup of patients, an efective, specific and safe mode of anti-asthmatic therapy is still missing. Imperative for the formulation of any innovative strategies for the treatment of asthma is the thorough knowledge of the pathophysiological mechanisms leading to the development of the disease. Allergic diseases are the consequence of aberrant immune reactions against common environmental antigens, such as pollen, food proteins or animal fur. It is commonly accepted by now that a dysregualtion of the T cell responses against these antigens are the main reason for the development of an allergic disease. In the case of allergic patients, production of so-called Th2-cytokines is increased, whereas Th1-cytokine production is relatively low. Production of the Th2-cytokines interleukin (IL)-4 and IL-13 induces increased production of allergen-specific IgE antibodies, resulting in immediate type of hypersensitivity reactions (early asthmatic reaction). Th2-cytokines IL-5, IL-3 and GM-CSF activate and recruit eosinophilic cells in the airways, leading to chronic eosinophilic airway inflammation and AHR (late asthmatic reaction). The exact mechanisms and the interaction of T cell cytokine production, IgE-production and eosinophilic AI is not fully understood and objective of the present presentation. For the immunological characterization of the basic mechanisms leading to the development of allergen-induced AI and AHR, the mouse was chosen as a model animal. Different modes of allergic sensitization and airway allergen challenge were established and compared to one another: sensitization with exclusive delivery of allergen via the airways, mimicking the natural way of sensitization and leading to moderate IgE-production, marginal AI and unspecifc AHR that is detectable in vitro by elektric field stimulation of tracheal segments; passive sensitization with allergen-specific IgE followed by allergen airway challenges, allowing the careful studies of IgE-dependent effects on AI and AHR; and systemic sensitization with allergen followed by repeated airway allergen challenges, leading to high IgE production and a profound eosinophilic AI. For detection of AHR following this mode of sensitization, two different in vivo methods were developed, invasive measurement of airway resistance and whole-body plethysmography of non-anesthesized animals. In the first two protocols (airway and passive sensitization), it was shown utilizing T-cell- and B-cell-deficient mouse strains and monoclonal antibodies against T cells or T cell cytokines, that for the development of AI and AHR the combined interaction of T-cell-mediated production of IL-5 and allergen-specific IgE-production was required. In contrast, in the mode of systemic sensitization, development of eosinophilic AI and in vivo AHR was independent of any Ig production or the presence of B cells, whereas IL-4- or IL-5-deficient mice or mice treated with anti-IL-5 antibodies prior to airway challenges did not develop any functional or structural abnormalities of the airways. In conclusion, these data show that treatment strategies aiming against increased IgE production (anti-IgE antibodies) may be effective in clinical situations with only limited airway inflammatory responses. In contrast, in patients with massive and predominant eosinophilic AI, approaches against the inflammatory component of the disease (anti-IL-4, anti-IL-5 antibodies) may be more promising for more specific treatment of bronchial asthma.

INTRODUÇÃO: A Asma Brônquica é caracterizada por obstrução ao fluxo aéreo, reversível ou não, e processo inflamatório pulmonar, caracterizado principalmente por eosinofilia. A persistência da inflamação pode induzir processo de reparo pulmonar associado à redução progressiva da função pulmonar. A recente descrição do sistema colinérgico anti-inflamatório, um mecanismo neural que suprime a resposta imune inata e controla a inflamação por inibição de citocinas proinflammatórias, e a detecção de alguns de seus componentes em células de vias aéreas sugerem uma importante participação deste sistema na fisiopatologia de doenças pulmonares. O principal mediador deste sistema é a acetilcolina (ACh), que é estocada em vesículas sinápticas pelo transportador vesicular de ACh (VAChT), proteína essencial para sua liberação. OBJETIVOS: Avaliar os efeitos da deficiência colinérgica por redução da VAChT nas alterações pulmonares observadas em modelo experimental de inflamação pulmonar induzida pela exposição crônica a ovoalbumina. METODOLOGIA: A redução colinérgica foi induzida pela modificação genética nos níveis de VAChT. Camundongos machos selvagens e mutantes foram submetidos ao protocolo de sensibilização subcutânea com ovoalbumina ou salina nos dias 0, 7 e 14. Após, foram submetidos a desafios inalatórios com ovalbumina a 1% ou inalações de salina por 20 minutos nos dias 26, 27 e 28. No dia 29, foi realizada a avaliação da mecânica pulmonar, da inflamação no lavado broncoalveolar e no tecido e análise histológica de remodelamento e expressão de MMP-9 e TIMP-1 por imunohistoquímica. Também foi quantificado por ELISA níveis de IL-4, IL-10 e de TNF-a no homogenato pulmonar. A análise estatística considerou um p<0,05 como significativo. RESULTADOS: Animais sensibilizados apresentaram hyperresponsividade brônquica, inflamação e edema peribrônquico e deposição de fibras colágenas e elásticas ao redor das vias aéreas comparado ao grupo salina (p<0,05). Além disso houve aumento de IL-4 no homogenato pulmonar e da expressão de MMP-9 e TIMP-1 nas células inflamatórias. Os animais mutantes, independente de serem ou não sensibilizados, apresentaram aumento de TNF-a no pulmão. Os animais mutantes que foram submetidos ao protocolo de sensibilização mostraram aumento da hiperresponsividade brônquica, do eosinófilos, do edema e da deposição de colágeno comparado aos animais selvagens que também foram sensibilizados com ovoalbumina. Estas alterações podem ser atribuídas ao aumento de IL-4 e de MMP-9/TIMP-1 que foi observado nos animais mutantes e sensibilizada em comparação com o os selvagens sensibilizados. Não houve diferença nos níveis de IL-10 nos grupos experimentais. Conclusão: A deficiência colinérgica piora a hiperresponsividade brônquica, a inflamação eosinofílica e o remodelamento, principalmente por interferir com a citocina pró-inflamatória IL-4 e na proporção de MMP-9 e TIMP-1. Estes dados sugerem que a via colinérgica antiinflamatória está envolvida na fisiopatogenia da asma e necessita ser mais investigada / BACKGROUND: Bronchial asthma is characterized by reversible or not airflow obstruction and pulmonary inflammation, mainly characterized by eosinophilia. The persistence of inflammation can induce lung repair process associated with progressive reduction in lung function. Recent evidence of the cholinergic anti-inflammatory system, a neural mechanism that suppresses the innate immune response and control inflammation by proinflammatory cytokines inhibition, and the detection of some of its components in airway cells suggest an important role of this system in pulmonary physiopathology. The main mediator of this system is acetylcholine (ACh), which is stored in synaptic vesicles by vesicular acetylcholine transporter (VAChT), an essential protein for ACh release. AIMS: To evaluate the effects of cholinergic deficiency by VAChT reduction on pulmonary alterations observed in an experimental model of pulmonary inflammation induced by chronic exposure to ovalbumin. METHODS: The cholinergic deficiency was induced by genetic modification on VAChT levels. Wild-type and mutant male mice were submitted to subcutaneous ovalbumin sensitization or saline protocol on days 0, 7 and 14. After, animals were submitted to inhalation challenge with ovalbumin 1% or saline for 20 minutes on days 26, 27 and 28. On day 29, we evaluated the pulmonary mechanics, inflammation in bronchoalveolar lavage and in airways, histological analysis of airway remodeling and the expression of MMP-9 and TIMP-1 by immunohistochemistry. It was also quantified by the levels of IL-4, IL-10 and TNF-a in lung homogenate. The statistical analysis were performed and a p<0.05 was considered significant. RESULTS: Sensitized animals presented bronchial hyperresponsividade, airway inflammation and edema and collagen and elastic fibers deposition of collagen and elastic fibers around the airways compared to saline group (p <0.05). Furthermore, there was an increase of IL-4 in lung homogenate and the expression of MMP-9 and TIMP-1 in inflammatory cells. The mutant animals, regardless the sensitization, showed an increase in lung content of TNF-a. The mutant and sensitized animals showed an increase in bronchial hyperresponsiveness, in eosinophils, edema and collagen deposition in airways compared to the wild type and sensitized animals. These changes can be attributed to increased IL-4 and MMP-9/TIMP-1 that were observed in mutant and sensitized animals. There was no difference in levels of IL-10 in the experimental groups. Conclusion: The cholinergic deficiency worsens bronchial hyperresponsiveness, eosinophilic inflammation, and airway remodeling mainly by interfering with the pro-inflammatory cytokine IL-4 and in MMP-9/TIMP-1 ratio. These data suggest that anti-inflammatory cholinergic pathway is involved in the asthma pathogenesis deserves further investigation

In der vorliegenden Studie wurde die Hypothese geprüft, daß Asthmatiker die Aufmerksamkeit von eigenen Körperprozessen ablenken und eine Ungenauigkeit bei der Interozeption relevanter Atemwegsobstruktionen aufweisen. Weiterhin prüften wir die Frage, inwieweit die postulierte Aufmerksamkeitsabwendung generalisiert ist und sich auch auf die nicht atemwegsbezogene Symptomwahrnehmung und die private Selbstaufmerksamkeit bezieht. Die Interozeptionsgenauigkeit wurde als Diskrepanz zwischen subjektivem Urteil und objektiver Atemfunktion bei spirometrischen Messungen berechnet, die anderen Variablen mittels Fragebögen operationalisiert. Es wurden insgesamt 91 Patienten einer Rehabilitationseinrichtung untersucht: 30 Asthmatiker, 30 Patienten mit chronisch obstruktiver Bronchitis (COB) und 31 Kontrollpatienten ohne Atemwegserkrankung. Die Ergebnisse deuten auf eine spezifisch atemwegsbezogene Aufmerksamkeitsablenkung sowie eine Überschätzung von Obstruktionen bei Asthmatikern hin. Überraschend zeigen auch die COB-Patienten auffällige Ergebnismuster in Richtung einer Unterschätzung von Obstruktionen sowie verminderter Selbstaufmerksamkeit. Die Ergebnisse lassen sich im Rahmen verhaltensmedizinischer Überlegungen interpretieren. / The hypothesis that asthmatic patients draw their attention away from bodily processes and show inaccurate interoception with regard to relevant airway obstructions was tested in this study. Additionally, we examined whether this postulated withdrawal of attention can also be generalized for the perception of non-airway related symptoms as well as for private self-consciousness. Accuracy of interoception was measured as the discrepancy between subjective judgement of obstruction and objective obstruction as shown in spirometric tests. Other variables were operationalized by self-reports. Ninetyone patients in a rehabilitation hospital were tested: 30 asthmatic patients, 30 patients with chronic obstructive bronchitis (COB), and 31 control subjects without any airway disease. Asthmatic patients showed attention withdrawal only with regard to bronchial airways. However, they also indicated an overestimation of airway obstruction. Surprisingly, deviant results were also found for the COB patients including underestimation of obstructions and lower self awareness. All results were interpreted from the perspective of behavioral medicine. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Neabejojama, kad tėvų tarpusavio nesutarimai gali būti vaiko streso priežastis. Sveikų vaikų tyrimai rodo, kad vedybiniai konfliktai gali būti ypač žalingi vaikams. Kaip šiuo atveju vedybiniai konfliktai siejasi su vaikų, sergančių bronchų astma, psichologiniu prisitaikymu tyrinėta dar nedaug. Šio tyrimo tikslas – patikrinti sąsajas tarp tėvų konfliktų raiškos, jų vaikų, sergančių BA, psichologinio prisitaikymo ir tam tikrų demografinių duomenų. Tyrime apklausti 192 vaikų, kurių amžius nuo 1,8 metų iki 12 metų amžiaus, tėvai. 86 vaikai, iš kurių 56 berniukai ir 30 mergaičių, serga lengva (N = 55) ir vidutine (N = 31) astmos forma. 106 to paties amžiaus vaikai, 55 berniukai ir 50 mergaičių, nesergančių jokia lėtine liga, sudarė kontrolinę grupę. Tyrime naudota Vaikų elgesio aprašai (CBCL/1½-5 ir CBCL6–18), Porų konfliktų ir problemų sprendimų skalė (CPS) bei vaiko aplinkos klausimynas. Tyrimo rezultatai rodo, kad vaikai, sergantys bronchų astma (BA), turi daugiau internalių sunkumų nei sveiki vaikai. Mergaitės, sergančios BA, turi daugiau eksternalių sunkumų nei sveikos jų bendraamžės. Sunkumų raiška, priklausomai nuo astmos sunkumo ir nuo sergančio vaiko lyties, nesiskiria. Nustatėme, kad ikimokyklinio amžiaus vaikai, sergantys bronchų astma, turi daugiau emocinių ir bendrų (elgesio ir emocinių) sunkumų nei sveiki jų bendraamžiai. Rezultatai atskleidė, kad BA sergančių vaikų tėvai (pagal mamų vertinimus) efektyviau sprendžia tarpusavio nesutarimus nei sveikų vaikų tėvai... [toliau žr. visą tekstą] / There is no doubt that parental conflicts can be the cause of child‘s stress. The studies of healthy children show that marital conflicts can be extremely harmful. However there are not many empirical studies of how marital conflicts relate to psychological adjustment in children with bronchial asthma. So the purpose of this study was to explore the relations between parental conflicts resolutions, their children with asthma psychological adjustment and certain demographic data. During the study parents of 192 children aged from 1,8 - 12 years were questionned. 86 children, 56 boys and 30 girls, were suffering from mild (N = 55) and moderate (N = 31) asthma forms. 106 of the same age children, 55 boys and 50 girls, without any chronic disease were used as a comparison group. In the study Child Behaviour Checklist (CBCL/1½-5 and CBCL6–18), the Conflicts and Problem – Solving Scales (CPS) and child‘s environmental questionnaire were used. The analysis of results showed that children with asthma have more internal difficulties than healthy children. Girls with asthma have more external difficulties as compared to their healthy peers. The expression of these difficulties does not differ depending on the form of asthma or child‘s with asthma gender. It was found that pre-school age children with asthma have more emotional and general (emotional and behavioural) difficulties than their healthy peers. The study showed that parents who had children with asthma (under the mothers... [to full text]

In der vorliegenden Studie wurde die Hypothese geprüft, daß Asthmatiker die Aufmerksamkeit von eigenen Körperprozessen ablenken und eine Ungenauigkeit bei der Interozeption relevanter Atemwegsobstruktionen aufweisen. Weiterhin prüften wir die Frage, inwieweit die postulierte Aufmerksamkeitsabwendung generalisiert ist und sich auch auf die nicht atemwegsbezogene Symptomwahrnehmung und die private Selbstaufmerksamkeit bezieht. Die Interozeptionsgenauigkeit wurde als Diskrepanz zwischen subjektivem Urteil und objektiver Atemfunktion bei spirometrischen Messungen berechnet, die anderen Variablen mittels Fragebögen operationalisiert. Es wurden insgesamt 91 Patienten einer Rehabilitationseinrichtung untersucht: 30 Asthmatiker, 30 Patienten mit chronisch obstruktiver Bronchitis (COB) und 31 Kontrollpatienten ohne Atemwegserkrankung. Die Ergebnisse deuten auf eine spezifisch atemwegsbezogene Aufmerksamkeitsablenkung sowie eine Überschätzung von Obstruktionen bei Asthmatikern hin. Überraschend zeigen auch die COB-Patienten auffällige Ergebnismuster in Richtung einer Unterschätzung von Obstruktionen sowie verminderter Selbstaufmerksamkeit. Die Ergebnisse lassen sich im Rahmen verhaltensmedizinischer Überlegungen interpretieren. / The hypothesis that asthmatic patients draw their attention away from bodily processes and show inaccurate interoception with regard to relevant airway obstructions was tested in this study. Additionally, we examined whether this postulated withdrawal of attention can also be generalized for the perception of non-airway related symptoms as well as for private self-consciousness. Accuracy of interoception was measured as the discrepancy between subjective judgement of obstruction and objective obstruction as shown in spirometric tests. Other variables were operationalized by self-reports. Ninetyone patients in a rehabilitation hospital were tested: 30 asthmatic patients, 30 patients with chronic obstructive bronchitis (COB), and 31 control subjects without any airway disease. Asthmatic patients showed attention withdrawal only with regard to bronchial airways. However, they also indicated an overestimation of airway obstruction. Surprisingly, deviant results were also found for the COB patients including underestimation of obstructions and lower self awareness. All results were interpreted from the perspective of behavioral medicine. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

This thesis includes set of published experimental results, which were obtained at the Department of Immunology, Second Faculty of Medicine Charles University within the project focused on the basal and applied research of the Primary immunedeficiencies (PID), particularly Common variable immunodeficiency (CVID). The first, theoretical part, is divided into two sections. The first section is dedicated to the general aspects of Primary antibody deficiencies (PAD). The second section is focused on epidemiology, ethiopathogenesis, classification, clinical and therapeutical aspects of CVID. The main consideration is devoted particularly to non-infectious complications, which significantly contribute to morbidity and mortality of CVID patients. The second part consists of the set of publications describing specific mechanisms of immune system dysregulation and their clinical manifestation, which are briefly commented. The spectrum of issues resolved within the project covers following basic aspects: 1) characteristics of lung complications in CVID from the point of view of bronchial asthma, 2) characteristics of associated malignancies, 3) significance of genetic background for the specific treatment, 4) therapy of CVID focused on aspects of immunoglobulin substitution. The results of the other...

Doctor Pharmaceuticae - DPharm / Underdiagnosis and undertreatment of asthma in children are barriers to optimal health care delivery and health, incurring substantial costs to both the families and health services. A tailored multifaceted educational outreach intervention ("academic detailing") was designed and implemented among private sector general practitioners (GPs) serving a poor working class urban community in Cape Town, South Africa. The intervention aimed to improve primary care childhood asthma by promoting the adoption of guideline-based key messages. The effectiveness of the intervention was tested in a randomised controlled trial, Chestiness and Asthma in Mitchell's Plain (CHAMP) (Zwarenstein 1999). This thesis describes the design, implementation and qualitative evaluation of the outreach intervention. Methods Qualitative interviews and quantitative sample surveys were conducted among GPs to identify and measure the prevalence of perceived barriers to optimal asthma care in children. A trained pharmacist visited GPs twice, promoting eight evidence-based primary care messages to overcome barriers to optimal care for asthma in children. The messages focused on key diagnostic indicators, a treatment algorithm based on severity, cost of drug therapies, inhaler and spacer use, and preventive treatment. These messages were formatted into attractive promotional material. The first visit promoted use of the messages, the second reinforced adoption in routine practice and assessed GPs' responses using unobtrusive qualitative data collection methods. The dialogue was tailored to each GP's needs. Results Thirty-two GPs received the intervention. All but one consented to both visits. At the first visit responses were varied. A few GPs were confused or suspicious; most were in agreement with the messages but seemed passive towards implementation; a few were keen to adopt the messages into their routine practice. Response at first visit was not predictive of use as assessed at the second. At the second visit, most GPs claimed that they personally agreed with and used the messages, with a large minority less enthusiastic. Conclusion The intervention appears to have been broadly accepted as evident from GPs' acceptance of the outreach pharmacist, but reports of complete adoption of the messages and use of the kit were less prevalent. This finding is consistent with and helps to explain the improved health outcomes of children with asthma in the CHAMP trial. The combination of qualitative and quantitative research methods was effective in identifying and assessing GPs' barriers. Further, the combination helped to confirm the determinants for the intervention. Unobtrusive qualitative methods provided valuable insight into GP behaviour in routine setting. Additional studies conducted in public sector pnmary care settings and for other diseases are needed to confirm the wider acceptability and effectiveness of multifaceted outreach interventions aimed at improving professional practice. Such an intervention in our study setting seemed successful for childhood asthma.

Detection of early pathophysiological changes of breathing in children with chronic respiratory disease MD. Vaclav Koucky - Ph.D. thesis Abstract Introduction: Currently, there are different methods for infant pulmonary function testing (iPFT) and morphological assessment of microscopic changes in endobronchial biopsy samples (EBB). In research setting, they allow detection of early pathophysiological changes of breathing in small children with chronic respiratory disease, respectively in risk of its development. Their clinical significance, however, is not fully acknowledged. The aim of this thesis is to evaluate the safety, feasibility and clinical significance of iPFT and EBB in infants younger than 2 years of age. In addition, the relationship between functional and morphological changes of respiratory tract and the function of peripheral chemoreceptors was studied in selected patients' subgroups. Methods: Fifty-five infants with cystic fibrosis (CF), 35 physician-confirmed recurrent wheezers (AB), 9 infants with congenital diaphragmatic hernia, 7 with interstitial lung disease (chILD) and 3 with primary ciliary dyskinesia (PCD) were enrolled. All infants underwent iPFT and relevant clinical history data were recorded. Based on patients' age, CF group was divided into CFmalí (< 6 months) and CFvelcí (>...