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Regular anti-inflammatory treatment is essential in treating persistent asthma. Most commonly, inhaled corticosteroids (ICS) are used. However, especially in children, there is concern about the long-term safety of ICS such that doses should be kept to a minimum. The use of theophylline has decreased because of frequent side-effects in therapeutic doses. In adults, there have been reports about an immunomodulatory effect of low-dose theophylline. To study the clinical and immunomodulatory effect in children, 36 patients (mean age 12.5 SD 2.4 years) with moderate, persistent asthma on regular ICS were recruited into a placebo-controlled, double-blind study. After a 6-week run-in period, patients received either theophylline 10 mg/kg bodyweight or placebo for 12 weeks. Diary cards, lung function, peripheral blood lymphocyte subpopulations and serum eosinophil cationic protein (sECP) were assessed. In the treatment group, mean serum theophylline was 7.1 mg/l. There was no change in symptoms or use of rescue medication. Mean (SD) peak expiratory flow (PEF) increased from 86% (24) to 95% (18) predicted. sECP decreased from 43.2 microg/l (32.5) to 26.5 microg/l (16.9) (p = 0.02). Lymphocyte subpopulations did not change. The study failed to show a beneficial clinical or an immunomodulatory effect of theophylline when used in low doses. These results do not support a more important role of theophylline in the long-term treatment of moderate childhood asthma.

Einleitung. Die bronchopulmonale Dysplasie (BPD) ist auch nach Einfuhrung der Surfactanttherapie eine schwerwiegende Folgeerkrankung des neonatalen Atemnotsyndroms. Anhand einer Kasuistik sollen mogliche Indikationen und Wirkmechanismen von inhalativem Stickstoffmonoxid (iNO) in der Therapie der BPD dargestellt werden. Kasuistik. Das Fruhgeborene der 25. SSW wurde wegen eines Atemnotsyndroms Grad 4 primar intubiert. Trotz Surfactantsubstitution und Hochfrequenzoszillationsbeatmung blieb das Kind hypoxisch. Durch die Applikation von iNO gelang eine Normoxygenierung. In der Folge entwickelte das Kind eine schwere BPD, sodass im Alter von 1 Jahr eine Lungentransplantation in Erwagung gezogen wurde. Erst die Langzeitapplikation von iNO uber nasalen CPAP (CPAP: kontinuierlich positiver Atemwegsdruck) erlaubte eine anhaltende Reduktion der Sauerstoffzufuhr. Im Alter von 2 Jahren benotigte das Kind keinen zusatzlichen Sauerstoff mehr. Diskussion. Die Applikation von iNO uber nasalen CPAP kann in Fallen einer schweren BPD, bei denen eine pulmonale Hypertonie mit Ventilations-Perfusions-Missverhaltnis im Vordergrund steht, moglicherweise eine effektive, wenig invasive Therapieoption darstellen. Die zusatzliche Schadigung des Lungenparenchyms durch hohe inspiratorische Sauerstoffkonzentrationen kann wirkungsvoll vermieden werden.

The mucosal surfaces are the first portals of entry for most infectious agents, among which respiratory and intestinal viruses are of greatest epidemiological importance. To combat these infections, the immune system uses unspecific and specific mechanisms. Unspecific responses include the production of virus-induced cytokines, such as type 1 interferons and natural killer (NK) cell activity, while specific immune responses mainly depend on cytotoxic T cells, which are important especially in the early course of a viral infection, and on antibodies. At the mucosal sites, antiviral secretory IgA antibodies play a major role in clearing viral infections and preventing or modifying disease after re-exposure. Passive transfer of virus-specific antibodies has been used in experimental and clinical settings to prevent or treat viral mucosal infections. In the future, the development of new mucosal vaccines promises to have the strongest impact on the epidemiology of viral infections.

Approximately 90% of infants and children with severe acquired laryngotracheal stenoses are tracheotomy dependent and therefore impaired in their physical and speech developments. In addition, tracheotomized infants can be endangered by the cannula due to the possible crusting of secretions or its dislocation. Thus, early repair of a stenosis is mandatory. Within the last 10 years, we successfully operated on 18 children with severe laryngotracheal stenoses. Ten children were treated with a modified Cotton technique. This paper reports our results of cricotracheal resection performed in 8 children since 1994 (age distribution: 7 months through age 15 years). Four children had Cotton grade II stenoses, three had grade III stenoses and one grade IV stenoses. In 3 patients a tracheotomy had been performed at another institution. Since their tracheostomas were too far caudal, they could not be included in the primary resection. All 8 children have been successfully decannulated. Five children without tracheotomies could be extubated uneventfully on the 5th postoperative day. All three primarily tracheotomized children needed further endotracheal stenting with T-tubes because of stomal and suprastomal collapse. Two of these latter children additionally required a tracheoplasty with rib cartilage grafts in order to stabilize the suprastomal trachea prior to decannulation. No patient experienced injuries to the recurrent laryngeal nerves or insufficiencies of the anastomosis. All children's voices were not impaired. This is the third report in literature of cricotracheal resections in infants and children, indicating that this effective, one-stage procedure is superior to laryngotracheal reconstruction with rib cartilage.

Kinder mit kraniofazialen Fehlbildungen neigen in besonderem Mas zu obstruktiven Atemwegstorungen. Eine besondere Rolle spielen Anomalien, die mit einer Unterentwicklung oder Rucklage des Unterkiefers einhergehen. Hierbei liegt der Zungengrund der Rachenhinterwand an und verlegt so die Luftwege. Durch Anwendung der Distraktionsosteogenese konnen eine Verlangerung der unterentwickelten Mandibula und dadurch eine Ventralisierung der Zunge erreicht werden. Drei kleine weibliche Patienten im Alter von 7–15 Monaten mit schweren syndromalen Erkrankungen und peripheren Atemwegobstruktionen bei mandibularer Mikrognathie wurden durch Verlangerung der Mandibula mittels Kallusdistraktion behandelt. Wegen Schluckunfahigkeit war bei allen 3 Kindern eine Gastrostomie bzw. eine permanente Nasogastralsonde angelegt worden. Bei der ersten kleinen Patientin, die schon kurz nach der Geburt tracheotomiert wurde, konnten 10 Tage nach Beginn der Distraktion Schluckversuche durchgefuhrt werden. Vor der geplanten Dekanulierung mus jedoch noch die Abtragung umfangreicher Trachealgranulationen erfolgen. Bei der 2. Patientin konnte am 6. Tag der Distraktion der Nasopharyngealtubus entfernt und auf eine geplante Tracheotomie verzichtet werden. Beim 3. Fall bildete sich eine therapierefraktare Schlafapnoe unter der Distraktion vollig zuruck. Unsere Erfahrungen zeigen, das die Distraktionsesteogenese zur Behandlung obstruktiver Atemstorungen in Verbindung mit Minderentwicklungen des Unterkiefers auf der Grundlage einer eingehenden interdisziplinaren Untersuchung mit genauer Lokalisation des Atemweghindernisses ein wertvolles alternatives Therapiekonzept darstellt.

Die Septische Granulomatose wird durch die Unfahigkeit von Phagozyten hervorgerufen, aufgenommene Erreger mit Hilfe von mikrobizidem reaktivem Sauerstoff abzutoten. Besonders Formen der Septischen Granulomatose mit Restaktivitat neigen dazu, andere Krankheitsbilder manchmal tauschend ahnlich nachzuahmen und den Behandler in eine diagnostische Falle zu locken. Eine klinisch bisher unauffallige 8jahrige Patientin zeigte viele Symptome, die sehr gut mit einer exogen allergischen Alveolitis vereinbar waren, wie u.a. eine ausgepragte restriktive Ventilationsstorung, ein suggestives Rontgenbild des Thorax, in der Mehrzahl CD8-positive Lymphozyten in der bronchoalveolaren Lavageflussigkeit sowie eine suggestive histologische Befundung. Hinweise auf die wahre Grunderkrankung, wie Neutrophilie und hoher Anti-Aspergillustiter konnten leicht ubersehen werden. Da auch eine infektiose Genese nicht auszuschliesen war, wurde die Patientin in Unkenntnis der Grunderkrankung mit einer Kombination aus Antibiotika und Prednisolon behandelt. Nach kurzzeitiger deutlicher Besserung kam es zu einer dramatischen respiratorischen Verschlechterung mit massivem nun im Tracheobronchialsekret nachweisbaren Aspergillusbefall. Die Patientin verstarb unter dem Bild eines ARDS in der respiratorischen Insuffizienz trotz erfolgreich zuruckgedrangter Aspergillusinfektion. Diskussion: In allen Fallen, bei denen die Septische Granulomatose zur Differentialdiagnose gehort, mus– insbesondere vor einer Steroidtherapie – eine adaquate Diagnostik erfolgen.

Fragestellung und Methode: Um den klinischen Verlauf des Asthma bronchiale, die Auspragung der Symptome und die Entwicklung der Lungenfunktion vom Kleinkindes- zum Schulalter zu untersuchen, wurden 100 Schulkinder (69 mannliche, 31 weibliche) mit der Diagnose Kleinkindesasthma in einem mittleren Alter von 9,1 Jahren nachuntersucht. 75 von 100 Kindern wurden in unserer Ambulanz vorgestellt und Lungenfunktionsmessungen einschlieslich einer Kaltluftprovokation durchgefuhrt. Von weiteren 25 Kindern wurden Fragebogen ausgewertet. Ergebnisse: Nur 27 % der Kinder waren frei von obstruktiven Symptomen; anamnestisch konnte bei 45 % eine Verbesserung, bei 24 % unveranderte und bei 4 % zunehmende Beschwerden beobachtet werden. Nur 11 von 75 (15 %) Kindern hatten normale Lungenfunktionswerte im symptomfreien Intervall. Ausgepragt pathologische Befunde wurden nachgewiesen: Uberblahung bei 34 %, zentrale Atemwegsobstruktion bei 59 % und periphere Obstruktion bei 52 %. 63 % der Kinder zeigten Zeichen der bronchialen Hyperreagibilitat nach Kaltluftinhalation oder in der initialen Lungenfunktion eine so ausgepragte Obstruktion, das nur ein Bronchospasmolysetest moglich war. Trotz dieser schlechten Ergebnisse inhalierten nur 34 % regelmasig, lediglich 28 % fuhrten eine entsprechend internationalen Konsensusempfehlungen ausreichende Therapie durch. Schlusfolgerung: Trotz fruhzeitiger Diagnose ist die weitere Entwicklung der nachuntersuchten Kinder nicht befriedigend. Da von der Mehrzahl der Kinder heute keine adaquate Therapie mehr durchgefuhrt wird, konnen wir den Einflus der Therapie auf die langfristige Prognose von fruhkindlichem Asthma im Rahmen dieser Studie nicht beurteilen. Die unzureichende Therapie-Compliance macht jedoch deutlich, das Schulungsprogramme fur Kinder und Eltern dringend notwendig sind.

In this study we evaluated antigen-specific in vitro responses of peripheral blood lymphocytes to lipopolysaccharide (LPS)-depleted food allergens in children who reacted to food challenge (cow's milk or hen's egg) with a deterioration of their atopic dermatitis (AD). Some of the children showed immediate symptoms (urticaria, bronchial asthma or gastrointestinal symptoms) as well. The proliferation of casein-stimulated lymphocytes from children reacting to cow's milk (age 0.7-5.9 years) was significantly higher (P < 0.01) than the proliferation of lymphocytes from 15 children with AD without milk allergy (age: 2.1-9.1 years). Twenty-eight T-cell clones (TCC) were established from the blood of three children sensitized to cow's milk and hen's egg who reacted to double-blind, placebo-controlled oral food challenge both with a deterioration of AD and with immediate symptoms. Surprisingly, 16 of 28 casein- or ovalbumin-specific TCC were CD8+. All TCC produced high amounts of IFN-gamma upon stimulation with concanavalin A. In addition, 75% of the CD4+ TCC and 44% of the CD8+ TCC secreted IL-4. Our results indicate that: (i) food-specific proliferation of blood lymphocytes can be detected in patients with clinically relevant food allergy with LPS-depleted allergens in vitro and (ii) circulating food-specific lymphocytes are CD4+ and CD8+ T cells with the capacity of producing both type 1 and type 2 cytokines.

Respiratory syncytial virus (RSV) may play an important role in allergic diathesis by creating a Th2-type immune response. Mycobacterium bovis bacillus Calmette-Guérin (BCG) is known to induce a Th1-type immune response, but the association of BCG vaccination and the suppression of allergy development remain controversial. We investigated the influence of BCG vaccination on the immune response to RSV in a mouse model. Balb/c mice were BCG vaccinated, RSV infected and ovalbumin (OVA) challenged. Mice were sacrificed one, two and four weeks after allergen exposure. Bronchoalveolar lavage was performed. Alveolar macrophages and lymphocytes from spleens and lung-associated lymph nodes were investigated for cytokine production and cell proliferation. Serum was tested for allergen-specific immunoglobulin-E (IgE). Lung eosinophilia was diminished by BCG immunisation. OVA-specific serum IgE was increased regardless of prior BCG vaccination. Interleukin-4 secretion of spleen lymphocytes increased in BCG-vaccinated mice only one week after allergen exposure but was comparable to non-vaccinated mice at four weeks. The reactivity of spleen lymphocytes towards concanavalin-A to secrete interferon-gamma was increased in the vaccinated group at the end of the observation period. Interleukin-6 and tumour necrosis factor-alpha secretion of alveolar macrophages as well as proliferation of stimulated thoracic lymph node cells were increased and prolonged in vaccinated mice. BCG immunisation led to a local suppression of the allergic reaction within the lung. No reduction of systemic IgE production was observed. Further studies are necessary to determine a possible time dependence of BCG immunisation.

Es werden Infekte der oberen und Infekte der unteren Atemwege unterschieden. Bezuglich der Infektionserreger stellen aber die Atemwege von der Nase bis zu den Alveolen ein Kontinuum dar. Gewisse Erreger zeigen Vorliebe fur bestimmte Abschnitte der Atemwege (Abb. 8.1).

A hybrid protein [Met-Ala-(His)(6) OprF(190-342)-OprI(21-83)] consisting of the mature outer membrane protein I (OprI) and amino acids 190-342 of OprF of Pseudomonas aeruginosa was expressed in Escherichia coli and purified by Ni(2+) chelate-affinity chromatography. After several studies in healthy volunteers, as well as in patients, had proven the tolerability and immunogenicity of the the OprF-OprI vaccine, after intra-muscular application, we developed an emulgel for intranasal immunization. For this purpose we combined a highly concentrated OprF-I with sodium dodecylsulfate as vehicle and the gel matrix natriumlauryl sulfate. After safety and pyrogenicity evaluations in animals, eight healthy adult human volunteers received the OprF-I gel intranasally three times at 2-week intervals. The vaccination was well tolerated and no side effects were observed. An antibody induction (IgG and IgA) could be detected in the sera. These data support continued clinical investigation of the protection against infections in cystic fibrosis patients and patients prone to P. aeruginosa infections.

Fur die sozialmedizinische Begutachtung von Erkrankungen der Atmungsorgane konnen mehrere Dimensionen der medizinischen Diagnostik von besonderer Bedeutung Scin.

Circulating alveolar macrophages and Type-Il-cells of the lung represent important cells of the respiratory tract with immunomodulatory activities. Alveolar macrophages are the first effector cells of the immune system in the lung to defend bacterial or viral infections. Macrophages influence several cell compartments via direct cell-cell interactions or by secreted products as there are different cytokines or chemokines. Type-ll-pneumocytes are the primary producer ot Surfactant. Additionally, these cells are able to interact with the immune system by secretion of Interleukin-1 (IL-1) and the expression of adhesion molecules as ICAM-1. Our group was interested in the influence of an infection with Respiratory syncytial virus (RSV) on the functions of alveolar macrophages and Typell-cells alone and the interactions between these two cell types. Using in vitro-cultures, it is difficult to examine the influence of one cell compartment of the lung on the other, for this purpose, we established a coculture system using human alveolar macrophages collected from bronchoalveolar lavage and the human cell line A549, representing the characteristics of Type-Il-cells, producing Surfactant, IL-1 and several chemokines i.e. Interleukin-8 (IL-8) and MCP-1. Alveolar macrophages were plated into a 24- well microtiterplate and A549 cells into a tissue culture insert which were placed into the well. To establish the coculture system the movement of the investigated cells through the membrane of the insert was measured to ensure, that no mixing of the cells during the culture occured. We could show, that a pore size of the membrane of 0.45 pm was necessary to inhibit a movement of the cells through the membrane. The cells were infected with RSV either the alveolar macrophages or the A549 cells and after 24 hours, we measured the virus concentration in the culture supernatant. Further, cell culture supernatants were collected at different time points and the concentrations of MCP-1, IL-8 and IL-1 were detected. Infected alveolar macrophages and A549 cells showed an increased secretion of IL-8 in comparison to not infected cells, whereas in the supernatant of cocultured infected alveolar macrophages and A549 cells the strongest increase in the concentration of IL-8 could be demonstrated. The coculture system described is a useful tool to determine interaction between cell compartments without cell-cell-interaction in different situations as there are i.e. infectious diseases.

Approximately 90% of infants and children with severe acquired laryngotracheal stenoses are tracheotomy dependent and therefore impaired in their physical and speech developments. In addition, tracheotomized infants can be endangered by the cannula due to the possible crusting of secretions or its dislocation. Thus, early repair of a stenosis is mandatory. Within the last 10 years, we successfully operated on 18 children with severe laryngotracheal stenoses. Ten children were treated with a modified Cotton technique. This paper reports our results of cricotracheal resection performed in 8 children since 1994 (age distribution: 7 months through age 15 years). Four children had Cotton grade II stenoses, three had grade III stenoses and one grade IV stenoses. In 3 patients a tracheotomy had been performed at another institution. Since their tracheostomas were too far caudal, they could not be included in the primary resection. All 8 children have been successfully decannulated. Five children without tracheotomies could be extubated uneventfully on the 5th postoperative day. All three primarily tracheotomized children needed further endotracheal stenting with T-tubes because of stomal and suprastomal collapse. Two of these latter children additionally required a tracheoplasty with rib cartilage grafts in order to stabilize the suprastomal trachea prior to decannulation. No patient experienced injuries to the recurrent laryngeal nerves or insufficiencies of the anastomosis. All children's voices were not impaired. This is the third report in literature of cricotracheal resections in infants and children, indicating that this effective, one-stage procedure is superior to laryngotracheal reconstruction with rib cartilage.

Subglottic laryngotracheal stenosis represents the most severe intubation injury and is increasingly encountered in children due to long-term ventilation during intensive care treatment. Since more than 90% of these children have tracheostomies their physical, psychosocial and speech development can be greatly impaired. A tracheostomy in infants can also be a potentially life-threatening condition, making necessary resolution of the laryngotracheal stenosis and removal of the tracheostoma as soon as possible. During the past 10 years, we have treated 46 children with laryngotracheal problems, including 18 children with severe laryngotracheal stenosis. Ten children (3 with grade II stenosis and 7 with grade III stenosis) were treated by laryngotracheal reconstruction using an anterior rib cartilage graft as described by Cotton. One child with posterior glottic stenosis required a posterior laminotomy with a second rib cartilage graft. Differing from the original method, we stabilized the enlarged endotracheal lumen postoperatively with a Montgomery t-tube. This was kept in place for 10 months on average (shortest period, 6 months; longest period, 12 months). All 10 children could be decannulated, and the tracheostoma closed. Three of the children were operated in other institutions and had a different technique prior to our intervention. Two of our operations failed initially. However, both patients were treated successfully by a second intervention (which was the fourth operation for one of the patients). The reasons for our modification, the operative technique and tips for postoperative management, as well as possible pitfalls and complications, are discussed.

Unter einer Atelektase versteht man einen Lungenanteil mit minder- oder unbelufteten Alveolen bei sonst normaler Parenchymstruktur. Die Ausdehnung kann dabei von diffusen Mikroatelektasen uber Segment- und Lappen-atelektasen bis hin zum Kollaps einer gesamten Lunge reichen. Fur teilbeluftete Lungenabschnitte wird im radiologischen Sprachgebrauch der Begriff Dystelektase verwandt, die als Vorstufe der Atelektase angesehen wird. Fur rezidivierende oder chronische Beluftungsstorungen im Bereich des Mittellappens, die oft mit chronisch obstruktiven Lungenerkrankungen assoziiert sind, wurde der Begriff Mittellappensyndrom gepragt. Auf die seltenen sog. primaren, bereits bei Geburt bestehenden Atelektasen soll hier nicht eingegangen werden.

Children with craniofacial malformations are at special risk for the development of peripheral airway obstruction. The problems are magnified in patients with retroposition or hypoplasia of the mandible. In these cases, the base of the tongue is posteriorly displaced, hereby decreasing the airway diameter. By application of distraction osteogenesis the mandible can be lengthened to move the base of the tongue forward and open the airway. Three female patients aged between 7, 11, and 15 months suffering from peripheral airway obstruction caused by mandibular hypoplasia were treated by gradual distraction. All of them had a gastrostomy or a nasogastral tube in place, respectively, due to severe nutrition problems. In the youngest patient tracheostomy was performed shortly after birth and was already planned in the 15-month-old child, who had received a permanent nasopharyngeal tube. The 11-month-old child suffered from severe refractory sleep apnea. Exercises in oral feeding were possible in the youngest patient after 10 days of distraction. In the oldest one, the airway tube was removed on the six day of distraction and, thus, tracheotomy was successfully avoided. In the 11-month-old child apneic events a rapidly decreased. Our experience suggests that distraction osteogenesis after careful preoperative evaluation can be successfully performed for the treatment of peripheral airway obstruction in patients with selected craniofacial anomalies.

Alveolar macrophages (AL) are the first line of defense against inhaled pathogens and are exposed to virus during the course of a respiratory syncytial virus (RSV) infection. Interference of virus with alveolar macrophage functions may contribute to the risk of acquiring secondary bacterial infections during or after respiratory tract infections with RSV or other viral agents. We studied whether murine AL get infected with RSV and whether they support viral replication in vitro. In addition, the effects of RSV on microbicidal and on immunoregulatory functions were examined. Only a subpopulation of AL expressed viral F proteins after exposure of these cells to RSV. Infected AL released only small amounts of infectious virus into the supernatant. The extent of virus replication in AL seemed to be dependent in part on the amount of IFN induced by the virus, as has been demonstrated by infection of lung tissue macrophages and AL in vitro. In general, RSV infection of pulmonary macrophages appeared to be abortive. Nevertheless, release of reactive oxygen intermediates, phagocytosis, and killing of protozoa were reduced in RSV-infected AL in comparison to noninfected AL. In contrast, RSV stimulated secretion of TNF-alpha, IL-1, and IL-6 in an infectious-dose dependent manner. Along with the increased cytokine release, accessory functions of AL were increased after RSV exposure. Thus, exposure of AL to RSV appeared to stimulate their immunoregulatory functions, whereas the microbicidal activity of these cells seemed to be severely diminished.

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract illness in infants. However, the mechanisms leading to resolution of RSV infections are poorly understood. Since alveolar macrophages play an important role in defending the respiratory tract against infectious agents we investigated the interactions of RSV with these cells. Murine alveolar macrophages were challenged in vitro with RSV at different multiplicities of infection. The percentage of macrophages expressing viral antigen was determined by staining with monoclonal anti-RSV antibodies and evaluation by fluorescence microscopy or FACS analysis. The ability of macrophages to support virus replication was measured by a plaque forming assay on HEp-2 cells. Cell lysates of macrophages contained only small amounts of viable RSV in comparison to disrupted HEp-2 cells. The amount of viable RSV as well as the percentage of macrophages expressing viral antigen decreased rapidly over time. Activated macrophages had a reduced virus load in comparison to resting macrophages. RSV infected macrophages released biologically active tumor necrosis factor (TNF) in a virus dose dependent manner. In contrast, a high virus inoculum resulted in reduced microbicidal activity and oxygen radical production. Our results suggest that RSV infection influences different functions of alveolar macrophages in various ways. Since TNF is thought to restrict viral replication in several cell types it may play a role in limiting virus replication.

Juvenile papillomatosis of the larynx is a disease of viral origin and is a rare cause of hoarseness and stridor in childhood. Although the tumours are basically benign, they may present problems in therapy due to their localisation and marked tendency to recur. According to the present state of knowledge, a combination of laser coagulation and alpha-interferon therapy is the treatment of choice. It can be applied on a long-term basis effectively and with few side effects due to individualised dosage determination. We report on a girl patient of 2 1/2 years of age with recurrent juvenile papillomatosis of the larynx. Long-term alpha-interferon therapy was so far successful in preventing progress of the pattern of findings. Treatment is well tolerated after the most suitable dose has been found for a particular patient. No side effects were seen that would have compelled us to discontinue the treatment. We are planning to continue interferon therapy for at least 1 to 2 years with regular endoscopic control.

Averting initial colonization of the respiratory tract with P. aeruginosa would be of great benefit for patients with cystic fibrosis (CF). Our approach to this problem is mucosal immunization with a vaccine prepared from the OMP fraction of a PAO-1 strain of P. aeruginosa. Sprague-Dawley rats were given 5 intragastric doses of the vaccine on 5 consecutive days and an intranasal booster dose 21 days later. Immunized animals developed high titers of OMP-specific IgG antibodies in serum and a specific IgA response in bronchioalveolar and small intestinal lavage samples, all determined by ELISA. When challenged 7 days after the booster (day 28) by intratracheal injection of live bacteria of a heterologous strain of P. aeruginosa the immunized rats showed enhanced bronchopulmonary bacterial clearance compared to nonimmunized controls, as indicated by bacterial counts from homogenized lung tissue taken 4 hrs after challenge. Thus, mucosal immunization with OMP vaccines might hinder initial colonisation of the lungs with P. aeruginosa.

Dihydrorhodamine 123 (DHR) attached to membranes of granulocytes (PMN) and monocytes is caused to fluoresce by reactive oxygen intermediates (ROI) indicating the ability of phagocytes to produce these microbicide metabolites in a flow microcytofluorimeter. Whole blood samples from five boys with known chronic granulomatous disease (CGD) and from their mothers (and from one father and one grandmother), were examined following erythrocyte lysis in order to test this new method. An incubation period of 10 min with phorbol-myristate-acetate, followed by another 15 min incubation period with DHR before flow microcytofluorimetric analysis of 5 or 10 x 10(3) phagocytes, was sufficient to obtain the following results. PMN and monocytes from four patients with CGD could clearly not produce any ROI whereas cells from one patient displayed decreased activity in ROI production as compared to cells from a healthy donor. The X-linked mode of inheritance was detected in six carriers by the presence of two different cell populations (one normal ROI-producing and one negative or less active population). All the phagocytes from one mother produced ROI in normal amounts suggesting an autosomal mode of inheritance. All in all, the method presented provides a fast and most simple tool to diagnose CGD, to determine a decrease or total lack of ROI production and to establish the mode of inheritance of the disease.

We report on a five-year-old patient with a chronic pneumonia of the upper left lobe of the lung, in whom a broncho-enteric sequestration with ectopic pancreas was found in the mediastinum. Reviewing the literature, different theories on the embryogenesis of this extremely rare anomaly are discussed.

Data of 124 patients with primary immunodeficiencies were examined in a retrospective study in respect of incidence and severity of bronchopulmonary immunodeficiencies. Relapsing pneumonias were seen in 40 patients (32.3%) and bronchiectases in 15 cases (12.1%). Children with severe antibody deficiencies or combined immunodeficiencies were involved particularly often. Avoidance of pulmonary complications is of special prognostic importance with these patients.

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by the defective generation of active oxygen metabolites by phagocytic cells. CGD can be associated with a condition called McLeod phenotype if a large X-chromosomal deletion includes the genes for gp91phox and the XK-protein. The absence of XK on erythrocyte membranes concomitantly leads to a reduced expression of Kell antigens. If transfused with red cells expressing these proteins, patients with CGD and McLeod phenotype become sensitized which may limit future transfusions. We present a patient with CGD and McLeod phenotype, who had received Kx- (the antigen of XK) and K- positive red cells at the age of 10 months; 9 years later he was given granulocyte transfusions following lung surgery because of pulmonary aspergillosis. Shortly thereafter he required a transfusion of red cells, to which he responded with a severe hemolytic adverse reaction. Antibodies against Kx- and K- antigens were detected. Hematopoietic stem cell transplantation (HSCT) is potentially curative in CGD and was planned for this boy at the age of 14 years because of progressive aspergillosis. Transfusions in this situation can only be given from Kx- and K- antigen negative donors suffering from McLeod syndrome themselves. Resources for these products are extremely limited. Furthermore any transplant would contain Kx- antigen and could potentially boost immunological reactions inducing graft rejection. To cope with these potential complications the following strategy was used: before HSCT autologous red cells as well as bone marrow for an autologous rescue therapy in case of graft rejection were cryopreserved. B-cells were depleted in the patient by two infusions of Mabthera (anti-CD20 antibody). Total body irradiation (12Gy), fludarabine and ATG were given for conditioning. No blood products were necessary during conditioning and before HSCT from a HLA- matched unrelated donor. Transfusions of platelets and red cells from Kx- antigen positive and K- negative donors were well tolerated 11 days after HSCT. No GvHD occurred on prophylaxis with CSA. Hematological and immunological reconstitution with complete donor chimerism was uneventful except a transient episode of immune mediated thrombocytopenia at 5 months after HSCT which responded promptly to steroids. After 10 months of follow up the patient is currently fully engrafted, in an excellent clinical condition and back to school. Conclusion: In patients with X- linked CGD screening for McLeod phenotype needs to be performed prior to transfusion of blood products. Even if sensitization to Kx- and K- antigens has occurred, HSCT can be curative as demonstrated for the first time in this report.

Pediatric lung or heart-lung transplantation (pL/HLTx) represents a challenge for an extraordinary patient population. The requirements in immunosuppressive therapy and the associated risks result in disappointing long term results, especially when the life expectancy of this age group is taken into account. Also, due to the size of these patients, the donor pool for the individual recipient is significantly smaller, compared to that of adult patients. We performed a retrospective analysis of our patient cohort and compared the results of pediatric to adult patients. Methods: Out of a total of more than 660 L/HLTx recipients at our institution, 65 patients (pts.) belong to the pediatric group ( 20 years), with 46 pts. between 16 and 20 years of age, 15 pts. between 11 and 15, 2 between 5 and 10, and 2 between 0 and 5. 13 underwent transplantation in 2003, 7 up to Sept. in 2004. Due to the severe organ shortage, we have begun to routinely transplant reduced size (RS) organs in the pediatric LTx group since 2003. Main underlying disease was CF (45%). 1 year survival was 66 7% vs. 77 2% in the adult group, 3 year survival was 56 8 %, compared to 69 2% survival in adults. Comparison of survival of RS size to non-RS size LTx shows no difference in outcome. As with all pediatric pts. undergoing solid organ transplants, we noted a significantly increased rate of rejections. Our data corroborate that pL/HLTx is associated with a differing scope of complications and therapeutic requirements. Since survival does not differ between RS LTx and non-RS LTx, RS LTx offers means to enlarge the donor pool for pediatric recipients. Due to the specific requirements pL/HLTx should be performed by specialized programs, and adapted treatment and monitoring regimes have to be developed, to increase the long term results following pL/HLTx.

We report on our experience in 8 patients with different forms of chronic interstitial lung disease. These included lymphocytic interstitial pneumonitis and chronic bronchiolitis. Clinical presentation consisted in tachypnoea, cyanosis, cough, crepitant rales and failure to thrive. Diagnostic work up included lung function studies in all patients, bronchoscopy with bronchoalveolar lavage (BAL) in 7 patients and open lung biopsy in 4 patients. Therapy included oral and inhaled steroids, inhalation with bronchodilators and oral hydroxychloroquine. While most of the patients did not respond to steroids alone, hydroxychloroquine improved the clinical and laboratory findings in a majority of our patients. Conclusion: Further controlled studies are required for propper evaluation of the effect of hydroxychloroquine in the treatment of chronic interstitial lung disease in children.

Averting initial colonization of the respiratory tract with P.aeruginosa would be of great benefit for patients with cystic fibrosis (CF). Our approach to this problem is mucosal immunization with a vaccine prepared from the OMP fraction of a PAO-1 strain of P.aeruginosa. Sprague-Dawley rats were given 5 intragastric doses of the vaccine on 5 consecutive days and an intranasal booster dose 21 days later. Immunized animals developed high titers of OMP-specific IgG antibodies in serum and a specific IgA response in bronchoalveolar and small intesinal lavage samples, all determined by ELISA. When challenged 7 days after the booster (day 28) by intratracheal injection of live bacteria of a heterologous strain of P.aeruginosa the immunized rats showed enhanced bronchopulmonary bacterial clearance compared to nonimmunized controls, as indicated by bacterial counts from homogenized lung tissue taken 4 hrs after challenge. Thus, mucosal immunization with OMP vaccines might hinder initial colonisation of the lungs with P.aeruginosa.

The effects of oral immunization with Pseudomonas aeruginosa (PAOI), Chlamydia trachomatis or respiratory syncytial virus (RSV) on the development of specific antibody responses in the intestine, respiratory tract and genital secretions was studied in several animal models. Oral immunization resulted in the development of specific immunity in distant mucosal sites. However, its role in influencing the outcome of reinfection challenge at the distant site varied with the antigen. Little or no protection was observed against infection with Pseudomonas aeruginosa in the respiratory tract. Limited protection was observed against respiratory tract infection with RSV. On the other hand oral immunization appeared to be quite effective in preventing respiratory or genital infection with Chlamydia trachomatis. Finally, preliminary studies have suggested that intestinal immunization via the process of breast feeding can also be employed as an effective means to induce anti-idiotypic immunity against RSV in the breas...