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Steen M Rønborg,1 Ulrik G Svendsen,2 Jesper S Micheelsen,3 Lars Ytte,4 Jakob N Andreasen,5 Lars Ehlers61The Pulmonology and Allergy Clinic of Copenhagen, Copenhagen, 2Bispebjerg Hospital, Copenhagen, 3Private ENT practice, Aalborg, 4General Practice Aalborg, 5ALK, Hørsholm, 6Aalborg University, Aalborg, DenmarkBackground: Grass pollen-induced allergic rhinoconjunctivitis constitutes a large burden for society. Up to 20% of European and United States (US) populations suffer from respiratory allergies, including grass pollen-induced allergic rhinoconjunctivitis. The majority of patients are treated with symptomatic medications; however, a large proportion remains uncontrolled despite use of such treatments. Specific immunotherapy is the only treatment documented to target the underlying cause of the disease, leading to a sustained effect after completion of treatment. The aim of this study was to compare the economic consequences of treating patients suffering from allergic rhinoconjunctivitis with either a grass allergy immunotherapy tablet (AIT) or subcutaneous immunotherapy (SCIT).Methods: A budget impact analysis was applied comparing SQ-standardized grass AIT (Grazax®; Phleum pratense, 75,000 SQ-T/2,800 BAU; ALK, Denmark) with SCIT (Alutard®; P. pratense, 100,000 SQ-U/mL; ALK, Denmark). Budget impact analysis included health care utilization measured in physical units based on systematic literature reviews, guidelines, and expert opinions, as well as valuation in unit costs based on drug tariffs, physician fees, and wage statistics. Budget impact analysis was conducted from a Danish health care perspective.Results: Treating patients suffering from allergic rhinoconjunctivitis with grass AIT instead of grass SCIT resulted in a total reduction in treatment costs of €1291 per patient during a treatment course. This cost saving implies that approximately 40% more patients could be treated with grass AIT per year without influencing the cost of treatment.Conclusion: Budget impact analysis showed that grass AIT is a cost-saving alternative to SCIT when treating patients with grass pollen-induced allergic rhinoconjunctivitis.Keywords: grass pollen, allergic rhinoconjunctivitis, allergy immunotherapy tablet, subcutaneous immunotherapy, health economics, budget impact analysis

Grazax is approved in 27 European countries for treatment of grass pollen-induced hay fever in adults with a proper diagnosis and clinically-relevant symptoms. Grazax is put under the tongue where it dissolves instantly. Treatment should be initiated at least 8-16 weeks prior to the start of the grass pollen season, and similar to traditional immunotherapy the treatment should continue for three years. The recommended dose is one tablet daily. In this review the clinical documentation is briefly discussed. The demonstrated efficacy is clinically relevant and the safety profile is acceptable. Complete documentation of long-term effects is still pending.

Study Objectives: In patients with terminal lung disease who were exercising, we assessed whether improved arterial O2 saturation with an increased fraction of inspired oxygen (FIO2) affects cerebral oxygenation., Design: Randomized, crossover., Patients and Methods: The cerebral changes in oxyhemoglobin (DeltaHbO2) and changes in deoxyhemoglobin (DeltaHb) levels were evaluated using near-infrared spectrophotometry and the middle cerebral artery (MCA) mean velocity (V(mean)) was determined by transcranial Doppler ultrasonography in 13 patients with terminal lung disease (New York Heart Association class III-IV). Patients were allocated to an FIO2 of either 0.21 or 0.35 during incremental exercise with 15 min between trials., Results: Peak exercise intensity (mean [+/- SE], 26 +/- 4 W) reduced the arterial O2 pressure (at rest, 64 +/- 3 mm Hg; during exercise, 56 +/- 3 mm Hg) and the arterial oxygen saturation (SaO2) [at rest, 92 +/- 2%; 87 +/- 2%; p < 0.05], while the arterial CO2 pressure was not significantly affected. The MCA V(mean) increased from 49 +/- 5 to 63 +/- 7 cm/s (p < 0.05) as did the DeltaHb, while the DeltaHbO2 remained unaffected by exercise. With an elevated FIO2, the SaO2 level (at rest, 95.8 +/- 0.7%; during exercise, 96.0 +/- 1.0%) and arterial O2 pressure (at rest, 102 +/- 11 mm Hg; during exercise, 100 +/- 8 mm Hg) were not significantly affected by exercise, and the levels of blood oxygenation remained higher than the values established at normoxia (p < 0.05). The MCA V(mean) increased to a level similar to that achieved during control exercise (ie, to 70 +/- 11 cm/s). In contrast to control exercise, DeltaHb decreased while DeltaHbO2 increased during exercise with 35% O2 (p < 0.05)., Conclusion: An O2-enriched atmosphere enabled patients with terminal lung disease to maintain arterial O2 saturation during exercise. An exercise-induced increase in cerebral perfusion was not affected by hyperoxia, whereby the enhanced availability of oxygenated hemoglobin increases cerebral oxygenation. The clinical implication of the study is that during physical activity patients with terminal lung disease are recommended to use an elevated FIO2 to protect cerebral oxygenation.

Objective: The lungs have dual blood supply: The bronchial and the pulmonary circulation. The importance of bronchial circulation is disputed. The purpose of this study was to establish an experimental model to examine the importance of the bronchial artery., Design: Comparative porcine experimental study. The surgical technique was evaluated in group A (n = 9). Group B (n = 8) underwent left bronchial arterial devascularization. In group C (n = 9) the left principal bronchus was devascularized, transsected, and reanastomosed. In groups B and C bronchial mucosal blood flow was studied with laser-Doppler velocimetry. Devascularization was controlled by angiography at section, and specimens were examined with conventional histology and scanning electron microscopy. The right bronchus served as control., Results: In group B devascularization caused considerable, yet insignificant reduction in bronchial mucosal blood flow index (p = 0.1282) postoperatively, and after 1 week (p = 0.0678), insignificant histologic (p > 0.2) changes, and no scanning electron microscopy differences. In group C devascularization with bronchial transsection caused significant reduction in mucosal blood flow index (p = 0.0277) postoperatively and after 1 week (p = 0.0277), significant histologic changes (p = 0.0277), and insignificant (p = 0.069) changes in scanning electron microscopy., Conclusion: Bronchial arterial devascularization with transsection caused significant physiologic and morphologic changes, and a model with bronchial devascularization should include transsection.

Background: Chimerism is suggested to predict a more favourable prognosis in solid organ transplantation., Material and Method: Forty-eight bronchoalveolar lavages from 10 patients (5 females and 5 males) who had received sex-mismatched donor lungs were monitored for varying periods of time, of up to 2 years, at regular intervals (median 3.0 (0.5-24) months). To investigate the chimerism in macrophages and lymphocytes in bronchoalveolar lavage cells a cloned 2.12 kilobase large biotinylated Y-chromosome-specific DNA-probe was used for in situ hybridization., Results: Donor macrophages disappeared in seven patients within the first 6 months after surgery (median 3.0 (1-6) months). But 15% donor macrophages could be detected in one patient 1 year and 10% in 2 patients two years after surgery. Donor lymphocytes disappeared in all patients within 3 months (median 1 (0.5-3) months). There was no correlation between periods or severity of acute rejection and percentage of donor macrophages and donor lymphocytes in bronchoalveolar lavage. None of the patients developed obliterative bronchiolitis., Conclusion: Macrophage chimerism in lung may exist for several years. Whilst our results do not elucidate the role of local macrophage chimerism, they do not currently support the view that chimerism prevents rejection.

Basiliximab and daclizumab are analogous immunosuppressive agents approved for clinical renal transplantation. Both drugs are gene manipulated chimeric human/murine monoclonal antibodies with specificity against the alpha-chain of the interleukin-2 receptor (IL-2R) on activated T lymphocytes. By combining the drugs with calcineurin inhibitor based immunosuppression, an inhibition of the interleukin-2 (IL-2) synthesis as well as the IL-2/IL-2R reception is obtained. Consequently, the allogeneic immune response is suppressed and the risk of acute rejection of the transplant is reduced. By treatment with basiliximab or daclizumab in the recommended doses, a blockade of the IL-2R is obtained for up to 12 weeks. The incidence of acute rejection episodes is reduced by approx. 33%. The incorporation of human amino acid sequences has almost eliminated the immunogenicity of the drugs and reduced their rates of elimination. The side effects of prophylactic treatment with basiliximab/daclizumab do not differ from those of placebo.

Background: Obliterative bronchiolitis (OB) is the principal long-term complication of lung and heart-lung transplantation. OB is characterized histologically by inflammation, epithelial cell loss, fibrosis, and obliteration of the terminal airways. The contribution of apoptosis and peroxynitrite formation in OB was examined and assessed whether immunohistochemical markers of these reactions in transbronchial biopsy specimens were predictive of OB development., Methods: Pulmonary tissue samples from lung transplant recipients with OB (n = 5) or without OB (control group; n = 7) were investigated by in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and nitrotyrosine immunohistochemistry. Furthermore, TUNEL and nitrotyrosine expression was compared between matched transbronchial biopsy specimens from the two patient groups., Results: Sections with active OB displayed a significantly increased number of TUNEL-positive epithelial cells and macrophages compared with very little TUNEL in control specimens. TUNEL was almost absent in inactive OB. Nitrotyrosine was detected in all samples of pulmonary tissue, but nitrotyrosine expression was more intense in patients with active OB. There was no apparent temporospatial correlation of TUNEL and nitrotyrosine expression, and in matched transbronchial specimens, these immunohistochemical markers failed to identify patients with imminent risk of developing OB., Conclusions: Apoptosis contributes to the pathophysiology of active OB but is apparently not directly paralleled by tissue peroxynitrite formation. In transbronchial biopsy specimens, markers of apoptosis and peroxynitrite formation are not valid predictors of OB and more studies are required to deliniate the role of these mechanisms in pulmonary allograft rejection.

Information about the existence and anatomy of arterial anastomoses with the porcine bronchial artery is lacking in the literature. Prior to basic physiological investigations in a porcine model related to lung transplantation with bronchial artery revascularisation, this study was designed to examine the anatomy of systemic arterial anastomoses with the bronchial artery system. Twenty pigs were studied in 3 groups. In 2 groups the heart-lung block was removed with all mediastinal structures. One group served for investigation of coronary-bronchial artery anastomoses and one for investigation of oesophageal-bronchial artery anastomoses. The systemic arteries to be examined were cannulated. The inflated heart-lung block was examined macroscopically with Evans blue, and radiographically after contrast injection. In the 3rd group intercostobronchial artery anastomoses were studied radiographically with the heart-lung block in situ. Coronary-bronchial artery anastomoses were demonstrated in 3 of the 5 pigs with an aortic 'pouch' technique, but contrast was very limited in 2 of these 3. Oesophageal arterial anastomoses with bronchial arterial branches and/or the pulmonary veins were demonstrated in 6 of the 7 pigs and more markedly than the coronary-bronchial anastomoses. Intercostobronchial artery anastomoses could not be demonstrated angiographically. It was concluded that the existence of coronary-bronchial and oesophageal-bronchial artery anastomoses in the pig appear to establish an arterial net between the base of the heart and the distal oesophagus. The resemblance to human oesophageal-bronchial artery anastomoses supports use of a porcine model for experimental studies.

Apoptosis is a form of programmed cell death, characterized by activation of endonucleases that cleave DNA into oligonucleosomal fragments, which can be identified by in situ terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL). This process has recently been implicated in cardiac and hepatic allograft rejection, and we investigated its contribution to acute pulmonary allograft rejection and cytomegalovirus (CMV) pneumonitis by in situ TUNEL of transbronchial biopsy specimens. In situ TUNEL was performed on 70 transbronchial biopsy samples collected from 25 pulmonary allograft recipients for diagnosis of acute rejection or CMV pneumonitis, and the number of apoptotic nuclei/mm2 was correlated with the rejection grade (International Society of Heart and Lung Transplantation classification). During acute pulmonary allograft rejection, apoptotic nuclei were demonstrated in pulmonary parenchymal cells and mononuclear infiltrating cells, and the number of apoptotic cells was positively correlated with the rejection grade. In addition, a marked increase in the density of apoptotic cells was found in pulmonary allografts with CMV pneumonitis. We conclude that apoptosis contributes to cell death during acute pulmonary allograft rejection and CMV infection.

Lung volume reduction surgery is a new surgical procedure for treatment of patients with pulmonary emphysema. At the operation the most peripheral parts of the lung are resected. Only 15-20% of the patients admitted for lung volume reduction surgery are suitable for operation. The preliminary results have demonstrated improvement in lung function in the majority of the patients. Most of the reports comprise small numbers of patients and have a short time of observation. The longest reported period of observation for a larger number of patients is 24 months and shows a continuing improvement in lung function, dyspnoea and six minute walk test. Because of the high incidence of emphysema, lung volume reduction is a procedure that could reach large extension in the future. However, better definition of criteria of inclusion and better evaluation of the operative procedures are needed.

Primary pulmonary hypertension (PPH) is defined as continuing increase of the blood pressure in the pulmonary arteries without any known reason. The expected incidence in Western Europe is one to two per one million inhabitants, which in Denmark is around five to ten new cases each year. The diagnosis PPH is established by excluding other known reasons for secondary pulmonary hypertension. Primary pulmonary hypertension is a progressive and incurable disease. The treatment of PPH is with vasodilatory agents and anti-coagulants with supplementary diuretics, digoxin and oxygen as second-line of treatment. The most important vasodilators are calcium-antagonist and Epoprostenol (prostacyclin PGI2). Lung transplantation or combined heart and lung transplantation is at the moment the only possible treatment for progressive PPH disease in Denmark. The one year survival after lung- or heart and lung transplantation for PPH are not as good as the survival among other patients who are heart and lung transplanted.

The pig is often used in experimental studies on the significance of bronchial artery circulation, but the anatomy of this artery is only poorly described. The purpose of this study was to improve the anatomical basis for experimental studies on the porcine bronchial artery circulation. The origin of the artery from the aorta is described in 32 pigs. Heart-lung blocks were perfused with saline and removed in 16 pigs, and the broncho-oesophageal orifice was identified and cannulated. In these 16 specimens the intrapulmonary ramification was studied by angiography, and the extrapulmonary distribution and supply area by injection of Evans Blue. The broncho-oesophageal artery originated from the aorta as a single trunk in 91%. Angiography showed that each principal bronchus was accompanied by 2 bronchial artery branches far into the lung parenchyma. The central branching pattern of the artery between the aorta and the principal bronchi was divided into 3 subtypes. Evans Blue showed communication with the whole mediastinum. The anatomical relations are described. It is concluded that the broncho-oesophageal artery divides to follow each bronchus with 2 bronchial branches. A nomenclature for these branches is suggested. The pig anatomy is suited for experimental investigations on the bronchial circulation.

There is a need to develop noninvasive methods for the diagnosis of Pneumocystis carinii pneumonia in patients unable to undergo bronchoscopy or induction sputum. Oral wash specimens are easily obtained, and P. carinii nucleic acid can be amplified and demonstrated by PCR. In routine clinical use, easy sample processing and single-round PCR are needed to ensure rapid analysis and to reduce the risk of contamination. We developed a single-round Touchdown PCR (TD-PCR) protocol with the ability to detect PCR inhibition in the specimen. The TD-PCR was evaluated in a routine diagnostic laboratory and was compared to a previously described PCR protocol (mitochondrial RNA) run in a research laboratory. Both PCR methods amplified a sequence of the mitochondrial rRNA gene of P. carinii. Paired bronchoalveolar lavage (BAL) and oral wash specimens from 76 consecutive human immunodeficiency virus type 1-infected persons undergoing a diagnostic bronchoscopy were included. The TD-PCR procedure was quicker than the mitochondrial PCR procedure (<24 versus 48 h) and, compared to microscopy, had sensitivity, specificity, and positive and negative predictive values of 89, 94, 93, and 91%, respectively, for oral wash specimens and 100, 91, 90, and 100%, respectively, for BAL specimens. Our results suggest that oral wash specimens are a potential noninvasive method to obtain a diagnostic specimen during P. carinii pneumonia infection and that it can be applied in a routine diagnostic laboratory.

In recent years, there has been increased interest in developing propellant-free inhalers for the treatment of patients with chronic obstructive airways disease. Various powder inhalators have been developed. A recent alternative to the dose-metered aerosols has been produced using the piezoelectric effect. This double-blind, double-dummy, randomized, dual-dose, four-period crossover study was designed to compare the effect of albuterol inhaled from the piezoelectric device (PED) and albuterol inhaled from the metered dose inhaler (MDI). The primary efficacy variables were forced expiratory volume in one second (FEV1) and area under the curve (AUC). Although we found a statistically significant device effect for the primary efficacy variables, the two treatments (PED [test] and MDI [reference]) are comparable. The only variable for which comparability was not found was time of onset. We found no dose differences. In conclusion, we found a similar effect of albuterol inhaled by a PED versus an MDI in patients with chronic obstructive airways disease.

Background: Measurements of postoperative spirometric values after pneumonectomy and lobectomy vary considerably, and few researchers have studied the changes in exercise capacity during maximal work after lung resection. The purpose of this study was to describe the postoperative alterations in cardiopulmonary function., Methods: Ninety-seven consecutive patients with lung malignancy were prospectively examined with maximal exercise test, spirometry, and arterial gas tensions. Fifty-seven patients were reinvestigated 6 months postoperatively., Results: In patients having lobectomy, forced expiratory volume in 1 second decreased 8%, and exercise capacity, expressed by maximal oxygen uptake and maximal work rate, significantly decreased 13%. In patients having pneumonectomy forced expiratory volume in 1 second significantly decreased 23%, but the loss in lung volume was partly compensated as measured by exercise capacity, which decreased only 16%. Generally patients with the smallest preoperative forced vital capacity had the smallest postoperative deterioration expressed in percentages. We found a weak correlation between alterations in maximal oxygen uptake and lung function after resection., Conclusions: Lobectomy is associated with only minor deterioration of lung function and exercise capacity. Pneumonectomy causes a decrease in pulmonary volumes to about 75% of the preoperative values, partly compensated in better oxygen uptake, which postoperatively was about 85% of the preoperative values. Alteration in forced expiratory volume in 1 second is a poor predictor of change in exercise capacity after pulmonary resection.

Objective: Our purpose was to study the 2-year patency of direct bronchial artery revascularization in lung transplantation. We wanted to clarify whether the revascularized bronchial artery system is functional after 2 years, whether bronchial artery vascularity changes with time, and whether posttransplantation bronchial artery disease is arteriographically evident after 2 years., Methods: Bronchial artery revascularization is performed by anastomosing the internal thoracic artery to as many bronchial artery orifices in the donor descending aorta as possible. Twenty-three patients surviving 2 years or more have had internal thoracic artery-bronchial arteriography performed 1 month and 2 years after transplantation. One-month and 2-year arteriograms have been compared., Results: Two-year patency of the internal thoracic artery conduit was 100%. The appearance of the bronchial arteries was unchanged after 2 years in 11 patients. A unilateral or bilateral increase in vascularity was found in two and seven patients, respectively. In three patients new vessels, not visible on the first arteriogram, had appeared. In four patients one or more small vessels visible on the first arteriogram had disappeared on the second arteriogram. We have found no arteriographic signs of bronchial artery disease, such as stenosis of the bronchial arteries, and no arteriographic evidence of arteriosclerotic disease in the internal thoracic artery., Conclusion: The internal thoracic artery is an excellent conduit for bronchial artery revascularization, with a 2-year patency of 100% in 23 patients. Only minor changes in the bronchial arteriograms have been found.

Thirty-one adult patients with asthma caused by house-dust mites (HDM) were included in this placebo-controlled, double-blind study to evaluate the efficacy and safety of specific immunotherapy (SIT) with biologically standardized extracts of HDM. The specific diagnosis was confirmed by skin prick tests, specific IgE, and bronchial provocation tests with HDM allergens. The patients were randomized to receive active treatment with extracts of either Dermatophagoides pteronyssinus (Dpt) or D. farinae (Dfa) (Alutard SQ, ALK, Denmark) or placebo injections. Twenty-three patients completed the study. After 1 year of treatment, we found a clinically important and significant reduction in both asthma medicine consumption (inhaled steroids 38% and beta 2-agonists 46%) and symptom score (57%) in the actively treated group, but not the placebo group. These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group. Additionally, there was a significant difference in the patients' scores for effect in favor of the actively treated group. Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group. Spirometric lung-function measurements showed a significant increase in forced expiratory volume in 1 s (FEV1) from 85% before to 89% of predicted values after treatment for the actively treated group. Peak-flow measurements at home showed no significant changes during the study. It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM.

En-bloc double lung transplantation with tracheal anastomosis and direct revascularization of the bronchial arteries to the left internal mammary artery has been carried out in Denmark since June 1992. Forty-seven patients (32 with alfa-1 antitrypsin deficiency, 11 with chronic obstructive pulmonary disease, two with cystic fibrosis and two with primary pulmonary hypertension), 25 men and 22 women, average age 39 years (17-64 years), have received their first double-lung transplant with bronchial artery revascularization. Arteriography of the internal mammary artery and bronchial arteries was performed in 42 (89%) of the patients from 1-150 days after the operation. Successful bronchial artery revascularization was demonstrated arteriographically in 40 patients, in two patients the arteriography failed to show bronchial artery revascularization. Arteriography was not performed in five patients due to early complications and death. Bronchoscopy showed rapid, uncomplicated airway healing in 42 patients. Mucosal necrosis under the tracheal anastomosis was found in three patients, and severe obstructive endobronchial growth of the fungus Aspergillus fumigatus was diagnosed in the last two patients. The one- and two-year survival is 83% (Kaplan-Meier). Eleven patients are dead, five due to pulmonary causes and six due to extra-pulmonary causes. Pulmonary function became normal in nearly all surviving patients between three to six months after the transplantation. In conclusion, en-bloc double-lung transplantation with bronchial artery vascularization has shown good short-term results, and the one- and two-year survival gives hope that a successful bronchial artery revascularization will improve the long-term survival following lung transplantation.

Both ventilation and perfusion scintigraphy are accurate predictors of post-operative ventilatory function. Previous attempts to predict post-operative exercise capacity after lung resection using radioisotope scintigraphy are few and results are conflicting. We studied 32 patients before and 6 months after pulmonary resection for bronchogenic carcinoma to assess the value of lung perfusion scintigraphy for the prediction of post-operative forced lung volumes and parameters on maximum exercise, including maximum ventilation and maximum oxygen uptake. Nine patients were lost to follow-up, and these patients differed from the reinvestigated patients only in the staging of the pulmonary carcinoma and not in preoperative lung function or exercise capacity. We found a clear relationship between the values predicted from a preoperative perfusion scintigraphy, spirometry and a maximum exercise study and the observed values measured 6 months post-operatively. The method underestimated the post-operative values of both spirometric and exercise measurements, especially in the higher range. Only in a few cases were the post-operative observed values less than the predicted values, and in these cases the difference was without clinical significance. Unexpected post-operative respiratory insufficiency was not observed. In conclusion, in patients in whom a pulmonary resection was performed, not only the post-operative spirometric values, but also the more functional related maximum exercise data can be predicted through the knowledge of a preoperative perfusion scintigraphy.

Background: Lung transplantation including direct bronchial artery revascularization (BAR) has produced promising early results in small clinical series., Methods: In Copenhagen primary en bloc double lung transplantation with BAR, with the left mammary artery used as conduit, has been performed in 47 patients from 1992 to the end of 1995. After introduction of the bloc into the recipient, the mammary-to-bronchial artery anastomosis is performed as the first anastomosis, allowing perfect exposure and early reperfusion. Internal mammary-bronchial artery arteriography has been performed routinely after operation., Results: Bronchoscopic examination performed in all patients documented normal airway healing in 42, disturbed in two, and complicated in three. Arteriography performed in 42 patients demonstrated complete BAR in 25, incomplete in 15, and failed BAR in 2. Failed BAR was associated with complicated airway healing. The 1- and 2-year survival rate (Kaplan-Meyer) is 83%. Eleven patients have died, only one within 30 days. The total incidence of bronchiolitis obliterans syndrome at 3 years (with Kaplan-Meier technique) is 33%. Successful BAR has also been performed with an adjusted technique in a limited number of heart-lung and single lung transplantations. Our total experience of BAR in any type of lung transplantation includes 65 patients with an arteriographic BAR success rate of 94% (50 of 53 examined patients)., Conclusions: Experience has improved the surgical technique and has made BAR reliable and safe, be it double lung, single lung, or heart-lung transplantation. Early results are good, but only follow-up will show if long-term results after lung transplantation will be improved by BAR. Already today, en bloc double lung transplantation with BAR is a viable alternative to sequential bilateral lung transplantation.

Background: On the basis of our experience with bronchial artery revascularization (BAR) in lung transplantation since its introduction in Copenhagen in 1992, a description of the surgical anatomy of the bronchial arteries and the results of attempted BAR in these patients will be presented., Methods: Since June 1992, BAR was performed in 50 en bloc double lung, six single lung, and nine heart-lung transplantations. The location, number, type, and size of each bronchial artery identified and revascularized were recorded. Our choice of conduit for BAR was the internal mammary artery. Routine internal mammary-bronchial arteriography was performed early after the transplantation to evaluate the result of BAR. All arteriograms were carefully studied together with the surgical records. The arteriographic results after attempted BAR were classified as complete, incomplete (bilateral, hemilateral, or poor), or failed. The surgical and arteriographic anatomy of the bronchial arteries has been described, and nomenclature for the as yet unnamed bronchial arteries has been developed., Results: During surgery 128 bronchial arteries were identified in the descending aorta of the 64 donor lung blocs. Internal mammary-bronchial arteriography was performed in 53 patients. BAR was complete in 32, incomplete in 18, and failed in 3. The number of bronchial arteries identified and revascularized in each case increased with experience. The central and intrapulmonary bronchial artery anatomy was described, and different patterns have been identified., Conclusions: Bronchial artery identification is reliable, but a learning process is involved. BAR is possible with a high success rate. Complete BAR is an obtainable goal in most cases.

Development of the surgical technique has minimized the incidence of airway problems associated with single as well as sequential bilateral lung transplantation. Although early results are good, long-term results remain unsatisfactory. The main problems after lung transplantation are pulmonary infections and the bronchiolitis obliterans syndrome. The bronchiolitis obliterans syndrome is usually considered to be chronic rejection, but a multifactorial genesis including airway ischemia has been suggested. We reviewed the literature relevant to direct bronchial artery revascularization during lung transplantation. Although information is limited, there are good reasons to believe that reestablishment of the dual blood supply to the transplanted lung is beneficial not only for healing of the airway anastomoses, but also for the airway and the lung responses to pathologic conditions. In small series, methods of bronchial artery revascularization have proved successful and have been associated with good early results. We believe it is justified to test the impact of direct bronchial artery revascularization on outcome after lung transplantation in large clinical series.

This paper describes the identification of important allergens from the granary weevil (Sitophilus granarius) (Sg). Sera from Danish bakers whose skin prick tests were positive to extracts of Sg were screened for IgE against Sg extracts. We found that 54% (n = 66) had elevated levels of IgE (RAST classes 1-3, by luminescent immunoassay) against whole-body extracts of Sg. The specificity of patient IgE was investigated in an inhibition-dot immunoblotting assay. IgE binding was inhibited in all sera but two, thus indicating that the patients' IgE was indeed specific for the Sg extract. In crossed immunoelectrophoresis, 23 different proteins were identified. All RAST-positive sera were investigated in crossed radioimmuno-electrophoresis. At least 11 proteins in the Sg extract were capable of binding IgE. All individual sera reacted with at least four different proteins. The two most prominent allergens bound IgE from 88% and 100%, respectively, of the patients. These two are considered to be the most important allergens from Sg, and will be useful as markers in environmental immunochemical assays to detect allergens in samples from bakeries, grain stores, etc.

This study investigated the specificity and efficacy of immunotherapy with Artemisia vulgaris (Artemisia) extract. We studied 25 patients with a more than two year lasting history of seasonal rhinoconjunctivitis and who had only two clinically important allergies, either to Artemisia and Betula verrucosa (Betula) or to Artemisia and Phleum pratense (Phleum). Patient selection was randomized and evaluation of results was conducted in double blind fashion. Twenty patients completed two years of specific immunotherapy. Nine patients were treated with extracts of Artemisia and 11 with extracts of either Betula (n = 3) or Phleum (n = 8). Treatment with Artemisia was followed by a significant decrease in skin sensitivity (p < 0.05) and eye sensitivity (p < 0.01) to Artemisia but not to Betula/phleum. No significant decrease was observed in medicine consumption or symptom scores. Patients treated with Betula or Phleum experienced a significant decrease in skin sensitivity to Betula or Phleum (p < 0.001), and eye sensitivity to Betula or Phleum (p < 0.05), but not to Artemisia and had significant decreases in medicine and symptom scores (p < 0.05) in Betula/phleum seasons but not in the Artemisia season. The treatment was both effective and specific with the one unexplained exception that both patient groups (Artemisia and Betula/Phleum) decreased their skin sensitivity to Artemisia.

The lower lobe of the left lung was transplanted from a mother to her child, who previously had received a bone marrow transplant from the mother because of an immune defect. After the bone marrow transplant the child had developed progressive pulmonary fibrosis (obliterative bronchiolitis). The surgical procedure and the early postoperative period has been uncomplicated. Immunosuppression with corticosteroids was only given for a short period, after which no immunosuppressive treatment has been given. The operation and results for both donor and recipient are described. The early results are promising, but rehabilitation is progressing slowly.