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Despite donor organ shortage, a large proportion of possible donor lungs are declined for transplantation. Criteria for accepting/declining lungs remain controversial because of the lack of adequate tools to aid in decision‐making. We collected, air‐inflated, and froze a large series of declined/unused donor lungs and subjected these lung specimens to CTexamination. Affected target regions were scanned by using micro‐CT. Lungs from 28 donors were collected. Two lungs were unused, six were declined for non–allograft‐related reasons (collectively denominated nonallograft declines, n = 8), and 20 were declined because of allograft‐related reasons. CTscanning demonstrated normal lung parenchyma in only four of eight nonallograft declines, while relatively normal parenchyma was found in 12 of 20 allograft‐related declines. CTand micro‐CTexaminations confirmed the reason for decline in most lungs and revealed unexpected (unknown from clinical files or physical inspection) CTabnormalities in other lungs. CT‐based measurements showed a higher mass and density in the lungs with CTalterations compared with lungs without CTabnormalities. CTcould aid in the decision‐making to accept or decline donor lungs which could lead to an increase in the quantity and quality of lung allografts. The authors show that CT scanning could aid in the decision to accept or decline donor lungs.

Despite donor organ shortage, a large proportion of possible donor lungs are declined for transplantation. Criteria for accepting/declining lungs remain controversial because of the lack of adequate tools to aid in decision-making. We collected, air-inflated, and froze a large series of declined/unused donor lungs and subjected these lung specimens to CT examination. Affected target regions were scanned by using micro-CT. Lungs from 28 donors were collected. Two lungs were unused, six were declined for non–allograft-related reasons (collectively denominated nonallograft declines, n = 8), and 20 were declined because of allograft-related reasons. CT scanning demonstrated normal lung parenchyma in only four of eight nonallograft declines, while relatively normal parenchyma was found in 12 of 20 allograft-related declines. CT and micro-CT examinations confirmed the reason for decline in most lungs and revealed unexpected (unknown from clinical files or physical inspection) CT abnormalities in other lungs. CT-based measurements showed a higher mass and density in the lungs with CT alterations compared with lungs without CT abnormalities. CT could aid in the decision-making to accept or decline donor lungs which could lead to an increase in the quantity and quality of lung allografts.

Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation. Air trapping and mosaic attenuation are typical radiological features of BOS; however, quantitative evaluation remains troublesome. We evaluated parametric response mapping (PRM, voxel‐to‐voxel comparison of inspiratory and expiratory computed tomography [CT] scans) in lung transplant recipients diagnosed with BOS(n = 20) and time‐matched stable lung transplant recipients (n = 20). Serial PRMmeasurements were performed prediagnosis, at time of BOSdiagnosis, and postdiagnosis (Tpre, T0, and Tpost, respectively), or at a postoperatively matched time in stable patients. PRMresults were correlated with pulmonary function and confirmed by microCTanalysis of end‐stage explanted lung tissue. Using PRM, we observed an increase in functional small airway disease (fSAD), from Tpreto T0(p = 0.006) and a concurrent decrease in healthy parenchyma (p = 0.02) in the BOSgroup. This change in PRMcontinued to Tpost, which was significantly different compared to the stable patients (p = 0.0002). At BOSdiagnosis, the increase in fSADwas strongly associated with a decrease in forced expiratory volume in 1 s (p = 0.011). Micro‐CTconfirmed the presence of airway obliteration in a sample of a BOSpatient identified with 67% fSADby PRM. We demonstrated the use of PRMas an adequate output to monitor BOSprogression in lung transplant recipients. The authors investigate the utility of parametric response mapping (voxel‐to‐voxel comparison of inspiratory and expiratory CT scans) in quantifying bronchiolitis obliterans syndrome diagnosis and progression.

Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation. Air trapping and mosaic attenuation are typical radiological features of BOS; however, quantitative evaluation remains troublesome. We evaluated parametric response mapping (PRM, voxel-to-voxel comparison of inspiratory and expiratory computed tomography [CT] scans) in lung transplant recipients diagnosed with BOS (n = 20) and time-matched stable lung transplant recipients (n = 20). Serial PRM measurements were performed prediagnosis, at time of BOS diagnosis, and postdiagnosis (Tpre, T0, and Tpost, respectively), or at a postoperatively matched time in stable patients. PRM results were correlated with pulmonary function and confirmed by microCT analysis of end-stage explanted lung tissue. Using PRM, we observed an increase in functional small airway disease (fSAD), from Tpreto T0(p = 0.006) and a concurrent decrease in healthy parenchyma (p = 0.02) in the BOS group. This change in PRM continued to Tpost, which was significantly different compared to the stable patients (p = 0.0002). At BOS diagnosis, the increase in fSAD was strongly associated with a decrease in forced expiratory volume in 1 s (p = 0.011). Micro-CT confirmed the presence of airway obliteration in a sample of a BOS patient identified with 67% fSAD by PRM. We demonstrated the use of PRM as an adequate output to monitor BOS progression in lung transplant recipients.

Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re‐evaluated the long‐term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention‐to‐treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD‐free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long‐term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long‐term CLAD prevalence and improves CLAD‐free survival, pulmonary function, and functional exercise capacity after LTx. This post hocanalysis of a randomized controlled trial demonstrates improved chronic lung allograft dysfunction‐free survival, pulmonary function, and exercise capacity with prophylactic azithromycin therapy after lung transplantation.

Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx.

Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1, FEF25–75, Tiffeneau index) and FeNO were assessed before and up to 12 months after initiation of azithromycin. Radiologic features, local inflammation assessed on airway biopsy (rejection score, IL-17+cells/mm2lamina propria) and broncho-alveolar lavage fluid (total and differential cell counts, chemokine and cytokine levels); as well as systemic C-reactive protein levels were compared between baseline and after 3 months of treatment. Airflow improved and FeNO decreased to baseline levels after 1 month of azithromycin and were sustained thereafter. After 3 months of treatment, radiologic abnormalities, submucosal cellular inflammation, lavage protein levels of IL-1β, IL-8/CXCL-8, IP-10/CXCL-10, RANTES/CCL5, MIP1-α/CCL3, MIP-1β/CCL4, Eotaxin, PDGF-BB, total cell count, neutrophils and eosinophils, as well as plasma C-reactive protein levels all significantly decreased compared to baseline (p < 0.05). Administration of azithromycin was associated with suppression of posttransplant lymphocytic airway inflammation and clinical improvement in lung allograft function.

This prospective, interventional, open‐label study demonstrates that treatment with azithromycin is effective in controlling posttransplant lymphocytic airway inflammation as it attenuates underlying IL‐17+T cell–mediated airway inflammation, ameliorates lung allograft function, and improves associated radiologic abnormalities. See editorial by Glanville on page 2681.

This study shows the effect of a genetic variation in the immunoglobulin G receptor on respiratory infections and survival.

Chronic rejection remains the most important complication after lung transplantation (LTx). There is mounting evidence that both rheumatoid arthritis and chronic rejection share similar inflammatory mechanisms. As genetic variants in the FCGR2Agene that encodes the immunoglobulin gamma receptor (IgGR) have been identified in rheumatoid arthritis, we investigated the relationship between a genetic variant in the IgGR gene and chronic rejection and mortality after LTx. Recipient DNA from blood or explant lung tissue of 418 LTx recipients was evaluated for the IgGR (rs12746613) polymorphism. Multivariate analysis was carried out, correcting for several co-variants. In total, 216 patients had the CC-genotype (52%), 137 had the CT-genotype (33%) and 65 had the TT-genotype (15%). Univariate analysis demonstrated higher mortality in the TT-genotype compared with both other genotypes (p < 0.0001). Multivariate analysis showed that the TT-genotype had worse survival compared with the CC-genotype (hazard ratio [HR] = 2.26, p = 0.0002) but no significance was observed in the CT-genotype (HR = 1.32, p = 0.18). No difference was seen for chronic rejection. The TT-genotype demonstrated more respiratory infections (total, p = 0.037; per patient, p = 0.0022) compared with the other genotypes. A genetic variant in the IgGR is associated with higher mortality and more respiratory infections, although not with increased prevalence of chronic rejection, after LTx.

This case report describes the evolution of pulmonary function findings (FVC, FEV1and TLC) and CT features with pirfenidone treatment for restrictive allograft syndrome following lung transplantation. Furthermore, we herein report hypermetabolic activity on 18F-FDG PET imaging in this setting, which could indicate active fibroproliferation and pleuroparenchymal remodeling. These findings may warrant further investigation.

The authors report on the use of pirfenidone to treat a patient with restrictive allograft syndrome after lung transplantation.

Background: Important characteristics determining the usefulness of a method for glomerular filtration rate (GFR) measurement are convenience, availability, and reproducibility.

The analgesic efficacy of tenoxicam, a newer injectable non-steroidal anti-inflammatory drug, for post-operative analgesia after abdominal or orthopaedic surgery in ASA Grade I/II patients is reported. Two hundred and fifty-six patients received a single dose of tenoxicam 40 mg intravenous (i.v.) at the end of surgery and this was repeated 24 h later. These patients were compared, with respect to pain or adverse events, with 258 patients that received placebo. All patients were monitored for the next 72 h. Overall, tenoxicam provided reliable analgesia with comparable pain scores at rest, moving and coughing. The cumulative rescue PCA-morphine consumption was always lower in the tenoxicam treated patients and was most marked at 4 and 24 h after the second injection of tenoxicam. This effect was more pronounced after abdominal surgery. The intravenous administration of tenoxicam was associated with a low incidence of adverse events and a high tolerability.

The analgesic efficacy of tenoxicam, a newer injectable non-steroidal anti-inflammatory drug, for post-operative analgesia after abdominal or orthopaedic surgery in ASA Grade I/II patients is reported. Two hundred and fifty-six patients received a single dose of tenoxicam 40 mg intravenous (i.v.) at the end of surgery and this was repeated 24h later. These patients were compared, with respect to pain or adverse events, with 258 patients that received placebo. All patients were monitored for the next 72 h. Overall, tenoxicam provided reliable analgesia with comparable pain scores at rest, moving and coughing. The cumulative rescue PCA-morphine consumption was always lower in the tenoxicam treated patients and was most marked at 4 and 24h after the second injection of tenoxicam. This effect was more pronounced after abdominal surgery. The intravenous administration of tenoxicam was associated with a low incidence of adverse events and a high tolerability.

Zusammenfassung: Das Ziel dieser Arbeit bestand darin, mit den heute zur Verfgung stehenden Mglichkeiten eine praktikable, effektive, sichere, kostengnstige Akutschmerztherapie auszuarbeiten. Dazu wurden verschiedene Prinzipien zugrunde gelegt: Kontinuierliche berwachung des Patienten whrend des gesamten Krankenhausaufenthalts, Einfhrung eines einfachen vier Punkte Scores zur Erfassung und Dokumentation des Schmerzes, Einfhrung eines Sedierungsscores, Anwendung der balancierten Analgesie und der „pre-emptive analgesia“, bedarfsorientierte Verabreichung von Medikamenten sowie das bertragen einer wesentlich hheren Verantwortung und Befugnis fr die Schmerztherapie auf die Pflegekrfte. Diese Prinzipien fanden ihren Niederschlag in Plnen und Algorithmen, die es den Pflegekrften und den Ansthesisten erlauben, die oben genannten Gedanken in die Tat umzusetzen. Abschlieend wird die Verbesserung der Schmerzbehandlung mit einer Studie dokumentiert.