RationaleArikace is a liposomal amikacin preparation for aerosol delivery with potent Pseudomonas aeruginosa killing and prolonged lung deposition.ObjectivesTo examine the safety and efficacy of 28days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with P aeruginosa.Methods105 subjects were evaluated in double-blind, placebo-controlled studies. Subjects were randomised to once-daily Arikace (70, 140, 280 and 560mg; n=7, 5, 21 and 36 subjects) or placebo (n=36) for 28days. Primary outcomes included safety and tolerability. Secondary outcomes included lung function (forced expiratory volume at one second (FEV1)), P aeruginosa density in sputum, and the Cystic Fibrosis Quality of Life QuestionnaireRevised (CFQ-R).ResultsThe adverse event profile was similar among Arikace and placebo subjects. The relative change in FEV1 was higher in the 560mg dose group at day 28 (p=0.033) and at day 56 (28days post-treatment, 0.093L +/- 0.203 vs -0.032L +/- 0.119; p=0.003) versus placebo. Sputum P aeruginosa density decreased >1 log in the 560mg group versus placebo (days 14, 28 and 35; p=0.021). The Respiratory Domain of the CFQ-R increased by the Minimal Clinically Important Difference (MCID) in 67% of Arikace subjects (560mg) versus 36% of placebo (p=0.006), and correlated with FEV1 improvements at days 14, 28 and 42 (p<0.05). An open-label extension (560mg Arikace) for 28days followed by 56days off over six cycles confirmed durable improvements in lung function and sputum P aeruginosa density (n=49).ConclusionsOnce-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection.

Background Chronic rhinosinusitis has a major impact on the quality of life of patients with cystic fibrosis (CF) and may contribute to progression of chronic lung disease. Despite multiple sinus surgeries, maxillary sinus involvement is a recurrent problem. The modified endoscopic medial maxillectomy (MEMM) permits debridement in the clinic, improves mucus clearance with nasal irrigations, and increases access for topical delivery of therapeutics. However, clinical outcomes of aggressive sinus surgery with regimented postoperative medical treatment have not been systematically evaluated. Methods CF patients completed the 22-Item Sinonasal Outcome Test questionnaires before sinus surgery (and bilateral MEMM) and at sequential postoperative visits. Objective measures included Lund-Kennedy endoscopic score and pulmonary function tests (forced expiratory volume at 1 second percent [FEV1%] predicted). Culture-directed antibiotic therapy, prednisone, and topical irrigations were initiated postoperatively. Results Twenty-two patients (mean age, 26.5 years; 4.9 prior sinus operations) underwent MEMM and sinus surgery. Symptom scores were significantly reduced at 60 days (primary outcome, 64.7 ± 18.4 presurgery versus 27.5 ± 15.3 postsurgery; p < 0.0001) and up to a year postoperatively (27.6 ± 12.6; p < 0.0001). Endoscopic scores were also reduced after surgery (10.4 ± 1.1 presurgery versus 5.7 ± 2.4 [30 days], 5.7 ± 1.4 [60 days], 5.8 ± 1.3 [120 days], and 6.0 ± 1.1 [1 year]; p < 0.0001)]. There were no differences in FEV1% predicted up to 1 year postoperatively, but hospital admissions secondary to pulmonary exacerbations significantly decreased (2.0 ± 1.4 versus 3.2 ± 2.4, respectively; p < 0.05). Conclusion Prospective evaluation indicates sinus surgery with MEMM is associated with marked improvement in sinus disease outcomes. Additional studies are necessary to confirm whether this treatment paradigm is associated with improved CF pulmonary disease.

SESSION TYPE: Critical Care Student/Resident Case Report Posters II

Lung transplantation is a therapeutic modality frequently used in end-stage lung disease. Unfortunately, lung transplant recipients have poor clinical outcomes, often due to the development of bronchiolitis obliterans syndrome (BOS). This process is often characterized by the pathologic findings of obliterative bronchiolitis: neutrophil influx and extracellular matrix remodeling leading to luminal obstruction and airway inflammation. The molecular mechanisms underlying BOS are poorly understood and disease-specific biomarkers are lacking. We report that in addition to increased levels of IL-8, the level of the neutrophil chemoattractant proline-glycine-proline (PGP) is elevated in BOS patient bronchoalveolar lavage (BAL) fluid. The enzymes responsible for generating PGP, matrix metalloproteases 8 and -9 and prolyl endopeptidase, are also elevated in these samples. Together, IL-8 and PGP account for most of the neutrophil chemoattractant capacity seen in BOS BAL fluid. Using specific neutralizing Abs to both IL-8 and PGP, we demonstrate that PGP is a prominent neutrophil chemoattractant found in BAL fluid from individuals at the time of diagnosis of BOS. These findings highlight the influence of a matrix-derived neutrophil chemoattractant in posttransplantation BOS and provide opportunities for the development of unique diagnostics and therapeutics to potentially improve disease outcomes.

To the Editor: Studies1Ratjen F Döring G Cystic fibrosis.Lancet. 2003; 361: 681-689Abstract Full Text Full Text PDF PubMed Scopus (913) Google Scholar, 2Elborn S The management of young adults with cystic fibrosis: ‘genes, jeans and genies.’.Disabil Rehabil. 1998; 20: 217-225Crossref PubMed Scopus (12) Google Scholar have shown that cystic fibrosis (CF) patients have limited knowledge of the genetics of CF. Previously, there was limited need to communicate this information: few CF patients lived to adulthood, and most who did could not reproduce.1Ratjen F Döring G Cystic fibrosis.Lancet. 2003; 361: 681-689Abstract Full Text Full Text PDF PubMed Scopus (913) Google Scholar, 2Elborn S The management of young adults with cystic fibrosis: ‘genes, jeans and genies.’.Disabil Rehabil. 1998; 20: 217-225Crossref PubMed Scopus (12) Google Scholar Genetic counseling focused on the patient's parents, who were counseled about the recurrence risk at the time of the diagnosis. Today, CF is a disease of adulthood.3Patient registry 2004 annual report. Cystic Fibrosis Foundation, Bethesda, MD2005Google Scholar In 2002, > 40% of CF patients in the United States were >18 years old; by 2010, it will be >50%. Together with advances in assisted reproductive technology, reproduction and recurrence risk are now important issues for adolescent and young adult CF patients.3Patient registry 2004 annual report. Cystic Fibrosis Foundation, Bethesda, MD2005Google Scholar, 4Lyon A Bilton D Fertility issues in cystic fibrosis.Paediatr Respir Rev. 2002; 3: 236-240Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 5McCallum TJ Milunsky JM Cunningham DL et al.Fertility in men with cystic fibrosis: an update on current surgical practices and outcomes.Chest. 2000; 118: 1059-1062Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar, 6Sawyer SM Tully MM Dovey ME et al.Reproductive health in males with cystic fibrosis: knowledge, attitudes, and experiences of patients and parents.Pediatr Pulmonol. 1998; 25: 226-230Crossref PubMed Scopus (47) Google Scholar A 19-item questionnaire was developed from the results of prior semistructured interviews with 18 CF patients aged 16 to 25 years. Knowledge-based questions (medical issues, inheritance, and reproductive options/risks) as well as communication patterns (preferred resources for learning about CF and preferred people with whom to talk about reproductive issues) were addressed. Recruited from the University of Alabama CF clinic population, 51 patients aged 15 to 29 years (mean, 21 years), 24 male (47%) and 27 female (53%), completed the questionnaire. The study was approved by the University of Alabama Institutional Review Board. Regarding autosomal recessive inheritance, only 33% knew that two carriers have a 25% chance of having a child with CF, and 25% knew that two carriers have a 50% chance of having a child who is a carrier. However, 82% knew that two carriers could have a child who did not have CF, and 52% knew that two carriers could have a child who did not carry CF. On their own reproductive risks, 59% knew that a CF patient had a 0% chance of having a child with CF if their partner was not a carrier, but only 26% knew that all their children would be carriers even if their partner was not a carrier. In the scenario of a CF patient with a CF carrier partner, 44% knew that a child had a 50% chance of having CF, and 24% knew that a child had a 50% chance of being a CF carrier. Most patients knew about their reproductive potential, as 96% responded that CF patients are able to have children. However, when asked about whether the chance for having children was different for male and female patients with CF, 65% answered that it was more difficult for men, 8% that it was more difficult for women, and 27% answered “not sure.” While 62% reported that they knew that there were options for male CF patients who wanted to have children, only 26% knew of assisted reproductive technology. Despite widespread availability, the lack of knowledge of adolescents and young adults with CF about the genetics of their disease continues. Furthermore, these patients are unaware of both modern technologies that could enable them to have biological children and the risk of those children having CF. This study illustrates the changing needs of patient education as medical knowledge progresses. CF patients would benefit from further genetic knowledge and counseling to enable them to make informed decisions about reproduction as they mature into adulthood.

BACKGROUND End-stage sarcoidosis is characterized by severe pulmonary fibrosis and is often poorly responsive to medical therapy. Lung transplantation, therefore, may be the only treatment option. Currently, there are few studies evaluating long-term outcomes following transplantation for these patients. Our aim was to evaluate post-transplant morbidity and survival of patients with sarcoid compared to recipients transplanted for idiopathic pulmonary fibrosis (IPF). METHODS We retrospectively examined 300 lung transplant recipients using a dedicated database. Over a 10-year period, 15 (5.0%) patients with sarcoidosis and 48 (16%) patients with IPF were identified. Primary outcome measures included rate and time to onset of bronchiolitis obliterans syndrome (BOS) and survival. RESULTS Recipients in the sarcoid group were younger and predominantly female compared to recipients in the IPF group. Five of 15 (33%) sarcoid patients developed BOS versus 15 of 48 (31%) IPF patients (p=1.0). There was no significant difference in the time to BOS onset. Median survival was 1,365 days for the sarcoid group and 1,593 days for the IPF group (Hazard Ratio 0.94 by Kaplan-Meier analysis; [95% CI] 0.33-2.67; p = 0.90). CONCLUSIONS We observe similar long term outcomes following lung transplantation for sarcoid and IPF recipients. Transplantation remains a treatment option for end-stage sarcoidosis, as BOS and survival rates are comparable to IPF.

PURPOSE: Bronchiolitis obliterans syndrome (BOS) is an important cause of mortality following lung transplantation. At our institution, standard treatment of BOS includes photopheresis therapy (P) and modification of immunosuppression (IS). Recent studies suggest that macrolide antibiotics may improve lung function in patients with BOS, likely by immunomodulatory effects. We hypothesized that the addition of Azithromycin (A) to our standard BOS regimen may improve lung function and post-transplant survival, compared to the standard regimen alone.

PURPOSE: Lung transplantation is a treatment option for patients with end-stage COPD; though, a survival benefit has not been proven. This may be in part due to difficulties with the selection of appropriate recipients as traditional markers of disease severity do not reliably predict survival. The IC/TLC ratio is a newly described measure of hyperinflation that performs well as a predictor of COPD survival. The aim of this study is to compare survival following lung transplantation to the predicted survival of COPD patients using the IC/TLC ratio.

To test whether MHC alleles associated with common variable immune deficiency (CVID) might also be over-represented in patients with normal serum immunoglobulin levels who suffer with recurrent sinopulmonary infections (RESPI), we identified 62 consecutive RESPI patients and compared their HLA-B and HLA-DR antigen frequencies to those of 60 consecutive patients with CVID, 1627 Alabama Caucasian bone marrow donors, and 997,230 published US Caucasians. Either HLA-B44, -B8, -DR3(17), or -DR7 was present in 74% of the RESPI and 85% of the CVID patients. HLA-B44 prevalence in particular proved identical between RESPI and CVID. When compared to US Caucasians, the increased prevalence of the four HLA alleles proved significant at P < 0.0001, P < 0.0001, P = 0.0005, and P = 0.02, respectively. When compared to Alabama Caucasians, only the increased prevalence of HLA-B44 achieved statistical significance (P = 0.0001). Inheritance of HLA-B44 may yield susceptibility to recurrent sinopulmonary infection even in the presence of normal serum immunoglobulin levels.

PURPOSE: COPD is the most common indication for lung transplantation. Appropriate timing of transplantation is challenging in this population, however, as patients may have a protracted clinical course despite high degrees of obstruction. The BODE Index is a simple grading system that has been validated as a predictor of the risk of death in patients with COPD. The aim of this study is to compare survival with lung transplantation to BODE-predicted survival without transplantation for patients with COPD.

The traditional incision for bilateral sequential lung transplantation is the bilateral anterolateral transsternal thoracotomy with approximation of the sternal fragments with interrupted stainless steel wire loops; this technique may be associated with an unacceptable incidence of postoperative sternal disruption causing chronic pain and deformity. Approximation of the sternal ends was achieved with peristernal cables that passed behind the sternum two intercostal spaces above and below the sternal division, which were then passed through metal sleeves in front of the sternum, the cables tensioned, and the sleeves then crimped. Forty-seven patients underwent sternal closure with this method, and satisfactory bone union occurred in all patients. Six patients underwent removal of the peristernal cables: 1 for infection (with satisfactory bone union after the removal of the cables), 3 for cosmetic reasons, 1 during the performance of a median sternotomy for an aortic valve replacement, and 1 in a patient who requested removal before commencing participation in football. This technique of peristernal cable approximation of sternal ends has successfully eliminated the problem of sternal disruption associated with this incision and is a useful alternative for preventing this complication after bilateral lung transplantation.

Background: The intensive care unit oxygen challenge is a routine screening test for donor lung function. An arterial Po-2 of < 300 mm Hg is generally considered evidence of inadequate pulmonary function that contraindicates the use of the lungs for transplantation.Methods: Between December 1, 2001 and January 24, N04, the intensive care unit oxygen challenge was compared with the Po-2 in samples drawn from each pulmonary vein confluence in the operating room in 91 donors (182 donor lungs) after the lungs were fully inflated (F-IO2 1.0). There were 62 males and 29 females, with a median age of 27.5 years (13.6 to 55.4 years).Results: In 40 lungs, the pulmonary vein P-O2 was > 300 mm Hg, whereas the PO2 was < 300 mm Hg on the last intensive care Unit 02 challenge. The difference between the intensive care unit Po-2 and the operating room pulmonary vein Po-2 was greatest for donors with the lowest intensive care unit Po-2. Of these 40 lungs, 8 were transplanted, all of whom had excellent graft function with a median intubation of 14.2 hours (6.1 to 23.8 hours). No patient sustained primary graft failure or an airway complication.Conclusions: The intensive care unit Po-2 is an unreliable screening test for donor lung function, particularly when one lung is clear and the other is unclear radiographically. In this setting, intraoperative surgical assessment and pulmonary venous Po-2 should be the basis for determining donor lung suitability. This strategy may provide an opportunity to increase donor lung availability. J Heart Lung Transplant 2005;24:1902-5. Copyright (c) 2005 by the International Society for Heart and Lung Transplantation.

PURPOSE: End-stage sarcoidosis is characterized by severe pulmonary fibrosis and often poorly responsive to medical therapy. Lung transplantation, therefore, may be the only treatment option. Currently, there are few studies evaluating long-term outcomes following transplantation for these patients. The aim of this investigation is to evaluate the post-transplant morbidity and mortality of patients with sarcoid, compared to recipients transplanted for idiopathic pulmonary fibrosis (IPF).

Bronchiolitis obliterans syndrome (BOS) is a major factor limiting long term survival after lung transplantation. A variety of pharmacologic immunosuppression modalities have been used without clear benefit. Photopheresis (photo) is associated with airflow stabilization in individual cases, but objective evidence for efficacy is lacking. This study examines the efficacy of photo in preventing loss of airflow to a higher grade of BOS or BOS death.