Intrabronchial Catheter Resuscitation for Respiratory and Cardiorespiratory Arrest.

INTRODUCTION: We sought to determine whether intrabronchial oxygenation would provide adequate gas exchange during both anesthesia induced apneic and cardiopulmonary arrest and cardiac massage (CPR). METHODS: Ten pigs underwent general anesthesia with mechanical ventilation. Blood gases were measured in each animal at 4 min intervals for up to 28 min. An intrabronchial catheter (4 L/min O2) was inserted through an endotracheal tube after respirator cessation. Group A animals (6) were resuscitated with the catheter but without CPR. Group B animals (4) were rendered apneic and cardioplegic and resuscitated by CPR for 28 min using the intrabronchial device. RESULTS: All group A animals were resuscitated and survived after 24 min of apnea. Mean pO2 decreased from 378 mmHg (95% confidence interval [CI], 288-468) to 292 mmHg (95% CI, 246-339), P = 0.009; pCO2 increased from 52 mmHg (95% CI, 43-61) to 137 mmHg (95% CI, 116-158), P < 0.0001; and pH decreased from 7.32 (7.29-7.36) to 6.98 (6.92-7.03), P < 0.0001. In a control animal bronchial catheter oxygen flow ceased at baseline and pO2 decreased from 268 to 30 mmHg by 20 min. In group B animals mean pO2 decreased from 426 mmHg (95% CI, 273-579) to 130 mmHg (95% CI, 92-168) after 28 min, P < 0.0001; pCO2 increased from 49 mmHg (95% CI, 41-58) to 73 mmHg (95% CI, 61-86), P = 0.03; and pH decreased from 7.34 (7.33-7.35) to 7.07 (6.98-7.16), P < 0.0001. In the control receiving intratracheal oxygen pO2 decreased from 324 to 88 mmHg after 16 minu of CPR. CONCLUSIONS: Intrabronchial oxygenation provides sustained hyperoxemia during complete apnea and cardiac arrest with CPR.

Extracorporeal Lung Support as a Bridge to Airway Stenting and Radiotherapy for Airway-Obstructing Pancoast Tumor.

Venovenous (V-V) extracorporeal membrane oxygenation (ECMO) is used for respiratory failure that is suspected to be reversible (bridge to recovery), or as a bridge to lung transplantation. Patients with proximal airway obstruction due to endobronchial malignancy can develop acute respiratory failure, and may benefit from V-V ECMO as a bridge to airway intervention, further treatment, and eventual recovery. We describe a case of a superior sulcus tumor with tracheobronchial and superior vena cava invasion causing both respiratory failure and superior vena cava syndrome. This was treated successfully with V-V ECMO, bronchial stenting, and radiotherapy.

The use of extended criteria donors decreases one-year survival in high-risk lung recipients: A review of the United Network of Organ Sharing Database.

OBJECTIVE: The study objective was to investigate the impact of matching donor quality to recipient severity on survival after lung transplant. METHODS: By using the Organ Procurement and Transplantation Network/United Network for Organ Sharing dataset, we analyzed lung transplant recipients from May 4, 2005, to December 31, 2012. By using adjusted Cox regressions, we identified extended criteria donors as those who had 1 or more of the following: age 65 years or more, smoking history of 20 pack-years or more, diabetes mellitus, or African-American race. All other donors were considered standard donors. Recipients were categorized by lung allocation score: lung allocation score less than 70 and lung allocation score 70 or greater. Our primary outcome was 1-year survival after lung transplantation. RESULTS: Of the 10,995 lung recipients, 3792 (34%) received extended criteria donor organs. Extended criteria donors were associated with an increased hazard of death (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.26-1.56; P < .001). One-year survival was 87% and 82% (P < .001) for recipients with a lung allocation score less than 70 and 80% and 72% (P = .017) for recipients with a lung allocation score 70 or greater who received standard donor and extended criteria donor organs, respectively. In Cox regression models, the hazard of death was increased for recipients with a lung allocation score less than 70 + extended criteria donor (HR, 1.42; 95% CI, 1.27-1.60; P < .001), recipients with a lung allocation score 70 or greater + standard donor (HR, 1.37; 95% CI, 1.10-1.71; P = .005), and was the highest for recipients with a lung allocation score 70 or greater + extended criteria donor (HR, 1.81; 95% CI, 1.40-2.33; P < .001) compared with recipients with a lung allocation score less than 70 + standard donor. CONCLUSIONS: Extended criteria donors are associated with reduced 1-year survival, and recipients with a lung allocation score 70 or greater who receive extended criteria donor organs have the lowest survival.

Venous Thromboembolic Complications of Lung Transplantation: A Contemporary Single-Institution Review.

BACKGROUND: The incidence and consequences of deep venous thrombosis (DVT) and pulmonary embolism (PE) have not been described recently in lung transplant recipients. We sought to characterize DVT and PE in a contemporary series of lung transplant recipients and describe their association with clinical outcomes. METHODS: The records of all lung transplant recipients from July 1, 2008, to June 30, 2013, were reviewed and analyzed. DVT was diagnosed by venous duplex ultrasonography. PE was diagnosed by computed tomography angiography, nuclear ventilation/perfusion scanning, or pulmonary angiography. RESULTS: The study comprised 117 patients who underwent 123 transplants. The median age was 63 years (range, 17 to 77 years). Forty-five patients (39%) had evidence of lower extremity DVT, 53 (45%) had no evidence of lower extremity DVT, and 19 (16%) were not tested. Fifty-three (45%) had evidence of upper extremity DVT, 30 (26%) had no evidence of upper extremity DVT, and 34 (29%) were not tested. Eighteen (15%) had evidence of PE, 82 (70%) had no evidence of PE, and 17 (15%) were not tested. A multivariable, stepwise Cox proportional hazards model revealed that the presence of lower extremity DVT (hazard ratio, 2.43; 95% confidence interval, 1.29 to 4.64), use of cardiopulmonary bypass (hazard ratio, 2.21; 95% confidence interval, 1.04 to 4.68), and unilateral lung transplantation (hazard ratio, 2.13; 95% confidence interval, 1.07 to 4.25) were associated with diminished survival. CONCLUSIONS: The incidence of DVT and PE in lung transplant recipients is high. Posttransplant surveillance and treatment based on findings are warranted.

Reoperative lung transplantation for donor-derived pulmonary mucormycosis.

A 64-year-old male with end-stage lung disease underwent right orthotopic lung transplantation. After doing well initially, he developed acute hypoxemic respiratory failure with allograft pneumonia. Donor operative cultures demonstrated mold of the Mucor species, which were corroborated by donor endobronchial cultures obtained near the right mainstem bronchial anastomosis. The patient was treated with reoperative bilateral orthotopic lung transplantation in combination with antifungal agents. The operation was performed successfully, using lungs donated after cardiac death and treated with ex vivo lung perfusion. The patient has recovered well, remaining on room air with good allograft function, without evidence of fungal disease.

Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with no known effective therapy. It is often assumed, but has not been objectively evaluated, that pulmonary inflammation subsides as IPF progresses. The goal of this work was to assess changes in the degree of inflammatory cell infiltration, particularly lymphocytic infiltration, over the duration of illness in IPF. METHODS: Sixteen patients with confirmed IPF were identified in patients whom surgical lung biopsy (SLB) was performed in early disease, and in patients whom lung transplantation was subsequently performed in end stage disease. A numerical scoring system was used to histologically quantify the amount of fibrosis, honeycomb change, fibroblastic foci, and lymphocyte aggregates in each SLB and lung explant tissue sample. Analyses of quantitative scores were performed by comparing paired, matched samples of SLB to lung explant tissue. RESULTS: Median time [1st, 3rd quartiles] from SLB to lung transplantation was 24 [15, 29] months. Histologic fibrosis and honeycomb change were more pronounced in the explant samples compared with SLB (P < 0.001 and P < 0.01, respectively), and most notably, higher numbers of lymphocyte aggregates were observed in the explant samples compared to SLB (P = 0.013). Immunohistochemical analyses revealed abundant CD3+ (T lymphocyte) and CD20+ (B lymphocyte) cells, but not CD68+ (macrophage) cells, within the aggregates. CONCLUSION: Contrary to the frequent assumption, lymphocyte aggregates were present in greater numbers in advanced disease (explant tissue) compared to early disease (surgical lung biopsy). This finding suggests that active cellular inflammation continues in IPF even in severe end stage disease.

Ambulatory veno-venous extracorporeal membrane oxygenation: innovation and pitfalls.

OBJECTIVE: End-stage lung disease and severe acute lung injury are complex entities that remain challenges to manage. Therapies include early institution of mechanical ventilation with positive end-expiratory pressure, permissive hypercapnia, pulmonary vasodilators, and complex fluid regimens. Veno-venous extracorporeal membrane oxygenation is an available treatment option for these patients but, in its conventional form, can be associated with significant complications. We present our early experience with an attempt to optimize extracorporeal membrane oxygenation, emphasizing reduced adjunctive mechanical ventilatory support and aggressive rehabilitation, with a goal of ambulation. This strategy has been enabled by the introduction of a dual-lumen draw and return cannula placed via the internal jugular vein. METHODS: The first 10 patients (mean age of 45.3 years, 8 male) treated with this strategy between January 1, 2009, and October 1, 2009, were retrospectively reviewed. The ambulatory extracorporeal membrane oxygenation strategy was initiated with an aim of minimal mechanical ventilation and aggressive rehabilitation. The patients were intended to be weaned from all respiratory support or bridged to transplantation. RESULTS: The mean duration of extracorporeal membrane oxygenation was 20 (9-59) days, with average mean blood flows of 3.5 (1.6-4.9) L/min, and levels of CO(2) removal and O(2) transfer of 228 (54-570) mL/min and 127 (36-529) mL/min, respectively. Six of 10 patients were weaned from respiratory support (N = 4) or underwent transplantation (N = 2) and survived to discharge from the hospital. The remaining 4 patients died of sepsis (N = 3) and withdrawal of care after renal failure (N = 1). Four of the 6 surviving patients were extubated and ambulatory while still on extracorporeal membrane oxygenation. During that time, 3 of the 4 patients exercised at the bedside, with the remaining patient able to undergo full cardiopulmonary rehabilitation, including treadmill walking. CONCLUSIONS: Improvements in the durability of membrane blood oxygenators and pumps have prompted renewed consideration of extracorporeal membrane oxygenation in patients with severe lung disease. This report describes an attempt to augment extracorporeal membrane oxygenation with the goal of ambulation by minimizing mechanical ventilatory support and using aggressive in-and-out-of-bed rehabilitation.

Variable prevalence of pulmonary hypertension in patients with advanced interstitial pneumonia.

BACKGROUND: Pulmonary hypertension may occur in patients with interstitial pneumonia and is associated with increased mortality. We sought to determine the prevalence of pulmonary hypertension in sub-groups of patients with interstitial pneumonia and to investigate possible associations between pulmonary vascular hemodynamics and pulmonary function. METHODS: The presence or absence of pulmonary hypertension was assessed in 70 patients with advanced interstitial pneumonia who underwent right heart catheterization. The associations of pulmonary hypertension with clinical characteristics and pulmonary function tests were analyzed. RESULTS: The prevalence of pulmonary hypertension in patients with idiopathic interstitial pneumonia was 29% vs 64% in patients with connective tissue disease-interstitial pneumonia (p = 0.013). African American patients had a significantly higher prevalence of pulmonary hypertension in the entire study population (81% vs 22%, p < 0.001) and in the idiopathic interstitial pneumonia group (70% vs 19%, p < 0.01). Regression analyses revealed no association between mean pulmonary artery pressure (mPAP) and forced vital capacity or mPAP and diffusion capacity of the lung for carbon monoxide in the entire cohort or in sub-groups of patients. CONCLUSIONS: African American patients and patients with connective tissue disease-interstitial pneumonia had a high prevalence of pulmonary hypertension. Non-African American patients with advanced idiopathic interstitial pneumonia (including idiopathic pulmonary fibrosis) had a low prevalence of pulmonary hypertension.

Roles of T lymphocytes in pulmonary fibrosis.

Infiltration of T lymphocytes in the lungs is common in patients with and in animal models of pulmonary fibrosis. The role of these cells in regulating the accumulation of extracellular matrix, particularly collagen, is not understood completely. Research literature provides evidence for a profibrotic, an antifibrotic, or no significant role of T lymphocytes in pulmonary fibrosis. This review offers a discussion of such evidence with the focus on phenotypes of pulmonary T lymphocytes and related profibrotic and antifibrotic mechanisms. It appears unlikely that T lymphocytic infiltration per se is the central driving force in most cases of pulmonary fibrosis. Instead, evidence suggests that T lymphocytes may modulate the inflammatory and healing responses in the lungs in a profibrotic or antifibrotic manner, depending on their phenotype. Phenotypic reshaping, rather than elimination of the infiltrating pulmonary T lymphocytes, may be a promising approach to improving outcomes in patients with pulmonary fibrosis.

Evaluation of the electronic version of the questionnaire for lung transplant patients.

UNLABELLED: Context-Recent modifications to the QLTP (Questionnaire for Lung Transplant Patients), including changing items from dichotomous to multiple dimension scaling, adding psychological symptoms, and converting to an electronic format (e-QLTP), made it necessary to reevaluate its reliability, validity, recipient satisfaction, and feasibility of administering the e-QLTP in the clinical setting. Purpose-To report the final modifications, psychometric properties, recipient satisfaction, and feasibility of administering the e-QLTP, a patient report outcome measure of symptoms and activity tolerance. Methods-Sixty lung recipients completed the original QLTP and the e-QLTP and rated their satisfaction with the e-version during a routine posttransplant evaluation; 65% (38 of 60) also completed a retest version. Correlations were computed for retest stability, concurrent validity between versions of the QLTP, and construct validity among the subscales of the e-QLTP and forced expiratory volumes in 1 second. Using the After Scenario Questionnaire, participants rated their satisfaction with the ease, amount of time, and support information when completing the e-QLTP. RESULTS: The e-QLTP and subscales were internally consistent (alpha = .73 - .90) and stable (intraclass correlations = .47 - .93). Significant correlations (P = .001) were found between the e-QLTP and the original QLTP (r = 0.53-0.56) and between the e-QLTP subscales and forced expiratory volumes in 1 second (r = 0.51 - 0.53). The overall mean satisfaction score was 1.27 (+/- 0.47). Conclusions-The e-QLTP is a reliable and valid measure of physical and psychological symptoms after lung transplantation. It is feasible to complete in the clinical setting and recipients are highly satisfied with its use. Its computerized functionality enhances assessment and management of symptoms over time.

A randomized trial of inhaled cyclosporine in lung-transplant recipients.

BACKGROUND: Conventional regimens of immunosuppressive drugs often do not prevent chronic rejection after lung transplantation. Topical delivery of cyclosporine in addition to conventional systemic immunosuppression might help prevent acute and chronic rejection events. METHODS: We conducted a single-center, randomized, double-blind, placebo-controlled trial of inhaled cyclosporine initiated within six weeks after transplantation and given in addition to systemic immunosuppression. A total of 58 patients were randomly assigned to inhale either 300 mg of aerosol cyclosporine (28 patients) or aerosol placebo (30 patients) three days a week for the first two years after transplantation. The primary end point was the rate of histologic acute rejection. RESULTS: The rates of acute rejection of grade 2 or higher were similar in the cyclosporine and placebo groups: 0.44 episode (95 percent confidence interval, 0.31 to 0.62) vs. 0.46 episode (95 percent confidence interval, 0.33 to 0.64) per patient per year, respectively (P=0.87 by Poisson regression). Survival was improved with aerosolized cyclosporine, with 3 deaths among patients receiving cyclosporine and 14 deaths among patients receiving placebo (relative risk of death, 0.20; 95 percent confidence interval, 0.06 to 0.70; P=0.01). Chronic rejection-free survival also improved with cyclosporine, as determined by spirometric analysis (10 events in the cyclosporine group and 20 events in the placebo group; relative risk of chronic rejection, 0.38; 95 percent confidence interval, 0.18 to 0.82; P=0.01) and histologic analysis (6 vs. 19 events, respectively; relative risk, 0.27; 95 percent confidence interval, 0.11 to 0.67; P=0.005). The risks of nephrotoxic effects and opportunistic infection were similar for patients in the cyclosporine group and the placebo group. CONCLUSIONS: Inhaled cyclosporine did not improve the rate of acute rejection, but it did improve survival and extend periods of chronic rejection-free survival. (ClinicalTrials.gov number, NCT00268515.).

HLA-specific antibodies are risk factors for lymphocytic bronchiolitis and chronic lung allograft dysfunction.

Bronchiolitis obliterans syndrome (BOS) represents a major limitation in lung transplantation. While acute rejection is widely considered the most important risk factor for BOS, the impact of HLA-specific antibodies is less understood. Of 51 lung recipients who were prospectively tested during a 4.2 +/- 1.6-year period, 14 patients developed HLA-specific antibodies. A multi-factorial analysis was performed to correlate the prevalence of BOS with HLA antibodies, persistent-recurrent acute rejection (ACR-PR), lymphocytic bronchiolitis, and HLA-A, -B, and -DR mismatches. HLA-specific antibodies were associated with ACR-PR (10/14 vs. 11/37 with no antibodies, p < 0.05), lymphocytic bronchiolitis (8/14 vs. 10/37, p < 0.05), and BOS (10/14, vs. 9/37, p < 0.005). Other risk factors for BOS were: lymphocytic bronchiolitis (13/18 vs. 6/33 with no lymphocytic bronchiolitis, p < 0.0001), ACR-PR (12/21 vs. 7/30 with no ACR-PR, p < 0.05), and the number of HLA-DR mismatches (1.7 +/- 0.48 in BOS vs. 1.2 +/- 0.63 without BOS, p < 0.05). The presence of antibodies exhibited a cumulative effect on BOS when it was associated with either lymphocytic bronchiolitis or ACR-PR. The complex relationship between the development of HLA antibodies and acute and chronic lung allograft rejection determines the importance of post-transplant screening for HLA-specific antibodies as a prognostic element for lung allograft outcome.

Are symptom reports useful for differentiating between acute rejection and pulmonary infection after lung transplantation?

BACKGROUND: Prompt treatment of acute rejection and pulmonary infection reduces morbidity and mortality in lung transplant recipients. Symptoms, spirometry, and bronchoscopy are used to detect these complications. Of these, symptom reporting is the least invasive, yet has received little critical examination. OBJECTIVE: To examine the potential for using reports of symptoms, such as cough and shortness of breath, to recognize clinically significant acute rejection and pulmonary infection after lung transplantation. METHODS: Symptoms reported during routine follow-up visits were compared between lung transplant recipients (LTR) with clinically significant acute rejection (grade >or= A2) and those without (grade A0 or A1) and between LTR with rejection (grade >or= A2) and those with pulmonary infection. RESULTS: LTR with rejection (grade >or= A2) reported more symptoms (P < .01) than did those without (grade A0, A1); however, the magnitude of difference was minimal. LTR with clinically significant acute rejection (grade >or= A2) reported symptoms at a rate comparable with those having pulmonary infection. CONCLUSIONS: Although symptoms may alert LTR to changes in their condition, no symptoms (respiratory, general, or activities of daily living [ADL]) differentiate between grades of rejection or pulmonary infection.

HLA-specific antibodies are associated with high-grade and persistent-recurrent lung allograft acute rejection.

BACKGROUND: The impact of HLA-specific antibodies is not well established in the acute rejection of lung allografts. Acute rejection represents the most important risk factor for the development of chronic lung allograft dysfunction. METHODS: We analyzed the pattern of HLA antibodies before and after transplantation in 54 patients, and correlated our data with the presence and frequency of high-grade and persistent-recurrent acute rejection, during the first 18 post-operative months. The diagnosis of acute rejection was based on histologic International Society for Heart and Lung Transplantation (ISHLT)-published criteria. RESULTS: Ten of 54 patients had a positive enzyme-linked immunoassay (ELISA) post-transplantation. In 90% of ELISA-positive patients, the presence of HLA antibodies was associated with persistent-recurrent acute rejections, compared with 34% in the ELISA-negative group (p < 0.005). There were 28 high-grade acute rejection episodes in the ELISA-positive group, compared with 36 in the ELISA-negative group (p < 0.0001). The ELISA-positive patients required a greater intensity of immunosuppressive therapy. The patients with ELISA-detected anti-HLA antibodies were at least 3-fold more likely to develop high-grade acute rejection and persistent-recurrent acute rejection, and 7-fold more likely to develop multiple episodes of persistent-recurrent acute rejection, compared with ELISA-negative patients. CONCLUSIONS: ELISA-based screening for the development of HLA antibodies is a reliable method that can identify lung transplant recipients at increased risk for high-grade and persistent-recurrent acute rejection. Although bronchiolitis obliterans appears as a point of no return in the evolution of lung-transplanted patients, early detection of risk factors for acute rejection could indirectly decrease the incidence of bronchiolitis obliterans. These lung-transplanted patients may benefit from an altered strategy of immunosuppression.

Using conceptual triangulation to develop an integrated model of the symptom experience of acute rejection after lung transplantation.

The aim of this study was to develop a comprehensive model of the symptom experience associated with the development of acute rejection after lung transplantation by integrating the findings from a theory-testing quantitative study that explored the physiologic aspects and a theory-generating qualitative study that explored the interpretive aspects. Findings from the multimethod studies were integrated using conceptual triangulation methods described by Foster (Adv Nurs Sci. 1997;20:1-12). The integrated model will guide the development of interventions to promote effective patterns of symptom recognition and reporting of acute rejection.

Pulmonary embolism on postmortem examination: an under-recognized complication in lung-transplant recipients?

INTRODUCTION: Postmortem reports highlight the importance of factors that individually or collectively limit survival. The prevalence of pulmonary embolism (PE) at autopsy in lung-transplant recipients has not been characterized previously. OBJECTIVE: We aimed to describe the prevalence of PE, infection, and acute and chronic rejection at autopsy and their respective contributions to death in lung-transplant recipients according to survival posttransplantation. METHODS: We retrospectively reviewed 126 autopsy reports performed in lung-and heart-lung-transplant recipients between June 1990 and September 2002. RESULTS: PE was identified at autopsy in 34 (27.0%) of 126 lung- and heart-lung-transplant recipients. The prevalence of autopsy-established PE was highest, at 36.4%, in the early group (1-30 days) compared with 20.0% and 23.8% in the intermediate (31-365 days) and late (>365 days) groups, respectively. Although fungal and viral pneumonia were noted most frequently in the early and intermediate groups, bacterial pneumonia was noted in 32% to 45% of autopsies over the posttransplant period. Acute cellular rejection and bronchiolitis obliterans were present in 29.5% and 2.3%, 40.0% and 17.5%, and 35.7% and 42.9% of patients in the early, intermediate, and late groups, respectively. The most frequent cause of death was bacterial infection. CONCLUSIONS: The prevalence of PE was highest in mechanically ventilated lung-transplant recipients in the early postoperative period. Heart-lung recipients were at lower risk for PE compared with double- and single-lung recipients. PE may be an under-appreciated complication contributing to respiratory failure in the early postoperative period.

Interventional techniques in the management of airway complications following lung transplantation.

The last four decades have seen tremendous advances in the field of pulmonary transplantation. Vast improvements in the areas of surgical transplantation techniques, immunosuppressive agents, and postoperative care have all contributed to improved survival of patients. Advances in noninvasive imaging and bronchoscopy have allowed the pulmonary transplant team to intervene early in patients presenting with airway complications, often using minimally invasive procedures such as endobronchial balloon dilation or stent placement, or both. Stent technology itself has also improved and stents may sometimes be customized for treatment of short airway lesions or to optimize continued airflow through the sides of stents by creating openings using balloons or bronchoscopically directed laser. Preliminary work with brachytherapy may be decreasing the need for secondary reinterventions. The authors present an overview of some of these conventional and novel approaches to the treatment of airway complications after lung transplantation.

Pattern and predictors of early rejection after lung transplantation.

BACKGROUND: Most lung transplant recipients experience improvement in their underlying pulmonary condition but are faced with the threat of allograft rejection, the primary determinant of long-term survival. Several studies examined predictors of rejection, but few focused on the early period after transplantation. OBJECTIVES: To describe the pattern and predictors of early rejection during the first year after transplantation to guide the development of interventions to facilitate earlier detection and treatment of rejection. METHODS: Data for donor, recipient, and posttransplant variables were retrieved retrospectively for 250 recipients of single or double lung transplants. RESULTS: Most recipients (85%) had at least 1 episode of acute rejection; 33% had a single episode; 23% had recurrent rejection; 3% had persistent rejection; 13% had refractory rejection; and 14% had clinicopathological evidence of chronic rejection. Serious rejection (refractory acute rejection or chronic rejection) developed in 27% of recipients. Compared with other recipients, recipients who had serious rejection had more episodes of acute rejection (P = .004), and the first acute episodes occurred sooner after transplantation (P = .01) and were of a higher grade (P = .002). CONCLUSIONS: Recipients who experienced higher grades for their first episode of acute rejection (P = .03) and higher cumulative rejection scores (P = .004) were significantly more likely than other recipients to have serious rejection during the first year after transplantation.

Statin use is associated with improved function and survival of lung allografts.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are widely used antilipidemic agents that are also immunomodulatory. We evaluated possible effects of these agents after lung transplantation by comparing outcomes of 39 allograft recipients, who were prescribed statins for hyperlipidemia, with those of 161 contemporaneous control recipients who did not receive these drugs. Acute rejection (>or= Grade II) was less frequently found in the statin group (15.1 versus 25.6% of biopsies, p < 0.01). None of 15 recipients started on statins during postoperative Year 1 developed obliterative bronchiolitis, whereas the cumulative incidence of this complication among control subjects was 37% (p < 0.01). Total cellularity, as well as proportions of inflammatory neutrophils and lymphocytes, were significantly lower in bronchoalveolar lavages of statin recipients. Among double lung recipients, those taking statins had significantly better spirometry: FVC (80 +/- 2 versus 70 +/- 1%) and FEV1 (87 +/- 2 versus 70 +/- 1%), as percentages of predicted values, and absolute FEV1/FVC (83.4 +/- 1.2 versus 78.6 +/- 0.5) (all p < 0.01). The 6-year survival of recipients taking statins (91%) was much greater than that of control subjects (54%) (p < 0.01). These data suggest statin use may have substantial clinical benefits after pulmonary transplantation.