0
Recent Advances in Chest Medicine |

Pulmonary Complications of Lung Transplantation FREE TO VIEW

Shahzad Ahmad, MD, FCCP; Oksana A. Shlobin, MD, FCCP; Steven D. Nathan, MD, FCCP
Author and Funding Information

From the Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, VA.

Correspondence to: Steven Nathan, MD, FCCP, Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, 3300 Gallows Rd, Falls Church, VA 22042; e-mail: steven.nathan@inova.org


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(2):402-411. doi:10.1378/chest.10-1048
Text Size: A A A
Published online

Lung transplantation is an effective treatment option for select patients with a variety of end-stage lung diseases. Although transplant can significantly improve the quality of life and prolong survival, a myriad of pulmonary complications may result in significant morbidity and limit long-term survival. The recognition and early treatment of these complications is important for optimizing outcomes. This article provides an overview and update of the pulmonary complications that may be commonly encountered by pulmonologists caring for these patients.

Figures in this Article

The number of lung transplants has continued to increase each year, with > 2,700 transplants performed worldwide in 2007.1 Lung transplant outcomes also appear to be improving incrementally, with the median survival increasing from 4.7 years in the late 1990s to 5.7 years for the 2000 to 2007 era. In 2005, a new lung allocation scoring system was introduced in the United States with the goal of prioritizing organ allocation based on the need for transplant and the likelihood of success. This system was designed to improve the overall transplant benefit and has resulted in shortened wait times and reduced mortality on the wait list. Thus far, the new system does not appear to have compromised survival, except for the sickest patients with the highest lung allocation scores whose posttransplant survival appears to be significantly reduced.1,2

Primary graft dysfunction (PGD), infection, and late graft failure account for the majority of deaths in the first year after lung transplant.1 Chronic allograft rejection or bronchiolitis obliterans syndrome (BOS) develops in the majority of patients by 5 years and is the key factor limiting the long-term survival of these patients. This review focuses on the major pulmonary complications encountered by the pulmonologist in providing care to this complicated and growing group of patients.

PGD is a leading cause of early posttransplant morbidity and mortality. It affects 10% to 25% of lung transplant recipients and is associated with a 30-day mortality that may be as high as 50%.3-7 It is characterized by the early development of diffuse parenchymal infiltrates associated with a reduced Pao2/Fio2 ratio (< 300) in the absence of cardiogenic pulmonary edema, hyperacute rejection, pulmonary venous anastomotic obstruction, or infection (Fig 1). PGD resembles ARDS and manifests histologically by a similar pattern of diffuse alveolar damage. It is thought to occur because of ischemia/reperfusion injury with damage to the pulmonary endothelium and epithelium.

Figure Jump LinkFigure 1. Primary graft dysfunction (PGD) after lung transplant. A, Preoperative chest radiograph of a 55-year-old woman with idiopathic pulmonary fibrosis. B, Grade 3 PGD 6 h after right lung transplant. C, Improvement after 5 days on extracorporeal membrane oxygenation. D, Complete resolution of PGD 2 weeks after transplant.Grahic Jump Location

The risk factors for PGD may be both donor and recipient related. Increasing age, smoking history, prolonged mechanical ventilation, aspiration pneumonia, trauma, and hemodynamic instability of the donor are all associated with a higher risk of PGD in the recipient.5,8 Recipient-related risk factors include elevated pretransplant pulmonary artery pressures, diffuse interstitial lung disease, and the transfusion of blood products.9,10

The International Society for Heart and Lung Transplantation (ISHLT) classification scheme categorizes the severity of PGD based on the Pao2/Fio2 ratio immediately postoperatively, and at 24, 48, and 72 h. It has been shown that the longer and the more severe the PGD, the greater the impact on patient outcomes.11

Preventive strategies have focused on improving lung preservation techniques, preventing barotrauma of donor lungs, modifying organ preservation solutions, and minimizing ischemic times.9,12,13 Inhaled nitric oxide has been studied but has not been shown to be an effective prophylactic agent.14,15

The treatment of PGD remains largely supportive. Management is similar to that of patients with ARDS, with low tidal volume ventilation and maintenance of patients’ volume status on the “dry” side with diuresis. Inhaled nitric oxide can be implemented for refractory hypoxemia, whereas extracorporeal membrane oxygenation can be a potentially lifesaving treatment, with a reported 42% survival rate in one study16,17 (Fig 1). Exogenous administration of surfactant has also been shown to attenuate reperfusion injury in animal models, and improvements in lung infiltrates and resolution of PGD have been reported in a small uncontrolled study.18

Exploring the link between PGD and chronic allograft rejection or BOS is an area of emerging interest. Recently, it was shown that PGD induces proinflammatory cytokines and upregulates human leukocyte antigen-II expression, which can then increase donor-specific alloimmunity, thereby mechanistically linking PGD and BOS.19

Infectious complications remain one of the most important causes of morbidity and mortality in lung transplant recipients.1,20 There are numerous reasons why lung recipients have a heightened predisposition to pulmonary infections. The lungs are more immunogenic than most other solid organs and therefore recipients generally require higher levels of immunosuppression. In addition, the donors are predisposed to aspiration and/or ventilator-associated pneumonias.21 Moreover, the allograft has direct exposure to microbes in the inspired air, the cough reflex is impaired because of graft denervation, there is abnormal mucociliary clearance, and lymphatic drainage is compromised during the procedure. Other potential complications, such as anastomotic strictures and infections of the native lung in single-lung recipients, may further increase the risk.

Bacterial pneumonias are frequent complications after lung transplant.20,21 Late-onset bacterial pneumonia can be associated with BOS and is frequently the precipitating event leading to mortality.22 The underlying primary disease may play a role, especially in cystic fibrosis recipients who have a higher propensity for upper airway colonization and infection with Pseudomonas aeruginosa. Atypical bacterial infection such as Chlamydia pneumonia can also be seen in lung transplant recipients. Resistant and nosocomial pathogens, especially Staphylococcus and Pseudomonas, are prevalent because of frequent antibiotic use and hospitalizations. These organisms should therefore be considered in the differential diagnosis for any infectious episode.

Infection with Mycobacterium tuberculosis may occur because of reactivation of a focus in the native lung or by transmission via the allograft. Colonization with nontuberculous mycobacteria occurs fairly frequently, with infections being reported occasionally.23,24

Cytomegalovirus (CMV) is one of the most important pathogens after lung transplant. All seropositive recipients are at risk, whereas seronegative recipients transplanted with a seropositive donor lung are at the highest risk of developing CMV infection and disease after lung transplant. The spectrum of involvement is defined as CMV infection (isolation of the virus in BAL or blood by culture, antigenemia, or polymerase chain reaction), CMV syndrome (viremia in conjunction with fever, leucopenia, or thrombocytopenia), or CMV disease (histologic evidence of viral cytopathic changes).

CMV may also provoke alterations of the immune system. This, in turn, may be associated with an increased risk of other opportunistic infections and a heightened predisposition for both acute and chronic rejection, possibly through increased antigen presentation.25

Other human herpes viruses, including herpes simplex virus and varicella zoster virus, can rarely be seen. Epstein-Barr virus (EBV) is strongly associated with posttransplant lymphoproliferative disease (PTLD), which has an incidence of 1% to 20%. PTLD is a heterogeneous group of lymphoproliferative disorders, ranging from reactive polyclonal hyperplasias to aggressive non-Hodgkin’s lymphomas. PTLD may result from a decreased EBV-specific T-cell immune response induced by immunosuppression and is seen more commonly in conjunction with cytolytic induction therapy.26 Heightened immunosuppression and EBV mismatching are also major risk factors for PTLD. Clinically, the symptoms and signs are as protean as those of lymphoma.26 Frequently, the disease may be heralded by chest CT scan findings of infiltrates, adenopathy, or masses. Biopsies of these are consistent with a lymphoproliferative disorder, which is usually of the B-cell type. Treatment consists of decreasing immunosuppression and starting antiviral therapy in the form of IV ganciclovir or oral valganciclovir. Standard chemotherapy may be indicated and anti-B-cell therapy with rituximab can also be undertaken in CD-20+ cases.

Other community-acquired viruses, such as rhinovirus, respiratory syncytial virus, parainfluenza, influenza A and B, adenoviruses, and 2009 influenza A(H1N1), can also cause infections in lung transplant recipients. The sequelae of these may include acute rejection and obliterative bronchiolitis/BOS.27

Fungal infections occur in 15% to 35% of lung transplant recipients, with Aspergillus and Candida species responsible for > 80% of these cases.28Aspergillus can result in a spectrum of manifestations, including colonization, infections of the bronchial anastomosis and tracheobronchial tree, invasive pneumonias, and disseminated disease.29 Chest CT scan, bronchoscopy, and the Aspergillus galactomannan assay may be helpful in diagnosing and differentiating these forms of aspergillosis. Along with other rare fungi such as Zygomycetes, Scedosporium, and Fusarium species, these organisms can be challenging to diagnose and treat. Early recognition and treatment is essential as the mortality rate for invasive fungal infections can be > 80%.

Primary immunization in the pretransplant period should be undertaken for influenza, 2009 influenza A(H1N1), Streptococcus pneumonia, tetanus, and hepatitis B. Live vaccines should be avoided after transplant. Routine postsurgical broad-spectrum antibiotic prophylaxis targeting the cultures from the donor lungs or known positive recipient cultures is commonly undertaken.

CMV prophylaxis in the form of IV ganciclovir and oral valganciclovir is administered routinely to at-risk patients for anywhere from 6 weeks to 12 months after transplant. In the past few years, oral valganciclovir-based regimens have shown greater efficacy against CMV infection and disease in solid organ transplant recipients.30-34 Recent data have shown that a 12-month prophylactic regimen is superior to shorter-duration regimens.30,31,34,35 Routine surveillance with serial CMV antigenemia testing and CMV DNA polymerase chain reaction is employed by most lung transplant programs.

Prophylaxis with sulfamethoxazole and trimethoprim is effective for the prevention of Pneumocystis pneumonia, with additional antimicrobial effects against Toxoplasma gondii, Nocardia, and Listeria species. Antifungal prophylaxis in the form of aerosolized Amphotericin B in the immediate postoperative period and itraconazole or voriconazole for 1 to 12 months are commonly employed.

Acute cellular rejection (ACR) can be seen at any time after the first week and is commonly seen in the first year posttransplant. Patients may present with cough, dyspnea, hypoxia, fever, rales on auscultation, decline in spirometry, or radiographic infiltrates.36 Findings of ground-glass opacities, septal thickening, and pleural effusions on CT scans suggest acute rejection; however, they have sensitivity as low as 35% and limited discriminatory value in excluding other processes.37 Because the clinical symptoms and signs are nonspecific, bronchoscopy with transbronchial biopsy and BAL are commonly employed. ACR tends to be a patchy process, and therefore a minimum of five alveolated biopsy specimens is recommended to provide adequate sensitivity.38 The diagnosis of ACR relies on the histologic identification of perivascular lymphocytic infiltrates (Fig 2). The ISHLT grading system for lung allograft rejection was revised in 2007 and is summarized in Table 1.

Figure Jump LinkFigure 2. Histopathology of acute lung allograft rejection (hematoxylin and eosin stain; original magnification × 40). A1, Grade A1 acute rejection with rare perivascular lymphocytes. A2, Grade A2 acute rejection with prominent perivascular mononuclear infiltrate. A3, Grade A3 acute rejection with extensive perivascular infiltrate extending into perivascular spaces. A4, Grade A4 acute rejection with diffuse mononuclear infiltrates with lung injury. (Reprinted with permission from Keith C. Meyer, MD.)Grahic Jump Location
Table Graphic Jump Location
Table 1 —Pathologic Grading of Lung Rejection

ISHLT = International Society for Heart and Lung Transplantation. Modified from the revised ISHLT guidelines for the nomenclature in the diagnosis of acute rejection.38

Surveillance biopsies in the first 6 months to 1 year after transplant are commonly employed to diagnose asymptomatic ACR, which may be found in a relatively high percentage (6.1%-39%) of patients.39-42 Various cytokine surrogate markers for ACR from BAL analysis have been studied; however, neither these nor BAL cellular composition have displayed adequate accuracy in discriminating rejection from infection.

The diagnosis and empiric treatment of ACR based solely on clinical signs or symptoms is suboptimal, and histopathologic analysis to diagnose and grade ACR is always encouraged. However, under certain circumstances, biopsies may be contraindicated or limited by procedure-related bleeding. In such scenarios, in the context of a high clinical index of suspicion and a BAL that does not show evidence of infection, an alternate approach might be to treat empirically with a bolus dose of solumedrol. If there is an associated clinical response, then a presumptive clinical diagnosis of ACR is reasonable and therapy can be continued. The treatment of acute allograft rejection usually consists of pulsed IV steroids, typically 500 mg to 1,000 mg of methylprednisolone, administered daily for three doses followed by an oral prednisone taper.43

Treatment of recalcitrant or recurrent rejection is more challenging. Repeating the pulsed steroids, altering the baseline immunosuppressive regimen, such as switching calcineurin inhibitors, or substituting azathioprine with mycophenolate mofetil represent some of the options. More aggressive therapy includes the use of cytolytic agents, such as polyclonal antithymocyte globulin or an anti-IL-2 receptor antagonist.

Chronic rejection is the leading cause of morbidity and late mortality after lung or heart-lung transplant.1 It is manifested pathologically as obliterative bronchiolitis (OB) (Fig 3) or clinically as BOS.44 OB is an inflammatory/fibrotic process that affects small airways or bronchioles.38 Because of the patchy nature of OB, the diagnosis is often missed by transbronchial lung biopsies. Documenting the histologic presence of OB is difficult, so the physiologic correlate of BOS has been established.45 The diagnosis of BOS is defined by an irreversible decline in the FEV1 after excluding alternative causes of allograft dysfunction, such as anastomotic complications, infection, ACR, heart failure, and progression or recurrence of the native disease.45 The BOS classification system is shown in Table 2.

Figure Jump LinkFigure 3. Histopathology of bronchiolitis obliterans (hematoxylin and eosin stain; original magnification ×200). A, Completely obliterated bronchiole in lung allograft. B, An adjacent section with elastic stain, highlighting the internal elastic lamina (arrows). (Reprinted with permission from Henry D. Tazelaar, MD.)Grahic Jump Location
Table Graphic Jump Location
Table 2 —BOS Classification System

BOS = bronchiolitis obliterans syndrome; BOS 0 p = potential BOS; FEF25%-75% = forced expiratory flow, midexpiratory phase. See Table 1 for expansion of the other abbreviation. Modified from the ISHLT guidelines.45

Data from the ISHLT registry attest to 28% and 74% of patients developing BOS by 2.5 years and 10 years, respectively.1 The course and loss of lung function may be insidious, over months to years, or abrupt, with a significant decline in lung function in a few weeks.46,47 BOS accounts for < 5% of deaths within the first year after lung transplant but is responsible for about one-quarter of deaths after the first year. A further ∼20% of patients die of graft failure, and, therefore, almost one-half of the patients who succumb beyond the first year will do so from some form of chronic allograft dysfunction.1 Respiratory infections may play a role in the onset and progression of BOS, with many patients subsequently colonized or infected with various organisms, including Pseudomonas aeruginosa and Aspergillus.22,48 A further ∼ 20% of patients succumb from non-CMV infections; how many of these are in the context of BOS remains unknown.

The pathogenesis of BOS is complex and involves both alloimmune and nonalloimmune mechanisms, alone and in combination.49 Alloimmune factors, such as ACR and lymphocytic bronchiolitis, are known to be associated with BOS. Alloimmune-independent factors such as PGD, allograft infections (especially CMV), airway ischemia, and gastroesophageal reflux might all foster an inflammatory milieu that initiates an alloimmune response.50 Several studies have shown that ACR and lymphocytic bronchiolitis are the most important risk factors for BOS.44,45,51-53 Additional risk factors include CMV and non-CMV respiratory infections, injury to the allograft, human leukocyte antigen mismatching, and organizing pneumonia.19,25,53

Strategies to detect early ACR with surveillance transbronchial biopsies may play a role in preventing BOS since even minimal ACR seems to be a predisposing risk factor.54,55 BAL neutrophilia is characteristic of BOS, and a combined neutrophilia and lymphocytosis without evidence of infection suggests BOS.56 However, BAL cell counts, cytokine levels, and other protein alterations lack sufficient sensitivity or specificity to be helpful in the diagnosis. CT scans can show evidence of air trapping with hyperlucency, a mosaic pattern of attenuation, thickened septal lines, and bronchiectasis.

The prevention and treatment of BOS have been largely unsuccessful.49 Augmentation of immunosuppression within the therapeutic classes is commonly undertaken.49,50 The diverse nature of the strategies employed for BOS attests to the lack of proven effective therapies and underscores this as a large unmet need in the field of lung transplantation. The various therapies reported in nonrandomized studies can be broadly categorized into trials of (1) cytolytic therapy, (2) switch therapy (azathioprine to mycophenolate mofetil; cyclosporine to tacrolimus), (3) add-on therapy (sirolimus, methotrexate, cyclophosphamide, inhaled corticosteroids, inhaled cyclosporine), and (4) ancillary immunomodulation, including macrolide therapy, total lymphoid irradiation, and extracorporeal photophoresis.49,57

Macrolides, specifically azithromycin and more recently clarithromycin, have been used for the treatment of BOS, with numerous reports attesting to the potential recovery of lung function in some patients.58-60 It appears that those patients with increased neutrophils (> 15%) on BAL are more likely to respond to azithromycin and it has been proposed recently that such patients be categorized as a distinct entity, termed “neutrophilic reversible allograft dysfunction.”61 It does appear likely that there are other forms of chronic lung allograft dysfunction that are not fully captured by the current BOS definition, and extricating patients with neutrophilic reversible allograft dysfunction might be the first step in providing a broader categorization.

Aerosolized cyclosporine has shown potential efficacy in the prevention of BOS in a single-center, randomized, placebo-controlled trial and is currently being subjected to further study through a multicenter, randomized, placebo-controlled study.62,63 Nissen fundoplication may be indicated for patients with BOS and associated gastroesophageal reflux disease, with reports attesting to subsequent recovery of lung function. Retransplant can be performed for advanced BOS in highly select patients, albeit with lower survival rates than de novo lung transplants.64 Similar to patients with any form of advanced lung disease, those with chronic allograft rejection may derive significant functional benefit from a course of pulmonary rehabilitation.

A number of factors predispose to large-airway complications posttransplant. These include airway ischemia due to sacrifice of the bronchial circulation, airway colonization and infection, and possibly airway-targeted alloimmunity.

Bronchial Stenosis

Bronchial stenosis is the most common airway complication and is usually seen within 2 to 9 months after transplant, with an incidence of between 1.6% and 32%.65 It is mostly seen at the surgical anastomosis but on rare occasions can occur distally. The latter type can be progressive and severe, resulting in “vanishing airway syndrome.”66 Bronchial stenosis may be asymptomatic or may present with declining expiratory flows, dyspnea, cough, or postobstructive pneumonia. Flexible bronchoscopy remains the gold standard for diagnosis. Several endoscopic techniques, including balloon bronchoplasty, cryotherapy, laser, and stent placement, can be used, with varying success. Immediate improvement in symptoms and flows in 90% of cases and long-term success in 50% of patients have been described.67-70

Bronchial Necrosis and Dehiscence

Bronchial necrosis and dehiscence is a rare complication with an incidence of between 1% and 10%. Partial dehiscence can be managed with temporary placement of self-expanding metallic stents, which then promote granulation tissue and serves as a scaffold for healing.67,71 Complete dehiscence is fortunately rare (1%) as it is associated with a high mortality, which is related to sepsis.

Exophytic Granulation Tissue

Exophytic granulation tissue can cause significant airway obstruction in up to 20% of patients. Concurrent infection with Aspergillus makes it refractory to therapy and increases its morbidity. Debridement by cryotherapy, laser vaporization, or Argon plasma coagulation can be effective.

Tracheobronchomalacia

Tracheobronchomalacia is usually seen within 4 months after transplant.72 Patients typically present with dyspnea, cough, obstructive defect on spirometry, and recurrent infections. Bronchoscopy remains the gold standard for diagnosis and shows dynamic airway collapse (Fig 4). Treatment remains challenging and, in cases of severe symptoms, airway stenting may be required.

Figure Jump LinkFigure 4. Bronchomalacia at the left main stem anastomosis. A, Inspiration. B, Expiration with significant collapse and luminal compromise at the anastomosis.Grahic Jump Location

Thromboembolic complications tend to occur at a high rate (8.6%) in lung transplant recipients.73 Pulmonary embolism may occur at any stage after transplant from preexisting or transplant-related risk factors. Patients may be predisposed to thromboembolic events related to their underlying primary condition, such as the various connective tissue disorders.74,75 It is also possible that the transplant process may result in a hypercoagulable state through a systemic inflammatory response or for mechanical reasons related to central lines. A high index of suspicion should exist in patients who present with shortness of breath associated with hypoxemia or exercise desaturation, especially if there is no change in their spirometry and no evidence of parenchymal infiltrates. The diagnosis is usually obtained via CT scan angiography. In cases where this is contraindicated by impaired renal function, a ventilation-perfusion scan may be helpful. The treatment is generally the same as for any patient with thromboembolism, although there may be a heightened risk of hemothorax in the early posttransplant period.

Pleural effusions occur commonly in the immediate posttransplant period. As a consequence of the transplant procedure, the pulmonary lymphatics are severed, which reduces the ability to clear any fluid from the pleural space. Ongoing effusion might prolong the need for chest tube drainage postoperatively, but usually not beyond the first week or two. If the thoracic duct is severed, as can occur in patients with extensive mediastinal adhesions, then there is a risk of chylothorax, which should be considered for any persistent effusion. After the immediate posttransplant period, the occurrence of pleural effusions is usually in the context of other causes such as empyema, or as a manifestation of a parapneumonic process, heart failure, pulmonary embolism, acute rejection, or trapped lung.

Certain diseases, such as sarcoidosis, lymphangioleiomyomatosis, and pulmonary Langerhans cell histiocytosis, may recur in the allograft. Noncaseating granulomas have been reported in up to two-thirds of sarcoidosis recipients on routine transbronchial biopsies. These are usually a histologic curiosity and rarely manifest clinically, although clinically significant recurrence and pulmonary nodules due to sarcoidosis have been reported posttransplant.

In the case of single-lung recipients, the native lung can be the source of significant pulmonary complications and should not be overlooked in the serial evaluation of these patients. Complications can include neoplasms, infections, pneumothoraces, and native lung herniation across the midline from progressive hyperinflation in the case of COPD single-lung recipients.76

The diagnostic algorithm for pulmonary symptoms in lung transplant recipients includes the consideration of additional nuances. Specifically, the acuity of onset of symptoms and time of occurrence posttransplant are important in honing in on the diagnostic possibilities. A schematic representation of the time course of major pulmonary complications is shown in Figure 5, with the time posttransplant represented on the x axis, the various complications on the y axis, and the relative incidence of the complication depicted by the vertical height. Testing to be considered in any patient presenting with pulmonary symptoms is shown in Figure 6. Not all tests need be performed in every patient and the need for each of these should be dictated by their clinical presentation.

Figure Jump LinkFigure 5. Timeline of pulmonary complications after lung transplant. The time of onset is shown on the x axis with the relative incidence depicted on the y axis. BOS = bronchiolitis obliterans syndrome. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 6. Algorithm and diagnostic considerations for the evaluation of pulmonary complications after lung transplant. AFB = acid fast bacilli; CHF = congestive heart failure; CMV Ag = cytomegalovirus antigenemia; CXR = chest radiograph; echo = echocardiography; GERD = gastroesophageal reflux disease; ID = infectious disease; PCP = Pneumocystis carini pneumonia; PCR = polymerase chain reaction; PH = pulmonary hypertension; RHC = right-sided heart catheterization; TBBx = transbronchial biopsies. See Figure 5 legend for expansion of other abbreviations.Grahic Jump Location

Although the long-term survival of lung transplant recipients has improved, pulmonary complications continue to plague their posttransplant course and remain a major cause of morbidity and mortality. As more of these patients are comanaged or discharged to the care of their community pulmonologists, a better understanding of the spectrum and impact of these complications, a heightened awareness, and preemptive management may favorably impact the outcomes of this complicated group of patients.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Nathan has received research funding from APT Pharmaceuticals. Drs Ahmad and Shlobin have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Christie JD, Edwards LB, Aurora P, et al. The registry of the International Society for Heart and Lung Transplantation: twenty-sixth official adult lung and heart-lung transplantation report-2009. J Heart Lung Transplant. 2009;2810:1031-1049. [CrossRef] [PubMed]
 
Russo MJ, Iribarne A, Hong KN, et al. High lung allocation score is associated with increased morbidity and mortality following transplantation. Chest. 2010;1373:651-657. [CrossRef] [PubMed]
 
Christie JD, Bavaria JE, Palevsky HI, et al. Primary graft failure following lung transplantation. Chest. 1998;1141:51-60. [CrossRef] [PubMed]
 
King RC, Binns OA, Rodriguez F, et al. Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation. Ann Thorac Surg. 2000;696:1681-1685. [CrossRef] [PubMed]
 
Christie JD, Kotloff RM, Pochettino A, et al. Clinical risk factors for primary graft failure following lung transplantation. Chest. 2003;1244:1232-1241. [CrossRef] [PubMed]
 
Christie JD, Sager JS, Kimmel SE, et al. Impact of primary graft failure on outcomes following lung transplantation. Chest. 2005;1271:161-165. [CrossRef] [PubMed]
 
Fiser SM, Kron IL, McLendon Long S, Kaza AK, Kern JA, Tribble CG. Early intervention after severe oxygenation index elevation improves survival following lung transplantation. J Heart Lung Transplant. 2001;206:631-636. [CrossRef] [PubMed]
 
de Perrot M, Bonser RS, Dark J, et al; ISHLT Working Group on Primary Lung Graft Dysfunction ISHLT Working Group on Primary Lung Graft Dysfunction Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part III: donor-related risk factors and markers. J Heart Lung Transplant. 2005;2410:1460-1467. [CrossRef] [PubMed]
 
Barr ML, Kawut SM, Whelan TP, et al; ISHLT Working Group on Primary Lung Graft Dysfunction ISHLT Working Group on Primary Lung Graft Dysfunction Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part IV: recipient-related risk factors and markers. J Heart Lung Transplant. 2005;2410:1468-1482. [CrossRef] [PubMed]
 
Whitson BA, Nath DS, Johnson AC, et al. Risk factors for primary graft dysfunction after lung transplantation. J Thorac Cardiovasc Surg. 2006;1311:73-80. [CrossRef] [PubMed]
 
Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D. ISHLT Working Group on Primary Lung Graft Dysfunction ISHLT Working Group on Primary Lung Graft Dysfunction Report of the ISHLT working group on primary lung graft dysfunction: Part II. Definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2005;2410:1454-1459. [CrossRef] [PubMed]
 
Oto T, Griffiths AP, Rosenfeldt F, Levvey BJ, Williams TJ, Snell GI. Early outcomes comparing Perfadex, Euro-Collins, and Papworth solutions in lung transplantation. Ann Thorac Surg. 2006;825:1842-1848. [CrossRef] [PubMed]
 
Schnickel GT, Ross DJ, Beygui R, et al. Modified reperfusion in clinical lung transplantation: the results of 100 consecutive cases. J Thorac Cardiovasc Surg. 2006;1311:218-223. [CrossRef] [PubMed]
 
Meade MO, Granton JT, Matte-Martyn A, et al. A randomized trial of inhaled nitric oxide to prevent ischemia-reperfusion injury after lung transplantation. Am J Respir. Crit Care Med. 2003;167:1483-1489. [CrossRef] [PubMed]
 
Botha P, Jeyakanthan M, Rao JN, et al. Inhaled nitric oxide for modulation of ischemia-reperfusion injury in lung transplantation. J Heart Lung Transplant. 2007;2611:1199-1205. [CrossRef] [PubMed]
 
Date H, Triantafillou AN, Trulock EP, Pohl MS, Cooper JD, Patterson GA. Inhaled nitric oxide reduces human lung allograft dysfunction. J Thorac Cardiovasc Surg. 1996;1115:913-919. [CrossRef] [PubMed]
 
Fischer S, Bohn D, Rycus P, Pierre AF, de Perrot M, Waddell TK, et al. Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: analysis of the Extracorporeal Life Support Organization (ELSO) registry. J Heart Lung Transplant. 2007;265:472-477. [CrossRef] [PubMed]
 
Kermeen FD, McNeil KD, Fraser JF, et al. Resolution of severe ischemia-reperfusion injury post-lung transplantation after administration of endobronchial surfactant. J Heart Lung Transplant. 2007;268:850-856. [CrossRef] [PubMed]
 
Bharat A, Kuo E, Steward N, et al. Immunological link between primary graft dysfunction and chronic lung allograft rejection. Ann Thorac Surg. 2008;861:189-195. [CrossRef] [PubMed]
 
Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007;35725:2601-2614. [CrossRef] [PubMed]
 
Dauber JH, Paradis IL, Dummer JS. Infectious complications in pulmonary allograft recipients. Clin Chest Med. 1990;112:291-308. [PubMed]
 
Sharples LD, McNeil K, Stewart S, Wallwork J. Risk factors for bronchiolitis obliterans: a systematic review of recent publications. J Heart Lung Transplant. 2002;212:271-281. [CrossRef] [PubMed]
 
Kesten S, Chaparro C. Mycobacterial infections in lung transplant recipients. Chest. 1999;1153:741-745. [CrossRef] [PubMed]
 
Chalermskulrat W, Sood N, Neuringer IP, et al. Non-tuberculous mycobacteria in end stage cysticfibrosis: implications for lung transplantation. Thorax. 2006;616:507-513. [CrossRef] [PubMed]
 
Freeman RB Jr. The ‘indirect’ effects of cytomegalovirus infection. Am J Transplant. 2009;911:2453-2458. [CrossRef] [PubMed]
 
Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med. 2005;56:29-44. [CrossRef] [PubMed]
 
Kumar D, Husain S, Chen MH, et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation. 2010;898:1028-1033. [CrossRef] [PubMed]
 
Solé A, Salavert M. Fungal infections after lung transplantation. Transplant Rev (Orlando). 2008;222:89-104. [CrossRef] [PubMed]
 
Singh N, Husain S. Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management. J Heart Lung Transplant. 2003;223:258-266. [CrossRef] [PubMed]
 
Zamora MR, Nicolls MR, Hodges TN, et al. Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation. Am J Transplant. 2004;410:1635-1642. [CrossRef] [PubMed]
 
Jaksch P, Zweytick B, Kerschner H, et al. Cytomegalovirus prevention in high-risk lung transplant recipients: comparison of 3- vs 12-month valganciclovir therapy. J Heart Lung Transplant. 2009;287:670-675. [CrossRef] [PubMed]
 
Humar A, Kumar D, Preiksaitis J, et al. A trial of valganciclovir prophylaxis for cytomegalovirus prevention in lung transplant recipients. Am J Transplant. 2005;56:1462-1468. [CrossRef] [PubMed]
 
Monforte V, Lopez C, Santos F, et al. A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-seropositive lung transplant recipients. Am J Transplant. 2009;95:1134-1141. [CrossRef] [PubMed]
 
Zamora MR, Davis RD, Leonard C. CMV Advisory Board Expert Committee CMV Advisory Board Expert Committee Management of cytomegalovirus infection in lung transplant recipients: evidence-based recommendations. Transplantation. 2005;802:157-163. [CrossRef] [PubMed]
 
Palmer SM, Limaye AP, Banks M, et al. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation. Ann Intern Med. 2010;15212:761-769. [PubMed]
 
Van Muylem A, Mélot C, Antoine M, Knoop C, Estenne M. Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation. Thorax. 1997;527:643-647. [CrossRef] [PubMed]
 
Gotway MB, Dawn SK, Sellami D, et al. Acute rejection following lung transplantation: limitations in accuracy of thin-section CT for diagnosis. Radiology. 2001;2211:207-212. [CrossRef] [PubMed]
 
Stewart S, Fishbein MC, Snell GI, et al. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant. 2007;2612:1229-1242. [CrossRef] [PubMed]
 
Guilinger RA, Paradis IL, Dauber JH, et al. The importance of bronchoscopy with transbronchial biopsy and bronchoalveolar lavage in the management of lung transplant recipients. Am J Respir Crit Care Med. 1995;1526 Pt 1:2037-2043. [PubMed]
 
Trulock EP, Ettinger NA, Brunt EM, Pasque MK, Kaiser LR, Cooper JD. The role of transbronchial lung biopsy in the treatment of lung transplant recipients. An analysis of 200 consecutive procedures. Chest. 1992;1024:1049-1054. [CrossRef] [PubMed]
 
Hopkins PM, Aboyoun CL, Chhajed PN, et al. Prospective analysis of 1,235 transbronchial lung biopsies in lung transplant recipients. J Heart Lung Transplant. 2002;21:1062-1067. [CrossRef] [PubMed]
 
Chakinala MM, Ritter J, Gage BF, et al. Yield of surveillance bronchoscopy for acute rejection and lymphocytic bronchitis/bronchiolitis after lung transplantation. J Heart Lung Transplant. 2004;2312:1396-1404. [CrossRef] [PubMed]
 
Yousem SA, Martin T, Paradis IL, Keenan R, Griffith BP. Can immunohistological analysis of transbronchial biopsy specimens predict responder status in early acute rejection of lung allografts? Hum Pathol. 1994;255:525-529. [CrossRef] [PubMed]
 
Verleden GM, Dupont LJ, Van Raemdonck DE. Is it bronchiolitis obliterans syndrome or is it chronic rejection: a reappraisal? Eur Respir J. 2005;252:221-224. [CrossRef] [PubMed]
 
Estenne M, Maurer JR, Boehler A, et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002;213:297-310. [CrossRef] [PubMed]
 
Lama VN, Murray S, Lonigro RJ, et al. Course of FEV(1) after onset of bronchiolitis obliterans syndrome in lung transplant recipients. Am J Respir Crit Care Med. 2007;17511:1192-1198. [CrossRef] [PubMed]
 
Jackson CH, Sharples LD, McNeil K, Stewart S, Wallwork J. Acute and chronic onset of bronchiolitis obliterans syndrome (BOS): are they different entities? J Heart Lung Transplant. 2002;216:658-666. [CrossRef] [PubMed]
 
Botha P, Archer L, Anderson RL, et al. Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome. Transplantation. 2008;855:771-774. [CrossRef] [PubMed]
 
Belperio JA, Lake K, Tazelaar H, Keane MP, Strieter RM, Lynch JP III. Bronchiolitis obliterans syndrome complicating lung or heart-lung transplantation. Semin Respir Crit Care Med. 2003;245:499-530. [CrossRef] [PubMed]
 
Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med. 2002;1664:440-444. [CrossRef] [PubMed]
 
Bando K, Paradis IL, Similo S, et al. Obliterative bronchiolitis after lung and heart-lung transplantation. An analysis of risk factors and management. J Thorac Cardiovasc Surg. 1995;1101:4-13. [CrossRef] [PubMed]
 
Husain AN, Siddiqui MT, Holmes EW, et al. Analysis of risk factors for the development of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 1999;1593:829-833. [PubMed]
 
Scott AI, Sharples LD, Stewart S. Bronchiolitis obliterans syndrome: risk factors and therapeutic strategies. Drugs. 2005;656:761-771. [CrossRef] [PubMed]
 
Khalifah AP, Hachem RR, Chakinala MM, et al. Minimal acute rejection after lung transplantation: a risk for bronchiolitis obliterans syndrome. Am J Transplant. 2005;58:2022-2030. [CrossRef] [PubMed]
 
Hachem RR, Khalifah AP, Chakinala MM, et al. The significance of a single episode of minimal acute rejection after lung transplantation. Transplantation. 2005;8010:1406-1413. [CrossRef] [PubMed]
 
Glanville AR. The role of bronchoscopic surveillance monitoring in the care of lung transplant recipients. Semin Respir Crit Care Med. 2006;275:480-491. [CrossRef] [PubMed]
 
Fisher AJ, Rutherford RM, Bozzino J, Parry G, Dark JH, Corris PA. The safety and efficacy of total lymphoid irradiation in progressive bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant. 2005;53:537-543. [CrossRef] [PubMed]
 
Gottlieb J, Szangolies J, Koehnlein T, Golpon H, Simon A, Welte T. Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation. 2008;851:36-41. [CrossRef] [PubMed]
 
Shitrit D, Bendayan D, Gidon S, Saute M, Bakal I, Kramer MR. Long-term azithromycin use for treatment of bronchiolitis obliterans syndrome in lung transplant recipients. J Heart Lung Transplant. 2005;249:1440-1443. [CrossRef] [PubMed]
 
Benden C, Boehler A. Long-term clarithromycin therapy in the management of lung transplant recipients. Transplantation. 2009;8710:1538-1540. [CrossRef] [PubMed]
 
Vanaudenaerde BM, Meyts I, Vos R, et al. A dichotomy in bronchiolitis obliterans syndrome after lung transplantation revealed by azithromycin therapy. Eur Respir J. 2008;324:832-843. [CrossRef] [PubMed]
 
Iacono AT, Johnson BA, Grgurich WF, et al. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006;3542:141-150. [CrossRef] [PubMed]
 
Study of cyclosporine inhalation solution (CIS) in improving bronchiolitis obliterans syndrome-free survival following lung transplantation (CIS001). http://clinicaltrials.gov/ct2/show/NCT00755781?term=lung+transplantation&rank=8. Accessed September 14, 2010.
 
Kawut SM, Lederer DJ, Keshavjee S, et al. Outcomes after lung retransplantation in the modern era. Am J Respir Crit Care Med. 2008;1771:114-120. [CrossRef] [PubMed]
 
Garfein ES, McGregor CC, Galantowicz ME, Schulman LL. Deleterious effects of telescoped bronchial anastomosis in single and bilateral lung transplantation. Ann Transplant. 2000;51:5-11. [PubMed]
 
Shah SS, Karnak D, Minai O, et al. Symptomatic narrowing or atresia of bronchus intermedius following lung transplantation vanishing bronchus intermedius syndrome (VBIS)[abstract]. Chest. 2006;1304:236S
 
Kapoor BS, May B, Panu N, Kowalik K, Hunter DW. Endobronchial stent placement for the management of airway complications after lung transplantation. J Vasc Interv Radiol. 2007;185:629-632. [CrossRef] [PubMed]
 
Herrera JM, McNeil KD, Higgins RS, et al. Airway complications after lung transplantation: treatment and long-term outcome. Ann Thorac Surg. 2001;713:989-993-. [CrossRef] [PubMed]
 
McArdle JR, Gildea TR, Mehta AC. Balloon bronchoplasty: its indications, benefits, and complications. Bronchol. 2005;12:123-127. [CrossRef]
 
De Gracia J, Culebras M, Alvarez A, et al. Bronchoscopic balloon dilatation in the management of bronchial stenosis following lung transplantation. Respir Med. 2007;101:27-33. [CrossRef] [PubMed]
 
Mughal MM, Gildea TR, Murthy S, Pettersson G, DeCamp M, Mehta AC. Short-term deployment of self-expanding metallic stents facilitates healing of bronchial dehiscence. Am J Respir Crit Care Med. 2005;1726:768-771. [CrossRef] [PubMed]
 
Simoff MJ, Sterman DH, Ernst A. Thoracic Endoscopy. Advances in Interventional Pulmonology. 2006; Malden, MA Blackwell Publishing
 
Izbicki G, Bairey O, Shitrit D, Lahav J, Kramer MR. Increased thromboembolic events after lung transplantation. Chest. 2006;1292:412-416. [CrossRef] [PubMed]
 
Yegen HA, Lederer DJ, Barr RG, et al. Risk factors for venous thromboembolism after lung transplantation. Chest. 2007;1322:547-553. [CrossRef] [PubMed]
 
Kahan ES, Petersen G, Gaughan JP, Criner GJ. High incidence of venous thromboembolic events in lung transplant recipients. J Heart Lung Transplant. 2007;264:339-344. [CrossRef] [PubMed]
 
King CS, Khandhar S, Burton N, et al. Native lung complications in single-lung transplant recipients and the role of pneumonectomy. J Heart Lung Transplant. 2009;288:851-856. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Primary graft dysfunction (PGD) after lung transplant. A, Preoperative chest radiograph of a 55-year-old woman with idiopathic pulmonary fibrosis. B, Grade 3 PGD 6 h after right lung transplant. C, Improvement after 5 days on extracorporeal membrane oxygenation. D, Complete resolution of PGD 2 weeks after transplant.Grahic Jump Location
Figure Jump LinkFigure 2. Histopathology of acute lung allograft rejection (hematoxylin and eosin stain; original magnification × 40). A1, Grade A1 acute rejection with rare perivascular lymphocytes. A2, Grade A2 acute rejection with prominent perivascular mononuclear infiltrate. A3, Grade A3 acute rejection with extensive perivascular infiltrate extending into perivascular spaces. A4, Grade A4 acute rejection with diffuse mononuclear infiltrates with lung injury. (Reprinted with permission from Keith C. Meyer, MD.)Grahic Jump Location
Figure Jump LinkFigure 3. Histopathology of bronchiolitis obliterans (hematoxylin and eosin stain; original magnification ×200). A, Completely obliterated bronchiole in lung allograft. B, An adjacent section with elastic stain, highlighting the internal elastic lamina (arrows). (Reprinted with permission from Henry D. Tazelaar, MD.)Grahic Jump Location
Figure Jump LinkFigure 4. Bronchomalacia at the left main stem anastomosis. A, Inspiration. B, Expiration with significant collapse and luminal compromise at the anastomosis.Grahic Jump Location
Figure Jump LinkFigure 5. Timeline of pulmonary complications after lung transplant. The time of onset is shown on the x axis with the relative incidence depicted on the y axis. BOS = bronchiolitis obliterans syndrome. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 6. Algorithm and diagnostic considerations for the evaluation of pulmonary complications after lung transplant. AFB = acid fast bacilli; CHF = congestive heart failure; CMV Ag = cytomegalovirus antigenemia; CXR = chest radiograph; echo = echocardiography; GERD = gastroesophageal reflux disease; ID = infectious disease; PCP = Pneumocystis carini pneumonia; PCR = polymerase chain reaction; PH = pulmonary hypertension; RHC = right-sided heart catheterization; TBBx = transbronchial biopsies. See Figure 5 legend for expansion of other abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Pathologic Grading of Lung Rejection

ISHLT = International Society for Heart and Lung Transplantation. Modified from the revised ISHLT guidelines for the nomenclature in the diagnosis of acute rejection.38

Table Graphic Jump Location
Table 2 —BOS Classification System

BOS = bronchiolitis obliterans syndrome; BOS 0 p = potential BOS; FEF25%-75% = forced expiratory flow, midexpiratory phase. See Table 1 for expansion of the other abbreviation. Modified from the ISHLT guidelines.45

References

Christie JD, Edwards LB, Aurora P, et al. The registry of the International Society for Heart and Lung Transplantation: twenty-sixth official adult lung and heart-lung transplantation report-2009. J Heart Lung Transplant. 2009;2810:1031-1049. [CrossRef] [PubMed]
 
Russo MJ, Iribarne A, Hong KN, et al. High lung allocation score is associated with increased morbidity and mortality following transplantation. Chest. 2010;1373:651-657. [CrossRef] [PubMed]
 
Christie JD, Bavaria JE, Palevsky HI, et al. Primary graft failure following lung transplantation. Chest. 1998;1141:51-60. [CrossRef] [PubMed]
 
King RC, Binns OA, Rodriguez F, et al. Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation. Ann Thorac Surg. 2000;696:1681-1685. [CrossRef] [PubMed]
 
Christie JD, Kotloff RM, Pochettino A, et al. Clinical risk factors for primary graft failure following lung transplantation. Chest. 2003;1244:1232-1241. [CrossRef] [PubMed]
 
Christie JD, Sager JS, Kimmel SE, et al. Impact of primary graft failure on outcomes following lung transplantation. Chest. 2005;1271:161-165. [CrossRef] [PubMed]
 
Fiser SM, Kron IL, McLendon Long S, Kaza AK, Kern JA, Tribble CG. Early intervention after severe oxygenation index elevation improves survival following lung transplantation. J Heart Lung Transplant. 2001;206:631-636. [CrossRef] [PubMed]
 
de Perrot M, Bonser RS, Dark J, et al; ISHLT Working Group on Primary Lung Graft Dysfunction ISHLT Working Group on Primary Lung Graft Dysfunction Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part III: donor-related risk factors and markers. J Heart Lung Transplant. 2005;2410:1460-1467. [CrossRef] [PubMed]
 
Barr ML, Kawut SM, Whelan TP, et al; ISHLT Working Group on Primary Lung Graft Dysfunction ISHLT Working Group on Primary Lung Graft Dysfunction Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part IV: recipient-related risk factors and markers. J Heart Lung Transplant. 2005;2410:1468-1482. [CrossRef] [PubMed]
 
Whitson BA, Nath DS, Johnson AC, et al. Risk factors for primary graft dysfunction after lung transplantation. J Thorac Cardiovasc Surg. 2006;1311:73-80. [CrossRef] [PubMed]
 
Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D. ISHLT Working Group on Primary Lung Graft Dysfunction ISHLT Working Group on Primary Lung Graft Dysfunction Report of the ISHLT working group on primary lung graft dysfunction: Part II. Definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2005;2410:1454-1459. [CrossRef] [PubMed]
 
Oto T, Griffiths AP, Rosenfeldt F, Levvey BJ, Williams TJ, Snell GI. Early outcomes comparing Perfadex, Euro-Collins, and Papworth solutions in lung transplantation. Ann Thorac Surg. 2006;825:1842-1848. [CrossRef] [PubMed]
 
Schnickel GT, Ross DJ, Beygui R, et al. Modified reperfusion in clinical lung transplantation: the results of 100 consecutive cases. J Thorac Cardiovasc Surg. 2006;1311:218-223. [CrossRef] [PubMed]
 
Meade MO, Granton JT, Matte-Martyn A, et al. A randomized trial of inhaled nitric oxide to prevent ischemia-reperfusion injury after lung transplantation. Am J Respir. Crit Care Med. 2003;167:1483-1489. [CrossRef] [PubMed]
 
Botha P, Jeyakanthan M, Rao JN, et al. Inhaled nitric oxide for modulation of ischemia-reperfusion injury in lung transplantation. J Heart Lung Transplant. 2007;2611:1199-1205. [CrossRef] [PubMed]
 
Date H, Triantafillou AN, Trulock EP, Pohl MS, Cooper JD, Patterson GA. Inhaled nitric oxide reduces human lung allograft dysfunction. J Thorac Cardiovasc Surg. 1996;1115:913-919. [CrossRef] [PubMed]
 
Fischer S, Bohn D, Rycus P, Pierre AF, de Perrot M, Waddell TK, et al. Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: analysis of the Extracorporeal Life Support Organization (ELSO) registry. J Heart Lung Transplant. 2007;265:472-477. [CrossRef] [PubMed]
 
Kermeen FD, McNeil KD, Fraser JF, et al. Resolution of severe ischemia-reperfusion injury post-lung transplantation after administration of endobronchial surfactant. J Heart Lung Transplant. 2007;268:850-856. [CrossRef] [PubMed]
 
Bharat A, Kuo E, Steward N, et al. Immunological link between primary graft dysfunction and chronic lung allograft rejection. Ann Thorac Surg. 2008;861:189-195. [CrossRef] [PubMed]
 
Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007;35725:2601-2614. [CrossRef] [PubMed]
 
Dauber JH, Paradis IL, Dummer JS. Infectious complications in pulmonary allograft recipients. Clin Chest Med. 1990;112:291-308. [PubMed]
 
Sharples LD, McNeil K, Stewart S, Wallwork J. Risk factors for bronchiolitis obliterans: a systematic review of recent publications. J Heart Lung Transplant. 2002;212:271-281. [CrossRef] [PubMed]
 
Kesten S, Chaparro C. Mycobacterial infections in lung transplant recipients. Chest. 1999;1153:741-745. [CrossRef] [PubMed]
 
Chalermskulrat W, Sood N, Neuringer IP, et al. Non-tuberculous mycobacteria in end stage cysticfibrosis: implications for lung transplantation. Thorax. 2006;616:507-513. [CrossRef] [PubMed]
 
Freeman RB Jr. The ‘indirect’ effects of cytomegalovirus infection. Am J Transplant. 2009;911:2453-2458. [CrossRef] [PubMed]
 
Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med. 2005;56:29-44. [CrossRef] [PubMed]
 
Kumar D, Husain S, Chen MH, et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation. 2010;898:1028-1033. [CrossRef] [PubMed]
 
Solé A, Salavert M. Fungal infections after lung transplantation. Transplant Rev (Orlando). 2008;222:89-104. [CrossRef] [PubMed]
 
Singh N, Husain S. Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management. J Heart Lung Transplant. 2003;223:258-266. [CrossRef] [PubMed]
 
Zamora MR, Nicolls MR, Hodges TN, et al. Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation. Am J Transplant. 2004;410:1635-1642. [CrossRef] [PubMed]
 
Jaksch P, Zweytick B, Kerschner H, et al. Cytomegalovirus prevention in high-risk lung transplant recipients: comparison of 3- vs 12-month valganciclovir therapy. J Heart Lung Transplant. 2009;287:670-675. [CrossRef] [PubMed]
 
Humar A, Kumar D, Preiksaitis J, et al. A trial of valganciclovir prophylaxis for cytomegalovirus prevention in lung transplant recipients. Am J Transplant. 2005;56:1462-1468. [CrossRef] [PubMed]
 
Monforte V, Lopez C, Santos F, et al. A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-seropositive lung transplant recipients. Am J Transplant. 2009;95:1134-1141. [CrossRef] [PubMed]
 
Zamora MR, Davis RD, Leonard C. CMV Advisory Board Expert Committee CMV Advisory Board Expert Committee Management of cytomegalovirus infection in lung transplant recipients: evidence-based recommendations. Transplantation. 2005;802:157-163. [CrossRef] [PubMed]
 
Palmer SM, Limaye AP, Banks M, et al. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation. Ann Intern Med. 2010;15212:761-769. [PubMed]
 
Van Muylem A, Mélot C, Antoine M, Knoop C, Estenne M. Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation. Thorax. 1997;527:643-647. [CrossRef] [PubMed]
 
Gotway MB, Dawn SK, Sellami D, et al. Acute rejection following lung transplantation: limitations in accuracy of thin-section CT for diagnosis. Radiology. 2001;2211:207-212. [CrossRef] [PubMed]
 
Stewart S, Fishbein MC, Snell GI, et al. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant. 2007;2612:1229-1242. [CrossRef] [PubMed]
 
Guilinger RA, Paradis IL, Dauber JH, et al. The importance of bronchoscopy with transbronchial biopsy and bronchoalveolar lavage in the management of lung transplant recipients. Am J Respir Crit Care Med. 1995;1526 Pt 1:2037-2043. [PubMed]
 
Trulock EP, Ettinger NA, Brunt EM, Pasque MK, Kaiser LR, Cooper JD. The role of transbronchial lung biopsy in the treatment of lung transplant recipients. An analysis of 200 consecutive procedures. Chest. 1992;1024:1049-1054. [CrossRef] [PubMed]
 
Hopkins PM, Aboyoun CL, Chhajed PN, et al. Prospective analysis of 1,235 transbronchial lung biopsies in lung transplant recipients. J Heart Lung Transplant. 2002;21:1062-1067. [CrossRef] [PubMed]
 
Chakinala MM, Ritter J, Gage BF, et al. Yield of surveillance bronchoscopy for acute rejection and lymphocytic bronchitis/bronchiolitis after lung transplantation. J Heart Lung Transplant. 2004;2312:1396-1404. [CrossRef] [PubMed]
 
Yousem SA, Martin T, Paradis IL, Keenan R, Griffith BP. Can immunohistological analysis of transbronchial biopsy specimens predict responder status in early acute rejection of lung allografts? Hum Pathol. 1994;255:525-529. [CrossRef] [PubMed]
 
Verleden GM, Dupont LJ, Van Raemdonck DE. Is it bronchiolitis obliterans syndrome or is it chronic rejection: a reappraisal? Eur Respir J. 2005;252:221-224. [CrossRef] [PubMed]
 
Estenne M, Maurer JR, Boehler A, et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002;213:297-310. [CrossRef] [PubMed]
 
Lama VN, Murray S, Lonigro RJ, et al. Course of FEV(1) after onset of bronchiolitis obliterans syndrome in lung transplant recipients. Am J Respir Crit Care Med. 2007;17511:1192-1198. [CrossRef] [PubMed]
 
Jackson CH, Sharples LD, McNeil K, Stewart S, Wallwork J. Acute and chronic onset of bronchiolitis obliterans syndrome (BOS): are they different entities? J Heart Lung Transplant. 2002;216:658-666. [CrossRef] [PubMed]
 
Botha P, Archer L, Anderson RL, et al. Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome. Transplantation. 2008;855:771-774. [CrossRef] [PubMed]
 
Belperio JA, Lake K, Tazelaar H, Keane MP, Strieter RM, Lynch JP III. Bronchiolitis obliterans syndrome complicating lung or heart-lung transplantation. Semin Respir Crit Care Med. 2003;245:499-530. [CrossRef] [PubMed]
 
Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med. 2002;1664:440-444. [CrossRef] [PubMed]
 
Bando K, Paradis IL, Similo S, et al. Obliterative bronchiolitis after lung and heart-lung transplantation. An analysis of risk factors and management. J Thorac Cardiovasc Surg. 1995;1101:4-13. [CrossRef] [PubMed]
 
Husain AN, Siddiqui MT, Holmes EW, et al. Analysis of risk factors for the development of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 1999;1593:829-833. [PubMed]
 
Scott AI, Sharples LD, Stewart S. Bronchiolitis obliterans syndrome: risk factors and therapeutic strategies. Drugs. 2005;656:761-771. [CrossRef] [PubMed]
 
Khalifah AP, Hachem RR, Chakinala MM, et al. Minimal acute rejection after lung transplantation: a risk for bronchiolitis obliterans syndrome. Am J Transplant. 2005;58:2022-2030. [CrossRef] [PubMed]
 
Hachem RR, Khalifah AP, Chakinala MM, et al. The significance of a single episode of minimal acute rejection after lung transplantation. Transplantation. 2005;8010:1406-1413. [CrossRef] [PubMed]
 
Glanville AR. The role of bronchoscopic surveillance monitoring in the care of lung transplant recipients. Semin Respir Crit Care Med. 2006;275:480-491. [CrossRef] [PubMed]
 
Fisher AJ, Rutherford RM, Bozzino J, Parry G, Dark JH, Corris PA. The safety and efficacy of total lymphoid irradiation in progressive bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant. 2005;53:537-543. [CrossRef] [PubMed]
 
Gottlieb J, Szangolies J, Koehnlein T, Golpon H, Simon A, Welte T. Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation. 2008;851:36-41. [CrossRef] [PubMed]
 
Shitrit D, Bendayan D, Gidon S, Saute M, Bakal I, Kramer MR. Long-term azithromycin use for treatment of bronchiolitis obliterans syndrome in lung transplant recipients. J Heart Lung Transplant. 2005;249:1440-1443. [CrossRef] [PubMed]
 
Benden C, Boehler A. Long-term clarithromycin therapy in the management of lung transplant recipients. Transplantation. 2009;8710:1538-1540. [CrossRef] [PubMed]
 
Vanaudenaerde BM, Meyts I, Vos R, et al. A dichotomy in bronchiolitis obliterans syndrome after lung transplantation revealed by azithromycin therapy. Eur Respir J. 2008;324:832-843. [CrossRef] [PubMed]
 
Iacono AT, Johnson BA, Grgurich WF, et al. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006;3542:141-150. [CrossRef] [PubMed]
 
Study of cyclosporine inhalation solution (CIS) in improving bronchiolitis obliterans syndrome-free survival following lung transplantation (CIS001). http://clinicaltrials.gov/ct2/show/NCT00755781?term=lung+transplantation&rank=8. Accessed September 14, 2010.
 
Kawut SM, Lederer DJ, Keshavjee S, et al. Outcomes after lung retransplantation in the modern era. Am J Respir Crit Care Med. 2008;1771:114-120. [CrossRef] [PubMed]
 
Garfein ES, McGregor CC, Galantowicz ME, Schulman LL. Deleterious effects of telescoped bronchial anastomosis in single and bilateral lung transplantation. Ann Transplant. 2000;51:5-11. [PubMed]
 
Shah SS, Karnak D, Minai O, et al. Symptomatic narrowing or atresia of bronchus intermedius following lung transplantation vanishing bronchus intermedius syndrome (VBIS)[abstract]. Chest. 2006;1304:236S
 
Kapoor BS, May B, Panu N, Kowalik K, Hunter DW. Endobronchial stent placement for the management of airway complications after lung transplantation. J Vasc Interv Radiol. 2007;185:629-632. [CrossRef] [PubMed]
 
Herrera JM, McNeil KD, Higgins RS, et al. Airway complications after lung transplantation: treatment and long-term outcome. Ann Thorac Surg. 2001;713:989-993-. [CrossRef] [PubMed]
 
McArdle JR, Gildea TR, Mehta AC. Balloon bronchoplasty: its indications, benefits, and complications. Bronchol. 2005;12:123-127. [CrossRef]
 
De Gracia J, Culebras M, Alvarez A, et al. Bronchoscopic balloon dilatation in the management of bronchial stenosis following lung transplantation. Respir Med. 2007;101:27-33. [CrossRef] [PubMed]
 
Mughal MM, Gildea TR, Murthy S, Pettersson G, DeCamp M, Mehta AC. Short-term deployment of self-expanding metallic stents facilitates healing of bronchial dehiscence. Am J Respir Crit Care Med. 2005;1726:768-771. [CrossRef] [PubMed]
 
Simoff MJ, Sterman DH, Ernst A. Thoracic Endoscopy. Advances in Interventional Pulmonology. 2006; Malden, MA Blackwell Publishing
 
Izbicki G, Bairey O, Shitrit D, Lahav J, Kramer MR. Increased thromboembolic events after lung transplantation. Chest. 2006;1292:412-416. [CrossRef] [PubMed]
 
Yegen HA, Lederer DJ, Barr RG, et al. Risk factors for venous thromboembolism after lung transplantation. Chest. 2007;1322:547-553. [CrossRef] [PubMed]
 
Kahan ES, Petersen G, Gaughan JP, Criner GJ. High incidence of venous thromboembolic events in lung transplant recipients. J Heart Lung Transplant. 2007;264:339-344. [CrossRef] [PubMed]
 
King CS, Khandhar S, Burton N, et al. Native lung complications in single-lung transplant recipients and the role of pneumonectomy. J Heart Lung Transplant. 2009;288:851-856. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
CHEST Collections
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543