A. Graft contaminated with oral flora organisms

Early after transplantation the allograft often encounters diffuse alveolar damage secondary to harvest injury. This type of diffuse injury increases the susceptibility to infections by microorganisms, especially in those with donors who had terminally aspirated. Presence of mouth flora (Neisseria, Hemophilus, viridans Streptococcus, diphtheroids, microaerophilic streptococcus, coagulase negative staphylococcus) in donor tracheal culture (DTC) has been shown to correlate with development of early post transplant infection in the recipient's thorax (pneumonia and mediastinitis). Infectious agents include P. aeruginosa, P. mirabilis, E. aerogenes, Acinetobacter, Candida species, and S. aureus. Although there is no correlation between the infectious isolates and DTC, the onset of early infection may be related to aspiration secondary to prolonged mechanical ventilation. Early infection results in lower 1 year survival of 35% (in contrast to 67% for those without early infection).

B. Anastomosis

Systemic (bronchial) arterial and lymphatic circulation to the lung are not reanastomosed at the time of transplantation and airway circulation depends on collaterals from the pulmonary arteries. Revascularization eventually takes place but not for several weeks. In the meantime, airway ischemia incurred is manifested in bronchial cartilage which may grossly appear as bronchomalacia. Furthermore, abnormal ciliary action in the donor epithelium, bronchial stenosis and lack of cough reflex due to denervation may result in microbial colonization and subsequent complications including abscess formation, dehiscence, and mediastinitis.

C. Alloimmune environment

The immunologic defense in the early allograft consisting of the host as well as the donor immune cells is not efficient in mounting a response against microorganisms. The donor bronchial associated lymphoid tissue (BALT), which normally functions as the primary mucosal defense against environmental pathogens, is one of the prime targets of acute graft rejection. Consequently, BALT in the allograft becomes depleted of lymphocytes and IgA and IgG secreting plasma cells, resulting in heightened susceptibility to infections.

In vitro studies have also shown that the allograft macrophages have impaired chemotactic but not phagocytic functions against microorganisms. There is also a lack of MHC compatibility between the donor macrophages and the recipient lymphocytes, compromising the communication required in mounting a cell mediated immune response.

D. Parenchymal remodeling secondary to Chronic Rejection

The most significant manifestation of chronic rejection is bronchiolitis obliterans (OB). The small airways develop dense scar occluding their lumen as a result of persistent immunologic injury. With time, the parenchyma undergoes remodeling involving not only the airways but also the vasculature, pleura, and interstitium. Interestingly, while the small airways obliterate, the large airways develop cylindrical bronchiectasis. Such changes result in altered airflow, decreased mucus clearances, and loss of ciliated respiratory epithelial cells. These airways are readily colonized by gram negative rods, particularly pseudomonas. Under these compromised circumstances, acute bronchitis and pneumonia are common complications.

E. Influence of Primary Disease

Patients with cystic fibrosis are known to have their upper airways and sinuses colonized by Pseudomonas species (aeruginosa and/or cepacia). Subsequent downstream infection in the allograft lung is common. Unfortunately, these Pseudomonas species are often resistant to currently available antibiotics and fatal results may ensue.

In patients receiving single lung transplants, the remaining structurally altered native lung may harbor infection and seed the allograft. Cases of invasive aspergillosis occurring in the native lung have been reported in patients with emphysema secondary to alpha-1-antitrypsin deficiency. In such circumstances, surgical intervention may be necessary if medical antimicrobial therapy fails.

F. Immunosuppression

The overall graft susceptibility depends on the type as well as the dose of immunosuppression. Survival of the graft depends on the balance between immunosuppression and rejection, since patients experiencing few and minor rejection episodes can expect to be maintained on low doses of immunosuppression consisting of cyclosporine (or FK506), prednisone, and/or immuran. However, the administration of pulse doses of steroids or antilymphocyte globulins during episodes of significant acute or active chronic rejection increases the susceptibility for infection.

Factors NOT thought to be associated with increased susceptibility: laterality of allograft, age, gender, and duration of cardiopulmonary bypass.