Infections in the Lung Transplant
III. Factors associated with infectious susceptibility in the
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
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).
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
manifested in bronchial cartilage which may grossly appear as bronchomalacia.
Furthermore, abnormal ciliary action in the donor epithelium, bronchial stenosis
lack of cough reflex due to denervation may result in microbial colonization and
subsequent complications including abscess formation, dehiscence, and
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
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
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
fatal results may ensue.
In patients receiving single lung transplants, the remaining
structurally altered native lung may harbor infection and seed the allograft.
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
The overall graft susceptibility depends on the type
as well as
the dose of immunosuppression. Survival of the graft depends on the
immunosuppression and rejection, since patients experiencing few and minor
episodes can expect to be maintained on low doses of immunosuppression
cyclosporine (or FK506), prednisone, and/or immuran. However, the
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