Infections in the Lung Transplant
Organ transplant recipients are susceptible to infection
their generalized immunosuppressed state. Furthermore, the allograft lung has
increased susceptibility due to its direct communication with the environment. The
lung transplant recipient experiences on average 3 episodes of infectious
complications and the type of infection depends on the clinical setting of the
transplanted patient (e.g. harvest injury, complication from primary disease,
airflow obstruction from chronic airway rejection). Therefore, awareness of the
clinical setting enhances diagnostic accuracy. This discussion will cover the
general mechanisms of infection, factors leading to increased susceptibility in the
allograft, types of infections, and the histologic differential diagnoses.
II. General Mechanisms of infection compared to other immunologic
In the respiratory tract, microorganisms either exist in
symbiosis with the airway tissue without causing disease (colonization) OR produce
disease by breaking through the defense barriers and invading into the parenchyma.
The balance between the host's immune system and the virulence of the microorganism
depends on a number of factors which evolve over the life of the allograft.
Airway Defense Barriers: Ciliated respiratory epithelium,
cough reflex, mucociliary clearance, reflex bronchoconstriction, immune effector
Alveolar Defense: Alveolar fluid contains surfactant,
phospholipids, enzymes, albumin, transferrin, alpha-1-antitrypsin, immunoglobulins,
and complement. Alveolar cells consist of macrophages (85%), lymphocytes (10%),
neutrophils (2%), eosinophils (<1%).
The same cell mediated immunologic process which participates
in defense against microorganisms also targets the donor histocompatibility
antigens. Acute cellular rejection involves CD4+ T-cells infiltrating the
allograft, predominantly in the perivascular and peribronchiolar regions. The
hallmark of chronic rejection is the development of irreversible scarring,
compromising the lumen of the small airways and the vessels. Interestingly, during
the active phase of chronic rejection, the predominant mononuclear cell type shifts
to CD8+ T-cells. In very active ACR and CR, there may be extensive tissue damage
with neutrophilic infiltration as a response to the necrosis. With prolonged
luminal compromise, the airways are colonized by microorganisms, which may later
become invasive. In such cases, the distinction from infection becomes difficult
and may be impossible at times.
C. Post Transplant Lymphoproliferative Disorder
PTLD is thought to be a lymphoproliferation of EBV infected
B-cells arising in the setting of over immunosuppression. The patients at risk are
those who encounter EBV as a primary infection during the post-transplant course.
The proliferation may be seen anywhere lymphoid tissue presides, although in lung
transplant recipients, presentation in the allograft is relatively common.
Histopathological manifestation appears as nodular sheets of atypical lymphoid cell
which are not dissimilar to Non-Hodgkins lymphomas. Some cases are similiar to
lymphomatoid granulomatosis or T-cell rich B-cell lymphomas with a large subset of
reactive T-cells. Reduction in immunosuppression often results in regression of