reported to cause diverse clinical symptoms including fever, skin rash, pneumonia, bone
marrow suppression, encephalitis, and rejection.
The respiratory viruses, particularly respiratory syncytial virus, influenza, parainfluenza,
adenovirus, and picornavirus, are increasingly recognized as significant pathogens in these
populations. Adenovirus may also cause pneumonia, occasionally with dysfunction of the
allograft (123). Respiratory syncytial virus and influenza have been found to be the most
common of the respiratory viruses causing severe infections in transplant recipients (124–130).
New antiviral medications may bring improved outcomes of picornavirus infections in this
population. Finally, a new virus, the human metapneumovirus, has recently been described
and may be a significant respiratory pathogen in immunocompromised transplant recipients,
particularly lung recipients. In this population, human metapneumovirus is a leading cause of
acute respiratory tract illness. The incidence and clinical spectrum at presentation are similar
to RSV, although the latter seems to be associated with a higher risk of chronic rejection
(131,132). Respiratory viruses may be associated with high morbidity, particularly in lung
transplant recipients and may appear as “culture-negative” pneumonia. Molecular methods,
such as reverse transcription-PCR assays allow the identification of respiratory viruses in
bronchoalveolar lavage (BAL) specimens (133). Advances in prevention, particularly with
regard to infection control practices, and to a lesser extent treatment have had a substantial
impact on the frequency and outcomes of this infection.
Considering the high mortality that some of these pathogens condition, the prompt
detection of the etiology is of the utmost importance. As with other critical patients,
differentiating pneumonia from other etiologies of pulmonary infiltrates can be extremely
difficult. In liver transplant patients, a CPIS score>6, abnormal temperature, and renal failure
(serum creatinine>1.5 mg/dL) were significant predictors of pneumonia (41). It is important
to bear in mind that some drugs, such as sirolimus, may cause pulmonary infiltrates (134).
Patients may develop dyspnea, cough, fatigue, and sometimes fever. Characteristic radio-
logical changes are bilateral lower-zone haziness. The presentation ranges from insidious to
fulminant, and usually there is a rapid response to sirolimus withdrawal.
Chest X rays predominantly show alveolar or interstitial infiltrates of variable extension.
However, nodular lesions are not uncommon. The differential diagnosis of a lung nodule in a
normal host includes many malignant and benign processes. However, in immunosuppressed
patients the most common causes are potentially life-threatening opportunistic infections that
may be treated and prevented. We have detected single or multiple lung nodules on the chest
radiograph in 10% of our HT patients (101).Aspergillusinfection was detected early after
transplantation (median 38 days, range 23–158), whereas N. asteroides and Rhodococcus
infections developed only later (median 100 days, range 89–100). Nodules due to CMV
occurred 16 to 89 days after HT (median 27 days). Patients withAspergilluswere, overall, more
symptomatic and were the only ones in our series to present neurological manifestations and
hemoptysis. CT is more sensitive than standard chest X ray in identifying the number of
lesions and may assist guided biopsy.
Etiological diagnosis is mandatory considering that only 50% of the empirical treatments
of pneumonia in HT patients are appropriate (64). For this reason, fast diagnostic procedures
that guide antimicrobial treatment are necessary. Etiological diagnosis may be performed by
using different techniques, so this requires careful tailoring to each single patient. Once
pneumonia is identified, blood cultures, respiratory samples for culture of bacteria,
mycobacteria, fungi, and viruses and urine forLegionellaandS. pneumoniaeantigen detection
must be sent to the laboratory (if possible, before starting antimicrobials). The rate of expected
bacteremia in patients with pneumonia is 16% to 29% (135). Demonstration of pathogenic
microorganisms (M. tuberculosis, Legionella, Cryptococcus, R. equi,orP. jiroveci) in a sputum
sample is diagnostic. PCR techniques may help improving diagnostic sensitivity (85). A
bronchoscopic sample with bronchial biopsy is preferable for CMV,Aspergillus,P. jiroveci,or
Legionellapneumonia. If pleural fluid is present it should also be analyzed. In our series of
nodular lesions in HT patients, etiological diagnosis was established within a median of eight
days (0–24) (Table 3). A median of 1.8 invasive techniques per patient was necessary to achieve
the diagnosis. Overall diagnostic yield was 60% for transtracheal aspiration, 70% for BAL, and
75% for transthoracic aspiration. BAL was the first positive technique in 58% of the patients.
396 Mun ̃oz et al.