The role of fibre-optic bronchoscopy in solid organ, transplant patients with pulmonary infections

RESPIRATORY MEDICINE

(1999) 93, 621-629

The role of fibre-optic bronchoscopy in solid organ, transplant patients with pulmonary infections S. NLJSAIR*

AND

M. R. KRAMER?

*The Pulmonary Institute, The Hadassah University Hospital and Hebrew University-Hadassah Medicine, Jerusalem, Israel +The Pulmonary Institute, Rabin Medical Center, Petah-Tikvah, Israel

School of

Organ transplantation is currently the standard therapy for patients with end-stage organ dysfunction. The immunosuppression caused by this therapy increases the rate of infection, particularly in the lungs. Early diagnosis is extremely important and fibre-optic bronchoscopy is a helpful tool in reaching diagnosis. Knowing the timing of various pathogens following transplantation, and the radiological picture as well as the prophylactic regimen, is helpful when specific pathogens are suspected. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsies are particularly helpful in diagnosis of bacterial cytomegalovirus (CMV) and pneumocytosis carinii pneumocytosis, and is considered a safe procedure. Open lung biopsy is reserved for those who have negative bronchoscopy with a reasonable prognosis. RESPIR. MED.

(1999) 93, 621-629

Introduction In the last decade an increasing number of immunocompromised patients have come to medical attention because of pulm,onary infiltrates of various aetiologies. Solid organ transplant recipients form an important and an increasingly growing subgroup of immunocompromised patients. Transplant patients may present at any time interval after the transplant with infections caused by bacteria, viruses, parasites or ftingi. In making the clinical decisions regarding the investigation and the management of these patients, different factors should be taken into account such as the type of immunosuppression, the transplanted organ adjacent to which the infectious process is taking place and the timing of the appearance of pulmonary infiltrates following the transplant. ‘Moreover, as the lung is exposed to the immediate surrounding environment, it is more likely to be exposed to infectious pathogens from the environment, particularly in lung transplant patients as the transplanted lung is markedly vulnerable to such infections. As a result of immunosuppressive therapy, the clinical manifestations of pulmonary infections in the transplant patient may be variably attenuated (e.g., corticosteroids

Paperreceived4 August 1998and acceptedin revisedform 20 April 1999. Correspondenceshould be addressedto: Mordechai R. Kramer, MD, Institute of Pulmonology, Rabin Medical Center, PetahTikvah 49100,Israel. Fax: +972-3-9216188 0954-6111/99/090621+09 $12.00/O

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decrease fever and azathioprine may induce leukopaenia). Similarly, the spectrum of roentgenographical findings is not different from normal hosts and may include lobar or localized infiltrates which may contain cavitations as in fungal pneumonia, or interstitial infiltrates common in other opportunistic infections such as Cytomegalovirus (CMV) pneumonitis and Pneumocystis carinii pneumonitis (PCP). The finding of pulmonary infiltrates on chest x-ray films may be otherwise explained by pulmonary congestion, embolism or alveolar haemorrhage. It is most important to recognize pulmonary infections as they carry a great risk for morbidity and mortality in these patients. The role of conventional methods of diagnosing pneumonia in the immunocompromised host are limited. The serological methods for the diagnosis of viral pneumonias such as caused by CMV have low sensitivity and specificity in the immunocompromised host because of decreased antibody production, due to immune suppression (1). The yield of sputum staining and culture in normal hosts is usually low, especially in atypical pneumonia. Therefore, many immunocompromised patients who are more likely to present with atypical pneumonias do not produce sufficient sputum to allow identification of a bacterial or other pathogen. The purpose of this review is to describe the current knowledge regarding the diagnostic yield of fibre-optic bronchoscopy (FOB) when utilized for thi investigation of pneumonias in solid organ transplant patients. Emphasis will be put on opportunistic pathogens such as Pneumocystis carinii and CMV, which are unique pathogens in .> these patients. 0

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7 6

I (a)

< 30 days

% %

0.8

2F

0.7

is

0.6

2-6 months

> 6 months

0.5 0.4 0.3 0.2 0.1 0

< 30 days Time

2-6 months > 6 months after transplantation

0 c 30 days

2-6 months z 6 months Time after transplantation

FIG 1. The incidence of specific pulmonary pathogens in ( q , bacterial; H, viral/CMV; q J,PCP; q fungal) organ transplant recipients at various time intervals after transplantation (incidence is described as events patient-’ year-‘) (3,4,8,73). (a) Heart-lung transplantation; (b) liver transplantation; (c) heart transplantation; (d) kidney transplantation.

Timing and types of various infections in organ transplantation

Special considerations heart-lung recipients

in lung and

In order to evaluate the role of FOB for pulmonary infiltrates in solid organ recipients, the types and timing of the various infections after transplant should be considered. Pulmonary infections in organ transplant patients are mostly caused by bacterial pathogens. During the first l-2 months after transplantation, there is a higher incidence of bacterial pneumonias caused by hospital-acquired pathogens (Gram-negative rods, staphylococci or Legionella pneurnophila), but in later stages pneumonia may be caused by community-acquired pathogens, such as Streptococcus pneumoniae or Mycoplasma pneumoniae (2). During the time interval of 2-4 months post-transplantation, there is a significant increase in the incidence of CMV-induced pneumonitis (Fig. 1). Additionally, there is a rise in the rate of fungal infections with an epidemiology which may partly reflect the incidence of endemic fungal infections, but also an increasing incidence of invasive Candida species and Aspergillosis infections. The incidence of PCP increases significantly 2-3 months post-transplantation and remains high during the first 6 months after transplantation. The differential diagnosis of new-onset pulmonary infiltrates in organ transplant patients also includes tuberculosis, nocardiosis, and malignant processes such as lymphoma and Kaposi’s sarcoma.

Infections involving the grafted lung in lung and heart-lung transplant recipients deserve special consideration. The susceptibility of the grafted lungs to infections results from local factors such as changes in the lymphatic drainage of the lungs. Denervation of the lungs and the anastomosis itself suppress the cough reflex, thus masking symptoms of pulmonary infection (3). Of the local immunological factors which affect the grafted lung, immune suppression plays a central role as a risk factor for bacterial and opportunistic pneumonia, as it increases the vulnerability of the grafted lung to pathogens. Additionally, allograft rejection can cause lung injury, leading to further damage to lung tissue structure such as the tendency to develop bronchiectasis in patients with post-transplant bronchiolitis obliterans, thus adding significant risk for infection. Moreover, in patients with a single lung transplantation, the remaining lung may serve as a source of infection. Similar to the sinuses in patients with cystic fibrosis. All these factors explain the higher rate of pulmonary infection in patients after heart-lung transplantation than after heart transplantation alone (4). Accordingly, lung and heart-lung transplant recipients not only have a higher incidence of bacterial pneumonia, but also of CMV pneumonitis and PCP, compared with heart transplant recipients.

FIBRE-OPTICBRONCHOSCOPYINTRANSPLANTPATIENTS 623 TABLE 1. The diagnostic yield of BAL and TBB in solid organ transplantation

Reference

Bronchoscopies (n>

Yield of BAL w>

Yield of TBB w>

Yield of BAL for specific pathogen (%)

Yield of TBB for specific pathogen (%)

Schulman (21)

39

63

46

CMV (20) PCP (89) Asperg (22) TB (NA)

Sibley (73)

128

NA

78

CMV (61) PCP (90) Asperg (75) TB (50) Bacterial (60) NA

Lung

Baz (22)

69

NA

48

NA

Lung/Heart-lung

Chan (23)

282

NA

67

NA

Cazzadori (4) Wallace (5) Sternberg (6)

33 7 58

27 85 69

57 NA NA

NA NA CMV (22) PCP (10) Bacterial (17)

Organ transplanted

Heart

Lung/Heart-lung

Kidney Kidney Kidney

Nocardia Legionella

Kidney Liver

Willcox (74) Allen (75)

28 54

NA* 42

45 NA

CMV (3) PCP (3) Rejection (40) TB (0.7) CMV (11) Bacterial (9) Rejection (3 5) CMV (8) PCP (I) Bacterial (80) Rejection (28) NA NA NA

(5) (7)

Fungi (7) NA PCP (22) CMV (22) HSV (7)

NA NA

Asperg, Aspergillosis: BMT, bone marrow transplant: CMV, cytomegalovirus: HSV, herpes simplex virus: NA, not available: PCP, Pneumocystis carinii pneumonitis: TB, tuberculosis. *Three patients underwent BAL which was positive.

The high incidence of pulmonary graft rejection and bacterial infections within the first few weeks after transplantation, combined with the increased incidence of CMV pneumonitis during 2-6 months after transplantation, has led to the use of routine surveillance broncho scopies during the first 2 years after transplantation in many centres.

Fibre-optic

bronchoscopy

(FOB)

FOB, with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB), has played an important role in the diagnosis of pulmonary infiltrates in the immunocompromised patient in the last decade. This minimally invasive procedure allows the identification of pulmonary pathogens by sampling of bronchoalveolar lavage fluid or by direct histopathological examination of lung tissue. These methods facilitate sampling of the distal airways for

cultures and cytological stains in an attempt to detect pathogens which reflect true distal airway infections, with much lessrisk of contamination by the oral and the upper airway flora, or by pathogens which merely colonize the upper airways (5). Several recent studies have attempted to evaluate the utility of BAL and TBB ‘in the immunocompromised host. In one retrospective study, the results of 157 bronchoscopic procedures, including both BAL and TBB, in 142 immunosuppressed patients were reviewed (see Table 1) (6). All patients were treated with empirical wide-spectrum antibiotic therapy prior to performing FOB with no satisfactory response. In the specific group of kidney transplant patients, BAL had a diagnostic yield of 27%. However, the diagnostic yield of TBB was 57.5%. The total additional diagnostic yield of TBB to BAL was 33 %. These results suggest an important role for TBB in addition to BAL whenever there is no additional significant risk and no contraindications to performing TBB.

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In another study (7) 19 bronchoscopies with BAL were performed to evaluate acute pulmonary infiltrates in a group of 18 immunocompromised patients, including AIDS patients, organ transplant patients and patients with solid tumours who were receiving cytotoxic chemotherapy. The bronchoscopy yielded a definite diagnosis in 72% of these patients. As a result of the overall findings at bronchoscopy, management was changed in 61% of the patients. In the group of patients who had BAL alone without an additional TBB, BAL was diagnostic in 75% of the patients and treatment management was consequently changed in 42%. Retrospectively, these results showed that the initial clinical diagnosis was correct in only 56% of the patients and that empirical therapy would have lead to incorrect management in 28%. These results demonstrate the importance, of performing BAL at an early stage after presentation with pulmonary infiltrates. In this series however, performing TBB did not increase the diagnostic yield. In a subgroup of seven renal transplant recipients, the diagnostic yield of bronchoscopy was 85% and the sensitivity was 71%, but with no additional diagnostic value for TBB compared to BAL. In another retrospective analysis, Sternberg et al. (8) evaluated kidney transplant recipients who had a combination of fever, pulmonary infiltrates and/or hypoxia. In 40% of these patients, the results of BAL lead to a change in the initial empirical antibiotic therapy. During the first 4 months, CMV infection was common, as would be expected (2). In instances where co-infections were found, CMV was the most common pathogen. Of five patients with PCP, three patients had also findings of CMV pneumonitis on histological examination. Two additional patients had proven CMV viremia, with no evidence of CMV pneumonitis on lung biopsy. Thus this study demonstrates that TBB serves an important role in recognizing co-infection with bacterial infection and viral or parasitic pathogens. In caseswhere CMV iS isolated in BAL fluid or CMV viremia is detected, a definite diagnosis of CMV pneumonitis could be determined by identifying CMV inclusion bodies within the pulmonary parenchyma.

The diagnostic utility of FOB for specific pathogens BACTERIAL

PNEUMONIA

Pneumonias caused by bacteria are most likely to occur within the first few weeks after transplantation (2), with lung and heart-lung transplantation patients being the most vulnerable (1,3). Transplant patients are more likely to be exposed to prolonged antibiotic treatment, be mechanically ventilated, have an in-dwelling nasogastric tube, or be given antacid therapy which elevates the stomach content pH: all well-known risk factors for nosocomial pneumonia. The most likely pathogens during the first weeks after transplant, include nosocomial pneumonias such as those caused by Gram-negative rods and Staphylococcus aureus. However, community pathogens such as Streptococcus

Pneumoniae, Haemophilus Influenza and Mycoplasma pneumoniae may also causepneumonia in these patients and are

still predominant in the later stages after the transplant procedure (l-3). Nosocomially acquired, Legionella infections tend to occur in the first few weeks after transplant. Characteristically, they are accompanied by changes in mental status and gastrointestinal disturbances, with widespread chest radiographical changes (9). Nocardia, particularly asteroides, is increasingly recognized as a pathogen of the late stages after solid organ transplantation, particularly in renal transplant patients, with an incidence of about 2% (10,ll). Besidesthe lungs, Nocardia has predilection for the skin and the brain. Interestingly, the incidence of nocardiosis in transplant patients has decreased since the use of cyclosporine compared with patients who received azathioprine in their immunosuppressive regimens (11). The routine administration of trimethoprim-sulphamethoxazole for prophylaxis in PCP has caused a reduction in bacterial and Nocardia infection, as noted after renal transplantation (14). Pseudomonas aeruginosa may be an important pathogen in early post-operatively stages and when lung transplantation is performed in patients with cystic fibrosis (12). Pseudomonas pneumonia is also seen at later stages after lung transplantation because of bronchiectatic changes in the lung parenchyma secondary to chronic inflammatory processes such as bronchiolitis obliterans (13). Some authorities have advocated the regular use of quinolones after bone marrow transplant (BMT) as prophylaxis for bacterial infections, but this is not routinely used in solid organ transplant recipients (15). It may be difficult to determine the incidence of bacterial pneumonias in transplant patients due to the low yield of standard methods in identifying bacterial pathogens and the high frequency of bacterial colonization of the airways. In a large group of BMT patients, the specific bacterial pathogens were identified in 52% of the infectious episodes of bacterial pneumonias which could not be explained by opportunistic pathogens or non-infectious processes(16). FOB with quantitative protected specimen brushing (PSB) and BAL cultures may significantly aid in investigating possible lower respiratory tract infections and distinguish them from bacterial colonization. (17). It is acceptable to diagnose pneumonia if the cultures of specimens acquired by protected specimen brushing (PSB) and BAL have bacterial organism counts above a certain threshold concentration. [i.e. PSB > 103, and BAL > lo4 colony forming units per ml (cfu/ml)] (17). PSB is a method with higher diagnostic specificity than simple sputum or sample is acquired by endotracheal aspiration for the diagnosis of nosocomial pneumonia and may better differentiate true infections from contamination. Several studies reviewing the results of bronchoscopic procedures in immunocompromised hosts including transplant patients have shown additional yield with BAL for diagnosing bacterial pneumonia (1X-20). The identification of Nocardia on a sputum smear requires a Ziehl-Nelsen stain but the culture may take 34 weeks to become positive (10). Legionella may be difficult to grow; however, examining respiratory secretionsusing the direct fluorescent antibody technique may allow a faster diagnosis (9). In

FIBRE-OPTICBRONCHOSCOPYINTRANSPLANTPATENTS

patients after heart transplantation, the sensitivity of BAL or PSB for identifying bacterial pathogens was 60% (21). Although FOB is useful for surveillance purposes after lung transplantation, the yield of the procedure is significantly increased when it is performed to evaluate a new infiltrate (8.7 vs. 0.6%) (22). A higher diagnostic advantage of PSB compared with BAL may result from a cautious policy followed by certain bronchoscopists, in which small amounts of fluid are used (24). These data support the use of BAL and PSB in evaluating transplant patients with new pulmonary infiltrates, as these methods improve the diagnostic yield of bacterial pneumonia and aid in differentiating bacteria from other non-bacterial pathogens.

Pneumocystis

carinii

This is a common protozoan pathogen in immunocompromised patients in whom T-lymphocyte dysfunction is a dominant mechanism of immune dysfunction. PCP is the most common opportunistic pulmonary infection in AIDS (20) strongly suggesting that Pneumocystis carinii exists in a latent form in normal hosts and is reactivated as the host’s immunity level is reduced. In organ transplant patients, PCP is most likely to occur within the first 2-6 months after transplant (2). Of organ transplant patients, lung and heart-lung transplant patients are particularly vulnerable to PCP (3,4). Very effective prophylaxis for the prevention of PCP after organ transplantation has been achieved by providing patients with oral trimethoprim-sulphamethoxazole (24,2.5) and, to a lesser degree of success, with inhalations of pentamidine ( 26). The diagnostic utilities of BAL and TBB for the diagnosis of PCP are comparable (6,21). This may be explained by the fact that Pneumocystis carinii is present in the alveoli (27-29), unlike CMV which is an intracellular pathogen, thus the yield of BAL in detecting CMV is relatively lower than the yield of detecting Pneumocystis

. .. camzz.

VIRAL

INFECTIONS

The incidence of herpetic infections in organ transplant patients increases significantly 4 weeks after organ transplantation. Primary infections, or reactivation of herpes simplex virus and herpes varicella virus are commonly characterized by their diagnostic cutaneous rashes (1,2). CMV is an important pathogen of pneumonia in transplant patients. In bone marrow recipients, CMV may play an important role in immune reactions, such as the induction and propagation of graft .versus host disease in the lung (30-32) and the pathogenesis of bronchiolitis obliterans (30,33). Such an association between bronchiolitis obliterans and CMV infection has been suggested in lung transplant patients has not been clarified (3,34). In lung and heart-lung transplant patients, surveillance bronchoscopies are routinely performed within the first 4-6 months in many centres (22,35) to allow early detection of

625

graft rejection or CMV pneumonitis. The definite diagnosis of CMV pneumonitis may be determined on the basis of CMV inclusion bodies within the lung parenchyma, obtained through TBB (3), or the presence of cells with cytopathic changes typical of CMV within the BAL fluid. Growing CMV in BAL cultures is not considered definitely diagnostic of CMV pneumonitis because it may only reflect viral shedding or colonization of the respiratory tract with CMV (36). However, in BMT patients there are indications that obtaining CMV from BAL cultures may be predictive of an episode of CMV pneumonitis (37,38). In organ transplant patients, growing CMV from BAL culture has a low positive predictive value for CMV pneumonitis. On the other hand, the detection of CMV inclusion bodies or antigenaemia may be predictive (39,40). In general, BAL has a higher sensitivity than TBB for detecting CMV (23,41). The reported yield of BAL for the diagnosis of CMV pneumonitis is 1463% (7,21), while TBB yields diagnosis in 20% of cases(21). A recent study has suggested that negative BAL culture in a lung graft can exclude CMV pneumonitis in most cases(42). Confirmation of the CMV diagnosis may possible using centrifugation culture (43) the shell vial culture technique (44), monoclonal antibodies (45) or the polymerase chain reaction (PCR) (46). Although these methods may be more sensitive and allow earlier diagnosis of CMV infection than BAL cytology, they have low specificity and thus their results must be interpreted cautiously.

FUNGAL

INFECTIONS

Fungal infections play an important role in morbidity and mortality in organ transplant patients. Essentially, the diagnosis of fungal pneumonia requires the demonstration of the fungal pathogen within the lung parenchyma. The incidence of fungal pneumonia increasessignificantly in the first 2 months after transplant (1,2). The most important fungal pathogens are Candida and Aspevgillus. While Candida mostly involves the upper tracheobronchial tree, Aspevgillus is capable of dissemination and invading the whole lung (27). , Immunocompromised patients who are particularly susceptible to Aspergillus infections. are granulocytopenic patients or those with cellular immunodeficiency. BMT patients are at a very high risk for Aspergillus infection within the first month after transplant (30) and the infection carries a high mortality rate. Aspergihs is the most common cause of fungal pneumonia in liver and kidney transplant patients (1). Twenty-five per cent of patients may develop a pulmonary infection with Aspergillus after lung transplantation, with the majority of these infections occurring within the first month (3). Trachea-bronchial involvement with invasive Aspergillus may further extend to involve the cartilage of the main bronchi (47). Other fungal pathogens in immunocompromised patients include Cryptococcus neojiormans, which may cause concurrent pulmonary and central nervous system infections (48), Mucormycosis, which is ,more likely to occur in

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KRAMER

diabetic and acidotic kidney transplant patients (49): and endemic fungi such as Histoplasmosis and Blastomycosis which cause pulmonary infection with a later dissemination (2). It has been shown that, in diagnosing fungal pneumonia, TBB has an additional diagnostic yield of 29% relative to BAL stain and culture (50). In a mixed group of immunocompromised patients, BAL had a very high sensitivity but a relatively low specificity for the detection of Candida infection (51); however, the specificity of finding other fungi within BAL secretions is much higher, with a relatively lower sensitivity (52,53). These findings strongly suggest that the presence of Candida in the BAL fluid may represent colonization by Candida rather than infection or contamination of the endoscopic instrument as it passes through the upper respiratory tract. Using PSB can overcome this problem of contamination, thus significantly increasing the yield of FOB for detection of fungal infection (51). The diagnostic sensitivity and specificity of BAL may be enhanced by culturing the secretions for fungi (53). Unfortunately, in invasive fungal infection such as Aspergillus, BAL is not capable of demonstrating blood-vessel invasion (53); therefore there TBB still has an important role in the diagnosis of pulmonary fungal infections. In many cases where FOB cannot make the diagnosis of fungal pneumonia, an open lung biopsy is required.

Mycobacferium mycobacferia

tuberculosis

diagnosis of TB through histological findings on TBB. Interestingly, similar findings regarding the yield of FOB for the diagnosis of TB in non-immunocompromised patients have been described (60) and suggest that sputum smear and culture are more reliable and cost-effective whenever sputum can be obtained (61). Generally the yield of TBB in the diagnosis of TB is higher than that of BAL. In a mixed subgroup group of immunocompromised patients only 50% patients had a BAL diagnostic for TB. (7). Newer diagnostic methods based on PCR technology may allow who had TB diagnosed by TBB, earlier diagnosis of TB in transplant patients who are iess likely to have a high load of TB bacilli, thus enabling early diagnosis by positive microscopic examination or growth on culture (62,63). In patients who are suspected clinically to have TB but who have negative results of acid-fast smear, a positive PCR result would encourage the initiation of antituberculous therapy at least until the final results of mycobacterial culture are available (63). However, it must be kept in mind that most of the PCR kits available today have a relatively low specificity. To summarize, there is an important role for TBB in patients suspected of having TB, in whom BAL fluid staining and culture may be inadequate for diagnosis. However, whenever sufficient sputum specimens can be obtained, these samples must be examined adequately as they have a high diagnostic yield and may omit the need for FOB. If FOB is performed, then the procedure should include TBB.

(TB) and other

TB in transplant patients mostly reflects the reactivation of an old TB focus. Another possible source of infection is the grafted organ (2). In the Western world, the incidence of mycobacterial infections after organ transplantation approaches I%, compared to an incidence of 0.1% in the general population, with 30% of the infections caused by atypical mycobacteria (54). In endemic areas, the incidence of TB infection among renal transplant patients may rise to 10-12’~ (55,56). Most of these infections occur at least 6 months after transplantation (57). Although the lungs are the main target organ involved in TB, there is a higher incidence of extrapulmonary disease in these patients than in normal hosts (2). Atypical mycobacteria also tend to be disseminated and may primarily involve cutaneous and articular tissue rather than presenting as a primary pulmonary infection (58). The recent resurgence of TB with the AIDS epidemic has lead to a re-evaluation of the diagnostic yield of bronchoscopy for the diagnosis of TB. In HIV-positive patients, acid-fast smears of specimens collected by BAL were positive in 19% of cases, while an equal percentage of transbronchial biopsies had granulomata within pulmonary tissue with a minimal percentage having positive acid-fast tissue staining (59). Culture of FOB specimens in the same study yielded Mycobacteria in 62% of the BAL specimens and 52% of the TBB specimens. Notably, the yield of sputum cultures was 89%. Nevertheless, using FOB in these patients proved to be important as it allowed early

Complications TBB is associated with a relatively low incidence of complications. The risk of complications after TBB in immunocompromised hosts does not exceed that of the general population. Unfortunately, thrombocytopaenia, which is common in BMT patients, and uraemia in renal transplant patients, prevent the performance of TBB in many casesbecause of the risk of bleeding. In one study, only four out of 106 (3.7%) patients had complications, of whom three had pneumothorax and one an intrapulmonary haemorrhage, with no known coagulopathy (5). In patients with pulmonary hypertension, intrapulmonary haemorrhage may be an important concern. In a recently described series of heart transplant patients who underwent TBB, only 15% had minimal intrapulmonary haemorrhages with volumes of lessthan 25 ml (21).

OPEN LUNG

BIOPSY (OLB)

In cases where FOB is not diagnostic; OLB should be considered. This method is considered the gold-standard for evaluation of lung infiltrates in the immunocompromised host. OLB is performed in up to one-third of these patients due to failure of previous less invasive diagnostic procedures, or due to rapid deterioration in the general state of the patient despite an adequate trial of empirical therapy. In a mixed group of 61 patients, OLB led to a

FIBRE-OFTICBRONCHOSCOPYINTRANSPLANTPATIENTS

definite diagnosis in 34 (56%) (64). Of these patients, 36% were immunosuppressed and OLB, while diagnostic in 59% of cases, led to a change of treatment in 77% of the patients. In a recent.retrospective review of the utility of OLB in a mixed group of patients, the subgroup which seemed to benefit most OLB were immunosuppressed patients (with only one patient after organ transplantation), as they had a high yield with the highest rate of unexpected diagnoses leading to a change in therapy (65). Unfortunately, this benefit was offset by a high mortality rate, which reflects the worse prognosis of this group of patients, resulting from their underlying conditions. OLB may lead to a change in the therapeutic strategy in one-third of lung transplant patients (66). The results from OLB in lung transplant patients suggest that it may be more important, and more likely to lead to a change in therapeutic strategy, when it is used for pulmonary infections, which appear at a later stage after transplant, compared with infections occurring within the first month (66). In heart transplant recipients, OLB was diagnostic in 78% of the patients in one series (67). Earlier studies have cast doubts on whether OLB is able to improve survival of patients with pulmonary infiltrates, probably reflecting the severity of the condition of these patients (68,69). The presence of several pathogens simultaneously may be partly responsible for this bad outcome (69). The general rate of complications of OLB is ll-18% (64,70,71), which result mainly from surgical technique. Such complications include bronchopleural fistulas and persistent air leak, which may require prolonged mechanical ventilation (64). There was no increase in the rate of infections related to the procedure in immunocompromised patients compared with normal hosts despite their vulnerability to such infections (64). Despite evidence that OLB in immunocompromised patients is very helpful in investigating opportunistic infections, especially those occurring at a late stage after transplant, it is still considered an invasive method which carries a certain risk for morbidity and mortality. Nevertheless, OLB remains the final diagnostic resort whenever FOB fails to provide a proper diagnosis in transplant patients with pulmonary infiltrates.

Conclusion The data presented were reflect the importance of early FOB in patients after organ transplantation, as this may lead to the early identification of pathogens in patients presenting with pulmonary infiltrates and fever. Due to the wide variety of possible infectious and noninfectious causes of pulmonary infiltrates in solid organ transplant patients, we recommend early performance of FOB, including TBB, whenever there is no contraindication. Such an approach will enable the prompt treatment of life-threatening complications and will protect the patient from unnecessary measures, which carry a high risk of morbidity.

627

FOB and TBB are relatively safe with a low rate of complications in solid organ transplant patients, and carry no excess rate of morbidity relative to non-transplant or non-immunocompromised patients. Even in critically ill transplant patients, there is a favourable risk-benefit ratio for performing FOB, due to the diagnostic information provided by BAL and TBB.

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