Current Practices in the Management of Respiratory Virus Infections in Lung Transplantation: A European Survey of Clinical Practice

Community-acquired respiratory viral (CARV) infections are common in lung transplant (LTx) recipients,1 and suspected to be a threat to graft stability,2 but specific guidelines for their management are lacking. We assessed current practices for both the diagnosis and treatment of CARV infections, and performed a web-based survey of 26 LTx centers from northern Europe (62% of active centers). Responses from 21/26 centers (80%) were obtained (online supplement, https://docs.google.com/forms/d/1S3CIhjCdsSOYb1IdZzW7-yj2CMs43ndd3uUVwm2p6IY/viewform.). For diagnosis of CARV, a majority of centers performed viral screening first in case of FEV1 decline (62% of centers) or planned endoscopy (57%). Local policies for diagnosis were variable, ranged from no screening even with lung function deterioration (38%) to extensive screening with systematic viral sampling at each outpatient visit (5%). Sampling was performed solely by nasopharyngeal swab (43%), solely by bronchoalveolar lavage (24%), or by either sampling technique (33%). Nearly all centers used multiplex PCR (92%) for virus identification, sometimes with viral culture (29%) or antigen detection (24%), although they are less sensitive than PCR.3 The centers did not differ in the respective importance of criteria used to diagnose CARV infections (P = 0.23, Friedman test, Figure 1). Virus detection per se was considered as one of the most important factors for diagnosing CARV infection, and of greater importance than radiological features (P = 0.002) or negativity of bacterial sampling (P = 0.004, Figure 1). Among all CARV infections, respiratory syncytial virus (RSV) infection was perceived as the most deleterious (P < 0.0001 versus rhinovirus), then para-influenzae virus (PIV) and human metapneumovirus (hMPV) infection (Figure 2). Physicians’ beliefs about the potential consequences of CARV infection did not significantly differ among centers (P = 0.09), with first the risk of chronic rejection (mean grade 7.1 ± 2 [from grade 0: completely disagree, to 10: completely agree]), then of bacterial infection (graded 6.6 ± 2.3), or acute rejection (graded 5.9 ± 3).FIGURE 1.: Importance of each parameter for the diagnosis of viral community-acquired respiratory virus (CARV) by clinicians (BAL, bronchoalveolar lavage; NAP, nasopharyngeal aspiration; FEV1, forced expiratory volume in 1 s; Friedman test). Horizontal lines are median, box edges are interquartile range, and whiskers are range.FIGURE 2.: Physicians’ perceived importance of each virus for the likelihood of symptomatic community-acquired respiratory virus (RSV, respiratory syncytial virus; PIV, para-influenzae virus; hMPV, human metapneumovirus). RSV was considered more pathogenic than bocavirus (*P < 0.0001), rhinovirus (**P < 0.0001), and coronavirus (***P = 0.049) (Friedman Test). Data are mean (SD).Specific antiviral treatment, mostly based on ribavirin, widely varied among centers (P < 0.001, Table 1). For severe CARV infections, only 33%–61% of centers considered treatment with ribavirin for RSV, PIV, and hMPV infections. In contrast, even with nonsevere CARV infections, including asymptomatic ones, about 15% of centers still started ribavirin for all patients (Table 1). Furthermore, 47% of centers never considered treatment regardless of clinical presentation with PIV/hMPV infections. Initiation of ribavirin depended on the detected virus: 80% for RSV, 38% for PIV, and 33% for hMPV (Table S1, additional data, SDC, https://links.lww.com/TP/B860). The perceived effectiveness of ribavirin was higher with RVS, PIV (P = 0.05 versus RSV), and hMPV (P = 0.17 versus RSV), but lower with other viruses (Figure S1, SDC, https://links.lww.com/TP/B860), almost to prevent chronic rejection (graded 5 [1–7], Table 2).TABLE 1.: Antiviral treatment administration by lung transplantation centers depending on the virus type and severity of the LTRI (n = 21)TABLE 2.: Physicians’ perceptions of the benefits of the use of ribavirin for viral LRTI (from 0: not effective at all to 10: very effective)Our study highlights the highly variable and sometimes opposite policies for managing CARV infections in LTx recipients among centers in northern Europe, ranging from no systematic screening and treatment to invasive detection and systematic use of antiviral treatment, although aggressive policies for diagnosis and treatment seemed to be independent in each center. This variability reflects the low level of evidence supporting the use of antiviral agents in LTx recipients, with only 1 prospective but nonrandomized study showing a positive impact of ribavirin use on outcome,4 and with only recent general guidelines for solid-organ Tx.5 Although with potential bias due to the lack of total coverage of Northern European LTx centers, this survey showed that physicians seem to almost all agree that CARV infection may be harmful after LTx in the long term, with an increased risk of subsequent chronic rejection. Hence, we urge randomized controlled trials on the effectiveness of antiviral treatments and the development of expert consensus guidelines for treating CARV infections.