Gastro-oesophageal reflux (GOR) and microaspiration are implicated in the pathophysiology of asthma, chronic obstructive pulmonary disease, interstitial lung disease and chronic lung allograft dysfunction.1 2 Aspiration, which is often asymptomatic, has been identified as a treatable allograft injury that may affect mortality.1 2

The potential for thoracic mechanical changes caused by advanced lung disease to predispose to reflux has been highlighted.2 Although aspiration could cause lung damage, alternatively reflux might represent a secondary event. Longitudinal data are lacking,2 so we have undertaken a prospective study of reflux in lung transplantation. This allowed investigations in patients where thoracic mechanical changes associated with advanced lung disease had improved. We hypothesised that reflux was prevalent and could develop at different times following transplantation in patients with good allograft function.

Methods

Between November 2007 and November 2008, 14 newly transplanted lung recipients were assessed with pH impedance monitoring (Ohmega, MMS, Utrecht, The Netherlands). Most patients tolerated the assessments but reported discomfort. A representative subset was verified by independent observers (AGNR, AJB). All patients were receiving treatment with proton pump inhibitors which remained unchanged during the study (see table 1 in online supplement).

Results

Nine patients were assessed for GOR at 3 and 6 months after lung transplantation using pH impedance; five patients refused a second test. The majority of assessments were abnormal,3 with marked variability with time following transplantation (fig 1). Notably, in four of nine patients overall assessments for reflux that were normal at 3 months became positive at 6 months (fig 1, table 1 in online supplement). All patients received standard immunosuppression at similar levels (n = 4) or decreased levels (n = 5) during the period of assessment (table 1 in online supplement).

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Figure 1

(A) Oesophageal acid (pH <4.0) exposure, expressed as percentage of monitoring time. (B) Total number of reflux events measured by impedance at 3 and 6 months after transplantation. The dotted lines indicate accepted European normal cut-off values (<4.5% for acid exposure and <58 for total number of reflux events3), indicating the presence of clinically significant gastro-oesophageal reflux in most of the patients, with inter-subject and intra-subject variability over time.

Discussion

This is the first longitudinal study of reflux following transplantation which shows that, although repeated measurements are practicable, they were not tolerated by all patients with only 9/14 agreeing to a second test in this series. High levels of GOR were seen, with marked variability in the first 6 months after transplantation. Most patients studied had received two donor lungs. Our results therefore suggest that reflux can occur in allograft recipients without frankly abnormal lung mechanics at a time of tapered-down immunosuppression.

GOR assessment is becoming adopted across lung transplant units due to its high prevalence and a suggested survival benefit of fundoplication.4 Reproducibility has not been assessed in the lung transplant population but, in normal subjects, impedance monitoring has been shown to be at least as reproducible as pH monitoring.5 Our results suggest that reflux may develop following negative initial assessments, but it is also possible that patients with reflux may improve with time. This emphasises that repeat assessments of GOR may be an advisable component of post-transplant follow-up. Our series demonstrates that multiple catheter-based assessments are unpopular with some patients, highlighting a need for identifying markers of GOR and aspiration which are specific and well tolerated.1

Although this represents the first longitudinal measurements of reflux following transplantation, our study was descriptive, not powered to detect changes with time and did not evaluate mechanisms. Further larger longitudinal studies are necessary. Such translational studies may be relevant to improving outcomes in lung transplantation and other lung and airway pathophysiologies.