SMALL AIRWAY DYSFUNCTION AFTER LUNG TRANSPLANTATION

To the Editor:

We read with interest the article by Arens and colleagues (1) who studied lung mechanics and small airway function in 15 patients with double-lung transplantation (DLT). Over the last 8 yr, we have followed up all heart-lung transplant (HLT) and DLT recipients at our institution with standard pulmonary function tests (PFTs) and measurements of ventilation distribution by single-breath washouts for N₂, He, and SF₆; overall, 950 single-breath washouts have been performed in 68 patients.

In agreement with Arens and colleagues (1) we observed that obliterative bronchiolitis (OB) produced an increase in the slope of the alveolar plateau for N₂ (SN₂). The slope for He and SF₆ also increased but because SHe increased more than SSF₆, the slope difference (SSF₆-SHe) became negative, suggesting that ventilation inhomogeneities were primarily located in the membranous and respiratory bronchioles. We also reported that indexes of ventilation distribution were more sensitive than standard PFTs to allograft dysfunction (2, 3).

In sharp contrast with Arens and colleagues (1), however, we found that stable lung transplant recipients had normal PFTs and distribution of ventilation. In 33 HLT patients, best postoperative values for VC, FEV₁, and FEF_25-75 averaged 99%, 100%, and 107% of predicted, respectively; and the best value for SN₂ during the VC test was 0.9%/L (75% of predicted) (3). Furthermore, average values obtained in 23 patients who were studied on 56 occasions when freedom of infection and rejection was established by transbronchial biopsies and bronchoalveolar lavage were 87% of predicted for VC, 89% of predicted for FEV₁, 89% of predicted for FEF_25-75, and 105% of predicted for SN₂. Similar results were obtained in DLT patients.

Why Arens and colleagues (1) found evidence of abnormalities in the small airways in 9 of 11 clinically stable DLT recipients is unclear, but our data indicate that this functional profile should not be regarded as representative of that of lung transplant recipients with adequate allograft function. In fact, this profile is consistent with early OB; comparison of the functional data reported in the paper with best post-transplant values may support this diagnosis by showing that the patients, though clinically stable, developed a deterioration in pulmonary function over time.

MARC ESTENNE

ALAIN VAN MUYLEM

Chest Service

Erasme University Hospital

Brussels, Belgium

1. Arens, R., J. M. McDonough, H. Zhao, N. P. Blumenthal, R. M. Kotloff, and M. M. Grunstein. 1998. Altered lung mechanics after double-lung transplantation. Am. J. Respir. Crit. Care Med. 158: 1403-1409 [Abstract/Free Full Text].

2. Van Muylem, A., M. Antoine, J. C. Yernault, M. Paiva, and M. Estenne. 1995. Inert gas single-breath washout after heart-lung transplantation. Am. J. Respir. Crit. Care Med. 152: 947-952 [Abstract].

3. Van Muylem, A., C. Melot, M. Antoine, C. Knoop, and M. Estenne. 1997. Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation. Thorax 52: 643-647 [Abstract].

From the Authors:

In their letter, Drs. Estenne and Van Muylem suggest that the elevated slope of phase 3 of the single breath N₂ washout test (N₂SP₃) in our Stable patients after double lung transplantation (1) could be indicative of early OB changes. In light of their studies (2, 3) in which patients after heart-lung transplantation and double-lung transplantation, free of infection and rejection, had normal PFT and N₂SP₃ values, the findings in our Stable group seem conflicting.

As mentioned in our article, the Stable subjects were defined as those patients who underwent double lung transplantation, were in a stable clinical condition at time of testing, and were not admitted to the hospital during the 12 mo prior to the study. This group had no evidence of significant infection or rejection (4) during this period, or deterioration in pulmonary function tests (PFT) to suggest obliterative bronchiolitis syndrome (5). Mean PFT were consistent with mild restriction and mild air trapping when compared to our control group and mean N₂SP₃ was mildly elevated suggesting nonuniform distribution of ventilation.

Our Stable group, although free of infection and rejection, was not similar to the group of patients studied by Drs. Estenne and Van Muylem. In our study, the mean time after transplantation was 31 mo versus 16 and 21 mo in the studies cited above. This difference could have impacted negatively on lung function over time in these patients. Based on mechanics studies, PFT, and N₂SP₃ measurements, the majority of our patients, although clinically stable, had evidence of subclinical lung dysfunction. This concern is raised later in our paper. However, we were wary of making a diagnosis of early OB since there are no definite criteria for this condition. At present, such a diagnosis can only be made retrospectively.

RAANAN ARENS

JOSEPH M. MCDONOUGH

Division of Pulmonary Medicine,

The Children's Hospital of Philadelphia,

Philadelphia, Pennsylvania

1. Arens, R., J. M. McDonough, H. Zhao, N. P. Blumenthal, R. M. Kotloff, and M. M. Grunstein. 1998. Altered lung mechanics after double-lung transplantation. Am. J. Respir. Crit. Care Med. 158: 1403-1409 .

2. Van Muylem, A., M. Antoine, J. C. Yernault, and M. Estenne. 1995. Inert gas single-breath washout after heart-lung transplantation. Am. J. Respir. Crit. Care Med. 152: 947-952 .

3. Van Muylem, A., C. Melot, M. Antoine, C. Knoop, and M. Estenne. 1997. Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation. Thorax 52: 643-647 .

4. Yousem, S. A., G. J. Berry, P. T. Cagle, A. N. Husain, R. H. Hruban, A. Marchevsky, P. N. Ohori, J. Ritter, S. Stewart, and H. D. Tazelaar. 1996. Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: lung rejection study group. J. Heart Lung Transplant. 15: 1-15 [Medline].

5. Cooper, J. D., M. Billingham, T. Egan, M. I. Hertz, T. Higenbottam, J. Lynch, J. Maurer, I. Paradis, G. A. Patterson, C. Smith, E. P. Trulock, C. Vreim, and S. L. Yousem. 1993. A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allograft. J. Heart Lung Transplant. 12: 713-716 [Medline].