Clinical lung and heart/lung transplantation
Comparison of Induced Sputum and Bronchoalveolar Lavage in Lung Transplant Recipients

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Background

Chronic lung rejection is characterized by obliterative bronchiolitis (OB) diagnosed based on spirometric criteria reflecting an already advanced process. Biologic markers such as bronchoalveolar lavage (BAL) neutrophilia or increased levels of chemokines (interleukin-8, RANTES [regulated on activation: normal T cell expressed and secreted]) have been proposed as early diagnosis tools. However, BAL is too invasive to be used as a routine strategy. Induced sputum (IS), however, is a non-invasive method of recovering bronchial cells.

Methods

The aim of this study was to compare BAL and IS differential cellular counts as well as IL-8 and RANTES levels between patients with bronchiolitis obliterans syndrome (BOS), recipients with good outcome and well-preserved lung function (non-BOS) and non-transplanted controls. We compared 34 BAL and IS findings obtained consecutively from 34 lung transplant recipients (LTRs), including 22 non-BOS and 12 BOS patients.

Results

IS results were compared with 19 samples from non-transplanted controls. IS was well tolerated. There was no correlation between BAL and sputum cell populations. BAL neutrophils and IL-8 levels were increased in BOS, and these parameters were positively correlated. Moreover, BAL neutrophils and IL-8 levels were both negatively correlated with respiratory function. Sputum evaluation allows discrimination of BOS from non-BOS by the presence of higher neutrophil and eosinophil counts. Moreover, IS neutrophils and eosinophils were both correlated with lung function parameters. In contrast to BAL, IL-8 level in sputum was not a useful predictive marker of BOS development. IS RANTES levels were higher in BOS than in healthy recipients and correlated significantly with IS eosinophils.

Conclusions

IS and BAL provide different but complementary data. In this study, IS appeared to be a useful, non-invasive tool for LTR monitoring. Furthermore, IS provides new insights into BOS pathogenesis, especially with regard to implication of eosinophils and its chemokine, RANTES, at the bronchial level.

Section snippets

Subjects

Consecutive LTRs were included from April 2002 to April 2005. We limited study eligibility to double-lung or heart–lung transplant patients who were either clinically healthy (i.e., no clinical symptom, FEV1 ≥80% of baseline, nitrogen slope <3% and normal leukocyte counts), or diagnosed as having BOS according to the ISHLT staging criteria.9 Single-lung transplant recipients were excluded because it could not be ascertained clearly whether the sputum sample came from the allograft or the native

Patients

Thirty-four LTRs (20 males and 14 females) and 19 controls were included in the study. Mean time since transplantation was 6 years and 5 months (6 years for non-BOS patients, 7 years and 11 months for BOS patients).

Thirty-two patients had undergone double-lung transplantation and 2 had heart–lung transplantation. The primary pulmonary diagnoses were cystic fibrosis (n = 20), bronchiectasis (n = 3), emphysema (n = 7), Langerhans cell histiocytosis (n = 2), pulmonary fibrosis (n = 1) and

Discussion

In this study, we have confirmed that recovering bronchial cells with sputum induction provides information for monitoring LTR respiratory tract inflammation. Furthermore, this procedure was successful in 84% of cases, a proportion even higher than that usually reported in asthma where IS has been extensively studied and validated.20, 21 This high percentage of IS success was to be expected in this LTR population that consisted of mainly cystic fibrosis patients. The diagnostic interest of IS

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    Supported by ARARD, Vaincre la Mucoviscidose and Assistance Publique—Hôpitaux de Marseille.

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