PDF Bronchiolitis Obliterans Syndrome in Lung Transplantation: 8 (Respiratory Medicine)

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Fluticasone, azithromycin, and montelukast treatment for new-onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation. A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome BOS post lung transplantation.

Vos et al. A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation. Additionally, longer term analysis of the treatment arms from this same RCT showed that prophylactic AZI was associated with significantly improved CLAD-free survival, pulmonary function, and functional exercise capacity versus the placebo group.

Prophylactic azithromycin therapy after lung transplantation: post hoc analysis of a randomized controlled trial. Am J Transplant. The efficacy of prophylactic azithromycin on bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

Int J Hematol. Because pathologic GER has been identified as a risk factor for developing LTX-BOS and anti-reflux surgery which has been associated with improvement in FEV1 in a number of observational studies can be performed with relative safety in LTX recipients who develop FEV1 decline consistent with the diagnosis of BOS, consideration for referral to an experienced surgeon for anti-reflux surgery is suggested, although this is a conditional recommendation based upon very low quality evidence. Because airway fibrosis is involved in the pathogenesis of OB, anti-fibrotic agents may be useful to treat BOS, and both pirfenidone and nintedanib have been recently approved for treatment of idiopathic pulmonary fibrosis.

Pre-clinical studies suggest that pirfenidone may be useful to prevent or ameliorate OB associated with LTX, and recent case reports suggest that pirfenidone may be useful to treat both obstructive and restrictive forms of LTX-associated CLAD. Pirfenidone: a potential therapy for progressive lung allograft dysfunction? Extracorporeal photopheresis as a new supportive therapy for bronchiolitis obliterans syndrome after allogeneic stem cell transplantation. Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients.

Primary lung transplantation for HCT-BOS or lung retransplantation for LTX-BOS are potential therapies for patients with progressive loss of lung function that is refractory to pharmacologic or other therapies, and satisfactory outcomes have been reported for both HCT recipients and for patients with refractory pulmonary dysfunction following LTX.

Impact of CLAD phenotype on survival after lung retransplantation: a multicenter study. Anti-fibrotic therapy e. Additionally, the ability to attain an early diagnosis of BOS is likely to play a key role in improving responses to new therapies for BOS. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Skip to Main Content.

Search in: This Journal Anywhere. Advanced search. Submit an article Journal homepage. Keith C. Pages Received 05 Jan How is BOS diagnosed? How can BOS be treated? Summary and conclusion References. Diagnosis and management of bronchiolitis obliterans syndrome following lung or hematopoietic cell transplantation. Introduction Both allogeneic hematopoietic cell transplantation HCT and lung transplantation LTX can rescue patients from disorders with poor prognoses and allow improved quality of life and prolonged survival.

Declaration of interests K. Article Metrics Views. Article metrics information Disclaimer for citing articles. Three of these progressed from Stage 0 to 0-p, two from Stage 0-p to 1, one from Stage 1 to 2 and three from Stage 2 to 3. Figure 1.

[Full text] Chronic lung allograft dysfunction following lung transplantation: cha | TRRM

Figure 2. This is the first study to examine EBC biomarkers in lung transplantation with progression to chronic rejection. Although other studies have examined EBC pH and cytokine levels, this study is the first to report on the non-specific markers of inflammation and oxidative stress, nitrogen oxides and hydrogen peroxide. It has shown that, despite immunosuppression, these non-specific markers of inflammation are elevated in the EBC of patients with lung transplants when compared to controls.

There was no difference in the levels of these biomarkers between the participants with BOS compared to those without, but longer term follow-up EBC might have been helpful. All other markers of inflammation including cytokines and pH did not differ between those with lung transplants and controls. The biomarker levels did not correlate with progression of BOS at one year follow up in participants with lung transplants, although the numbers were small. The finding that lung transplant participants had higher levels of markers of oxidative stress and inflammation in the EBC of lung transplant recipients, despite immunosuppression, is consistent with other studies [].

The heterogeneous nature of both the indication for transplantation, as well as the complications and immunosuppression means that the subgroups in this study are limited by small sample sizes and between subject variability, but the results do allow estimates for suitable power in future studies. We have used the consensus diagnostic criteria for BOS, but a much larger study could examine subtypes of BOS, any markers suggesting progression of BOSO-p and any progression of disease [20].

The cytokines IL-8, IL and IL were undetectable in the majority of the samples, and the levels detected did not differ between the groups. This study however used a different EBC collection apparatus and concentrated their samples using the technique of lyophilisation.

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In addition to this they pooled samples from participants from each group and reported relative increases in levels. This would mean that its role in differentiating between those with and without BOS would be limited due to lack of specificity.


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The low levels of cytokines in EBC are in part due to the sample representing highly diluted airway lining fluid, with even when using highly sensitive available commercial assays. The cytokines studied have previously demonstrated a significant increases in the EBC of those with BOS and were chosen for this study after considering the current theoretical pathophysiology of this disorder [16,19]. Due to this difficulty in detecting cytokines in EBC, any clinical utility of cytokine examination will need refinement in the future with more sensitive assays. Lyophilisation and subsequent reconstitution in a smaller volume is a technique which can be used on EBC samples and can concentrate biomarkers by a factor up to thirty-times [21].

This or other concentrating techniques may help in the detection and subsequent analysis of cytokines in EBC and should be used in future studies if cytokine levels are to be reliably detected. Comparison with BAL may be appropriate but few studies have shown good correlation between the two techniques and they probably sample different lung compartments [17]. Those with infection were not recruited due to the complexity of adding a further variable in the analyses.

There were several methodological limitations of in this study. Some subjects were mildly breathless, therefore only small amounts of EBC able to be collected and hence not all the assays were able to be performed for each participant. EBC collection was unsuccessful in a number of the potential subjects, mainly as they felt breathless during the procedure.

Lung transplantation for bronchiolitis obliterans syndrome after allo-SCT

Although the EBC collection only requires tidal breathing, some found this procedure provoked a sensation of breathlessness. The use of an alternative EBC collection apparatus would also be useful to validate the differences found in the non-specific markers of pH, NO x and H 2 O 2.

It has been suggested that NO x is a biomarker that is especially subject to contamination from collection devices and the surrounding environment and hence the results from our study do require validation by other studies [11,17,23]. In conclusion EBC can be used to demonstrate inflammation non-invasively in the lungs of those with lung transplants.

Markers of non-specific inflammation such as nitrogen oxides and hydrogen peroxide are inexpensive, simple assays of markers that are reliably detected in EBC compared to cytokine levels, and the clinical applicability of these markers warrants further research [14,24]. Further development is needed to assess the potential of cytokines in the EBC as a diagnostic tool with more sensitive assays or methods of concentrating EBC to ensure that the appropriate analyses may be performed in all subjects.

A review of bronchiolitis obliterans syndrome and therapeutic strategies

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