Hematopoietic Allograft Impacts Lung Function, Inflammation
Background: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function.
Methods: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant.
Results: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (−5.9%, 95% CI: -8.9 to −2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively).
Conclusion: Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.
The use of allogeneic hematopoietic stem cell transplant (HSCT) as a treatment for haematological malignancies is increasing as the benefits of this intervention are applied to a wider patient population. However, although this intervention is associated with a variety of pulmonary complications, including infection and graft-versus-host disease, most of the available data has utilised regular lung function measures that are taken at least 6–12 months after the allograft or retrospective clinical studies. These do not give a detailed picture of the early effects on the lung after receiving an allograft and in particular do not quantify pulmonary inflammation during this time period. This is important as 5-45% of deaths from allogeneic HSCT (depending on indication) occur within 100 days after receiving a HSCT and the cause of death can often be as a result of pulmonary complications. Hence, intensive monitoring of lung physiological outcome measures may provide insights into the natural history of the impact of receiving an allogeneic HSCT on the lungs, as well as assessing if changes in respiratory function tests have prognostic value. To be applicable in the clinical setting such tests will need to be ideally readily deliverable at regular clinic visits. We thus chose spirometry (Forced Expiratory Volume in one second and Forced Vital Capacity) and exhaled nitric oxide, a measure of pulmonary inflammation, as simple measures of lung physiological health.
We have established a cohort of patients who received an allogeneic HSCT and prospectively collected data on lung function and exhaled nitric oxide to assess the impact of this intervention on pulmonary function and a biomarker of pulmonary inflammation. We have also assessed if these outcomes are associated with survival, and thus may provide a potential biomarker that could be used to stratify patients who have received a transplant.
Abstract and Introduction
Abstract
Background: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function.
Methods: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant.
Results: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (−5.9%, 95% CI: -8.9 to −2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively).
Conclusion: Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.
Introduction
The use of allogeneic hematopoietic stem cell transplant (HSCT) as a treatment for haematological malignancies is increasing as the benefits of this intervention are applied to a wider patient population. However, although this intervention is associated with a variety of pulmonary complications, including infection and graft-versus-host disease, most of the available data has utilised regular lung function measures that are taken at least 6–12 months after the allograft or retrospective clinical studies. These do not give a detailed picture of the early effects on the lung after receiving an allograft and in particular do not quantify pulmonary inflammation during this time period. This is important as 5-45% of deaths from allogeneic HSCT (depending on indication) occur within 100 days after receiving a HSCT and the cause of death can often be as a result of pulmonary complications. Hence, intensive monitoring of lung physiological outcome measures may provide insights into the natural history of the impact of receiving an allogeneic HSCT on the lungs, as well as assessing if changes in respiratory function tests have prognostic value. To be applicable in the clinical setting such tests will need to be ideally readily deliverable at regular clinic visits. We thus chose spirometry (Forced Expiratory Volume in one second and Forced Vital Capacity) and exhaled nitric oxide, a measure of pulmonary inflammation, as simple measures of lung physiological health.
We have established a cohort of patients who received an allogeneic HSCT and prospectively collected data on lung function and exhaled nitric oxide to assess the impact of this intervention on pulmonary function and a biomarker of pulmonary inflammation. We have also assessed if these outcomes are associated with survival, and thus may provide a potential biomarker that could be used to stratify patients who have received a transplant.
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