Clinical trial NCT01735526: Lung Diffusing Capacity for Nitric Oxide and Carbon Monoxide After Hematopoietic Stem-cell Transplantation
Official title: Changes in Lung Diffusing Capacity for Nitric Oxide and Carbon Monoxide After Allogeneic Versus Autologous Hematopoietic Stem-cell Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lung Disease
Keywords: Allogeneic and autologous
hematopoietic stem-cell transplantation
Lung diffusing capacity
for nitric oxide
carbon monoxide
Lung tissue density
microvascular damage
Lead sponsor: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Sponsor class: OTHER
First posted: 2012-11-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All consecutive patients undergoing allogeneic and autologous HSCT for hematological malignancies.

Brief summary: Early after allogeneic hematopoietic stem-cell transplantation (allo-HSCT), reductions of absolute lung volume and diffusing capacity for carbon monoxide (DLCO) are frequently detected even in the absence of overt idiopathic pneumonia syndrome (IPS). It can be hypothesized that these changes might be due to an occult intersitial lung disease associated with infections, acute Graft-versus-Host Disease (aGvHD), myeloablative conditioning regimens or any combination of these. To test this hypothesis, we will simultaneously measure the lung diffusing capacity for nitric oxide (DLNO) and DLCO and estimate the changes of membrane diffusing capacity (DM) and pulmonary capillary volume (Vc) by the DLNO/DLCO ratio. As we hypothesize that GHVD should be intuitively absent amongst autologous HSCT (auto-HSCT) recipients, we will compare the changes in DLNO/DLCO ratio showed by the latter group with those of subjects undergoing allo-HSCT.

Detailed description: In allogeneic hematopoietic stem-cell transplantation (allo-HSCT) recipients, early reductions of absolute lung volume and diffusing capacity for carbon monoxide (DLCO) are frequently detected even in the absence of overt idiopathic pneumonia syndrome (IPS)\[PMID: 22221781\]. Two months after allo-HSCT, we have recently shown an increase in lung tissue density determined by quantitative CT scan \[PMID: 22898044\]. It can be hypothesized that these parenchymal changes might be due to an occult intersitial lung disease associated with infections, acute Graft-versus-Host Disease (aGvHD), myeloablative conditioning regimens or any combination of these \[PMID: 21531955\]. To test this hypothesis, we will simultaneously measure the lung diffusing capacity for nitric oxide (DLNO) and DLCO. Assuming, for clinical purposes, that the reaction rate of NO with blood hemoglobin is infinite so that DLNO = DMNO = DMCO\*alpha (alpha = NO/CO diffusivity ratio), as to partition the effect of HSCT on membrane diffusing capacity (DM) and pulmonary capillary volume (Vc) we will use the DLNO/DLCO ratio \[PMID:16478855\]. As we hypothesize that GHVD should be intuitively absent amongst autologous HSCT (auto-HSCT) recipients, we will compare the changes in DLNO/DLCO ratio showed by the latter group with those of subjects undergoing allo-HSCT.

Eligibility criteria: Inclusion Criteria:

* baseline spirometry, lung volumes, and DLCO of the subjects included in the analysis must be within the predicted normal range
* all patients must be in stable clinical conditions at the time of study

Exclusion Criteria:

* a history of bronchial asthma, chronic obstructive pulmonary disease, or other significant respiratory disease

Primary outcomes:
measure: Changes in DLNO/DLCO ratio after allo- versus autologous HSCT
timeFrame: Before and 2-6 months after HSCT
Secondary outcomes:
measure: Changes in lung tissue density after allo- versus autologous HSCT
timeFrame: Before and 2-6 months after HSCT
Other outcomes:
Locations:
city: Genoa
country: Italy
facility: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro
Study officials:
affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
name: Giovanni Barisione, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bacigalupo A, Chien J, Barisione G, Pavletic S. Late pulmonary complications after allogeneic hematopoietic stem cell transplantation: diagnosis, monitoring, prevention, and treatment. Semin Hematol. 2012 Jan;49(1):15-24. doi: 10.1053/j.seminhematol.2011.10.005.
citation: Barisione G, Pompilio PP, Bacigalupo A, Brusasco C, Cioe A, Dellaca RL, Lamparelli T, Garlaschi A, Pellegrino R, Brusasco V. Airway distensibility with lung inflation after allogeneic haematopoietic stem-cell transplantation. Respir Physiol Neurobiol. 2012 Oct 15;184(1):80-5. doi: 10.1016/j.resp.2012.07.021. Epub 2012 Aug 8.
citation: Panoskaltsis-Mortari A, Griese M, Madtes DK, Belperio JA, Haddad IY, Folz RJ, Cooke KR; American Thoracic Society Committee on Idiopathic Pneumonia Syndrome. An official American Thoracic Society research statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome. Am J Respir Crit Care Med. 2011 May 1;183(9):1262-79. doi: 10.1164/rccm.2007-413ST.
citation: van der Lee I, Zanen P, Grutters JC, Snijder RJ, van den Bosch JMM. Diffusing capacity for nitric oxide and carbon monoxide in patients with diffuse parenchymal lung disease and pulmonary arterial hypertension. Chest. 2006 Feb;129(2):378-383. doi: 10.1378/chest.129.2.378.
citation: Barisione G, Bacigalupo A, Brusasco C, Scanarotti C, Penco S, Bassi AM, Lamparelli T, Garlaschi A, Pellegrino R, Brusasco V. Mechanisms for reduced pulmonary diffusing capacity in haematopoietic stem-cell transplantation recipients. Respir Physiol Neurobiol. 2014 Apr 1;194:54-61. doi: 10.1016/j.resp.2014.01.018. Epub 2014 Feb 1.