Respiratory Impedance and Obliterative Bronchiolitis - Full Text View

Purpose

The aim of the present study will be to test the hypothesis that changes in within-breath total respiratory input impedance (Zrs) may provide an early evidence of obliterative bronchiolitis after allogeneic hematopoietic stem cell transplantation (HSCT). Before and after HSCT, Zrs will be measured by a modified forced oscillation technique (FOT) during spontaneous breathing both at baseline and 30 min after albuterol inhalation . Such technique may be particularly sensitive to small changes in lung mechanics observed in the early stages of peripheral airflow obstruction.

Condition	Intervention
Hematopoietic Stem Cell Transplantation Obliterative Bronchiolitis	Drug: albuterol

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Predictive Value of Within-breath Respiratory Input Impedance in the Early Diagnosis of Obliterative Bronchiolitis After Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:

Drug Information available for: Albuterol Levalbuterol Levalbuterol hydrochloride Albuterol sulfate Levalbuterol tartrate

U.S. FDA Resources

Further study details as provided by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:

Primary Outcome Measures:

Airway Distensibility With Lung Inflation After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) [ Time Frame: 2 weeks before and 2 months after HSCT ] [ Designated as safety issue: No ]
We studied 26 subjects, 2 weeks before and 2 months after HSCT. Within-breath respiratory system conductance (Grs) at 5, 11 and 19 Hz was measured by forced oscillation technique (FOT) at functional residual capacity (FRC) and total lung capacity (TLC)

Secondary Outcome Measures:

Post-HSCT Changes in Lung Tissue Density [ Time Frame: Before and 2 months after HSCT ] [ Designated as safety issue: No ]
Changes in lung tissue density were measured by quantitative computed tomography(CT) scan 2 weeks before and 2 months after HSCT

Enrollment:	26
Study Start Date:	December 2010
Study Completion Date:	June 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: albuterol Twenty-six consecutive patients undergoing allogeneic HSCT for hematological malignancies were studied. All patients were in stable clinical conditions at the time of study. All patients received a myeloablative conditioning regimen either including or not including total body irradiation. Spirometry, lung volumes, FOT and lung CT scan were obtained before the start of conditioning treatment and, approximately, two months after HSCT. On each study day, all the above measurements were taken before and 30 min after inhaling four consecutive albuterol doses, of 100 mcg each, through a valved-holding chamber. DLco was measured only after bronchodilator inhalation.	Drug: albuterol 400 mcg by inhalation Other Name: Broncovaleas pressurized solution

Arms

Assigned Interventions

Experimental: albuterol

Twenty-six consecutive patients undergoing allogeneic HSCT for hematological malignancies were studied. All patients were in stable clinical conditions at the time of study. All patients received a myeloablative conditioning regimen either including or not including total body irradiation. Spirometry, lung volumes, FOT and lung CT scan were obtained before the start of conditioning treatment and, approximately, two months after HSCT. On each study day, all the above measurements were taken before and 30 min after inhaling four consecutive albuterol doses, of 100 mcg each, through a valved-holding chamber. DLco was measured only after bronchodilator inhalation.

Drug: albuterol

400 mcg by inhalation

Other Name: Broncovaleas pressurized solution

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Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

consecutive, clinically-stable, outpatients undergoing allogeneic HSCT (sourcing from bone marrow) for hematological malignancies
values of standard PFTs within normal range before HSCT
good collaboration during the maneuvers

Exclusion Criteria:

patients showing any spirometric and/or volumetric abnormality before HSCT
poor collaboration and/or coordination during the maneuvers
any clinically-significant respiratory disease (bronchial asthma, COPD, cystic fibrosis, etc.) before HSCT

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01255449

Locations

Italy
U.O. Medicina Preventiva e del Lavoro, Laboratorio di Fisiopatologia Respiratoria, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro
Genova, Italy, 16132

Sponsors and Collaborators

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Investigators

Principal Investigator:

Giovanni Barisione, MD

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

More Information

Publications:

Barisione G, Pompilio PP, Bacigalupo A, Brusasco C, Cioè A, Dellacà 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.

Rodríguez-Roisin R, Roca J, Grañena A, Agustí AG, Marín P, Rozman C. Lung function in allogeneic bone marrow transplantation recipients. Eur Respir J. 1989 Apr;2(4):359-65.

Gore EM, Lawton CA, Ash RC, Lipchik RJ. Pulmonary function changes in long-term survivors of bone marrow transplantation. Int J Radiat Oncol Biol Phys. 1996 Aug 1;36(1):67-75.

Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56.

Chien JW, Duncan S, Williams KM, Pavletic SZ. Bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation-an increasingly recognized manifestation of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2010 Jan;16(1 Suppl):S106-14. Epub 2009 Nov 5. Review.

Soubani AO, Uberti JP. Bronchiolitis obliterans following haematopoietic stem cell transplantation. Eur Respir J. 2007 May;29(5):1007-19. Review.

Otulana BA, Higenbottam T, Ferrari L, Scott J, Igboaka G, Wallwork J. The use of home spirometry in detecting acute lung rejection and infection following heart-lung transplantation. Chest. 1990 Feb;97(2):353-7.

Van Muylem A, Mélot C, Antoine M, Knoop C, Estenne M. Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation. Thorax. 1997 Jul;52(7):643-7.

Mead J. The lung's "quiet zone". N Engl J Med. 1970 Jun 4;282(23):1318-9. No abstract available.

Cosio M, Ghezzo H, Hogg JC, Corbin R, Loveland M, Dosman J, Macklem PT. The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med. 1978 Jun 8;298(23):1277-81.

Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med. 2002 Aug 15;166(4):440-4. Review. No abstract available.

Kjeldgaard JM, Hyde RW, Speers DM, Reichert WW. Frequency dependence of total respiratory resistance in early airway disease. Am Rev Respir Dis. 1976 Sep;114(3):501-8.

Hayes DA, Pimmel RL, Fullton JM, Bromberg PA. Detection of respiratory mechanical dysfunction by forced random noise impedance parameters. Am Rev Respir Dis. 1979 Nov;120(5):1095-100.

Dellacà RL, Santus P, Aliverti A, Stevenson N, Centanni S, Macklem PT, Pedotti A, Calverley PM. Detection of expiratory flow limitation in COPD using the forced oscillation technique. Eur Respir J. 2004 Feb;23(2):232-40.

Dellacà RL, Pompilio PP, Walker PP, Duffy N, Pedotti A, Calverley PM. Effect of bronchodilation on expiratory flow limitation and resting lung mechanics in COPD. Eur Respir J. 2009 Jun;33(6):1329-37. Epub 2009 Jan 22.

Chalker RB, Celli BR, Habib RH, Jackson AC. Respiratory input impedance from 4 to 256 Hz in normals and chronic airflow obstruction: comparisons and correlations with spirometry. Am Rev Respir Dis. 1992 Sep;146(3):570-6.

Farré R, Peslin R, Rotger M, Barberá JA, Navajas D. Forced oscillation total respiratory resistance and spontaneous breathing lung resistance in COPD patients. Eur Respir J. 1999 Jul;14(1):172-8.

Grimby G, Takishima T, Graham W, Macklem P, Mead J. Frequency dependence of flow resistance in patients with obstructive lung disease. J Clin Invest. 1968 Jun;47(6):1455-65.

Barisione G, Bacigalupo A, Crimi E, Van Lint MT, Lamparelli T, Brusasco V. Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation. Eur Respir J. 2008 Dec;32(6):1576-82. Epub 2008 Aug 6.

Barisione G, Bacigalupo A, Crimi E, Brusasco V. Acute bronchodilator responsiveness in bronchiolitis obliterans syndrome following hematopoietic stem cell transplantation. Chest. 2010 Aug 19; [Epub ahead of print]

Responsible Party:	Giovanni Barisione, MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
ClinicalTrials.gov Identifier:	NCT01255449 History of Changes
Other Study ID Numbers:	FOT-BOS-01
Study First Received:	December 6, 2010
Results First Received:	September 18, 2012
Last Updated:	December 22, 2012
Health Authority:	Italy: Ministry of Health

Keywords provided by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:

Forced oscillation technique
Respiratory input impedance
Allogeneic hematopoietic stem cell transplantation
Obliterative bronchiolitis

Additional relevant MeSH terms:

Bronchiolitis
Bronchiolitis Obliterans
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Albuterol
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions

Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on May 23, 2013

Respiratory Impedance and Obliterative Bronchiolitis (FOT-BOS)