Respiratory Impedance and Obliterative Bronchiolitis

NCT01255449 | Completed Results DMC

• 1 other identifier: FOT-BOS-01
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hematopoietic Stem Cell Transplantation; Obliterative Bronchiolitis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Airway Distensibility With Lung Inflation After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

  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)

  2 weeks before and 2 months after HSCT

Secondary Outcomes (1)

• Post-HSCT Changes in Lung Tissue Density

  Before and 2 months after HSCT

Study Arms (1)

albuterol

EXPERIMENTAL

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

Interventions

albuterol DRUG

400 mcg by inhalation

Also known as: Broncovaleas pressurized solution

albuterol

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

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, 16132, Italy

Location

Related Publications (20)

• Rodriguez-Roisin R, Roca J, Granena A, Agusti AG, Marin P, Rozman C. Lung function in allogeneic bone marrow transplantation recipients. Eur Respir J. 1989 Apr;2(4):359-65.

  PMID: 2661259 BACKGROUND

• 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. doi: 10.1016/s0360-3016(96)00123-x.

  PMID: 8823260 BACKGROUND

• 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. doi: 10.1016/j.bbmt.2005.09.004.

  PMID: 16338616 BACKGROUND

• 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. doi: 10.1016/j.bbmt.2009.11.002. Epub 2009 Nov 5.

  PMID: 19896545 BACKGROUND

• Soubani AO, Uberti JP. Bronchiolitis obliterans following haematopoietic stem cell transplantation. Eur Respir J. 2007 May;29(5):1007-19. doi: 10.1183/09031936.00052806.

  PMID: 17470622 BACKGROUND

• 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. doi: 10.1378/chest.97.2.353.

  PMID: 2298060 BACKGROUND

• Van Muylem A, Melot 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. doi: 10.1136/thx.52.7.643.

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• Mead J. The lung's "quiet zone". N Engl J Med. 1970 Jun 4;282(23):1318-9. doi: 10.1056/NEJM197006042822311. No abstract available.

  PMID: 5442364 BACKGROUND

• 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. doi: 10.1056/NEJM197806082982303.

  PMID: 651978 BACKGROUND

• Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med. 2002 Aug 15;166(4):440-4. doi: 10.1164/rccm.200201-003pp. No abstract available.

  PMID: 12186817 BACKGROUND

• 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. doi: 10.1164/arrd.1976.114.3.501.

  PMID: 970731 BACKGROUND

• 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. doi: 10.1164/arrd.1979.120.5.1095.

  PMID: 507525 BACKGROUND

• Dellaca 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. doi: 10.1183/09031936.04.00046804.

  PMID: 14979497 BACKGROUND

• Dellaca 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. doi: 10.1183/09031936.00139608. Epub 2009 Jan 22.

  PMID: 19164347 BACKGROUND

• 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. doi: 10.1164/ajrccm/146.3.570.

  PMID: 1519830 BACKGROUND

• Farre R, Peslin R, Rotger M, Barbera 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. doi: 10.1034/j.1399-3003.1999.14a29.x.

  PMID: 10489847 BACKGROUND

• 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. doi: 10.1172/JCI105837.

  PMID: 5653219 BACKGROUND

• 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. doi: 10.1183/09031936.0139807. Epub 2008 Aug 6.

  PMID: 18684842 BACKGROUND

• Barisione G, Bacigalupo A, Crimi E, Brusasco V. Acute bronchodilator responsiveness in bronchiolitis obliterans syndrome following hematopoietic stem cell transplantation. Chest. 2011 Mar;139(3):633-639. doi: 10.1378/chest.10-1442. Epub 2010 Aug 19.

  PMID: 20724742 BACKGROUND

• 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.

  PMID: 22898044 RESULT

MeSH Terms

Conditions

Bronchiolitis Obliterans

Interventions

Albuterol

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Dr. Giovanni Barisione
• Organization: IRCCS Azienda Ospedaliera Universitaria San Martino IST - Genova, Italy

giovanni.barisione@hsanmartino.it

+39010555

Study Officials

• Giovanni Barisione, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 6, 2010
• First Posted: December 7, 2010
• Study Start: December 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: June 1, 2012
• Last Updated: January 31, 2013
• Results First Posted: January 31, 2013

Record last verified: 2012-12

Locations

IT (1)