title: Pilot safety study of intrabronchial instillation of bone marrow-derived mononuclear cells in patients with silicosis.
abstract: BACKGROUND
  Silicosis is an occupational disease for which no effective treatment is currently known. Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) has shown to be safe in lung diseases. However, so far, no studies have analyzed whether bronchoscopic instillation of autologous BMDMCs is a safe route of administration in patients with silicosis.
  
  
  METHODS
  We conducted a prospective, non-randomized, single-center longitudinal study in five patients. Inclusion criteria were age 18-50 years, chronic and accelerated silicosis, forced expiratory volume in 1 s <60 % and >40 %, forced vital capacity ≥60 % and arterial oxygen saturation >90 %. The exclusion criteria were smoking, active tuberculosis, neoplasms, autoimmune disorders, heart, liver or renal diseases, or inability to undergo bronchoscopy. BMDMCs were administered through bronchoscopy (2 × 10(7) cells) into both lungs. Physical examination, laboratory evaluations, quality of life questionnaires, computed tomography of the chest, lung function tests, and perfusion scans were performed before the start of treatment and up to 360 days after BMDMC therapy. Additionally, whole-body and planar scans were evaluated 2 and 24 h after instillation.
  
  
  RESULTS
  No adverse events were observed during and after BMDMC administration. Lung function, quality of life and radiologic features remained stable throughout follow-up. Furthermore, an early increase of perfusion in the base of both lungs was observed and sustained after BMDMC administration.
  
  
  CONCLUSIONS
  Administration of BMDMCs through bronchoscopy appears to be feasible and safe in accelerated and chronic silicosis. This pilot study provides a basis for prospective randomized trials to assess the efficacy of this treatment approach. CLINICAL TRIALS.
  NCT01239862 Date of Registration: November 10, 2010.
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Institute of Biophysics Carlos Chagas Filho, da Saude Science Center, Federal University of Rio de Janeiro, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil. mmorales@biof.ufrj.br.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.affiliation: Nuclear Medicine Service, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. sergioalsouza@gmail.com.
authors.forename: Sérgio A L
authors.initials: SA
authors.lastname: Souza
authors.affiliation: Institute of Thoracic Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. lploivos@uninet.com.br.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Loivos
authors.affiliation: Institute of Thoracic Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. malima@globo.com.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Lima
authors.affiliation: Institute of Thoracic Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. amirszklo@gmail.com.
authors.forename: Amir
authors.initials: A
authors.lastname: Szklo
authors.affiliation: Laboratory of Cellular and Molecular Cardiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. leandrovairo@yahoo.com.br.
authors.forename: Leandro
authors.initials: L
authors.lastname: Vairo
authors.affiliation: Laboratory of Cellular and Molecular Cardiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. kasaitaus@yahoo.com.br.
authors.forename: Taís H K
authors.initials: TH
authors.lastname: Brunswick
authors.affiliation: Nuclear Medicine Service, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. bianca.gutfilen@gmail.com.
authors.forename: Bianca
authors.initials: B
authors.lastname: Gutfilen
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Institute of Biophysics Carlos Chagas Filho, da Saude Science Center, Federal University of Rio de Janeiro, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil. mlopes0811@gmail.com.|Laboratory of Pulmonary Investigation, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. mlopes0811@gmail.com.
authors.forename: Miquéias
authors.initials: M
authors.lastname: Lopes-Pacheco
authors.affiliation: Institute of Thoracic Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. ajaraujo@hucff.ufrj.br.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Araújo
authors.affiliation: Institute of Thoracic Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. pneumoalex@globo.com.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Cardoso
authors.affiliation: Laboratory of Cellular and Molecular Cardiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. rcoeli@biof.ufrj.br.
authors.forename: Regina C
authors.initials: RC
authors.lastname: Goldenberg
authors.affiliation: Laboratory of Pulmonary Investigation, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. prmrocco@gmail.com.
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
authors.affiliation: Nuclear Medicine Service, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. leamirian@gmail.com.
authors.forename: Lea M B
authors.initials: LM
authors.lastname: Fonseca
authors.affiliation: Institute of Thoracic Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. jrlapa@hotmail.com.
authors.forename: José R
authors.initials: JR
authors.lastname: Lapa e Silva
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D001999:Bronchoscopy / Q000379:methods*; D005240:Feasibility Studies; D005434:Flow Cytometry; D005541:Forced Expiratory Volume; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008137:Longitudinal Studies; D008168:Lung / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D055420:Perfusion Imaging; D010865:Pilot Projects; D011446:Prospective Studies; D011653:Pulmonary Diffusing Capacity; D012829:Silicosis / Q000628:therapy*; D015899:Tomography, Emission-Computed, Single-Photon; D014109:Total Lung Capacity; D014182:Transplantation, Autologous; D014797:Vital Capacity