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Expert Interviews
Respiratory Disorders, Immunology CE/CME accredited

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Optimizing management of bronchiolitis obliterans syndrome: Current strategies, future directions

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Dr Michael Perch is the director of the national Danish lung transplant programme at Rigshospitalet and associate professor of Clinical Medicine in the Department of Clinical Medicine at the University of Copenhagen in Denmark. read more

Dr Perch has been on the board of the National Danish Transplant Society for 12 years, including 4 years as chairman. He also serves on the Scientific Advisory Committee for the Centre for Personalised Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE) and the board for the Management of Post-Transplant Infections in Collaborating Hospitals (MATCH). He is currently on the Scandiatransplant board and is also the associate medical director of the International Thoracic Transplant Registry, the chair of the European Respiratory Society Transplantation Group 8.02, and the treasurer of the European Society of Heart and Lung Transplantation.

Dr Perch actively contributes to numerous academic clinical trials. His expertise extends to primary graft dysfunction, chronic lung allograft dysfunction, infections and immunosuppression. Additionally, he plays a key role in the development and study of treatments within interventional pulmonology.

Dr Michael Perch discloses: Advisory board or panel fees from TFF Pharmaceuticals and Zambon. Consultancy fees from Novo Nordisk, Ryme Medical and Takeda. Grants/research support from Pulmonx. Speaker bureau fees from AstraZeneca and Takeda.

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Dr Howard J Huang is the medical director of the lung transplant programme at Houston Methodist JC Walter Jr. Transplant Center and an associate professor of Clinical Medicine at Weill Cornell Medical College, Houston, TX, USA. read more

Dr Huang completed an internal medicine internship and residency at Parkland Memorial Hospital/UT Southwestern Medical Center in Dallas, and a fellowship in pulmonary and critical care medicine at Barnes Jewish Hospital/Washington University School of Medicine in St. Louis, Missouri. In 2014 Dr Huang became the associate medical director of Lung Transplantation and director of Lung Transplant Research. He has received funding from the National Institutes of Health, the American Thoracic Society and the International Society for Heart and Lung Transplantation. Dr Huang combines his interests in clinical and translational research with helping lung transplant patients achieve better long-term outcomes.

Dr Howard Huang discloses: Advisory board or panel fees from CareDx, Lung Bioengineering and Zambon. Speaker bureau fees from Boehringer Ingelheim and Takeda.

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Dr Aldo Iacono is a professor of cardiovascular and thoracic surgery at the Zucker School of Medicine at Hofstra/Northwell Health, and the medical director of the Northwell Health Lung Transplantation Program in Hempstead, NY, USA. read more

Dr Iacono is widely recognized as an expert in lung transplantation and advanced lung diseases and he currently leads a multidisciplinary surgical and medical team in providing clinical and academic care. Dr Iacono has vast experience in the field since 1992 having developed lung transplant programmes in clinical and academic medicine, and surgery, at the University of Pittsburgh and the University of Maryland School of Medicine. He was awarded the rank of Distinguished Professor in 2017 by the University of Maryland. Dr Iacono has authored over 120 publications. Alongside his clinical work, teaching and training fellows is a priority for Dr Iacono, having mentored over 95 surgical residents and fellows, including the current surgical director of cardiothoracic transplant at Northwell Health.

Dr Aldo Iacono discloses: Other financial or material support (royalties, patent, etc.): Patent for aerosol cyclosporine. Stock or shareholder (self-managed) of AI Therapeutics (relationship terminated).

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Dr Aldo Iacono is a professor of cardiovascular and thoracic surgery at the Zucker School of Medicine at Hofstra/Northwell Health, and the medical director of the Northwell Health Lung Transplantation Program in Hempstead, NY, USA. read more

Dr Iacono is widely recognized as an expert in lung transplantation and advanced lung diseases and he currently leads a multidisciplinary surgical and medical team in providing clinical and academic care. Dr Iacono has vast experience in the field since 1992 having developed lung transplant programmes in clinical and academic medicine, and surgery, at the University of Pittsburgh and the University of Maryland School of Medicine. He was awarded the rank of Distinguished Professor in 2017 by the University of Maryland. Dr Iacono has authored over 120 publications. Alongside his clinical work, teaching and training fellows is a priority for Dr Iacono, having mentored over 95 surgical residents and fellows, including the current surgical director of cardiothoracic transplant at Northwell Health.

Dr Aldo Iacono discloses: Other financial or material support (royalties, patent, etc.): Patent for aerosol cyclosporine. Stock or shareholder (self-managed) of AI Therapeutics (relationship terminated).

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  • Downloads including slides are available for this activity in the Toolkit
Learning Objectives

After watching this activity, participants should be better able to:

  • Describe the pathogenesis of BOS and the burden on patients post-lung transplantation
  • Apply practical guidance to the diagnosis of BOS after lung transplantation
  • Evaluate the current and emerging treatment options for BOS in lung transplant recipients
Overview

Three experts discuss the pathogenesis, diagnosis and treatment for bronchiolitis obliterans syndrome (BOS).

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of pulmonologists, transplant physicians and internists involved in the management of patients with BOS.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Dr Michael Perch discloses: Advisory board or panel fees from TFF Pharmaceuticals and Zambon. Consultancy fees from Novo Nordisk, Ryme Medical and Takeda. Grants/research support from Pulmonx. Speaker bureau fees from AstraZeneca and Takeda.

Dr Howard Huang discloses: Advisory board or panel fees from CareDx, Lung Bioengineering and Zambon. Speaker bureau fees from Boehringer Ingelheim and Takeda.

Dr Aldo Iacono discloses: Other financial or material support (royalties, patent, etc.): Patent for aerosol cyclosporine. Stock or shareholder (self-managed) of AI Therapeutics (relationship terminated).

Content reviewer

Carolina Leon, BSN, MSN, ARNP-BC, has no relevant financial relationships to disclose.

Touch Medical Contributors

Katrina Lester has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 23 May 2024. Date credits expire: 23 May 2025.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

This activity is CE/CME accredited

To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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Topics covered in this activity

Respiratory Disorders / Immunology
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touchEXPERT OPINIONS
Optimizing management of bronchiolitis obliterans syndrome: Current strategies, future directions
0.75 CE/CME credit

Question 1/5
In a prospective, German single-centre cohort study of LTx recipients who developed severe CLAD and significant disability, what was the average DALYs per patient?

CLAD, chronic lung allograft dysfunction; DALYs, disability-adjusted life years; LTx, lung transplantation.

A prospective, German single-centre cohort study of 1,025 LTx recipients between 2010–2020 reported that patients with severe CLAD who developed significant disability lost 1.3 life years and lived for 0.8 years with their disability, adding up to an average 2.1 DALYs (range 2.0–2.7) per patient.

Abbreviations
CLAD, chronic lung allograft dysfunction; DALYs, disability-adjusted life years; LTx, lung transplantation.

Reference
Diel R, et al. Adv Respir Med. 2023;91:432–44.

Question 2/5
When discussing the pathogenesis of post-LTx BOS with colleagues, which of the following descriptions would you use?

BOS, bronchiolitis obliterans syndrome; IL, interleukin; LTx, lung transplantation.

BOS, an obstructive phenotype of CLAD, occurs as a consequence of recurrent injuries to the lung allograft, which are either immune or non-immune related, and result in excessive scarring and aberrant healing.1

BOS in LTx recipients is a host-versus-graft effect, whereas BOS post-HSCT derives from graft-versus-host mediated rejection mechanisms, in which T cells play a major role.2 Mucus hyperconcentration and epithelial hypoxia are hallmarks of non-cystic fibrosis bronchiectasis,3 and upregulation of cytokines IL-4 and IL-13 are implicated in type 2 asthma.4

Abbreviations
BOS, bronchiolitis obliterans syndrome; CLAD, chronic lung allograft dysfunction; HSCT, haematopoietic stem cell transplantation; IL, interleukin; LTx, lung transplantation.

References

  1. Royer P-J, et al. Transplantation. 2016;100:1803–14.
  2. Glanville AR, et al. ERJ Open Res. 2022;8:00185-2022.
  3. Dickinson JD, et al. Am J Respir Crit Care Med. 2024;209:347–59.
  4. Dunican EM, Fahy JV. Ann Am Thorac Soc. 2015;12(Suppl. 2):S144–9.
Question 3/5
Your patient, who received a double LTx 18 months ago, has experienced a 30% decline in their baseline FEV1 over the last 4 months. Which of the following tools would you use to confirm a diagnosis of definite CLAD and phenotype their condition?

BAL, bronchoalveolar lavage; CLAD, chronic lung allograft dysfunction; CT, computerized tomography; FEV1 forced expiratory volume in one second; LTx, lung transplantation; PFTs, pulmonary function tests; TLC, total lung capacity.

Following a diagnosis of definite CLAD, the disease is phenotyped using a combination of PFTs (spirometry and TLC) and CT scans.1 The ratio FEV1/FVC is indicative of an obstructive (<0.7) vs restrictive (>0.7) CLAD phenotype, with decline in TLC of ≥10% further supporting a restrictive phenotype. CT opacities are associated with restrictive disease, but not obstructive.1

Transbronchial biopsy and BAL detect treatable causes of reduced lung function prior to diagnosing CLAD, but are not used for disease phenotyping.1 Oscillometry is an emerging tool that lacks standardized protocols for routine clinical use.2

Abbreviations
BAL, bronchoalveolar lavage; CLAD, chronic lung allograft dysfunction; CT, computerized tomography; FVC, forced vital capacity; FEV1, forced expiratory volume in one second; PFTs, pulmonary function tests; TLC, total lung capacity.

References

  1. Verleden GM, et al. J Heart Lung Transplant. 2019;38:493–503.
  2. Sarkar S, et al. Cureus. 2023;15:e47935.
Question 4/5
Your patient who received a single LTx is being treated with tacrolimus-based immunosuppression to prevent rejection. Due to declining lung function, you are investigating probable BOS. BAL results indicate airway neutrophilia. Based on available data, which of the following treatment options would you select?

BAL, bronchoalveolar lavage; BOS, bronchiolitis obliterans syndrome; LTx, lung transplantation.

Available evidence suggests that the presence of airway neutrophilia (detected by BAL) and early treatment initiation are factors that increase the likelihood of response to azithromycin in patients with BOS.1 Treatment is recommended even prior to a definite BOS diagnosis.1 Montelukast may be effective in patients with late-onset BOS stage 1 who are azithromycin-refractory.2 RATG is a second-line BOS therapy.3 Pirfenidone has been investigated in BOS, but is not approved.3

Abbreviations
BAL, bronchoalveolar lavage; BOS, bronchiolitis obliterans syndrome; RATG, rabbit anti-thymocyte globulin.

References

  1. Meyer KC, et al. Eur Respir J. 2014;44:1479–503.
  2. Ruttens D, et al. PLoS ONE. 2018;13:e0193564.
  3. Glanville AR, et al. ERJ Open Res. 2022;8:00185-2022.
Question 5/5
What is a key benefit of treating patients with post-LTx BOS with aerosolized vs oral cyclosporine?

BOS, bronchiolitis obliterans syndrome; LTx, lung transplantation.

The primary advantage of aerosolized vs oral cyclosporine is that large concentrations of therapeutically active drug are delivered directly into the lungs, with consequent reductions in the amount of drug circulating systemically.1 Inhaled L-CsA is under investigation in patients with post-LTx BOS alongside tacrolimus-based standard of care immunosuppression.2-4 Oral and aerosolized cyclosporine are both administered twice daily.1-5

Abbreviations
BOS, bronchiolitis obliterans syndrome; L-CsA, liposomal cyclosporine A; LTx, lung transplantation.

References

  1. Iacono A, et al. ERJ Open Res. 2019;5:00167-2019.
  2. ClinicalTrials.gov. NCT03657342. Available at: https://clinicaltrials.gov/study/NCT03657342 (accessed 3 May 2024).
  3. ClinicalTrials.gov. NCT03656926. Available at: https://clinicaltrials.gov/study/NCT03656926 (accessed 3 May 2024).
  4. ClinicalTrials.gov. NCT04039347. Available at: https://clinicaltrials.gov/study/NCT04039347 (accessed 3 May 2024).
  5. Matsuda Y, et al. Interact Cardiovasc Thorac Surg. 2014;19:171–3.
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