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.

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.

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.

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.

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.