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Azithromycin reduces airway inflammation and improves forced expiratory volume in 1 s (FEV1) in chronic rejection or bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Azithromycin prophylaxis might prevent BOS.A double-blind randomised controlled trial of azithromycin (n540) or placebo (n543), initiated at discharge and administered three times a week for 2 yrs, was performed in 2005-2009 at the Leuven University Hospital (Leuven, Belgium). Primary end-points were BOS-free and overall survival 2 yrs after LTx; secondary end-points were acute rejection, lymphocytic bronchiolitis and pneumonitis rate, prevalence of pseudomonal airway colonisation or gastro-oesophageal reflux, and change in FEV1, airway and systemic inflammation over time. Patients developing BOS were assessed for change in FEV1 with open-label azithromycin.BOS occurred less in patients receiving azithromycin: 12.5 versus 44.2% (p50.0017). BOS-free survival was better with azithromycin (hazard ratio 0.27, 95% CI 0.092-0.816; p50.020). Overall survival, acute rejection, lymphocytic bronchiolitis, pneumonitis, colonisation and reflux were comparable between groups. Patients receiving azithromycin demonstrated better FEV1 (p50.028), and lower airway neutrophilia (p50.015) and systemic C-reactive protein levels (p50.050) over time. Open-label azithromycin for BOS improved FEV1 in 52.2% patients. No serious adverse events were noted.Azithromycin prophylaxis attenuates local and systemic inflammation, improves FEV1 and reduces BOS 2 yrs after LTx.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Bronchiolitis obliterans syndrome (BOS) is the leading cause of death after lung transplantation. Treatment is challenging, as the precise pathophysiology remains unclear.We hypothesize that T H 17 lineage plays a key role in the pathophysiology of BOS by linking T-cell activation to neutrophil influx and chronic inflammation.

Airway colonisation with Pseudomonads, especially Pseudomonas aeruginosa, is common in lung transplant (LTx) recipients. The current authors investigated whether pseudomonal colonisation affects the prevalence of bronchiolitis obliterans syndrome (BOS) after lung transplantation.In the present retrospective study, 92 double (SS)LTx recipients (26 cystic fibrosis (CF) and 66 non-CF patients), with at least two consecutive post-operative bronchoalveolar lavage or sputum cultures evaluated for Pseudomonads, were included. Freedom of BOS was investigated in postoperatively colonised and noncolonised patients.The current study has shown post-operative airway colonisation to be an independent risk factor for BOS stage o1 and to be associated with a worse BOS stage o1-free survival in univariate analysis, especially in CF SSLTx recipients. Multivariate analysis demonstrated a trend for colonisation only as an independent risk factor for BOS; however, this pointed to a possible role in the development of BOS.In conclusion, pseudomonal airway colonisation after lung transplantation may be associated with an increased prevalence of bronchiolitis obliterans syndrome, especially in cystic fibrosis patients. Possible pathophysiological mechanisms in the development of bronchiolitis obliterans syndrome need further investigation, although the induction of neutrophilic airway inflammation seems to be its main characteristic.

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