Lieven Dupont

Lung transplantation is currently considered as an ultimate live-saving treatment for selected patients suffering from end-stage pulmonary disease. Long-term survival, however, is hampered by chronic rejection, or chronic lung allograft dysfunction (CLAD). Recently, various phenotypes within CLAD have been identified, challenging the established clinical definition of bronchiolitis obliterans syndrome (BOS). Some patients with presumed BOS, for instance, demonstrate an important improvement in forced expiratory volume in the first second of expiration (FEV₁) after treatment with azithromycin. These patients are characterized by the presence of excess (≥15%) bronchoalveolar lavage (BAL) neutrophils, in absence of concurrent infection. This phenotype of CLAD has been redefined as neutrophilic reversible allograft dysfunction (NRAD), and these patients generally have a very good prognosis after diagnosis. Another group of patients with CLAD develop a restrictive rather than an obstructive pulmonary function defect (defined as a decline in total lung capacity of at least 10%) and demonstrate persistent interstitial and ground-glass opacities on chest computed tomographic (CT) scan. This phenotype is called restrictive allograft syndrome (RAS), and patients with RAS have a much worse prognosis after diagnosis. This review further discusses both of these CLAD phenotypes that do not fit the classical definition of BOS. Potential pathophysiological mechanisms, etiology, diagnosis, prognosis, and treatments are discussed.

There is a relative lack of information about the death rate and morbidity of non-cystic fibrosis bronchiectasis and most studies are limited due to referral bias. We wanted to assess death rate and morbidity in those patients at our hospital.

Rheumatic diseases as well as inflammatory bowel disease (IBD) have been associated with the occurrence of non-cystic fibrosis bronchiectasis (NCFB). There are few data on NCFB and adverse events from immunosuppressive or biological response modifier therapy in patients with rheumatoid arthritis (RA) or IBD and NCFB. We identified 37 patients with NCFB and rheumatic disease, and nine patients with inflammatory bowel disease that received immunomodulatory treatment. We retrospectively analysed adverse pulmonary events. In nine patients with RA, the association between disease activity score (DAS) and spirometry was analysed in a small cohort study. Pulmonary side effects occurred in 50% of patients, most commonly respiratory infections, and resulted in a change of immunomodulatory treatment in 37% of patients. Spirometry and exacerbation rate was not different in NCFB patients with RA or IBD as compared with NFCB due to other causes. The incidence of pulmonary adverse events was highest in patients treated with conventional immunomodulatory treatment, especially methotrexate, as compared with patients with NCFB treated with newer biological therapies. Three patients were started on azithromycin because of recurrent bronchitis and had no events afterwards. Serial assessment of DAS and spirometry showed that a rise in DAS was associated with lung function decline and vice versa. Currently used immunosuppressive drugs can be used in NCFB albeit under close follow-up. The role of azithromycin for infection prevention needs further research. An association between DAS and lung function was shown.