Effect of SARS-CoV-2 infection on anti-HLA antibodies and de novo donor specific antibodies incidence in lung transplant recipients.

PURPOSE: There are no clear guidelines on how to handle immunosuppression in lung transplant recipients (LTRs) infected by SARS-CoV-2. Antimetabolite reduction with corticosteroid escalation is the most frequent strategy. The aim of this study was to determine the effect of this therapeutic approach on the incidence of de novo donor specific-antibodies (dnDSA). METHODS: We retrospectively analysed a cohort of 27 LTRs diagnosed with SARS-CoV-2 infection between September 2020 and April 2021 with available anti-HLA antibodies screening before and after infection. Managed as per the centre's SARS-CoV-2 protocol, the treatment modalities included specific virostatic treatment, convalescent plasma administration, reduction or discontinuation of mycophenolate and transient corticosteroid escalation initiated in the second week post-infection. RESULTS: All 27 patients received virostatics: 15 (55.6%) remdesivir and 12 (44.4%) favipiravir. In addition, 18 patients (66.7%) underwent convalescent plasma therapy. Of the 27 patients, 25 (92.6%) received mycophenolate as a part of their maintenance immunosuppressive regimen, which was temporarily reduced in 10 (37%) and discontinued in 15 LTRs (55.6%), the median resumption times for mycophenolate daily doses of at least 1000 mg being 13 days (IQR 11.0-63.5) and 59 days (IQR 26.0-130.0), respectively. Corticosteroids were escalated in 25 patients (92.6%), of whom 9 (33.3%) received IV methylprednisolone (median 80 mg/day; IQR 80-187.5) and 16 (59.3%) had oral prednisone adjusted (median 20 mg/day; IQR 16.3-38.8). The median time to revert to the corticosteroid dosage of ≤20 mg/day was 42 days (IQR 36.0-87.0). Notably, no dnDSA were detected in any LTR between 1 and 9 months from the onset of the SARS-CoV-2 infection. CONCLUSION: Our findings suggest that antimetabolite cessation with a transient corticosteroid escalation is a safe therapeutic strategy regarding anti-HLA dynamics in SARS-CoV-2 infected LTRs.

Continued Smoking in Lung Transplant Patients: A Cross Sectional Survey.

INTRODUCTION: Smoking is associated with a higher incidence of post-lung transplantation complications and mortality. Prior to inclusion on the lung transplant waiting list in the Czech Republic, patients are supposed to be tobacco free for at least 6 months. Our aim was to determine the prevalence of smoking, validated by urinary cotinine, among patients post lung transplantation and prior to inclusion on the transplant waiting list. METHODS: Between 2009 and 2012, we conducted a cross-sectional survey of urinary cotinine to assess tobacco exposure in 203 patients in the Lung Transplant Program in the Czech Republic. We measured urinary cotinine in 163 patients prior to inclusion on the transplantation waiting list, and 53 patients post bilateral lung transplantation. RESULTS: 15.1% (95% CI 0.078 to 0.269) of all lung transplant recipients had urinary cotinine levels corresponding to active smoking; and a further 3.8% (95% CI 0.007 to 0.116) had borderline results. Compared to patients with other diagnoses, patients with COPD were 35 times more likely to resume smoking post- transplantation (95% CI 1.92 to 637.37, p-value 0.016). All patients who tested positive for urinary cotinine levels were offered smoking cessation support. Only one Tx patient sought treatment for tobacco dependence, but was unsuccessful. CONCLUSION: Smoking resumption may be an underrecognized risk for lung transplantation recipients, particularly among patients with chronic obstructive pulmonary disease. More rigorous screening, as well as support and treatment to stop smoking among these patients are needed.

Ivacaftor in cystic fibrosis adults: Czech experience with six years of follow-up.

AIMS: Ivacaftor is a revolutionary treatment option for cystic fibrosis (CF) patients with G551D and other gating mutations. The aim of this study was to evaluate the clinical status of patients on ivacaftor who were followed for up to 6 years together with an evaluation of ivacaftor therapy in one patient with an initial FEV1 less than 40% of predicted value. METHODS: Data on development of clinical status and sinopulmonary-related therapies were obtained from patient health records during ivacaftor treatment lasting for up to six years and were compared with an equivalent period before ivacaftor administration. RESULTS: Five CF adults with a median age 28.6 years (range 21.4-35.6 years) with median FEV1 45% pred. (range 16-85% pred.) were included in the study. Four subjects were also participants in the STRIVE and PERSIST studies. Altogether, twenty-four patient-years of ivacaftor treatment were analyzed. The median FEV1 decline per year decreased from -4.5 to -0.9% pred. (P = 0.043). Reduction in number of days on antibiotic treatment and hospital stays was 21% (P < 0.001) and 75% (P = 0.003), respectively. Improvement and stabilization of lung function was observed for up to six years of treatment. In a patient with severe airway obstruction, an increase in the FEV1 value (30.4% from baseline) was documented during the first twelve months of treatment. CONCLUSION: Ivacaftor therapy resulted in improved and stabilized lung function in up to six years of treatment with a reduction in number of days on antibiotic treatment and hospital stays. Its efficiency was also displayed in a patient with severe airway obstruction.