Recombinant Allergens Combined with Biological Markers in the Diagnosis of Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis Patients▿

Allergic bronchopulmonary aspergillosis (ABPA) is a frequent complication in cystic fibrosis patients. The diagnosis remains difficult and requires a combination of clinical, radiological, biological, and mycological criteria. The aim of this study was to analyze the added value of two recombinant antigens, rAspf4 and rAspf6, associated with the detection of specific IgG; precipitins; total IgE; and Aspergillus fumigatus in sputum for the diagnosis of ABPA. In a retrospective study, we determined the specific IgE responses to these recombinants in 133 sera of 65 cystic fibrosis patients. We selected an average of five serum samples from each of the 17 patients with ABPA (13 proven and 4 probable ABPA) and from 3 patients with Aspergillus bronchitis and rhinosinusitis. One serum sample for the 45 patients without ABPA was tested. The sensitivity of specific IgE detection against rAspf4 calculated per patient (92.3%) was significantly higher (P < 0.05) than that of rAspf6 (53.8%). When rAspf4 IgE detection was associated with anti-Aspergillus IgG enzyme-linked immunosorbent assay (ELISA) and precipitin detection, the sensitivity rose to 100%. The specificities of rAspf4 and rAspf6 IgE detection were 93.7% and 91.6%, respectively. Other diagnostic criteria had slightly lower specificities (87.5% for anti-Aspergillus IgG ELISA, 89.6% for precipitins, 84.4% for total IgE, and 85.0% for positive A. fumigatus culture in sputum). In conclusion, this retrospective study showed the relevance of rAspf4 IgE detection, in combination with other biological markers (Aspergillus IgG ELISA, precipitins, and total IgE), for improving the biological diagnosis of ABPA

Dramatic improvement in survival after lung transplantation over time: a single center experience.

International audienceLung transplantation (LT) is a recognized procedure for selected patients with end-stage respiratory failure. We performed 123 LT, including 32 single lung, 84 double lung, and 7 heart-lung transplantations in 48 patients with chronic obstructive pulmonary disease (COPD), 13 patients with pulmonary hypertension (PH), 33 with cystic fibrosis (CF), and 29 with interstitial lung disease (ILD) between July 1990 and January 2008. Survival was compared for periods before and after December 2001. The mean age of patients was 44.4 years (range 16-66.5 years); 84 (69%) were men. Before LT, 1 second forced expiratory volume was 28.7% +/- 18.1% and PaCO(2) = 6.3 kPa. Fifty-five patients were on noninvasive ventilation. Cold ischemia time was 320 +/- 91 minutes. Cardiopulmonary bypass (CPB) was used in 77 patients (64%). There were 18 early surgical reinterventions, 8 extracorporeal membrane oxygenations, and 38 bronchial stent insertions among 206 at-risk bronchial sutures. Crude survivals were 69%, 58%, 41%, and 18% at 1, 2, 5, and 10 years, respectively. Comparing before (n = 70 with 15 CF) vs after December 2001 (n = 53 with 17 CF), survivals were 63% vs 78%, 51% vs 71%, and 33% vs 60% at 1, 2, and 5 years, respectively (P = .01) and for CF patients, 52% vs 100%, 52% vs 94%, and 25% vs 94% at 1, 2, and 5 years, respectively (P = .005). There was significant improvement in survival before and after 2001 in 123 LT and particularly among CF patients. Improvement in survival after LT may be related to the sum of numerous changes in our practice since December 2001, including the use of pulmonary rehabilitation pre-LT, extracellular pneumoplegia, statins, macrolides for chronic rejection, monitoring of Epstein-Barr blood load, changes in maintenance immunosuppressants, as well as position movement up the coordinator nurse and learning curve

Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

International audienceRationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at 1 and 3 months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. Measurements and Main Results: Elexacaftor-tezacaftor- ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV1 = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV1 was +15.1 (+13.8 to +16.4; P < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; P < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P < 0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only 2 received a transplant, and 1 died. By September 2020, only five patients were still on the transplantation path. Compared with the previous 2 years, a twofold decrease in the number of lung transplantations in patients with CF was observed in 2020, whereas the number of deaths without transplantation remained stable. Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended