Bronchopulmonary penetration of isavuconazole in lung transplant recipients.

Isavuconazole's (ISA) pharmacokinetics was studied among lung transplant recipients to evaluate its bronchopulmonary penetration. This study included 13 patients and showed mean serum concentrations of 3.30 (standard deviation [SD] 0.45), 5.12 (SD 1.36), and 6.31 (SD 0.95) at 2 h, 4 h, and 24 h respectively. Mean concentrations in the epithelial lining fluid were 0.969 (SD 0.895), 2.141 (SD 1.265), and 2.812 (SD 0.693) at the same time points. ISA is a drug with a tolerable safety profile that achieves adequate concentrations in the lung.

Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services.

BACKGROUND: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. METHODS: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. RESULTS: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. CONCLUSIONS: The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images.

Peripheral blood eosinophilia as a marker of acute cellular rejection in lung transplant recipients.

Previous studies in solid organ transplantation have shown a relationship between circulating eosinophil (EOS) counts and the presence of acute cellular rejection (ACR). However, the relationship between this potential biomarker and ACR in lung transplant (LTx) patients remains unclear. OBJECTIVE: To assess the association between EOS and the presence of acute cellular rejection in lung transplant recipients. MATERIALS AND METHODS: Retrospective study of 583 transbronchial biopsies (TBB) performed in 256 lung transplant patients between 2012 and 2018. We analyzed age, sex, underlying pathology, date of transplant, indications for TBB, presence and degree of ACR, and the simultaneous absolute and relative EOS. RESULTS: ACR were observed in 170 of 583 TBB (29.2%). EOS in patients with ACR were higher than in patients without ACR (203.6 ± 248/mm3 vs 103.1 ± 153/mm3; p < 0.001). High levels of both absolute and relative EOS were associated with the presence of ACR regardless of the underlying disease (odds ratio [OR] 1.003; 95% confidence interval [CI], 1.002-1.004; OR 1.226; 95% CI, 1.120-1.342) and time after transplant (OR 1.003; 95% CI, 1.002-1.004 and OR 1.239; 95% CI, 1.132-1.356). Moreover, both absolute and relative EOS were strongly associated with moderate and severe grades of ACR (OR 3.55; 95% CI, 3.00-4.10 and OR 3.56; 95% CI, 3.00-4.12). CONCLUSIONS: EOS are elevated in ACR, especially in moderate or severe ACR. Increased vigilance for ACR is therefore advisable in lung transplant recipients with elevated EOS.

Interrupted versus continuous suture for bronchial anastomosis in lung transplantation: does it matter?

OBJECTIVES: Bronchial anastomotic complications remain a major concern in lung transplantation. We aim to compare 2 different techniques, continuous suture (CS) versus interrupted suture (IS) by analysing airway complications requiring intervention. METHODS: Lung transplantations between January 2015 and December 2020 were included. Airway complications requiring intervention were classified following the 2018 International Society for Heart and Lung Transplantation consensus and analysed comparing 3 groups of patients according to surgical technique: group A, both anastomosis performed with CS; group B, both with interrupted; and group C, IS for 1 side and CS for the contralateral side. RESULTS: A total of 461 anastomoses were performed in 245 patients. The incidence of airway complications requiring intervention was 5.7% [95% confidence interval (CI): 2.8-8.6] per patient (14/245) and 3.7% (95% CI: 2.0-5.4) per anastomosis (17/461). Complications that required intervention were present in 5 out of 164 (3.1%) anastomosis with interrupted technique, and in 12/240 (5%) with CS. No significant differences were found between techniques (P = 0.184). No statistical differences were found among group A, B or C in terms of incidence of anastomotic complications, demographics, transplant outcomes or overall survival (log-rank P = 0.513). In a multivariable analysis, right laterality was significantly associated to complications requiring intervention (OR 3.7 [95% CI: 1.1-12.3], P = 0.030). Endoscopic treatment was successful in 12 patients (85.7%). Retransplantation was necessary in 2 patients. CONCLUSIONS: In summary, although it seems that anastomotic complications requiring intervention occur more frequently with CS, there are no statistical differences compared to IS. Endoscopic treatment offers good outcomes in most of the airway complications after lung transplantation.

[Is endoscopic treatment of bronchopleural fistula useful?]. / 'Es útil el tratamiento endoscópico de las fístulas bronquiales?

OBJECTIVE: New endoscopic techniques have been developed as an alternative to surgical treatment of bronchopleural fistula. The objective of this study was to analyze our experience with endoscopic treatment of such fistulas. MATERIAL AND METHODS: We conducted a retrospective study of patients with bronchopleural fistula diagnosed by fiberoptic bronchoscopy. Patient characteristics, underlying disease, fistula size, and outcome of endoscopic treatment were analyzed. The endoscopic technique consisted of injection of fibrin sealants (Histoacryl and/or Tissucol) through the catheter of the fiberoptic bronchoscope. RESULTS: Between 1997 and 2004, 18 patients were diagnosed with bronchopleural fistula by fiberoptic bronchoscopy. All were men with a mean (SD) age of 62 (12) years. Bronchopleural fistula was diagnosed after neoplastic surgery in 16 patients, in the bronchial suture after lung transplantation in 1 patient, and concurrently with pleural effusion due to hydatidosis in the remaining patient. The size of the fistula ranged from 1 mm to 10 mm (mean 3.6 [2.7] mm). Fibrin sealants were applied in 14 patients, 2 underwent direct surgery after diagnosis, and the bronchopleural fistula closed spontaneously in the remaining 2. The fibrin sealant used was Histoacryl in 12 patients and Tissucol in 2. Pleural drainage was employed simultaneously and antibiotic therapy was administered at the discretion of the surgeon. The 4 patients whose bronchopleural fistula was associated with empyema also underwent pleural lavage. In 12 patients the fistulas closed as a result of the endoscopic technique (85.7%), and no complications were observed. For 85.7%, fewer than 3 applications of fibrin sealant were necessary. CONCLUSIONS: The success rate of closure of bronchopleural fistula with fibrin sealants injected under guidance with fiberoptic bronchoscopy is high and there are no complications. This technique can render surgery unnecessary.

Cytomegalovirus Immunoglobulin for Prophylaxis and Treatment of Cytomegalovirus Infection in the (Val)Ganciclovir Era: A Single-Center Experience.

BACKGROUND: Evidence concerning the effectiveness of anti-cytomegalovirus immunoglobulin (CMVIg) following lung transplantation in the era of new antiviral agents is limited and controversial. MATERIAL AND METHODS: At-risk patients (donor seropositive/recipient seronegative [D+/R-] and R+) received valganciclovir for 3 months (R+) or 6 months (D+/R). CMVIg (2 mg/kg) was given to D+/R- patients on days 1, 4, 8, 15, and 30 post-transplant, then monthly for a further year. Patients with valganciclovir-induced leukopenia were switched to CMVIg (2 mg/kg) prophylaxis. Tissue-invasive disease was treated with intravenous ganciclovir with CMVIg (2 mg/kg) every other day for 1 week and then weekly until discharge. RESULTS: Of 159 patients analyzed, 26 (17%) were D+/R-. Cytomegalovirus (CMV) viremia was more frequent in D+/R- recipients than in R+ patients (61% vs. 35%; P<0.05), but developed at a similar time (mean 10±6 vs. 11±7 months) and resolved in all cases following treatment. One patient developed clinical and laboratory signs of CMV syndrome (fever >38°C), leukopenia, and detection of CMV in blood. Ten patients developed tissue-invasive disease after completion of prophylaxis (5 pneumonitis and 5 gastrointestinal disease); all were successfully treated with combined intravenous ganciclovir and CMVIg. None of the 18 donor seropositive/recipient seronegative patients who were switched from valganciclovir to CMVIg for persistent leukopenia developed CMV viremia during treatment. No cases of CMV infection or disease were attributable to ganciclovir-resistant strains. During follow-up, 44 patients died (4/26 R+/D- [15%], 40/133 R+ [30%), none directly due to CMV infection. CONCLUSIONS: Combined prophylaxis with valganciclovir and CMVIg delayed CMV viremia and tissue-invasive disease in D+/R- lung transplant recipients, and prevented CMV-related mortality and development of ganciclovir resistance. CMVIg monotherapy prophylaxis was effective in R+ patients with ganciclovir-related toxicity.

[Aspergillus tracheobronchitis in a lung transplant recipient]. / Traqueobronquitis aspergilar en paciente sometido a trasplante pulmonar.

BACKGROUND: Aspergillus tracheobronchitis is an uncommon cause of pulmonary aspergillosis and almost exclusively affects lung transplant recipients. There is no lung tissue involvement, thus the tracheobron-chial tree is only affected. Patients are asymptomatic, so it is important to make an early diagnosis to prevent progression of the infection and airway complications. Several prophylaxis and treatment strategies have proven to improve the prognosis. CLINICAL CASE: This is the case of a 56 year-old man who underwent bilateral lung transplant for chronic obstructive pulmonary disease (COPD) and developed Aspergillus tracheobronchitis. He received the usual prophylaxis with nebulized liposomal amphotericin B every 48 h. Routine bronchoscopy performed 2 weeks after transplantation showed inflammation with the presence of pseudomembranes that produced a 50% stenosis of the right bronchial anastomosis. Biopsy of the pseudomembranes and bronchial aspirate yielded Aspergillus fumigatus. The patient started treatment with voriconazole twice a day, bronchial debridement through bronchoscopy was carried out, and the treatment with nebulized liposomal amphotericin B was continued every other day. Ten weeks later, there were no endobronchial lesions and the bronchial aspirate cultures were negative. CONCLUSIONS: Aspergillus tracheobronchitis is a complication of the lung transplant recipient. Early diagnosis and prompt antifungal therapy, including new antifungal agents and local debridement, may significantly improve the outcome.

Feasibility, tolerability, and outcomes of nebulized liposomal amphotericin B for Aspergillus infection prevention in lung transplantation.

BACKGROUND: Nebulized amphotericin B deoxycholate (n-ABD) is used to prevent Aspergillus infection in lung transplantation. Nebulized liposomal amphotericin B (n-LAB) is another option; however, no clinical data are available on the results of n-LAB for this purpose. METHODS: In an observational study performed in 2 centers to assess the feasibility, tolerability, and outcomes of n-LAB prophylaxis, 104 consecutive patients undergoing prophylaxis with n-LAB were compared with 49 historical controls who received n-ABD. Patient follow-up lasted 12 months. The n-LAB prophylaxis regimen was 25 mg thrice weekly starting on the first post-operative day and continuing to 60 days, 25 mg once weekly from 60 to 180 days, and the same dose once every 2 weeks thereafter. RESULTS: Aspergillus infection developed in 8 of 104 patients (7.7%) with n-LAB prophylaxis (5 colonization, 1 simple tracheobronchitis, 1 ulcerative tracheobronchitis, and 1 invasive pulmonary infection). Ulcerative tracheobronchitis and invasive pulmonary aspergillosis were regarded as invasive disease; hence, the rate of invasive disease was 1.9% (2 patients). The control group had similar rates of Aspergillus infection (10.2%; p = 0.6) and invasive disease (4.1%; p = 0.43). In 3 patients (2.9%), n-LAB was withdrawn due to bronchospasm in 2 and nausea in 1. In the control group, prophylaxis was stopped in 2 patients (4.1%) because of bronchospasm (p = 0.7). CONCLUSIONS: At the dose and frequency described, n-LAB seems effective, safe, and convenient for the prevention of Aspergillus infection in lung transplant patients.

Results of clinical lung transplant from uncontrolled non-heart-beating donors.

BACKGROUND: The scarcity of grafts for lung transplant and the growing number of candidates expecting an organ has led to an increase of deaths in patients waiting for lung transplantation. Non-heart-beating donors (NHBD) represent a promising source of grafts for those who are involved in clinical lung transplantation. We present the results of our series of 17 out-of-hospital NHBD lung transplantations performed since 2002. METHODS: We have collected data from 17 donors and recipients involved in NHBD lung transplants since 2002, as well as data referring to the type of procedure and peri-operative events. We describe the incidence of post-operative complications with special attention to primary graft disfunction (PGD), bronchial healing, bronchiolitis obliterans syndrome (BOS), and survival. We used Kaplan-Meier method to obtain the survival curve. RESULTS: G2-G3 PGD was reported in 9 patients (53%), with a complete restoration of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio in 170 hours for G2 and 168 hours for G3. There were no deaths directly related to PGD. Acute rejection was detected in 7 patients (41%), 4 of which exceeded grade 1. The incidence of BOS after transplantation was 1 (7%) of 14 patients during the first year, 2 (11%) of 9 in the second year, and 2 (50%) of 4 in the third year. Hospital mortality rate was 17%. The survival rates were 82% at 3 months, 69%, at 1 year, and 58% at 3 years. CONCLUSIONS: Mid-term results confirm the adequacy of uncontrolled NHBD as a promising complementary source of lung donors for clinical transplant.