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Nocardiosis is a disease that mainly affects immunocompromised patients. Inhaled corticosteroids are standard of care for asthma. This treatment can induce respiratory infections but no case of bronchiolitis nocardiosis have been described so far. A 58-year-old man, with a controlled moderate allergic asthma, started since two years coughing and having dyspnoea during efforts. Within two months, although inhaled corticosteroids were increased to high doses, symptoms worsened linked to a severe obstructive ventilatory disorder as pulmonary function tests (PFT) revealed. Small-scale lesions (Nocardia abscessus. After six months of Sulfamethoxazole/Trimethoprim, PFT results improved and chest CT became completely normal. We therefore present the case of a bronchiolitis nocardiosis with several bronchial syndrome and the only immunosuppressive factor found are inhaled corticosteroids (ICS).

A fourth dose of SARS-CoV-2 vaccine is recommended in solid-organ transplant (SOT) recipients, but the immunogenicity is poorly known.We conducted a retrospective, observational, monocentric study between the 1st January 2021 and 31st March 2022 of the anti-Spike antibody titers after one to four doses of vaccine in SOT.825 SOT were included. Median age at first vaccine injection was 61.2 (IQR 50.9-69.3) years; 66.7 % were male; 63.4 % had received four vaccine doses. The proportion of participants with a strong humoral response (260 BAU/mL) increased with the number of vaccine doses: 10.6 % after the 1st dose (D1), 35.1 % after the 2nd (D2), 48.5 % after the 3rd (D3), and 65.1 % after the 4th (D4) (p 0.001). Among the tested patients, the proportion with a detectable humoral response was significantly higher after D4 than after D3 (47 % vs 22 %, p = 0.01). Liver transplant recipients had more frequently a strong humoral response after D2, D3 and D4 (OR = 5.3, 3.7 and 6.6 respectively when compared with other organ transplant recipients, p 0.001). In kidney transplant recipients, belatacept-containing regimen was associated with a lower rate of detectable humoral (9 % vs 40 %, p = 0.025) after D3, but there was no statistical difference after D4.A fourth dose should be proposed to SOT recipients who did not developed an immune response after 3 doses. Kidney transplant recipients receiving belatacept have a poorer, although frequently detectable response.

Do three COVID-19 vaccine doses induce a serological response in lung transplant recipients?We retrospectively included 1071 adults (551 [52%] males) at nine transplant centres in France. Each had received three COVID-19 vaccine doses in 2021, after lung transplantation. An anti-spike protein IgG response, defined as a titre264 BAU·mLMedian follow-up after the first dose was 8.3 [6.7-9.3] months. A vaccine response developed in 173 (16%) patients. Factors independently associated with a response were younger age at vaccination, longer time from transplantation to vaccination, and absence of corticosteroid or mycophenolate therapy. After vaccination, 51 (5%) patients (47 non-responders [47/898, 5%] and 4 [4/173, 2%] responders) experienced COVID-19, at a median of 6.6 [5.1-7.3] months after the third dose. No responders had severe COVID-19, compared to 15 non-responders, including six who died of the disease.Few lung transplant recipients achieved a serological response to three COVID-19 vaccine doses, indicating a need for other protective measures. Older age and use of mycophenolate or corticosteroids were associated with absence of a response. The low incidence of COVID-19 might reflect vaccine protection

Question addressed by the studyDo three coronavirus disease 2019 (COVID-19) vaccine doses induce a serological response in lung transplant recipients?MethodsWe retrospectively included 1071 adults (551 (52%) males) at nine transplant centres in France. Each had received three COVID-19 vaccine doses in 2021, after lung transplantation. An anti-spike protein IgG response, defined as a titre >264 BAU·mL−1after the third dose (median (interquartile range (IQR)) 3.0 (1.7–4.1) months), was the primary outcome and adverse events were the secondary outcomes. Median (IQR) age at the first vaccine dose was 54 (40–63) years and median (IQR) time from transplantation to the first dose was 64 (30–110) months.ResultsMedian (IQR) follow-up after the first dose was 8.3 (6.7–9.3) months. A vaccine response developed in 173 (16%) patients. Factors independently associated with a response were younger age at vaccination, longer time from transplantation to vaccination and absence of corticosteroid or mycophenolate therapy. After vaccination, 51 (5%) patients (47 non-responders (47/898 (5%)) and four (4/173 (2%)) responders) experienced COVID-19, at a median (IQR) of 6.6 (5.1–7.3) months after the third dose. No responders had severe COVID-19 compared with 15 non-responders, including six who died of the disease.ConclusionsFew lung transplant recipients achieved a serological response to three COVID-19 vaccine doses, indicating a need for other protective measures. Older age and use of mycophenolate or corticosteroids were associated with absence of a response. The low incidence of COVID-19 might reflect vaccine protectionviacellular immunity and/or good adherence to shielding measures.

The management of immunosuppressors in solid organ transplantation requires pharmacological therapeutic monitoring with regular adaptation of the dosage to the residual level. An obvious cause of these fluctuations is drug interactions, particularly for mTOR inhibitors and anti-calcineurin drugs, which are highly metabolized by cytochromes P450. A 72-year-old lung transplanted man, treated by tacrolimus and everolimus in the long term, had his residual immunosuppressor levels unbalanced by the introduction of sotorasib, which is used for metastatic pulmonary adenocarcinoma. This imbalance is explained by the fact that sotorasib is an inducer of CYP3A4 and an inhibitor of PGP, but the strength of the interaction has never been studied. This will have required a threefold increase in dosages and weekly monitoring before satisfactory residual levels were achieved.

Survival after lung transplantation (LTx) still remains limited by chronic lung allograft dysfunction (CLAD), thought to represent a form of chronic rejection. We investigated whether the immune checkpoint HLA-G/ILT2 expressed by peripheral T-cell subpopulations could predict CLAD.We used data for 150 LTx recipients from COLT (Cohort-For-Lung-Transplantation) cohort with ≥1 available blood sample at 1-, 6-, or 12-months post-Tx. Analysis of T cells by flow cytometry focused on the ILT2 receptor of HLA-G and other markers (CD57, CD25, CD127). T-cell subset analyses compared stable patients and those with CLAD at 3 years post-LTx.With data for 78 stable and 72 CLAD patients, among 21 T-cell subsets expressing ILT2, only CD4+CD57+ILT2+ T cells were associated with outcome. At 1-month post-Tx, low proportion of CD4+CD57+ILT2+ T cells was associated with reduced 3-year incidence of CLAD (CD4+CD57+ILT2+ T cells ≤ first IQR [25%] vsfirst IQR, log-rank test, p = 0.028). Furthermore, the incidence of CLAD was higher with2.6- vs ≤2.6-fold increased proportion of CD4+CD57+ILT2+ T cells over the first year post-LTx (3-year freedom frequencies: 27% [95%CI: 8-50] vs 64% [95%CI: 48-77] (log-rank test, p = 0.014). On multivariable analysis, increased proportion of CD4+CD57+ILT2+ T cells over the first year predicted CLAD (hazard ratio 1.25; 95%CI: 1.09-1.44; p = 0.001). Focusing on CD4+CD57+ILT2+ T cells, we demonstrated ex vivo that they are cytotoxic CD4+ T cells, selectively inhibited by HLA-G.Our data suggest that an early increase of CD4+CD57+ILT2+ T cells after LTx may be associated with CLAD onset.

International audience; BACKGROUND: A concern about the susceptibility of immunocompromised patients to the worldwide pandemic of coronavirus disease 2019 (COVID-19) has been raised. We aimed at describing COVID-19 infections in the French cohort of lung transplant (LT) patients. METHODS: Multicenter nationwide cohort study of all LT recipients with COVID-19 diagnosed from March 1 to May 19, 2020. Recipient main characteristics and their management were retrieved. Hospitalization characteristics, occurrence of complications and survival were analyzed. RESULTS: Thirty-five LT patients with a COVID-19 infection were included. Median age was 50.4 (40.6-62.9) years, 16 (45.7%) were female, and 80% were double-LT recipients. Infection was community-acquired in 25 (71.4%). Thirty-one (88.6%) required hospitalization, including 13 (41.9%) in the intensive care unit. The main symptoms of COVID-19 were fever, cough, and diarrhea, present in 71.4%, 54.3%, and 31.4% of cases, respectively. Extension of pneumonia on chest CT was moderate to severe in 51.4% of cases. Among the 13 critically ill patients, 7 (53.9%) received invasive mechanical ventilation. Thrombotic events occurred in 4 patients. Overall survival rate was 85.7% after a median follow-up of 50 days (41.0-56.5). Four of 5 nonsurvivors had had bronchial complications or intensification of immunosuppression in the previous weeks. On univariate analysis, overweight was significantly associated with risk of death (odds ratio, 16.0; 95% confidence interval, 1.5-170.6; P = 0.02). CONCLUSIONS: For the 35 LT recipients with COVID-19, the presentation was severe, requiring hospitalization in most cases, with a survival rate of 85.7%. Copyright

Background and objective Around 25% of patients with neuro-muscular diseases (NMD) are treated by home noninvasive ventilation (NIV) through an oronasal mask. However, there is growing evidence that nasal masks require lower NIV pressures and result in fewer residual obstructive events. We hypothesized that nasal masks would improve efficacy and reduce side effects compared to oronasal masks in this population. Methods open label, cross-over, randomized, study in 2 tertiary care hospitals. Patients with NMD treated by home NIV were randomized for one-week periods to nasal and oronasal interfaces respectively (cross-over). At the end of each period, nocturnal polygraphy (monitoring mouth opening) under NIV, synchronized with transcutaneous partial pressure in CO2 (tcCO2) was performed. Data were collected from the NIV built-in software and NIV side-effects were collected. Intention-to-treat and per protocol analyses were performed. The primary outcome was mean nocturnal SpO2. The secondary outcomes were: percentage of sleep with SpO2 Results Thirty patients with NMD were included. There were no between-group differences for either the primary or secondary outcomes. Post hoc comparisons showed that changing between interfaces reduced NIV efficacy: mean nocturnal SpO2 (p = 0.04), ODI (p = 0.01), mean tcCO2 (p = 0.048), side-effects (p = 0.008). Conclusion Nasal masks did not improve NIV efficacy or reduce side effects compared to oronasal masks in patients with NMD treated by home NIV. The efficacy of NIV is reduced during the transition to another interface, requiring close monitoring. Registration number: NCT03458507 .

Resume Les progres en transplantation pulmonaire permettent aux femmes en âge de procreer d’envisager de devenir meres. Lors d’un projet de grossesse, une adaptation des immunosuppresseurs et des therapeutiques associees est necessaire. Elle doit tenir compte des effets teratogenes et fœtotoxiques des medicaments, ainsi que des modifications pharmacocinetiques rencontrees au cours de la grossesse. De plus en plus de donnees sont actuellement disponibles sur la gestion des medicaments immunosuppresseurs et des traitements associes au cours de la grossesse chez les patientes transplantees. Nous rapportons ici deux cas d’adaptation de la prise en charge therapeutique, avant et pendant la grossesse, pour deux patientes transplantees pulmonaire ou cardio-pulmonaire. Afin d’eviter la survenue de complications pour la mere et l’enfant, une analyse de la litterature a ete necessaire pour adapter la prise en charge de chaque patiente.

Background Metallic airway stents for malignant airway obstruction are considered safe, yet are not without complications. This study reviews the role of computed tomography (CT) airway measurements for planning stent placement in malignant airway obstruction before the actual therapeutic procedure to avoid invasive diagnostic evaluation before the stent placement and to reduce complications. Methods This study is a retrospective review of information from a stent order database and medical records of patients receiving stents for malignant airway obstruction at a university hospital over a 12-year period. CT scans were used to determine stent diameter by calculating mean diameters of healthy adjacent zones (proximal and distal), stent length (length of diseased airway), and location and number of potential stents. Results of CT planning before bronchoscopy were judged by complication rates. Results Patient population consisted of 69 patients, 61.7±14.0 years old, 40 males, in whom 92 stents were inserted. The most frequent cause of airway obstructions was tracheobronchial cancer (32). All patients had nitinol stent placement; 66 stents were covered and 26 were uncovered. Follow-up time was 1 to 1067 days (median: 35 days). Complication rate was 10.1% and mainly involved the patients with tracheal obstruction (6). Complications included stent fractures (2), migration (2), granuloma (1), and infectious tracheitis (2). One early death within 24 hours after the procedure was not related to stent placement. Five patients required follow-up therapeutic bronchoscopy to treat the complications. Conclusions These results suggest that prestent planning by noninvasive method of obtaining CT scan provides optimal stent size and position, possibly avoiding a diagnostic bronchoscopy and reducing complications. Further prospective study is needed to confirm these results because of limitation of this study's design.

Background Sphincter pharyngoplasty (SP) appears to be the more “physiologic” surgical technique to treat velopharyngeal incompetence (VPI). This procedure creates a dynamic sphincter of variable diameter and keeps the flexibility of the soft palate. SP also induces velopharyngeal size reduction, mainly in the transverse diameter, which may cause upper airway (UA) occlusions during sleep. Aim To prospectively evaluate the effects of SP by a modified Orticochea procedure on sleep structure and sleep respiratory disturbances. Methods Polysomnographic studies before and after surgery in 17 consecutive patients treated by a modified Orticochea procedure SP for VPI. Results For the whole group, SP did not induce significant impairment of apnea-hypopnea index or nocturnal oxygen saturation. Slow-wave sleep (SWS) was significantly reduced after surgery (25 ± 9% of total sleep time [TST] vs 28 ± 9% of TST before SP [p = 0.04]). Following surgery, there was a trend for an increase in the microarousal index) (p = 0.09) and more specifically in respiratory-related microarousals. Conclusion SP, although creating a clinically obvious reduction of velopharyngeal diameter, generally did not lead to the occurrence of an obstructive sleep apnea syndrome. However, we found a significant reduction of SWS quantity and a trend toward an increase in the number of cortical microarousals. These findings suggest that the reduction of UA diameter associated with the surgical technique leads to increases in respiratory effort sufficient to induce sleep fragmentation and SWS reduction, even in the absence of apneas or hypopneas.

Advances in lung transplantation allow the women of childbearing age to consider becoming mothers. When planning to become pregnant, a therapeutic drug management of immunosuppressive drugs and associated therapies is required. It must take into account teratogenic and fetotoxic drugs, as well as pharmacokinetic changes encountered during pregnancy. Increasingly data are currently available on the management of immunosuppressive drugs and associated therapies during pregnancy. We report the case management of drug therapy before and during pregnancy in two patients after a lung or heart-lung transplantation. To prevent the emergence of complications for mother and child, a literature review has been necessary to manage drug therapies of each patient.

Advances in lung transplantation allow the women of childbearing age to consider becoming mothers. When planning to become pregnant, a therapeutic drug management of immunosuppressive drugs and associated therapies is required. It must take into account teratogenic and fetotoxic drugs, as well as pharmacokinetic changes encountered during pregnancy. Increasingly data are currently available on the management of immunosuppressive drugs and associated therapies during pregnancy. We report the case management of drug therapy before and during pregnancy in two patients after a lung or heart-lung transplantation. To prevent the emergence of complications for mother and child, a literature review has been necessary to manage drug therapies of each patient.

After lung transplantation (LT), immunoglobulin (Ig) G plasma concentrations6 g/L are common and correlate with an increased risk of chronic lung allograft dysfunction (CLAD) and a poorer survival.We conducted an open substitution intervention with nonspecific intravenous Ig (IVIg), in all patients with IgG plasma less than 6 g/L post-LT in 54 of 84 consecutive recipients since 1998 who survived more than 3 months. Pre-LT and post-LT events were retrospectively analyzed.Both substituted and nonsubstituted groups demonstrated similar donor or recipient characteristics and events over a median follow-up of 2.8 years (Q1-Q3, 1.4-5.7], except for initial diagnosis with more chronic obstructive pulmonary disease patients and less cases of pulmonary arterial hypertension in NS group. Intravenous Ig substitution started 3.5 months (0.5-9.4) after transplantation and lasted 4.5 months after (1.0-17.7), mean cumulative dose was 52.8±47.7 g. In multivariate Cox regression model, hypogammaglobulinemic patients who were substituted with IVIg had actually a 5-year survival (hazard ratio, 0.63; 95% confidence interval, 0.26-1.49; P=0.29) and CLAD-free 5-year survival (hazard ratio, 0.51; 95% confidence interval, 0.15-1.67; P=0.27) really close to nonhypogammaglobulinemic and nonsubstituted patients. Complementary analysis using propensity score and time-dependent analysis showed that survival and CLAD-free survival were not different in both groups.Intravenous Ig post-LT achieved similar survival and CLAD-free survival in recipients with hypogammaglobulinemia as compared to those with normal IgG plasmatic rate. A randomized control trial is required to confirm benefic effects of IVIg and disentangle mechanisms, including protection from infections, acute cellular and humoral rejections in patients with hypogammaglobulinemia after LT.

Summary A persistent phrenic palsy after interscalene block is a rare but possibly severe complication particularly in patients with previous lung function impairment or co-morbidities. We report the case of a patient, with a past history of post-traumatic diaphragmatic eventration, who presents a persistent respiratory insufficiency leading to long term non-invasive ventilation following interscalene block for rotator cuff shoulder surgery. A preoperative careful evaluation of patients addressed to interscalene block could avoid such long term complications.

Our objective was to investigate characteristics risk factors and outcomes of patients with chronic pulmonary aspergillosis (CPA).The Aspergillosis Committee prospectively collected Aspergillus notifications from January 2000 to December 2011. A retrospective analysis of data was performed.Among 1614 notifications registered, 44 cases of CPA in non-immunocompromised patients were identified. The median age was 65 years (Q1-Q3: 54-75), the median body mass index (BMI) was 20 kg/m(2) (Q1-Q3: 16-22) and 15 had chronic obstructive pulmonary disease. All patients had a positive specific serum precipitin antibody titer. Radiological presentations were: cavitations [single n = 31 (70%); multiple n = 12 (27%)] containing mycetomas [n = 18 (41%)], consolidations [n = 19 (43%)], emphysema [n = 15 (34%)] and sequelae of mycobacterial infection [n = 10 (23%)]. The median duration of follow-up was 30 months (Q1-Q3: 14-55). The median duration of antifungal treatment was 6 months (Q1-Q3: 3-12). Outcomes were unfavorable in 14 patients, and 12 (27%) died. Analysis by multivariate Cox regression model with bootstrapping showed that a higher BMI and a lower Charlson index score were predictive of favorable evolution, hazard ratio (95% confidence interval): BMI (+1) = 0.83 (0.71-0.97), Charlson (+1) = 1.37 (1.01-1.85). When analyses were restricted to chronic CPA and chronic necrotizing pulmonary aspergillosis, the multivariate Cox regression model showed that both BMI and Charlson index score were not statistically significant.Our results provide data on clinical characteristics and outcomes of CPA emphasizing the role of preexisting chronic respiratory conditions and protective effect of preserved BMI and lower Charlson index score.

International audience; Background: Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other sotid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. Methods: In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. Results: Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. Conclusions: We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

Sphincter pharyngoplasty (SP) appears to be the more "physiologic" surgical technique to treat velopharyngeal incompetence (VPI). This procedure creates a dynamic sphincter of variable diameter and keeps the flexibility of the soft palate. SP also induces velopharyngeal size reduction, mainly in the transverse diameter, which may cause upper airway (UA) occlusions during sleep.To prospectively evaluate the effects of SP by a modified Orticochea procedure on sleep structure and sleep respiratory disturbances.Polysomnographic studies before and after surgery in 17 consecutive patients treated by a modified Orticochea procedure SP for VPI.For the whole group, SP did not induce significant impairment of apnea-hypopnea index or nocturnal oxygen saturation. Slow-wave sleep (SWS) was significantly reduced after surgery (25 +/- 9% of total sleep time [TST] vs 28 +/- 9% of TST before SP [p = 0.04]). Following surgery, there was a trend for an increase in the microarousal index) (p = 0.09) and more specifically in respiratory-related microarousals.SP, although creating a clinically obvious reduction of velopharyngeal diameter, generally did not lead to the occurrence of an obstructive sleep apnea syndrome. However, we found a significant reduction of SWS quantity and a trend toward an increase in the number of cortical microarousals. These findings suggest that the reduction of UA diameter associated with the surgical technique leads to increases in respiratory effort sufficient to induce sleep fragmentation and SWS reduction, even in the absence of apneas or hypopneas.