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Introduction: COVID-19 raises concerns for lung transplant recipients (LTX) due to the lung as a target organ in immunocompromised patients. Aims and objectives: Evaluating COVID-19 course, treatments received, radiological and functional evolution in LTX. Methods: We conducted a retrospective study of LTX with a PCR confirmed diagnosis of COVID-19. Results: 42 LTX were included from 18/03/2020 until 01/02/2021. Mean age was 54y (19-73), mean time after LTX 68mo (7-194). 30 (71%) LTX were hospitalised with a mean duration of 14d (1-41). Seven (17%) needed ICU, 5 (12%) endotracheal intubation and 1 (2%) VV ECMO. 4 (10%) died. From the 7 patients in ICU, 4 were aged>65y, 2 had diabetes, 2 hypertension, 2 BMI>30. In all hospitalised patients immunosuppression was adapted (mycophenolate mofetil withdrawn for at least 2 weeks, low level of calcineurin inhibitors, 5 day course of azithromycin 500mg). 8 (19%) received hydroxychloroquine, 8 (19%) remdesivir, 9 (21%) COVID-19 convalescent plasma and 9 (21%) higher corticosteroid dose. 4 (10%) LTX experienced recurrent COVID-19. 3 (7%) developed acute rejection shortly after COVID-19. In LTX with follow-up chest CT (n=15) minimal sequellae were described. Mean decrease in FEV1 compared to baseline at 1, 3 and 6 months was, respectively, -133mL (IQR -190 to 35, n=28), -176mL (IQR -330 to 75, n=16) and -48mL (IQR -140 to 90, n=11). No patient met criteria for onset of CLAD. Conclusions: We found a higher mortality and more severe disease course in LTX than in the healthy population. Recurrence of COVID-19 is a frequent event. At mid-term, we did not observe significant new incidence of CLAD onset. Treatment of COVID-19 and risk of CLAD after COVID-19 in LTX require further studies.

Item does not contain fulltext BACKGROUND: Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolised by CYP3A4 and CYP3A5, and it has been shown that the CYP3A inducer rifampin reduces isavuconazole exposure. By extrapolation, the concomitant use of isavuconazole with moderate and strong CYP450 inducers is contraindicated, although it is known that some CYP450 inducers are less potent in comparison with rifampin. OBJECTIVES: We aim to document exposure to isavuconazole in patients concomitantly treated with a CYP450 inducer that is less potent compared to rifampin. Moreover, although it is well known that CYP3A enzymes are important for the metabolism of isavuconazole, this induction effect has never been studied in combination with the patient's CYP3A genotype. PATIENTS: We report three patients treated with both isavuconazole and a CYP3A inducer that is less potent compared to rifampin (rifabutin or phenobarbital), in whom we determined isavuconazole concentrations. RESULTS: These cases suggest that the CYP3A4/5 genotype is an important determinant for isavuconazole exposure and that it might also influence the CYP450 induction interaction. CONCLUSIONS: CYP3A inducers that are less potent compared to rifampin, may be combined with isavuconazole in patients with loss of CYP3A5 activity (CYP3A5*3/*3). Therapeutic drug monitoring is recommended during this combination. However, low-isavuconazole exposure was observed in the extensive metaboliser with CYP3A4*1/*1 and CYP3A5*1/*3 alleles.

Several case reports and small case series have been published on coronavirus disease 2019 infection after solid organ transplantation; however, thus far there are limited data on coronavirus disease 2019 infections in lung transplant patients. In the present single-center case series we discuss 10 lung transplant patients with a documented severe acute respiratory syndrome coronavirus 2 infection, diagnosed with nasopharyngeal swab in 8 and bronchoalveolar lavage in 2. Eight of 10 patients needed hospital admission, of whom 1 was in the intensive care unit. He died after 2 weeks from multiple organ failure. The remaining nine patients recovered. Cell cycle inhibitors were withheld in all patients, whereas the calcineurin inhibitor and corticosteroids were continued at the same dose, with an acceptable outcome. ispartof: AMERICAN JOURNAL OF TRANSPLANTATION vol:20 issue:11 pages:3234-3238 ispartof: location:United States status: published

Pulmonary lymphomatoid granulomatosis (PLG) is a rare angiocentric and angiodestructive EBV-associated lymphoproliferative disorder which almost always affects the lungs. PLG is more commonly diagnosed in patients with immunodeficiency and is associated with Epstein-Barr virus (EBV). 'Drug induced PLG' or 'iatrogenic immunodeficiency-associated lymphoproliferative disorder' is a special form of PLG described in patient with inflammatory bowel diseases treated with Azathioprine.We report a case of drug-induced PLG in a 68-year-old patient with Crohn's disease presenting with pain at the right hemithorax, fatigue and shortness of breath with a pulmonary mass.Although initial diagnostic findings were misleading, an open lung biopsy eventually led to the diagnosis of drug-induced PLG.The diagnosis of PLG is challenging because the disease is rare and the histological features can be very subtle. Correct diagnosis relies on histopathology and immunohistochemical staining and EBV RNA in situ hybridization with sampling of large and different amounts of pathologic tissue in the hands of expert pathologists. In drug-induced PLG specifically, withdrawal of the immunosuppressive agent can lead to disease regression.

A lung transplant recipient was diagnosed with penicilliosis due to Talaromyces marneffei, a fungus endemic in South-East Asia, which was acquired by donor transmission. This first case of Talaromyces marneffei-transmission by transplantation underscores that current globalisation of travelling necessitates increased vigilance for transmission of unusual pathogens in organ recipients. ispartof: Mycoses vol:60 issue:3 pages:213-217 ispartof: location:Germany status: published

There is growing awareness of the need for advance care planning in patients with chronic obstructive pulmonary disease (COPD). However, do-not-resuscitate (DNR) order implementation remains a challenge in clinical practice. We retrospectively analysed an observational cohort of 569 COPD patients with 2.5–8 years of follow-up in secondary care, to evaluate potential determinants and the prognostic significance of DNR order implementation and specification. 345 patients (61%) had no DNR order, of whom 27% died during a median (interquartile range (IQR)) follow-up of 1935 (1290–2448) days. 194 (39%) patients had a DNR order, of whom 17 had the order at baseline and 82% died (median (IQR) follow-up 528 (137–901) days), while 177 received an order during follow-up and 76% died (median (IQR) follow-up 1322 (721–2018) days). 88% of DNR orders were implemented during hospitalisation. 58% of the patients with a DNR order died within the first year after admission; of them, 66% died in the hospital. Age, forced expiratory volume in 1 s, chronic oxygen dependency and previous mechanical ventilation were significantly and independently associated with DNR order implementation. DNR order specification was significantly associated with increased mortality, even after adjustment for age and disease severity. These findings identify DNR orders as independent determinants of mortality, mainly implemented just before death., DNR orders in COPD patients are preferentially given to older patients with severe disease and are usually implemented during hospitalisation, close to the moment of death. Early end-of-life care planning in COPD remains difficult and challenging http://ow.ly/BGJk30hJCZ5

Background: There is growing awareness of the need for advanced care planning in patients with COPD. The appropriate moment to discuss DNR orders in these patients remains a difficult clinical decision. Aims and objectives: To evaluate the use and time point of DNR orders as part of advanced care planning in COPD patients in a tertiary care centre in Belgium. Methods: Retrospective analysis of patient files of 569 COPD patients with a median follow-up (FU) of years (median + IQR). Results: 30 patients were excluded for undergoing lung transplantation or lost to FU. 345 patients received no DNR order, of whom 94 (27%) died (median FU 2557 days). 194 patients received a DNR order, of whom 149 (82%) died (median FU 2583 days). Patients with DNR had lower FEV1 (44% pred. vs. 56% pred.). Median time between first DNR order and death was 163 days; 28% and 43% died within 30 days and 90 days, respectively. 50% died in hospital; 12% died in the ICU or ER. Most frequent DNR order was 9no CPR and no intubation9 (40%); most frequent motivation was 9poor respiratory status9 (65%). The majority (86%) of DNR orders were written during hospitalization, of which 20% in the ICU or ER. Only 19 out of 539 patients (4%) got DNR orders during outpatient visits. Conclusions: COPD patients receiving a DNR order have a high probability of dying. The majority of DNR orders is made during hospitalization, with only 4% during stable conditions in ambulatory FU. These data are reflecting the difficulties with advanced care planning in COPD.

Up to 80% of patients with cystic fibrosis (CF) may have increased gastroesophageal reflux and aspiration of duodenogastric contents into the lungs. We aimed to assess aspiration in patients with CF by measuring duodenogastric components in induced sputum and to investigate whether the presence of bile acids (BAs) in sputum was correlated with disease severity and markers of inflammation.In 41 patients with CF, 15 healthy volunteers, 29 patients with asthma, and 28 patients with chronic cough, sputum was obtained after inhalation of hypertonic saline. Sputum supernatant was tested for BA and neutrophil elastase. Spirometry and BMI were assessed on the day of sputum collection.Two of 15 healthy patients (13%), eight of 29 patients (28%) with asthma, four of 28 patients (14%) with chronic cough, and 23 of 41 patients (56%) with CF had BA in sputum. BA concentrations were similar in patients who are positive for BA with genotype F508del homozygote, F508del heterozygote, and other CF mutations and were not related with BMI and age. Patients with CF with BA in sputum had a higher concentration of neutrophil elastase compared with patients without BA in sputum (31.25 [20.33-54.78] μg/mL vs 14.45 [7.11-27.88] μg/mL, P.05). There was a significant correlation between BA concentrations and dynamic lung volumes (FEV(1) % predicted [r = -0.53, P.01], FVC% [r = -0.59, P.01]) as well as with number of days of antibiotic IV treatment (r = 0.58, P.01).BAs are present in the sputum of more than one-half of patients with CF, suggesting aspiration of duodenogastric contents. Aspiration of BA was associated with increased airway inflammation. In patients with BA aspiration, the levels of BA were clearly associated with the degree of lung function impairment as well as the need for IV antibiotic treatment.

This study aims to analyse antibiotic treatment of respiratory tract infections in ambulatory care in Belgium by: a) mapping antibiotic consumption over time and breaking down antibiotic consumption by infection type; b) discussing antibiotic treatment as recommended by Belgian guidelines; and c) reviewing the current evidence on the cost- effectiveness of antibiotic treatment. IMS Health data showed that the total volume of antibiotic consumption in ambulatory care in Belgium has increased over the years. Antibiotic consumption mainly originated from the use of broad-spectrum penicillins. The volume of fluoroquinolone use remains well controlled. Policy makers need to target the main drivers of inappropriate antibiotic consumption rather than a specific class of antibiotics when they aim to promote better use of antibiotics in ambulatory care. A s-lactam-based therapy for CAP is recommended as first choice in Belgian guidelines and moxifloxacin is advocated for CAP outpatients with comorbid conditions or outpatients in whom infection with atypical pathogens needs to be considered. Because of its high eradicating power against the target organisms and because H. influenzae is the main pathogen to be covered, amoxicillin-clavulanic acid may be a first choice to treat COPD exacerbations, although this choice is subject to debate. Moxifloxacin is recommended in case of IgE-mediated s-lactam allergy or severe intolerance to s-lactam antibiotics for the treatment of COPD exacerbations or for the treatment of upper respiratory tract infections on the rare occasion that antibiotic treatment is warranted. One study supported the cost- effectiveness of first-line treatment of CAP with moxifloxacin in Belgium.

This review summarizes recent developments in the diagnosis and treatment of fungal pneumonia, with an emphasis on invasive pulmonary aspergillosis.Improvements in nonculture-based fungal diagnostics, early implementation of pulmonary high resolution, or spiral computed tomography scanning and a recent expansion of the antifungal armamentarium have greatly improved the outcome of immunocompromised patients with invasive aspergillosis. However, the field is changing: new pathogens (such as Zygomycetes) are emerging, and novel risk groups (ICU patients in particular) are being identified.Galactomannan antigen detection is a valuable tool for evaluating patients at risk for invasive aspergillosis (as a screening assay on serum samples from neutropenic patients or as a confirmatory assay on bronchoalveolar lavage fluid samples, in general), but should be used in conjunction with modern imaging techniques. beta-D-Glucan and PCR assays are still investigational. Voriconazole is the drug of choice for invasive aspergillosis, whereas liposomal amphotericin B at 3 mg/kg per day is the preferred alternative in case of contraindication, drug-related side-effects, or intolerance. Whenever possible, optimal antifungal therapy should be complemented by surgical debridement of necrotic tissue. The added value of combination therapy is still unproven. Therapeutic drug monitoring of mold-active azoles should be implemented in order to minimize toxicity and maximize efficacy. Lipid-based formulations of amphotericin B, and to a lesser extent voriconazole, are the drugs of choice for non-Aspergillus related fungal pneumonia. Although active in prophylaxis, the efficacy of posaconazole in confirmed infections remains controversial.

Clinical image of an asymmetrical mediastinal widening due to tuberculosis of mediastinal lymph nodes, without evidence of pulmonary tuberculosis. Image at first presentation and after successful treatment, showing normalization of the mediastinum.

We present two patients with inflammatory bowel disease who, despite negative tuberculosis screening, developed a de novo tuberculosis infection after the start of anti tumor necrosis factor alpha treatment. We discuss current screening methods and their limitations, the approach after positive screening and the timing to resume anti-TNFα treatment after TB infection. We shortly mention the immune reconstitution inflammatory syndrome (IRIS), described in a few cases after the stop of anti-TNFalpha while treating the tuberculosis infection. We conclude with some remaining questions concerning tuberculosis in IBD patients.

This article analyzes patterns of consumption of fluoroquinolones and documents the in vitro resistances of Streptococcus pneumoniae isolates to fluoroquinolones in the ambulatory care setting in Belgium over time. The volume of fluoroquinolone consumption has fallen consistently since 2003. Fluoroquinolones were used primarily for their registered indications (i.e., urinary tract infections and lower respiratory tract infections). The MIC distributions of moxifloxacin and levofloxacin in S. pneumoniae isolates remained stable during 2004 to 2009, and the level of resistance to moxifloxacin and levofloxacin was low (≤1%).

Background Chronic idiopathic cough (known as cough hypersensitivity syndrome) is defined by cough in the absence of an identifiable cause. Gabapentin has been suggested as a treatment but evidence is scarce. The aim of our study was to describe the clinical features of patients with unexplained chronic cough and to investigate the effect of gabapentin (600 mg twice a day for a minimal duration of 4 weeks) in reducing cough symptoms. Methods A patient cohort analysis was performed. Patients were retrieved using a query in our medical database for the words ‘cough’ and ‘gabapentin’ in 2011. Patients without a clear etiology of cough despite having performed a stepwise diagnostic approach, were included. Medical records of these patients were analyzed. A telephonic survey was performed and patients were asked to retrospectivally rate their cough when they attended the outpatient clinic. They were then asked to rate their cough after treatment with gabapentin. A scale from one to ten was used to score cough severity. They were also questioned about the triggers inducing cough. To evaluate the cough severity score, the results were correlated with questions of the Leicester Cough Questionnaire. Results We recruited 51 patients (87% female) with a mean age of onset of 47 years (± 14 y) and an average cough duration of 48 months. The most frequently reported cough triggers included change of temperature (57%), talking (49%) and odours (45%). In 67% of patients, the urge to cough was located in the throat area. Thirty-five patients effectively took the prescribed gabapentin. The average improvement in cough score was 2.8/10 (p Conclusion Chronic idiopathic cough were predominantly middle-aged women, frequently reporting various cough triggers. We also demonstrated that gabapentin can significantly improve cough in these patients. Responders tend to have higher pre-treatment severity scores and have a history of an airway infection.