Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with CT Brody score and lung function in cystic fibrosis patients.

OBJECTIVES: To demonstrate, in patients with cystic fibrosis (CF), the correlation between three-dimensional dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements and computed tomography Brody score (CF-CT) and lung function testing (LFT). METHODS: Twenty-one patients (median age, 25 years; female, n = 8) with a range of CF lung disease and five healthy volunteers (median age, 31 years; female, n = 2) underwent OE-MRI performed on a 1.5-T MRI scanner. Coronal volumes were acquired while patients alternately breathed room air and 100% oxygen. Pre-oxygen T1 was measured. Dynamic series of T1-weighted volumes were then obtained while breathing oxygen. T1-parameter maps were generated and the following OE-MRI parameters were measured: oxygen uptake (ΔPO2max), wash-in time and wash-out time. High-resolution CT and LFT were performed. The relationship between CF-CT, LFT and OE-MRI parameters were evaluated using Pearson correlation for the whole lung and regionally. RESULTS: Mean CF-CT was 24.1±17.1. Mean ΔPO2max and mean wash-in as well as skewness of wash-out showed significant correlation with CF-CT (ΔPO2max: r = -0.741, p < 0.001; mean wash-in: r = 0.501, p = 0.017; skewness of wash-out: r = 0.597, p = 0.001). There was significant correlation for the whole lung and regionally between LFT parameters and OE-MR (ΔPO2max: r = 0.718, p < 0.001; wash-in: r = -0.576, p = 0.003; wash-out skewness: r = -0.552, p = 0.004). CONCLUSIONS: Functional lung imaging using OE-MRI has the capability to assess the severity of CF lung disease and shows a significant correlation with LFT and CF-CT. KEY POINTS: • Oxygen-enhanced MRI might play a future role in evaluation and follow-up of cystic fibrosis. • Heterogeneity of parameter maps reflects localised functional impairment in cystic fibrosis. • Avoidance of cumulative radiation burden in CF is feasible using OE-MRI.

Correction to: Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with CT Brody score and lung function in cystic fibrosis patients.

The original version of this article, published on 13 April 2018, unfortunately contained a mistake.

Conservative management of distal leg necrosis in lung transplant recipients.

Critical limb ischemia (CLI) with distal leg necrosis in lung transplant recipients (LTR) is associated with a high risk for systemic infection and sepsis. Optimal management of CLI has not been defined so far in LTR. In immunocompetent individuals with leg necrosis, surgical amputation would be indicated and standard care. We report on the outcome of four conservatively managed LTR with distal leg necrosis due to peripheral arterial disease (PAD) with medial calcification of the distal limb vessels. Time interval from lung transplantation to CLI ranged from four years (n = 1) to more than a decade (n = 3). In all cases a multimodal therapy with heparin, acetylsalicylic acid, iloprost and antibiotic therapy was performed, in addition to a trial of catheter-based revascularization. Surgical amputation of necrosis was not undertaken due to fear of wound healing difficulties under long-term immunosuppression and impaired tissue perfusion. Intensive wound care and selective debridement were performed. Two patients developed progressive gangrene followed by auto-amputation during a follow-up of 43 and 49 months with continued ambulation and two patients died of unrelated causes 9 and 12 months after diagnosis of CLI. In conclusion, we report a conservative treatment strategy for distal leg necrosis in LTR without surgical amputation and recommend this approach based on our experience.

Hepatitis From Spiroplasma sp. in an Immunocompromised Patient.

A 70-year-old lung transplant recipient patient was admitted with fever, nausea, abdominal pain, peripheral edema and pronounced weakness. An initial work-up for presumed infection revealed cholestatic hepatitis, leukocytosis and thrombocytopenia, but failed to detect a pathogen. An increased glucose uptake exclusively in the liver was demonstrated by positron emission tomography. Liver biopsy showed basophilic inclusions in the cytoplasm of hepatocytes. Broad- range 16S rRNA gene PCR followed by sequence analysis yielded Spiroplasma sp. in two independent blood samples and the liver biopsy, confirming Spiroplasma sp. as the causative agent. Antibiotic treatment with doxycycline and azithromycin led to complete recovery.

Exposure to moxifloxacin and cytomegalovirus replication is associated with skin squamous cell carcinoma development in lung transplant recipients.

BACKGROUND: Lung transplant recipients (LTR) are at increased risk for squamous cell carcinoma of the skin (SCC), but risk factors (RF) are incompletely understood. OBJECTIVE: To assess associations between exposure to certain medications and viral infections, and subsequent SCC development. METHODS: Retrospective study examining incidence and potential RF for SCC in LTR transplanted from 1992 to 2010 followed up at one centre. Cumulative incidence and Cox proportional hazards regression models were used to evaluate RF in the first year post-transplant for SCC formation during the follow-up. RESULTS: In 205 analysed LTR, 46 patients were diagnosed with SCC during a median follow-up of 4.9 years. The cumulative incidences of first SCC were 16.7% and 34.1%, for 5 and 10 years post-transplantation respectively. Multivariable analysis identified CMV replication (HR 7.69, 95% CI 2.93-20.2, P < 0.001) and moxifloxacin exposure (HR 2.35, 95% CI 1.15-4.81, P = 0.020) during the first year post-transplantation as independent RF for SCC development during follow-up. CONCLUSION: In our cohort, moxifloxacin use and CMV replication during the first year post-transplantation were associated with increased risk for SCC. These two factors could be indicators of over-immunosuppression. Their role in SCC development requires investigations in larger cohorts and prospective studies.

Clinical features and outcomes of influenza infections in lung transplant recipients: a single-season cohort study.

BACKGROUND: For lung transplant recipients (LTRs) influenza infections pose a considerable risk for complications. These infections have mainly been described in hospitalized patients. The aim of this study was to describe characteristics of predominantly outpatient-treated influenza infections. METHODS: We conducted a single-season (2010/2011) retrospective observational study using database information of our cohort. Patients with evidence for respiratory tract infection received empirical oseltamivir and an oral antibiotic, pending results from nasopharyngeal swab analysis. In laboratory-confirmed influenza infection, treatment was continued and serial weekly swabs were performed until virologic results were negative. RESULTS: We identified 22 infections in 21 of 173 patients followed up; influenza A virus was diagnosed in 13 and influenza B virus in 9 infections. Leading presenting symptoms were cough and rhinorrhea. Oseltamivir was given within 48 h of symptom onset in 13 infections and within 72 h in 21 infections. Prolonged viral shedding (PVS) for ≥ 7 days was detected in 15 infections; median shedding duration for influenza A was 21 days. In univariable analysis, viral load (VL) at diagnosis was associated with extended duration of shedding (P = 0.006). Multivariable analysis confirmed this association. Bronchiolitis obliterans syndrome stage increased in 3 patients at 6-month follow-up. CONCLUSION: In this study, PVS of influenza virus was detected in the majority of LTRs and high VL at diagnosis was predictive for prolonged shedding, which occurred despite extended antiviral therapy.

Lung transplantation in children following bone marrow transplantation: a multi-center experience.

Allogenic BMT has been successfully performed as a treatment for hematologic diseases with an expected long-term survival. This survival is truncated by respiratory complications including airway obstruction especially BO. Chronic GVHD has been reported to precede almost all cases reported. LTx has become a therapeutic life-saving option for patients with end-stage lung disease that maybe offered for the treatment of GVHD. We report a multi-center experience of pediatric LTx following BMT in 11 patients age- and gender-matched with 11 controls who received LTx for end-stage lung disease secondary to CF. Overall death was 36.4% over a follow-up period of 19 months (range 3-36 months) for the cases and 27.3% for the control group followed for 17 months (range 8-32 months). Median FEV1 one yr post-transplant for the cases was 78% predicted compared with 67.3% predicted for the controls. The median for episodes of infection was comparable at a median of one episode per patient through the entire follow-up period among both groups. Acute rejection episodes were significantly higher in the control group with a median of one episode per patient in the control group compared to none within the cases. Our data suggest that LTx may be a valuable therapeutic option for children with end-stage lung disease post-BMT with comparable survival outcome to that after LTx in children for other indications such as CF. Hospital stay was significantly longer in our case group. Infection rate was comparable between groups albeit type of infection varied. Significantly and of interest is that acute rejection episodes were non-existent in these cases.

Undercarboxylated osteocalcin and bone mass in 8-12 year old children with cystic fibrosis.

UNLABELLED: Young adults with cystic fibrosis (CF) frequently develop bone disease. One suggested aetiological factor is suboptimal vitamin K status with impaired carboxylation of osteocalcin and abnormal bone formation. METHODS: We measured bone mineralization and turnover in thirty-two 8-12 year old CF patients (14 boys) using Dual Energy X-ray absorptiometry (whole body (WB) and lumbar spine (LS)), 25-OH Vitamin D, PTH and markers of bone formation (plasma osteocalcin, N-terminal pro-peptide of type 1 collagen (P1NP)), plus an indirect measure of vitamin K status, undercarboxylated osteocalcin (uc-OC). RESULTS: LS bone mineral density (BMD) standard deviation (SD) scores were < -1.0 in 20% of subjects. Size-adjusted LS and WB bone mass was normal. Compared to reference data, % uc-OC was high and P1NP low. LS bone mass was predicted by % uc-OC but not other markers (0.4% decrease in size-adjusted LSBMC (p=0.05); 0.04 SD decrease in LSBMAD (p=0.04) per 1% increase in uc-OC). CONCLUSION: Markers suggestive of sub-optimal vitamin K status and low bone formation were present despite normal size-adjusted bone mass. The association between LSBMC and % uc-OC is consistent with the hypothesis that sub-optimal vitamin K status is a risk factor for CF bone disease. This should ideally be investigated in an intervention trial.

Esophagopericardial fistula, septic shock and intracranial hemorrhage with hydrocephalus after lung transplantation.

A 57-year old woman underwent lung transplantation for non-specific interstitial pneumonia. Primary graft dysfunction was diagnosed requiring continued use of extracorporeal membrane oxygenation (ECMO). Within three days she developed recurring hemothoraces requiring two surgical evacuations. After ECMO removal a series of complications occurred within four months: femoral thrombosis, persisting tachycardic atrial fibrillation, pneumopericardium with an esophagopericardial fistula and purulent pericarditis, septic shock, multiorgan failure and intracerebral hemorrhage with ventricular involvement requiring external ventricular drainage. Interdisciplinary management coordinated by the intensive care specialist, transplant surgeon and pulmonologist with various interventions by the respective specialists followed by intensive physical rehabilitation allowed for discharge home on day 235 post transplant. Subsequently quality of life was considered good by the patient and family.

[Non-cystic fibrosis bronchiectasis: diagnosis and treatment]. / Non-CF-Bronchiektasen: Diagnostik und Therapie.

Bronchiectasis is the term used for irreversibly dilated airways. Exact epidemiological information on the frequency of bronchiectasis is not available, but the morphological findings are increasingly detected and the associated syndrome is more frequently diagnosed due to improved imaging techniques and increased awareness among chest physicians. The workup of these patients includes a wide panel of investigations guided by patient history and clinical presentation. Despite thorough evaluation the aetiology frequently remains unclear. Chronic infection with Pseudomonas aeruginosa is associated with a severe course of the disease and its detection has impacts on the therapeutic management. Chest physiotherapy, mucoactive substances and antibiotics are the mainstay of therapy. In this review the evaluation of bronchiectasis and the recent therapeutic insights for non-cystic fibrosis bronchiectasis are discussed.

Bilateral lung transplantation for pediatric idiopathic pulmonary arterial hypertension: a multi-center experience.

Many children with idiopathic pulmonary arterial hypertension (IPAH) experience disease progression despite advanced medical therapy. In these children, heart-lung or bilateral lung transplantation (BLTx) remain the only therapeutic options when other treatments fail. Data on functional outcome after BLTx in children with IPAH are limited. We report a multi-center experience of BLTx for pediatric IPAH. We performed a retrospective study including 25 centers within the International Pediatric Lung Transplant Collaborative. Children with IPAH who underwent BLTx were included (1996-2006). Twenty-three children underwent BLTx for IPAH, most of whom were in WHO class III or IV level of function pre-transplantation. At 6 months post-transplantation, 82% of children reported improvement in level of function to WHO class I. The median FEV(1) was 89% (12-126) of predicted at 12 months post-transplantation. Ten patients (44%) developed BOS at a median of 42 months (3-85), of whom five died at a median of 27 months (4-86) post-transplantation. Overall mortality was 4% at 3 months post-transplantation. The median survival for children in this cohort was 45 months (2-123). Our data suggest that BLTx is a valuable therapeutic option for children with end-stage IPAH with outcomes comparable to that after heart-lung transplantation in children with pulmonary arterial hypertension or those patients undergoing lung transplantation for other indications. In the majority of children, a good cardiopulmonary function is possible following BLTx, making BLTx a good therapeutic option and maximizing donor organ utilization by allowing more hearts to be available for children needing cardiac transplantation.

Surveillance bronchoscopy in children during the first year after lung transplantation: Is it worth it?

BACKGROUND: Since January 2002, routine surveillance bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy has been performed in all paediatric recipients of lung and heart-lung transplants at the Great Ormond Street Hospital for Children, London, UK, using a newly revised treatment protocol. AIMS: To report the prevalence of rejection and bacterial, viral or fungal pathogens in asymptomatic children and compare this with the prevalence in children with symptoms. PARTICIPANTS: The study population included all paediatric patients undergoing single lung transplantation (SLTx), double lung transplantation (DLTx) or heart-lung transplantation between January 2002 and December 2005. METHODS: Surveillance bronchoscopies were performed at 1 week, and 1, 3, 6 and 12 months after transplant. Bronchoscopies were classified according to whether subjects had symptoms, defined as the presence of cough, sputum production, dyspnoea, malaise, decrease in lung function or chest radiograph changes. RESULTS: Results of biopsies and BAL were collected, and procedural complications recorded. 23 lung-transplant operations were performed, 12 DLTx, 10 heart-lung transplants and 1 SLTx (15 female patients). The median (range) age of patients was 14.0 (4.9-17.3) years. 17 patients had cystic fibrosis. 95 surveillance bronchoscopies were performed. Rejection (> or =A2) was diagnosed in 4% of biopsies of asymptomatic recipients, and in 12% of biopsies of recipients with symptoms. Potential pathogens were detected in 29% of asymptomatic patients and in 69% of patients with symptoms. The overall diagnostic yield was 35% for asymptomatic children, and 85% for children with symptoms (p < 0.001). The complication rate for bronchoscopies was 3.2%. CONCLUSIONS: Many children have silent rejection or subclinical infection in the first year after lung transplantation. Routine surveillance bronchoscopy allows detection and targeted treatment of these complications.

The Chrispin-Norman score in cystic fibrosis: doing away with the lateral view.

The Chrispin-Norman chest radiograph scoring (CNS) system is widely used to assess respiratory disease progression in cystic fibrosis (CF). Frontal and lateral chest radiographs were performed. The present authors developed a modified CNS, which obviates the need for the lateral film. This study compares the original and the current authors' modified scoring system. A total of 50 chest radiographs from CF children, taken between August and December 2003, were scored according to the original and modified CNS. Two observers scored all 50 chest radiographs, scoring in random order the frontal radiographs, and separately the frontal and lateral radiographs together. There was no evidence of a difference between the methods for either observer, using the Bland and Altman 95% limits of agreement as follows: observer 1 (-2.0-1.9), and observer 2 (-1.77-2.2). No evidence of a difference between the observers for either method was found, comparing the 95% limits of agreement (-5.5-5.7) with the modified CNS (-5.6-6.4). In conclusion, in terms of the final score, good agreement was found between the use of the original and modified Chrispin-Norman score. In addition, low inter-observer variability was shown for both methods. The use of the modified Chrispin-Norman chest radiograph scoring system to stage disease severity in cystic fibrosis removes the need for a lateral chest radiograph.

Role of sensory neuropeptides in PIV-3-infection-induced airway hyperresponsiveness in guinea pigs.

Viral respiratory tract infections are known to induce transient airway hyper-responsiveness. The role of the nonadrenergic noncholinergic neuropeptide system on virus-induced airway hyperresponsiveness was studied in the guinea pig. Ten guinea pigs were inoculated with parainfluenza 3 virus (PIV-3.2 x 10(6) PFU) by nasal route. 16 animals served as untreated controls. Viral infection was proven by histological changes and by demonstration of viral antigen using immunohistochemical techniques. Four days after inoculation, airway responsiveness to inhaled acetylcholine (ACH) aerosol was measured in anesthetized and tracheotomized guinea pigs. The ACH concentration which produced an increase of 100% in pulmonary resistance (PC100 RI) and in dynamic elastance (PC100 Edyn) was calculated from a 5-step ACH dose-response curve (0.125, 0.25, 0.5, 1.0 and 2.0% ACH). Two further groups of 8 PIV-3-infected guinea pigs and 8 noninfected control animals were pretreated with capsaicin in increasing doses (50, 100, 125 and 150 mg/kg) on 4 consecutive days starting 6 days before virus inoculation. Measurements of airway responsiveness to ACH were performed 4 days after virus inoculation. Another 5 uninfected control animals were pretreated only with the solvent for capsaicin and inoculated with virus-free cell supermatant. PIV-3 infection increased airway responsiveness to ACH compared to noninfected controls [PC100 RI 0.81 vs. > 2.0% ACH (median). p < 0.002 PC100 Edyn 0.52 vs. 1.07% ACH (median), p < 0.01]. In capsaicin-pretreated PIV-3-infected animals, airway hyperresponsiveness was completely prevented compared to the virus-infected group without capsaicin pretreatment (PC100 RI > 2.0 vs. 0.81% ACH, p < 0.01; PC100 Edyn 1.42 vs. 0.52% ACH p < 0.01). As neuropeptide depletion with capsaicin completely prevented the increase in airway constrictory response to ACH following virus infection, we conclude that neuropeptides are effectively involved in PIV-3-induced airway hyperresponsiveness in the guinea pig.