16q24.1 microdeletion in a premature newborn: Usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn.

OBJECTIVE:: Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn and multiple congenital malformations. DESIGN:: Descriptive case report. SETTING:: Genetic department and neonatal intensive care unit of a tertiary care children's hospital. INTERVENTIONS:: None. PATIENT:: We report the case of a preterm male infant, born at 26 wks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 wks of gestation. Karyotype analysis was normal, and a 22q11.2 microdeletion was excluded by fluorescence in situ hybridization analysis. A cesarean section was performed due to fetal distress. The patient developed persistent pulmonary hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hrs of life. MEASUREMENTS AND MAIN RESULTS:: An autopsy revealed partial atrioventricular canal malformation and showed bilateral dilation of the renal pelvocaliceal system with bilateral ureteral stenosis and annular pancreas. Array-based comparative genomic hybridization analysis (Agilent oligoNT 44K, Agilent Technologies, Santa Clara, CA) showed an interstitial microdeletion encompassing the forkhead box gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins. Some features were less prominent due to the gestational age. CONCLUSIONS:: Our review of the literature shows that alveolar capillary dysplasia with misalignment of pulmonary veins is rare but probably underreported. Prematurity is not a usual presentation, and histologic features are difficult to interpret. In our case, array-based comparative genomic hybridization revealed a 16q24.1 deletion, leading to the final diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins. It emphasizes the usefulness of array-based comparative genomic hybridization analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory persistent pulmonary hypertension and multiple congenital malformations.

Importance of ENaC-mediated sodium transport in alveolar fluid clearance using genetically-engineered mice.

The lung possesses specific transport systems that intra- and extracellularly maintain salt and fluid balance necessary for its function. At birth, the lungs rapidly transform into a fluid (Na(+))-absorbing organ to enable efficient gas exchange. Alveolar fluid clearance, which mainly depends on sodium transport in alveolar epithelial cells, is an important mechanism by which excess water in the alveoli is reabsorbed during the resolution of pulmonary edema. In this review, we will focus and summarize on the role of ENaC in alveolar lung liquid clearance and discuss recent data from mouse models with altered activity of epithelial sodium channel function in the lung, and more specifically in alveolar fluid clearance. Recent data studying mice with hyperactivity of ENaC or mice with reduced ENaC activity clearly illustrate the impaired lung fluid clearance in these adult mice. Further understanding of the physiological role of ENaC and its regulatory proteins implicated in salt and water balance in the alveolar cells may therefore help to develop new therapeutic strategies to improve gas exchange in pulmonary edema.

Prospective comparison of clinical prognostic scores in elderly patients with pulmonary embolism.

Background: The Geneva Prognostic Score (GPS), the Pulmonary Embolism Severity Index (PESI), and its simplified version (sPESI) are well known clinical prognostic scores for pulmonary embolism (PE).Objectives: To compare the prognostic performance of these scores in elderly patients with PE. Patients/Methods: In a multicenter Swiss cohort of elderly patients with venous thromboembolism, we prospectively studied 449 patients aged ≥65 years with symptomatic PE. The outcome was 30-day overall mortality. We dichotomized patients as low- vs. higher-risk in all three scores using the following thresholds: GPS scores ≤2 vs. >2, PESI risk classes I-II vs. III-V, and sPESI scores 0 vs. ≥1. We compared 30-day mortality in low- vs. higher-risk patients and the areas under the receiver operating characteristic curve (ROC). Results: Overall, 3.8% of patients (17/449) died within 30 days. The GPS classified a greater proportion of patients as low risk (92% [413/449]) than the PESI (36.3% [163/449]) and the sPESI (39.6% [178/449]) (P<0.001 for each comparison). Low-risk patients based on the sPESI had a mortality of 0% (95% confidence interval [CI] 0-2.1%) compared to 0.6% (95% CI 0-3.4%) for low-risk patients based on the PESI and 3.4% (95% CI 1.9-5.6%) for low-risk patients based on the GPS. The areas under the ROC curves were 0.77 (95%CI 0.72-0.81), 0.76 (95% CI 0.72-0.80), and 0.71 (95% CI 0.66-0.75), respectively (P=0.47). Conclusions: In this cohort of elderly patients with PE, the GPS identified a higher proportion of patients as low-risk but the PESI and sPESI were more accurate in predicting mortality.

Aorto-bronchial and aorto-pulmonary fistulation after thoracic endovascular aortic repair: an analysis from the European Registry of Endovascular Aortic Repair Complications.

OBJECTIVES: To learn upon incidence, underlying mechanisms and effectiveness of treatment strategies in patients with central airway and pulmonary parenchymal aorto-bronchial fistulation after thoracic endovascular aortic repair (TEVAR). METHODS: Analysis of an international multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2012 with a total caseload of 4680 TEVAR procedures (14 centres). RESULTS: Twenty-six patients with a median age of 70 years (interquartile range: 60-77) (35% female) were identified. The incidence of either central airway (aorto-bronchial) or pulmonary parenchymal (aorto-pulmonary) fistulation (ABPF) in the entire cohort after TEVAR in the study period was 0.56% (central airway 58%, peripheral parenchymal 42%). Atherosclerotic aneurysm formation was the leading indication for TEVAR in 15 patients (58%). The incidence of primary endoleaks after initial TEVAR was n = 10 (38%), of these 80% were either type I or type III endoleaks. Fourteen patients (54%) developed central left bronchial tree lesions, 11 patients (42%) pulmonary parenchymal lesions and 1 patient (4%) developed a tracheal lesion. The recognized mechanism of ABPF was external compression of the bronchial tree in 13 patients (50%), the majority being due to endoleak formation, further ischaemia due to extensive coverage of bronchial feeding arteries in 3 patients (12%). Inflammation and graft erosion accounted for 4 patients (30%) each. Cumulative survival during the entire study period was 39%. Among deaths, 71% were attributed to ABPF. There was no difference in survival in patients having either central airway or pulmonary parenchymal ABPF (33 vs 45%, log-rank P = 0.55). Survival with a radical surgical approach was significantly better when compared with any other treatment strategy in terms of overall survival (63 vs 32% and 63 vs 21% at 1 and 2 years, respectively), as well as in terms of fistula-related survival (63 vs 43% and 63 vs 43% at 1 and 2 years, respectively). CONCLUSIONS: ABPF is a rare but highly lethal complication after TEVAR. The leading mechanism behind ABPF seems to be a continuing external compression of either the bronchial tree or left upper lobe parenchyma. In this setting, persisting or newly developing endoleak formation seems to play a crucial role. Prognosis does not differ in patients with central airway or pulmonary parenchymal fistulation. Radical bronchial or pulmonary parenchymal repair in combination with stent graft removal and aortic reconstruction seems to be the most durable treatment strategy.

Fluoroscopic-Guided Radial Endobronchial Ultrasound Without Guide Sheath For Peripheral Pulmonary Lesions: A Safe And Efficient Combination.

BACKGROUND: Several guidelines recommend computed tomography scans for populations with high-risk for lung cancer. The number of individuals evaluated for peripheral pulmonary lesions (PPL) will probably increase, and with it non-surgical biopsies. Associating a guidance method with a target confirmation technique has been shown to achieve the highest diagnostic yield, but the utility of bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy as guidance without a guide sheath has not been reported. METHODS: We conducted a retrospective analysis of bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy procedures for the investigation of PPL performed by experienced bronchoscopists with no specific previous training in this particular technique. Operator learning curves and radiological predictors were assessed for all consecutive patients examined during the first year of application of the technique. RESULTS: Fifty-one PPL were investigated. Diagnostic yield and visualization yield were 72.5 and 82.3% respectively. The diagnostic yield was 64.0% for PPL ≤20mm, and 80.8% for PPL>20mm. No false-positive results were recorded. The learning curve of all diagnostic tools showed a DY of 72.7% for the first sub-group of patients, 81.8% for the second, 72.7% for the third, and 81.8% for the last. CONCLUSION: Bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy as guidance is safe and simple to perform, even without specific prior training, and diagnostic yield is high for PPL>and ≤20mm. Based on these findings, this method could be introduced as a first-line procedure for the investigation of PPL, particularly in centers with limited resources.

Endovascular treatment of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia.

PRINCIPLES: To assess the efficiency and complication rates of vaso-occlusion of pulmonary arteriovenous malformations (PAVMs) in Rendu-Osler-Weber disease (hereditary haemorrhagic telangectasia; HHT). METHODS: Seventy-two patients were investigated in our institution for HHT between March 2000 and November 2011. Sixteen presented PAVMs (22.2%), and 11 (68.8%) were treated with vaso-occlusion for a total of 18 procedures. Procedures included coils, plugs and combined approaches. Immediate success and recurrence rate, complication were recorded, as well as persistent and new PAVMs during clinical and computed tomography (CT) follow-up. RESULTS: Eighteen procedures were performed and a total of 37 PAVMs were treated, 19 with coils, 16 with plugs and 2 with combined treatment. Mean CT follow-up time was 41 months (1‒164). No major complication was observed. One distal translocation was treated during the same intervention. Two PAVMs persisted after treatment (5.7%), both treated by means of plug embolisation. One new PAVM was observed during follow-up CT. PAVMs with an afferent artery of less than 3mm or asymptomatic PAVMs were not treated. CONCLUSION: Recent studies have demonstrated that vaso-occlusion has become the gold standard treatment for PAVM. This study is in accordance with previous results and shows a minimal complication rate and little recurrence, whether by coils, plugs, or combined treatments.

Successful Surgical Pulmonary Embolectomy for Massive Perinatal Embolism after Emergency Cesarean Section.

Pregnant women are exposed to an increased risk for developing pulmonary embolism (PE), a main cause for maternal mortality. Surgical pulmonary embolectomy is one important therapeutic and potential life-saving armamentarium, considering pregnancy as a relative contraindication for thrombolysis. We present a case of a 36-year-old woman with massive bilateral PE after emergent caesarean delivery, requiring reanimation by external heart massage. The onset of massive intrauterine bleeding contraindicated thrombolysis and emergency surgical pulmonary embolectomy, followed by a hysterectomy, were preformed successfully. Acute surgical pulmonary embolectomy may be an option in critically diseased high-risk patients, requiring a multiteam approach, and should be part of the therapeutic armamentarium of the attending cardiac surgeon.

Simultaneous acute pulmonary embolism and isolated septal myocardial infarction in a young patient

While the overall incidence of myocardial infarction (MI) has been decreasing since 2000 [1], there is an increasing number of younger patients presenting with MI [2]. Few studies have focused on MI in very young patients, aged 35 years or less, as they only account for a minority of all patients with myocardial infarction [3]. According to the age category, MI differs in presentation, treatment and outcome, as illustrated in table 1. Echocardiography is considered mandatory according to scientific guidelines in the management and diagnosis of MI [4,5,6]. However, new imaging techniques such as cardiac magnetic resonance (CMR) and computed tomography (CT) are increasingly performed and enable further refinement of the diagnosis of MI. These techniques allow, in particular, precise location and quantification of MI. In this case, MI was located to the septum, which is an unusual presentation of MI. The incidence of pulmonary embolism (PE) has also increased in young patients over the past years [7]. Since symptoms and signs of PE may be non-specific, establishing its diagnosis remains a challenge [8]. Therefore, PE is one of the most frequently missed diagnosis in clinical medicine. Because of the widespread use of CT and its improved visualization of pulmonary arteries, PE may be discovered incidentally [9]. In the absence of a congenital disorder, multiple and/or simultaneous disease presentation is uncommon in the young. We report the rare case of a 35 year old male with isolated septal MI and simultaneous PE. The diagnosis of this rare clinical entity was only possible by means of newer imaging techniques.

THE PREVALENCE AND PREDICTION OF PULMONARY FIBROSIS IN AN

This thesis describes an ancillary project to the Early Diagnosis of Mesothelioma and Lung Cancer in Prior Asbestos Workers study and was conducted to determine the effects of asbestos exposure, pulmonary function and cigarette smoking in the prediction of pulmonary fibrosis. 613 workers who were occupationally exposed to asbestos for an average of 25.9 (SD=14.69) years were sampled from Sarnia, Ontario. A structured questionnaire was administered during a face-to-face interview along with a low-dose computed tomography (LDCT) of the thorax. Of them, 65 workers (10.7%, 95%CI 8.12—12.24) had LDCT-detected pulmonary fibrosis. The model predicting fibrosis included the variables age, smoking (dichotomized), post FVC % splines and post- FEV1% splines. This model had a receiver operator characteristic area under the curve of 0.738. The calibration of the model was evaluated with R statistical program and the bootstrap optimism-corrected calibration slope was 0.692. Thus, our model demonstrated moderate predictive performance.

Socio-demographic factors, smoking, symptoms, morbidities and pulmonary function and quality of life in individuals with a heavy smoking history

Objective: To determine which socio-demographic, exposure, morbidity and symptom variables are associated with health-related quality of life among former and current heavy smokers. Methods: Cross sectional data from 2537 participants were studied. All participants were at ≥2% risk of developing lung cancer within 6 years. Linear and logistic regression models utilizing a multivariable fractional polynomial selection process identified variables associated with health-related quality of life, measured by the EQ-5D. Results: Upstream and downstream associations between smoking cessation and higher health-related quality of life were evident. Significant upstream associations, such as education level and current working status and were explained by the addition of morbidities and symptoms to regression models. Having arthritis, decreased forced expiratory volume in one second, fatigue, poor appetite or dyspnea were most highly and commonly associated with decreased HRQoL. Discussion: Upstream factors such as educational attainment, employment status and smoking cessation should be targeted to prevent decreased health-related quality of life. Practitioners should focus treatment on downstream factors, especially symptoms, to improve health-related quality of life.

The effects of administration of a nuclear factor kappa-B inhibitor on pulmonary endothelial dysfunction after cardiopulmonary bypass: impact on oxygenation and hemodynamics and development of therapeutic and preventive modalities in a porcine model

Introduction: La circulation extracorporelle (CEC) peut entraîner une dysfonction endothéliale pulmonaire et l’hypertension pulmonaire. Le SN50 agit au niveau de la signalisation cellulaire pour prévenir ces réactions à la CEC et pourrait renverser la dysfonction endothéliale pulmonaire post-CEC sans effets néfastes sur l’hémodynamie. Méthodes: Quatre groups de porcs ont reçu un parmi quatre traîtements avant de subir 90 minutes de CEC et 60 minutes de reperfusion: (1) milrinone nébulisé; (2) sildenafil nébulisé; (3) placebo nébulisé; et (4) SN-50 intraveineux. Un monitoring hémodynamique invasif a été utilisé. La réactivité vasculaire des artères pulmonaires de deuxième ordre a été évaluée face à l’acétylcholine et la bradykinine. Résultats: Le sildénafil produit une augmentation significative de la pression de l’artère pulmonaire (PAP) moyenne à 60 minutes de reperfusion par rapport au début de la chirurgie. Les relaxations dépendantes de l’endothélium face à la bradykinine étaient meilleurs dans les groupes milrinone et SN-50 et surtout dans le groupe sildénafil par rapport au groupe placébo. Le SN-50 produisait de moins bonnes relaxations dépendantes de l’endothélium face à l’acétylcholine que les autres traitements incluant placébo. Conclusion: Le sildénafil prévient mieux la dysfonction endothéliale pulmonaire que les autres traitements. Les bénéfices du SN-50 sont possiblement sous-estimés vu que la dose n’a pas pu être ajustée à la durée de CEC. Le sildenafil inhalé mérite une étude plus importante chez l’humain et le SN-50 dans un model de CEC animal.

Effects of pulmonary rehabilitation program in a patient with severe asthma diagnosis

Objective: to present the effectiveness of pulmonary rehabilitation programs in the treatmentof a patient with asthma, this is the case of a young Caucasian girl —17 years old— with severe asthma diagnosis, with symptoms since she was eight years old, 10th grade student. Method: She was referred to the program of Pulmonary Rehabilitation after three hospitalizations during the last year due to asthmatic crises, dyspnoea in activities of daily living, and intolerance to physical exercise. In the initial evaluation, a patient with non-controlled asthma was found; she was receiving short-acting medication admitting that she was not complying with regular use and with a prescribed dose of the pharmacological treatment and that she ignored the importance of this commitment for optimal evolution. The patient expressed concern about the progressive deterioration at her respiratory and functional level during the last year and her fear and anxiety for not being able to breathe during activities befitting her age. Results: One month after receiving bronchodilators and long-acting steroids permanently and complying with recommendations about regular use and adequate inhalatory technique, the patient was included in a three-times a-week program of pulmonary rehabilitation during eight weeks for upper and lower extremity endurance and resistance training. Conclusion: This intervention showed significant changes in the patient at functional level and a greater social participation.

Quality of life and Chronic Obstructive Pulmonary Disease

The Chronic Obstructive Pulmonary Disease (COPD) has a progressive and irreversible character and it’s associated to the triad of dyspnea, exercise limitation and the evident deterioration of quality of life. In the United States the prevalence of COPD in adult population is approximately of 6% in men, and 1 to 3% in women and it’s the fourth cause of mortality by no transmissible chronic diseases. In 1993, the National Health Interview Surgery considered that 12 millions of Americans suffer from chronic bronchitis and 2 million had emphysema. These two affections are responsible for more than 13% of the hospitalizations. As this affection progresses, patients experience a diminution in quality of life related to health (CVRS), their capacity to work get worse and their participation in physical and social activities reduces. Nevertheless, it has been confirmed that the isolated evaluation of COPD seriousness, defined by the reduction of the Forced Expiratory Volume in the First Second (FEV1), does not provide enough information to know the health state perceived by the patients. The fact that the CVRS is the result of the interaction of multiple physical, psychological and social factors, unique for each individual, can explain this finding. This paper is a general and updated approach to the integral handling of patients with COPD, and it discusses the concept of quality of life, related to health improvement.

Description and analysis of pulmonary rehabilitation care programs current state in four cities of Colombia

Purpose: there are many studies reporting the benefits of pulmonary rehabilitation, but few of them exhibit the behavior and activities of these services. This article presents the characteristics of services, parts management and training level of team members, in addition to the variables or instruments used to measure the effectiveness and impact in these programs. Method: it was made a cross sectional convenience sample which included seven pulmonary rehabilitation services in four Colombian cities (Bogotá, Medellín, Manizales and Cali), selected by the coverage, for having at least one year of experience and for being formally established and recognized nationwide. The interdisciplinary team of each service answered a survey that was validated through a pilot test and expert consensus. Participation was voluntary. Results: labor onset pulmonary rehabilitation services correspond to an average of a decade, with COPD and asthma pathologies of attention. The programs are characterized by an outpatient treatment with an average duration of eight to twelve weeks, with a frequency of an hour three times a week. Also, the director of the service is regularly a pulmonologist and the coordinator a physiotherapist (57.14%). The posgradual training of these professionals is notable, and they report to have procedural, administrative and communicative skills, but qualify regular there research skills. The physical and technological resources are well tested. 71.42% have done impact studies, but only 28.57% have been published. All have in common training in upper limbs, lower limbs, respiratory muscles, counseling, functional assessment and quality of life. The effectiveness and impact of programs is measured by the walking test, quality of life questionnaires and activities of daily living.