Decompression of the thoracic duct: A novel transcatheter approach.

In patients with total cavopulmonary connections, elevated central venous pressures (CVP) have detrimental effects on the lymphatic system causing an imbalance in fluid production and drainage of the interstitium. This combination may result in life-threatening lymphatic complications including plastic bronchitis (PB), protein losing enteropathy (PLE), chylothorax, and ascites. While embolization of the abnormal lymphatics has greatly improved outcomes from these complications, alternative treatment strategies have been proposed that would result in improved lymphatic drainage while leaving the lymphatic system intact. We report two novel transcatheter approaches for thoracic duct (TD) decompression in two patients who developed PLE after completion of the Fontan procedure as part of staged palliation for congenital heart disease. In addition, one patient had severe concurrent PB. In both patients, a connection was created between a left superior vena cava (LSVC) to the left atrium allowing for a nonsurgical method to decompress the TD. This procedure resulted in significant clinical and laboratory improvement of both patients' PLE and other symptoms of lymphatic dysfunction.

Why chronic cough in children is different.

Recently, there have been robust changes in our knowledge of the neurophysiology of cough and novel clinical etiologies. Specifically, cough hypersensitivity in adults and protracted bacterial bronchitis (PBB) in children have been increasingly investigated, and differences between chronic cough in children and adults have been widely reported. In young children, postinfectious cough, bronchiectasis, airway malacia, PBB, and asthma appear to be the main causes of cough; however, by adolescence, the causes of cough are more likely to become those common in adults, namely, gastroesophageal reflux, asthma, and upper airway syndrome. These differences are attributed to changes in various characteristics of the respiratory tract, immune system, and nervous system between children and adults. New knowledge about the neural aspects of cough has revealed a complex network of pathways that initiate cough. The effect of inflammation on cough neural processing occurs at multiple peripheral and central sites within the nervous system. Evidence exists that direct or indirect neuroimmune interaction induces a complex response, which can be altered by mediators released by the sensory or parasympathetic neurons and vice versa. During childhood, the respiratory tract and the nervous system undergo a series of anatomical and physiological maturation processes that produce the cough neural circuits. Alterations provoked by various pathological processes, noxious agents, infection, and inflammation during the developmental period can lead to persistent or irreversible modifications, which may explain why many adult patients, in addition to expressing high cough sensitivity, remain refractive to disease-specific therapies.

Predictors of Adverse Outcomes in Uncomplicated Lower Respiratory Tract Infections.

PURPOSE: Presentation with acute lower respiratory tract infection (LRTI) in primary care is common. The aim of this study was to help clinicians treat patients presenting with LRTI in primary care by identifying those at risk of serious adverse outcomes (death, admission, late-onset pneumonia). METHODS: In a prospective cohort study of patients presenting with LRTI symptoms, patient characteristics and clinical findings were recorded and adverse events identified over 30 days by chart review. Multivariable logistic regression analyses identified predictors of adverse outcomes. RESULTS: Participants were recruited from 522 UK practices in 2009-2013. The analysis was restricted to the 28,846 adult patients not referred immediately to the hospital. Serious adverse outcomes occurred in 325/28,846 (1.1%). Eight factors were independently predictive; these characterized symptom severity (absence of coryza, fever, chest pain, and clinician-assessed severity), patient vulnerability (age >65 years, comorbidity), and physiological impact (oxygen saturation <95%, low blood pressure). In aggregate, the 8 features had moderate predictive value (area under the receiver operating characteristic curve 0.71, 95% CI, 0.68-0.74); the 4% of patients with ≥5 features had an approximately 1 in 17 (5.7%) risk of serious adverse outcomes, the 35% with 3 or 4 features had an intermediate risk (1 in 50, 2.0%), and the 61% with ≤2 features had a low (1 in 200, 0.5%) risk. CONCLUSIONS: In routine practice most patients presenting with LRTI in primary care can be identified as at intermediate or low risk of serious outcome.

Time course of nocturnal cough and wheezing in children with acute bronchitis monitored by lung sound analysis.

Cough and wheezing are the predominant symptoms of acute bronchitis. Hitherto, the evaluation of respiratory symptoms was limited to subjective methods such as questionnaires. The main objective of this study was to objectively determine the time course of cough and wheezing in children with acute bronchitis. The impact of nocturnal cough on parent's quality of life was assessed as secondary outcome. In 36 children (2-8 years), the frequency of nocturnal cough and wheezing was recorded during three nights by automated lung sound monitoring. Additionally, parents completed symptom logs, i.e., the Bronchitis Severity Score (BSS), as well as the Parent-proxy Children's Acute Cough-specific Quality of Life Questionnaire (PAC-QoL). During the first night, patients had 34.4 ± 52.3 (mean ± SD) cough epochs, which were significantly reduced in night 5 (13.5 ± 26.5; p < 0.001) and night 9 (12.8 ± 28.1; p < 0.001). Twenty-two patients had concomitant wheezing, which declined within the observation period as well. All subjective parameters (BSS, Cough log and PAC-QoL) were found to be significantly correlated with the objectively assessed cough parameters.Conclusion: Long-term recording of cough and wheezing offers a useful opportunity to objectively evaluate the time course of respiratory symptoms in children with acute bronchitis. To assess putative effects of pharmacotherapy on nocturnal bronchitis symptoms, future studies in more homogeneous patient groups are needed. What is Known: • Cough and wheezing are the predominant symptoms of acute bronchitis. • There is a diagnostic gap in long-term assessment of these respiratory symptoms, which needs to be closed to optimize individual therapies. What is New: • Long-term recording of nocturnal cough and wheezing allows for objective evaluation of respiratory symptoms in children with acute bronchitis and provides a tool to validate the efficacy of symptomatic bronchitis therapies.

Colistin Use in Patients with Chronic Kidney Disease: Are We Underdosing Patients?

Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m² for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45⁻95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2⁻2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.

Vitamin D and respiratory health in the Busselton Healthy Ageing Study.

BACKGROUND AND OBJECTIVE: The relationship between vitamin D and respiratory disease was examined by cross-sectional analysis of a large community-based sample. METHODS: Serum 25-hydroxyvitamin D (25OHD) and history of respiratory disease, symptoms (recorded by questionnaire) and spirometry were measured in 5011 adults aged 45-69 years. Adjustments were made for age, sex, season and smoking (Model A), plus body mass index (BMI) and physical activity level (Model B), plus history of chronic diseases (Model C). RESULTS: Mean (SD) age was 58 (SD 6) years with 45% males, 10% current smokers and 12% taking vitamin D supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the three models (1.17% higher, compared with the 50-100 nmol/L group in Model C). CONCLUSION: Low levels of serum 25OHD were independently associated with asthma, bronchitis, wheeze and chest tightness after three levels of adjustment for potential confounders. Higher vitamin D levels were associated with higher levels of lung function.

Increased Sputum IL-17A Level in Non-asthmatic Eosinophilic Bronchitis.

BACKGROUND: Non-asthmatic eosinophilic bronchitis (NAEB) is one common cause of chronic cough which is characterized as airway eosinophilic inflammation like asthma but lack of airway hyper-responsiveness. Previous studies showed that Th2-pathway plays a role in NAEB, but the role of non-Th2 pathway in mechanism of NAEB remains unknown. Recently, IL-17A, a Th17-pathway cytokine, has been demonstrated to be involved in asthma development. However, the relationship between Th17-pathway and NAEB is unknown. METHODS: We aim to assess the airway level of IL-17A in the subjects with NAEB. Relationships between the IL-17A level and airway function in NAEB or asthma are also observed. We measured IL-17A concentrations in the sputum supernatant from 12 subjects with EB, 16 subjects with asthma [9 eosinophilic asthmatic (EA) and 7 non-eosinophilic asthmatic (NEA) according to the sputum eosinophil ≥ 3%], and 9 healthy control subjects. RESULTS: Increasing IL-17A level was found in NAEB group (29.65 ± 8.13 pg/ml), EA group (32.45 ± 3.22 pg/ml), and NEA group (29.62 ± 6.91 pg/ml) compared with the healthy control group (17.05 ± 10.30 pg/ml) (P < 0.05, P < 0.01, P < 0.05, respectively). The sputum IL-17A level was correlated with FENO (r = 0.44, P < 0.01), FEV1/FVC% (r = - 0.38, P < 0.05), MMEF%pred (r = - 0.34, P < 0.05), and sputum neutrophil% (r = 0.33, P < 0.05) in total. CONCLUSION: Th17-pathway may play a role not only in asthmatics, but also in subjects with NAEB, as reflected by increasing IL-17A concentrations in sputum supernatant.

Echocardiographic characteristics in Fontan patients before the onset of protein-losing enteropathy or plastic bronchitis.

BACKGROUND: It was this study's objective to evaluate the echocardiographic characteristics and flow patterns in abdominal arteries of Fontan patients before the onset of protein-losing enteropathy (PLE) or plastic bronchitis (PB). DESIGN: In this retrospective cohort investigation, we examined 170 Fontan patients from 32 different centers who had undergone echocardiographic and Doppler ultrasound examinations between June 2006 and May 2013. Follow-up questionnaires were completed by 105 patients a median of 5.3 (1.5-8.5) years later to evaluate whether one of the complications had occurred since the examinations. RESULTS: A total of 91 patients never developed PLE or PB ("non-PLE/PB"); they were compared to 14 affected patients. Eight of the 14 patients had already been diagnosed with "present PLE/PB" when examined. Six "future PLE/PB" patients developed those complications later on and were identified on follow-up. The "future PLE/PB" patients presented significantly slower diastolic flow velocities in the celiac artery (0.1 (0.1-0.5) m/s vs 0.3 (0.1-1.0) m/s (P = .04) and in the superior mesenteric artery (0.0 (0.0-0.2) m/s vs 0.2 (0.0-0.6) m/s, P = .02) than the "non-PLE/PB" group. Median resistance indices in the celiac artery were significantly higher (0.9 (0.8-0.9) m/s vs 0.8 (0.6-0.9) m/s, (P = .01)) even before the onset of PLE or PB. CONCLUSION: An elevated flow resistance in the celiac artery may prevail in Fontan patients before the clinical manifestation of PLE or PB.

Impulse oscillometry measurement of distal airways obstruction in depleted uranium-exposed Gulf War veterans.

INTRODUCTION: A cohort of Gulf War I veterans who sustained exposure to depleted uranium undergoes biennial surveillance for potential uranium-related health effects. We performed impulse oscillometry and hypothesized that veterans with higher uranium body burdens would have more obstructive abnormalities than those with lower burdens. METHODS: We compared pulmonary function of veterans in high versus low urine uranium groups by evaluating spirometry and oscillometry values. RESULTS: Overall mean spirometry and oscillometry resistance values fell within the normal ranges. There were no significant differences between the high and low uranium groups for any parameters. However, more veterans were classified as having obstruction by oscillometry (42%) than spirometry (8%). CONCLUSIONS: While oscillometry identified more veterans as obstructed, obstruction was not uranium-related. However, the added sensitivity of this method implies a benefit in wider surveillance of exposed cohorts and holds promise in identifying abnormalities in areas of the lung historically described as silent.

Successful Treatment of Protein-Losing Enteropathy and Plastic Bronchitis by Biphasic Cuirass Ventilation in a Patient with Failing Fontan Circulation.

We present a 16-year-old male patient with hypoplastic left heart syndrome who developed protein-losing enteropathy (PLE) and plastic bronchitis (PB) after a Fontan operation. He received medical therapies, including albumin infusion, unfractionated heparin, and high-dose anti-aldosterone therapy but could not obtain clinical relief. Biphasic cuirass ventilation (BCV) led to expectoration of bronchial casts and prompt resolution of PB. Notably, clinical symptoms related to PLE were dramatically improved after starting BCV. A brief period of BCV increased stroke volume from 26±1.4 to 39±4.0 mL. This case suggests that BCV could be an effective treatment for PLE in patients with failing Fontan circulation.

Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency.

PURPOSE: Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older). METHODS: Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups. RESULTS: After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients. CONCLUSIONS: These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for continued longitudinal study of pediatric and early-onset CVID patients to further characterize accrual of features over time.

ERS statement on protracted bacterial bronchitis in children.

This European Respiratory Society statement provides a comprehensive overview on protracted bacterial bronchitis (PBB) in children. A task force of experts, consisting of clinicians from Europe and Australia who manage children with PBB determined the overall scope of this statement through consensus. Systematic reviews addressing key questions were undertaken, diagrams in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement constructed and findings of relevant studies summarised. The final content of this statement was agreed upon by all members.The current knowledge regarding PBB is presented, including the definition, microbiology data, known pathobiology, bronchoalveolar lavage findings and treatment strategies to manage these children. Evidence for the definition of PBB was sought specifically and presented. In addition, the task force identified several major clinical areas in PBB requiring further research, including collecting more prospective data to better identify the disease burden within the community, determining its natural history, a better understanding of the underlying disease mechanisms and how to optimise its treatment, with a particular requirement for randomised controlled trials to be conducted in primary care.

Non-asthmatic eosinophilic bronchitis and its relationship with asthma.

Non-asthmatic eosinophilic bronchitis (NAEB) is an important cause of chronic cough. NAEB shares similar eosinophilic inflammation of airway and response to corticosteroids with asthma. However, in contrast to asthma, NAEB subjects have no airflow obstruction and airway hyperresponsiveness. The pathogenesis of NAEB are involved with many inflammatory cells such as eosinophils, lymphocytes, mast cells, cytokines and inflammatory mediators, includingTh2 cytokines, histamine, leukotrines, prograndins and oxidative stress. The different locations of inflammatory cells and the inflammatory mediators level may explain this difference between EB and asthma. There is no study on dose and duration of treatment. On the prognosis of NAEB, long term follow-up study suggested that NAEB should be a distinct entity rather than an early stage of asthma or COPD. The relapse rate is high after treatment. Assessing sputum eosinophils after treatment is useful to identify those at risk of relapse.

Invasive Aspergillus Pseudomembranous and Obstructive Tracheo-bronchitis in an Immuno-competent Patient.

A 19 year female, presented with life threatening haemoptysis and cough with minimum expectoration for 3 months. Bronchoscopy showed multiple nodules in airway. The direct microscopy and culture of sputum revealed fungal elements and Aspergillus flavus respectively. Serum Galactomannan was positive. Thus diagnosis of invasive aspergillus tracheo-bronchitis made. She responded to voriconazole. Aspergillus tracheo-bronchitis is a rare form of invasive pulmonary aspergillosis in immuno-competent host. Aspergillus spp in respiratory samples should not be routinely discarded as colonization.

Mast cells are associated with exacerbations and eosinophilia in children with severe asthma.

The role of mast cells in the pathogenesis of childhood asthma is poorly understood. We aimed to estimate the implication of airway mucosal mast cells in severe asthma and their relationship with clinical, functional, inflammatory and remodelling parameters.Bronchial biopsies were performed in 36 children (5-18 years) with severe asthma: 24 had frequent severe exacerbations and/or daily symptoms in the previous year (symptomatic group), and 12 had few symptoms and a persistent obstructive pattern (paucisymptomatic group). Nine children without asthma were included as control subjects. We assessed mast cells in the submucosa and airway smooth muscle using c-kit antibodies and in the entire biopsy area using Giemsa.The number of submucosal mast cells was higher in the symptomatic group than in the paucisymptomatic group (p=0.02). The number of submucosal mast cells correlated with the number of severe exacerbations (p=0.02, r=0.37). There were positive correlations between the number of submucosal mast cells (p<0.01, r=0.44), airway smooth muscle mast cells (p=0.02, r= 0.40), mast cells stained by Giemsa (p<0.01, r=0.44) and submucosal eosinophils.Mast cells are associated with severe exacerbations and submucosal eosinophilic inflammation in children with severe asthma.

Exposure to urban PM1 in rats: development of bronchial inflammation and airway hyperresponsiveness.

BACKGROUND: Several epidemiological and laboratory studies have evidenced the fact that atmospheric particulate matter (PM) increases the risk of respiratory morbidity. It is well known that the smallest fraction of PM (PM1 - particulate matter having a diameter below 1 µm) penetrates the deepest into the airways. The ratio of the different size fractions in PM is highly variable, but in industrial areas PM1 can be significant. Despite these facts, the health effects of PM1 have been poorly investigated and air quality standards are based on PM10 and PM2.5 (PM having diameters below 10 µm and 2.5 µm, respectively) concentrations. Therefore, this study aimed at determining whether exposure to ambient PM1 at a near alert threshold level for PM10 has respiratory consequences in rats. METHODS: Rats were either exposed for 6 weeks to 100 µg/m(3) (alert threshold level for PM10 in Hungary) urban submicron aerosol, or were kept in room air. End-expiratory lung volume, airway resistance (Raw) and respiratory tissue mechanics were measured. Respiratory mechanics were measured under baseline conditions and following intravenous methacholine challenges to characterize the development of airway hyperresponsiveness (AH). Bronchoalveolar lavage fluid (BALF) was analyzed and lung histology was performed. RESULTS: No significant differences were detected in lung volume and mechanical parameters at baseline. However, the exposed rats exhibited significantly greater MCh-induced responses in Raw, demonstrating the progression of AH. The associated bronchial inflammation was evidenced by the accumulation of inflammatory cells in BALF and by lung histology. CONCLUSIONS: Our findings suggest that exposure to concentrated ambient PM1 (mass concentration at the threshold level for PM10) leads to the development of mild respiratory symptoms in healthy adult rats, which may suggest a need for the reconsideration of threshold limits for airborne PM1.

Respiratory symptoms, sleep-disordered breathing and biomarkers in nocturnal gastroesophageal reflux.

BACKGROUND: Nocturnal gastroesophageal reflux (nGER) is associated with respiratory symptoms and sleep-disordered breathing (SDB), but the pathogenesis is unclear. We aimed to investigate the association between nGER and respiratory symptoms, exacerbations of respiratory symptoms, SDB and airway inflammation. METHODS: Participants in the European Community Respiratory Health Survey III in Iceland with nGER symptoms (n = 48) and age and gender matched controls (n = 42) were studied by questionnaires, exhaled breath condensate (EBC), particles in exhaled air (PEx) measurements, and a home polygraphic study. An exacerbation of respiratory symptoms was defined as an episode of markedly worse respiratory symptoms in the previous 12 months. RESULTS: Asthma and bronchitis symptoms were more common among nGER subjects than controls (54 % vs 29 %, p = 0.01; and 60 % vs 26 %, p < 0.01, respectively), as were exacerbations of respiratory symptoms (19 % vs 5 %, p = 0.04). Objectively measured snoring was more common among subjects with nGER than controls (snores per hour of sleep, median (IQR): 177 (79-281) vs 67 (32-182), p = 0.004). Pepsin (2.5 ng/ml (0.8-5.8) vs 0.8 ng/ml (0.8-3.6), p = 0.03), substance P (741 pg/ml (626-821) vs 623 pg/ml (562-676), p < 0.001) and 8-isoprostane (3.0 pg/ml (2.7-3.9) vs 2.6 pg/ml (2.2-2.9), p = 0.002) in EBC were higher among nGER subjects than controls. Albumin and surfactant protein A in PEx were lower among nGER subjects. These findings were independent of BMI. CONCLUSION: In a general population sample, nGER is associated with symptoms of asthma and bronchitis, as well as exacerbations of respiratory symptoms. Also, nGER is associated with increased respiratory effort during sleep. Biomarker measurements in EBC, PEx and serum indicate that micro-aspiration and neurogenic inflammation are plausible mechanisms.

Growth, Nutritional Status, and Pulmonary Function in Children with Chronic Recurrent Bronchitis.

Bronchitis is a common health problem in children. Frequent bronchitis in infancy increases the risk of developing chronic respiratory diseases. The aim of the study was to assess the level of growth and the nutritional status in children and youths with special regard to the level of body fatness assessed by measuring skin-fold thickness. Relationships between somatic development, pulmonary function and the course of the disease were also explored. The study was carried out using anthropometric and spirometric measurements and also information on the severity and course of the disease in 141 children with chronic or recurrent bronchitis. All of the subjects were patients of the Pulmonary Medicine and Allergology Center in Karpacz, Poland. The mean body height did not differ significantly between the children examined and their healthy peers. However, the infection-prone children had excessive body fatness and muscle mass deficiency. The increased level of subcutaneous adipose tissue occurred especially in children with short duration of the disease, i.e. a maximum of 1 year. The functional lung parameters were generally normal. The presence of atopic diseases such as allergic rhinitis or atopic dermatitis did not impair the course of the children's somatic development. Also, long-term disease or the presence of additional allergic diseases did not impair lung function in the examined children. Taking appropriate preventive measures is recommended to achieve and maintain normal body weight in children who receive therapy due to bronchitis.