Supplemental Oxygen Requirement Research Articles

Early administration of inhaled corticosteroids for preventing chronic lung disease in very low birth weight preterm neonates.

Chronic lung disease (CLD) remains a common complication among preterm infants. There is increasing evidence that inflammation plays an important role in the pathogenesis of CLD. Due to their strong anti-inflammatory properties, corticosteroids are an attractive intervention strategy. However, there are growing concerns regarding short- and long-term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects. To determine the impact of inhaled corticosteroids administered to preterm infants with birth weight up to 1500 grams (VLBW) beginning in the first two weeks after birth for the prevention of CLD as reflected by the requirement for supplemental oxygen at 36 weeks' postmenstrual age (PMA). Randomised and quasi-randomised trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 5 January 2016), MEDLINE (1966 to 5 January 2016), Embase (1980 to 5 January 2016), CINAHL (1982 to 5 January 2016), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web-site (1990 to May 2016). We included in this review randomised controlled trials of inhaled corticosteroid therapy initiated within the first two weeks of life in VLBW preterm infants. We evaluated data regarding clinical outcomes, including: CLD at 28 days or 36 weeks' PMA; mortality; combined outcome of death or CLD at 28 days of age and at 36 weeks' PMA; the need for systemic corticosteroids; failure to extubate within 14 days; and adverse effects of corticosteroids. All data were analysed using Review Manager (RevMan) 5. Meta-analyses were performed using relative risk (RR) and risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, the number needed to treat for an additional beneficial outcome (NNTB) was calculated. We used the GRADE approach to assess the quality of evidence. According to GRADE the quality of the studies was moderate. Three additional trials are included in this update. The present review includes data analyses based on 10 qualifying trials that enrolled 1644 neonates. There was no significant difference in the incidence of CLD at 36 weeks' PMA in the inhaled steroid versus the placebo group (5 trials, 429 neonates) among all randomised (typical RR 0.97, 95% CI 0.62 to 1.52; typical RD -0.00, 95% CI -0.07 to 0.06). There was no heterogeneity for this outcome (typical RR I² = 11%; typical RD I² = 0%). There was a significant reduction in the incidence of CLD at 36 weeks' PMA among survivors (6 trials, 1088 neonates) (typical RR 0.76, 95% CI 0.63 to 0.93; typical RD -0.07, 95% CI -0.13 to -0.02; NNTB 14, 95% CI 8 to 50). There was a significant reduction in the combined outcome of death or CLD at 36 weeks' PMA among all randomised neonates (6 trials, 1285 neonates) (typical RR 0.86, 95% CI 0.75 to 0.99; typical RD -0.06, 95% CI -0.11 to -0.00) (P = 0.04); NNTB 17, 95% CI 9 to infinity). There was no significant heterogeneity for any of these analyses (I² = 0%). A lower rate of reintubation was noted in the inhaled steroid group compared with the control group in one study. There were no statistically significant differences in short-term complications between groups and no differences in adverse events at long-term follow-up reported. Long-term follow-up of infants enrolled in the study by Bassler 2015 is ongoing. Based on this updated review, there is increasing evidence from the trials reviewed that early administration of inhaled steroids to VLBW neonates is effective in reducing the incidence of death or CLD at 36 weeks' PMA among either all randomised infants or among survivors. Even though there is statistical significance, the clinical relevance is of question as the upper CI limit for the outcome of death or CLD at 36 weeks' PMA is infinity. The long-term follow-up results of the Bassler 2015 study may affect the conclusions of this review. Further studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short- and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.

Evaluation and Documentation of Supplemental Oxygen Requirements is Rarely Performed in Patients Hospitalized With COPD.

Rationale: Patients hospitalized with chronic obstructive pulmonary disease (COPD) who require supplemental oxygen (O2) are at increased risk of hospital readmissions. There is a paucity of information regarding quality of evaluation and documentation regarding the need for supplemental O2 in this population. Objective: To determine the extent to which evaluation and documentation regarding the need for supplemental O2 occurs prior to hospital discharge in patients with COPD. Methods: We conducted a two-center retrospective cohort study of hospitalized adults with a physician diagnosis of COPD. We reviewed electronic health records to ascertain whether patients underwent evaluation beyond rest oximetry documenting hypoxemia and if there was adequate documentation of supplemental O2 requirements prior to discharge. Results: Of 526 patients hospitalized with a primary or secondary discharge diagnosis of COPD, 335 patients (mean age 69 years, 78% with diagnosis of COPD exacerbation) met eligibility criteria. Overall, 1 in 5 (22%, 73/335) hospitalized patients with COPD had an evaluation beyond rest oximetry for supplemental O2 requirements during admission. Adequate documentation of supplemental O2 requirements occurred in even fewer patients (16%, 54/335). Both evaluation (26% versus 5%, p=0.002) and documentation (19% versus 4%, p=0.001) of supplemental O2 requirements were more common in patients hospitalized for a COPD exacerbation compared to those hospitalized with COPD but without an exacerbation. Conclusions: Evaluation and documentation of supplemental O2 requirements beyond rest oximetry occur infrequently in patients hospitalized with COPD.

Congenital Diaphragmatic Hernia Defect Size and Infant Morbidity at Discharge.

Survival for infants with congenital diaphragmatic hernia (CDH) has gradually improved, yet substantial burden of disease remains. Although larger CDH defect sizes increase mortality, the association between defect size and morbidity has not been reported. Our objective was to evaluate the association of defect size with pulmonary, neurologic, and gastrointestinal morbidity at the time of hospital discharge. An international, prospective cohort study was performed. Patient demographics, intraoperative defect size, and clinical outcomes were reviewed. The primary outcome was morbidity at the time of discharge, which entailed supplemental oxygen requirement, abnormal neurologic clinical and radiographic findings, gastroesophageal reflux, supplemental nutrition, or pulmonary-, neurologic-, or gastrointestinal-related medications. A total of 3665 patients were included in the study cohort. Overall survival was 70.9%, and 84.0% of survivors were discharged from the hospital (16.0% transferred). Median age at discharge was 38 days (interquartile range [IQR] 23-69) and ranged from 22 (IQR 16-32) days for "A" (smallest) defects to 89 (IQR 64-132) days for "D" (largest) defects (P < .001). Of those discharged from the hospital, 1522 (74.2%) had pulmonary (n = 660, 30.2%), neurologic (n = 446, 20.4%), or gastrointestinal (n = 1348, 61.7%) morbidities, and multiple morbidities were diagnosed in 701 (34.7%) patients. On multivariable regression analyses incorporating key patient characteristics, defect size was consistently the greatest predictor of overall morbidity, hospital length of stay, and duration of ventilation. Infants with CDH are commonly discharged with ≥1 major morbidities. The size of the diaphragmatic defect appears to be the most reliable indicator of a patient's hospital course and discharge burden of disease.

Supplemental Oxygen Requirements of Critically Injured Adults: An Observational Trial.

The optimal amount of oxygen to deploy with pararescue personnel for combat casualty care is currently unknown. The purpose of this prospective observational trial was to determine the proportion of trauma patients requiring supplemental oxygen, whether high or low flow rates were needed, and to evaluate associations between injury characteristics and oxygen requirements. Over 6 months, dedicated study assistants observed oxygen requirements and delivery during the first 3 hours of emergency care for trauma patients meeting our institution's highest level trauma team activation criteria. The mean age of 204 enrolled subjects was 37 years, 79% were male, median injury severity score was 9 (interquartile range 1-21), 58% suffered penetrating injuries. Most (69%) were admitted; 17% went directly to the operating room, and 38% went directly to the intensive care unit from the emergency department. 136/160 nonintubated patients were managed with no or low-flow supplemental oxygen. Penetrating injuries were less likely to require supplemental oxygen (relative risk 0.65, 95% confidence interval 0.50-0.84). Subjects with Glasgow Coma Scale scores <15, abdominal or chest injury, or hypotension were more likely to require supplemental oxygen. There is significant opportunity to reduce the need for high-flow oxygen delivery to the battlespace.

Physiological and biological predictors of length of stay and recovery in adults with acute asthma: An observational cohort study.

Asthma is a prevalent, chronic disease associated with significant risk to patients and cost to healthcare systems. Accurate estimates of length of stay and recovery are important for patient information, physician prognostication, and management of inpatient beds. To assess factors affecting length of stay and time to recovery in adults with acute asthma. We prospectively recruited adult asthmatic non-smokers admitted with an asthma exacerbation. Participants were assessed for demographics, symptoms, medications, bloods including blood count, clotting status, and cytokines. Results were analyzed for correlation and subsequently in a regression model. One hundred twenty-six participants were recruited of which 75.4% were female. Mean age was 40.0 and mean length of stay was 3.98 days. Length of stay was associated with lower APTT ratio (<P = 0.001), oxygen requirement (P = 0.02), increased AST (P = 0.005), increasing age (P = 0.02), and lower %predicted FEV1 (P = 0.02). Longer time to recovery was associated with plasma IL-12 >1 pg/mL (P = 0.04). Older participants with lower FEV1 and supplemental oxygen requirements are likely to remain in hospital longer. Activation of the "intrinsic" clotting pathway correlates with an increased length of stay as does a raised serum AST. Detectable IL-12 in plasma correlates with slower recovery and this may be due to poor response to corticosteroids.

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants &lt; 29 weeks’ gestation

BackgroundBronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks’ gestation.Methods/designThis is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks’ gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks’ postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks’ PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed α =0.05).DiscussionDHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants.Trial registrationAustralia and New Zealand Clinical Trial Registry: ACTRN12612000503820. Registered 09 May 2012.

Human parechovirus type 3 infection: Cause of apnea in infants born prematurely

Four infants born prematurely presented with multiple apnea episodes caused by human parechovirus type 3 (HPeV3) infection. All patients required oxygen supplementation, and one patient required mechanical ventilation. HPeV3 infection might be included in the differential diagnosis of apnea in neonates and young infants, especially those born prematurely.

Right- versus left-sided congenital diaphragmatic hernia: a comparative outcomes analysis

PurposeRight-sided congenital diaphragmatic hernia (R-CDH) occurs in up to 25% of all CDH cases, but has been less widely studied compared to left-sided defects. We sought to compare characteristics and outcomes of left- versus right-sided defects in a large cohort of CDH patients who underwent standardized treatment and follow-up at a single institution. MethodsWe retrospectively reviewed charts of all CDH patients in our pulmonary hypoplasia program from January 2002 through December 2014. Categorical variables were analyzed by Fisher's exact test and continuous variables by Mann–Whitney t-test (p≤0.05). ResultsA total of 330 CDH patients were treated more than the 12-year study period, with 274 (83%) left-sided and 56 (17%) right-sided cases identified. Specific pulmonary morbidities were associated with R-CDH, with increased duration of nitric oxide therapy, increased requirement for tracheostomy, increased requirement for supplemental oxygen at the time of NICU discharge, and increased chronic pulmonary hypertension with requirement for long-term Sildenafil therapy. ConclusionsIn this series, R-CDH was not associated with increased mortality, but was associated with increased requirement for pulmonary vasodilatory therapy and requirement for tracheostomy. The high incidence of pulmonary complications indicates increased severity of pulmonary hypoplasia in R-CDH, supporting a role for delivery in tertiary centers with expertise in CDH management.

Acute undifferentiated febrile illness in patients presenting to a Tertiary Care Hospital in South India: clinical spectrum and outcome

Background:Acute undifferentiated febrile illness (AUFI) may have similar clinical presentation, and the etiology is varied and region specific.Materials and Methods:This prospective observational study was conducted in a tertiary hospital in South India. All adult patients presenting with AUFI of 3–14 days duration were evaluated for etiology, and the differences in presentation and outcome were analyzed.Results:The study cohort included 1258 patients. A microbiological cause was identified in 82.5% of our patients. Scrub typhus was the most common cause of AUFI (35.9%) followed by dengue (30.6%), malaria (10.4%), enteric fever (3.7%), and leptospirosis (0.6%). Both scrub typhus and dengue fever peaked during the monsoon season and the cooler months, whereas no seasonality was observed with enteric fever and malaria. The mean time to presentation was longer in enteric fever (9.9 [4.7] days) and scrub typhus (8.2 [3.2] days). Bleeding manifestations were seen in 7.7% of patients, mostly associated with dengue (14%), scrub typhus (4.2%), and malaria (4.6%). The requirement of supplemental oxygen, invasive ventilation, and inotropes was higher in scrub typhus, leptospirosis, and malaria. The overall mortality rate was 3.3% and was highest with scrub typhus (4.6%) followed by dengue fever (2.3%). Significant clinical predictors of scrub typhus were breathlessness (odds ratio [OR]: 4.96; 95% confidence interval [CI]: 3.38–7.3), total whole blood cell count >10,000 cells/mm3 (OR: 2.31; 95% CI: 1.64–3.24), serum albumin <3.5 g % (OR: 2.32; 95% CI: 1.68–3.2). Overt bleeding manifestations (OR: 2.98; 95% CI: 1.84–4.84), and a platelet count of <150,000 cells/mm3 (OR: 2.09; 95% CI: 1.47–2.98) were independent predictors of dengue fever.Conclusion:The similarity in clinical presentation and diversity of etiological agents demonstrates the complexity of diagnosis and treatment of AUFI in South India. The etiological profile will be of use in the development of rational guidelines for control and treatment of AUFI.

Congenital Cystic Adenomatoid Malformation: A Tertiary Care Hospital Experience.

Congenital Cystic Adenomatoid Malformation (CCAM) is an uncommon developmental deformity affecting the terminal respiratory structures. It is characterized by broncho pulmonary foregut malformations. The reason behind it is an arrest in lung development between 4th and 7th week of fetal life. The present study was conducted to assess the clinical and radiological profile and also to study the role of surgical intervention in patients with CCAM. All patients with clinical suspicion or provisional diagnosis of CCAM were included in the study. A clinical questionnaire was prepared to collect data. Computed Tomography (CT) chest with High Resolution Computed Tomography (HRCT) was done for all the patients. Patients were assessed by paediatric surgeon and eligible patients were operated. The procedure conducted was usually open thoracotomy under general anaesthesia. The affected lobes were removed and specimens were sent for histopathological analysis. All included patients were followed up prospectively to find out about their current level of health. Via telephonic interview they were asked about their overall growth, quality of life, activity, rate of respiratory infections and requirement of hospital admission. Total 15 patients with diagnosis of CCAM were included in the study. Of them, 8 (53.3%) were male. The commonest presentation was cough 13(86%), breathing difficulty 11(73%), fever 9(60%), recurrent pneumonia 4(26%), hypoxia requiring oxygen supplementation 6(40%), others 2(12%). Thirteen patients required surgical intervention and underwent lobectomy. There were 2 cases of type I, one each of type II and III, 3 case of type IV while 5 were intermediate type. There was no procedure related mortality. The median duration of hospital stay and all were successfully discharged with median duration of stay 11±16 days. The study concludes that if recognized early, surgical removal of affected lung prevents the complications like recurrent pulmonary infections. The surgery is well tolerated without any post-operative mortality or morbidity.

Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection.

Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.

Plasma concentrations and sedative effects of a dexmedetomidine, midazolam, and butorphanol combination after transnasal administration in healthy rabbits.

Plasma concentrations of dexmedetomidine (D=0.1mg/kg), midazolam (M=2mg/kg), and butorphanol (B=0.4mg/kg) were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) after their simultaneous (DMB) transnasal (TN) administration to healthy rabbits. Time-dependent changes in sedation and antinociception were evaluated by measuring a sedation score based on rabbit's posture, loss of the righting, palpebral and pedal withdrawal reflexes and by instrumental monitoring of rectal temperature, heart rate, arterial blood pressure, pulse-oximetry, and capnometry. The peak plasma concentration (Cmax ) of each drug was reached within 5min (Tmax ) from DMB-TN administration along with deep sedation and analgesia. Such effects subsided after 45min into a moderate sedation and analgesia lasting for additional 15min. All rabbits awakened spontaneously and uneventfully 90min after DMB-TN administration. During the anesthetic procedure, arterial blood pressure markedly decreased and respiratory depression ensued requiring oxygen supplementation. The results of this study show that all three molecules of the DMB combination were absorbed through the TN route, inducing deep sedation and analgesia suitable for minor surgical procedures. Such combination should be used with caution in rabbits bearing cardiovascular or respiratory diseases because of its ability to induce hypotension and respiratory depression.

Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Following Hematopoietic Stem Cell Transplantation or Chemotherapy--Results from the Italian Therapeutic Use Protocol

Introduction Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable, potentially life-threatening complication of chemotherapy (CT) given as conditioning for hematopoietic stem cell transplantation (HSCT), or as primary treatment. Severe hepatic VOD/SOS, traditionally defined by occurrence of multi-organ dysfunction/failure (MOD/MOF), may be associated with mortality rates &gt;80%. In the European Union, defibrotide is approved for treatment of severe VOD/SOS post-HSCT. It is not approved in the United States, but is available through an expanded-access program. Here, we report the results of an Italian therapeutic use program, defibrotide treatment protocol (TUT), in which defibrotide was provided upon physician request for treatment of patients with VOD/SOS. Methods This was a multicenter, single-arm, open-label program of defibrotide treatment in patients with hepatic VOD/SOS, with or without MOD/MOF, from 2010-2014. Patients were eligible if they were diagnosed with VOD/SOS having met ≥2 of the following criteria: bilirubin (&gt;2 mg/dL), ascites, unexplained weight gain &gt;5% above baseline (weight on day 1 of HSCT conditioning or CT), or hepatomegaly. Patients with biopsy-proven VOD/SOS were also eligible. Exclusion criteria were use of anticoagulants (beyond those for IV line maintenance), significant uncontrolled acute bleeding (transfusions after dialysis were allowed), pregnancy, and hemodynamic instability requiring &gt;2 vasopressor drugs. MOD/MOF was defined as renal (creatinine &gt;3x baseline, creatinine clearance or glomerular filtration rate &lt;40% of baseline, or dialysis dependence) or pulmonary (oxygen saturation &lt;90% on room air, requiring oxygen supplementation, or ventilator dependence) dysfunction. Patients were treated with defibrotide 25 mg/kg/d in 4 divided doses given intravenously over 2 hours each. Outcomes included survival at day +100 post-HSCT or post-CT and adverse events (AEs). VOD/SOS and MOD/MOF were not reported as AEs unless the event was considered serious. Demographics and AEs were analyzed using descriptive statistics; efficacy was estimated by the SAS/STAT LifeTest Procedure. Results A total of 98 patients had hepatic VOD/SOS (92% had VOD/SOS post-HSCT [81% allogeneic, 10% autologous, 1% unknown], 8% post-CT); of these, 21% had MOD/MOF and 79% did not. Median age was 13.4 years (range 0-68; 57 [58%] aged &lt;18 years and 41 [42%] ≥18 years), 55% were male, and 65% were white. The most common primary diseases were acute myelogenous leukemia (25%) and acute lymphoblastic leukemia (19%). The most common prophylaxis regimens for graft-vs-host disease (GvHD) were reported as cyclosporine + methotrexate (38%), cyclosporine (12%), and cyclosporine + methotrexate + other (12%); tacrolimus- and sirolimus-containing regimens, which have been associated with development of VOD/SOS, were received by 5% and 4% of patients, respectively. The median defibrotide dose was 25 mg/kg/d (range, 6.15-40.0) and median duration of treatment was 14 days (range: 1-84). The estimated day +100 survival for all patients was 68.4% (95% CI, 58.0%-76.7%). Day +100 survival in post-HSCT patients was 67.0% (95% CI, 56.2%-75.8%) and for post-CT patients was 85.7% (95% CI, 33.4%-97.9%). Across the entire study, 38 deaths were reported; primary causes were progression of VOD/SOS and MOD/MOF (44.7%), infection (21.1%), GvHD (15.8%), and disease progression (13.2%). Treatment-emergent AEs were reported in 21% of patients in this therapeutic use program; the most common (reported in ≥2 patients) were MOD/MOF (9%), VOD/SOS (6%), and cytomegalovirus infection and acute respiratory distress syndrome (2% each). Treatment-related AEs were reported by 5% of patients, and included hemorrhagic cystitis, urinary tract hemorrhage, hemorrhages (unspecified), hemorrhagic diathesis, and pulmonary hemorrhage (1 patient each). Serious AEs were reported in 15% of patients, most commonly MOD/MOF (7%), VOD/SOS (4%), and acute respiratory distress syndrome (2%). Conclusion In the Italian therapeutic use program, defibrotide treatment protocol (TUT), approximately one-fifth of the patients with hepatic VOD/SOS had MOD/MOF. The estimated survival rate of 68.4% at day +100, and the AE profile, was consistent with efficacy and safety data reported in previous studies in similar VOD/SOS patient populations. Support: Jazz Pharmaceuticals. Disclosures Off Label Use: Defibrotide is an investigational treatment for hepatic veno-occlusive disease/sinusoidal obstruction syndrome in the United States.. Amber:Jazz Pharmaceuticals: Employment, Equity Ownership. Banerjee:Jazz Pharmaceuticals: Employment, Equity Ownership. Finetto:Gentium S.p.A.: Employment; Jazz Pharmaceuticals: Equity Ownership.

Human Metapneumovirus Infection in Jordanian Children: Epidemiology and Risk Factors for Severe Disease.

Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection in young children. Our objectives were to define HMPV epidemiology and circulating strains and determine markers of severe disease in Jordanian children. We conducted a prospective study from March 16, 2010 to March 31, 2013 using quantitative reverse transcription-polymerase chain reaction to determine the frequency of HMPV infection among children <2 years old admitted with fever and/or acute respiratory illness to a major government hospital in Amman, Jordan. HMPV was present in 273 of 3168 (8.6%) of children presenting with acute respiratory tract infection. HMPV A2, B1 and B2, but not A1, were detected during the 3-year period. HMPV-infected children were older and more likely to be diagnosed with bronchopneumonia than HMPV-negative children. HMPV-infected children with lower respiratory tract infection had higher rates of cough and shortness of breath than children with lower respiratory tract infection infected with other or no identifiable viruses. Symptoms and severity were not different between children with HMPV only compared with HMPV coinfection. Children with HMPV subgroup A infection were more likely to require supplemental oxygen. In a multivariate analysis, HMPV subgroup A and age <6 months were independently associated with supplemental oxygen requirement. HMPV is a leading cause of acute respiratory tract disease in Jordanian children <2 years old. HMPV A and young age were associated with severe disease. Ninety percent of HMPV-infected hospitalized children were full term and otherwise healthy, in contrast to high-income nations; thus, factors contributing to disease severity likely vary depending on geographic and resource differences.

A Multidisciplinary Team Approach to the Care of Patients With Advanced Interstitial Lung Disease (ILD) in the Outpatient Setting

SESSION TITLE: Diffuse Lung Disease Posters SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: A significant number of patients with idiopathic pulomary fibrosis (IPF) are hospitalized during their disease course; hospitalizations from respiratory causes are associated with increased mortality. We examined the outcomes associated with our outpatient-based patient-centered multidisciplinary care model for advanced ILD, including looking at ER visits, hospitalizations, and in-hospital deaths. METHODS: A retrospective chart review was completed on patients with known advanced ILD who had undergone outpatient multidisciplinary assessment, either at an ILD clinic or in the community, and had individualized action plans for effective symptom management in place that were escalated based on patient needs. Data was collected on demographics, diagnosis, disease severity, periodic multidisciplinary assessments, symptom-based action plans (for dyspnea, cough, respiratory infections, etc) and advance care planning. Follow-up data was collected on subsequent ER visits, hospitalizations, and overall functional status. RESULTS: 12 Patients were reviewed; 10 had a diagnosis of IPF. Mean DLCO and supplemental oxygen requirements at latest assessments were 24% and 15L, respectively. All patients were seen by a multidisciplinary care team consisting of physicians, respiratory therapists, physiotherapists, occupational therapists, dieticians and nurses. All patients had home care, advance directives, and action plans in place. Mean follow-up period from initial assessment to death was 8 months (1-21 months). There were no presentations to ER and only 8 total admissions to hospital among 12 patients (mean of 0.67) following initial multidisciplinary assessments. 7 Patients were managed at home, 1 in hospice and 2 on palliative care wards in the days prior to death. One patient died in hospital; one patient is still alive. All patients were independent of their BADLs in the weeks prior to death or latest assessment. CONCLUSIONS: Implementation of an outpatient multidisciplinary care model for advanced ILD may lead to decreased acute care utilization, including ER visits and hospitalizations. Use of individualized, symptom-based action plans help patients maintain (better symptom control, independence, and the ability to live at home. CLINICAL IMPLICATIONS: Effective symptom management in ILD can decrease burden the on patients, families, and health care systems, minimizing the need for acute care hospitalization. This may have a significant positive impact on mortality in this patient population. DISCLOSURE: The following authors have nothing to disclose: Jean Du Plessis, Meena Kalluri, Janice Richman-Eisenstat No Product/Research Disclosure Information

Impact of bacteria in nasal aspirates on disease severity of bronchiolitis

Background: The effect of potentially pathogenic bacteria (PPB) on disease severity in patients with bronchiolitis is understudied. Methods: This prospective study was carried out in the Children's Hospital of Soochow University during the 2012–2013 autumn and winter seasons. We enrolled consecutive children < 2 years of age hospitalized with an attending physician's diagnosis of bronchiolitis. Nasopharyngeal aspirate samples were tested for multiple respiratory viruses and cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Results: In all, 30% (188 patients) were positive for Strep. pneumoniae, H. influenzae, M. catarrhalis, and Staph. aureus. Length of stay (LOS) for patients with PPB was 4.0 days (interquartile range, IQR, 25th–75th percentile: 3.0–6.0 days) versus 3.0 days (IQR, 3.0–5.0 days) for patients without PPB (p < 0.001). However, requirement and duration of supplemental oxygen were not significantly different between the two groups. H. influenzae was an independent risk factor for hospital LOS ≥ 5.0 days (adjusted odds ratio, 1.75; 95% confidence interval, 1.06–2.91). The presence of PPB was not associated with increased risk of supplemental oxygen requirement. Conclusions: Our study demonstrated that pediatricians should evaluate for PPB in patients with bronchiolitis, especially when they present with RSV infection, fever or percentage of neutrophils > 40%. The presence of H. influenzae in nasal aspirates is associated with longer LOS in patients with bronchiolitis.

Predictors of complications following adenotonsillectomy in children with severe obstructive sleep apnea

ObjectiveTo identify pre-operative risk factors predicting complications following adenotonsillectomy in children with severe OSA. MethodsRetrospective chart review in an academic tertiary care center. Children with symptoms of OSA with overnight polysomnography (PSG) revealing apnea–hypopnea index (AHI) >10, who underwent adenotonsillectomy with overnight postoperative observation between 2008 and 2012. Univariate logistic regression was used to assess odds ratio (OR) of individual risk factors versus postoperative complications such as overnight desaturations <90%, length of stay (LOS)>24h, supplemental oxygen requirement, and transfer to a higher level of care. ResultsAll patients (n=157) with severe OSA were observed overnight. Mean age was 5.3±3.7 years. Twenty-five (15.9%) patients had LOS>24h. Forty-two (26.8%) had overnight desaturations <90%. AHI ≥15 and O2 saturation nadir <80% on preop polysomnography (PSG) were independent predictors of post-op O2 saturation <90% and LOS>24h. (p<0.05). PSG minimum saturation <80% was the strongest predictor of all variables examined with an OR of 6.98 (3.15–15.48, 95% CI) for desaturation <90% and 5.19 (2.11–12.75, 95% CI) for LOS>24h. Preop PSG O2 saturation<90% predicted overnight post op oxygen requirement with an OR of 3.38 (1.39–8.25, 95%CI). ConclusionsPreoperative polysomnography yields significant independent predictors of post-op complications in children with OSA. While AHI is a significant independent predictor, minimum O2 saturation on preop PSG appeared the strongest predictor when <80%. Patients with these risk factors, especially low O2 on PSG, warrant overnight observation with continuous pulse oximetry.

Long-term pulmonary function in children with recessive polycystic kidney disease

BackgroundNeonatal autosomal-recessive polycystic kidney disease (ARPKD) is associated with pulmonary hypoplasia and severe respiratory distress. There is no published information on long-term lung function in ARPKD survivors.MethodsPulmonary function tests, including...

The Role of Human Milk Immunomodulators in Protecting Against Viral Bronchiolitis and Development of Chronic Wheezing Illness.

Infants who are breastfed are at an immunological advantage when compared with formula fed infants, evidenced by decreased incidence of infections and diminished propensity for long term conditions, including chronic wheeze and/or asthma. Exclusive breastfeeding reduces the duration of hospital admission, risk of respiratory failure and requirement for supplemental oxygen in infants hospitalised with bronchiolitis suggesting a potentially protective mechanism. This review examines the evidence and potential pathways for protection by immunomodulatory factors in human milk against the most common viral cause of bronchiolitis, respiratory syncytial virus (RSV), and subsequent recurrent wheeze in infants. Further investigations into the interplay between respiratory virus infections such as RSV and how they affect, and are affected by, human milk immunomodulators is necessary if we are to gain a true understanding of how breastfeeding protects many infants but not all against infections, and how this relates to long-term protection against conditions such as chronic wheezing illness or asthma.

Hyperoxia promotes polarization of the immune response in ovalbumin-induced airway inflammation, leading to a TH17 cell phenotype.

Previous studies have demonstrated that hyperoxia-induced stress and oxidative damage to the lungs of mice lead to an increase in IL-6, TNF-α, and TGF-β expression. Together, IL-6 and TGF-β have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in response to ovalbumin-induced acute airway inflammation. Airway inflammation was induced in female BALB/c mice by intraperitoneal sensitization and intranasal introduction of ovalbumin, followed by challenge methacholine. After the methacholine challenge, animals were exposed to hyperoxic conditions in an inhalation chamber for 24 h. The controls were subjected to normoxia or aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of hyperoxia, the number of macrophages and lymphocytes decreased in animals with ovalbumin-induced airway inflammation, whereas the number of neutrophils increased after ovalbumin-induced airway inflammation. The results showed that expression of Nrf2, iNOS, T-bet and IL-17 increased after 24 of hyperoxia in both alveolar macrophages and in lung epithelial cells, compared with both animals that remained in room air, and animals with ovalbumin-induced airway inflammation. Hyperoxia alone without the induction of airway inflammation lead to increased levels of TNF-α and CCL5, whereas hyperoxia after inflammation lead to decreased CCL2 levels. Histological evidence of extravasation of inflammatory cells into the perivascular and peribronchial regions of the lungs was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes polarization of the immune response toward the TH17 phenotype, resulting in tissue damage associated with oxidative stress, and the migration of neutrophils to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin-induced acute airway inflammation is relevant to preventing or treating asthmatic patients that require oxygen supplementation to reverse the hypoxemia.