Pulmonary hypertension screening in children with sickle cell disease.

BACKGROUND: Screening for pulmonary hypertension (PHT) is recommended in children with sickle cell disease (SCD). However, best approaches are poorly described. We examined the utility of PHT symptoms, echocardiogram (ECHO), N-terminal-pro hormone brain natriuretic peptide (NT-proBNP), and BNP to screen for PHT in the SCD pediatric population. METHODS: Children (8-18 years old) with SCD-HbSS and HbSthal° were prospectively included and underwent PHT screening. The screening consisted of a comprehensive PHT symptoms evaluation, ECHO measurement, and NT-proBNP and BNP levels. RESULTS: A total of 73 patients were included (mean age 12 ± 5.7 years; >80% on hydroxyurea), of which 37% had a symptom consistent with PHT, including exertional dyspnea (26.5%), fatigue (17.6%), palpitation (14.7%), and chest pain (10.3%). ECHO was obtained in 53 (72.6%) patients, with only ECHO of 48 patients included in the final analysis. Elevated ECHO peak tricuspid regurgitant jet velocity (TRV) >2.5 m/s or indirect findings to suggest PHT were seen in only two of 48 (4.2%). No significant differences were seen between those with and without PHT symptoms when compared for NT-proBNP, BNP, hemoglobin, pulmonary function testing, fractional exhaled nitric oxide, asthma, oxygen saturation, and sleep apnea. CONCLUSION: PHT symptoms are not consistent with ECHO, NT-proBNP nor BNP findings in children with SCD. PHT prevalence based on TRV was low in children on hydroxyurea, therefore screening may not be warranted for this group.

Sleep Apnea Screening in Children With Sickle Cell Anemia.

BACKGROUND: Screening for obstructive sleep apnea (OSA) is recommended by current guidelines in children with sickle cell anemia (SCA), but no specific approach is described. The Pediatric Sleep Questionnaire (PSQ) is a validated detection tool for OSA in children. We assessed the utility of PSQ to screen for OSA in children with concomitant SCA and snoring. MATERIALS AND METHODS: A prospective study, in children 4 to 18 years old with SCA. Subjects were assessed for snoring and PSQ administered at the same visit. All children with snoring were then referred for polysomnography. RESULTS: A total of 106 subjects were screened. Habitual snoring prevalence was 51/106 (48.1%). In the snoring group, OSA was detected in 83.9% (apnea-hypopnea index [AHI] ≥1.0/h) and 22.6% (AHI ≥5.0/h), respectively. Sensitivity and specificity of PSQ in children with snoring was 46.2% and 20.0% (AHI ≥1.0/h), and 57.1% and 50.0% (AHI ≥5.0/h), respectively. Physician assessment for snoring had a high sensitivity of 70.3% but low specificity of 58.4% (AHI ≥1.0/h), and 87.5% and 41.5% (AHI ≥5.0/h), respectively. CONCLUSION: PSQ is a poor screening tool for detection of OSA in those children with SCA who snore. Physician assessment for snoring could however be an initial approach before polysomnography.

Unexpected results of a randomized quality improvement program for children with severe asthma.

Objective: To assess whether an asthma intervention program reduces treatment days outside the home among children with severe asthma receiving comprehensive care (CC) in our center.Methods: Between October 21, 2014 and September 28, 2016, children with severe asthma were randomized to receive CC alone (n = 29) or CC plus the asthma intervention program (n = 34) which involved collaboration with pharmacists and school nurses, motivational interviewing, and tracking the one-second forced expiratory volume at home. All patients were followed through March 31, 2017. Frequentist and Bayesian intent-to-treat analyses were performed.Results: The asthma intervention program doubled the telephone calls between the staff and families (753 vs 356 per 100 child years for the intervention group vs. control group; Rate Ratio [RR], 2.11 [95% confidence interval, 1.29-3.45]). Yet, we found no evidence that it reduced the composite number of days of healthcare outside home which includes: clinic visits, ED visits, and hospital admissions (1179 vs 958 per 100 child-years in the intervention group vs. control group; [RR], 1.23 [95% CI, 0.82-1.84]) or secondary outcomes which are individual components (clinic visits, ED visits, hospitalizations, PICU admissions and school absences; RR 1.15 - 2.30; p > 0.05). Bayesian analysis indicated a 67% probability that the intervention program increases total treatment days outside the home and only a 14% probability of a true decrease of >20% as originally hypothesized.Conclusion: A multi-component intervention program provided to children with severe asthma failed to reduce and may have increased days of healthcare outside home and school absenteeism.

Validation of the breathmobile case identification survey for asthma screening in children with sickle cell disease.

Background: Asthma is a chronic airway disorder with variable/recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an inflammation. The expert panel report of the National Heart Lung and Blood Institute recommends asthma screening in sickle cell disease (SCD); however, specific approach is not mentioned. We hypothesize that the breathmobile case identification survey (BCIS) is a valid asthma screening tool in children with SCD.Methods: This prospective, single-center study enrolled 129 SCD patients aged 5 to 18 years from March 2016 to March 2018. All patients completed BCIS, spirometry, and fractional exhaled nitric oxide (FeNO). A single pulmonologist blinded to the BCIS results evaluated patients for asthma.Results: Asthma prevalence was 41%. Male gender (60.4%; p = 0.041), allergic rhinitis (86.8%; p < 0.01), hydroxyurea usage (73.6%; p < 0.01), and family history of asthma (34%; p < 0.01) were higher but not self-reported parental asthma history, eczema, and tobacco smoke exposure in the asthma group compared to the nonasthma group. FEV1 (p = 0.003), FVC (p = 0.02), FEV1/FVC (p = 0.053), and FEF25-75% (p = 0.02) were lower in asthma. FeNO levels were comparable in both groups. The sensitivity, specificity, positive predictive value, and negative predictive value of the abbreviated BCIS were 67.3%, 90.8%, 83.3%, and 80.2% for asthma; and 82.1%, 90.8%, 76.7%, and 93.2% for persistent asthma, respectively. Persistent asthma patients had a trend of higher hydroxyurea use (82.8% vs. 58.3%; p = 0.049) and tobacco smoke exposure (55.2% vs. 29.2%; p = 0.057) compared to intermittent asthma.Conclusion: We have validated the BCIS to screen for asthma in SCD. Spirometry but not FeNO may support an asthma diagnosis.

Easy Breathing: A Review of the Impact of Air Quality on Pediatric Health Outcomes.

Preventable environmental factors such as exposure to poor air quality are predicted to affect 23% of all global deaths. Although there have been efforts to reduce air pollution through federal guidelines for vehicle and industrial emissions, the air in the United States remains far from clean. Children and pregnant women have been identified as high-risk populations who are particularly susceptible to the negative effects of poor air quality. This paper provides an overview of health concerns related to poor air quality, pediatric considerations from pregnancy through childhood, the importance of increased awareness of air quality assessment and prevention in patient encounters, and current advocacy efforts and legislation.

Characteristics and Outcomes of Children with Clinical History of Atopic Versus Non-atopic Asthma Admitted to a Tertiary Pediatric Intensive Care Unit.

BACKGROUND: Children admitted to the Pediatric Intensive Care Unit (PICU) with status asthmaticus have variable clinical courses, and predicting their outcomes is challenging. Identifying characteristics in these patients that may require more intense intervention is important for clinical decision-making. OBJECTIVE: This study sought to determine the characteristics and outcomes, specifically length of stay and mortality, of atopic versus non-atopic asthmatics admitted to a PICU with status asthmaticus. METHODS: A retrospective study was conducted at a children's hospital from November 1, 2008 to October 31, 2013. A total of 90 children admitted to the PICU were included in the analysis. Patients were divided into two groups based on the presence of specific historical data indicative of a clinical history of atopy. Children were considered to be atopic if they had a parental history of asthma, a personal history of eczema, or a combined history of wheezing (apart from colds) and allergic rhinitis (diagnosed by a medical provider). The median hospital Length Of Stay (LOS), PICU LOS, cardiopulmonary arrest, and mortality were compared between atopic and non-atopic asthma groups. Regression models were used to estimate the LOS stratified by atopic or non-atopic and by history of intubation in present hospitalization. RESULTS: Median hospital LOS for atopic children was 5.9 days (IQR of 3.8-8.7) and 3.5 days (IQR of 2.2-5.5) for non-atopic asthmatics (z = 2.9, p = 0.0042). The median PICU LOS was 2.5 days (IQR 1.4-6.1) for atopic asthmatics and 1.6 days (IQR 1.1-2.4) for non-atopic asthmatics (z = 2.5, p = 0.0141). The median LOS was significantly higher for atopic intubated patients compared to non-atopic intubated patients (p=0.021). Although there was an increased tendency towards intubation in the atopic group, the difference was not significant. There was no significant difference in cardiopulmonary arrest or mortality. CONCLUSION: A clinical history of atopic asthma in children admitted to the PICU with status asthmaticus was associated with longer length of stays The longest LOS was observed when atopic patients required intubation.

The Effect of Comprehensive Medical Care on the Long-Term Outcomes of Children Discharged from the NICU with Tracheostomy.

BACKGROUND: Survival of infants with complex care has led to a growing population of technology-dependent children. Medical technology introduces additional complexity to patient care. Outcomes after NICU discharge comparing Usual Care (UC) with Comprehensive Care (CC) remain elusive. OBJECTIVE: To compare the outcomes of technology-dependent infants discharged from NICU with tracheostomy following UC versus CC. METHODS: A single site retrospective study evaluated forty-three (N=43) technology-dependent infants discharged from NICU with tracheostomy over 5½ years (2011-2017). CC provided 24-hour accessible healthcare-providers using an enhanced medical home. Mortality, total hospital admissions, 30-days readmission rate, time-to-mechanical ventilation liberation, and time-to-decannulation were compared between groups. RESULTS: CC group showed significantly lower mortality (3.4%) versus UC (35.7%), RR, 0.09 [95%CI, 0.12-0.75], P=0.025. CC reduced total hospital admissions to 78 per 100 child-years versus 162 for UC; RR, 0.48 [95% CI, 0.25-0.93], P=0.03. The 30-day readmission rate was 21% compared to 36% in UC; RR, 0.58 [95% CI, 0.21-1.58], P=0.29). In competing-risk regression analysis (treating death as a competing-risk), hazard of having mechanical ventilation removal in CC was two times higher than UC; SHR, 2.19 [95% CI, 0.70-6.84]. There was no difference in time-to-decannulation between groups; SHR, 1.09 [95% CI, 0.37-3.15]. CONCLUSION: CC significantly decreased mortality, total number of hospital admissions and length of time-to-mechanical ventilation liberation.

Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model.

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of morbidity and mortality in vulnerable populations. Macrolides have received considerable attention for their anti-inflammatory actions beyond their antibacterial effect. We hypothesize that prophylactic azithromycin will be effective in reducing the severity of RSV infection in a mouse model. METHODS: Four groups of BALB/c mice were studied for 8 days: Control (C), RSV-infected (R), early prophylaxis with daily azithromycin from days 1 to 8, (E), and late prophylaxis with daily azithromycin from days 4 to 8 (L). Mice were infected with RSV on day 4, except for the control group. All groups were followed for a total of 8 days when bronchoalveolar lavage cell count and cytokines levels were measured. Mouse weight, histopathology, and mortality data were obtained. RESULTS: Prophylactic azithromycin significantly attenuated post-viral weight loss between group R and both groups E and L (P = 0.0236, 0.0179, respectively). IL-6, IL-5, and Interferon-Gamma were significantly lower in group L (P = 0.0294, 0.0131, and 0.0056, respectively) compared with group R. The total cell count was significantly lower for group L as compared with group R (P < 0.05). Mortality was only observed in group R (8%). Lung histology in the prophylactic groups showed diminished inflammatory infiltrates and cellularity when compared with group R. CONCLUSION: Prophylactic azithromycin effectively reduced weight loss, airway inflammation, cytokine levels and mortality in RSV-infected mice. These results support the rationale for future clinical trials to evaluate the effects of prophylactic azithromycin for RSV infection.

Use of Nasal Non-Invasive Ventilation with a RAM Cannula in the Outpatient Home Setting.

BACKGROUND: Nasal non-invasive-ventilation (Nasal NIV) is a mode of ventilatory support providing positive pressure to patients via a nasal interface. The RAM Cannula is an oxygen delivery device that can be used as an alternative approach to deliver positive pressure. Together they have been successfully used to provide respiratory support in neonatal in-patient settings. OBJECTIVE: To describe the outpatient use of Nasal NIV/RAM Cannula as a feasible alternative for home respiratory support in children with chronic respiratory failure. METHODS: We performed a retrospective case series of 18 children (4 months to 19 years old) using the Nasal NIV/RAM Cannula in the Pediatric Pulmonary Clinic at the McGovern Medical School, UTHealth (2014-16). Consideration for Nasal NIV/RAM Cannula utilization included: inability to wean-off in-patient respiratory support, comfort for dyspnea, intolerability of conventional mask interfaces and tracheostomy avoidance. RESULTS: Average age was 7 years. 50% were Caucasian, 38% African-American and 11% Hispanics. Pulmonary disorders included: chest wall weakness (38%), central control abnormalities (33%), obstructive lung disease (16%) and restrictive lung disease (11%). Indications for Nasal NIV/RAM Cannula initiation included: CPAP/BPAP masks intolerability (11%), dyspnea secondary to chest wall weakness (38%) and tracheostomy avoidance (50%). Average length of use of Nasal NIV/RAM Cannula was 8.4 months. Successful implementation of Nasal NIV/Ram Cannula was 94%. One patient required a tracheostomy following the use of Nasal NIV/RAM Cannula. Significant decrease in arterial PaCO2 pre and post Nasal NIV/RAM cannula initiation was notable (p=0.001). CONCLUSION: Outpatient use of Nasal NIV/RAM Cannula may prove to be a feasible and save treatment alternative for children with chronic respiratory failure, chest wall weakness, dyspnea and traditional nasal/face mask intolerance to avoid tracheostomy.

Anti-inflammatory effect of prophylactic macrolides on children with chronic lung disease: a protocol for a double-blinded randomised controlled trial.

INTRODUCTION: Recent studies suggest that the high mortality rate of respiratory viral infections is a result of an overactive neutrophilic inflammatory response. Macrolides have anti-inflammatory properties, including the ability to downregulate the inflammatory cascade, attenuate excessive cytokine production in viral infections, and may reduce virus-related exacerbations. In this study, we will test the hypothesis that prophylactic macrolides will reduce the severity of respiratory viral illness in children with chronic lung disease by preventing the full activation of the inflammatory cascade. METHODS AND ANALYSIS: A randomised double-blind placebo-controlled trial that will enrol 92 children to receive either azithromycin or placebo for a period of 3-6 months during two respiratory syncytial virus (RSV) seasons (2015-2016 and 2016-2017). We expect a reduction of at least 20% in the total number of days of unscheduled face-to-face encounters in the treatment group as compared with placebo group. Standard frequentist and Bayesian analyses will be performed using an intent-to-treat approach. DISCUSSION: We predict that the prophylactic use of azithromycin will reduce the morbidity associated with respiratory viral infections during the winter season in patients with chronic lung disease as evidenced by a reduction in the total number of days with unscheduled face-to-face provider encounters. ETHICS AND DISSEMINATION: This research study was approved by the Institutional Review Board of the University of Texas Health Science Center in Houston on 9 October 2014. On completion, the results will be published. TRIAL REGISTRATION NUMBER: NCT02544984.