Screening for asthma in preschool children with sickle cell disease.

BACKGROUND: Asthma in preschool children is poorly defined, proving to be a challenge for early detection. The Breathmobile Case Identification Survey (BCIS) has been shown to be a feasible screening tool in older SCD children and could be effective in younger children. We attempted to validate the BCIS as an asthma screening tool in preschool children with SCD. METHODS: This is a prospective, single-center study of 50 children aged 2-5 years with SCD. BCIS was administered to all patients and a pulmonologist blinded to the results evaluated patients for asthma. Demographic, clinical, and laboratory data were obtained to assess risk factors for asthma and acute chest syndrome in this population. RESULTS: Asthma prevalence (n = 3/50; 6%) was lower than atopic dermatitis (20%) and allergic rhinitis (32%). Sensitivity (100%), specificity (85%), positive predictive value (30%), and negative predictive value (100%) of the BCIS were high. Clinical demographics, atopic dermatitis, allergic rhinitis, asthma, viral respiratory infection, hematology parameters, sickle hemoglobin subtype, tobacco smoke exposure, and hydroxyurea were not different between patients with or without history of ACS, although eosinophil was significantly lower in the ACS group (p = 0.0093). All those with asthma had ACS, known viral respiratory infection resulting in hospitalization (3 RSV and 1 influenza), and HbSS (homozygous Hemoglobin SS) subtype. CONCLUSION: The BCIS is an effective asthma screening tool in preschool children with SCD. Asthma prevalence in young children with SCD is low. Previously known ACS risk factors were not seen, possibly from the beneficial effects of early life initiation of hydroxyurea.

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.

Nasal Nitric Oxide Levels: Improving the Diagnosis of Primary Ciliary Dyskinesia in Puerto Rico.

Primary Ciliary Dyskinesia (PCD) is a rare genetic disease characterized by motile cilia dysfunction with a prevalence of 1 in 16,309 individuals in Hispanic populations. In Puerto Rico, the prevalence of PCD is unknown. Diagnosis of PCD in Puerto Rico is challenging due to the lack of diagnostic technology. Algorithms for PCD diagnosis include clinical history, genetic testing, ciliary biopsy, and nasal Nitric Oxide (nNO) levels. For the first time, this study successfully implemented and measured the nNO levels in subjects with the RSPH4A (c.921+3_921+6del (intronic)) as a diagnostic tool to complement the current algorithm for PCD diagnosis on the island. The nNO level differentiated homozygous subjects with PCD due to the RSPH4A (c.921+3_921+6del (intronic)) founder mutation compared to healthy gender-age matched controls and subjects with VUS or negative genetic testing for PCD. The acquisition of state-of-the-art diagnostic tools such as nNO positively impacted and expanded our current PCD diagnostic capabilities in Puerto Rico for our founder genetic mutation. The addition of nNO technology promotes earlier disease screening and recognition for patients with PCD on the island. The access to nNO helped us to properly characterize the PCD diagnosis for patients with the RSPH4A (c.921+3_921+6del (intronic)). As a result, our findings will allow us to be part of the national PCD foundation registry and represent Puerto Rican Hispanics in future PCD multicentric clinical trials.

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.

Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

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.

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.

Resolution of airflow obstruction on polysomnography after laryngotracheal reconstruction with anterior tracheal wall suspension in a patient with DiGeorge Syndrome.

DiGeorge Syndrome (DGS) may be associated with airway abnormalities including laryngomalacia and suprastomal collapse of the trachea (SCT), which may lead to sleep disordered breathing (SDB). We present a 4-year-old boy with DGS, SCT, and SDB by polysomnography (PSG) while the tracheostomy tube was capped. The patient underwent anterior tracheal wall suspension (ATWS) with concurrent tracheostomy decannulation. Following the repair, the patient experienced improved airway patency visually and by PSG with resolution of obstructive sleep apnea and hypoventilation. ATWS is an effective method to repair SCT in selected patients and may lead to early decannulation and improvement of SDB.

SFTPC gene mutation p.R167Q in a premature infant.

We present an infant who was born premature at 23 weeks gestation with bronchopulmonary dysplasia and a SFTPC gene mutation, p.R167Q, who had a complicated neonatal course requiring 4 months of mechanical ventilation. Over time, his clinical course has improved, and he only requires oxygen by nasal cannula and low dose hydroxychloroquine, suggesting that p.R167Q mutation contributed to his clinical course and may manifest with a variable disease pattern making long-term prognostication difficult in the immediate newborn period.

Do the neighboring residues in a polypeptide affect the electron distribution of an amino acid significantly? A quantitative study using the quantum theory of atoms in molecules (QTAIM).

Geometries, as well as bond and atomic properties obtained with the atoms-in-molecules theory applied on B3LYP/6-31++G//B3LYP/6-31G charge densities, of the N-formyl amides of the nine tripeptides obtained by combining glycine, alanine, and serine around a central glycine residue were analyzed to check how the properties of the central residue are modified by other amino acids bonded to it. All of the molecules were optimized from an alpha-helix conformation that was also displayed by the optimized structure. Significant variations of the geometry (especially remarkable for dihedral angles) and atomic properties of the central glycine residue are observed when it is attached to a serine residue whose side chain is involved in a hydrogen bond.

On the applicability of resonance forms in pyrimidinic bases. II. QTAIM interpretation of the sequence of protonation affinities.

The atomic properties of neutral and protonated forms of uracil and some model compounds, computed from B3LYP/6-31++G//B3LYP/6-31G charge densities with the QTAIM theory, indicate that sigma electron reorganization plays a significant role in the protonation processes. This reorganization is substantially different for O=C-C=C and O=C-C-X (X = N, O) units, involving transfers of electron population between all atoms in the first case but not across the C-X bond in the second unit. O-Protonation is basically favored over the N-protonation because of the lower electron population transferred to the proton. The stability sequence of N-protonated forms can be rationalized in terms of the closer position of the proton, when attached to N3, to regions of larger electron population (carbonyl groups).