[Show abstract][Hide abstract] ABSTRACT: RATIONALE: There has been a parallel increase in the prevalence of asthma and use of acetaminophen since the 1980s. This association has prompted investigation into the link between acetaminophen use and asthma, which can be plausibly explained by several biological mechanisms. Our objective was to determine whether there was an association between antipyretic use and outcomes of children with acute asthma exacerbations.
METHODS: We performed a retrospective study of hospitalized children with acute asthma to explore the relationship between antipyretic use and asthma course. Patient demographics, asthma history and clinical courses were compared based on antipyretic use and dosage.
RESULTS: In this convenience sample of 300 children with acute asthma admitted to both the ward and the ICU, 16% (n=48) received only acetaminophen during their hospitalization, 4% (n=11) received only ibuprofen, 4% (n=12) received both, and 76% (n=229) received neither. Children who received acetaminophen received a total median dose of 15 mg/kg (25-75% IQR 13-30 mg/kg). There were no differences in age, gender or race between the groups of children who received acetaminophen, ibuprofen or neither. In addition, there were no differences in previous medical conditions or asthma history (previous hospitalizations, intensive care admissions or intubations for asthma) between the groups. However compared to children who received neither antipyretic, children who received acetaminophen had significantly higher admission Modified Pulmonary Index Scores (median 10, 25-75% IQR 7-12 vs. median 8, 25-75% IQR 6-10; p<0.001), greater incidence of ICU admission (39% vs. 8%; p=0.007) and longer hospital lengths of stay (LOS) (59 ± 43 vs. 40 ± 34 hours; p=0.006). Those who received acetaminophen were also more likely to be treated with continuous albuterol, IV steroids, and magnesium during their hospital stay (p<0.05) compared to those who received no antipyretic. Compared to patients who received ibuprofen, patients who received acetaminophen had significantly longer ICU LOS (22.2 + 34.3 vs 4.4 + 14.4 hours; p=0.007). Patients who received any antipyretic were more likely to have infectious symptomatology on admission, fevers, to receive antibiotics and to be diagnosed with a bacterial or viral infection. In multiple regression analysis, both ICU admission & acetaminophen dosage remained significantly associated with LOS, while ibuprofen dosage did not.
CONCLUSIONS: In this cohort of children hospitalized with an acute asthma exacerbation, those who received acetaminophen were 6 times more likely to be admitted to the ICU and total acetaminophen dosage was associated with hospital LOS.
American Thoracic Society International Conference; 05/2015
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: Social media is becoming an increasingly important communication tool. Hospitals use social media sites to provide the public with accurate and up-to-date medical information, for marketing purposes, and to connect patients with physicians and other patients. Patients use social media to find information about hospitals and providers and to help inform their healthcare choices. However, there are no studies comparing social media presence to hospital quality. Our objective was to determine if there is an association between highly ranked Children's Hospitals and measures of online social influence. METHODS: We conducted a study of Children's Hospitals that were ranked in the Top 50 in 10 different specialties by US News and World Report. Hospital quality was quantified using the number of Top 50 rankings for that hospital. Social media presence was quantified using the primary metric of the hospital's Klout score, a continuous score that is determined utilizing data from multiple social media sites incorporating factors such as followers, interactions and connectivity. RESULTS: A total of 86 Children's Hospitals were ranked in the Top 50 by US News and World Report in at least one specialty; 65 of which had unique Twitter accounts and were included in this analysis. The median number of Top 50 rankings of the hospitals was 7 rankings (25-75% IQR 3-10). The median Klout score of the hospitals was 53 (25-75% IQR 48-60). There was a significant association between higher number of US News rankings and higher Klout scores (r 2 =0.24, p<0.001). There was also a significant association between high number of US News rankings and number of Twitter followers (r 2 =0.26; p<0.001) but not with number of "likes" or number "talking about" on Facebook. CONCLUSIONS: In this study of highly ranked Children's hospitals, there was a significant association between high social media influence scores and higher numbers of Top 50 US News rankings. CLINICAL IMPLICATIONS: Patients looking for highly rated Children's Hospitals could reasonably make assumptions based on social media presence.
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective: Bronchiolitis is one of the top causes of hospitalization of infants in the United States. Several clinical factors have been associated with hospitalization; however, few studies have examined factors related to severe disease. Our goal was to describe the clinical characteristics and hospital course of children admitted with bronchiolitis and to identify factors related to intensive care unit (ICU) admission in this population. Methods: We conducted a retrospective review of all children less than 2 years of age admitted to a children's hospital with bronchiolitis between July 2008 - July 2011. Demographic and clinical data were collected including information regarding hospital course, treatments received and respiratory pathogens. Results: During the study period, 734 children were admitted to the hospital with bronchiolitis, 22% of whom were admitted to the ICU and 10% of whom were intubated and mechanically ventilated. Admission to the ICU was associated with younger age [110 (45-210) days vs. 69 (35-149) days, p<0.001] and history of premature birth (OR 1.7, 95% CI 1.1-2.4, p=0.01), but not with race or ethnicity. The use of respiratory treatments was common in the children admitted to the ICU but was not associated with shortened durations of hospitalization. In addition, neither prematurity nor young age were associated with either increased duration of hospitalization or with increased likelihood of mechanical ventilation. Conclusions: During acute bronchiolitis infections, younger children and those with a history of prematurity were more likely to be admitted to the ICU with severe disease.
Journal of Asthma 08/2014; 52(3):1-20. DOI:10.3109/02770903.2014.956893 · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Backround: Bronchiolitis infections are responsible for a significant number of hospital admissions, outpatient visits, and deaths annually in the US. Certain populations are at higher risk for severe disease and receive Palivizumab as prevention for RSV, the most common cause of bronchiolitis. However, the majority of those hospitalized for bronchiolitis are previously healthy with no known predisposing factors. We hypothesized that there are genetic polymorphisms that may predispose children to more severe disease during bronchiolitis infections.
Methods: In this case-control study, DNA samples were collected from three populations of children: those who have never required hospitalization for respiratory infection (control group, n=100), those hospitalized due to bronchiolitis to a Medical/Surgical ward (case MS, n=59), & those hospitalized with bronchiolitis in the Pediatric Intensive Care Unit requiring mechanical ventilation (case ICU, n=84). Genotyping was performed and included TLR4 mutations ASP299Gly & Thr399Ile, Surfactant protein D Met11Thr polymorphism, RANTES -28C/G, -403C/G, & In1.1T/C polymorphisms, & CX3CR1-T280M polymorphism.
Results: Two hundred and forty three children were included in this study. Of these, 56% (n=137) were male, 79% (n=193) were Caucasian, and 15% (n=37) were African-American; 50% (n=122) were Hispanic and of these 76% (n=93/122) were Puerto-Rican. There were no significant differences in gender, race or ethnicity between the children in the three populations. When comparing candidate gene frequency in these populations, we found no associations with severe disease (either admission to ICU or ward) with the TLR4, Surfactant protein D, or the CX3CR1 genotypes. However, we found that African-American children with the RANTES G-403A C/C genotype were significantly more likely to require ICU admission for bronchiolitis than those without this gene (OR 12.0, 95% CI 1.90-75.72; p=0.008). Linear regression was performed to assess the impact of this individual polymorphism on severity of illness. The model was statistically significant(x2 (1, N=29) = 8.76; p=0.003) and explained between 26% and 35% of the variance in illness severity.
Conclusions: In this population, African-American children with the RANTES G-403A C/C genotype were 12 times more likely to require ICU admission & mechanical ventilation during bronchiolitis infections than those without this gene. Identification of specific genetic risk factors may allow for improved targeting of prophylactic therapy.
American Thoracic Society International Conference; 05/2014
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Bronchiolitis is a frequent cause of hospitalization in infants and children. Oftentimes, these children undergo extensive laboratory and radiographic investigation in search of concomitant bacterial infections. However, these workups are rarely indicated in otherwise healthy children. We developed an evidence-based pathway to guide the care of children with bronchiolitis aimed at reducing unnecessary testing (including RSV testing, chest radiography, and invasive bacterial cultures) and unnecessary treatments (such as empiric antibiotics). OBJECTIVE: To evaluate the impact of a bronchiolitis pathway on the incidence of chest radiography, virologic and bacteriologic testing, and antibiotic use in a cohort of hospitalized children. DESIGN/METHODS: A retrospective chart review was conducted of all children admitted to the general inpatient wards of Connecticut Children's Medical Center with bronchiolitis from October 2010 to May 2013, before and after institution of the pathway in January 2012. Children aged 2 months to 1 year were included. Children with complex medical problems, children born prematurely, and children admitted to the ICU were excluded from the pathway and from this review. RESULTS: A total of 171 children were admitted to the hospital with bronchiolitis during the study period who met inclusion criteria: 119 before and 52 after pathway initiation. The mean age of the children was 168 + 90 days and 62% were male. The use of the pathway was associated with a significantly decreased frequency of chest radiography (90% vs 74%; p=0.02). However, there was no significant change in the frequency of viral testing (94% vs. 89%; p=0.31), or in the frequency of blood cultures performed (20% vs. 9%; p=0.15), urine cultures performed (10% vs 7%; p=0.75), or empiric antibiotics administered (34% vs. 25%; p=0.33). CONCLUSIONS: In this population of otherwise healthy children admitted with bronchiolitis, the frequency of bacteriologic and virologic testing, the frequency of chest radiography, and the frequency of empiric antibiotics remains unacceptably high, even following the initiation of an evidence-based treatment pathway. These results likely reflect a failure of awareness or adoption of the pathway by staff. Additional education regarding these evidence-based recommendations may result in further reduction of targeted interventions.
[Show abstract][Hide abstract] ABSTRACT: Continuous beta-agonist therapy, typically in the form of inhaled albuterol, is the first line therapy for the treatment of acute and severe bronchospasm in children. Although this treatment is commonly used, concerns about cardiotoxicity have been raised. We aimed to investigate the cardiotoxic effects of continuous beta-agonist therapy in children.
We conducted a retrospective review of children admitted to the intensive care unit (ICU) between May 2008 and April 2009, who were treated with continuous beta-agonist therapy (intravenous and nebulized).
Twenty of the 36 children treated with continuous albuterol had repeated serum troponin-T and lactate levels measured. Eleven patients (55%) were also treated with continuous intravenous terbutaline. Elevated levels of troponin-T levels were found in 25% of children, and elevated lactate levels were found in 60%. However, all returned to normal levels within 48 hours of ICU admission, despite continued beta-agonist therapy. No children experienced arrhythmias during therapy. There was no association between intravenous terbutaline use and elevated troponin-T [odds ratio (OR), 1.3; 95% CI, 0.2-10.3] or with elevated serum lactate (OR, 0.6; 95% CI, 0.1-3.7). There was also no association between elevated troponin-T or lactate and ICU or hospital length of stay.
In this small study, a significant proportion of children had elevated serum troponin-T and lactate levels while receiving inhaled continuous beta-agonist therapy, irrespective of intravenous therapy. However, these abnormal values all returned to normal within 48 hours of ICU admission and were not associated with increased duration of hospitalization.
World Journal of Pediatrics 03/2014; 10(4). DOI:10.1007/s12519-014-0467-z · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A change in our children's hospital coverage model to providing full-time in-house supervision by intensivists allowed us to evaluate the impact of this change on patient safety outcomes. Our aim was to determine whether in-house attending coverage influenced the prevalence and outcomes of pediatric code events.
We conducted a retrospective review of all code events between October 2005 and October 2007 (before in-house intensivist supervision) and compared the prevalence, interventions, and outcomes of these codes with those occurring between April 2008 and April 2010 (after in-house intensivist supervision). A code event was defined as any activation of the code system.
One hundred eighty-seven bed children's hospital.
All children with code events.
There were 99 codes during these two periods: 39 codes occurring prior to in-house intensivist coverage (of which eight on the ward and 31 in the ICU) and 60 occurring following in-house attending coverage (30 on the ward and 30 in the ICU). Survival was significantly improved following the implementation of in-house coverage (odds ratio, 4.3; 95% CI, 1.7-10.8; p = 0.003). There was no significant change in the overall rate of codes during these two periods (0.82 codes/1,000 patient-days before implementation vs 1.17 codes/1,000 patient-days after implementation). However, there were significantly more codes on the ward following in-house intensivist coverage (0.2 codes/1,000 patient-days before implementation vs 0.71 codes/1,000 patient-days after implementation; p = 0.013). An intensivist was significantly more likely to be present during these events (odds ratio, 28; 95% CI, 3-273; p = 0.001); however, the acuity of the children with codes on the ward was significantly lower during the in-house coverage period (p = 0.001). There were no changes in the rate or outcomes of codes occurring in the ICU with this change in coverage.
In the period following implementation of in-house intensivist supervision, children with code events were more likely to survive to hospital discharge. Having an intensivist in-house 24 hr/d, 7 d/wk may be associated with improved outcomes in hospitalized children.
Pediatric Critical Care Medicine 12/2013; 15(3). DOI:10.1097/PCC.0000000000000056 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pediatric Critical CareSESSION TYPE: Original Investigation SlidePRESENTED ON: Wednesday, October 30, 2013 at 07:30 AM - 09:00 AMPURPOSE: Bronchiolitis is a common respiratory infection in infants that is sometimes treated with albuterol. To determine response to albuterol, providers use subjective clinical assessments that may not be reliable. In intubated infants, assessment of response can be determined using pulmonary mechanics and respiratory system resistance (Rrs). The purpose of this study was to compare providers' clinical assessment of response to the measurement of response defined by pulmonary mechanics.METHODS: Before and 20 minutes following albuterol therapy, a nurse (RN), respiratory therapist (RT) and physician (MD) performed simultaneous examinations and assessed response to albuterol in a population of intubated infants with bronchiolitis. Providers were also asked to rate degree of wheezing, aeration and expiratory time using a 5-point Likert scale. Measurements of ventilator-derived pulmonary mechanics were obtained at these same times. Providers were blinded to the pulmonary mechanics and to the other providers' assessments.RESULTS: Seventy-five paired pre- and post-albuterol clinical assessments were made by providers in 25 infants (median age 44 days, 25-75% IQR 30-81 days). Using pulmonary mechanics, response to albuterol was defined using two thresholds: improvement in Rrs by >20% from baseline and improvement by >30% from baseline. Using the 20% threshold, 36% of children (9/25) were responders; using the 30% threshold, 12% (3/25) were responders. With either definition, providers made poor clinical determinations of response. With the 20% threshold, the positive predictive values (PPVs) of RNs, RTs and MDs were 38%, 25% and 25% respectively, and the negative predictive values (NPVs) were 67%, 54% and 59%. With the 30% threshold, the PPVs of RNs, RTs and MDs were 6%, 8% and 13% respectively, with NPVs of 78%, 85% and 88%, respectively. When comparing assessments of wheezing, aeration and expiratory time between RNs, RTs and MDs, there was poor agreement between groups of providers in all parameters (kappa<0.6).CONCLUSIONS: A provider's clinical assessment is not a reliable method for determining response to albuterol in children with bronchiolitis.CLINICAL IMPLICATIONS: Without assessment of pulmonary mechanics, caution should be used in classifying children with bronchiolitis as responders to albuterol.DISCLOSURE: The following authors have nothing to disclose: Christopher Carroll, Kathleen Sala, Craig SchrammNo Product/Research Disclosure Information.
[Show abstract][Hide abstract] ABSTRACT: Quality Improvement in the ICU IISESSION TYPE: Original Investigation SlidePRESENTED ON: Tuesday, October 29, 2013 at 04:30 PM - 05:30 PMPURPOSE: Handoffs are a recognized potential source of medical errors and play an important role in patient safety. Improving the quality of handoffs between the operating room (OR) and the intensive care unit (ICU) is particularly important, as the high complexity and instability of the patient population can lead to a higher risk of medical errors. Our aim was to determine if we could intervene to improve the quality of handoffs in children admitted to the ICU postoperatively.METHODS: Intervention: A structured handoff tool was developed using a multidisciplinary approach, which included key participants and a checklist of critical steps. Beginning in May 2012, this tool was instituted for children admitted to the ICU post-operatively. Evaluation: Compliance with key steps was audited in real time using a checklist. Data regarding clinical characteristics and outcomes of the patients were collected and the AHRQ Hospital Survey on Patient Safety Culture was administered.RESULTS: Between May 2012 and January 2013, 205 children were admitted to the ICU post-operatively. Overall, handoffs were performed 94% of the time; ranging from 82% in May to 100% starting in August. Attendance by key providers ranged from 37% to 100% and there was 100% compliance with critical steps in the conducted handoffs. Surgical subspecialty, time of return from OR, and ICU length of stay were not associated with frequency of attendance or compliance with handoff. Written positive comments were reported in 15% of handoffs; there were no negative comments. Seventy staff members in the ICU completed the safety culture survey (96% response rate); 67% of respondents disagreed with the statement "problems often occur in the exchange of information across hospital units" in contrast with 42% (446/1063) for the hospital overall (P<.001), 13% (2/15) on the previous year's survey in the ICU (P<.001) and 44% for the overall AHRQ benchmark.CONCLUSIONS: Use of structured handoff tools for children admitted to the ICU post-operatively is feasible and well received by staff.CLINICAL IMPLICATIONS: Improving handoffs in the ICU may play a successful part in promoting a culture of safety and enhancing communication.DISCLOSURE: The following authors have nothing to disclose: Christopher Carroll, Kathleen Sala, Andrea BeninNo Product/Research Disclosure Information.
[Show abstract][Hide abstract] ABSTRACT: RATIONALE: Near fatal asthma is among the most common causes of critical illness in children. There may be genotypic differences that are associated with severity of illness in children with asthma. Thromboxane A2 and its receptor, TBXA2R, are involved in constriction of respiratory smooth muscle, and genetic polymorphisms of the TBXA2 receptor (TBXA2R+924 T>C) have been previously reported to be associated with asthma and atopy. However, this association has not been explored in a cohort of children with more severe exacerbations. We conducted a candidate gene study to explore the relationship between this gene and near fatal asthma in children.
METHODS: We performed genotyping of the TBXA2R in a cohort of children admitted to the hospital with an asthma exacerbation. Near fatal asthma was defined as: (a) treatment with intubation and mechanical ventilation, (b) presence of respiratory acidosis (pCO2 > 45), or (c) Modified Pulmonary Index Score (MPIS) > 12 after 2 hours on ≥ 20 mg/hour of continuous albuterol. Patient demographics, clinical history and genotypes were compared in children with and without near fatal asthma.
RESULTS: In this cohort of 105 children, 19% (n=20) had a near fatal asthma exacerbation. There were no differences in age (7.9 +3.1 vs. 9.2 + 4.0 years; p=0.18), male gender (40% vs. 49%; p=0.61), race (65% vs. 52% Caucasian; p=0.41), or ethnicity (60% vs. 38% Hispanic; p=0.12) between those with and without near fatal asthma. In addition, there were no differences in baseline asthma severity classification or previous hospitalizations, intensive care admissions or ED visits for asthma between the two groups. In this cohort, 47 children had the C/C genotype of the TBXA2R+924, 11 had the T/T genotype, and 44 were heterozygous. Children with the C/C genotype were almost 5 times more likely to have a near fatal asthma exacerbation than those of other genotypes (OR 4.7, 95% CI 1.6-14.2; p=0.01). These children were also significantly more likely to have a history of an ICU admission at any time during their childhood (OR 2.7, 95% CI 1.1-6.3; p=0.03). A history of atopy (allergic rhinitis, eczema or other allergies) was not associated with TBXA2R+924 genotype or with the development of a near fatal exacerbation in this cohort.
CONCLUSIONS: In this cohort of children with asthma, those with the C/C genotype of the TBXA2R+924 gene were 5 times more likely to develop near fatal asthma when admitted to the hospital with an acute exacerbation.
American Thoracic Society International Conference; 05/2013
[Show abstract][Hide abstract] ABSTRACT: Status asthmaticus is a frequent cause of admission to a pediatric intensive care unit. Prompt assessment and aggressive treatment are critical. First-line or conventional treatment includes supplemental oxygen, aerosolized albuterol, and corticosteroids. There are several second-line treatments available; however, few comparative studies have been performed and in the absence of good evidence-based treatments, the use of these therapies is highly variable and dependent on local practice and provider preference. In this article the pathophysiology and treatment of status asthmaticus is discussed, and the literature regarding second-line treatments is critically assessed to apply an evidence basis to the treatment of this severe disease.
Critical care clinics 04/2013; 29(2):153-66. DOI:10.1016/j.ccc.2012.12.001 · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: SESSION TYPE: Pediatric Critical CarePRESENTED ON: Sunday, October 21, 2012 at 01:15 PM - 02:45 PMPURPOSE: Respiratory failure, although a relatively rare occurrence, carries a high burden of morbidity in children with asthma, with some requiring significant durations of mechanical ventilatory support. However, there are other children who require only short durations of intubations for status asthmaticus. Our objective was to characterize this population of children with status asthmaticus who require only brief durations of mechanical ventilation.METHODS: We conducted a retrospective review of children intubated for status asthmaticus using the multicenter VPS database. Clinical characteristics of children intubated for less than 24 hours were compared to those intubated for longer durations.RESULTS: Between 2009-2011, there were 2,746 children included in the VPS database who met study criteria; 1,030 (38%) were intubated less than 24 hours, and 1,716 were intubated for longer than 24 hours. The mean duration of intubation for children intubated for less than 24 hours was 9.6 + 7.2 hours compared to 6.9 + 8.0 days for children intubated more than 24 hours. Children intubated for less than 24 hours were older (78 ± 66 vs 64 ± 65 months, p<0.0001), and less likely to be African-American (OR 0.75, 95% CI 0.62-0.90, p=0.003) than children intubated for longer than 24 hours. There were no other significant differences in race/ethnicity or in gender between the two groups. Finally, of those intubated less than 24 hours, 94% were intubated outside the ICU, whereas only 59% of those intubated for more than 24 hours were intubated outside the ICU (OR 10, 95% CI 7.62-13.0, p<0.0001). Those associations persisted when accouting for illness severity on regression analysis.CONCLUSIONS: When compared to children intubated for longer durations, children with status asthmaticus who were intubated for less than 24 hours were older, less likely to be African-American, and 10 times more likely to be intubated outside of the ICU.CLINICAL IMPLICATIONS: These children with short durations of intubation may represent an acute asphyxial asthma phenotype or potentially a lower threshold for intubation by providers outside of the ICU setting.DISCLOSURE: The following authors have nothing to disclose: Ranjini Srinivasan, Richard Uluski, Kathleen Sala, Laurie Karamessinis, Sharon Smith, Christopher CarrollNo Product/Research Disclosure InformationConnecticut Children's Medical Center, Hartford, CT.
[Show abstract][Hide abstract] ABSTRACT: SESSION TYPE: Pediatric Chest DiseasePRESENTED ON: Sunday, October 21, 2012 at 10:30 AM - 11:45 AMPURPOSE: Acute asthma is a common cause of illness and hospitalization in children. Children of Hispanic ethnicity are disproportionately affected with asthma and may be at risk for more severe disease. Genetic factors, specifically polymorphisms of the β2-adrenergic receptor (ADRβ2), may play a role in a child's severity of illness during an acute asthma exacerbation although the specific nature of this association is not well established.METHODS: We performed genotyping of the ADRβ2 at amino acid positions 16 and 27 in a cohort of 205 children admitted to the hospital with asthma over a 9-year period. Clinical factors and genotypes of the ADRβ2 were compared to outcomes while stratifying by race/ethnicity. A severe exacerbation was defined as admission to the intensive care unit (ICU).RESULTS: In this cohort, 64 children of Hispanic ethnicity were admitted to the hospital, 61% (n=39) of whom had at least one admission the the ICU for severe asthma. ICU admission was not associated with age, gender or insurance status. However, Hispanic children with severe persistent asthma were significantly more likely to have been admitted to the ICU compared to those with other asthma classifications (OR 9.4; 95% CI 1.1-78.4; p=0.04). Hispanic children with the Arg16Gly-Gln27Gln genotype were also 8 times more likely to be admitted to the ICU with a severe exacerbation than those with other genotype of the ADRβ2 (OR 8.4; 95% CI 1.7-41.0; p=0.009), even when accounting for asthma classification. Also in this cohort, 68 Caucasian and 59 African-American children were admitted to the hospital, 75% (n=51) and 66% (n=39) of whom were admitted to the ICU at last once. There were no associations between genotype and admission to the ICU in these groups.CONCLUSIONS: In a cohort of children admitted with acute asthma, Hispanic children with the Arg16Gly-Gln27Gln genotype of the ADRβ2 were at greater risk for severe disease during an exacerbation.CLINICAL IMPLICATIONS: Genetic factors may influence the development of a more severe asthma phenotype during acute exacerbations.DISCLOSURE: The following authors have nothing to disclose: Christopher Carroll, Kathleen Sala, Aaron Zucker, Craig SchrammNo Product/Research Disclosure InformationConnecticut Children's Medical Center, Hartford, CT.
[Show abstract][Hide abstract] ABSTRACT: Children with asthma and respiratory failure comprise a small but significant subset of children with acute asthma. In addition to clinical and historical factors that have been associated with respiratory failure, there may also be genetic factors that predispose some asthmatic children to intubation and mechanical ventilation. However, this has not previously been assessed in this population. We hypothesized that genetic polymorphisms of the β(2)-adrenergic receptor (ADRβ(2)) are associated with intubation and mechanical ventilation in children with asthma.
We performed genotyping of the ADRβ(2) in a pooled cohort of 104 children admitted to the intensive care unit (ICU) with a severe asthma exacerbation between 2002 and 2008. Genotype of the ADRβ(2) was compared with intubation for respiratory failure.
At amino acid position 16, 33% (n = 34) of children were homozygous for the glycine allele (Gly16Gly), 15% (n = 16) were homozygous for the arginine allele (Arg16Arg), and 52% (n = 54) were heterozygous (Arg16Gly). At amino acid position 27, 54% (n = 56) of children were homozygous for the glutamine allele (Gln27Gln), 8% (n = 8) were homozygous for the glutamic acid allele (Glu27Glu), and 38% (n = 40) were heterozygous (Gln27Glu). The haplotypes at these positions were Arg16Gly-Gln27Gln (29%, n = 30), Arg16Gly-Gln27Glu (22%, n = 23), Gly16Gly-Gln27Glu (16%, n = 17), Arg16Arg-Gln27Gln (16%, n = 17), Gly16Gly-Gln27Gln (9%, n = 9), and Gly16Gly-Glu27Glu (8%, n = 8). Twelve children in this cohort were intubated for respiratory failure. Intubation was not associated with age, obesity, race/ethnicity, or NHBLI asthma classification. However, children with the Arg16Gly-Gln27Gln haplotype were significantly more likely to be intubated and mechanical ventilated (OR = 4.2; 95% CI = 1.2-14.5; p = .036) than children with other haplotypes of the ADRβ(2). When examining the subset of intubated children, those with the Arg16Gly-Gln27Gln haplotype trended towards longer ICU length of stay (329 ± 270 vs. 124 ± 57 hours; p = .09), but this was not statistically significant.
Children with the Arg16Gly-Gln27Gln haplotype of the ADRβ(2) were four times more likely to be intubated and mechanically ventilated during severe asthma exacerbations. Genetic factors may influence the development of a more severe asthma phenotype during acute exacerbations.
Journal of Asthma 08/2012; 49(6):563-8. DOI:10.3109/02770903.2012.701362 · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bronchiolitis is a common cause of critical illness in infants. Inhaled β(2)-agonist bronchodilators are frequently used as part of treatment, despite unproven effectiveness. The purpose of this study was to describe the physiologic response to these medications in infants intubated and mechanically ventilated for bronchiolitis.
We conducted a prospective trial of albuterol treatment in infants intubated and mechanically ventilated for bronchiolitis. Before and for 30 minutes following inhaled albuterol treatment, sequential assessments of pulmonary mechanics were determined using the interrupter technique on repeated consecutive breaths.
Fifty-four infants were enrolled. The median age was 44 days (25-75%; interquartile range (IQR) 29-74 days), mean hospital length of stay (LOS) was 18.3 ± 13.3 days, mean ICU LOS was 11.3 ± 6.4 days, and mean duration of mechanical ventilation was 8.5 ± 3.5 days. Fifty percent (n = 27) of the infants were male, 81% (n = 44) had public insurance, 80% (n = 41) were Caucasian, and 39% (n = 21) were Hispanic. Fourteen of the 54 (26%) had reduction in respiratory system resistance (Rrs) that was more than 30% below baseline, and were defined as responders to albuterol. Response to albuterol was not associated with demographic factors or hospitalization outcomes such as LOS or duration of mechanical ventilation. However, increased Rrs, prematurity, and non-Hispanic ethnicity were associated with increased LOS.
In this population of mechanically ventilated infants with bronchiolitis, relatively few had a reduction in pulmonary resistance in response to inhaled albuterol therapy. This response was not associated with improvements in outcomes.
Journal of Asthma 06/2012; 49(7):688-96. DOI:10.3109/02770903.2012.685541 · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During severe exacerbations, asthmatic children vary significantly in their response to high-dose continuous β(2) -adrenergic receptor (ADRβ(2) ) agonist therapy. Genetic polymorphisms have been identified within the ADRβ(2) that may be functionally relevant, but few studies have been performed in this population. Our hypothesis was that genotypic differences are associated with magnitude of response to ADRβ(2) agonist treatment during severe asthma exacerbations in children.
Children aged 2-18 years admitted to the ICU (intensive care unit) with a severe asthma exacerbation between 2006 and 2008 were eligible. Genotyping of the ADRβ(2) was performed.
Eighty-nine children consented and were enrolled. Despite similar clinical asthma scores on admission, children with the Gly(16) Gly genotype at amino acid position 16 had significantly shorter ICU length of stay (LOS) and hospital LOS, compared to children with Arg(16) Arg and Arg(16) Gly genotypes. Children with either the Gln(27) Glu or Glu(27) Glu genotype at amino acid position 27 also had significantly shorter ICU LOS and hospital LOS compared to children with the Gln(27) Gln genotype. The Arg(16) Gly-Gln(27) Gln haplotype was associated with the longest ICU LOS, but this was not statistically different from other haplotypes.
In this cohort of children with severe asthma exacerbations, ADRβ(2) polymorphisms were associated with responses to therapy. Knowledge of the genetic profile of children with asthma may allow for targeted therapy during acute exacerbations.
[Show abstract][Hide abstract] ABSTRACT: Asthma exacerbations are one of the most common causes of hospitalization in children and account for approximately 10,000 intensive care unit (ICU) admissions per year in the United States. Despite the prevalence of this disease in children, the factors associated with the development of these severe exacerbations are largely unknown.
A retrospective case-control study was conducted involving all eligible children admitted to the hospital with asthma for a 1-year period. Potential associated factors and outcomes of children admitted to the ICU with a severe exacerbation (cases) were compared to those of children with acute asthma admitted to the ward (controls).
A total of 188 children were hospitalized with asthma during the study period, 57 (30%) of whom required admission to the ICU. There were no differences in age, gender, or race between cases and controls. Children admitted to the ICU were significantly more likely to have an allergy or irritant-triggered exacerbation than children admitted to the ward (OR 3.9; 95% CI 1.9-8.2; p = .0003). Additionally, children in the ICU had a significantly shorter duration of illness before being admitted to the hospital compared to those admitted to the ward (1.7 ± 2.3 vs. 3.4 ± 4.8 days; p = .002).
In this retrospective review, severe asthma exacerbations in children are associated with a more rapid onset of symptoms and are more likely to be associated with allergens or irritants, supporting the importance of atopy in this population.
Journal of Asthma 06/2011; 48(6):558-64. DOI:10.3109/02770903.2011.585411 · 1.83 Impact Factor