Assessment of comorbid symptoms in pediatric autonomic dysfunction.

PURPOSE: Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning. METHODS: The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains. RESULTS: We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI. CONCLUSION: This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers.

Creating a data dictionary for pediatric autonomic disorders.

PURPOSE: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders. METHODS: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which to harmonize. Some definitions needed mild modification from original sources. The next tier of sources included published consensus statements, followed by Internet sources. In the absence of appropriate sources, we created a definition. RESULTS: A total of 589 terms were listed and defined in the dictionary. Terms were organized by Signs/Symptoms, Triggers, Co-morbid Disorders, Family History, Medications, Medical Devices, Physical Examination Findings, Testing, and Diagnoses. CONCLUSION: Creation of this data dictionary becomes the foundation of future clinical care and investigative research in pediatric autonomic disorders, and can be used as a building block for a subsequent adult autonomic data dictionary.

Hemodynamic characteristics of postural hyperventilation: POTS with hyperventilation versus panic versus voluntary hyperventilation.

Upright hyperventilation occurs in ~25% of our patients with postural tachycardia syndrome (POTS). Poikilocapnic hyperventilation alone causes tachycardia. Here, we examined changes in respiration and hemodynamics comprising cardiac output (CO), systemic vascular resistance (SVR), and blood pressure (BP) measured during head-up tilt (HUT) in three groups: patients with POTS and hyperventilation (POTS-HV), patients with panic disorder who hyperventilate (Panic), and healthy controls performing voluntary upright hyperpnea (Voluntary-HV). Though all were comparably tachycardic during hyperventilation, POTS-HV manifested hyperpnea, decreased CO, increased SVR, and increased BP during HUT; Panic patients showed both hyperpnea and tachypnea, increased CO, and increased SVR as BP increased during HUT; and Voluntary-HV were hyperpneic by design and had increased CO, decreased SVR, and decreased BP during upright hyperventilation. Mechanisms of hyperventilation and hemodynamic changes differed among POTS-HV, Panic, and Voluntary-HV subjects. We hypothesize that the hyperventilation in POTS is caused by a mechanism involving peripheral chemoreflex sensitization by intermittent ischemic hypoxia. NEW & NOTEWORTHY Hyperventilation is common in postural tachycardia syndrome (POTS) and has distinctive cardiovascular characteristics when compared with hyperventilation in panic disorder or with voluntary hyperventilation. Hyperventilation in POTS is hyperpnea only, distinct from panic in which tachypnea also occurs. Cardiac output is decreased in POTS, whereas peripheral resistance and blood pressure (BP) are increased. This is distinct from voluntary hyperventilation where cardiac output is increased and resistance and BP are decreased and from panic where they are all increased.

Postural Hyperventilation as a Cause of Postural Tachycardia Syndrome: Increased Systemic Vascular Resistance and Decreased Cardiac Output When Upright in All Postural Tachycardia Syndrome Variants.

BACKGROUND: Postural tachycardia syndrome (POTS) is a heterogeneous condition. We stratified patients previously evaluated for POTS on the basis of supine resting cardiac output (CO) or with the complaint of platypnea or "shortness of breath" during orthostasis. We hypothesize that postural hyperventilation is one cause of POTS and that hyperventilation-associated POTS occurs when initial reduction in CO is sufficiently large. We also propose that circulatory abnormalities normalize with restoration of CO2. METHODS AND RESULTS: Fifty-eight enrollees with POTS were compared with 16 healthy volunteer controls. Low CO in POTS was defined by a resting supine CO <4 L/min. Patients with shortness of breath had hyperventilation with end tidal CO2 <30 Torr during head-up tilt table testing. There were no differences in height or weight between control patients and patients with POTS or differences between the POTS groups. Beat-to-beat blood pressure was measured by photoplethysmography, and CO was measured by ModelFlow. Systemic vascular resistance was defined as mean arterial blood pressure/CO. End tidal CO2 and cerebral blood flow velocity of the middle cerebral artery were only reduced during head-up tilt in the hyperventilation group, whereas blood pressure was increased compared with control. We corrected the reduced end tidal CO2 in hyperventilation by addition of exogenous CO2 into a rebreathing apparatus. With added CO2, heart rate, blood pressure, CO, and systemic vascular resistance in hyperventilation became similar to control. CONCLUSIONS: We conclude that all POTS is related to decreased CO, decreased central blood volume, and increased systemic vascular resistance and that a variant of POTS is consequent to postural hyperventilation.

Cardiorespiratory function after operation for pectus excavatum.

OBJECTIVE: We performed a review of current data to determine the effect that operation has on pulmonary function, aerobic capacity, and stroke volume in patients with pectus excavatum. STUDY DESIGN: Two reviewers independently assessed clinical trials and collected data on interventions and outcomes. To qualify for inclusion, a study had to include preoperative and postoperative assessment, provide outcomes in either a published percentile or qualified matched control form to control for interval growth, and include only original patient groups. RESULTS: Postoperative total lung capacity for patients who had Ravitch repair was significantly lower (SMD, 0.71 [CI -1.06, -0.36]; I(2) = 19.6%) than preoperative. Based on 2 studies after removal of the Nuss bar, FEV(1) was significantly increased from preoperative values (SMD, 0.39 [CI, 0.03, 0.74]; I(2) = 0%). Stroke volume increased after surgery (SMD, 0.40 [CI, 0.10, 0.70]; I(2) = 0%) after Ravitch repair. There was a trend toward improved exercise tolerance, but it was not statistically significant. CONCLUSIONS: Total lung capacity was decreased after Ravitch repair, and FEV(1) was increased after Nuss bar removal. Stroke volume may be increased after Ravitch repair. Exercise tolerance was not improved after either type of surgical repair.

Dalhousie dyspnea scales: Pictorial scales to measure dyspnea during induced bronchoconstriction.

The aim of this study was to validate our Dalhousie Dyspnea Scales in children referred for histamine bronchoprovocation challenge. Seventy-four children rated their dyspnea after each FEV(1) measurement following inhalation of doubling histamine concentrations from 0.125 to 8.0 mg/ml by the standard tidal breathing method. Serial FEV(1) and dyspnea rating using the Dalhousie Dyspnea Scales were recorded and Kendall's tau was computed for dyspnea rating versus fall in FEV(1). Subjects were split into those with positive (DeltaFEV(1) >or= 20% with PC(20)

Dalhousie dyspnea scales: construct and content validity of pictorial scales for measuring dyspnea.

BACKGROUND: Because there are no child-friendly, validated, self-report measures of dyspnea or breathlessness, we developed, and provided initial validation, of three, 7-item, pictorial scales depicting three sub-constructs of dyspnea: throat closing, chest tightness, and effort. METHODS: We developed the three scales (Throat closing, Chest tightness, and Effort) using focus groups with 25 children. Subsequently, seventy-nine children (29 children with asthma, 30 children with cystic fibrosis. and 20 children who were healthy) aged 6 to 18 years rated each picture in each series, using a 0-10 scale. In addition, each child placed each picture in each series on a 100-cm long Visual Analogue Scale, with the anchors "not at all" and "a lot". RESULTS: Children aged eight years or older rated the scales in the correct order 75% to 98% correctly, but children less than 8 years of age performed unreliably. The mean distance between each consecutive item in each pictorial scale was equal. CONCLUSION: Preliminary results revealed that children aged 8 to 18 years understood and used these three scales measuring throat closing, chest tightness, and effort appropriately. The scales appear to accurately measure the construct of breathlessness, at least at an interval level. Additional research applying these scales to clinical situations is warranted.

Canadian Pediatric Asthma Consensus guidelines, 2003 (updated to December 2004): introduction.

BACKGROUND: Although guidelines for the diagnosis and management of asthma have been published over the last 15 years, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian asthma consensus report, important new studies, particularly in children, have highlighted the need to incorporate this new information into asthma guidelines. OBJECTIVES: To review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the Canadian Asthma Consensus Report, 1999 and its 2001 update with a major focus on pediatric issues. METHODS: Diagnosis of asthma in young children, prevention strategies, pharmacotherapy, inhalation devices, immunotherapy and asthma education were selected for review by small expert resource groups. In June 2003, the reviews were discussed at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published up to December 2004 were subsequently reviewed by the individual expert resource groups. RESULTS: This report evaluates early life prevention strategies and focuses on treatment of asthma in children. Emphasis is placed on the importance of an early diagnosis and prevention therapy, the benefits of additional therapy and the essential role of asthma education. CONCLUSION: We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This guide for asthma management is based on the best available published data and the opinion of health care professionals including asthma experts and educators.

Relationship between FEV1 and peak oxygen uptake in children with cystic fibrosis.

Cross-sectional data do not truly convey the manner in which declining lung function affects peak oxygen uptake (peak VO2) within a given patient with cystic fibrosis. We hypothesized that there would be a concomitant decline in peak VO2 with FEV1 over time. Twenty-eight children aged 8-17 years with cystic fibrosis performed annual ergometer tests over a 5-year period to determine peak VO2 and within-patient predictors of change in peak VO2. Analysis was done using a mixed-effects model. During the study period, the annual decline in FEV1 averaged 2.7% of the predicted value per year. Peak VO2 fell during the observation period in 70% of patients, with an average annualized decline of 1.9 ml x min(-1) x kg(-1). This rate of decline was greater in older children in contrast to younger children, some of whom had an improvement in peak VO2 over the first few years, consistent with growth and maturation. There was no difference in this rate of decline between sexes, but girls started with a slightly lower peak VO2 (37.9 vs. 45.1 ml x min(-1) x kg(-1)). In patients with FEV1 <80% predicted, declining FEV1 was highly correlated with falling peak VO2, whereas it remained stable over 4-5 years in patients whose FEV1 was >80% predicted and remained in that range. We conclude that peak VO2 remains stable or rises slightly over time in younger patients, while it shows a downward trend in older children with CF, particularly once FEV1 falls below 80% predicted. Peak VO2 is correlated with FEV1 during childhood in patients with cystic fibrosis, and both FEV1 and age influence peak VO2.

Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076].

BACKGROUND: Bronchiolitis is the most common cause of lower respiratory tract illness in infancy, and hospital admission rates appear to be increasing in Canada and the United States. Inhaled beta agonists offer only modest short-term improvement. Trials of racemic epinephrine have shown conflicting results. We sought to determine if administration of racemic epinephrine during hospital stay for bronchiolitis improved respiratory distress, was safe, and shortened length of stay. METHODS: The study was a randomized, double-blind controlled trial of aerosolized racemic epinephrine compared to salbutamol every one to 4 hours in previously well children aged 6 weeks to < or = 2 years of age hospitalized with bronchiolitis. The primary outcome was symptom improvement as measured by the Respiratory Distress Assessment Instrument (RDAI); secondary outcomes were length of stay in hospital, adverse events, and report of symptoms by structured parental telephone interview one week after discharge. RESULTS: 62 children with a mean age of 6.4 months were enrolled; 80% of children had Respiratory Syncytial Virus (RSV). Racemic epinephrine resulted in significant improvement in wheezing and the total RDAI score on day 2 and over the entire stay (p < 0.05). The mean LOS in the epinephrine arm was 2.6 days (95% CI 2, 3.2) v. 3.4 days in those in the salbutamol group (95% CI 2.6, 4.2) (p > 0.05). Adverse events were not significantly different in the two arms. At one week post-discharge, over half of parents reported that their child still had a respiratory symptom and 40% had less than normal feeding. CONCLUSION: Racemic epinephrine relieves respiratory distress in hospitalized infants with bronchiolitis and is safe but does not abbreviate hospital stay. Morbidity associated with bronchiolitis as identified by parents persists for at least one week after hospital discharge in most infants.

Measurement of exercise cardiac output by thoracic impedance in healthy children.

The purpose of this study was to track changes in stroke volume during exercise by impedance cardiography in order to validate the method, and to obtain such data in a large number of healthy children for reference purposes. One hundred and fifteen healthy children (aged 7-19 years) performed progressive exercise to voluntary exhaustion with work increments every minute on a cycle ergometer. Oxygen uptake (VO(2)) was measured on a breath-by-breath system. Cardiac output was measured with an ICG-M501 impedance cardiograph. Stroke volume was normalized for body surface area and expressed as stroke volume index. Cardiac output was regressed against VO(2), and differences between stroke volume index at rest and exercise were assessed by repeated measures analysis of variance. Cardiac output increased linearly with VO(2) in all subjects: individual slopes and intercepts averaged 5.16 (1.56) l.min(-1) per l.min(-1) VO(2), and 4.25 (1.92) l.min(-1), respectively [mean (SD)]. Stroke volume index rose by an average of 29% from rest to exercise, reaching a maximum of 52 ml.m(-2) in boys and girls. Most subjects demonstrated a continuous, gentle rise in stroke volume index with increasing work rate, though a minority demonstrated a falling index as work increased above the anaerobic threshold, despite rising cardiac output. Impedance cardiography accurately tracks cardiac output and can be a useful clinical and research tool in pediatric cardiology and exercise physiology.

Practice variation among pediatric emergency departments in the treatment of bronchiolitis.

OBJECTIVES: Bronchiolitis is the most common disease of the lower respiratory tract in the first year of life. Treatment is controversial, with studies giving conflicting views on the benefits of bronchodilators and steroids. The objectives of this study were 1) to characterize the management of bronchiolitis in pediatric emergency departments (PEDs) in Canada, 2) to determine patient outcomes following emergency department (ED) visits, and 3) to provide descriptive data regarding bronchiolitis symptoms and family/personal medical history of these patients. METHODS: A prospective consecutive cohort of children with bronchiolitis presenting to seven Canadian PEDs was enrolled during a seven-to-21-day period. Standardized interviews with parents provided data regarding symptoms, previous treatment, and past history. Charts were reviewed for treatment, investigations, and disposition. Telephone follow-up at two to three weeks collected information regarding duration of illness and return visits. RESULTS: Two hundred thirty-seven (91%) of 260 eligible patients were enrolled. One hundred eighty-nine patients (80%) had both an interview and chart review, and 48 (20%) had only chart reviews; follow-up was completed for 163 (69%) patients. One hundred fifteen (63%) had seen their primary care provider during their illness prior to the ED visit. Seventy-three percent of patients (range per site 59-100%) were treated in the ED with bronchodilators (usually salbutamol or epinephrine) and 5% (range per site 0-14%) with oral steroids. Twenty-four percent (58/237) were prescribed bronchodilators on discharge, 3% (7/237) inhaled steroids, and 2% (5/237) oral steroids. Chi-square tests indicated significant practice variation by site in ED bronchodilator use (p < 0.001) and bronchodilator use at discharge (p = 0.0003). Admission rate was 31% (range by site 22-43%), 17% of patients had more than one ED visit, and 1% were admitted more than once. Admission rates were increased in younger children, children with comorbidities, and children with lower oxygen saturation. Viral studies were obtained in 53%, with 76% of these positive for respiratory syncytial virus (RSV). Median duration of cough was 12 days, poor sleeping and irritability eight days, and wheeze and poor feeding seven days. CONCLUSIONS: This study prospectively describes the treatment of bronchiolitis in the pediatric ED. The findings are consistent with the literature regarding the reported use of bronchodilators; however, use of steroids was found to be much lower than reported in other studies. Bronchodilator use in the ED and at discharge varied significantly by site. The results capture variation in treatment practices in Canadian PEDs, which may be the result of discordant randomized controlled trial evidence. Further research is needed to establish best practices.

Determinants of physical fitness in children with asthma.

RATIONALE: This study was designed to examine the relationships among weight, asthma severity, physical activity, and aerobic fitness in children with asthma. SUBJECTS AND METHODS: Sixty-four asthmatic children 8 to 12 years old (53% female) were assessed while attending a summer asthma camp. Measures included height and weight, spirometry, histamine bronchial provocation challenge, maximal aerobic power, and questionnaires to quantify habitual activity, perceived activity limitations due to asthma, perceived competence in physical activity, and attitudes toward physical activity. Asthma severity was determined from spirometric indices (forced expiratory volume during the first second), degree of airway hyperresponsiveness, and amount of medication prescribed. RESULTS: There was no correlation between asthma severity and aerobic fitness. Only perceived competence at physical activity was found to have a significant correlation with aerobic fitness. Appropriate-weight, overweight, or obese (defined by body mass index) children all had similar results for maximum aerobic power and level of habitual activity. However, overweight or obese children reported greater limitation of physical activity. Their asthma-impairment scores were higher than the scores of appropriate-weight peers, although standard measures of pulmonary function were no different among groups. The higher asthma-severity scores were related to greater medication needs in the overweight or obese children with asthma. CONCLUSIONS: Lower maximum aerobic power in asthmatic children is related more to how capable they perceive themselves than to asthma severity. Overweight asthmatic children experience greater limitation of physical activity and thus are prescribed more medication, although by standard measures of asthma severity, they are very similar to normal-weight peers with asthma. Efforts should be directed at understanding the reasons responsible for reduced exercise tolerance before escalating pharmacologic treatment.