Budesonide suspension nebulization treatment in Chinese pediatric patients with cough variant asthma: a multi-center observational study

Objective: To describe the impact of nebulized budesonide inhalation suspension (BIS) on guardian-reported symptoms in Chinese pediatric patients with cough variant asthma (CVA).

Methods: This was a secondary analysis of a prospective, non-interventional study conducted at 39 Chinese sites. Patients with CVA aged?≤5 years were classified according to the severity of baseline symptoms: mild (symptom score?≤3) or severe (symptom score?>3). Daytime and night-time symptom scores, disease control, use of bronchodilators, and improvements in symptoms control were compared after 1, 3, 5 and 7 weeks of treatment between groups. Results: Among 914 patients, 821 (89.8%) completed the 7-week treatment. Among all patients, 368 (40.3%) were classified as mild CVA and 529 (57.9%), as severe CVA. Symptom scores in the severe group were higher than those in the mild group at weeks 1, 3, and 5 (p?< 0.05), but not at week 7 (p?> 0.05). Further, more patients in the mild group achieved disease control at any time point (98.6% at 3 weeks and 99.7% at 7 weeks), compared with the patients in the severe group (p?< 0.001). The proportion of patients requiring bronchodilators differed between the groups until week 5 (p?< 0.001). No severe or drug-related adverse events were reported. Conclusions: Individualized BIS treatment should be formulated according to the severity of baseline symptoms in CVA patients. Patients with mild CVA showed improvement after a shorter treatment time, while patients with severe CVA might require a longer time to respond to the treatment.     

Ozone: a trigger for hospital pediatric asthma emergency room visits

A time-series study was carried out in Paris from January 1 to December 31, 1988 with the aim of investigating the association between urban air pollution and daily emergency room visits for asthma in a pediatric hospital. Levels of black smoke, sulfur dioxide, nitrogen dioxide, and ozone were monitored throughout the study area, and meteorological data were collected. Influenza epidemics and pollen periods were identified. Health data were collected from a pediatric hospital emergency room. Case definition of asthma attacks was based on clinical diagnosis. Children were included in the study if: 1) they were 1 to 15 years old; 2) they had doctor-diagnosed asthma and were followed in our asthma outpatient clinic; and 3) they were residents in the Paris region. The relation between daily asthma visit counts and air pollution levels was assessed, using a multiple linear regression model and taking into account temporal variations and autocorrelation in the data. A thousand and twenty visits for asthma were observed during the study period. A positive statistical association was found between daily asthma visits and daily variations of ozone levels (1 day after exposure, relative risk = 1.52 [95% confidence interval: 1. 06-2.19]) after controlling for monthly and weekly variations, influenza epidemics, periods of pollen exposure, and daily mean temperature (2 days' lag). This study underlines the significant role of ozone as a trigger for asthma attacks in children.     

Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma

OBJECTIVES: A fixed combination of long-acting beta(2)-agonists (LABA) plus inhaled corticosteroids (ICS) has never been proven to reduce asthma exacerbations vs ICS alone in children. This 12-month, double-blind, randomized study in 341 children (age range, 4 to 11 years) with asthma uncontrolled on ICS investigated whether a novel regimen using budesonide/formoterol for maintenance and reliever therapy (Symbicort maintenance and relief therapy [SMART]) [Symbicort; AstraZeneca R&D, Lund, Sweden] could reduce exacerbations. METHODS: Patients received SMART (budesonide/formoterol 80/4.5 microg qd maintenance plus additional inhalations for symptom relief), budesonide/formoterol 80/4.5 microg qd for maintenance (fixed combination), or higher-dose budesonide 320 microg qd (fixed-dose budesonide). Blinded as-needed medication (terbutaline 0.4 microg) was provided in both fixed-dose groups. RESULTS: SMART prolonged the time to first exacerbation vs fixed-dose budesonide (p = 0.02) and fixed-dose combination (p < 0.001). Rates of exacerbation requiring medical intervention were reduced by 70 to 79% with SMART vs fixed-dose budesonide and fixed-dose combination (0.08/patient vs 0.28/patient and 0.40/patient, respectively; both p < 0.001). Mild exacerbation days and awakenings were significantly lower with SMART; yearly growth improved by 1.0 cm vs fixed-dose budesonide (p < 0.01). CONCLUSION: The SMART regimen using budesonide/formoterol for both maintenance and as-needed symptom relief reduces the exacerbation rate compared with both fixed-dose combination and higher fixed-dose ICS alone in children with asthma.     

Direct percutaneous endoscopic jejunostomy: a case series in pediatric patients.

BACKGROUND: Direct percutaneous endoscopic jejunostomy (DPEJ) is a well-known approach to deliver postpyloric enteral nutrition support to individuals who cannot tolerate gastric feeding. DPEJ addresses many of the shortcomings of jejunal feeding tubes placed through percutaneous endoscopic gastrostomy tubes. The safety and efficacy of DPEJ in adults has been previously reported. There are no reports on the use of DPEJ in pediatric patients. OBJECTIVE: Our purpose was to report on 5 pediatric patients who underwent DPEJ placement between January 2000 and January 2003 over the available follow-up periods. DESIGN: Retrospective case series. SETTING: University of Utah Health Sciences Center and the Medical University of South Carolina. PATIENTS: Five patients, age range 4 to 17 years. MAIN OUTCOME MEASUREMENTS: Rate of successful tube placement, major and minor complications, and outcomes including weight gain and recurrent aspiration after DPEJ placement. RESULTS: All 5 attempted DPEJs were placed successfully with 2 minor complications of peristomal leakage and peristomal skin infection. One DPEJ was replaced 2 years after placement because of fungal degradation. The mean weight gain among all patients was 10.3 kg in a mean of 22.6 months. LIMITATIONS: Retrospective, small series. CONCLUSIONS: DPEJ placement appears to be a safe and effective approach to enteral nutritional support in pediatric patients requiring long-term access to the jejunum. No major complications occurred and all patients gained weight after tube placement.     

Endoscopic retrograde cholangiography for pediatric choledocholithiasis: Assessing the need for endoscopic intervention

AIM:To assess pediatric patients for choledocholithiasis.We applied current adult guidelines to identify predictivefactors in children.METHODS:A single-center retrospective analysis was performed at a tertiary children's hospital.We evaluated 44 consecutive pediatric patients who underwent endoscopic retrograde cholangiography(ERCP) for suspected choledocholithiasis.Patients were stratified into those with common bile duct stones(CBDS) at ERCP vs those that did not using the American Society of Gastrointestinal Endoscopy(ASGE) guidelines(Very Strong and Strong criteria) for suspected CBDS.RESULTS:CBDS were identified in 84% at the time of ERCP.Abdominal ultrasound identified CBDS in 36% of patients.Conjugated bilirubin ≥ 0.5 mg/d L was an independent risk factor for CBDS(P = 0.003).The Very Strong(59.5%) and Strong(48.6%) ASGE criteria identified the majority of patients(P = 0.0001).A modified score using conjugated bilirubin had a higher sensitivity(81.2% vs 59.5%) and more likely to identify a stone than the standard criteria,odds ratio of 25.7 compared to 8.8.Alanine aminotransferase and gamma-glutamyl transferase values identified significant differences in a subset of patients with odds ratio of 4.1 and 3.25,respectively.CONCLUSION:Current adult guidelines identified the majority of pediatric patients with CBDS,but specific pediatric guidelines may improve detection,thus decreasing risks and unnecessary procedures.     

Histopathology of severe childhood asthma: a case series

BACKGROUND: To date, little has been published describing the pathology of severe childhood asthma. The currently accepted model of asthma holds that persistent airway inflammation leads to various symptoms of asthma, airway hyperresponsiveness, and airway remodeling that ultimately results in permanent loss of lung function. METHODS: Evaluation of six children referred to the National Jewish Medical and Research Center with difficult-to-control asthma, despite aggressive anti-inflammatory therapy, who underwent bronchoscopy with endobronchial biopsy to better characterize their disease. RESULTS: In every case, endobronchial biopsies revealed changes consistent with airway remodeling characterized by thickening of the basement membrane, smooth-muscle hypertrophy, with varying degrees of goblet-cell and submucous gland hyperplasia. The degree of subbasement membrane thickening did not appear to correlate with baseline FEV(1), ultimate FEV(1) following aggressive therapy, or lability in lung function. In five of six cases, there was minimal to no histologic evidence for airway inflammation with mild and patchy submucosal lymphocytic infiltration noted; eosinophils and neutrophils were not present. Further, the majority of the patients achieved normal FEV(1) values despite significant subbasement membrane thickening, counter to the current beliefs regarding airway remodeling and irreversible loss of lung function. CONCLUSIONS: This case report highlights some of the shortcomings of the current inflammatory paradigm for severe asthma. Despite little evidence of ongoing airway inflammation, many of the subjects displayed significant lung function lability. The lack of inflammation argues against steroid resistance at a cellular level, although it could be argued that inflammation may have been distal to the site sampled. Additionally, normal to nearly normal lung function was achieved despite the presence of significant remodeling. These findings suggest the need to look beyond inflammation to fully treat severe asthma and ultimately alter its progression.     

Airway pressure release ventilation: a pediatric case series

Airway pressure release ventilation (APRV) is a relatively new mode of mechanical ventilation (MV) first described in animal studies in 1987 and in humans in 1988. It is a time-triggered, time-cycled, pressure-limited mode where a high level of continuous positive airway pressure (CPAP) is maintained with brief regular releases in pressure, and spontaneous breathing is allowed throughout the cycle. In theory, it is consistent with a lung protective approach while having some hypothetical advantages over HFOV. The use of this mode of ventilation in pediatrics has been limited. The authors describe their experience with this mode of ventilation in a series of pediatric patients.     

Intravenous magnesium for acute asthma: failure to decrease emergency treatment duration or need for hospitalization.

STUDY OBJECTIVE: To evaluate the efficacy of routine early administration of i.v. magnesium to patients with acute asthma. DESIGN: Prospective, randomized clinical trial. SETTING: Urban teaching hospital emergency department. TYPE OF PARTICIPANTS: One hundred twenty consecutive patients aged 18 to 65 years with acute asthma unresponsive to a single albuterol treatment. INTERVENTIONS: All patients received oxygen, 125 mg i.v. methylprednisolone, and hourly albuterol inhalation therapy. The study group also received 2 g i.v. magnesium sulfate infused over 20 minutes. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical characteristics were similar in both groups. Hospitalization was necessary in 13 of 58 patients who received magnesium (22%; 95% confidence intervals [CI], 13% to 32%) and 11 of 62 control patients (17%; 95% CI 10% to 26%; P = .523). Duration of ED treatment in discharged patients was 224 +/- 75 minutes in the magnesium group (95% CI, 208 to 240 minutes) and 228 +/- 90 minutes in the control group (95% CI, 209 to 247 minutes, P = .832). In addition, changes in peak expiratory flow were not statistically different. CONCLUSION: Routine early administration of IV magnesium in acute asthma does not alter treatment outcome.     

Diarrhea etiology in a pediatric emergency department: a case control study

Background.?The etiology of childhood diarrhea is frequently unknown. Methods.?We sought Aeromonas, Campylobacter, Escherichia coli O157:H7, Pleisiomonas shigelloides, Salmonella, Shigella, Vibrio, and Yersinia (by culture), adenoviruses, astroviruses, noroviruses, rotavirus, and Shiga toxin-producing E. coli (STEC; by enzyme immunoassay), Clostridium difficile (by cytotoxicity), parasites (by microscopy), and enteroaggregative E. coli (EAEC; by polymerase chain reaction [PCR] analysis) in the stools of 254 children with diarrhea presenting to a pediatric emergency facility. Age- and geographic-matched community controls without diarrhea (n?=?452) were similarly studied, except bacterial cultures of the stool were limited only to cases. Results.?Twenty-nine (11.4%) case stools contained 13 Salmonella, 10 STEC (6 O157:H7 and 4 non-O157:H7 serotypes), 5 Campylobacter, and 2 Shigella. PCR-defined EAEC were present more often in case (3.2%) specimens than in control (0.9%) specimens (adjusted odds ratio [OR], 3.9; 95% confidence interval [CI], 1.1-13.7), and their adherence phenotypes were variable. Rotavirus, astrovirus, and adenovirus were more common among cases than controls, but both groups contained noroviruses and C. difficile at similar rates. PCR evidence of hypervirulent C. difficile was found in case and control stools; parasites were much more common in control specimens. Conclusions.?EAEC are associated with childhood diarrhea in Seattle, but the optimal way to identify these agents warrants determination. Children without diarrhea harbor diarrheagenic pathogens, including hypervirulent C. difficile. Our data support the importance of taking into account host susceptibility, microbial density, and organism virulence traits in future case-control studies, not merely categorizing candidate pathogens as being present or absent.     

Leprosy case series in the emergency room: A warning sign for a challenging diagnosis

Leprosy can be considered a dissimulated disease, mainly when presented as atypical cases leading to mistaken diagnosis at the emergency setting. Herein we report six patients referred to the emergence room with hypotheses of acute myocardial infarction and arterial and venous thrombosis, although with chronic neurological symptoms; the seventh patient was referred with a wrong suspicion of infected skin ulcer. Positive findings included hypo-anesthetic skin lesions and thickened nerves; 100% were negative for IgM anti-phenolic glycolipid-I, while 71.4%, 100% and 42.8% were positive for IgA, IgM and IgG Mce1A. RLEP-PCR was positive in all patients. Ultrasound of peripheral nerves showed asymmetric and focal multiple mononeuropathy for all patients. Unfortunately, in many patients leprosy is often misdiagnosed as other medical conditions for long periods thus delaying initiation of specific treatment. This paper is intended to increase physicians’ awareness to recognize leprosy cases presented as both classical and unusual forms, including in emergency department.     

Predictors of prior asthma specialist care among pediatric patients seen in the emergency department for asthma

Background: Asthma guidelines recommend specialist care for patients experiencing poor asthma outcomes during emergency department (ED) visits. The prevalence and predictors of asthma specialist care among an ED population seeking pediatric asthma care are unknown. Objective: To examine, in an ED population, factors associated with prior asthma specialist use based on parental reports of prior asthma morbidity and asthma care. Methods: Parents of children ages 0 to 17?years seeking ED asthma care were surveyed regarding socio-demographics, asthma morbidity, asthma management and current asthma specialist care status. We compared prior asthma care and morbidity between those currently cared for by an asthma specialist versus not. Multivariable logistic regression models to predict factors associated with asthma specialist use were adjusted for parent education and insurance type. Results: Of 150 children (62% boys, mean age 4.7?years, 69% Hispanic), 22% reported asthma specialist care, 75% did not see a specialist and for 3% specialist status was unknown. Care was worse for those not seeing a specialist, including under-use of controller medications (24% vs. 64%, p?<?0.001) and asthma action plans (20% vs. 62%, p?<?0.001). Multivariable logistic regression revealed that lack of recommendation by the primary care physician reduced the odds of specialist care (OR 0.01, 95% CI <0.01, 0.05, p?<?0.001). Conclusions: Asthma specialist care was infrequent among this pediatric ED population, consistent with the sub-optimal chronic asthma care we observed. Prospective trials should further investigate if systematic referral to asthma specialists during/after an ED encounter would improve asthma outcomes.     

Children's use of emergency departments for asthma: persistent barriers or acute need?

Our objective was to explore, in a predominantly Latino inner-city population, why caregivers bring their children with asthma to the ED (emergency department). We conducted bilingual parent surveys and medical chart abstractions of a consecutive ED sample consisting of 234 children with asthma (69% Latino; 54% Spanish-speaking) and their caregivers. Outcome measures included: (1) the acute need for ED services based on objective physiological measures, (2) the extent to which these children experienced barriers to quality primary care for asthma before the ED visit, and (3) the relative importance caregivers assigned to worsening symptoms versus perceived barriers to non-ED care when deciding to bring their child to the ED. Most children had moderate or severe asthma attacks. In the prior month, only 33% went to a primary care provider, 83% had used a bronchodilator, and 63%, an age-appropriate spacer device. Seventy-five percent of caregivers cited perceived acute need, instead of barriers to primary care, as the most important reason for using the ED. This perception of acute need was associated with moderate or severe asthma attacks according to objective physiological measures, after controlling for health and sociodemographic characteristics. Children with asthma who use the ED encounter barriers to primary care, but caregivers' perception of acute need--validated by independent measures of attack severity--dominates caregivers' decision to use the ED. Ensuring continuity of care for children with asthma would involve not only improving various aspects of access to and quality of primary non-ED care--including parent education about early recognition and treatment of asthma attacks--but also providing families with practical low-cost alternatives for 24-hour care and assuring linkages between the ED and sources of primary care.     

Occupational asthma: a case of Baker's asthma.

Asthma is one of the most prominent respiratory diseases worldwide. It is defined by airflow limitation and/or airway hyperresponsiveness and can be exacerbated by a number of environmental allergens. When allergic asthma exacerbations are attributed to stimuli in a particular work environment, then occupational asthma must be considered. Incidence estimates vary, but in 1999 the Surveillance of Work-Related and Occupational Respiratory Disease in the United Kingdom estimated 4293 incident cases of occupational respiratory disease, an increase of 1427 cases over the previous year. Occupational asthma represented 26% of these cases. Baker's asthma is one of the most frequently reported types of occupational asthma in several countries. Diagniostic steps include thorough history, careful exam, and demonstration of functional reversible airflow obstruction. Treatment modalities used for occupational asthma are similar to those used in the management of other forms of asthma, with particular attention to reducing the level of exposure to the inciting allergen.     

Ciclesonide reduces the need for oral steroid use in adult patients with severe, persistent asthma

STUDY OBJECTIVES: Oral corticosteroids (OCS) may be associated with systemic adverse events (AEs), which can be reduced by replacing OCS with inhaled corticosteroids (ICS). The potential of ciclesonide, a novel ICS, to reduce OCS use in patients with severe, persistent asthma was evaluated in this study. DESIGN: A phase III, 12-week, international, multicenter, double-blind, placebo-controlled, parallel-group study. PATIENTS: Adult and adolescent patients (> or = 12 years old; n = 141) with severe, persistent, oral steroid (prednisone)-dependent asthma. INTERVENTIONS: Patients were randomized to receive ciclesonide (640 mug/d or 1,280 microg/d [ex-actuator]) bid or placebo for 12 weeks. Weekly evaluations determined eligibility for prednisone dose reduction based on predetermined criteria. MEASUREMENTS AND RESULTS: The prednisone dose was significantly reduced by 47% and 63% in the groups receiving ciclesonide, 640 microg/d, and ciclesonide, 1,280 microg/d, respectively, vs an increase of 4% in the placebo group (both p < or = 0.0003) at week 12. By week 12, prednisone was discontinued by approximately 30% of patients in the ciclesonide-treated groups, vs 11% of patients in the placebo group (both p < or = 0.04). FEV1 improved significantly at week 12 in the ciclesonide treatment groups vs placebo (p < 0.03). The occurrence of local and systemic AEs was comparable between all treatment groups. CONCLUSION: Study results suggest that ciclesonide significantly reduces the need for OCS in patients with severe, persistent asthma, while maintaining asthma control.     

A cost-effectiveness threshold analysis of a multidisciplinary structured educational intervention in pediatric asthma

Objective: Asthma educational interventions have been shown to improve several clinically and economically important outcomes. However, these interventions are costly in themselves and could lead to even higher disease costs. A cost-effectiveness threshold analysis would be helpful in determining the threshold value of the cost of educational interventions, leading to these interventions being cost-effective. The aim of the present study was to perform a cost-effectiveness threshold analysis to determine the level at which the cost of a pediatric asthma educational intervention would be cost-effective and cost-saving. Methods: A Markov-type model was developed in order to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a single uncontrolled before-and-after study performed with Colombian asthmatic children. Cost data were obtained from official databases provided by the Colombian Ministry of Health. The main outcome was the variable “quality-adjusted life-years” (QALYs). Results: A deterministic threshold sensitivity analysis showed that the asthma educational intervention will be cost-saving to the health system if its cost is under US$513.20. Additionally, the analysis showed that the cost of the intervention would have to be below US$967.40 in order to be cost-effective. Conclusions: This study identified the level at which the cost of a pediatric asthma educational intervention will be cost-effective and cost-saving for the health system in Colombia. Our findings could be a useful aid for decision makers in efficiently allocating limited resources when planning asthma educational interventions for pediatric patients.     

Clinical pathway improves pediatrics asthma management in the emergency department and reduces admissions

Objective: Poor adherence to the National Institute of Health (NIH) Asthma Guidelines may result in unnecessary admissions for children presenting to the emergency department (ED) with exacerbations. We determine the effect of implementing an evidence-based ED clinical pathway on corticosteroid and bronchodilator administration and imaging utilization, and the subsequent effect on hospital admissions in a US ED. Methods: A prospective, interventional study of pediatric (≤21 years) visits to an academic ED between 2011 and 2013 with moderate-severe asthma exacerbations has been conducted. A multidisciplinary team designed a one-page clinical pathway based on the NIH Guidelines. Nurses, respiratory therapists and physicians attended educational sessions prior to the pathway implementation. By adjusting for demographics, acuity and ED volume, we compared timing and appropriateness of corticosteroid and bronchodilator administration, and chest radiograph (CXR) utilization with historical controls from 2006 to 2011. Subsequent hospital admission rates were also compared. Results: A total of 379 post-intervention visits were compared with 870 controls. Corticosteroids were more likely to be administered during post-intervention visits (96% vs. 78%, adjusted OR 6.35; 95% CI 3.17-12.73). Post-intervention, median time to corticosteroid administration was 45?min faster (RR 0.74; 95% CI 0.67-0.81) and more patients received corticosteroids within 1?h of arrival (45% vs. 18%, OR 3.5; 95% CI 2.50-4.90). More patients received?>?1 bronchodilator dose within 1?h (36% vs. 24%, OR 1.65; 95% CI 1.23-2.21) and fewer received CXRs (27% vs. 42%, OR 0.7; 95% CI 0.52-0.94). There were fewer admissions post-intervention (13% vs. 21%, OR 0.53; 95% CI 0.37-0.76). Conclusion: A clinical pathway is associated with improved adherence to NIH Guidelines and, subsequently, fewer hospital admissions for pediatric ED patients with asthma exacerbations.     

Menthol-induced asthma: a case report.

A case of asthma due to menthol is reported in a 40-year-old woman with no history of asthma or any other allergy. During the last two years, the patient had presented dyspnea, wheezing and nasal symptoms when exposed to mentholated products such as toothpaste and candies. The etiology was suggested by the history of exposure and diagnosis was established by skin tests and bronchial challenge with menthol. The patient achieved control of symptoms by avoiding menthol and its derivatives.