Anti-inflammatory dosing of theophylline in the treatment of status asthmaticus in children.

BACKGROUND: Low-dose theophylline has been recognized for its ability to restore histone deacetylase-2 activity which leads to improved steroid responsiveness and thus improved clinical outcome. We retrospectively evaluated the effect of low-dose theophylline therapy in pediatric patients hospitalized for an acute asthma exacerbation as a proof of concept study. METHODS: We compared patients who received low-dose theophylline (5-7 mg/kg/day) in addition to current standard of care to patients who were treated with current standard of care alone. The primary outcome of the study was hospital length of stay (LOS). Generalized linear mixed-effects modeling (GLMM) was used to test whether receiving theophylline independently predicted outcomes. A Cox (proportional hazards) regression model was also developed to examine whether theophylline impacted LOS. RESULTS: After adjustment for illness severity measures, theophylline significantly reduces LOS (ß=-21.17, P<0.001), time to discontinue oxygen (ß=-15.88, P=0.044), time to spirometric improvement (ß=-16.60, P=0.014), and time to space albuterol (ß=-23.2, P<0.001) as well as reduced costs (ß=-US$2,746, P<0.001). Furthermore, theophylline significantly increased the hazards of being discharged from the hospital (hazards ratio =1.75, 95% confidence interval 1.20-2.54, P=0.004). There was no difference in side effects between patients who receive low-dose theophylline and those who did not. CONCLUSION: The results of this retrospective study suggest low-dose theophylline may have a positive effect in acute status asthmaticus. This study suggests that further research with a prospective, randomized, double-blinded, placebo controlled trial may be warranted to confirm and extend our findings.

Exercise-induced bronchospasm, asthma control, and obesity.

Exercise-induced bronchospasm (EIB) commonly affects patients with asthma. However, the relationship between EIB and asthma control remains unclear. Exercise limitation due to asthma might lead to reduced physical activity, but little information is available regarding obesity and EIB in asthma. A recent survey evaluated the frequency of EIB and exercise-related respiratory symptoms in a large number of patients with asthma. The survey results were reanalyzed to address any relationship between EIB and asthma control and obesity. A nationwide random sample of children aged 4-12 years (n = 250), adolescents aged 13-17 years (n = 266), and adults aged ≥18 years (n = 1001) with asthma were interviewed by telephone. Questions in the survey addressed asthma symptoms in general, medication use, and height and weight. Asthma control was categorized using established methods in the Expert Panel Report 3. Body mass index (BMI) was calculated using standard nomograms and obesity was defined as a BMI ≥ 30 kg/m(2). Most children (77.6%), adolescents (71.1%), and adults (83.1%) had either "not well" or "very poorly" controlled asthma. Children with "not well" controlled asthma reported a history of EIB significantly more often than those with "well" controlled" asthma. Asthma patients of all ages who had "not well" and "very poorly" controlled asthma described multiple (four or more) exercise-related respiratory symptoms significantly more often than those with "well-controlled" asthma. Obesity was significantly more common in adolescents with "not well" and "very poorly" controlled asthma and adults with "very poorly" controlled asthma. Children, adolescents, and adults with asthma infrequently have well-controlled disease. A history of EIB and exercise-related respiratory symptoms occur more commonly in patients with not well and very poorly controlled asthma. Obesity was found more often in adolescents and adults, but not children, with asthma, which was not well and very poorly controlled.

Exercise-induced bronchospasm: a case study in a nonasthmatic patient.

PURPOSE: To provide an overview of the clinical presentation, diagnosis, and management of exercise-induced bronchospasm (EIB) without underlying asthma. DATA SOURCES: Case presentation and review of the EIB Landmark Survey. CONCLUSIONS: EIB is a common and well-described occurrence in patients with asthma, as well as in patients with no overt respiratory condition. Treatment with a short-acting beta-agonist before starting exercise is effective, yet this treatment approach is underutilized in the majority of patients with asthma. IMPLICATIONS FOR PRACTICE: This case highlights the implications of undermanaged EIB and the disconnect between healthcare provider recommendations and the beliefs and behaviors in patients with EIB. Inhaled short-acting beta-agonists can attenuate EIB in 80%-95% of patients and are effective during 2-3 h of exercise. Patients with a compromised level of physical activity because of EIB who do not respond to conventional treatment strategies should be referred to a respiratory specialist for diagnostic evaluation and confirmation of underlying asthma. Nurse practitioners should remain vigilant to identify untreated EIB and ensure that affected patients understand the condition and appropriate treatment options.

Exercise-induced bronchospasm: implications for patients with or without asthma in primary care practice.

Exercise-induced bronchospasm (EIB) can represent a substantial barrier to physical activity. We present the cases of two patients with EIB, one with asthma, and one without asthma, who were evaluated at our primary care practice. The first case was a 44-year-old man with a history of seasonal allergic rhinitis but no asthma, who reported difficulty breathing when playing tennis. The second case was a 45-year-old woman who presented with persistent, generally well-controlled asthma, who was now experiencing bouts of coughing and wheezing during exercise. In both cases, an exercise challenge was used to diagnose EIB, and patients were prescribed a short-acting beta agonist to be used immediately before initiating exercise. EIB is a frequently encountered problem among patients presenting to primary care specialists. Affected patients should be made aware of the importance of proactive treatment with a short-acting beta agonist before initiating any exercise.

Obstructive sleep apnea in poorly controlled asthmatic children: effect of adenotonsillectomy.

BACKGROUND: Asthma and obstructive sleep apnea (OSA) in children share multiple epidemiological risk factors and the prevalence of snoring is higher in asthmatic children, suggesting that the latter may be at increased risk for OSA. Since both asthma and OSA are inflammatory disorders, we hypothesized that polysomnographically demonstrated OSA would be more frequent among poorly controlled asthmatics (PCA), and that treatment of OSA, if present, would ameliorate the frequency of acute asthmatic exacerbations (AAE). METHODS: Children with PCA were referred for an overnight sleep study, and adenotonsillectomy (tonsillectomy and adenoidectomy, T&A) was performed if OSA was present. Frequency of asthma symptoms and exacerbations were compared. RESULTS: Ninety-two PCA children, ages 3-10 years, with a mean frequency of AAE of 3.4 ± 0.4/year were prospectively referred for a sleep study. OSA (i.e., AHI > 5/hrTST) was present in 58 patients (63.0%; OR: 40.9, 12.9-144.1, P < 0.000001 compared to the prevalence of OSA in a non-asthmatic population). Information at 1-year follow-up was available for 35 PCA children after T&A. The annual frequency of AAE, rescue inhaled use, and asthma symptoms in this sub-group decreased compared to no changes in the group without OSA. CONCLUSIONS: The prevalence of OSA is markedly increased among PCA children and treatment of OSA appears to be associated with substantial improvements in the severity of the underlying asthmatic condition.

Exercise-induced bronchospasm in children with asthma in the United States: results from the Exercise-Induced Bronchospasm Landmark Survey.

Despite the availability of effective therapies, uncontrolled asthma remains a common problem. Previous large surveys suggest that exercise-related respiratory symptoms may be a significant element of uncontrolled asthma. The Exercise-Induced Bronchospasm (EIB) Landmark Survey is the first comprehensive, national survey evaluating EIB awareness and impact among the general public, asthma patients, and health care providers. This study was designed to evaluate the prevalence and impact of exercise-related respiratory symptoms in children (aged 4-17 years) with asthma. A national survey was conducted with parents of 516 children diagnosed with asthma or taking medications for asthma in the prior year. The majority of parents reported that their child experienced one or more exercise-related respiratory symptom and almost one-half (47.4%) experienced four or more symptoms. Most commonly reported symptoms were coughing, shortness of breath, and wheezing. Respondents reported that asthma limited their child's ability to participate either "a lot" or "some" in sports (30%), other outdoor activities (26.3%), and normal physical exertion (20.9%). Only 23.1% of children with exercise-related respiratory symptoms were reported to take short-acting beta-agonists such as albuterol "always" or "most of the time" before exercising. Exercise-related respiratory symptoms among pediatric asthma patients are common and substantially limit the ability of children to participate normally and perform optimally in physical activities. Such symptoms may reflect uncontrolled underlying asthma that should be evaluated and treated with appropriate controller medications. Despite the availability of preventative therapy, many children do not use short-acting bronchodilators before exercise as recommended in national guidelines.

Impact of exercise-related respiratory symptoms in adults with asthma: Exercise-Induced Bronchospasm Landmark National Survey.

An estimated 5-20% of the general population and up to 90% of people with asthma experience exercise-induced bronchospasm (EIB). The EIB Landmark Survey is the first comprehensive study on exercise-related respiratory symptoms in the United States. Two surveys were conducted: the first surveyed adults (≥18 years) in the general public and the second surveyed adults with asthma or taking medications for asthma in the prior year. Parameters assessed included exercise-related respiratory symptoms, activity levels, and short-acting beta-antagonist (SABA) use. In the general public survey (n = 1085), 8% were currently diagnosed with asthma. However, 29% reported experiencing one or more of six respiratory-related symptoms during or immediately after exercising. In the EIB in adult asthma survey (n = 1001), although >80% of adults experienced one or more of six exercise-related respiratory symptoms, only 30.6% reported a diagnosis of EIB. Almost one-half (45.6%) of adults with asthma reported that they avoid physical activities because of symptoms. Despite symptoms, only 22.2% of respondents took SABAs before exercise "always" or "most of the time"; 36.3% took rescue medications after or during exercise. Exercise-related respiratory symptoms limit physical activities and negatively impact daily lives. However, adults in the United States lack awareness of EIB. Although many subjects stated that their asthma symptoms limit their physical activity, few adhered to treatment guidelines by using SABAs appropriately before exercising. Findings from this survey support the need for better communication about the proper evaluation and management of EIB in the community and in asthma patients.

Inhaled Corticosteroids Should Be Used in Infants and Preschoolers with Recurrent Wheezing.

The infant or child presenting to the physician's office with persistent or recurrent wheezing during the first 2 years of life poses, often times, a diagnostic dilemma, and a therapeutic challenge. Until very recently, no guidelines were present to help the clinician navigate the very limited treatment options. The diagnosis of asthma in the very young is primarily difficult because of the lack of consistency of what is called asthma, and the failure to recognize the different phenotypes of asthma at different ages. Many classification and phenotypic descriptions have been proposed, but they continue to cause more confusion to already confused parents and perplexed physicians. Although these studies have provided much insight into the natural history of wheezy disorders, they have failed to affect clinical management to a large extent. Controversy persists as to when and why and how long inhaled corticosteroids (ICS) should be used in wheezy infants. Based on the current knowledge in this age group, ICS seems to be indicated in infants with multi-triggers wheeze, and in infants with a positive asthma predictive index. This article reviews the different phenotypic presentations of wheezy infant, the role and indications of ICS in this situation, and, finally, suggests a treatment plan based on the apparent cause of wheezing.

Once- vs twice-daily budesonide/formoterol in 6- to 15-year-old patients with stable asthma.

OBJECTIVE: To assess efficacy/tolerability of once-daily budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide pMDI (primary) and twice-daily budesonide/formoterol (secondary) in children/adolescents with asthma stabilized with twice-daily budesonide/formoterol. METHODS: This 12-week multicenter, double-blind randomized controlled study (www.clinicaltrials.gov identifier NCT00646321) included 521 patients aged 6 to 15 years with mild/moderate persistent asthma. Patients stabilized during a 4- to 5-week run-in with twice-daily budesonide/formoterol pMDI 40/4.5 microgx2 inhalations (160/18 microg daily) received twice-daily budesonide/formoterol pMDI 40/4.5 microgx2 inhalations (160/18 microg daily), once-daily budesonide/formoterol pMDI 80/4.5 microgx2 inhalations (160/9 microg daily; evening), or once-daily budesonide pMDI 80 microgx2 inhalations (160 microg daily; evening). RESULTS: Once- or twice-daily budesonide/formoterol was more effective than budesonide for evening peak expiratory flow (primary variable) at the end of the 24-hour once-daily dosing interval (P

A randomized controlled trial to evaluate the effectiveness of a distance asthma learning program for pediatricians.

OBJECTIVES: To assess provider acceptability of a distance learning program for pediatric asthma and pilot test its effects on physician knowledge, attitudes and treatment practices. DESIGN: Randomized controlled trial. SETTING: Louisville and the surrounding central Kentucky region. PARTICIPANTS: Twenty-four pediatricians in clinical practice. Interventions. A distance learning program for pediatric asthma consisting of Web- or CD-ROM-based multimedia learning modules and two teleconference calls. OUTCOME MEASURES: Learner satisfaction and change in physician asthma knowledge, attitudes, and treatment behavior at 1 to 4 months (short term) and 6 to 8 months (long term). RESULTS: Pediatricians had graduated from medical school a mean of 11.6 years before baseline (SD +/-8.9); 56% were female. On all learner satisfaction items, the average score was a 4.0 or greater on a 5-point scale, indicating a favorable response from the participants. Participants in the education group reported increased familiarity with asthma guideline for prescribing daily-inhaled corticosteroids compared to control physicians (p = .03) at short-term follow-up. Participants also expressed increased confidence in selecting a medicine for patients requiring a low-dose inhaled steroid (p = .03). However, these differences were not seen at long-term follow-up. Compared to the control group, there was no significant increase in the proportion of patients receiving inhaled steroids for persistent asthma at short- or long-term follow-up. CONCLUSIONS: Pediatricians utilizing an asthma distance learning program expressed a high degree of learner satisfaction. The program was associated with a temporary increase in familiarity and confidence in implementing components of the asthma guidelines.

Retrospective claims study of fluticasone propionate/salmeterol fixed-dose combination use as initial asthma controller therapy in children despite guideline recommendations.

BACKGROUND: According to current asthma treatment guidelines, single-entity inhaled corticosteroids (ICSs) should be used as initial controller therapy in children with mild to moderate persistent asthma. Long-acting beta(2)-agonists (LABAs) can be added to therapy for those patients whose asthma is not well controlled with a single-entity ICS. OBJECTIVES: The goal of this study was to examine whether the claims history for children in a US insured population indicate proper fluticasone propionate/ salmeterol (FPS) fixed-dose combination use in accordance with recommended asthma guidelines and a US Food and Drug Administration (FDA) advisory and black box warning regarding LABA use. A comparison of study-drug charges was also conducted. METHODS: Data from a US commercial insurance database were used in this retrospective study to evaluate pharmacy and medical claims for children between October 2004 and September 2006 (ie, the index period). An index date corresponding to the date of the first FPS claim was assigned to each patient. Eligible patients were aged 4 to 11 years and had >/=1 pharmacy claim for FPS during the index period. Those patients receiving 1 FPS prescription dose strength on the index date who were continuously enrolled for benefits during the preindex period (ie, the 365 days before the index date) were included in the study. Disease severity was assigned based on asthma-related pharmacy (frequency and/or incidence of oral corticosteroid, LABA, montelukast, and >365 doses of a short-acting beta(2)-agonist) and medical (asthma-related urgent care clinic or emergency department visits or hospitalizations) claim histories during the preindex period. RESULTS: A total of 13,306 patients between the ages of 4 and 11 years on the index date were included in the study; their mean (SD) age was 8.9 (1.9) years. The majority of the patients were male (60.7%). Of the total FPS claims, 55.2% were for patients with no evidence of pharmacy or medical claims in the 365 days before the first FPS claim that would warrant ICS/LABA combination therapy according to asthma treatment guidelines. There were no large changes in preindex ICS claims over the course of the study in response to an FDA-issued advisory and black box warning regarding the use of LABAs. Median drug charges for single-entity ICS use were $98 compared with $168 for FPS therapy. CONCLUSIONS: ICS/LABA combination treatment was used as initial therapy in 55.2% of children with mild to moderate asthma in this claims database population, contrary to the recommendations of current asthma treatment guidelines. The FDA advisory and black box warning for LABA use had little observed impact on the number of single-entity ICS claims.

Basketball clinic educates asthmatic children.

Healthy Hoops Kentucky is a new and innovative health program in Jefferson County, Kentucky that teaches asthmatic children (9-13 years) and their families how to manage the disease through the appropriate use of medications, proper nutrition, monitored exercise, and recreational activities. The Healthy Hoops Kentucky program includes asthma screenings at selected YMCA after-school care facilities and community health fairs, asthma awareness seminars for sports and school coaches, and a half-day basketball event held once a year, featuring local university coaches and current and former college basketball players.

Atypical mycobacterial infection in sequestrated lung in an infant presenting with chronic pneumonitis and recurrent wheezing.

An infant was referred to us for persistent cough and recurrent wheezing. Chest X-ray showed an abnormal shadow in the right lower lobe. A volumetric contrast-enhanced computerized tomography (CT) scan of the chest revealed an abnormal blood vessel extending from the descending aorta to the right lower lobe and anomalous venous drainage from the right lower lobe into inferior vena cava. Angiography confirmed the CT scan findings. Pulmonary sequestration associated with scimitar syndrome was subsequently diagnosed. Patient underwent right lower lobectomy and right inferior pulmonary vein was anastomosed into the left atrium. Pathological examination after surgery revealed epitheloid granuloma in the sequestrated lung parenchyma and mycobacteria in the draining lymph nodes. This is a rare case of pulmonary sequestration associated with scimitar syndrome and complicated by mycobacterial infection.

Update on National Asthma Education and Prevention Program pediatric asthma treatment recommendations.

The National Asthma Education and Prevention Program (NAEPP) published an update on selected topics from the 1997 Guidelines for the Diagnosis and Management of Asthma and provided new evidence-based recommendations for asthma treatment. Selected topics on the long-term management of asthma in children addressed the efficacy of inhaled corticosteroids (ICSs) compared with other asthma medications (i.e., as-needed beta(2)-adrenergic agonists and other controllers) in mild and moderate persistent asthma and the safety of long-term ICS use. The effects of early intervention with ICSs on asthma progression also were evaluated. An important new aspect of the treatment update entails the recommendation of ICSs as the controller medication of choice for all severities of persistent asthma in children. Additionally, on the basis of studies in adults, the Expert Panel suggested that long-acting beta(2)-adrenergic agonists are now the preferred adjunct to ICSs in children with moderate or severe persistent asthma. Based on long-term data in children, ICS therapy was deemed safe in terms of growth, bone mineral density, ocular effects, and hypothalamic pituitary adrenal axis function. Although members of the NAEPP Expert Panel determined that the effects of early intervention with ICSs on decline in lung function have not been adequately studied, they found that the effects on asthma control were substantial.

Rational approach to the wheezy infant.

The infant or child presenting to the physician's office with persistent or recurrent wheezing during the first two year's of life poses a diagnostic dilemma. A careful medical history should document risk factors for persistent wheezing, including maternal smoking, feeding practices, environmental history, and family history of asthma or cystic fibrosis (CF). A suggested diagnostic approach to the causes of infantile wheezing is outlined. A chest radiograph is non-specific, but may suggest a congenital airway anomaly. Infant pulmonary function testing (IPFT) can help differentiate between central airflow (intrathoracic, extrathoracic, or fixed) and peripheral airflow obstruction. The infant with either intrathoracic, extrathoracic, or fixed airflow obstruction on the PFT may benefit from flexible fiberoptic bronchoscopy. The infant with either an intrathoracic or fixed airway obstruction should undergo an upper gastrointestinal (UGI) series to evaluate the anatomy for extrinsic tracheal compression. The response to treatment with anti-inflammatory therapy may suggest an inflammatory disease such as asthma or CF. The infant with peripheral airflow obstruction and a good response to bronchodilators (> or =25%) using the forced exhalation technique is given the diagnosis of infantile asthma. The infant with peripheral airflow obstruction and no response to bronchodilators should be evaluated further for possible gastroesophageal reflux disease (GERD), and for other causes, which are associated with wheezing symptoms.