Asthma prevalence and control among schoolchildren residing near outdoor air pollution sites.

INTRODUCTION: Outdoor air pollution (OAP) contributes to poor asthma outcomes and remains a public health concern in Pittsburgh. The purpose of this study was to determine the prevalence of childhood asthma and its rate of control among Pittsburgh schoolchildren residing near OAP sites. METHODS: Participants were recruited from schools near OAP sites. Asthma prevalence and control were assessed using a validated survey. Demographics and socioeconomic status were collected by survey, BMI was calculated, secondhand smoke (SHS) exposure was assessed by salivary cotinine levels, and OAP was assessed by mobile platform monitoring. Multivariate analysis adjusted for confounders. RESULTS: In 1202 Pittsburgh elementary school students surveyed, 50.9% were female, average age was 8.5 years (SD = 1.9), 52.2% were African American and 60.6% had public health insurance. SHS exposure was relatively high at 33.9%, 17.1% of students were obese, and 70% had exposure to particulate matter (PM2.5) greater than the World Health Organization standard of 10 µg/m3. Overall prevalence of asthma was 22.5% with PM2.5, nitric oxide (NOx), sulfur (S), and zinc (Zn) significantly related to odds of asthma. Among the 270 children previously diagnosed with asthma, 59.3% were not well controlled with PM2.5, black carbon, and silicon (Si) significantly related to odds of uncontrolled asthma. CONCLUSIONS: These results demonstrate that asthma prevalence and poor disease control are significantly elevated in Pittsburgh schoolchildren exposed to high levels of OAP. Future efforts need to focus on primary prevention of asthma by reducing exposure to OAP in at risk populations.

Evaluation of the ocular safety associated with the exhalation delivery system with fluticasone.

Background: Intranasal corticosteroids (INCS) are the cornerstone of treatment for chronic rhinosinusitis. Although INCS are generally considered safe and effective, there is a concern that chronic use may lead to ocular adverse effects. Objective: To assess ocular safety of the exhalation delivery system with fluticasone propionate (EDS-FLU) in patients with chronic rhinosinusitis with nasal polyps. Methods: Ocular safety data were collected during two randomized, double-blind, placebo controlled studies with open-label extensions. Ophthalmologists performed tonometry, slit-lamp, and visual acuity examinations to assess intraocular pressure (IOP) and the presence of cataracts. Ocular examinations were conducted before double-blind treatment, at the end of the 16-week double-blind phase, and at the end of the 8-week open-label phase. The results of pooled data from patients who received EDS-FLU 186 µg (n = 160), EDS-FLU 372 µg (n = 161), and EDS-placebo (n = 161) twice daily are reported here. Results: At the end of the double-blind phase, six patients developed elevated average IOP > 21 mm Hg: two patients (1.2%) in the EDS-placebo group, three patients (1.9%) in the EDS-FLU 186 µg group, and one patient (0.6%) in the EDS-FLU 372 µg group. In addition, 6 of 482 patients developed cataracts: 3 patients in the EDS-placebo group, 2 patients in the EDS-FLU 186 µg group, and 1 patient in the EDS-FLU 372 µg group. At the end of the open-label phase, two additional patients showed IOP > 21 mm Hg and two additional patients developed cataracts. Conclusion: No increased risk of elevated IOP was detected with EDS-FLU; the rate of cataract development was similar to EDS-placebo and to that reported with other INCS.Clinical trials NCT01622569 and NCT01624662, www.clinicaltrials.gov.

Clinical features of adolescents with chronic idiopathic or spontaneous urticaria: Review of omalizumab clinical trials.

BACKGROUND: Adults and adolescents were included in 3 phase 3 omalizumab trials in chronic idiopathic urticaria (CIU): ASTERIA I, ASTERIA II, and GLACIAL. OBJECTIVE: To describe the baseline clinical profile of adolescent patients with CIU enrolled in the omalizumab trials to add to the limited literature available on CIU in this population. METHODS: Data for patient demographics, baseline clinical disease characteristics, medical history, and previous CIU medication information (not efficacy assessments) from phase 3 omalizumab trials were pooled and descriptive statistical analyses performed for adolescent (12 to <18 years old) and adult (≥18 years old) subgroups. Inferential analysis was inappropriate, partly because of small sample size in the adolescent subgroup. RESULTS: The pooled population of 975 patients with CIU included 39 adolescents (4.0%). Demographics of adolescents and adults with CIU were similar, but compared with adults, fewer adolescents had positive Chronic Urticaria Index test results. Baseline clinical disease characteristics were also similar between the subgroups, with the number of previous CIU medications slightly lower in adolescents compared with adults. Medical history and existing conditions in adolescents tended to be more allergy than cardiovascular related, and fewer experienced angioedema compared with adults. CONCLUSION: Pooled data indicate differences in baseline demographic and clinical characteristics between adult and adolescent patient subgroups. This finding helps augment our understanding of the clinical profile of CIU in adolescents, but larger-scale studies in this population are warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL).

Inhaled corticosteroids: Effects on growth and bone health.

BACKGROUND: Both slowed growth in children and reduced bone mineral density (BMD) are systemic effects of corticosteroids, and there is concern about the degree to which these systemic effects affect growth and BMD. OBJECTIVE: To engage in a data-driven discussion of the effects of inhaled corticosteroids (ICSs) on growth in children and BMD. METHODS: Articles were selected based on their relevance to this review. RESULTS: Studies of ICSs in children in which growth was a secondary outcome have revealed slowed growth associated with low doses of budesonide, fluticasone propionate, and beclomethasone dipropionate. In the study of budesonide, the effect was permanent, and in the study of fluticasone propionate, the effect was long-lasting, but it is unclear whether the effect was permanent. However, the results of studies in which growth was the primary outcome were mixed. Slowed growth was detected in a study of beclomethasone dipropionate; however, slowed growth was not detected in a study of ciclesonide or flunisolide. A decrease in BMD acquisition in children was associated with high doses but not low to medium doses of ICSs. In adults, there was a dose-related effect of ICSs on BMD. Both higher daily dose and larger cumulative dose were associated with increased bone density loss. CONCLUSION: Because of the systemic effects on growth and bone health, children should be monitored for growth using stadiometry every 3 to 6 months and BMD should be monitored yearly in patients being treated with high doses of ICSs.

The tall and the short: Repainting the landscape about the growth effects of inhaled and intranasal corticosteroids.

BACKGROUND: Earlier 1-year growth studies that used older inhaled corticosteroid (ICS) formulations consistently showed that ICS, but not intranasal corticosteroids (INCS), produced a small ∼1 cm/y growth effect that appeared to be nonprogressive and noncumulative. Studies that lasted for >1 year showed that such treatment during childhood did not affect final adult height. Collectively, these studies led to the beliefs that (1) the small short-term effect on growth is unimportant, (2) there is no long-term harm, and (3) any small risk is easily outweighed by the benefit. This led to the cavalier use of ICS and INCS in children and approval of some INCS for over-the-counter sales for children as young as 2 years of age. METHODS: Literature search using Pub-Med. RESULTS: More recent studies, with improved scientific designs, have challenged and overturned the earlier beliefs. Moreover, some of the newer ICS formulations have negative, robust growth studies (designed per FDA guidance and detected no growth effect). CONCLUSIONS: This review focused on the new evidence and how it will change the way that we use ICS and INCS in children with allergy and asthma in both clinical practice and research, with a renewed focus on safety. There also are significant implications for future iterations of asthma guidelines. The goal was to identify the proper amount of new concern about ICS and INCS, not to generate undue steroid "phobia."

Sinus and adenoid inflammation in children with chronic rhinosinusitis and asthma.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma frequently coexist in children and adults. However, the precise pathophysiologic mechanism of this interaction is still poorly understood, especially in children, owing to the lack of direct measurements of mucosal inflammation in the upper airways. OBJECTIVE: To determine the pathophysiologic mechanism by analyzing the expression of a large array of inflammatory cytokines and chemokines in the sinus and adenoid tissues surgically removed from pediatric patients with CRS refractory to medical management. METHODS: Twenty-eight children 2 to 12 years old diagnosed with CRS with or without asthma and 10 controls were included in this prospective, nonrandomized study. Mucosal expression of 40 inflammatory cytokines was measured with a multiplex assay and was normalized to total tissue protein. RESULTS: Compared with children with CRS and without asthma, children with CRS and asthma had significantly higher sinus levels of tumor necrosis factor-α and adenoid levels of epidermal growth factor, eotaxin, fibroblast growth factor-2, growth-related oncogene, and platelet-derived growth factor-AA. CONCLUSION: The inflammatory response in the upper airway mucosa of children with asthma and CRS was similar, but more severe, compared with children with CRS without asthma. This observation is consistent with the hypothesis that asthma in these patients is caused or exacerbated by severe upper airway disease and supports the concept that treating sinus disease is paramount in the management of chronic asthma in children using, for the first time, direct measurements of airway inflammation in children.

The Future of Sublingual Immunotherapy in the United States.

Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC). The Food and Drug Administration (FDA) in the USA has approved three SLIT tablets for the treatment of AR and ARC in relation to pollen. Specifically, Grastek® and Oralair® are two formulations approved to treat patients suffering with AR/ARC to grass pollen, and Ragwitek™ is a formulation approved to treat patients suffering with AR/ARC to ragweed pollen. Although these approvals provide support for physicians to prescribe SLIT, barriers to prescribing SLIT still remain such as FDA approval for additional formulations, a standard dose and dosing schedule, and cost/insurance coverage. In order to further support the use of SLIT, research is currently being conducted to expand the indication for SLIT to other common comorbidities to AR/ARC. For example, allergic asthma, food allergies, and atopic dermatitis are other diseases which are being explored. The future of SLIT in the USA is unknown; however, education will be necessary for both providers and patients.

Diagnosis and treatment of nasal and ocular allergies: the Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys.

BACKGROUND: Allergic rhinoconjunctivitis (ARC) is managed by a number of health care professional specialties, whose practice styles may vary. OBJECTIVE: To survey patients and health care professionals about the diagnosis and treatment of ARC. METHODS: The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys were telephone surveys of randomly selected patients and health care professionals in the United States in 2012. Participants were 2,765 people ever diagnosed as having nasal and/or ocular allergies and 500 practitioners in 7 specialties who were treating ARC. RESULTS: Adult respondents to the patient survey reported that their allergies had been diagnosed most often by physicians in family practice (46%) rather than by allergists/immunologists (17%) or otolaryngologists (11%). Children's allergies had been diagnosed most often by pediatricians (41%) and family practitioners (22%). Most respondents with conditions diagnosed by an allergist/immunologist (94.9%) or otolaryngologist (62.7%) had been given an allergy test, but the test was not given to most patients with conditions diagnosed by family practitioners (61.3%) or pediatricians (64.9%). Most patients (75.8%) were treating their allergies with over-the-counter medications, and 53.5% were taking prescription medications. Allergen immunotherapy was being used by 33% (adult) or 28% (child) patients of allergist/immunologists, 25% (adult) or 24% (child) patients of otolaryngologists, and 8% and 10% of patients of family practitioners and pediatricians, respectively. CONCLUSION: Most patients took nonprescription medications for their allergy symptoms or were treated by general practitioners, who did not use allergy testing when diagnosing ARC. Most patients seen by allergist/immunologists and otolaryngologists were evaluated with allergy tests, and most allergen immunotherapy was provided by allergy specialists.

An asthma sports camp series to identify children with possible asthma and cardiovascular risk factors.

BACKGROUND: The prevalence of asthma and obesity in children has increased over the past several years, with obesity being associated with higher rates of asthma. In response to known disparities in asthma prevalence and morbidity, along with barriers to diagnosis, assessment and education, a comprehensive asthma sports camp series was developed and implemented. OBJECTIVE: The primary objective was to evaluate the effectiveness of utilizing a sports camp model to identify children with undiagnosed and uncontrolled asthma, and to provide recommendations for follow-up care. The secondary objectives were to identify the presence of and associations between related co-morbidities and risk factors for asthma morbidity such as obesity, hypertension and exposure to tobacco smoke; and to assess asthma medication use. METHODS: Six daylong camps at an inner-city university were offered to children 5-17 years of age over a period of two years. Asthma, body mass index, blood pressure (BP) and carbon monoxide screenings were conducted at each camp. RESULTS: In this sample, 43.7% of children had previously diagnosed asthma, and 12.6% were classified as having potential, undiagnosed asthma. Of the children with previously diagnosed asthma, 76% were considered uncontrolled. Thirty-eight percent were determined to be overweight or obese and 17% had elevated BP. CONCLUSIONS: An interdisciplinary sports camp model can be used to identify children with undiagnosed and uncontrolled asthma and cardiovascular risk factors; and to provide recommendations for follow-up care.

Effect of cetirizine on symptom severity and quality of life in perennial allergic rhinitis.

The effect of cetirizine on quality of life (QOL) in subjects with perennial allergic rhinitis (PAR) has been previously evaluated using generic instruments. While generic QOL tools are used across various conditions, disease-specific instruments evaluate the impact of treatment on areas that are affected by that particular condition. This study evaluated the effect of cetirizine on symptom severity and health-related QOL, using a disease-specific instrument, in adults with PAR. This randomized, double-blind, placebo-controlled study was conducted at 15 U.S. centers outside the pollen allergy season. After a 1-week placebo run-in period, qualified subjects aged 18-65 years with PAR were randomized to once-daily cetirizine 10 mg (n = 158) or placebo (n = 163) for 4 weeks. Change from baseline in total symptom severity complex (TSSC) and overall Rhinitis Quality of Life Questionnaire (RQLQ) scores were primary efficacy end points. Cetirizine produced significantly greater improvements in mean TSSC for each treatment week (p < 0.05) and for the entire 4-week treatment period (p = 0.005) compared with placebo. After 4 weeks, cetirizine-treated subjects reported significantly greater overall improvement in RQLQ scores compared with placebo-treated subjects (p = 0.004). After 1 week, cetirizine produced significant improvements in the nasal symptoms, practical problems, and activities RQLQ domain scores compared with placebo (p < 0.05). After 4 weeks, cetirizine-treated subjects reported significant reductions in these RQLQ domain scores and in emotion domain scores compared with placebo-treated subjects (p < 0.05). Cetirizine 10 mg daily produced significant improvements in symptom severity and allergic rhinitis-related QOL compared with placebo in adults with PAR.

The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) survey: patients' experience with allergen immunotherapy.

Allergen immunotherapy (AIT) is used for the treatment of allergic rhinoconjunctivitis as a subcutaneous injection (subcutaneous immunotherapy [SCIT]). Extracts used for SCIT are also used off-label to formulate a liquid delivered as sublingual drops (sublingual immunotherapy [SLIT]). This study was designed to survey patients' experiences and beliefs regarding SCIT and SLIT. People who had ever been diagnosed with nasal and/or ocular allergies were identified in a 2012 telephone survey of U.S. households. Respondents were asked questions about their or their child's use of SCIT and SLIT and their beliefs about AIT. Of 2765 respondents, 46.5% had ever heard of AIT and 22.7% had ever initiated it: 20.9% with SCIT and 1.8% with SLIT (p < 0.0001). The most frequently cited reason for beginning AIT was that symptoms were unresolved with other medications (SCIT, 32.1%; SLIT, 14.0%). Some or full symptom relief was reported by 74.9% of respondents treated with SCIT and 66.0% of those treated with SLIT (p = 0.17 for SCIT versus SLIT). Approximately one-third of respondents who had ever heard of or had been treated with AIT said "don't know" when asked if immunotherapy controls allergy symptoms for years (33.6%), is a very safe treatment (29.3%), or can cure allergy symptoms (27.5%). Effective relief of allergy symptoms was cited most often as the primary benefit of SCIT (37.8%) and convenience was the primary benefit of SLIT (14%). Only one-fifth of respondents had ever been treated with AIT, largely with SCIT. More than one-half of respondents had never heard of AIT and respondents' beliefs indicated a need for educational efforts.

Ocular and nasal allergy symptom burden in America: the Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys.

Previous nationwide surveys of allergies in the United States have focused on nasal symptoms, but ocular symptoms are also relevant. This study determines the effects of ocular and nasal allergies on patients' lives. Telephone surveys of randomly selected U.S. households (the patient survey) and health care providers (provider survey) were conducted in the United States in 2012. Study participants were 2765 people ≥5 years of age who had ever been diagnosed with nasal or ocular allergies and 500 health care providers in seven specialties. Respondents to the patient survey reported a bimodal seasonal distribution of allergy symptoms, with peaks in March to May and September. Nasal congestion was the most common of the symptoms rated as "extremely bothersome" (39% of respondents), followed by red, itchy eyes (34%; p = 0.84 for difference in extreme bothersomeness of nasal and ocular symptoms). Twenty-nine percent of respondents reported that their or their child's daily life was impacted "a lot" when allergy symptoms were at their worst. Workers rated their mean productivity at 29% lower when allergy symptoms were at their worst (p < 0.001 compared with no symptoms). Providers reported that itchy eyes was the symptom causing most patients to seek medical treatment by pediatricians (73%), ophthalmologist/optometrists (72%), and nurse practitioners or physician assistants (62%), whereas nasal congestion was the symptom causing most patients to seek treatment from otolaryngologists (85%), allergist/immunologists (79%), and family medicine practitioners (64%). Ocular and nasal allergy symptoms substantially affected patients' lives and were comparable in their impact.

A critical review of the effects of inhaled corticosteroids on growth.

Inhaled corticosteroids (ICSs) are an effective therapy for the treatment of persistent asthma of all severities because they reduce symptoms, improve lung function, and reduce underlying inflammation. Although ICSs are generally safe for long- term use, there is concern among physicians and patients about potential systemic side effects, including growth inhibition in children. This continued concern of systemic side effects may negatively affect the compliance to ICS treatment. Based on the current guidance to industry from the Food and Drug Administration (FDA), some efficacy and safety studies on ICSs performed in the 1990s had limitations in their design to evaluate the effect of ICS therapy on growth as a safety end point. A review of studies performed with currently available ICSs and their level of conformance with the FDA guidance are presented in this article. The 1-year studies show a small, dose-dependent effect of most ICSs on childhood growth, with some differences across various ICS molecules and across individual children. Some ICSs at the doses studied did not affect childhood growth using rigorous study designs. Most studies did not conform completely with the FDA guidance. The data on effects of childhood ICS use on final adult height are conflicting, but one recent well-designed study showed an effect, clearly warranting additional studies.

Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents.

BACKGROUND: Allergy immunotherapy tablet (AIT) treatment might be a safe and convenient form of specific immunotherapy but it has not been investigated in North American children and adolescents. OBJECTIVE: We sought to investigate the efficacy and safety of timothy grass AIT treatment in North American children/adolescents with grass pollen-induced allergic rhinoconjunctivitis (ARC) with or without asthma. METHODS: Three hundred forty-five subjects (5-17 years old) were randomized to once-daily grass AIT treatment (2,800 bioequivalent allergen units, 75,000 standardized quality tablet, approximately 15 µg of Phl p 5) or placebo approximately 16 weeks before the 2009 grass pollen season (GPS). Treatment continued through the GPS. Daily symptoms and allergy rescue medication use were recorded. The primary end point was the total combined score (TCS) of the daily symptom score (DSS) and daily medication score (DMS) for the entire GPS. DSS, DMS, Rhinoconjunctivitis Quality of Life Questionnaire score, and Phl p 5-specific IgG4 and IgE-blocking factor levels were secondary end points. Safety was assessed through adverse events. RESULTS: Eighty-nine percent of subjects were multisensitized. TCS, DSS, DMS, and Rhinoconjunctivitis Quality of Life Questionnaire score versus placebo improved 26% (P = .001), 25% (P = .005), 81% (P = .006), and 18% (P = .04). Phl p 5-specific IgG4 and IgE-blocking factor levels were significantly higher at the peak and end of the GPS (P < .001). Treatment was well tolerated. Adverse events were generally mild and transient. Although no investigator-assessed systemic allergic reactions were reported, 1 grass AIT-treated subject experienced an event indicating a systemic reaction (lip angioedema, dysphagia, and cough). CONCLUSIONS: Use of once-daily timothy grass AIT treatment effectively treats timothy grass (cross-reactive with Festucoideae grasses) pollen-induced ARC in North American children 5 years and older. Given its convenient administration, lack of dose build-up requirement, safety profile, and efficacy, AIT treatment might become an important addition to the North American ARC treatment armamentarium.

Is This Medication Safe for My Child? How to Discuss Safety of Commonly Used Medications With Parents.

All drugs have potential side effects, but thoughtful use can maximize benefits while minimizing risks. Children should not be considered just small adults regarding drug safety because their growth and development are discordant with their ability to sense and self-report drug side effects. Detecting side effects requires vigilance and education from prescribers to parents, who are tasked with monitoring their child over time. A drug's safety profile is published in the package label after pivotal trials are conducted in relatively small and sometimes narrow segments of the population during the U.S. Food and Drug Administration approval process. Drug safety profiles can change as data from postmarketing reports and long-term monitoring during phase IV trials emerge. As such, prescribers are obligated to maintain current understanding of any changes to drug labels. Discussing potential side effects, monitoring, and when to report concerns can be a time-consuming process during patient encounters. This review offers current information regarding potential side effects of some of the most commonly used medications for allergic conditions, asthma, and atopic dermatitis. This information and discussion will hopefully assist clinicians in their conversations with parents, including advice surrounding prescribing medication to minimize adverse effects, parental monitoring, and documentation.

Sublingual immunotherapy in patients with allergic rhinoconjunctivitis.

Sublingual immunotherapy (SLIT) is a well-established treatment option for allergic rhinitis in several European countries, but it is considered investigational in the United States. Studies conducted in Europe provided a large body of evidence supporting the safety and efficacy of SLIT, but those studies used allergen products that are different from those that are likely to be approved in the United States, and many of them were not controlled, randomized, double-blinded trials. This review summarize research conducted on the efficacy, safety, and mechanisms of SLIT published during the past year, with a focus on ragweed and grass antigens. Results of recent US studies document the safety and efficacy of SLIT and have started to yield insight into the mechanisms of SLIT.

Effects of inhaled mometasone furoate on growth velocity and adrenal function: a placebo-controlled trial in children 4-9 years old with mild persistent asthma.

OBJECTIVE: To assess the effects of long-term mometasone furoate delivered via a dry powder inhaler (MF-DPI) on growth velocity and hypothalamic-pituitary-adrenal axis function in children with asthma. STUDY DESIGN: Children aged 4-9 years with asthma (n = 187) were randomized to MF-DPI 100 µg (delivered dose; actuated dose is 110 µg) once daily in the morning (QD AM), 100 µg twice daily (BID), 200 µg QD AM, or placebo for 52 weeks followed by a 3-month follow-up period. The primary outcome was growth velocity calculated from stadiometric heights recorded at each visit. Secondary outcomes included serum and 12-h urinary cortisol, serum osteocalcin, and urinary N-telopeptide. RESULTS: MF-DPI 100 µg QD AM treatment did not significantly affect growth velocity compared with placebo (-0.10 ± 0.31 cm/y, p = 0.76). When the effect of a total daily dose of 200 µg MF-DPI on growth velocity was examined, no significant effect was demonstrated for MF-DPI 100 µg BID compared with placebo (-0.64 ± 0.39 cm/y, p = 0.10), although the change in mean growth velocity with MF-DPI 200 µg QD AM reached statistical significance (-0.70 ± 0.29 cm/y, p = 0.02). The effects of all examined doses of MF-DPI on mean plasma cortisol levels were similar to cortisol changes seen in the placebo group, suggesting an absence of drug-related effects. No differences in 12-h urinary cortisol or other outcomes were observed between groups. CONCLUSIONS: One year of treatment with a total daily dose of 100 µg of MF-DPI in the morning resulted in no significant difference, whereas a total daily dose of 200 µg of MF-DPI was associated with some changes in growth velocity when compared with placebo. The differences in growth velocity, and the absence of drug-related cortisol effects, support the use of a total daily dose of 100 µg of MF-DPI in children aged 4-9 years with mild persistent asthma.

Complications and Health Care Resource Utilization Associated with Systemic Corticosteroids in Children and Adolescents with Persistent Asthma.

BACKGROUND: Limited comparative data are available on the impact of systemic corticosteroid (SCS) use in children and adolescents. OBJECTIVE: To determine if asthmatic children and adolescents treated with SCS have a higher likelihood of developing complications versus those not receiving SCS and to examine health care resource utilization (HCRU) in this population. METHODS: A retrospective study of data from children and adolescents with persistent asthma retrieved from the MarketScan database, a large US health claims data set, for the period 2000 to 2017 was performed. Propensity score matching was used to pair patients in the SCS and control cohorts. For complications, SCS subgroups (≥4 or 1-3 annual prescriptions) were compared with asthmatic controls without SCS using logistic regression, and for HCRU, cohorts were compared using negative binomial regression. RESULTS: A total of 67,081 patients were included (SCS: 23,898; control: 43,183). The odds of having a complication were 2.9 (95% confidence interval [CI], 2.5-3.2; P < .001) and 1.6 (95% CI, 1.6-1.7; P < .001) times higher in the ≥4 and 1 to 3 SCS groups, respectively, in the first year of follow-up versus controls. For asthma-related hospitalizations, the incidence rate ratio (IRR) was 6.9 (95% CI, 5.6-8.6) and 3.1 (95% CI, 2.8-3.4) times greater in the ≥4 SCS and 1 to 3 SCS groups, respectively, versus controls; for asthma-related emergency department visits, IRR was 5.0 (95% CI, 4.4-5.6) and 2.9 (95% CI, 2.7-3.0) times greater, respectively, versus controls (all P < .01). CONCLUSION: Children and adolescents receiving SCS for persistent asthma have an increased risk of developing complications and have greater HCRU in the first year of follow-up versus those without SCS exposure.

Effect of therapeutic doses of mometasone furoate on cortisol levels in children with mild asthma.

Corticosteroids are the foundation of pharmacologic treatment for children with asthma. However, high-dose inhaled corticosteroid treatment can cause hypothalamic-pituitary-adrenal (HPA) axis suppression. We investigated the effect of three doses of mometasone furoate administered via dry-powder inhaler (MF-DPI) on the HPA axis in children. Fifty children (6-11 years) with mild asthma of > or =6 months' duration were randomized to MF-DPI, 100 (n = 13), 200 (n = 13), or 400 micrograms b.i.d. (n = 12), or placebo (n = 12) for 29 days. The primary end point was change from baseline in the 12-hour area under the plasma-cortisol-concentration-time curve (AUC). Secondary parameters included plasma cortisol response to cosyntropin stimulation and 24-hour urinary free cortisol concentrations. Compared with placebo, AUC changes associated with treatments of MF-DPI, 100 or 200 micrograms b.i.d., were not significant, whereas a significant change was observed with MF-DPI, 400 micrograms b.i.d. (27%; p = 0.05). Responses to cosyntropin stimulation and urinary cortisol measurements were similar to placebo with all MF-DPI doses. All regimens were well tolerated. MF-DPI did not have a significant effect on plasma or urinary cortisol levels at doses up to 200 micrograms b.i.d. in children with mild asthma. Higher MF-DPI doses may potentially suppress the HPA axis.

Allergic rhinitis, histamine, and otitis media.

Otitis media (OM) is a common and costly medical condition, especially in children. Most episodes of OM are associated with an upper respiratory viral infection and are short-lived and self-limiting with or without medical treatment. However, chronic OM with effusion (OME) has significant sequelae, is refractory to most medical treatments, and frequently requires surgical intervention. The pathophysiology of OME is complex and involves both eustachian tube (ET) dysfunction and middle ear pressure dysregulation. OM likely results from an increase in blood flow to and, thus, gas loss from the middle ear, in combination with a dysfunctional ET that can not resupply that gas. These processes could be induced by viral and/or allergen-driven inflammation. A large body of epidemiologic and mechanistic evidence supports a role for allergic rhinitis as a risk for OM. Indeed, evidence also supports a role for histamine in both conditions. However, not all such evidence is supportive of this relationship and a causal relationship between the two conditions has not been definitively proven. Moreover, therapeutic trials using common allergy therapies have either not been conducted or showed no benefit in OM. This prompted the 2004 clinical practice guidelines on OM to conclude that no recommendations could be made for "... allergy management as a treatment for OME based on insufficient evidence of therapeutic efficacy or a causal relationship between allergy and OME." Nonetheless, given the strong likelihood of allergy as a risk factor for OM, allergic rhinitis patients should be evaluated for OM and patients with OME should be considered for an allergy evaluation. If significant allergic rhinitis is diagnosed in a patient with OME, it should be treated aggressively (as in any case of moderate to severe allergic rhinitis) until further studies are conducted. No definitive conclusions about a role for food allergy in causing or treating OM can be made. Clearly, more studies are needed to examine the relationship between these two important conditions.