Anupama Kewalramani

Implementation of an Infectious Disease Fellow-Managed Penicillin Allergy Skin Testing Service

An inpatient penicillin allergy skin testing program can be successfully managed by infectious diseases fellows under attending supervision offering a novel practice area for infectious diseases practitioners.

The impact of food allergy on asthma

Food allergy is a potentially severe immune response to a food or food additive. Although a majority of children will outgrow their food allergies, some may have lifelong issues. Food allergies and other atopic conditions, such as asthma, are increasing in prevalence in Western countries. As such, it is not uncommon to note the co-existence of food allergy and asthma in the same patient. As part of the atopic march, many food allergic patients may develop asthma later in life. Each can adversely affect the other. Food allergic patients with asthma have a higher risk of developing life-threatening food-induced reactions. Although food allergy is not typically an etiology of asthma, an asthmatic patient with food allergy may have higher rates of morbidity and mortality associated with the asthma. Asthma is rarely a manifestation of food allergy alone, but the symptoms can be seen with allergic reactions to foods. There may be evidence to suggest that early childhood environmental factors, such as the mother’s and child’s diets, factor in the development of asthma; however, the evidence continues to be conflicting. All food allergic patients and their families should be counseled on the management of food allergy and the risk of developing co-morbid asthma.

Automated actuation of nasal spray products: determination and comparison of adult and pediatric settings

Objective: To determine and compare patient-relevant settings for automated nasal spray actuation stations from adult and pediatric hand data. Methods: Twenty adults and 20 pediatric participants were asked to spray Flonase® Nasal Spray six times in a Hand Actuation Monitor, which records force and displacement data in 5-ms increments. Settings for force- and velocity-controlled actuation stations were determined from the data using a predefined set of calculations. Results: For force-controlled settings, hand spraying by children resulted in lower actuation forces, and longer force rise, hold and fall times. Pediatric velocity-controlled actuator settings were lower for travel, compression velocity, and release velocity compared with adults. The pediatric spray weight recorded during hand spraying was significantly lower than the spray weight generated by adult participants. Adult participants were able to generate full sprays with each attempt, whereas 11 out of 120 actuations performed by pediatric participants resulted in partial and ‘no spray’ events. No differences in spray weight were detected in participants who chose to actuate the nasal spray using both hands. Conclusions: A predefined set of calculations was used to determine patient-relevant settings from force and displacement hand data for force- and velocity-controlled automated actuation stations. This study determined and quantified, for the first time, the differences in hand spraying between adults and children.

Clinical Effects of Probiotics Are Associated With Increased Interferon-γ Responses in Very Young Children With Atopic Dermatitis

Prescott SL, Dunstan JA, Hale J, Breckler L, et al. Clin Exp Allergy. 2005;35:1557–1564 PURPOSE OF THE STUDY. The authors recently demonstrated that young children with moderate-to-severe atopic dermatitis (AD) had significant clinical improvement in the severity and extent of their disease with the use of probiotics. The purpose of this study was to assess the effects of probiotics on underlying immune function and relate that to clinical improvement. STUDY POPULATION. Fifty-six Australian children aged 6 to 23 months with moderate-to-severe AD (based on a modified scoring AD [SCORAD] index of ≥25). METHODS. Subjects were randomly assigned to receive probiotics (1 × 109 colony-forming units of Lactobacillus fermentum; n = 26) or placebo (n = 27) twice daily for 8 weeks. Peripheral blood mononuclear cells were isolated from 53 children at baseline and at 8 and 16 weeks (8 weeks after the supplementation period). Cytokine (interleukin 5 [IL-5], IL-6, IL-10, IL-13, interferon γ [IFN-γ], and tumor necrosis factor α [TNF-α]) responses to allergens (egg ovalbumin, β-lactoglobulin, and house dust mite), vaccines (tetanus toxoid and diphtheria toxoid), intestinal flora (heat-killed L fermentum), skin flora (heat-killed Staphylococcus aureus), S aureus enterotoxin B (SEB), and mitogen (phytohemagglutinin) were assessed. RESULTS. The children who received probiotics showed a significant increase in T-helper 1 cytokine IFN-γ responses to SEB and phytohemagglutinin at 8 and 16 weeks compared with baseline. The increase in IFN-γ response to SEB was directly proportional to the decrease in the severity of AD during the study period. After supplementation with probiotics (week 8) children had significantly higher TNF-α responses to heat-killed L fermentum and heat-killed S aureus compared with those in the placebo group. This was not sustained at 16 weeks. IL-13 (a T-helper type 2 cytokine) responses to ovalbumin decreased significantly during the supplementation period, but this was not sustained after its discontinuation. No other effects of probiotics were seen on allergen-specific responses. CONCLUSIONS. Probiotics led to an increase in IFN-γ responses to nonspecific stimuli (SEB and phytohemagglutinin) and an increase in TNF-α responses to skin and intestinal flora. Clinical improvement in AD severity with probiotics was associated with significant increases in the T-helper 1 IFN-γ responses and altered responses to skin and intestinal flora but not consistent effects on allergen-specific responses. REVIEWER COMMENTS. It is interesting to note that this study did not show any consistent effects of probiotics on allergen-specific responses, which suggests more of an impact on innate immune pathways rather than allergen-specific ones. The results of this study show some promise for the use of probiotics in children with AD. However, there are many variables that need to be addressed, such as impact of underlying food allergy, exposure to antibiotics, and environmental factors. Larger studies are needed to further demonstrate clinical efficacy (short-term and long-term), to determine optimal timing and dosing of treatment, to further investigate immunologic mechanisms, and to determine the impact of probiotic treatment on later development of other atopic disorders (eg, asthma) in young children with AD.

Rapid Effects of Inhaled Corticosteroids in Acute Asthma: An Evidence-Based Evaluation

Rodrigo GJ. Chest. 2006;130:1301–1311 PURPOSE OF THE STUDY. To analyze available evidence on the early (1–4 hours) clinical impact of inhaled corticosteroids (ICSs) for adults and children with an acute asthma exacerbation in the emergency department (ED). STUDY POPULATION. A total of 470 adults (≥18 years old) and 663 children (6 months to 17 years old) seen in the ED or an equivalent care setting with a diagnosis of acute asthma. METHODS. A search was conducted of Medline (1966 to February 2006) and Embase (1974 to February 2006) databases, the Cochrane Controlled Trials Register, bibliographic reviews of primary research, review articles, and citations from texts. Randomized, double-blind, placebo-controlled trials conducted in the ED or equivalent care setting comparing ICSs to placebo or systemic corticosteroids were analyzed. Primary outcome measures included hospital admission and ED discharge rates. Secondary outcomes were spirometric measures, clinical symptoms, heart and respiratory rates, oxygen saturation, and adverse effects, all measured from 1 to 4 hours of the protocol. RESULTS. Fifty articles were identified on the initial search, and 17 of these randomized, double-blind, placebo-controlled studies (6 included adults and 11 included children) met the above-stated criteria. Eight studies compared ICSs with placebo, 3 compared ICSs plus systemic corticosteroids (SCSs) with SCSs, and 6 compared ICSs with SCSs. ICS doses used in the trials ranged from 400 μg to 2 mg dispensed by inhaler or nebulizer, and the ICSs used included fluticasone (3 studies), budesonide (8), flunisolide (2), dexamethasone (1), and beclomethasone (3). “Multiple-dose” protocols administered ≥3 doses of ICS at ≤30-minute intervals, and “single-dose” protocols administered ≤2 doses at ≤30-minute intervals or ≥1 dose at >30-minute intervals. Six studies examined the discharge rates 2 to 3 hours after multidose ICS treatment and found that a significantly greater proportion of ICS-treated patients were discharged early from the ED compared with those treated with either placebo or SCS (odds ratio: 4.7). Patients who received multiple ICS doses along with β agonists also had improvement in spirometric and clinical scores, with evidence of a dose-response relationship. There was a significantly lower admission rate in the patients treated with multiple-dose ICSs. The number of patients needed to treat with ICSs to prevent 1 hospital admission was 10. CONCLUSIONS. This study suggests that ICS treatment provides early beneficial effects (1–2 hours) when they were used in multiple-dose amounts administered in time intervals of ≤30 minutes. REVIEWER COMMENTS. This meta-analysis suggests that ICSs given early in multiple doses with β agonists may have a place in the ED for treatment of acute exacerbations of asthma. Previous studies have shown that asthmatic patients have a significant increase in airway mucosal blood flow compared with nonasthmatic patients. Repeated high doses of ICSs could work by decreasing airway blood flow, leading to enhanced bronchodilator action when administered simultaneously with β agonists. Additional study is needed to determine the most effective dose and delivery system in different patient populations to obtain an optimal effect.

Aerosol Therapy by Pressured Metered-Dose Inhaler-Spacer in Sleeping Young Children: To Do or Not to Do?

Esposito-Festen J, Ijsselstijn H, Hop W, van Vliet F, de Jongste J, Tiddens H. Chest. 2006;130:487–492 PURPOSE OF THE STUDY. To determine the feasibility of aerosol administration with a metered-dose inhaler (MDI) spacer in sleeping young children. STUDY POPULATION. Thirty children (18 boys) from the Netherlands between 6 and 23 months of age were treated with inhalation therapy twice per day for recurrent wheezing in the previous month. METHODS. Parents were trained to use a metal chamber (NebuChamber) with a face mask to administer 200 μg of budesonide aerosol. A filter was placed between the spacer and face mask to trap and then measure the aerosol inhaled from the spacer. The study included 1 run-in week and 2 test weeks. The families were visited at home 4 times in the 3 weeks. At the 1-week run-in, the parents practiced the procedure with a placebo MDI while the child was awake. In weeks 2 and 3, they administered 1 puff while the child was awake (awake administration), 1 puff before bedtime, and 1 puff while the child was asleep (sleep administration). Parents then were asked to score the childs asthma symptoms and degree of cooperation and the feasibility of administration. Filters were washed, and budesonide amounts were measured by high-performance liquid chromatography and spectrophotometry. RESULTS. Twenty-one children fully completed the study, and a total of 350 awake-administration filters and 331 sleep-administration filters were collected. The mean filter dose was significantly higher for awake administration (47% ± 26%) than that for sleep administration (16% ± 13%). The median variability dose for awake administration was 50%, whereas it was 110% for sleep administration. Poor cooperation was noted for 29% of the awake administrations. In 69% of the sleep administrations, the child woke up, and in 75% of these cases, the child was distressed. Twenty-two percent of parents reported mask-positioning problems while the child was sleeping. Mean symptoms scores were 1.4 ± 2.2 (0 = no symptoms, 4 = severe symptoms; maximum score = 12 for sum of cough, wheeze, and shortness of breath). CONCLUSIONS. Administering aerosol therapy during sleep has been suggested as a way to overcome cooperation problems in young children, but this study suggests that this is not the answer. REVIEWER COMMENTS. The study included 30 children, and only 21 completed the study; a larger study would need to be performed with design modifications. One significant concern about the study design is that the children did not receive active drug during the study because the design required capturing the drug in a filter to determine drug delivery (which may explain the high drop-out rate). Furthermore, the design of the study did not allow for a means to determine clinical efficacy or lung deposition of the drug. In the interim, pediatricians may want to reconsider recommending dosing of aerosolized medications during sleep.