Allergen Inhalation Challenge, Refractoriness, and the Effects of Ibuprofen

Background: Bronchoprovocation challenges use direct and indirect acting stimuli to induce airflow obstruction. Indirect stimuli, either non-allergic/non-IgE mediated (e.g. exercise, mannitol) or allergic/IgE mediated (i.e. allergen inhalation model), trigger mast cells to release bronchoconstricting mediators (e.g. cysteinyl leukotrienes, histamine). Performing repeat challenges within a short timeframe (e.g. 3 hours) with non-allergic indirect stimuli results in a diminished refractory response to the second challenge. Cross refractoriness occurs between indirect stimuli. It follows that repeat bronchoprovocation with allergen might exhibit refractoriness that might be altered by ibuprofen. This study was designed to assess the response to a second allergen challenge performed 24 hours after an initial one to determine if the response is refractory. If refractoriness developed, the study aimed to determine whether a single dose of ibuprofen would alter the refractory response to the second allergen challenge. The study design also allowed for the assessment of the effect of ibuprofen on allergen challenge outcomes, including indices of airway inflammation. Methods: Thirteen mild atopic asthmatics were enrolled in a randomized, double-blind, placebo controlled, cross-over study. Ibuprofen (400mg) or placebo was administered one hour prior to the first of two allergen challenges performed 24 hours apart. Blood and sputum eosinophils, airway responsiveness to methacholine, and levels of fractional exhaled nitric oxide were assessed before and seven hours after each allergen challenge. All data were log transformed, and differences in geometric means were analyzed by paired t-tests. Results: After placebo, early asthmatic responses for the two challenges were not significantly different (p = 0.82). A single 400 mg dose of ibuprofen decreased both the early (p = 0.03; n = 12) and late asthmatic responses (p = 0.03; n = 3) Conclusion: Allergen challenges conducted 24 hours apart do not exhibit refractoriness. A single dose of ibuprofen inhibits early and late asthmatic responses to allergen bronchoprovocation. Ibuprofen should be withheld for at least 24 hours prior to investigations utilizing allergen bronchoprovocation

The utility of psychotropic drugs on patients with Fetal Alcohol Spectrum Disorder (FASD): a systematic review

BACKGROUND: Treatment of the complications arising from Prenatal Alcohol Exposure (PAE) has largely been focused on psychosocial and environmental approaches. Research on the use of medications, especially psychotropic medications, has lagged behind. OBJECTIVES: This systematic review sought to investigate psychotropic medication related findings and outcomes in those diagnosed with Fetal Alcohol Spectrum Disorder (FASD). METHODS: Comprehensive searches were conducted in seven major databases (Medline/PubMed, Scopus, Web of Knowledge, Embase, PsycINFO, Cochrane Library, and PsycARTICLES) up to February 2017. Key search terms with synonyms were mapped on these databases. There were no timeline restrictions and no grey literature searches. Two reviewers independently assessed 25 studies that met the inclusion criteria. Most studies were reviews of treatment and retrospective case series. RESULTS: Two crossover randomized trials were reported, and the findings were not amenable to meta-analysis. Several conditions (depression, agitation, seizures, and outburst) combined with the most frequent presentation, ADHD, to represent the rationale for prescribing psychotropic medications. Second-generation antipsychotics were found to improve social skills, but the paucity of data limited the extent of clinical guidance necessary for the field. CONCLUSIONS: The systematic review showed that there are some clinical evidence displaying the validity of psychopharmacological interventions in people with FASD, which varies across the spectrum of disease severity, age, and gender. There is a need for more clinical evidence-based studies in addition to clinical expert opinions to substantiate an optimal ground for individualized management of FASD. The study protocol for this review was registered in PROSPERO with registration number CRD42016045703