Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy.

Background: Immunotherapy is promising as an efficacious treatment for food allergy. Other food allergy treatments are also under development. However, adverse allergic events during treatment, as well as during oral food challenges, are common and reporting is not standardized.

Changes in Neutrophil-Lymphocyte or Platelet-Lymphocyte Ratios and Their Associations with Clinical Outcomes in Idiopathic Pulmonary Fibrosis.

Identification of prognostic and predictive biomarkers in idiopathic pulmonary fibrosis (IPF) could aid assessment of disease severity and prediction of progression and response to treatment. This analysis examined reference ranges for neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in IPF, and the relationship between NLR or PLR changes and clinical outcomes over 12 months. This post hoc analysis included patients with IPF from the Phase III, double-blind trials of pirfenidone, ASCEND (NCT01366209) and CAPACITY (NCT00287716 and NCT00287729).

Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry.

Background: Pragmatic use of the anti-fibrotic medications pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) in the United States (US) has not been studied and may be different from international settings due to structural differences between health care systems. This study examined the relationship between patient- and site-level characteristics and anti-fibrotic (a) use and (b) selection.

Methods: Data from the Pulmonary Fibrosis Foundation Patient Registry was used to perform univariable and multivariable regressions with generalized linear mixed models.

Physician characteristics associated with treatment initiation patterns in idiopathic pulmonary fibrosis.

Pirfenidone and nintedanib are oral antifibrotic agents approved for the treatment of idiopathic pulmonary fibrosis (IPF). Real-world data on factors that influence IPF treatment decisions are limited. Physician characteristics associated with antifibrotic therapy initiation following an IPF diagnosis were examined in a sample of US pulmonologists.

Pirfenidone in patients with idiopathic pulmonary fibrosis and more advanced lung function impairment.

Background: Patients with idiopathic pulmonary fibrosis (IPF) demonstrate a range of lung function impairment. However, the efficacy of antifibrotics compared with placebo has not been assessed in patients with more advanced disease. This post-hoc analysis investigated the efficacy and safety of pirfenidone versus placebo in patients with IPF and more advanced lung function impairment, defined as percent predicted forced vital capacity (%FVC) < 50% and/or percent predicted carbon monoxide diffusing capacity <35%.

Efficacy of Pirfenidone in the Context of Multiple Disease Progression Events in Patients With Idiopathic Pulmonary Fibrosis.

Background: Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown.

Methods: Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis.

Dose modification and dose intensity during treatment with pirfenidone: analysis of pooled data from three multinational phase III trials.

Introduction: Temporary dose modifications, such as reductions or interruptions, may allow patients to better manage adverse events (AEs) associated with pirfenidone use and continue treatment for idiopathic pulmonary fibrosis (IPF). However, the impact of such dosing adjustments on efficacy and safety is uncertain.

Methods: Patients randomised to receive treatment with pirfenidone 2403 mg/day or placebo in the Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY (Study 004 (NCT00287716)) and Study 006 (NCT00287729))) and Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND (Study 016 (NCT01366209)) trials were included in the analysis (n=1247).

Effect of pirfenidone on gastric emptying in a rat model.

Introduction: Gastrointestinal (GI) adverse events (AEs) are commonly reported in patients with idiopathic pulmonary fibrosis who are treated with pirfenidone. Taking pirfenidone with a substantial amount of food or dividing the dose over the course of a meal has been reported to reduce the frequency of GI AEs in clinical practice. In humans, the maximum plasma concentration (C) of pirfenidone was reduced when the drug was taken with food compared with the fasting state, and the lower C was associated with a reduction in GI AE rates.

Real-World Practice Patterns for Prevention and Management of Potential Adverse Events with Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis.

Introduction: Pirfenidone is an oral antifibrotic agent approved for idiopathic pulmonary fibrosis (IPF). Real-world data on adverse event (AE) management for pirfenidone are limited. Strategies for managing potential antifibrotic therapy AEs were examined in a sample of US pulmonologists.

Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO.

Background: Patients included in clinical trials do not necessarily reflect the real-world population.

Objective: To understand the characteristics, including disease and comorbidity burden, of patients with asthma receiving omalizumab in a real-world setting.

Methods: The Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (PROSPERO) was a US-based, multicenter, single-arm, and prospective study.

Valved Holding Chambers and In Vitro Metered Dose Inhaler Performance: Effects of Flow Rate and Inhalation Delay.

Background: Multiple factors may influence the performance of a metered dose inhaler (MDI) when used with a valved holding chamber (VHC or "spacer").

Methods: Andersen Cascade Impactor measurements were conducted for three MDI products and two different VHCs using a specially designed system that accommodated variable delay times between MDI actuation and introduction of the aerosol into the impactor, and allowed reduced flow through the VHC while the impactor was operated at 28.3 L/min.

Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products.

Importance: All intravenous (IV) iron products are associated with anaphylaxis, but the comparative safety of each product has not been well established.

Objective: To compare the risk of anaphylaxis among marketed IV iron products.

Design, Setting, And Participants: Retrospective new user cohort study of IV iron recipients (n = 688,183) enrolled in the US fee-for-service Medicare program from January 2003 to December 2013.

International Guidelines for Bioequivalence of Locally Acting Orally Inhaled Drug Products: Similarities and Differences.

International regulatory agencies have developed recommendations and guidances for bioequivalence approaches of orally inhaled drug products (OIDPs) for local action. The objective of this article is to discuss the similarities and differences among these approaches used by international regulatory authorities when applications of generic and/or subsequent entry locally acting OIDPs are evaluated. We focused on four jurisdictions that currently have published related guidances for generic and/or subsequent entry OIDPs.

Developing an in vitro understanding of patient experience with hydrofluoroalkane-metered dose inhalers.

As a result of the Montreal Protocol on Substances that Deplete the Ozone Layer, manufacturers of metered dose inhalers began reformulating their products to use hydrofluoroalkanes (HFAs) as propellants in place of chlorofluorocarbons (CFCs). Although the new products are considered safe and efficacious by the US Food and Drug Administration (FDA), a large number of complaints have been registered via the FDA's Adverse Events Reporting System (FAERS)-more than 7000 as of May 2013. To develop a better understanding of the measurable parameters that may, in part, determine in vitro performance and thus patient compliance, we compared several CFC- and HFA-based products with respect to their aerodynamic performance in response to changes in actuator cleaning interval and interactuation delay interval.

Impact of study design on the evaluation of inhaled and intranasal corticosteroids' effect on hypothalamic-pituitary-adrenal axis function.

In part I of this review, an overview of the designs of hypothalamic-pituitary-adrenal (HPA) axis studies in the setting of inhaled corticosteroids (ICS) or intranasal corticosteroids (INS) use was discussed. Part II provides detailed discussion on the HPA axis evaluation results for each common ICS and INS, and how these results are possibly affected by the factors of study design. Significant adrenal suppression at conventional ICS/INS doses appears to be rare in clinical settings.

Impact of study design on the evaluation of inhaled and intranasal corticosteroids' effect on hypothalamic-pituitary-adrenal axis function, part I: general overview of HPA axis study design.

Inhaled and intranasal corticosteroids (ICS and INS) are among the mainstays of the treatment for asthma and allergic rhinitis, respectively, and also carry the potential to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Several important factors affect the interpretability of trials investigating the impact of ICS and INS on the HPA axis. This paper reviews 106 published clinical trials, peer-reviewed articles, and New Drug Application reviews of approved ICS and INS, using MEDLINE and Drugs@FDA database.

Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma.

Background: Risk of anaphylaxis is included in the prescribing information for omalizumab, but the nature of these reactions merits further elaboration.

Objective: To describe cases of anaphylaxis associated with omalizumab administration in patients with asthma.

Methods: We reviewed spontaneous postmarketing adverse event reports submitted to the US Food and Drug Administration's Adverse Event Reporting System database and to the manufacturers of omalizumab and cases published in the literature through December 2006.

Long-term immunologic effects of broad-spectrum aeroallergen immunotherapy.

Background: Limited data exist regarding extended, long-term immunologic effects of immunotherapy in polysensitized individuals. To study possible long-term effects, skin tests and specific IgE levels were obtained from subjects who had previously received broad-spectrum aeroallergen immunotherapy years before.

Methods: Eighty-two subjects (78% male, mean age 23 years) previously enrolled in a randomized, placebo-controlled trial of immunotherapy for treatment of childhood allergic asthma were reevaluated in adulthood (mean follow-up interval, 10.

Irreversible lung function deficits in young adults with a history of childhood asthma.

Background: Asthma, traditionally characterized as reversible airway obstruction, might lead to structural changes and permanent impairment.

Objective: We sought to study the frequency, severity, and reversibility of pulmonary deficits in adults with a history of moderate-to-severe childhood allergic asthma.

Methods: Subjects (n = 121) previously enrolled in a randomized trial of immunotherapy for childhood asthma were recalled.

Adult asthma severity in individuals with a history of childhood asthma.

Background: Childhood asthma can have a range of outcomes in adulthood.

Objective: To identify clinical features and exposures associated with persistence and severity of childhood asthma in adulthood.

Methods: Eighty-five of 121 subjects previously enrolled in a study of immunotherapy for childhood allergic asthma (age 5-12 years) were re-evaluated with allergy skin testing, spirometry, and interviews about asthma symptoms and medications.