FDA Public Workshop Summary-Addressing Challenges in Inhaled Antifungal Drug Development.

Allergic bronchopulmonary aspergillosis and invasive fungal diseases represent distinct infectious entities that cause significant morbidity and mortality. Currently, administered inhaled antifungal therapies are unapproved, have suboptimal efficacy, and are associated with considerable adverse reactions. The emergence of resistant pathogens is also a growing concern. Inhaled antifungal development programs are challenged by inadequate nonclinical infection models, highly heterogenous patient populations, low prevalence rates of fungal diseases, difficulties defining clinical trial enrollment criteria, and lack of robust clinical trial endpoints. On September 25, 2020, the US Food and Drug Administration (FDA) convened a workshop with experts in pulmonary medicine and infectious diseases from academia, industry, and other governmental agencies. Key discussion topics included regulatory incentives to facilitate development of inhaled antifungal drugs and combination inhalational devices, limitations of existing nonclinical models and clinical trial designs, patient perspectives, and industry insights.

Respiratory inductance plethysmography in healthy 3- to 5-year-old children.

STUDY OBJECTIVES: Because of the challenges of using standard measurements such as spirometry to measure respiratory function in 3- to 5-year-old children, there may be a role for respiratory inductive plethysmography (RIP), which is noninvasive and requires minimal subject cooperation. In this study, we described normative values of thoracoabdominal motion and timing mechanics in 3- to 5-year-old children, and hypothesized positional dependence of these measurements in this age group. DESIGN: We measured relative thoracoabdominal motion during tidal breathing using the phase angle (Phi), the labored breathing index, and the phase relation during the total breath and timing mechanics with the ratio of time to peak tidal expiratory flow to expiratory time (TPTEF/TE). SETTING: Preschools within the greater Philadelphia area and the Pulmonary Office of The Children's Hospital of Philadelphia. PATIENTS OR PARTICIPANTS: Fifty healthy children between 3 years and 5 years of age. INTERVENTIONS: RIP. MEASUREMENTS AND RESULTS: All measures varied with position. Thoracoabdominal motion was nearly synchronous in the sitting position and most asynchronous in the supine position (Phi, 15.7 +/- 4.0 degrees vs 56.1 +/- 4.3 degrees, respectively; p < 0.001). This also led to an increase in the TPTEF/TE from the sitting to the supine positions (30.3 +/- 1.4% vs 37.0 +/- 1.6%, respectively; p < 0.001). Measurements of thoracoabdominal motion and timing mechanics did not change with age, weight, height, or gender. CONCLUSIONS: We conclude that the positional dependence of these measurements is due to the alteration in respiratory mechanics between the sitting, standing, and supine positions. We further conclude that if RIP is to be a useful longitudinal measure of respiratory function in this age range, comparison measurements should be made in the same position.