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Characterizing respiratory exacerbations in primary ciliary dyskinesia

原发性纤毛运动障碍呼吸加重的特征

基本信息

批准号：
10655640
负责人：
THOMAS W FERKOL
金额：
$ 23.14万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10655640
关键词：
16S ribosomal RNA sequencing 2019-nCoV Absenteeism Acceleration Acute Airway Disease Ancillary Study Antibiotic Resistance Antibiotic Therapy Antibiotics Bacteria Biological Assay Bronchiectasis Characteristics Chronic Clinical Clinical Trials Complement Coughing Data Decision Making Detection Enrollment Fatigue Fever Fibrosis Frequencies Funding Future Gene Expression Gene Expression Profile Genetic Diseases Home Immune response Impairment Infection Inflammation Inflammatory Response Inherited Intervention Trial Knowledge Longitudinal Studies Lower Respiratory Tract Infection Lung diseases Measures Modeling Molecular Morbidity - disease rate Mucociliary Clearance Nose Obstructive Lung Diseases Outcome Parents Patients Persons Phenotype Pneumonia Population Predictive Value Prevention Primary Ciliary Dyskinesias Productivity Protocols documentation Rare Diseases Research Design Research Personnel Respiratory System Respiratory Tract Infections Role Sampling Schools Severities Source Specimen Sputum Surrogate Endpoint Testing Time United States Food and Drug Administration United States National Institutes of Health Universities Upper respiratory tract Viral Virus Virus Diseases Washington Work airway obstruction clinical outcome measures clinically significant cytokine design evidence based guidelines experience health care service utilization high risk improved microbial microbiome parent project pathogen prevent resistance gene respiratory respiratory virus risk stratification specific biomarkers transcriptomics trial design viral detection

项目摘要

ABSTRACT Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous, orphan disease characterized by pro- gressive upper and lower respiratory tract infections and inflammation. Similar to other suppurative lung dis- eases, people with primary ciliary dyskinesia experience episodic, acute respiratory exacerbations, clinically characterized by increasing productive cough, fever and fatigue, that are typically treated with antibiotics and increased airway clearance. Acute respiratory exacerbations cause significant morbidity and substantial health care utilization, school or work absenteeism, and in some suppurative airway diseases accelerate structural airway damage and airway obstruction. Given their negative impact on the lives of people with primary ciliary dyskinesia, exacerbations have been targets for interventional trials designed to establish evidence-based guide- lines for their prevention and treatment. However, the infectious precipitants that likely cause acute respiratory exacerbations are frequently undefined and could be important factors for clinical trials. This ancillary study will involve subjects with primary ciliary dyskinesia already enrolled in an NIH-funded parent longitudinal study RDCRN Protocol 5907) that is designed to define the key characteristics of respiratory exacerbations and eval- uate potential predictors and time to first exacerbations. The first Specific Aim will examine molecular approaches to detection of viruses and bacteria in patients with PCD to define the baseline microbial state and the microbial phenotype of respiratory exacerbations, using assays that can be performed on self-collected samples obtained in the home, which will test two complementary hypotheses, that the microbial phenotype of a baseline sputum sample can predict the frequency and severity of acute respiratory tract illnesses, and the microbial phenotype of a sputum sample obtained during an ARI can predict the severity of the episode. In the second Aim 2, we will use nasal gene expression profiles to characterize host response to acute respiratory tract illnesses, testing the hypothesis that assessment of the host response will distinguish between viral infections with and without clinical manifestations. This ancillary study that will enhance the parent project by further refining the characterization of respiratory tract exacerbations, and establish the feasibility of microbial phenotyping of subjects at baseline and during exacerbations on respiratory samples collected at home. We will examine the feasibility of microbial phe- notyping of subjects at baseline and during exacerbations, thus determining the role of infectious precipitants and inflammatory responses during respiratory tract exacerbations. Specifically, it will provide a highly detailed characterization of the bacteria and viruses causing acute exacerbations in the PCD population, providing pilot data that will better define respiratory tract exacerbations as a key endpoint for future clinical trials.

摘要