Multicenter International Cross-Sectional Evaluation of Pulmonary Alveolar Proteinosis Trial
- Conditions
- Pulmonary Alveolar Proteinosis
- Registration Number
- NCT03007134
- Lead Sponsor
- Children's Hospital Medical Center, Cincinnati
- Brief Summary
The purpose of this study is to (1) compare a technically improved assay with an existing assay used to measure serum anti-GM-CSF antibodies in stored serum samples previously obtained from patients diagnosed with either primary, secondary, congenital or idiopathic pulmonary alveolar proteinosis (PAP), other chronic diseases or disease-free, healthy individuals; (2) determine the prevalence and levels of anti-GM-CSF autoantibodies and (3) define the breadth of the autoimmune antibody responses in primary PAP patients from the United States, Japan, Australia, and Europe using previously collected serum samples; and (4) using a chart review approach, compare the clinical, radiologic and laboratory features of primary PAP patients to determine if differences exist among patients in these globally geographically distributed regions.
- Detailed Description
The Rare Lung Disease Consortium (RLDC), a group of geographically-dispersed clinical research sites, has been established to conduct collaborative clinical research regarding rare lung diseases. The collaborative work includes diagnostic, therapeutic and other studies in patients with pulmonary alveolar proteinosis (PAP), lymphangioleiomyomatosis (LAM), alpha-1 antitrypsin deficiency (AATD), or hereditary interstitial lung diseases. These patients can have delayed or incorrect diagnoses, and sub-optimal clinical management. The present protocol is focused to individuals with PAP.
PAP occurs as primary, secondary, congenital and idiopathic forms. RLDC investigators have previously shown that primary PAP is strongly associated with high levels of circulating, neutralizing anti-GM-CSF autoantibodies. Absence of GM-CSF bioactivity is thought to impair alveolar macrophage and blood neutrophil functions including reduced surfactant catabolism (alveolar macrophages - thought to result in surfactant accumulation in primary PAP) and immune dysfunction (neutrophil dysfunction, and possibly macrophage dysfunction - thought to increase the risk of infection in primary PAP). Secondary PAP is caused by an underlying condition believed to impair alveolar macrophage surfactant catabolism. Secondary PAP is related to other conditions, including myelogenous leukemias, infections and environmental exposures. Congenital PAP is caused by mutations in the genes encoding surfactant protein (SP)-B, SP-C or the ABCA3 transporter. Idiopathic PAP is that which results from unknown mechanisms. Anti-GM-CSF autoantibodies appear to be absent in secondary, congenital and idiopathic PAP.
This cross sectional study protocol is designed to evaluate the autoimmune aspect of PAP in patients that are currently being followed by clinical investigators in the Rare Lung Disease Consortium (RLDC). The study involves a retrospective chart review and serological analysis of preexisting, stored serum samples from individuals diagnosed with PAP. Thus, this study will not involve any direct interactions or contact with PAP patients or any other study participants. It will yield diagnostic information regarding the use of anti-granulocyte macrophage-colony stimulating factor (GM-CSF) autoantibody testing in patients with PAP. It will also yield information about the extent of the autoimmune response in primary PAP. In addition, the study will compare/contrast the clinical phenotypes of individuals with anti-GM-CSF autoantibody-positive PAP in various regions of the world. A stringent evaluation of the autoimmune aspects of PAP including rigorous anti-GM-CSF antibody testing will provide a better understanding of PAP and is expected to confirm the usefulness of serum anti-GM-CSF antibody testing in the clinical diagnosis of PAP. The study will evaluate the rate of serious or opportunistic infections and other clinical and demographic data from patients in various regions of the world to determine if significant differences exist, which will provide important knowledge regarding infectious and other complications associated with PAP.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 73
Data and Serum must be from individuals of any age with confirmed diagnosis of PAP based on the following criteria:
- Radiographic features consistent with PAP
- Pathological or cytological findings consistent with PAP determined by either open lung biopsy, transbronchial biopsy or bronchoalveolar lavage cell/fluid cytology.
- Elevated anti-GM-CSF autoantibody concentration, when available
Ability of the international PI's and their research coordinators to ship samples in compliance with this study.
- No established diagnosis of PAP
- Incomplete chart records in which >25% of the requested data is unable to be confirmed.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Standardize the anti-GM-CSF autoantibody ELISA 1 year To compare a novel assay to an existing assay used to measure anti-GM-CSF autoantibodies in banked serum samples previously collected from individuals diagnosed with primary, secondary, congenital or idiopathic PAP, other chronic disorders, or disease-free, healthy individuals.
- Secondary Outcome Measures
Name Time Method Breadth of the autoimmune antibody phenotype of individuals with autoimmune PAP 3 years Autoimmune antibody phenotype of individuals with autoimmune PAP
Disease severity variability among autoimmune PAP patients from various geographic locations 2 years Severity of the disease at onset among PAP patients from different global geographic regions
Tobacco use among PAP patients 2 years Variability of tobacco use among PAP patients from different global geographic regions
Geographic distribution of anti-GM-CSF autoantibody levels 1 years GM-CSF autoantibody concentration in patients with autoimmune PAP
Number of secondary infections that occur in patients with primary PAP 2 years Number of participants documented to have had a secondary infection(s)
Age of onset PAP symptoms 2 years Range of age at onset of symptoms of PAP among PAP patients from different global geographic regions
Age at the time of definitive PAP diagnosis 2 years Range of age at the time of definitive pathologic diagnosis of PAP among PAP patients from different global geographic regions
Gender distribution among PAP patients 2 years Gender distribution among PAP patients from different global geographic regions
Major medical history comparison among PAP patients 2 years Variability of associated major medical diagnoses among PAP patients from different global geographic regions
Length of time from onset of symptoms and definitive diagnosis of autoimmune PAP 2 years Length of time between the onset of symptoms and a definitive pathologic diagnosis of PAP among PAP patients from different global geographic regions
Type of secondary infections that occur in patients with primary PAP 2 years List the specific organisms documented to have infected PAP patients
Trial Locations
- Locations (6)
Brody School of Medicine
🇺🇸Greenville, North Carolina, United States
Ruhrlandklinik Essen
🇩🇪Essen, Germany
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Niigata Medical and Dental School
🇯🇵Niigata, Japan
Clinica Malattie Apparato Respiratorio Università di Pavia
🇮🇹Pavia, Italy
NHO Kinki-Chuo Chest Center
🇯🇵Osaka, Japan