Clinical Trial: Multicenter International Cross-Sectional Evaluation of Pulmonary Alveolar Proteinosis Trial

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Multicenter International Cross-Sectional Evaluation of Pulmonary Alveolar Proteinosis Trial

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 Summary:

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
Sponsor: Children's Hospital Medical Center, Cincinnati

Current Primary Outcome: Standardize the anti-GM-CSF autoantibody ELISA [ Time Frame: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Geographic distribution of anti-GM-CSF autoantibody levels [ Time Frame: 1 years ]
    GM-CSF autoantibody concentration in patients with autoimmune PAP
  • Breadth of the autoimmune antibody phenotype of individuals with autoimmune PAP [ Time Frame: 3 years ]
    Autoimmune antibody phenotype of individuals with autoimmune PAP
  • Age of onset PAP symptoms [ Time Frame: 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 [ Time Frame: 2 years ]
    Range of age at the time of definitive pathologic diagnosis of PAP among PAP patients from different global geographic regions
  • Length of time from onset of symptoms and definitive diagnosis of autoimmune PAP [ Time Frame: 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
  • Gender distribution among PAP patients [ Time Frame: 2 years ]
    Gender distribution among PAP patients from different global geographic regions
  • Tobacco use among PAP patients [ Time Frame: 2 years ]
    Variability of tobacco use among PAP patients from different global geographic regions
  • Major medical history comparison among PAP patients [ Time Frame: 2 years ]
    Variability of associated major medical diagnoses among PAP patients from different global geographic regions
  • Disease severity variability among autoimmune PAP patients from various geographic locations [ Time Frame: 2 years ]
    Severity of the disease at onset among PAP patients from different global geographic regions
  • Number of secondary infections that occur in patients with primary PAP [ Time Frame: 2 years ]
    Number of participants documented to have had a secondary infection(s)
  • Type of secondary infections that occur in patients with primary PAP [ Time Frame: 2 years ]
    List the specific organisms documented to have infected PAP patients


Original Secondary Outcome: Same as current

Information By: Children's Hospital Medical Center, Cincinnati

Dates:
Date Received: November 28, 2016
Date Started: July 2007
Date Completion:
Last Updated: December 29, 2016
Last Verified: December 2016