Study of the Etiology and Immunological Pathogenesis in Acute Exacerbation of Idiopathic Pulmonary Fibrosis (AE-IPF)

NCT02509364 | Unknown

• 1 other identifier: SPH150715
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Idiopathic pulmonary fibrosis (IPF) is a highly heterogeneous and lethal pathological process with limited therapeutic options, which is the most common and severe of the idiopathic interstitial pneumonias (IIPs). During the past 20 years, the incidence of IPF increased significantly. Most of IPF patients show a median survival time of 2-3 years after diagnosis. Five-year survival rate is 30%-50%. It's difficult to diagnose in the early stage of IPF. Once the patients go to hospital, it's already in the late stage. Now there is no effective therapy except lung transplant for IPF in clinical application. Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a fatal condition with high mortality (over 80%). Its etiology and pathogenesis remain unknown. There is a lack of effective treatment for it. Based on the investigators' long-term clinical observation, most cases of AE-IPF initially got "common cold" and had coryza, more cough, nasal obstruction，rhinorrhea, sore throat, some patients had fever, headache, and etc. Some of these patients' condition developed very rapidly and then became very severe similar to the situation of acute respiratory distress syndrome (ARDS). Why these AE-IPF patients were so hypersensitive to "cold"? What were the immunologic and pathological mechanisms of their lung lesions after patients exposed to "common cold"? How to effectively offer interventional treatment for AE-IPF? All the above questions are yet to be explained clearly. In the investigators' previous retrospective study, the investigators found that there were some obviously imbalanced immune responses in IPF patients, including increased cluster of differentiation 4 (CD4) T cell population, immunoglobulin and complements. The investigators also found highly expressed inflammatory cytokines (IL-17, MIG and IL-9) and high detection rates of pathogens in AE-IPF patients, especially serum immunoglobulin M (IgM) antibody of some respiratory virus. These findings provide a strong suggestion that there are some imbalance of immunologic function in IPF and there are relationship between AE-IPF and infection, especially "Cold" virus infection might be a key trigger for AE-IPF.

Conditions

Interstitial Lung Diseases

Keywords

AE-IPF

Outcome Measures

Primary Outcomes (7)

• Virus RNA by pathogen test chip and second generation sequencing in AE-IPF

  Testing of pathogen nucleic acid chips:Based on PathGEN® Pathogen Chip Kit (PathGEN Dx, Singapore). Next Generation Sequencing (NGS) has become the powerful tool in pathogen identification based on its rapidness and sensitivity. The final report will provide the species classification of the bacteria and viruses, as well as corresponding designator.

  up to 30 weeks

• Macrophage phenotype and function

  Subtype and functional testing on phenotype and function of Macrophage cell in IPF/AE-IPF patients.

  up to 30 weeks

• Dendritic cell (DC) phenotype and function

  Subtype and functional testing on phenotype and function of DC in IPF/AE-IPF patients.

  up to 30 weeks

• T cell phenotype and function

  Subtype and functional testing on phenotype and function of T cell in IPF/AE-IPF patients.

  up to 30 weeks

• B cell phenotype and function

  Subtype and functional testing on phenotype and function of B cell in IPF/AE-IPF patients.

  up to 30 weeks

• Expression of IL-17 in AE-IPF

  The investigators will evaluate the expression of IL-17 by proteomics in IPF/AE-IPF patients.

  up to 30 weeks

• Expression of MIG in AE-IPF

  The investigators will evaluate the expression of MIG by proteomics in IPF/AE-IPF patients.

  up to 30 weeks

Study Arms (3)

AE-IPF

Diagnosis criteria for AE-IPF: * Diagnosed IPF patient experiences unexplained dyspnea within 1 month * With objective evidence of hypoxia and new onset of pulmonary infiltration based on imaging examination * With other diagnosis like pulmonary embolism, pneumothorax or heart failure excluded.

Other: No intervention

Stable-IPF

Diagnosis criteria for Stable-IPF: * Exclusion of other known causes of ILDs * Presence of a usual interstitial pneumonitis (UIP) pattern on high-resolution computed tomography (HRCT) * Specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy.

Other: No intervention

Health control

Healthy volunteer

Other: No intervention

Interventions

No intervention OTHER

AE-IPF; Health control; Stable-IPF

Eligibility Criteria

• Age: 54 Years - 74 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subject cohorts: Cohort 1: Stable IPF group (n\>150); Cohort 2: AE-IPF group (n\>50); Cohort 3: healthy control group (n\>100). All the IPF patients have been enrolled according to relevant diagnosis criteria. The criteria of AE-IPF include: diagnosed IPF patient experiences unexplained dyspnea within 1 month, with objective evidence of hypoxia and new onset of pulmonary infiltration based on imaging examination, and with other diagnosis like pulmonary embolism, pneumothorax or heart failure excluded.Serial observation of the change of pathogens based on at least two times of sample collection. Healthy control group recruits healthy population based on physical exam, with no definite respiratory disease and normal chest X ray results.

You may qualify if:

• Clinical diagnosis of IPF:
• Presence of a UIP pattern on HRCT
• Specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy.
• Clinical diagnosis of AE-IPF:
• Diagnosed IPF patient experiences unexplained dyspnea within 1 month
• With objective evidence of hypoxia and new onset of pulmonary infiltration based on imaging examination
• With other diagnosis like pulmonary embolism, pneumothorax or heart failure excluded.

You may not qualify if:

• Not applicable.

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (1)

Shanghai Pulmonary Hospital, Tongji University

Shanghai, Shanghai Municipality, 200433, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

Sputum, throat swab, BALF and blood will be collected in this study.

MeSH Terms

Conditions

Lung Diseases, Interstitial

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Study Officials

• Huiping Li, MD,PhD

  Shanghai Pulmonary Hospital, Tongji University, Shanghai, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: July 20, 2015
• First Posted: July 28, 2015
• Study Start: August 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: September 1, 2017
• Last Updated: July 28, 2015

Record last verified: 2015-07

Locations

CN (1)