Prevalence of Different Haptoglobin Phenotypes in Patients With COPD- Frequent Exacerbators Versus Non Exacerbators

NCT01745419 | Completed

• 1 other identifier: CMC-12-0121-CTIL
• Study Type: observational
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic obstructive pulmonary disease (COPD) is a common disease in smokers. COPD has a slowly deteriorating course, punctuated by exacerbations- acute events characterized by increasing shortness of breath and putrid sputum. Exacerbations of COPD may be precipitated by several factors, most commonly infections. Exacerbation frequency generally increases with declining lung function. However, some patients with COPD consistently experience a higher rate of exacerbations than others despite similar severity of COPD. This has led researchers to postulate the existence of a distinct subgroup of "frequent exacerbators" . Recent work has also brought attention to a subset of patients who experience remarkably few exacerbations despite significantly impaired lung function. Careful characterization of both of these extreme subgroups of COPD may offer additional insights into why certain patients are prone to frequent exacerbations while others remain relatively protected. Haptoglobin (Hp) is a protein produced predominately by the liver . In humans two types of genes for Hp exist (1 and 2) with possible combinations of these two genes- 1-1, 1-2, or 2-2. The Hp 2 gene is believed to have arisen from the Hp 1 gene in human evolution. Subsequently the prevalence of the Hp 2 allele has spread throughout the world, probably as a result of its ability to provide a selective advantage against infectious disease. The Hp 1-2 combination is a very common one. In most western countries, the prevalence of the Hp genotypes is 16% Hp 1-1, 36% Hp 2-2 and 48% Hp 2-1. The Hp gene form has been shown to be associated with disease. Specifically, Hp phenotypes have been found to affect propensity to atherosclerosis in Diabetic individuals. There have been several studies suggesting that the Hp 2-2 phenotype is associated with a protection against infectious complications. In view of the importance of respiratory infections on COPD exacerbations, and of the gained knowledge of Haptoglobin subtypes on propensity to infection, we propose to investigate whether Haptoglobin subtypes are in correlation with the "frequent exacerbator" phenotype of COPD. We postulate that, since people with Hp 1-1 are more prone to infection, the frequency of the Hp 1-1 phenotype will be higher in "frequent exacerbators" of COPD than in "non- exacerbators". To test our hypothesis we propose to determine Hp phenotype in two groups of COPD patients: one with frequent exacerbations and one with no exacerbations, and compare the relative frequency of the 1-1 phenotype in the two groups.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

COPD; Exacerbation; Haptoglobin

Outcome Measures

Primary Outcomes (1)

• Prevalence of Hp 1-1 phenotype

  Prevalence as percentage of Hp 1-1 phenotypes in each group of patients

  1 visit- approximately 2 hours.

Study Arms (2)

COPD Frequent Exacerbators

COPD patients having experienced at least two episodes of acute exacerbations in the former 12 months. (Acute exacerbations are defined as worsening symptoms requiring treatment with systemic steroids (oral or parenteral) or antibiotics, a visit to the emergency room, and/or admission to a hospital. Events separated by at least 21 days are considered as separate events of exacerbation.)

COPD non- exacerbators

COPD patients who have not experienced exacerbations in the former 24 months. (Acute exacerbations are defined as worsening symptoms requiring treatment with systemic steroids (oral or parenteral) or antibiotics, a visit to the emergency room, and/or admission to a hospital. Events separated by at least 21 days are considered as separate events of exacerbation.)

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with COPD

You may qualify if:

• Patients diagnosed with COPD according to GOLD guidelines1
• Age 40-100 years
• Smoking history of \> 10 pack - years
• Spirometry consistent with airflow obstruction (FEV1/FVC ratio \< 70%)
• Moderate to severe airflow obstruction (FEV1\<60%)
• At least two episodes of acute exacerbations in the former 12 months, or no exacerbations in the former 24 months. (Acute exacerbations are defined as worsening symptoms requiring treatment with systemic steroids (oral or parenteral) or antibiotics, a visit to the emergency room, and/or admission to a hospital. Events separated by at least 21 days are considered as separate events of exacerbation.)

You may not qualify if:

• Patients with a history of any of the following conditions will be excluded from the study:
• Active Tuberculosis
• Pulmonary fibrosis or Asbestosis
• Organ transplantation
• Lung volume reduction surgery
• Previous lung or lobe resection.

Sponsors & Collaborators

• Carmel Medical Center: lead
• Technion, Israel Institute of Technology: collaborator

Study Sites (1)

Pulmonology Institute, Carmel Medical Center

Haifa, 34362, Israel

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

3 ml of Serum will be collected from each patient

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michal Shteinberg, MD, PhD

  Pulmonology Institute, Carmel Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Michal Shteinberg, MD, PhD

Study Record Dates

• First Submitted: December 5, 2012
• First Posted: December 10, 2012
• Study Start: January 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: June 1, 2016
• Last Updated: July 28, 2016

Record last verified: 2016-07

Locations

IL (1)