Pneumocystis in Pathogenesis of HIV-associated Emphysema

NCT00869544 | Completed DMC

• 2 other identifiers: IRB06061515R01HL083461-05
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

A. Statement of Hypotheses: HIV-infected patients have an increased incidence of emphysema compared to non-HIV-infected smokers, and it has been hypothesized that this accelerated disease progression is the result of one or more latent infections that amplifies the pulmonary inflammatory response to cigarette smoke. Pneumocystis is one infectious agent that likely plays a key role in the development of HIV-associated emphysema. Colonization with Pneumocystis has been demonstrated in HIV-infected subjects, and HIV-infected smokers are particularly susceptible to Pc colonization regardless of CD4 cell count or use of prophylaxis. Pneumocystis colonization is also increased in non-HIV-infected patients with chronic obstructive pulmonary disease (COPD) and is directly related to the severity of the disease. The presence of Pneumocystis in the lungs, even at low levels as seen in colonization, produces inflammatory changes similar to those seen in COPD, with increases in the numbers of neutrophils and cytotoxic CD8+ lymphocytes. We propose that Pneumocystis accelerates emphysema in HIV-infected smokers by stimulating inflammation and tissue destruction. We will examine the role of co-infection with Pneumocystis in the pathogenesis of HIV-associated emphysema and the mechanism by which it causes emphysema progression. These studies will lead to information that will provide a rational basis for prevention and therapy of HIV-associated emphysema and provide a model for emphysema in the general population

Conditions

HIV Infections; Pneumocystis Pneumonia; Emphysema; Chronic Obstructive Pulmonary Disease; Asthma

Keywords

HIV; smoker; emphysema; antiretrovirals; COPD

Outcome Measures

Primary Outcomes (1)

• Pc colonization

  The main endpoints that will be assessed are the extent of Pc colonization in this population and its relationship to lung function, inflammatory cells and cytokines, and proteases.

  5 years

Study Arms (1)

HIV

Those positive for HIV and those negative but at high risk for HIV. Both positive and negative for HIV who smoke and those who do not smoke. Both HIV positive and negative with and without asthma and/or COPD

Eligibility Criteria

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

Study Population

patients who have been determined to attend the UPMC HIV/AIDS program and/or participants in the Pitt Mens study.

You may qualify if:

• Subject is Male / Female 18years of age or older.
• Subject has been previously determined to be HIV-infected or has been participating in the Pitt Men's study or is seen at the UPMC HIV/AIDS program

You may not qualify if:

• Subject is experiencing acute onset of shortness of breath, cough, fevers or heart conditions problems such as tachycardia, angina or arrhythmias
• Female subject has told us she is pregnant (this might affect pulmonary function values,we will not require pregnancy testing.)
• Subject has had an MI, CVA, or cardiovascular event within the past 3 months.
• Subject has had eye or abdominal surgery within past 3 months.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

UPMC Montefiore Hospital, CTRC MUH, Keystone Bldg.

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (5)

• Gingo MR, Lucht L, Daly KR, Djawe K, Palella FJ, Abraham AG, Bream JH, Witt MD, Kingsley LA, Norris KA, Walzer PD, Morris A. Serologic responses to pneumocystis proteins in HIV patients with and without Pneumocystis jirovecii pneumonia. J Acquir Immune Defic Syndr. 2011 Jul 1;57(3):190-6. doi: 10.1097/QAI.0b013e3182167516.

  PMID: 21372726 BACKGROUND

• Morris A, Netravali M, Kling HM, Shipley T, Ross T, Sciurba FC, Norris KA. Relationship of pneumocystis antibody response to severity of chronic obstructive pulmonary disease. Clin Infect Dis. 2008 Oct 1;47(7):e64-8. doi: 10.1086/591701.

  PMID: 18724825 BACKGROUND

• Morris A, Gingo MR, George MP, Lucht L, Kessinger C, Singh V, Hillenbrand M, Busch M, McMahon D, Norris KA, Champion HC, Gladwin MT, Zhang Y, Steele C, Sciurba FC. Cardiopulmonary function in individuals with HIV infection in the antiretroviral therapy era. AIDS. 2012 Mar 27;26(6):731-40. doi: 10.1097/QAD.0b013e32835099ae.

  PMID: 22210636 BACKGROUND

• Gingo MR, Wenzel SE, Steele C, Kessinger CJ, Lucht L, Lawther T, Busch M, Hillenbrand ME, Weinman R, Slivka WA, McMahon DK, Zhang Y, Sciurba FC, Morris A. Asthma diagnosis and airway bronchodilator response in HIV-infected patients. J Allergy Clin Immunol. 2012 Mar;129(3):708-714.e8. doi: 10.1016/j.jaci.2011.11.015. Epub 2011 Dec 15.

  PMID: 22177327 BACKGROUND

• Gingo MR, Nouraie M, Kessinger CJ, Greenblatt RM, Huang L, Kleerup EC, Kingsley L, McMahon DK, Morris A. Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals. Ann Am Thorac Soc. 2018 Feb;15(2):192-199. doi: 10.1513/AnnalsATS.201606-492OC.

  PMID: 29313714 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

oral wash blood sputum BAL

MeSH Terms

Conditions

HIV Infections; Pneumonia, Pneumocystis; Emphysema; Pulmonary Disease, Chronic Obstructive; Asthma

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lung Diseases, Fungal; Mycoses; Bacterial Infections and Mycoses; Pneumocystis Infections; Respiratory Tract Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity

Study Officials

• Alison Morris-Gimbel, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 25, 2009
• First Posted: March 26, 2009
• Study Start: August 1, 2007
• Primary Completion: September 1, 2010
• Study Completion: July 1, 2013
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

US (1)