Environmental Factor, November 2009, National Institute of Environmental Health Sciences
Researchers Find Link Between Cholesterol and Asthma
By Robin Arnette
High cholesterol levels have been linked to a variety of illnesses such as heart attack, stroke and diabetes, but recent research published in the Journal of Allergy and Clinical Immunology suggests that cholesterol may also play a role in asthma.
Researchers from NIEHS, SRA International and Rho Federal Systems, led by NIEHS Principal Investigator Michael B. Fessler, M.D.,(http://www.niehs.nih.gov/research/atniehs/labs/lrb/host-def/index.cfm) have concluded that serum total cholesterol (TC) and non high-density lipoprotein cholesterol (non-HDL-C) are inversely related to asthma and wheeze in a representative sample of the U.S. population. The authors noted that this finding in the overall population was chiefly driven by a marked relationship among Mexican Americans (MAs). This study (http://www.ncbi.nlm.nih.gov/pubmed/19800678?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) signifies the first documented association between cholesterol and asthma in a national survey and the first to identify a determinant that may contribute to or serve as a biological marker for the reduced prevalence and morbidity of asthma in MAs.
Stavros Garantziotis, M.D., the medical director of the NIEHS Clinical Research Unit (CRU) (http://www.niehs.nih.gov/research/clinical/join/durham/index.cfm) said, "The results highlight the fact that patients need to be evaluated within the context of their individual genetic background when looking for clues and treatment options."
Before they initiated the investigation, Fessler and his colleagues were aware of the work that had been done in other labs regarding the relationship between cholesterol and inflammation. A few groups had determined that dyslipidemia - a condition marked by abnormal concentrations of lipids or lipoproteins in the blood - caused vascular inflammation through the activation of innate immunity. Other laboratories had discovered evidence that cholesterol metabolism and inflammation were linked in the lung.
The team's main goal was to test for an independent relationship between serum cholesterol concentrations and asthma prevalence, but it also wanted to test for a relationship between serum cholesterol and wheeze requiring medical attention, a strong indicator of poorly controlled asthma and other obstructive lung disease.
To this end, the Fessler group conducted a cross-sectional study of 7005 subjects, aged six years and older, who participated in the National Health and Nutrition Examination Survey (NHANES) 2005 - 2006, a program designed to assess the health and nutritional status of the U.S. population. Participants were classified into five racial/ethnic groups: non-Hispanic white (NHW), non-Hispanic black (NHB), MA, other Hispanic and other/multi-race. The NHANES measured serum TC and HDL-C, and administered questionnaires to assess physician-diagnosed asthma and wheeze.
At the start of the project, the group was unsure of what it would find. "We didn't know whether cholesterol was going to have any relationship with asthma," Fessler explained. "There wasn't a lot of precedent for how to approach it."
The results demonstrated that serum TC and non-HDL-C were lower in patients with asthma and wheeze compared to those without these illnesses. When the racial/ethnic results were examined, team members found that this inverse relationship was specific to MAs. They found no difference in HDL-C levels between asthmatics and non-asthmatics. In addition, the relationship was independent of body mass index (BMI), an established asthma risk factor, and serum C-reactive protein (CRP), an inflammatory biomarker.
The data confirmed and built upon findings from other groups that had reported that MAs have the lowest prevalence of asthma in the country, despite increased asthma risk factors such as low socioeconomic status and obesity. Fessler said the reasons why this demographic group exhibits these features of asthma are unknown, but noted that further investigation into the topic may provide valuable information on asthma pathogenesis and treatment.
Darryl Zeldin, M.D., acting director of the NIEHS Clinical Research Program (http://www.niehs.nih.gov/research/clinical/index.cfm) and a co-author on the paper, said that even though the results should be independently confirmed in another cohort, the study raised some interesting clinical questions. He added, "Is serum cholesterol a predictive biomarker of asthma diagnosis or treatment responsiveness? Do statins or other cholesterol lowering agents modify asthma risk? Further research will be necessary to address these issues in a more conclusive way."
Citation: Fessler MB, Massing MW, Spruell B, Jaramillo R, Draper DW, Madenspacher JH, Arbes SJ, Calatroni A, Zeldin DC. (http://www.ncbi.nlm.nih.gov/pubmed/19800678?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) 2009. Novel relationship of serum cholesterol with asthma and wheeze in the United States. J Allergy Clin Immunol Oct 2 [Epub ahead of print].
Rising Star in Clinical Research
Fessler, who holds dual appointments in the Laboratory of Respiratory Biology and the Clinical Research Program at NIEHS, recently received thefor "novel and innovative research contributions in the field of Environmental Health Science." The award is open to tenure-track investigators who have received their terminal degrees within the last 15 years and who have been at NIEHS for five years or less. "I'm pleased that people think that I'm on the right path," Fessler said. "It helps to validate some hard work."
When Fessler refers to the hard work he's been doing, one can see why he was a good candidate for the Early Career Award. In addition to the cholesterol and asthma work, he is actively involved in another research project at the CRU. He collects blood from volunteers and isolates different leukocyte subtypes for ex vivo signaling studies. Fessler said that he became interested in this kind of analysis during his pulmonary critical care fellowship at National Jewish Health (http://www.nationaljewish.org/), formerly the National Jewish Medical and Research Center, in Denver, Colo. He said that depending on how one looks at his signaling work, it could be called clinical, translational or basic research. Fessler is currently collaborating with another group to determine if its immortalized human cell line results pertain to his primary human cell preparations. Fessler also plans to test hypotheses derived from cell lines and rodent models by the use of the NIEHS Environmental Polymorphisms Registry (EPR). (http://www.niehs.nih.gov/research/clinical/join/epr/)
One would think that Fessler spends all of his waking hours in the laboratory, but he also finds time to produce outstanding postdoctoral fellows. One of Fessler's trainees, David Draper, Ph.D., recently won a Fellows Award for Research Excellence (FARE) and travelled to the NIH Research Festival to give a ten minute symposium talk. Being chosen to speak at the Festival is an honor since only a few FARE winners are chosen.
"This job is a fun and exciting opportunity for me," Fessler concluded. "It has been a transformative experience and continues to be a work in progress."