Asthma in the elderly: Current understanding and future research needs—a report of a National Institute on Aging (NIA) workshop
Authors: Nicola A. Hanania, Monroe J. King, Sidney S. Braman, Carol Saltoun, Robert A. Wise, Paul Enright, Ann R. Falsey, Sameer K. Mathur, Joe W. Ramsdell, Linda Rogers, David A. Stempel, John J. Lima, James E. Fish, Sandra R. Wilson, Cynthia Boyd, Kushang V. Patel, Charles G. Irvin, Barbara P. Yawn, Ethan A. Halm, Stephen I. Wasserman, Mark F. Sands, William B. Ershler, Dennis K. Ledford
Journal: Journal of Allergy and Clinical Immunology (2011)

Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population. Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population. The proportion of persons older than 65 years in the United States is currently about 13% but is projected to grow from about 40 million in 2005 to more than 86 million by 2050, accounting for 25% of the population. The age group with the largest growth will be those older than 85 years, which is estimated to be more than 1 million by 2050.1Lutz W. Sanderson W. Scherbov S. 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Recognizing the paucity of research, the many challenges that exist in the recognition and treatment of asthma in older adults, and the opportunity to bridge geriatrics and the clinical specialties that focus on asthma, the National Institute on Aging (NIA) sponsored a Workshop on Asthma in the Elderly in Herndon, Virginia, on September 8 and 9, 2008. The workshop was planned by a committee of 6 physician-scientists from US academic institutions or from the Division of Geriatrics and Clinical Gerontology in the NIA. The planning committee selected speakers and participants for their expertise in asthma, pulmonology, allergy/immunology, primary care, emergency medicine, geriatrics, and/or gerontologic science (see the list of participants in Appendix 1). The immediate goals of this workshop were to summarize the current understanding of the mechanisms of asthma in older persons and to identify knowledge gaps and research opportunities leading to improved medical care and health outcomes for older persons with asthma. These research opportunities are discussed in the body of this report and summarized in Table I.7Craig B.M. Kraus C.K. Chewning B.A. Davis J.E. Quality of care for older adults with chronic obstructive pulmonary disease and asthma based on comparisons to practice guidelines and smoking status.BMC Health Serv Res. 2008; 8: 144Crossref PubMed Scopus (13) Google Scholar, 8Blanchette C.M. Gutierrez B. Ory C. Chang E. Akazawa M. Economic burden in direct costs of concomitant chronic obstructive pulmonary disease and asthma in a Medicare Advantage population.J Manag Care Pharm. 2008; 14: 176-185PubMed Google Scholar, 9Yancik R. Ershler W. Satariano W. Hazzard W. Cohen H.J. Ferrucci L. Report of the National Institute on Aging task force on comorbidity.J Gerontol A Biol Sci Med Sci. 2007; 62: 275-280Crossref PubMed Google ScholarTable IIdentified future research needsThe aging lung Large, longitudinal, and more complete studies to determine the effects of aging on the function of the respiratory system Improved knowledge about lung structure-function relationships in older age using techniques of imaging and measures of lung function not requiring effort (eg, high-resolution computed tomographic scanning and forced oscillation) Improved assessment of lung processes underlying airflow limitation attributable to aging versus COPD or asthma, especially in asthmatic patients who smoke Studies to examine the effects of aging in ethnic groups and the role of genderEpidemiology, effect, diagnosis, and management Determine the true prevalence and cost of asthma in the older population Develop a uniform definition of asthma to be applied to health care records that will distinguish asthma from COPD and mixed asthma/COPD Evaluate evidence-based treatment algorithms for older asthmatic patients, such as those developed by the National Heart, Lung, and Blood Institute and Global Initiative For Asthma guidelines7Craig B.M. Kraus C.K. Chewning B.A. Davis J.E. Quality of care for older adults with chronic obstructive pulmonary disease and asthma based on comparisons to practice guidelines and smoking status.BMC Health Serv Res. 2008; 8: 144Crossref PubMed Scopus (13) Google Scholar Assess the effect of asthma treatment, including direct medical costs of care, indirect costs of care, and value of treatment in improving quality of life8Blanchette C.M. Gutierrez B. Ory C. Chang E. Akazawa M. Economic burden in direct costs of concomitant chronic obstructive pulmonary disease and asthma in a Medicare Advantage population.J Manag Care Pharm. 2008; 14: 176-185PubMed Google Scholar, 9Yancik R. Ershler W. Satariano W. Hazzard W. Cohen H.J. Ferrucci L. Report of the National Institute on Aging task force on comorbidity.J Gerontol A Biol Sci Med Sci. 2007; 62: 275-280Crossref PubMed Google Scholar Assess the effect of comorbid conditions, especially COPD and congestive heart failure, on asthma9Yancik R. Ershler W. Satariano W. Hazzard W. Cohen H.J. Ferrucci L. Report of the National Institute on Aging task force on comorbidity.J Gerontol A Biol Sci Med Sci. 2007; 62: 275-280Crossref PubMed Google Scholar Characterize phenotypes of elderly asthma with regard to responses to therapy and long-term outcomes based on age of onset, duration of disease, and environmental triggers Develop algorithms for electronic medical record systems that are asthma-specific Evaluate effects of current asthma medications in older patients compared with younger patients Identify pharmacogenetic determinants of response to asthma medications in older adults Identify simpler and safer drug delivery systems and schedules for older adults Develop simple methods to differentiate COPD from asthma exacerbations in older adultsEpigenetics and environmental and microbiological triggers Understand how environmental or aging-related factors affect epigenetic changes in asthma in older adults Identify differences between older and younger asthmatic patients or between LSA and LOA with regard to inflammation, remodeling, intracellular mechanisms, responses to environmental pollutants, and allergy sensitization and their effects on the metabolism and action of asthma drugs Identify naturally occurring age-related changes in airway cellular patterns Develop animal models of age-related airway inflammation Understand the significance of allergy sensitization associated with asthma in older adults (eg, through larger prospective studies) Identify the utility of allergy tests, either skin tests or serum specific IgE measurement, in reflecting allergy sensitization in older adults Identify the role of the microbiome in patients with LOA Understand the role of non-IgE mechanisms in older adults' inflammatory responses to inhalant allergens or pollutants (eg, TH17 lymphocytes producing IL-17 or protease receptor responses to molds and dust mites) Determine the roles of adaptive versus innate immune mechanisms on asthma development, progression, and response to treatment in older adults Determine whether there are environmental pollutants peculiar to institutional settings Identify viruses and other microbiological agents responsible for, and the mechanisms by which they cause, asthma exacerbations in older adults, which might lead to the development of vaccine- or antiviral drug–based interventions Determine effects of asthma medications, viral or bacterial load, or allergy status on susceptibility to exacerbations in older patients Define rates of infection and specific pathogens in older asthmatic patients Distinguish roles of innate immunity in eosinophilic versus neutrophilic asthma Open table in a new tab In addition, the NIA, in collaboration with the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases, recently issued a set of program announcements inviting research proposals on asthma in older adults (http://grants.nih.gov/grants/guide/pa-files/PA-10-263.html, http://grants.nih.gov/grants/guide/pa-files/PA-10-264.html, and http://grants.nih.gov/grants/guide/pa-files/PA-10-265.html). It is a central principle of gerontology that aging itself is not a disease.10Ling S.M. Simonsick E.M. Ferrucci L. A painful interface between normal aging and disease.J Gerontol A Biol Sci Med Sci. 2007; 62: 613-615Crossref PubMed Google Scholar Yet there are physiological changes within organs, tissues, and cells that result in diminished functional reserve and thereby increased susceptibility to stressors, disease, or both. A second principle is that these aging changes are highly variable and account for the great constitutional heterogeneity among older persons from very "fit" to very "frail." In fact, the concept of frailty, both its causes and consequences, has become a focus of concentrated gerontologic investigation. At the root of age-associated physiological changes are a number of genetic, epigenetic, and environmental factors.11Ferrucci L. Giallauria F. Guralnik J.M. 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The number of divisions turns out to be more important than the actual amount of time passed. Thus cells held in a quiescent state for months, when allowed back into a proliferative environment, will continue approximately the same number of divisions as those that were allowed to proliferate without a quiescent period.19Cristofalo V.J. Cell culture aging: insights for cell aging in vivo?.Aging (Milano). 1999; 11: 1-3PubMed Google Scholar The question remains whether this in vitro phenomenon is relevant to animal aging. One suggestive observation is that fibroblasts cultured from samples of old skin undergo fewer cycles of replication than those from young skin.20Schneider E.L. Mitsui Y. The relationship between in vitro cellular aging and in vivo human age.Proc Natl Acad Sci U S A. 1976; 73: 3584-3588Crossref PubMed Google Scholar Furthermore, when various species are compared, replicative potential is directly and significantly related to lifespan.21Rohme D. 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Report of the National Institute on Aging task force on comorbidity.J Gerontol A Biol Sci Med Sci. 2007; 62: 275-280Crossref PubMed Google Scholar Yet, regardless of the pathway taken to frailty, the clinical picture has common features, including a reduction in lean body mass (sarcopenia), loss of bone mass (osteopenia), cognitive impairment, functional decline, and anemia. On the basis of data derived from large cohorts of elderly patients, Fried et al23Fried L.P. Tangen C.M. Walston J. Newman A.B. Hirsch C. Gottdiener J. et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156Crossref PubMed Google Scholar have offered an operational definition of frailty incorporating an assessment of 5 specific characteristics to ascribe a frailty index. On this 5-point scale, a score of 3 or more has been shown to be independently predictive of a range of adverse clinical outcomes, including acute illness, falls, hospitalization, nursing home placement, and early mortality.23Fried L.P. Tangen C.M. Walston J. Newman A.B. Hirsch C. Gottdiener J. et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156Crossref PubMed Google Scholar, 24Bandeen-Roche K. Xue Q.L. Ferrucci L. Walston J. Guralnik J.M. Chaves P. et al.Phenotype of frailty: characterization in the women's health and aging studies.J Gerontol A Biol Sci Med Sci. 2006; 61: 262-266Crossref PubMed Google Scholar, 25Fried L.P. Hadley E.C. Walston J.D. Newman A.B. Guralnik J.M. 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Increased serum levels of certain proinflammatory cytokines, most notably IL-6, are increasingly present with advancing age and to a greater extent with frailty.27Ershler W.B. Keller E.T. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty.Annu Rev Med. 2000; 51: 245-270Crossref PubMed Scopus (566) Google Scholar, 28Leng S.X. Yang H. Walston J.D. Decreased cell proliferation and altered cytokine production in frail older adults.Aging Clin Exp Res. 2004; 16: 249-252Crossref PubMed Google Scholar Furthermore, the appearance of this and other inflammatory markers has been associated with a number of adverse clinical outcomes, including decreased strength and mobility, falls, dementia, and mortality.27Ershler W.B. Keller E.T. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty.Annu Rev Med. 2000; 51: 245-270Crossref PubMed Scopus (566) Google Scholar From the perspective of those who study aging, there is an important distinction made between median (life expectancy) and maximum lifespan. Over the past several decades, with the advent of modern sanitation, refrigeration, and other public health measures, including vaccination and antibiotics, there has been a dramatic increase in median survival.29Christensen K. Vaupel J.W. Determinants of longevity: genetic, environmental and medical factors.J Intern Med. 1996; 240: 333-341Crossref PubMed Google Scholar Early deaths have been diminished, and more patients are reaching old age. In the United States today, life expectancy now approaches 80 years.30Arias E. 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Lifespan is finite and varies generally from species to species and much less so within species. Mice live, on average, 2½ years, monkeys 30 years, and human subjects about 90 years. Among species, larger animals generally live longer than smaller animals, but within species, smaller animals are likely to live longer. It is clear that aging is not entirely explained by DNA sequence. For example, mice and bats have only 0.25% difference in their primary DNA sequence, but bats live for 25 years, 10 times longer than mice. A commonly held notion is that regulation of gene expression accounts for a longevity difference between species. It is now clearly established that certain specific genes can alter lifespan, at least in lower animals, but whether these same genes regulate "aging" is still in question. For example, transgenic Drosophila species expressing increased copies of the free radical scavenging enzymes superoxide dismutase and catalase live on average a third longer than the appropriate controls.32Orr W.C. Sohal R.S. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster.Science. 1994; 263: 1128-1130Crossref PubMed Google Scholar In even lower species (eg, yeast and nematodes) the identification of specific genes that influence lifespan33Murakami S. Johnson T.E. A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans.Genetics. 1996; 143: 1207-1218Crossref PubMed Google Scholar, 34Sun J. Kale S.P. Childress A.M. Pinswasdi C. Jazwinski S.M. 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Leveraging on well-characterized existing cohorts, when possible, is recommended. The lungs, like other organs, age and exhibit continued loss of function as a person grows old. Lung function is traditionally assessed by means of a number of standardized methods. The most common measurement used is spirometry with the determination of FEV1 and forced vital capacity (FVC). FEV1 and FVC both show continuous decreases of between 25 and 30 mL with each year of life after about age 20 years.39Janssens J.P. Pache J.C. Nicod L.P. Physiological changes in respiratory function associated with ageing.Eur Respir J. 1999; 13: 197-205Crossref PubMed Google Scholar The cause of this decrease is usually attributed to the loss of the driving forces for airflow as a result of reduced respiratory muscle performance, loss of static elastic recoil, or both.39Janssens J.P. Pache J.C. Nicod L.P. 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