asthma in the elderly

Asthma in the elderlyBoonthorn

3 November 2010

Outline

•Biology of aging▫Immunosenescence

•Epidemiology•Pathogenesis•Risk factor•Special characteristics of asthma in elderly

▫Asthma VS COPD•Diagnosis•Management

Biology of aging

•Aging is natural process and not a disease▫Aging lung

aging process may be contributing factor to deterioration of lung function with progressive age

▫Proinflammatory condition associated with dysregulated immune system

▫Play significant role in pathogenesis of many chronic inflammatory diseases eg. Alzheimer’s dementia, cardiovascular disease, type 2 DM

Current Opinion in Pulmonary Medicine 2010, 16:55–59

Immunosenescence• changes in the innate and adaptive immune response

associated with increased age• Increased susceptibility to infection, malignancy and

autoimmunity, decreased response to vaccination, and impaired wound healing

• facilitate persistence of asthma into late adulthood or development of asthma after the age of 50 to 60 years

J Allergy Clin Immunol 2010;126:690-9.

Age-related changes in innate immunity

Cell type Changes with aging

Epithelial cells Decreased ciliary beat frequency and clearance Microtubular disarrangements

Dendritic cells Reduced phagocytosis and pinocytosisIncreased IL-6 and TNF-α productionDiminished TLR expression and function

Monocytes/macrophages

Reduced phagocytosisReduced MHC clas II expressionReduced cytokine and chemokine secretionReduced generation of NO and superoxide

J Allergy Clin Immunol 2010;126:690-9.Clinical immunology, Principles and Practice.Third edition.

Age-related changes in innate immunity


Neutrophils Reduced phagocytosis ,bactericidal activity Reduced chemotaxisReduced ROS production

NK cells Increased numbersReduced cytotoxicityReduced proinflmmatory cytokine and chemokine productionReduced proliferative response to IL-2

NKT cells Reduced numbersReduced proliferation

Eosinophils Reduced degranulationReduced superoxide production


Age-related changes in adaptive immunity


T cells Reduced Naïve T cell countIncrease memory and effector T cell countReduced response and proliferationReduced CD28 expressionAccumulation of CD8+CD28+ T cellsReduced TCR diversityReduced signal transduction

B cells Reduced generation of B cell precursorsIncrease No. of B1 cellsReduced BCR diversityReduced size and number of GCReduced expression of co-stimulatory moleculeReduced Ab affinity, Isotype switch, Ab specific to foreign AgIncrease Ab specific to self-Ag


Role of immunosenescence on features of asthma. potential mechanism and clinical effect of immunosenescence on long-term asthma, late-onset asthma, and asthma exacerbations in the elderly


Prevalence of asthma in the US among different age groups.Data are from the 1999 National Health Interview Study

Drugs & Aging 2000 Nov; 17 (5):385-397.

Epidemiology• In 2004, the US prevalence of asthma for those 65 years

or older was 7%, with 1,088,000 reporting an asthma attack in the previous 12 months.

• Older asthmatic patients are more likely to be underdiagnosed, undertreated and hospitalized than younger

• highest death rate (51.3 per million people) of any age group .

• Older women are hospitalized more than twice as often as older men

Current Opinion in Pulmonary Medicine 2010,16:55–59

Asthma mortality rates by age, per 1,000,000, age-adjusted to the 1970 Standard Million

The American Journal of Medicine, Vol 122, No 1, January 2009

Phenotype of asthma in the elderly

Respiration 1998;65:347–353

Potential mechanisms for asthma phenotypes in the elderly

long-standing asthma late-onset asthma

Age of onset (years)

Child or youngadult (<40)

Adult (>40)

Genetic role Likely gene by environment Likely epigenetic, including oxidative stress and shortened telomeres

Infection Viral – rhinovirus and RSV Viral – RSV, influenza and bacterial (e.g. Chlamydia pneumoniae), microbial superantigens

Allergy Likely Unlikely

Inflammation Th2 driven, eosinophilic Th1 or Th2 driven, neutrophilic and/or eosinophilic, innate immunity, Th-17, Proteases

Environment Allergens, daycare,school and workplace

Workplace, dwelling type (house, apartment and Institutional)


Pathogenesis • Airway inflammation plays a major role in asthma

including AIE• IL-6, prominent in older adults with generalized

inflammation, may increase IL-17 and decrease Treg cells, resulting in predominately neutrophilic inflammation in the lungs

• Resistance of different inflammatory cells to initiate apoptosis in asthmatic patients, causing persistence of airway inflammation

Current Opinion in Pulmonary Medicine 2010, 16:55–59

Risk factor

• Genes, and especially epigenetic changes • Respiratory infections

▫ viral [rhinovirus and RSV]▫ bacteria▫ Superantigen (staphylococcal enterotoxins)

• Atopy• Obesity

▫ increased inflammation and may cause mechanical impairment of diaphragm excursion

• Female sex▫ prevalence, hospitalization and higher death ratesCurrent Opinion in Pulmonary Medicine 2010,16:55–59

Studies examining early versus late-onset asthma


Special characteristics of asthma in elderly

• Lung function decreases with age, and decrease greater in men

• reduced response to bronchodilators and glucocorticoids• Rarely IgE mediated, and often develops with

component of irreversible airway obstruction• immunosenescence

▫Naive T cells decrease, memory T cells increase, and B-cell function decreases, but lesser decrease in innate immunity

▫Eosinophil function remains the same, but neutrophil numbers increase


Age-related decline in FEV1 by strata in men aged 18–80 yearsderived from linear mixed effects modelsMean FEV1 is corrected for height, weight, and age at first survey

Am J Respir Crit Care Med Vol 171. pp 109–114, 2005.


1. great variability in the duration and severity of the disease2. onset can have been at any time since childhood but more often begins in middle age or later3. many of these patients have severe irreversible obstruction unrelated to the duration of the diseaseThese patients are random selection

of approximately 1,200 patients 65 years of age or older given diagnosis of asthma at Mayo Clinic in 1993



•Coexistence of asthma and COPD in elderly patients due to ▫Cigarette smoking ▫Exposure to airborne endotoxin▫Latent adenovirus in respiratory epithelial cells


Non-proportional Venn diagram of chronic obstructive pulmonary disease (COPD)

Thorax. 2008 September ; 63(9): 761–767.

Asthma and COPD

Asthma-specific feature COPD specific feature

• Reversibility• Airway inflammation (E)• Th2-cytokine pattern• Reduced elastic recoil due

to edema• Perfusion of

underventilated areas (esp. during exacerbation)

• Irreversible airflow obstruction (predominantly)

• Destruction of alveoli• Reduced elastic recoil due

to loss of lung tissue• Ventilation of

underperfused area• Response to

anticholinergic agents

Clinical immunology, Principles and Practice.Third edition.

Common feature - Airflow obstruction - Shift of tidal breathing towards TLC during exacerbation

Clinical and physiological characteristics of obstructive airway syndromes

Thorax 2009;64:728–735.

Percentage of adults (by gender) with airflow obstruction who have an overlap syndrome with increasing age. Males are shown in the black bars and females in the white bars

Thorax 2009;64:728–735.

Differentiating features of COPD and asthmaCOPD Asthma

(early-onset)Asthma (late-onset)

Overlap syndrome

Onset Mid life Early life 65 y or older May have history of asthma in early life

Risk factors Smoking Atopy, airway hyperresponsiveness

Atopy, irritant exposures

Smoking, aging

Symptoms Slowly progress Intermittent, worse atnight/morning

Intermittent, poorperception of symptoms

Slowly progressive

Family history May be present Frequently present

May be present May be present

FEV1/FVC <70% ≥70% <70% <70%

FEV1% predicted <80% >80% <80% <80%

Bronchodilator response

Absent present present Absent


Diagnostic challenges of asthma in the elderly

• confused with COPD and heart failure• Spirometry

▫ underutilized in primary care setting▫ parameters define asthma in aging population▫ performance of effective testing

• postbronchodilator PFT• Alterations in perception of airway obstruction due to

aging ▫ underestimation of disease severity and delay in seeking advice

• Several systemic comorbidities may coexist with AIE


Diagnostic details that affect management after the diagnosis of asthma has been established

• Age at onset• Upper airway disease, sinusitis, and polyps• ADR

▫ Aspirin, beta blocker, including eyedrops, and ACEI

• Coexisting diseases• Pack-years of cigarette smoking or passive exposure• Past or present occupational exposures• Domestic exposures to irritants, allergens, and stimulants of

innate immunity• Persistent airway obstruction despite therapy• Total and specific IgE levels• Abnormal chest radiographic or CT scan resultsJ Allergy Clin Immunol 2010;126:681-7.

Management challenges of asthma in the elderly

• Physicians overlooking appropriate treatment of asthma• Patient do not want to or cannot afford to take

‘prophylactic’ or preventive medicines• psychomotor and cognitive disabilities affect choice of

inhaler delivery systems• drug interactions and increased incidence of ADRs• lack of many drug trials involving elderly asthma


Details of asthma control important in elderly patients

• Control exposure to environmental agents• Monitor skill of inhaling aerosol medications• Establish ‘‘personal best’’ FEV1• Add oral medications, such as leukotriene antagonists or

low-dose theophylline, for patients with severe asthma• If there is a concern about cardiotoxicity of b-adrenergic

agonists, substitute anticholinergic aerosols• Manage osteoporosis and other coexisting diseases• Influenza and pneumococcal immunization


Beta agonist

Chest 2004;125;2309-2321

SMART trial• possible link between LABA and respiratory-related

deaths in asthmatic patients >12 yr ( mean 40)• subjects using LABA without ICS compared with

placebo, occurred primarily in African Americans• respiratory-related deaths

▫ (24 vs 11; RR, 2.16; 95% CI, 1.06 to 4.41)

• asthma-related deaths ▫ (13 vs 3; RR, 4.37; 95% CI, 1.25 to 15.34)

• combined asthma-related deaths or life-threatening experiences ▫ (37 vs 22; RR, 1.71; 95% CI, 1.01 to 2.89)

CHEST 2006; 129:15–26.

Anticholinergic Medications• Cochrane review (22 studies)1

▫ statistically significant improvements in daytime dyspnea and peak flow measurements in patients treated with inhaled anticholinergic agents compared with placebo

▫ no difference between anticholinergic plus SABA and SABA alone in the improvement of symptoms or PEF (maintenance Rx)

• Meta-analysis (23 RCT)2

▫ Reduction in hospitalization and improved spirometric function with combination therapy when compared with SABA alone

• asthma guidelines recommend combining inhaled ipratropium with SABA therapy in moderate or severe asthma exacerbations

1.Cochrane Database Syst Rev. 2004;3:CD0032692.Thorax. 2005;60:740-746.

Corticosteroids• Adult patients with asthma did not sustain a significant

loss of BMD from ICS use1

▫ Adverse effects may be seen only after many years of high-dose inhaled corticosteroid use

• study of 38,325 (age>66) more using ICS or INCS2

▫ increased risk of ocular HT and open-angle glaucoma with prolonged administration (OR 1.44; 1.01-2.06)

• study of 3677 patients (aged >70) inhaled beclomethasone or budesonide ( 1mg/d, >2 yrs.)3

▫ increased risk for cataracts (OR 3.40; 1.49-7.76)

1. CHEST 2003; 124:2329–23402. JAMA. 1997;277:722-7273. JAMA. 1998;280:539-543.

Leukotriene Receptor Antagonists

•ACCEPT trial▫4-week open-label trial of zafirlukast that included

321 asthmatic patients (aged >66)▫statistically significant improvements in symptoms

and morning PEF with zafirlukast, ( less than in younger groups )

▫Side effects in seniors were only slightly more common than in younger adults (17.5% vs 18.8%)

Ann Allergy Asthma Immunol 2000;84:217–225.

Anti-immunoglobulin-E Therapies• 2511 asthmatic patients aged 6 to 75 years

▫Omalizumab use was associated with a reduction of asthma exacerbations by 38% and emergency department visits by 47%

▫subgroup analysis showed beneficial effects among all age groups, improvements in patients aged > 65 years did not reach statistical significance

Allergy 2005: 60: 302–308

Drugs that decrease theophylline clearance

Drugs & Aging 2000 Nov; 17 (5): 385-397

Potential issues with technique of inhalation treatment for older people

Lancet 2010; 376: 803–13

Model representing the multidimensional assessment of asthma in older adults withmultidisciplinary intervention

Lancet 2010; 376: 803–13

Take home message

•Asthma in elderly▫Underdiagnosis and undertreatment▫Multidimentional aspects of aging, disease

concurrence and comorbidity and patient preference

asthma in the elderly

Health & Medicine

phenotype of asthma

asthma exacerbations

persistence of asthma

asthma phenotypes

term asthma

development of asthma

asthma attack

features of asthma