Asthma in the elderly
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Asthma in the elderly
- 1. Asthma in the elderly Boonthorn 3 November 2010
- 2. Outline • Biology of aging ▫ Immunosenescence • Epidemiology • Pathogenesis • Risk factor • Special characteristics of asthma in elderly ▫ Asthma VS COPD • Diagnosis • Management
- 3. 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–
- 4. 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.
- 5. 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 pinocytosis Increased IL-6 and TNF-α production Diminished TLR expression and function Monocytes/macrophages Reduced phagocytosis Reduced MHC clas II expression Reduced cytokine and chemokine secretion Reduced generation of NO and superoxide J Allergy Clin Immunol 2010;126:690-9. Clinical immunology, Principles and Practice.Third edition.
- 6. Age-related changes in innate immunity Cell type Changes with aging Neutrophils Reduced phagocytosis ,bactericidal activity Reduced chemotaxis Reduced ROS production NK cells Increased numbers Reduced cytotoxicity Reduced proinflmmatory cytokine and chemokine production Reduced proliferative response to IL-2 NKT cells Reduced numbers Reduced proliferation Eosinophils Reduced degranulation Reduced superoxide production J Allergy Clin Immunol 2010;126:690-9. Clinical immunology, Principles and Practice.Third edition.
- 7. Age-related changes in adaptive immunity Cell type Changes with aging T cells Reduced Naïve T cell count Increase memory and effector T cell count Reduced response and proliferation Reduced CD28 expression Accumulation of CD8+CD28+ T cells Reduced TCR diversity Reduced signal transduction B cells Reduced generation of B cell precursors Increase No. of B1 cells Reduced BCR diversity Reduced size and number of GC Reduced expression of co-stimulatory molecule Reduced Ab affinity, Isotype switch, Ab specific to foreign Ag Increase Ab specific to self-Ag J Allergy Clin Immunol 2010;126:690-9. Clinical immunology, Principles and Practice.Third edition.
- 8. 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 J Allergy Clin Immunol 2010;126:690-9.
- 9. 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.
- 10. 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
- 11. 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
- 12. Phenotype of asthma in the elderly Respiration 1998;65:347–353
- 13. Phenotype of asthma in the elderly Respiration 1998;65:347–353
- 14. Potential mechanisms for asthma phenotypes in the elderly long-standing asthma late-onset asthma Age of onset (years) Child or young adult (<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) Current Opinion in Pulmonary Medicine 2010,16:55–59
- 15. 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
- 16. 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 rates Current Opinion in Pulmonary Medicine 2010,16:55–59
- 17. Studies examining early versus late-onset asthma Current Opinion in Pulmonary Medicine 2010,16:55–59
- 18. 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 J Allergy Clin Immunol 2010;126:681-7.
- 19. Age-related decline in FEV1 by strata in men aged 18–80 years derived from linear mixed effects models Mean FEV1 is corrected for height, weight, and age at first survey Am J Respir Crit Care Med Vol 171. pp 109–114, 2005.
- 20. Special characteristics of asthma in elderly 1. great variability in the duration and severity of the disease 2. onset can have been at any time since childhood but more often begins in middle age or later 3. 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 J Allergy Clin Immunol 2010;126:681-7.
- 21. Special characteristics of asthma in elderly • Coexistence of asthma and COPD in elderly patients due to ▫ Cigarette smoking ▫ Exposure to airborne endotoxin ▫ Latent adenovirus in respiratory epithelial cells J Allergy Clin Immunol 2010;126:681-7.
- 22. Non-proportional Venn diagram of chronic obstructive pulmonary disease (COPD) Thorax. 2008 September ; 63(9): 761–767.
- 23. 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
- 24. Clinical and physiological characteristics of obstructive airway syndromes Thorax 2009;64:728–735.
- 25. 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.
- 26. Differentiating features of COPD and asthma COPD 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 hyperresponsiven ess Atopy, irritant exposures Smoking, aging Symptoms Slowly progress Intermittent, worse at night/morning Intermittent, poor perception 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 J Allergy Clin Immunol 2010;126:702-9.
- 27. 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 Current Opinion in Pulmonary Medicine 2010,16:55–59
- 28. 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 results J Allergy Clin Immunol 2010;126:681-7.
- 29. 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 Current Opinion in Pulmonary Medicine 2010,16:55–59
- 30. 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 J Allergy Clin Immunol 2010;126:681-7.
- 35. 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.
- 36. 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:CD003269 2.Thorax. 2005;60:740-746.
- 37. 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; 124:2329–2340 2. JAMA. 1997;277:722-727 3. JAMA. 1998;280:539-543.
- 38. 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.
- 39. 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
- 40. Drugs that decrease theophylline clearance Drugs & Aging 2000 Nov; 17 (5): 385-397
- 41. Potential issues with technique of inhalation treatment for older people Lancet 2010; 376: 803–13
- 42. Model representing the multidimensional assessment of asthma in older adults with multidisciplinary intervention Lancet 2010; 376: 803–13
- 43. Take home message • Asthma in elderly ▫ Underdiagnosis and undertreatment ▫ Multidimentional aspects of aging, disease concurrence and comorbidity and patient preference
Notas del editor
- anatomic and physiologic changes seen in asthma have also been described in the
- The US population over the age of 65 years is projected to grow from about 40 million in 2005 asthma in the elderly, is handicapped by the difficulty of identifying appropriate subjects based on physicians’ diagnoses or on patients’ recollections. Physicians are often reluctant to make the diagnosis, and the accuracy has varied over time and in different locations. include subjects who have only asthma and exclude those who have coexisting lung diseases. Data about death from asthma are conflicting. Death certificates are often inaccurate
- (group 1: 65 years or older, n = 50) with younger patients (group 2: !40 years, n = 99)
- group A: onset before 40, n = 22) were compared with patients developing symptoms later in their lives (group B: onset after 40, n = 22).
- The roles of different inflammatory pathways and mediators of inflammation described in asthma have not been well studied in the elderly with asthma
- staphylococcal enterotoxins can amplify airway inflammation and thus may have an important role in the pathogenesis and progression of asthma
- Allergies are commonly associated with LSA, but much less likely to be associated with LOA Older age of onset is associated with less allergy sensitization. allergy tests in older patients do not seem to correlate well with nasal provocation studies or the presence of allergens in the home environment
- The reasons for the decrease include stiffening of the chest wall, reduced respiratory muscle function, and an increase in residual volume from loss of elastic recoil.
- The values are the best recorded after inhalation of b-adrenergic bronchodilator and are not necessarily the best that could have been obtained after a course of systemic glucocorticoid treatment. The duration of asthma was dated from the first physician’s diagnosis or the first symptoms of wheezing and shortness of breath, whichever came first. There was no difference in the results of patients who received primary care at Mayo Clinic and those referred from other cities. Only 32% of these patients had FEV1 after bronchodilator of greater than 60% of predicted normal value, and 20% had FEV1 of less than 50% of predicted normal value
- Reversible AO,reversible airflow obstruction with improvement in FEV1 after bronchodilator; irreversible AO, incompletely reversible airflow obstruction, postbronchodilator FEV1 is <80%; irreversible AO+BDR,incompletely reversible airflow obstruction with significant bronchodilator responsiveness (BDR); irreversible AO+BHR, incompletely reversible airflow obstruction with significant bronchial hyperresponsiveness with fall in FEV1 after bronchoconstrictor. The label ‘asthma’ can be applied to reversible AO,irreversible AO+BDR and irreversible AO+BHR. Chronic obstructive pulmonary disease (COPD) can be applied to each of the conditions with irreversible AO+BHR. Overlap syndrome is present in irreversible AO+BDR and irreversible AO+BHR.
- The subsets comprising COPD are shaded. Subset areas are not proportional to the actual relative subset sizes. Asthma is by definition associated with reversible airflow obstruction although, in variant asthma, special manoeuvres may be necessary to make the obstruction evident. Patients with asthma whose airflow obstruction is completely reversible (subset 9) are not considered to have COPD. Because in many cases it is virtually impossible to differentiate patients with asthma whose airflow obstruction does not remit completely from persons with chronic bronchitis and emphysema who have partially reversible airflow obstruction with airway hyperreactivity, patients with unremitting asthma are classified as having COPD (subsets 6, 7 and 8). Chronic bronchitis and emphysema with airflow obstruction usually occur together (subset 5), and some patients may have asthma associated with these two disorders (subset 8). Individuals with asthma who have been exposed to chronic irritation, as from cigarette smoke, may develop chronic productive cough, which is a feature of chronic bronchitis (subset 6). Persons with chronic bronchitis and/or emphysema without airflow obstruction (subsets 1, 2 and 11) are not classified as having COPD. Patients with airway obstruction due to diseases with known aetiology or specific pathology such as cystic fibrosis or obliterative bronchiolitis (subset 10) are not included in this definition.
- spirometry, which are essential to diagnose airway obstruction in this population, continues to be underutilized in the primary care setting. Even when these tests are utilized, confusion exists as to what physiologic parameters define asthma in the aging population
- Thirteen single-dose trials and 20 longer duration trials single-dose trials, seven were of asthma, five were on COPD and one reported data on both. mean age of 56.6 years
- 14 were of asthma and 6 were of COPD Mean age of 52.2 years in these trials, which ranged in duration from 3 days to 1 year with a mean trial duration of 4.7 months
- For trials lasting from 3 days to 1 year, 2-agonist treatment Mean age 40 yr for SMART increase re
- none of which included only seniors
- no controlled trials confirming the benefits of inhaled maintenance corticosteroid therapy in elderly asthmatic patients Current users of high doses of inhaled steroids prescribed regularly for 3 or more months were at an increased risk with an OR of 1.44 (95% confidence interval, 1.01-2.06).
- Irrespective of device selection, the practitioner must demonstrate the technique, and provide regular assessment and instruction. Minimisation of polypharmacy of inhaler devices is recommended. pMDI=pressurised metered dose inhaler. DPI=dry powder inhaler
- Multidimensional assessment is represented by the spokes of the wheel and the multidisciplinary intervention by the outer rim of wheel. LABD=long acting bronchodilator. WAP=written action plan