MANAGING ASTHMA IN PATIENTS WITH COMORBIDITIES
| A PRACTICE APPROACH TO PROBLEMS IN ASTHMA MANAGEMENT —Allan T. Luskin, MD, Associate Clinical
Professor of Medicine, University of Wisconsin Medical School, Madison
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| Obstructive lung disease in older population: should be viewed as continuum of lung disorders rather than series
of individual diseases; most older patients have comorbidity—asthma can overlap with fixed airflow obstruction; multiple
disorders can coexist with lung disease (eg, gastroesophageal reflux disease [GERD], laryngopharyngeal reflux disease
[LPRD], hypertension, obesity); multiple diseases increase risk for drug interactions; among elderly, side effects—
rare with inhaled medication; associated with oral medication occur at lower doses than among younger individuals; underreported,
underdiagnosed, underappreciated
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| Drug side effects in elderly: β-agonists—inhaled drugs generally free of side effects; high-dose nebulized therapy
associated with clinically relevant hypokalemia; drug may be poorly tolerated by older people with preexisting hypokalemia
associated with use of oral corticosteroids or diuretics; systemic therapy increases incidence of ventricular
ectopy, particularly in patients also being treated with theophylline who have preexisting coronary artery disease
(CAD)
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 | Anticholinergic drugs, eg, ipratropium (Atrovent) or tiotropium: generally safe; xerostomia—common in elderly; exacerbated
by anticholinergics; concern when swallowing impaired; closed-angle glaucoma—mandates using closed-
mouth inhaling technique or spacer when administering Atrovent; dry powder inhaler (ie, tiotropium) safe; diplopia—
develops when patient with preexisting visual impairment walks into drug cloud
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| Systemic steroids: some data suggest side effects occur at lower doses; inhaled corticosteroids—associated with few
serious side effects; potent steroids increase risk for thrush among patients with preexisting xerostomia and poor dentition;
skin bruising—reported in elderly receiving beclomethasone equivalent dose of 100 µg; side effects at relatively
low corticosteroid doses suggest systemic bioavailability and should prompt reduction in dosing by using, eg, long-acting
bronchodilator or leukotriene modifier
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| Theophylline: no evidence of significant metabolic problems in otherwise healthy elderly patients; congestive heart failure
(CHF) and liver disease alter drug pharmacokinetics; CHF causes decrease of 50% to 80% in metabolism of theophylline;
in elderly, side effects can occur at therapeutic levels
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| Leukotriene modifiers: data suggest zileuton can triple risk for hepatotoxicity in 65- to 70-yr-old women; montelukast
not associated with significant drug interactions or pharmacokinetic issues in elderly; zafirlukast associated with decrease
in elimination in elderly; point—unless specific reason exists for using zafirlukast, montelukast drug of choice
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| Rhinitis therapy in elderly: not worth risk; first-generation antihistamines—associated with anticholinergic effects;
pose significant risk for sedation and ataxia in elderly (ataxia associated with marked risk for hip fracture and subsequent
death); relatively contraindicated in elderly; decongestants—can cause significant problems, eg, ≥120-mg dose
of pseudoephedrine increased risk for hypertension among diabetics; other side effects include prostatism and central nervous
system (CNS) effects; monoamine oxidase (MAO) inhibitors—area of additional concern
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| Drugs that exacerbate asthma: glaucoma therapy—always ask patient about eye drops for glaucoma; cholinergic
drugs (eg, pilocarpine); anticholinesterases (eg, physostigmine-type drugs) can cause bronchospasm and bronchorrhea;
β-blockers—poorly understood; patients at risk of developing problems with β-blockers can be difficult to identify (ie,
β-agonist bronchodilation not predictive; methacholine challenge relatively predictive); some patients do well until they
develop cataclysmic bronchospastic event in association with infection or exertion in cold weather; cough associated
with angiotensin-converting enzyme (ACE) inhibitors—develops in 5% to 10% of patients; unresponsive to β-agonists;
may be attenuated by nedocromil or leukotriene modifiers; rarely eliminated by switching to different ACE inhibitor;
angiotensin receptor blockers—associated with lower incidence of cough; sedatives—contraindicated in elderly;
increase sleep apnea
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| Coping with comorbidity: glaucoma—prostaglandins preferred; if patient needs β-blocker, betaxolol preferable to
timolol; carbonic anhydrase inhibitors acceptable; cholinesterase inhibitors must be monitored carefully
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| Aspirin sensitivity: analgesic alternatives include acetaminophen, codeine, or propoxyphene; anti-inflammatory
alternatives—modest doses of nonacetylated salicylates acceptable; higher-dose nonsteroidal anti-inflammatory
agents (NSAIDs) can cross-react with aspirin and other nonsteroidal agents; acetaminophen problematic when dose
>1000 mg; cyclooxygenase-2 (COX-2) inhibitors usually well tolerated, even without leukotriene modifier
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| Stroke or myocardial infarction (MI) prevention: dipyridamole and clopidogrel—safe unless administered with aspirin;
if aspirin prescribed, implement aspirin desensitization program; alternative drugs—expensive and require clearance
from health maintenance organization (HMO)
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| Hypertension: anticholinergics, β-agonists, and leukotriene modifiers considered safe; topical corticosteroids exert negligible
effect; problematic drugs—oral α-agonists contraindicated; theophylline safe unless given intravenously (IV);
systemic corticosteroids can increase blood pressure by 10 to 20 mm Hg in sensitive patients; drugs used to manage
hypertension— β-blockers (some individuals seem to be more sensitive to side effects); diuretics generally acceptable
(watch for hypokalemia in patients receiving β-agonists); diuretics can increase viscosity of sputum and decrease mucokinesis
in sputum producers who have some degree of chronic obstructive bronchitis in addition to reversible lung
disease; ACE inhibitors, α-blockers, and calcium channel blockers considered safe
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| CAD: anticholinergics and leukotriene modifiers safe; inhaled β-agonists safe, unless high doses administered to patient
with hypoxia; theophylline generally safe (arrhythmogenic side effects avoided when drug used in low doses and hypoxia
corrected in acute situations); topical steroids exert no effect; nasal decongestants contraindicated; first-generation
antihistamines associated with increased ectopy
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| Heart disease: avoid β-blockers; calcium channel blockers and class I and IV antiarrhythmics acceptable; nitrates acceptable
when used with appropriate precautions; class II antiarrhythmics can cause bronchospasm
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| General guidelines: acceptable options include—topical steroids; using montelukast as leukotriene modifier of choice;
low-dose theophylline therapy (monitor drug-drug interactions and levels); administering minimal doses of corticosteroids;
using second-generation antihistamines only (azelastine [Astelin] generally acceptable; sedation may be greater
problem in elderly); caveats—avoid α-agonists and β-blockers; in acute situations, monitor electrolytes and O2 more
closely than in younger patients
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| Drug-drug interactions: antibiotics—tetracycline can interact with ACE inhibitors; trimethoprim-sulfamethoxazole
can cause thrombocytopenia when administered with other sulfonamide-based agents; quinolones interact with warfarin,
theophylline, and glyburide
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| GERD: antacids—avoid; associated with pharmacodynamic interactions; H2 -blockers—cimetidine associated with
most drug-drug interactions; ranitidine, famotidine, and nizatidine less problematic for drug interactions; proton pump
inhibitors (PPIs)—omeprazole (Prilosec; now over-the-counter [OTC]) causes more drug interactions than lansoprazole
(Prevacid) or esomeprazole (Nexium)
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| Geriatric rhinitis: normal physiologic processes of aging include cartilaginous weakening, glandular atrophy, and decreased
microvascular blood flow, leading to decreased airway, thicker mucus, frequent throat clearing, and sense of
postnasal drip; medications (eg, first-generation antihistamines, diuretics, some anxiolytics, β-blockers) exert drying
effect; allergy and GERD compound these effects
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| Management of mucus: minimize drying medications—reduce use of first-generation antihistamines; avoid α-agonists
and some antihypertensive agents; exert caution when administering nasal steroids (worsen dryness, cause crusting,
bleeding, and bruising); use—normal saline for dryness; nasal rinses to improve mucus flow and minimize
crusting; hypertonic saline when managing acute sinusitis
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| Chronic obstructive pulmonary disease (COPD): progressively limited air flow—not fully reversible; associated
with abnormal inflammatory response of lungs to noxious particles or gases (primarily tobacco smoke; occupational
dust and fumes; indoor and outdoor pollution)
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| COPD in young adults: rapidly increasing in prevalence; frequently undetected; 70% of people diagnosed with COPD
<65 yr of age; associated with—environmental tobacco smoke; low socioeconomic status; childhood infections; being
“chesty” child; occupational exposure
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| Key issues: COPD appears to interact or overlap with asthma to produce synergistic or additive effect; not all people who
smoke tobacco develop significant lung disease (atopy and history of childhood disease exert additive effect and render
some individuals susceptible to toxic effects of tobacco smoke); diagnostic clues—smoking history of ≥10 pack-
years; dyspnea; chronic cough with or without sputum production; onset of respiratory symptoms during 40s; persistent
or recurrent respiratory infection; points—active asthma and cigarette smoking major risk factors for chronic obstructive
bronchitis; embarrassment over disease often keeps patient from seeking help early on
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| Classic case example: patient presents with—shortness of breath on mild exertion; suggestive smoking history; slowly
progressive symptomatology; chronic cough; objective findings—decreased forced expiratory volume in 1 sec
(FEV1 ) and forced vital capacity (FVC); FEV1 /FVC ratio of 59%; minimal improvement in FEV1 and FVC; exhaled
nitric oxide (eNO) of 33 ppb; data show patient—has poor reversibility; probably has COPD; also has eosinophilic
inflammatory event, ie, asthma; eNO may be factor that can help determine management approach
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| Treatment of COPD: patients must stop smoking to halt decline in lung function (inhaled corticosteroids and other
anti-inflammatory agents ineffective in this respect); bronchodilators—treatment mainstay; improve function; not
anti-inflammatory; tiotropium—marginally better bronchodilator than salmeterol (both agents appropriate for
COPD); similar to ipratropium in reducing hospitalization and exacerbations, and improving endurance
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| Inhaled corticosteroids: necessary to manage inflammation due to ongoing asthmatic component; beneficial when used
with or without long-acting β-agonist (LABA); decrease frequency and severity of exacerbations; do not modify long-
term decline in lung function; not every patient responds to inhaled corticosteroids—cigarette smoking can reduce
response to inhaled and oral corticosteroids; trial of inhaled corticosteroids can assess potential response, ie, patients
symptomatic on maximum bronchodilator therapy should receive 6 to 12 wk of corticosteroids; observations—
increased fracture risk associated with >700-µg dose of beclomethasone dipropionate (BDP) or equivalent administered
for ≥2 yr; younger patients with asthma overlap and severe disease exacerbations benefit from inhaled corticosteroid
given alone or in combination with long-acting bronchodilator
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| Points: smoking cessation crucial; exercise programs—improve exercise tolerance and symptoms of dyspnea and fatigue;
benefit virually all patients; weight loss—enables patients to exercise, reduces sleep apnea and reflux disease;
sleep evaluation—often appropriate; Epworth sleepiness scale useful in elderly; health education—improves overall
health status and ability to cope with disease; anxiety and depression increase risk for rehospitalization
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| Conclusions on COPD management: history of smoking and poor reversibility of airflow indicative of coexisting
COPD; initiate bronchodilator therapy whenever dyspnea or other symptoms limit activity (LABAs and/or tiotropium
useful); inhaled corticosteroids—mandatory when asthma present (bronchodilators alone do not eliminate symptoms)
or eNO elevated; trial helpful in patients with pure COPD
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| Additional observations: elderly or postmenopausal patients on anything more than lowest dose of inhaled corticosteroids
require exercise and vitamin D and calcium supplementation; immunotherapy not contraindicated in United States
for elderly patients who have significant allergic component; potential caffeine risk—some data suggest caffeine may
increase patient’s risk of developing hypertensive response to pseudoephedrine or phenylephrine
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| SAMTER’S TRIAD: ASTHMA WITH NASAL POLYPOSIS AND ASPIRIN SENSITIVITY —K. Christopher McMains,
MD, Assistant Professor, Department of Otolaryngology, University of Texas Health Sciences Center, San Antonio
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| Samter’s triad: defines association between asthma, nasal polyposis, and aspirin sensitivity; NSAID ingestion responsible
for 25% of acute admissions of asthma patients requiring ventilation; incidence of aspirin sensitivity 30% to 40%
among patients with Samter’s triad; pathophysiology—common respiratory epithelium theory (currently favored concept;
suggests asthma and rhinosinusitis different phenotypic expressions of common derangement); arachidonic acid
metabolism implicated in disease process
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| Aspirin desensitization: indicated in patients with—concomitant disease requiring aspirin for maintenance; asthma
requiring high-dose steroid maintenance; refractory sinus disease requiring multiple surgeries; contraindicated in
patients—with unstable asthma or asthma unresponsive to steroids; who receive β-blockers; who might not be able to
continue daily aspirin maintenance
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| Revision functional endoscopic sinus surgery (FESS): data show—FESS benefits patients with Samter’s triad;
addition of desensitization decreases likelihood that patients with Samter’s triad will require additional surgical intervention
over 2-yr period
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Educational Objectives
| The goal of this program is to educate the listener about current concepts in the management of some airway diseases. After
hearing and assimilating this program, the clinician will be better able to:
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| 1. Describe the complexities of managing obstructive airway disease in older individuals.
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| 2. Avoid potential drug complications associated with the management of elderly asthma patients.
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| 3. Explore options for managing older asthma patients with coexisting medical problems.
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| 4. Diagnose and manage patients with chronic obstructive pulmonary disease (COPD).
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| 5. Discuss an approach to the management of patients with Samter’s triad.
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Discussed on This Program
Acetaminophen (N -acetyl-P -aminophenol; APAP) [several trade names and preparations]
Alendronate sodium [Fosamax]
Aspirin (acetylsalicylic acid; ASA) [several trade names and preparations]
Azelastine HCl [Astelin, Optivar]
Beclomethasone dipropionate (several trade names and preparations)
Betaxolol HCl [Betoptic, Betoptic S, Kerlone]
Budesonide (several trade names and preparations)
Caffeine (several trade names)
Calcium (several trade names and preparations)
Cimetidine [Cimetidine Oral Solution, Tagamet, Tagamet HB 200]
Clopidogrel bisulfate [Plavix]
Codeine PO4
Cyproheptadine HCl
Dipyridamole [Persantine, Persantine IV]
Esomeprazole magnesium [Nexium]
Famotidine [Pepcid, Pepcid AC, Pepcid RPD]
Fluticasone propionate (several trade names and preparations)
Formoterol fumarate [Foradil Aerolizer]
Glyburide (glibenclamide) [DiaBeta, Glynase PresTab, Micronase]
Ipratropium bromide [Atrovent]
Lansoprazole [Prevacid, Prevacid IV]
Methacholine chloride [Provocholine]
Montelukast sodium [Singulair]
Nedocromil sodium [Alocril, Tilade]
Nizatidine [Axid AR, Axid Pulvules]
Omeprazole [Prilosec, Prilosec OTC, Rapinex]
Phenylephrine HCl (several trade names and preparations)
Physostigmine salicylate [Antilirium]
Pilocarpine (several trade names and preparations)
Prednisone (several trade names and preparations)
Propoxyphene (dextropropoxyphene) [Darvon-N, Darvon Pulvules
Pseudoephedrine HCl (d-isoephedrine HCl) [Several trade names and preparations]
Ranitidine HCl [Zantac, Zantac 75, Zantac EFFERdose]
Salmeterol xinafoate [Serevent Diskus]
Terfenadine [Seldane] (discontinued 7/98)
Tetracycline HCl [Sumycin 250, Sumycin 500, Sumycin Syrup]
Theophylline (several trade names and preparations)
Timolol maleate [Betimol, Blocadren, Isatol, Timoptic, Timoptic-XE]
Tiotropium bromide [Spiriva, Spiriva HandiHaler]
Trimethoprim-sulfamethoxazole (co-trimoxazole; TMP-SMZ) [several trade names and preparations]
Vitamin D
Warfarin sodium [Coumadin]
Zafirlukast [Accolate]
Zileuton [Zyflo]
Suggested Reading
Barua P, O’Mahony MS: Overcoming gaps in the management of asthma in older patients: new insights. Drugs Aging
22:1029, 2005; Kaminsky DA, Marcy TW: COPD and smoking cessation motivation. Chest 125:1958, 2004;
Keam SJ, Keating GM: Tiotropium bromide. A review of its use as maintenance therapy in patients with COPD.
Treat Respir Med 3:247, 2004; Luskin AT: Achieving asthma control: the need for risk assessment. Manag Care 14:12,
2005; Luskin AT et al: The relationship between prescribed and delivered doses of inhaled corticosteroids in adult asthmatics.
J Asthma 38:645, 2001; Newnham DM: Asthma medications and their potential adverse effects in the elderly:
recommendations for prescribing. Drug Saf 24:1065, 2001.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed:
Dr. Luskin is affiliated with Aventis, Genentech, Inc., Merck & Co, Inc., and Schering-Plough.
Dr. Luskin gave his scientific presentation at Controversies in Asthma and Allergies: 2006, presented February 11, 2006,
in San Francisco, CA, by the Allergy, Asthma, & Immunology Foundation of Northern California and the American Academy
of Allergy, Asthma, and Immunology; Dr. McMains gave his scientific presentation at the Annual Combined Otolaryngological
Spring Meetings (COSM) Conference of the American Rhinologic Society held May 12-14, 2005, in
Boca Raton, FL. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production
of this program.
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