asthma: co-existing and co-morbid conditions

Richard F. Lockey, M.D.Division of Allergy and Immunology

Department of Internal MedicineUniversity of South Florida

College of Medicineand

James A. Haley Veterans’ Medical CenterTampa, Florida

Asthma: Co-Existing and Co-Morbid Conditions

Learning Objectives

At the completion of this presentation, the participant should be able to:

1.Have knowledge of co-existing and co-morbid conditions of asthma

2.Understand that asthma cannot be properly treated unless these conditions are addressed

1. Food2. Rhinosinusitis

a. Allergicb. Non-allergicc. Infectiousd. Nasal polyposise. Other

3. Gastroesophageal Reflux Disease (GERD)

4. Vocal Cord Dysfunction (VCD)

5. Obesity6. Osteopenia and

Osteoporosis

7. Psychological Problems

8. Churg-Strauss Disease

9. Sleep Apnea

10. Pregnancy

11. COPD versus Asthma

12. Eczema

13. Smoking Cessation

14. Infection (Vaccination)

15. Bronchiectasis and Cystic Fibrosis

16. Exercise-Induced Asthma

17. Others- Endocrine, Conjunctivitis,Congestive Heart Failure, Pulmonary Embolism, Medications

18. Primary Ciliary Dyskinesia

Introduction• Asthma is perhaps the most treatable of all

chronic diseases.

• For optimal outcomes, co-existing and co-morbid conditions must be identified and treated.

• Co-morbid conditions and their diagnosis and treatment should be included in asthma guidelines

Questions for patients with asthma (children and adults as appropriate)

1. History + ask and think about co-morbid conditions

2. Complete physical examination3. Spirometry and flow volume loop, as

necessary

4. Risk factors for various co-morbid conditions (almost everyone has risk factors)

5. Psychological profile

Questions for patients with asthma (children and adults as appropriate)

6. Sleep profile

7. Weight assessment

8. Smoking (drinking and drug) assessment

9. Diet – appropriate calcium and vitamin D. Exercise (walk 1.5 miles) or stand (1.5 hours)

10. Dexa bone scan?

11. Rhinoscopy, as indicated

12. Vaccination assessment

13. Others as necessary

Risk factors for exacerbation of difficult-to-treat asthma

39 had 3 severe exacerbations/yr136 subjects 29 had 1 severe exacerbation/yr

Brinke , et al. Eur Respir J 2005; 26: 812.

Conclusions1) Odds ratio (OR) associated with 3

exacerbationsa) severe sinus disease, OR 3.7b) GERD, OR 4.9c) URIs, OR 6.9d) Psychological dysfunction, OR 10.8e) Obstructive sleep apnea, OR 3.4

2) All patients with frequent exacerbations had 1/5 while 52% had 3/5

Brinke , et al. Eur Respir J 2005; 26: 812.

Risk Factors for Fatal Asthma>> Social history

- Low socioeconomic status or inner-city residence

- Illicit drug use

- Major psychosocial problems

>> Co-morbidities

- Cardiac disease

- Other chronic lung disease

- Chronic psychiatric disease-Adapted from NIH/NHLBI National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma: Clinical practice guidelines. Bethesda (MD): 2007-Guilbert T et al. In Middleton 7th ed. Allergy: Principles and Practice, 2009, p 1323

Rhinosinusitis

Rhinosinusitis (Allergic, Nonallergic, Infectious) and Asthma

Incidence and Association1. Rhinitis (all kinds) linked to sinusitis

(rhinosinusitis) and to nasal polyps – all of which are co-morbid conditions of asthma

2. Up to 70% of patients with asthma alsopresent with rhinosinusitis.

Annesi-Maesano I. Allergy 1999;54 (suppl) 7-13


Incidence and Association

3. Allergic rhinitis can be a precursor of asthma

4. Deterioration of rhinitis symptoms negatively impacts bronchial responsiveness and conversely adequate management of rhinitis improves asthma

5. Chronic sinus disease may be linked to severe asthma

Bachert C et al. In: Middleton 7th ed. Allergy: Principles and Practice, p 991


Incidence and Association

6. Postulated that perennial allergic and non-allergic rhinitis rather than seasonal rhinitis predisposes to

“sinusitis”

7. Controlling infectious sinusitis may decrease asthma medication needs

Moss MH et al. In: Middleton 6th ed. Allergy: Principles and Practice, 2003, p 1225

Nasal Polyps and Asthma1. Nasal polyps unusual in atopic patients2. 40 – 80% of aspirin-exacerbated asthma

subjects have nasal polyps and 15% of polyp patients have aspirin-exacerbated asthma

3. Nasal polyps in 37 – 48% of patients with cystic fibrosis (some patients have concomitant asthma)

4. Bronchial hypersensitivity exists in many patients with polyps

Bachert C et al. In: Middleton 7th ed. Allergy: Principles and Practice, p 991

Gastroesophageal Reflux Disease

(GERD)

Atypical symptoms of GERD

• Chest pain

• Hoarseness

• Chronic cough

• Sore throat

• Wheezing– 80% of subjects with

asthma may have GERD

• Throat clearing

(feels like “cotton- ball” which cannot clear)

• Globus

• Laryngospasm

• Dental erosion

-Mujica et al. Postgrad Med 1999-DeVault et al. Am J Gastroenterol 1999

Symptoms of GERD in Childhood

• Regurgitation especially after eating• Signs of esophagitis (irritability, arching,

choking, gagging, feeding aversion)

Symptoms resolve in most by 12-24 mo• Older children abdominal and chest discomfort• Also, stridor, obstructive apnea, or lower

airway disease

Orenstein S et al. Nelson 17th ed., 1217

Prevalence of GERD in Children

• Abnormal pH probes common and many such patients have no clinical symptoms

Chiquette et al. J Asthma 2002;39:135

Khoshoo et al. Chest 2003;123:1008

Sheikh et al. Pediatr Pulmonol 1999;28:181

Cochrane Data Base Review of GERD Treatment for Asthma in Adults and

Children (2006)• 12 randomized controlled trials of Rx for GERD in adults and

children• 2 independent reviewers• Interventions included proton pump inhibitors (6), H2 receptor

antagonists (5), surgery and conservative management (1)• Temporal relationship in 4 trials found between asthma and

GERD• Anti-reflux Rx did not consistently improve lung function,

asthma symptoms, nocturnal asthma and medication use• Conclusion: No overall improvement but subgroups may gain

benefit; albuterol use may be decreased

GERD and Chronic Rhinosinusitis

• Upper respiratory symptoms frequent among subjects with symptomatic GERD Dx’d by esophageal study

• GERD associated with chronic rhinosinusitis in children and adults

-Theodoropoulos DS et al. Am J Resp Crit Care Med 2001;164:72-6-Barbero GJ. Otolaryngol Clin North Am 1996;29:27-38-Phipps CD et al. Arch Otolaryngol Head Neck Surg 2000;126:831-6-Ulualp SO et al. Am J Rhinol 199;13:197-202-DiBaise et al. Ann Int Med 1998;1291078-83

Vocal Cord Dysfunction (VCD)

Vocal Cord Dysfunction (VCD)Definition of VCD• Paradoxical adduction (closure) of the vocal cords/

folds during inspiration and/or early expiration• “Irritable larynx syndrome”• Episodic laryngeal dysfunction triggered by irritant

exposures or can occur spontaneously with variable clinical manifestations: chronic cough, frequent throat-clearing, globus pharyngeus, choking episodes, dysphonia, masquarades as asthma; exercise–induced asthma, or complicates asthma

-Mikita JA, et al., All Asthma Proc 2006;27:411.-Bahrainwala AH, et al., Curr Opin Pulm Med 2001;7:8.-Byrd RP, et al., Postgrad Med 2000;108:37.-Balkissoon R, In: Nonallergic Rhinitis, Baraniuk JN, Shusterman D (eds): Informa

Healthcare USA, Inc., New York, pp. 411, 2007.

VCD

Diagnostic Criteria1) Paradoxical inspiratory

adduction of anterior 2/3 vocal folds on laryngoscopy

2) ± Posterior diamond-shaped glottic gap

3) Variable extrathoracic obstruction on flow volume loops

posteriorposterior

anterioranterior

Spirometry and Flow Loop• FEV1 (88% of predicted),

no bronchodilator response.

Flattened inspiratory loop

Vocal Cord Dysfunction (VCD)

National Jewish Health95 subjects with asthma and/or VCDa. 42 had VCD aloneb. 53 had VCD with asthmac. 28% had been intubatedd. Misdiagnosed with asthma for average

of 4.8 yrse. “Very sick patients” with VCD

Newman AB et al. Am J Resp Crit Care Med 1995;152:1382

Psychosocial Problems


• Stress is linked to many diseases – asthma is no exception

• Stress may alter immune system in direction of Th2 response

• Depression particularly dangerous – especially for severe asthma

• Psychological problems are particularly dangerous for a patient with severe asthma

Bloomberg GR, Chen E. Immunol Allergy Clin N Am 2005;25,83


• Stress associated with increased prevalence of asthma

• Stress associated with increased exacerbations

• ? whether asthmatic children have significantly more total anxiety disorders, lower self-esteem, greater functional impairment, past school problems, past psychiatric illnesses, and familial stress

-Guilbert T et al. In Middleton 7th ed. Allergy: Principles and Practice, 2009, pp 1319-1343 -Wright RJ et al. Am J Respir Crit Care Med 2002;165:358-365-Sandberg S et al. Lancet 2000;356:982-987

Asthma and Sleep Apnea


DefinitionObstructive Sleep Apnea Syndrome (OSAS) is:

1. Complete or partial collapse of the upper airways during sleep with consequent cessation of breathing despite ongoing respiratory effort plus coexistent daytime somnolence2. Coexistent daytime somnolence (disabling)

-Staevska MP, Baraniuk JN. Rhinitis and Sleep Apnea. In: Baraniuk J, -Shusterman D (eds). Nonallergic Rhinitis, 2007, Informa Healthcare, New York, 449-472

Asthma and Sleep ApneaAdult SymptomsAt least one of the following 3 observations:1. Patient complaints of unintentional sleep

episodes during wakefulness, daytime sleepiness, unrefreshing sleep, fatigue, or insomnia

2. Patient wakes up at night with breath holding, gasping, or choking

3. Bed partner observes symptoms of loud snoring and/or breathing interruptions-

Staevska MP, Baraniuk JN. Rhinitis and Sleep Apnea. In: Baraniuk J, Shusterman D (eds). Nonallergic Rhinitis, 2007, Informa Healthcare, New York, 449-472

Asthma and Sleep ApneaSymptoms - Children1. The caregiver reports snoring and/or labored or

obstructed breathing during sleep.

2. The caregiver observes at least one of the following: - Paradoxical inward rib cage motion during

inspiration movement arousals - Diaphoresis - Neck hyperextension during sleep - Excessive daytime sleepiness, hyperactivity, or

aggressive behavior - Slow rate of growth - Morning headaches - Secondary enuresis

Staevska MP, Baraniuk JN. Rhinitis and Sleep Apnea. In: Baraniuk J, Shusterman D (eds). Nonallergic Rhinitis, 2007, Informa Healthcare, New York, 449-472

Asthma and Sleep Apnea Prevalence of Obstructive Sleep

Apnea-Hypopnea (OSAH) in Severe versus Moderate Asthma

1. 23 of 26 (88%) with severe asthma, 15 of 26 (58%) with moderate asthma, 8 of 26 (31%) controls without asthma had apnea-hypopnea index ≥ 15 events/hour

Using more restrictive criteria, 50% severe, 23% moderate, and 12% (control) of subjects had obstructive sleep apnea (OSA)

2. No correlation between severity of sleep-disordered breathing and asthma severity

Julien JY et al. J Allergy Clin Immunol 2009;124:371-6


1. Risk of sleep apnea increases with nasal obstruction, large adenoids and tonsils, and elongated face.

2. Rhinitis appears to increase the risk of obstructive sleep apnea.

3. Many other risk factors associated with sleep apnea include obesity, gastroesophageal reflux, endocrine problems, and others.

Asthma and Infection (Vaccination)

Influenza

• Influenza is a trigger for the development of asthma as well as exacerbates asthma

• Influenza infection leads to decline in lung function. It increases the risk of hospitalization and death in patients with COPD– May cause up to 30% of COPD

exacerbations/year

Influenza Vaccine

• An injectable trivalent, inactivated viral vaccine (TIV) composed of seasonal H3N2, H1N1, and Influenza B

• A live attenuated vaccine (LIAV) is also available• Studies show no increase in symptoms after

vaccination• Low to medium dose ICS does not affect vaccine

responsiveness– High dose ICS does decrease response to Influenza

B• Current evidence is conflicting on the effectiveness of

influenza vaccination in preventing morbidity and mortality in COPD and asthma

• Influenza vaccination is recommended in asthmatics and COPD based upon the known complications of influenza infection

CDC. MMWR: Recommendations and Reports 2009;58:1-52 (RR-8)

Streptococcus pneumoniae• Colonization occurs frequently in patients with

COPD and asthma and increases the risk for exacerbation as well as invasive disease

• Currently, a 23-valent polysaccharide vaccine (PPV-23) is recommended for use in:– Adults ≥ 65– ≥ 2 years whom are at risk for invasive disease

• Revaccination is recommended for:– ≥ 65 if previous dose was given at age < 65– Patients at risk for invasive disease– Should be given no sooner than 5 years after

previous dose-Talbot T et al. N Engl J Med 2005;352:2082-90-Juhn YJ et al. J Allergy Clin Immunol 2008;122:719-23

Streptococcus pneumoniae

• The risk of pneumonia is 11% to 17% in two studies of asthma.

• The Advisory Committee on Immunization Practices (ACIP) recommends all adults with asthma(19-64 yrs) receive the vaccine for S. pneumoniae (PPV-23).

-Talbot T et al. -Talbot T et al. N Engl J Med N Engl J Med 2005;352:2082-902005;352:2082-90-Juhn YJ et al. -Juhn YJ et al. J Allergy Clin Immunol J Allergy Clin Immunol 2008;122:719-232008;122:719-23-Jung J et al. -Jung J et al. J Allergy Clin Immunol J Allergy Clin Immunol 2010;125;217-212010;125;217-21

Pertussis

• 5,000-7,000 cases occur each year in the U.S. • Adults can serve as a reservoir for infection of

children due to waning immunity• Infection with B. pertussis can lead to

exacerbations of both asthma and COPD• A combination vaccine of tetanus, diphtheria,

and pertussis [Adacel (TdaP)] is recommended in these patients as a single dose vaccination for adults age 19-64– Vaccination has been shown to reduce the number

of cases by 44%

CDC. CDC. MMWR: Recommendations and Reports 1997;46:1-25(RR-7)CDC. MMWR: Recommendations and Reports 2006;55:1-37 (RR-17)

Herpes Zoster• Reactivation of Varicella Zoster leads to significant

morbidity in aging adults, and patients on high dose inhalational or oral steroids (<20mg/day prednisone) may be at higher risk.

• Zostavax has been shown to reduce the incidence of herpes zoster reactivation by 51.3% and post-herpetic neuralgia by 66.5%.

• Recommended for all adults (60 and older) as a single dose. Also recommended for all asthmatics and patients with COPD, 60 years and older if on ≤ 20mg/day of prednisone (or equivalent glucocorticosteroid).

CDC. MMWR: Recommendations and Reports 2008;57:1-30 (RR-5)

Conclusions• Asthma is perhaps the most treatable of all

chronic diseases.• For optimal outcomes, co-existing and co-

morbid conditions must be identified and a appropriately treated.

• Co-existing and co-morbid conditions should be part of asthma guidelines

asthma: co-existing and co-morbid conditions

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