Jennifer McCallister, MD April 5, 2013 Sex Differences in Asthma
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Jennifer McCallister, MD April 5, 2013
Sex Differences in Asthma
Objectives
Epidemiology Mechanisms Clinical applications
Asthma Prevalence by Age & Sex
0
2
4
6
8
10
12
0 to 4
5 to 14
15 to
19
20 to
24
25 to
34
35 to
64
65 and grea
ter
MaleFemale
Moorman et al. MMWR Surveill Summ 2007; 56 (8), 1-54.
Presenter
Presentation Notes
Asthma is one of the most common pulmonary diseases worldwide, affecting an estimated 300 million people and resulting in approximately 250,000 per year. Interesting trends in asthma prevalence and severity have been observed related to sex and age as illustrated here.
Asthma Prevalence by Age & Sex
Total asthma prevalence in U.S. Male 7.0 % Female 9.3 %
Children aged 0-17 years Male 11.3 % Female 7.9 %
Akinbami et al. Natl Health Stat Report. 2011 Jan 12;(32):1-14.
Asthma Mortality
At-risk-based death rate from asthma higher in females 2005-2009, National Health Statistics Report in
U.S. 1.29 females vs. males
Akinbami et al. Natl Health Stat Report. 2011 Jan 12;(32):1-14.
Asthma Morbidity
Women with asthma report More frequent asthma symptoms1
Poorer quality of life1
Greater healthcare utilization1-3
More frequent courses of systemic3 corticosteroids
Despite better baseline pulmonary function2-4
1. Sinclair, et al. J. Asthma 2006;43:363 2. Osborne, et al. AJRCCM, 1998;157:123. 3. Lee, et al. J Asthma 2006;43:179. 4. Wijnhoven, et al. J Asthma 2003; 40:189.
Asthma Exacerbations & Emergency Department Presentations
Women More likely to be admitted1-2
Describe symptoms as more severe3
Despite Better pulmonary function1-3
Less hypercapnia4
1. Singh, et al. Arch Intern Med 1999;159:1237. 2. Awadh, et al. Respir Med 1996;90:485. 3. Cydulka, et al. Ann Emerg Med, 2001;38(2):123. 4.Trawick, et al. Chest 2001;119:115.
Presenter
Presentation Notes
Clinically similar refers to baseline characteristics (insurance, age at diagnosis, medication use, prior admissions for asthma, etc)
Singh, A. K. et al. Arch Intern Med 1999;159:1237-1243.
Sex Differences Among Adults Presenting to the ED with Acute Asthma
Presenter
Presentation Notes
Restrospective review of 1228 patients presenting to ED at Mass General with acute asthma; both and initial and follow-up PEFR (%predicted) were higher for women. Despite this, women were more likely to be admitted to the hospital for further care (OR 2.2 (CI 1.3-4.0)
Patients Reporting Severe Distress in 24 hours Prior to Seeking ED Care
Cydulka, et al. Ann Emerg Med, 2001;38(2):123.
%
Presenter
Presentation Notes
Women were more likely than men to report “severe” complaints in terms of symptom frequency, intensity, and resulting activity limitations; women with moderate exacerbations were especially likely to describe their exacerbations as causing “severe” activity limitations
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Trawick, D. R. et al. Chest 2001;119:115-119
Comparison of pCO2 Levels in Women vs. Men Hospitalized for Asthma
Presenter
Presentation Notes
Yale-New Haven Hospital, 10-yr retrospective study of high-risk patients (2 admits for asthma or status asthmaticus); Proportions of each gender requiring admission to MICU (15.65% women vs. 11.67% men) and intubation (8%women vs 5% men) were similar. Do differences in the ventilatory response to hypercapnea or in the tolerance to airway obstruction contribute to gender differences in asthma?
Gender Bias in Diagnosis of Obstructive Lung Diseases? Chapman et al surveyed 192 primary care
physicians using hypothetical case and interview Cough and dyspnea in smoker 6 versions of case differing in age & sex of patient
Asked to provide most likely diagnosis and choose diagnostic studies Later given spirometry with irreversible airflow
obstruction
Chapman et al. Chest 2001; 119:1691-1695.
Presenter
Presentation Notes
6 versions of case, differing only in age and sex of patient; later presented with spirometry with moderate or severe airflow obstruction without BD response
Gender Bias in Diagnosis of Obstructive Lung Diseases? Initial diagnosis COPD: 65% men vs. 49% women (p<0.05) Asthma: 32% men vs. 44% women
After spirometry COPD: 76% men vs. 65% women Asthma: 22% men vs. 32% women
Chapman et al. Chest 2001; 119:1691-1695.
Presenter
Presentation Notes
Spirometry significantly improved diagnosis, narrowed gender differences, however only 22% of surveyed physicians ordered this test. CONCLUSIONS: North American physicians underdiagnose COPD, especially in women. Spirometry improves diagnosis, but is underused.
Sex Differences in Consistency of Care with National Asthma Guidelines?
Men (%) Women (%) p Possess ICS 68 71.9 0.007 Use daily ICS 58.3 49.6 0.001 Action Plan 51.1 52.5 ns Peak-flow monitoring
21.0 20.4 ns
Avoid Triggers 49.0 52.2 ns Asthma
specialist 43.1 37.7 0.001
Krishnan, et al. Arch Intern Med, 2001; 161:1660.
n= 5062
Presenter
Presentation Notes
Evaluated 5062 patients enrolled in 16 HCO’s and surveyed regarding compliance with 1991 NAEPP guidelines focusing on possible race and sex differences; differences in asthma care by sex were small and tended to favor women. However, fewer african americans reported care c/w recommendations than whites (not included in this slide)
Adherence to Inhaled Corticosteroid Regimens Self-reported compliance higher in women1
Adherence 28% lower in women (p=0.08) HMO prescription-refill data2
No sex differences in adherence in research trial for COPD3
1. Lindberg et al, 2001. Int J Qual Health Care;13(5):375. 2. Williams et al, 2007. JACI;119(1):168. 3. Turner et al, 1995. Chest;108(2)394.
Influence of Sex on Metered-dose Inhaler Technique Un-coached MDI technique observed in 59
subjects (26 female & 33 male) Inspiratory flow rate Timing of actuation Inspiratory volume Breath-holding time
Acceptable maneuvers 25% subjects 43% males 4% females (p<0.001)
Goodman et al, 1994. AJRCCM;150(5):1256.
Presenter
Presentation Notes
Gender differences independent of age (20-81 yrs) and type of obstructive lung disease (asthma or emphysema)
Perception of Air-flow Obstruction
Inspiratory muscle strength (PImax) significantly reduced in females with mild-moderate asthma Associated with more dyspnea and short-acting
beta-agonist use (SABA) With training, female subjects increased PImax
with resulting decrease in dyspnea and SABA use
Weiner, et al. Chest, 2002; 122(1):197.
Presenter
Presentation Notes
Inspiratory muscle strength as assessed by maximal inspiratory mouth pressure (PImax)
Is Bronchial Hyperresponsiveness (BHR) More Common in Women?
Study n BHR Men BHR Women Differences related to
FEV1? Britton, et al. 1994
2,415 --- OR 2.05 (CI 1.6-2.7)
YES
Leynaert, et al. 1997
799 (2 populations)
A: 11.9% B: 29.5%
A: 33.7% B: 43.2%
NO NO
Norrman, et al. 1998
1448 10.6% 15.0% NO
Manfreda, et al. 2004
2,962 1.76 (CI 1.36-2.28)
NO
Presenter
Presentation Notes
In the studies that reveal gender differences in BHR, most suggest BHR is increased in women. BHR is known to be independently associated (inversely realted) to FEV1
Women and Tobacco Smoke
Increased BHR may relate to increased susceptibility to tobacco smoke Female smokers at higher risk for tobacco-
related loss in pulmonary function1-3
Recovery of lung function is greater in women who stop smoking4
1. Dransfield et al, 2006. Respir Med;100(6):1110. 2. Prescott et al, 1997. Eur Respir J;10(4):822. 3. Xu et al, 1994. Eur Respir J;7(6):1056. 4. Connet et al, 2003. Am J Epidemiol;157(11):973.
Presenter
Presentation Notes
Studies of patients with COPD have revealed that women are at higher risk for suffering tobacco-related loss of pulmonary function. Interestingly, when women stop smoking, they seem to recover more lung function than men.
Tobacco and BHR cont.
Lung Health Study Current smokers with mild-to-moderate
obstruction BHR more common in women (85.1% vs 58.9%) More women (46.6% vs 23.9%) responded to ≤ 5
mg/ml methacholine BHR related to pack-years tobacco use only in
women (p=0.044)
Tashkin et al, 1992. Am Rev Respir Dis;145(2):301.
Presenter
Presentation Notes
Methacholine testing in 5,877 current smokers with mild-to-mod obstruction (FEV1/FVC .63)
Estrogen, Progesterone, & Asthma
Patterns in asthma prevalence & severity correlate with key transition points in the reproductive cycle No clearly established link between asthma &
female sex hormones Menstrual-related asthma (MRA) Pregnancy Menopause & post-menopausal hormone use
Prevalence of Menstrual-related Asthma (MRA) 35 to 40% of women report increased symptoms
near onset of menses1-2
Menstrual-related asthma Reductions in peak expiratory flow rates (PEFR) Increased β-agonist use in perimenstrual period
(Days -5 to 5)
1. Hanley SP,1981. Br J Dis Chest;75(3):306. 2. Gibbs et al, 1984. Thorax;39(11):833. 3. Shames et al, 1998. Ann Allergy Asthma Immunol;81(1):65.
Presenter
Presentation Notes
Clinically significant=urgent care visits
BHR and MRA
Pauli et al compared 11 women with asthma and no prior MRA to 29 controls1
No changes in spirometry or BHR over menstrual cycle either group
Asthma symptoms deteriorated (p=0.001) & PEFR decreased (p=0.045) from follicular to luteal phase
Tan et al evaluated 15 asthmatics without MRA2
Increased BHR to adenosine 5’-monophosphate from follicular to luteal phase (p<0.05)
1. Pauli et al, 1989. Am Rev Respir Dis;140(2):358. 2. Tan et al, 1997. AJRCCM;155(4):1273.
Presenter
Presentation Notes
Several authors have investigated influence of the menstrual cycle on BHR, no conclusive patterns have been established. Follicular Day 1 to 6, Luteal Day 21 to 24
Inflammatory Markers in MRA
In women with self-reported MRA1
Sputum eosinophilia and exhaled nitric oxide (eNO) increased at time of menses
Correlated with increase in asthma symptoms In women with PMA and decreases of PEFR2
>40% from baseline with menses LTC4 increased during premenstrual phase Pranlukast administration prevented decrease in
PEFR
1. Oguzulgen et al, 2002. J Asthma;39(6)517. 2. Nakasato et al, 1999. JACI; 104(3):585.
Menopause, Hormone Replacement Therapy (HRT), & Asthma
Nurses’ Health Study1
RR 2.30 (CI 1.69-3.14) newly diagnosed asthma and postmenopausal HRT in current estrogen users when compared to never users
Copenhagen City Heart Study2
Weak association between self-reported asthma and asthma symptoms in postmenopausal women using HRT
1. Barr et al, 2004. Arch Intern Med;164(4):379. 2. Lange et al, 2001. Thorax;56(8):613.
What does this mean clinically?
Is Sex Specific Analysis of Asthma Symptoms Profiles Helpful? Current national guidelines emphasize routine
assessment of asthma control Lack information about whether sex-specific
assessment measures should be considered
Effect of Sex on Asthma Symptoms & Triggers
010203040506070
Dyspnea Frustrated Cough ChestTightness
Smoke Weather/airpollution
Male Female
Sinclair et al. J Asthma 2006;43:363.
Sex Differences in Asthma Symptoms Profiles & Control Assessment
American Lung Association Asthma Clinical Research Center (ALA-ACRC) network of 19 clinical research centers dedicated to research of asthma treatment
Retrospectively reviewed baseline data for 1612 adults enrolled in 4 previously published studies
McCallister et al. AJRCCM 2011; 183: A4309.
Sex Differences in Asthma Symptoms Profiles & Control Assessment
Sex specific analysis of item responses to standardized asthma questionnaires Juniper Asthma Control Questionnaire (ACQ) Juniper mini-Asthma Quality of Life Questionnaire
(mini-AQLQ) Asthma Symptom Utility Index (ASUI)
1325 poorly controlled (ACQ ≥1.5) 287 controlled (ACQ <1.5)
McCallister et al. AJRCCM 2011; 183: A4309.
Results Despite better pulmonary function and less rescue
inhaler use, women noted More asthma symptoms Poorer quality of life
Unique symptom profiles predominate in women Cough Nocturnal symptoms Environmental triggers
Currently available questionnaires may not detect sex specific differences in asthma symptom profiles
McCallister et al. AJRCCM 2011; 183: A4309.
Self-regulation Intervention for Women with Asthma Asthma management program including salient
sex role-related and gender role-related issues Benefit to women when compared to standard
treatment approaches Improved asthma related quality of life Decreased healthcare utilization Decreased use of short-acting bronchodilators
1. Clark, et al. Chest 2007;132:88. 2. Clark, et al. Gender Med 2010;7:125.
Conclusions
33
Asthma affects men and women differently No unifying explanation Clinical implications should be considered
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