Sex & Gender in Acute Care Medicine

Sex & Gender in Acute Care Medicine Chapter 3: Pulmonary Disease

Chapter 3: Pulmonary Disease Stacey Poznanski and Rita Cydulka

Case Study • A 45 year old female smoker presents to ED with cough and wheezing x 3 days • She reports increased sputum production • She denies fever, chills, night sweats, hemoptysis • Her heart rate is 105, BP 125/85, respiratory rate of 21, O2 saturation 93% on room air, temp 98.5°

Case Study • On exam, she has no JVD and a tachycardic but regular rate • Lung exam with diffuse tight wheezes • Extremities with no clubbing, cyanosis, or edema • Patient has a history of asthma and uses albuterol MDI and an inhaled corticosteroid daily

Case Study • The patient has smoked 1.5 packs of cigarettes per day for the past 25 years and continues to smoke • This is her third “asthma attack” in two months

Introduction • This chapter highlights the influence of sex and gender on 3 conditions: • Tobacco Abuse • Asthma • Chronic Obstructive Pulmonary Disease (COPD) • This chapter addresses the role of sex and gender in each of these 3 disease processes and analyzes gaps in current knowledge and recommendations for future research

Tobacco Abuse • Tobacco use is the leading cause of preventable morbidity and premature mortality in the US • Accounts for 1 in 5 deaths each year • In 2004, tobacco abuse cost the US an estimated $193 billion in lost productivity and health care costs • Sex-specific factors likely play in role in tobacco-related morbidity and mortality

Smoking in History • In the early 1900s, smoking was considered a male behavior • For women, smoking in public was seen as defiant and radical • However, for a new generation of women seeking equal rights, smoking became a “symbol of emancipation” • By the 1920s, cigarettes became associated with the youthful, educated working woman

Smoking in History • The tobacco industry began marketing cigarettes to women • Notably, Lucky Strikes included testimonials about the benefits of cigarettes for weight loss • Women’s smoking rates rose from 6% in 1924 to 18% in 1935 • For American men, smoking prevalence peaked in the 40s and 50s at 67%

Smoking in History • For women, smoking rates peaked at approximately 44% in 1964 – around the time of the Surgeon General’s Report on Smoking and Health • The report described cigarette use a causal factor in lung disease and increased deaths from coronary artery disease • At this time, research subjects were generally male

Smoking in History • Since then, smoking rates have declined for both sexes – but more slowly in women • Effects of smoking in women were underrepresented in the 1964 Surgeon General’s report • A 1980 report predicted that the sequelae of smoking in women would become more prominent in subsequent decades

Clinical Manifestations • This sex-related trend in smoking rates has led to a shift in sex-specific prevalence, morbidity, and mortality of tobacco-related illnesses • Since 1950, lung cancer rates among women have increased more than 500% • Incidence and death rates for men have been steadily decreasing since the 1990s

Clinical Manifestations • After several decades of increasing lung cancer mortality in women, rates have finally plateaued • COPD mortality rates have followed a similar trend • Historically, COPD has been associated with men (“blue bloater” vs. “pink puffer”) • For the past 10 years, the number of deaths from COPD has been higher in women

Clinical Manifestations • Women reached their current COPD mortality rate faster than men did 20 to 30 years before • Women may be more vulnerable to the effects of cigarette use than men • Some studies suggest a greater decline in forced expiratory volume in 1 second (FEV1) in women in response to equal amounts of tobacco • Other studies suggest the opposite, an increased susceptibility in men compared to women

Clinical Manifestations • A recent meta-analysis found evidence of faster decline in lung function in female smokers >45-50 years old compared to male smokers • Estrogen may affect the metabolism of cigarette smoke through cytochrome P450 pathways • Each cigarette may represent greater exposure in women’s smaller airways

Smoking Cessation • Globally, far fewer women use tobacco than men (10% vs 48%, respectively) • However, WHO reports that use among women is increasing and may double by 2025 • As it becomes more socially acceptable for women to adopt men’s social roles and behaviors • Researchers must consider social changes, marketing, and the reasons why men and women initiate smoking

Smoking Cessation • In general, women have more difficulty quitting than men • They often experience less success than men in initial quit attempts, • Greater negative affective responses during withdrawal, • And less successful cessation with nicotine replacement therapy

Smoking Cessation • The Lung Health Study (LHS) found that women had higher rates of relapse to cigarette smoking • And had less frequent, shorter quit attempts • Education correlated with cessation success in both sexes • But women with less than a high school education were significantly less likely to quit than men with equal educational background

Smoking Cessation • Possible link between phases of the menstrual cycle, physiological response to nicotine, and depressive symptoms • Although more research is needed, timing of quit attempts in relation to the menstrual cycle may impact success • Research also indicates that women fail in situations involving negative emotions (financial stress)

Smoking Cessation • Men, on the other hand, fail in situations involving positive emotions (social events) • Men – but not women – are more likely to be successful if they experience negative health outcomes or social pressure to quit • Fear of weight gain has been a barrier to cessation and a reason for relapse, especially in women

Smoking Cessation • Women are more likely than men to acknowledge this concern as a negative influence on their motivation to quit • In the LHS, despite efforts to minimize weight gain, a weight gain of 20% or more over baseline was reported in 7.6% of men and 19.1% of women

Acute Management • Prevalence rates of smoking in US EDs tend to be higher than the general population • In one prospective study, as high as 48% of ED patients in 3 US cities were current smokers • EDs are often the main source of care for the uninsured • >79% of adult smokers in the ED are contemplating quitting or preparing to quit

Acute Management • The ED visit may be the ideal opportunity to provide cessation interventions • Although there are certainly barriers to ED intervention (including resources, time, and provider training), several studies report successful implementation of smoking cessation programs in the ED

Acute Management • Given the sex- and gender-specific differences in the motivation to smoke and the ability to quit, studies suggest that sex and gender sensitive interventions increase cessation rates • The Smokefree Women site (www.women.smokefree.gov) provides evidence-based information to increase women’s motivation to quit

Acute Management • Gender-specific materials have also been created for men • The book, The Right Time, The Right Reasons: Dads Talk About Reducing and Quitting Smoking, encourages men to consider the advantages of being a dad who doesn’t smoke • Available at www.facet.ubc.ca

Prevention • Compared to adults, smoking rates among adolescents are on the rise • Cigarettes, historically a symbol of liberation for women, continue to be a symbol of independence and maturity for youth

Prevention • Lack of intent to pursue college degree, high school dropout status, and single-parent household all correlate with increased risk of tobacco initiation • Tobacco control efforts must address cultural, psychosocial, and sociodemographic factors involved in the decision to smoke • Additionally, these factors are often influenced by sex and gender

Conclusion • Public health efforts since the 1960s have resulted in declining prevalence of smoking in adults • Still, more than 20% of Americans smoke and smoking among adolescents is rising • Rates of lung cancer and COPD are increasing in women • We need effective, sex- and gender-specific prevention and cessation programs

Asthma • Asthma affects an estimated 39.5 million Americans and more than 300 million people worldwide • In 2011, females were 14% more likely than males to have been diagnosed with asthma, although age is also factor • From 2002-2007, the annual economic cost of asthma in the US was $56 billion ($50 billion in direct health care cost)

Gender Risk • Studies consistently demonstrate that asthma prevalence rates by gender change with age • Before puberty, asthma is 16% more prevalent in boys • In adulthood, prevalence is 62% greater in women • Prevalence in women decreases after menopause

Gender Risk • Additionally, asthmatic women report a peri-menstrual worsening of symptoms • This suggests that sex hormones may play a role in asthma, although the exact mechanism is yet to be determined • Thus far, studies on the role of sex hormones have been inconclusive

Gender Risk • There are many theories as to how sex hormones may affect asthma • It is thought that estrogen may be involved in signaling pathways related to organ functioning • Testosterone may play a role in the relaxation of airway smooth muscle

Gender Risk • Adding to the complexity of the role of sex hormones, as many as 42% of pregnant asthmatics require hospitalization • Two large studies found post-menopausal hormone replacement to be associated with increased risk of newly diagnosed asthma • Asthma is not only more common in women but also more severe • In 2011, 8 million women reported an asthma attack compared to 5 million men

Natural History • Asthma is generally a chronic illness with reversible exacerbations and a relatively good prognosis • However, asthma can cause a permanent decrease in lung function and increase mortality • Overall, mortality from asthma is low (0.15 per 1000 persons with asthma from 2007-2009)

Natural History • Asthma death rates were >30% higher for women than men from 2007 to 2009 • These results do not adjust for women having a higher prevalence as adults and a higher death rate compared to children • Data on sex-specific differences in mortality are conflicting and difficult to distinguish from age-related effects

Clinical Manifestations Asthma is characterized by: Gender Matters A patient’s ability to detect changes in airflow depends on his/her ability to perceive it Poor perceivers may not be able to recognize symptoms Literature suggests that men and women perceive and/or experience asthma symptoms differently • Airway inflammation, causing episodes of reversible airflow obstruction • Wheezing • Dyspnea • Chest tightness • Cough

Clinical Manifestations • Women perceive more difficulty controlling their asthma than men • They describe more frequent, more severe symptoms and worse impact on quality of life • despite using similar medications and having similar or better pulmonary function compared to men

Clinical Manifestations • Women: • Have higher numbers of unscheduled physician visits • Have more frequent use of oral corticosteroids and rescue beta agonist inhalers • Are 50% more likely to report ongoing symptoms after discharge

Clinical Manifestations • Men may report fewer symptoms because they find their symptoms less concerning or because they practice denial • Increased bronchial responsiveness in women could explain differences in perceived airflow obstruction • Increased susceptibility to cigarette smoke may also contribute to bronchial hyperresponsiveness

Clinical Manifestations • Inspiratory muscle strength is significantly greater in men and is inversely related to dyspnea • The exact mechanisms of the differences in symptom perception, psychosocial associations, airway responsiveness, and other factors are unknown and warrant further research

Diagnosis • The same diagnostic approach is used for asthmatic men and women • When taking a history in women, additional questioning should address reproductive health to identify sex-related triggers (i.e., timing of exacerbations with the menstrual cycle)

Diagnosis • Hallmark presentation of asthma includes a history of episodic cough, chest tightness, and dyspnea • Physical exam may reveal wheezes • Exam findings and vital signs are often unreliable predictors of degree of airway obstruction • A quality history and pulmonary function testing are crucial to diagnosis and evaluation

Diagnosis • In both sexes, it is often difficult to assess the severity or predict the course of an asthma exacerbation in the ED • Spirometry is often not available • Patients with significant airflow obstruction may be unable to accurately perform forced airway maneuvers

Diagnosis • Study by Piovesan et al. (2006) found that peak expiratory flow rate (PEFR) may be useful in predicting outcomes in acute asthma • A PEFR ≥40% after 15 min. of treatment showed significant power in predicting a favorable outcome • A PEFR <30% after 15 min. of treatment was predictive of a poor outcome • Studies suggest that women may need more time and instruction on correct use of peak flow meters compared to men

Diagnosis • Without objective measures to assess level of obstruction, patients (especially men) may be undertreated • Women with an equal degree of obstruction may perceive their symptoms as more severe – so objective measures cannot be the sole factor • Patients with worsening symptoms that are unresponsive to therapy should be referred for formal spirometry and testing to rule out COPD

Acute Management • Treatment of an acute asthma exacerbation in the ED should correct tissue oxygenation, alleviate any reversible bronchospasm, remove underlying triggers, and respond to complications • Treatment may include oxygen, adrenergic agents, anticholinergics, corticosteroids and magnesium

Acute Management • Some recognized triggers of asthma include: • Tobacco smoke, air pollution, occupational exposures, gastroesophageal reflux disease, exercise, medications (NSAIDs, beta-blockers) • If triggers are identified, a plan should be made to limit patient’s exposure • Expert consensus recommends spirometric testing as soon as possible once patient is stable

Acute Management • Further research is needed on sex-specific approaches to treatment and assessment • Gender-specific approaches have shown benefit • An RCT (Clark et al.) of a telephone intervention for women that emphasized sex and gender role factors in asthma management • Found significant improvements in health status and quality of life among intervention subjects

Prevention • Although there is no known way to prevent the development of asthma, methods of controlling exacerbations are well-established: • Early referral to spirometry for patients with respiratory symptoms and those at risk for asthma • Smoking cessation counseling • Sex-specific asthma education • Weight loss – Obesity appears to be a major risk factor for asthma development in women

Clinical Outcomes • Sex differences may affect clinical outcomes, specifically resource utilization and morbidity • Women adhere more closely to asthma management guidelines • Are more likely to have a PCP • Despite having better pulmonary function, less hypoxia, similar maintenance medications and ED treatment, adult women are still hospitalized more frequently than men

Sex & Gender in Acute Care Medicine