Over the next 25 years, the global prevalence of chronic obstructive pulmonary disease (COPD) is expected to grow by as much as 23%. Importantly, a majority of these cases are projected to occur in women. In the United States, an increased prevalence in women has also been reported.
Why, then, is COPD still considered a disease that mostly affects older men smokers?
“I think that we oversimplified COPD for many years as being a tobacco-related lung disease, and more men smoked tobacco,” said Jamie Garfield, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University and pulmonologist at the Temple Lung Center in Philadelphia. “We saw it more in men because we were looking for it more in men.”
“While tobacco is one of the greatest risk factors for the development of the disease, today, there are people with COPD who never smoked cigarettes, the greatest proportion of whom are women,” said Garfield.
According to recent estimates, 1 in 4 people diagnosed with COPD had never smoked.
Distinct Presentations in Women
Overall, about 16 million people with COPD remain undiagnosed, and many appear to be women. As greater numbers of cases in women continue to emerge, greater recognition and diagnosis are essential.
Improving diagnosis in women means challenging common misconceptions around COPD presentation, most importantly, recognizing it as a disease that encompasses multiple and often mixed presentations vs one of two phenotypic traits: Pink puffers and blue bloaters, that are learned in medical school.
“Women tend to be younger when they present; perhaps this is part of the predilection of practitioners to diagnose asthma,” said Dawn L. DeMeo, MD, associate professor of medicine at Harvard Medical School and a pulmonary and critical care specialist at Brigham and Women’s Hospital in Boston. “They tend to have lower smoking histories, suggesting higher susceptibility. And they may manifest more shortness of breath.” In addition to shortness of breath, women are likely to report more exacerbations, added Meilan K. Han, MD, professor of medicine and chief of the Division of Pulmonary and Critical Care at the University of Michigan Health, Ann Arbor, Michigan.
DeMeo underscored an important consideration for primary care specialists: Women tend to present with more (or more distinct) comorbidities such as anxiety and depression, which data have linked to COPD-related breathlessness.
Although the reasons underlying these distinct presentations are unclear, several theories have been proposed and explored.
“Women experience more rapid lung function decline over time, and some theories include the fact that their lungs and air sacs are smaller,” said Han, who is also a spokesperson for the American Lung Association, Chicago.
The rate of this decline also appears to accelerate during the menopausal transition, suggesting a hormonal component combined with other personal exposures, explained DeMeo. “The lung is very estrogen-sensitive,” she said, although the exact drivers are still in question.
Lifetime Medical History
Because diagnosis is often delayed or missed in women, they’ve historically presented with more advanced disease progression, resulting in a greater number of hospitalizations.
“Making a diagnosis of COPD early is the best thing we can do, regardless of the patient is a man or a woman,” said Garfield. “The diagnosis requires hearing the history and understanding the risk factors.”
Garfield said she asks all her patients to share more about where they were born, significant details about their birth (for example, being born prematurely), the activities they enjoyed as children, and where they traveled and when.
“Primary care doctors need to be asking patients to take them through their lifetimes, the things they do, their early- and late-life exposures, regardless if symptoms seem typical or atypical,” she advised.
In women especially, occupational exposures reveal important clues. For instance, biomass fuel for cooking and heating (most frequently observed in lower-to-middle income countries), air pollution, firewood burning or indoor smoke pollution, and regular exposure to chemicals, vapors, gas, dust, and fumes often drive COPD cases in women.
“There’s data — although controversial — that would suggest that women with the same cigarette or environmental exposures as men are more likely to develop lung injury or chronic lung disease,” said Garfield.
Additionally, social determinants of health should be considered.
“We know that social determinants of health are such important drivers of lung health, for example, the intersectionality between COPD and poverty, food deserts,” DeMeo said, emphasizing that differences in presentation and severity vary not only by sex but also within groups of women.
Confirming Diagnosis
Despite multiple but unique presentations in women, shortness of breath and frequent exacerbations are red flags that should have physicians automatically thinking of COPD.
It’s equally important to consider the overlap between asthma and COPD, which can delay treatment and referral, Garfield noted.
“The key is spirometry,” said Han. “Studies suggest that women are less likely to get diagnosed with COPD and more likely to be diagnosed with asthma when doctors don’t get spirometry. The opposite is also true; when doctors conduct spirometry, they tend to get it right.”
A Prescription for Change
COPD costs the nation roughly $24 billion annually in direct and indirect medical costs, and that amount is expected to substantially increase within the next 5 years or so, according to Josie Cooper, executive director of the Alliance for Patient Access, a national nonprofit organization focused on policies related to patient access and patient-centered care, and head of the COPD Action Alliance, Washington, DC.
“It’s also linked with a whole host of comorbid conditions, such as high blood pressure, high cholesterol, heart disease, and diabetes,” said Cooper.
Primary care physicians are often the first point of contact for women with COPD and comorbidities. They are in the best position to not only select effective treatments or refer patients out to pulmonologists but also ensure that women who smoke are offered behavioral and pharmacological management, are fully vaccinated to prevent diseases that might cause exacerbations, and consider pulmonary rehabilitation, which can help control breathlessness and depression or anxiety.
Lack of awareness and understanding of how COPD presents and progresses in women has been a costly proposition for the medical community. The key is to catch and treat the disease as early as possible, tailor and personalize management, and recognize that COPD is more than a lifetime of tobacco smoking, especially in women.
Garfield and DeMeo reported no relevant financial relationships of interest.
Han reported receiving personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, Roche, Dev Pro, Aerogen, Polarion, Regeneron, Amgen, UpToDate, Altesa BioSciences, Owkin, Medscape, National Association of Colleges and Employers, MDBriefCase, Integrity, and Medwiz. She had received either in-kind research support or funds paid to the institution from the National Institutes of Health, Novartis, Sunovion, Nuvaira Inc., Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation, and the American Lung Association. She had participated in Data and Safety Monitoring Boards for Novartis and Medtronic, with funds paid to the institution. She had received stock options from Meissa Vaccines and Altesa BioSciences.
Cooper reported that the Alliance for Patient Access receives financial support from AbbVie, Acadia Pharmaceuticals, Alnylam, Amgen, Amneal, ANI Pharmaceuticals, AstraZeneca, Axsome Therapeutics Inc., Biogen, Boehringer Ingelheim, BridgeBio, Bristol Myers Squibb, Eli Lilly and Company, Glaukos, GlaxoSmithKline, Johnson & Johnson Healthcare Systems Inc., Lundbeck, Merck, Neurocrine Biosciences, Novavax, Novo Nordisk, Otsuka, Regeneron, Sage, Sanofi, Swedish Orphan Biovitrum, Supernus, Teva, Vertex, Viatris, and Viridian.