PUMPING IRONY: A Breathtaking Trend

When I read the other day that the percentage of Americans who smoke cigarettes had fallen for the first time into the single digits, I couldn’t help but think of our longtime next-door neighbor Sue and her fervent attachment to the toxic leaf.

Sue had a distinctive cough, low and growly, that often announced her presence. When she wandered over to our backyard patio to chat about one thing or another, she typically carried three cigarettes and a portable ashtray. I don’t think she was any more surprised than we were when, in her late 70s, she was diagnosed with lung cancer. She underwent chemo and lost her hair, but she seemed to focus her complaints on her oncologist’s insistence that she quit smoking — an edict she mostly ignored. Sue didn’t quite make it to 80.

I suppose it’s not surprising to learn that our dwindling affection for cigarettes has produced a gradual reduction in lung-cancer cases, but recent research suggests the disease is flourishing among an unsuspected— and unsuspecting — population: people who have never smoked.

A 2024 study reported that lung-cancer cases among nonsmokers — when considered as a disease separate from lung cancer among smokers — ranked fifth among the most common causes of cancer-related deaths worldwide in 2020. The Centers for Disease Control and Prevention estimates that nonsmokers account for as many as one in five lung-cancer cases in the United States each year.

And researchers at University College London last month highlighted the challenges of this illness for patients and clinicians in a paper published in the journal Trends in Cancer. As corresponding author Deborah Caswell, PhD, notes, lung cancer in nonsmokers (LCINS) is a biologically and clinically distinct disease that defies conventional diagnostic approaches. “Prevention and screening strategies that work for smokers don’t automatically translate to never-smokers,” she explains, “and identifying non-smoking risk factors is essential to finding the subgroups who could benefit from targeted screening and prevention.”

The various factors that researchers believe contribute to the disease, however, are difficult to measure. There seems to be some genetic predisposition, Caswell notes, and there is some consensus forming around the hazardous effects of air pollution, radon gas, radiation, and secondhand smoke. But “much of the supporting evidence is retrospective,” she writes, “and the relative risk associated with each of these exposures is modest, so justifying costly screening or therapy is difficult.”

When someone without a history of smoking displays the most common symptoms of LCINS — coughing, fatigue, and difficulty swallowing — physicians will seldom suspect lung cancer, delaying a diagnosis and necessary treatment. As a result, the disease may progress further than in typical lung-cancer cases, often reaching metastatic stages, before it’s accurately diagnosed. At that point, palliative care often becomes the only option.

And even when the disease is diagnosed at an early stage, LCINS can be more difficult to treat than lung cancer in smokers, Caswell explains. It develops fewer mutations, for instance, which makes it less likely to respond to immune checkpoint inhibitors that often prove effective in more conventional cases.

That’s why Caswell and her colleagues are urging preventive measures, such as screening individuals with a genetic predisposition to the disease, encouraging household radon monitoring, and limiting exposure to air pollution, radiation, and secondhand smoke. This may be the best approach to reducing the prevalence of LCINS. The first step, however, is sounding the alarm.

“We anticipate that raising awareness of LCINS will lead to an increased interest in defining ‘high-risk never-smoker’ subgroups, the development of cost-effective screening protocols for those subgroups, and the building of prevention/interception trials in which the benefits clearly outweigh the harms,” she says.

The word seems to be getting out. Around the same time that our neighbor Sue was going through chemo, we heard that a young woman at the other end of the block was also being treated for lung cancer. She was in her early 50s, had never smoked, and was known to be physically active and otherwise in excellent health.

But, unlike Sue, she pulled through.

We learned later that the young woman had detected high levels of radon gas in her basement after her diagnosis and ordered the installation of a mitigation system. And, last summer, we noticed the young, nonsmoking, couple who bought Sue’s house did the same.

I can almost imagine Sue arguing that it wasn’t the cigarettes after all.