Another reason to quit smoking: Results of a prospective study examining smoking, COPD, and suicide

Smoking remains a considerable public health concern.¹ In 2020, an estimated 30.8 million adults in the United States (US) were current smokers.¹ Smoking is associated with numerous adverse health effects.¹ In the US, more than 16 million adults have been diagnosed with a smoking-related illness and as a result, are at higher risk of poor health outcomes including death.¹ Chronic Obstructive Pulmonary Disease (COPD) is an illness of special concern in smokers.² Studies have found that patients who smoke and are diagnosed with COPD frequently suffer from poor mental health outcomes³ including death by suicide.^4-5 For example, in a meta-analysis of five case-control studies, Sampaio et al. (2019) observed that patients with COPD were nearly twice as likely to die by suicide than patients without COPD.⁵ The factors that may contribute to this observation, however, have not been fully elucidated. In particular, the field lacks knowledges about the role that COPD diagnosis and symptom severity may play in the risk of suicide among smokers. This information could inform risk stratification and treatment.

In this issue of CHEST, Adviento and colleagues present the results of a prospective cohort study that addresses key gaps in knowledge about the association between smoking, COPD, and suicide. ⁶ Using a well-characterized population of 9,930 patients from the 21-center longitudinal COPDGene study, the authors examined clinical predictors of suicide in patients who are current or former heavy smokers and have pulmonary symptoms ranging in severity from normal spirometry to severe COPD. The authors followed patients for a median of 7.8 years. The novel design of the study allowed the authors to begin to decouple potential risk factors of suicide that are typically strongly correlated. In doing so the authors have elucidated several independent risk factors of death by suicide in this population. In Cox regression models, Adviento et al. investigated an array of factors that may explain the relationship between smoking, COPD, and suicide. Of particular interest, was the inclusion of a subjective measure of disease (the modified Medical Research Council Dyspnea Scale, mMRC) as well as several, objectives measure of disease such as spirometry, six-minute walk distance, and use of supplemental oxygen. The authors found that the risk of suicide was significantly higher among patients with the following features: dyspnea (mMRC≥2), current smoking, younger age, white race, lower BMI, and use of sedative/hypnotics.

A chief finding of the study includes the result that heavy smokers who died by suicide were twice as likely to report symptoms of dyspnea (mMRC≥2) as compared to heavy smokers who did not die by suicide. Surprisingly, there was no significant association between objective measures of COPD such as airflow limitation and suicide. This finding is intriguing and somewhat in conflict with extensive literature that has postulated that suicide risk may be due to disease-driven changes in brain chemistry that are caused by chronic hypoxia.^4,7 For example, researchers have proposed that because oxygen is necessary as part of serotonin synthesis and low serotonin is implicated in suicidal behavior,⁷ patients may be at greater risk of suicide in the case of conditions associated with decreasing arterial oxygen pressure such as COPD⁸ or cigarette consumption.⁹ Rather than pointing to a close association of suicide with markers of chronic hypoxia, the results of this current study, however, draw particular attention to the prospect that a patient’s subjective experience of their health state (rather than the actual health state) may play a prominent role in the risk of suicide. It’s possible that patients may feel distress over experiencing symptoms such as dyspnea and that this, in turn, may impact their daily functioning or life satisfaction. This theory would align other findings reported in the literature.¹⁰ For example, in a 20-year, nationwide longitudinal study of adults in Finland, Koivumaa-Honkanen et al. (2001) found that patients who were dissatisfied with their life at baseline were three times more likely to die by suicide over the 20-year follow-up than those who were satisfied with their life.¹⁰ The findings held true even after accounting for baseline health status (sick versus healthy) and adjusting for other covariates including smoking status (current versus non). Of course, as Adviento et al. suggest, it is also possible that the relationship between subjective experiences of illness and suicide may simply be driven by underlying untreated (or undertreated) mental illness such as depression or anxiety.

Another result in this study that deserves attention includes the finding that the risk of suicide was significantly higher among patients using sedative/hypnotics. There is ample evidence that sedative/hypnotics are associated with risk of suicide.¹¹ The etiology of the relationship, however, remains unclear.¹¹ There are several theories. For example, sedative/hypnotics may worsen mood (e.g., depression) and thereby, increase risk of suicide. Sedative/hypnotics may also result in disinhibition, a feature linked to suicide.¹¹ Conversely, because insomnia is associated with suicidal behavior, it is conceivable that symptoms of insomnia have not responded to treatment.¹¹ Hypnotics can also be used as a method of overdose.¹¹ In the end, the findings emphasize the importance of monitoring smokers for sleep, mood and behavioral changes and exercising caution in prescribing large quantities of sedative/hypnotics to this population.

In conclusion, Adviento et al. have provided the scientific community with new insights into the relationship between smoking, COPD, and suicide. Certainly, the study emphasizes yet another reason why smoking is detrimental to the health and well-being of patients. The results reiterate the critical need to promote smoking cessation as a strategy to reduce morbidity and mortality in the population. Patients who are heavy smokers will also be helped by having access to mental health treatment. Patients with comorbid COPD and depression or anxiety, in particular, can benefit from pulmonary rehabilitation.¹² Suicide risk assessment in this population may also be improved by incorporating into the clinical evaluation specific factors such as current smoking, use of sedatives and the presence of dyspnea. Finally, the results of this study point to the need for future research to clarify the precise nature of the relationship between subjective symptoms of disease and suicide to inform risk assessment and the design of effective treatments. Ultimately, this work could lead to important progress towards the prevention of suicide, a key focus area of interest in the US.