Smoking tobacco causes up to 90% of prevalent COPD in the United States and continues to be a public health concern, with the current US prevalence of smoking at 21%.11,12
Despite recent improvements in the rate of smoking in the US, the rate of decline has slowed notably.12
Moreover, the worldwide prevalence of smoking remains high, particularly in countries with developing economies.13–15
Among patients with COPD, smoking cessation is the only intervention that modifies the rate of lung loss16
and only one of two therapies that have been demonstrated to reduce mortality.5,17
Unlike all other therapies that can be offered among patients with COPD, the cost-effectiveness of smoking cessation programs is unquestioned despite having relatively low proportions of successful quitters.5,16
In addition to proven benefits of smoking cessation on the rate of lung function decline, the Lung Health Study demonstrated that the smoking cessation intervention resulted in the development of fewer symptoms, including dyspnea, cough, sputum production and wheezing.3
We demonstrated that relative to current smokers, ex-smokers had a significant reduction in their risk of COPD exacerbation and that this effect was dependent on the duration of remaining tobacco free. This effect was apparent among those with and without prior recognition of COPD. In the context of the recent attention paid to pharmacological treatments to reduce exacerbation and improve symptoms, a greater emphasis is needed to address smoking cessation.
Our results have a potential basis in the known biology of tobacco smoke and COPD exacerbation risk. Tobacco smoke is a potent stimulant of the inflammatory response, and chronic inflammation has been suggested to contribute to COPD pathogenesis.18
The inflammatory response to tobacco smoke appears to be greater among people who are susceptible to developing COPD.19,20
Inflammation has been suggested as an important factor that may predispose individuals to increased risk of exacerbations. Recent data suggest that higher CRP concentrations, a general marker of inflammation, were associated with an increased risk of COPD exacerbations and mortality.21
In addition, similar studies have observed that markers of the host response to tobacco smoke may be important predictors of COPD exacerbations and symptoms.22–24
Inhaled corticosteroids that modify these markers of inflammation have been demonstrated to reduce the risk of COPD exacerbation.25
Interestingly, among patients with severe COPD, inflammation has been demonstrated to persist years after smoking cessation,26,27
and there are few data about whether modification in the rate of airflow obstruction is similar to those individuals with mild to moderate disease.
In our unadjusted models, we observed an increased risk of exacerbation associated with individuals who had reported stopping smoking for up to 5 years. This unadjusted observation fits with previous studies and may be consistent with the hypothesis of improved ciliary function leading to increased sputum production, clearance and symptoms.28–31
However, there is also the possibility of an indication bias leading to this finding in that individuals who have smoked for long periods of time often have some factors predisposing to future exacerbations, such as increasing dyspnea or prior exacerbations. Previous COPD exacerbation is a strong predictor of future exacerbations and may account for some of the unadjusted findings.32
This is further supported by the fact that after adding markers of COPD severity, including previous COPD exacerbations, we no longer find an increased risk of exacerbation associated with smoking cessation.
The decreased risk of exacerbation was greatest among individuals who did not have previously acknowledged COPD. There are a number of potential explanations for this finding. The effects of smoking cessation on the rate of lung function decline, and symptoms are only known for patients with mild to moderate disease.16
Because most patients with COPD present with symptoms relatively late in the disease course, it is not known whether smoking cessation would modify the rate of lung destruction and residual inflammation associated with severe disease. Because information provided about lung function and other health conditions may not facilitate quitting tobacco,33
our data provide additional support for recommending smoking cessation in all individuals regardless of the presence or absence of disease.
There are a number of explanations for our findings that do not necessarily imply a biological rationale. Smoking cessation may be accompanied by other healthy behaviors, such as improved adherence to medical therapy or curtailing heavy alcohol use that may reduce the risk of exacerbation. This would not however diminish our findings in that any positive accompanying health behavior would likely be welcome. In addition, the duration of smoking cessation may lead providers to attribute presentations for exacerbations to diagnoses other than COPD. In addition, individuals who stopped smoking earlier in their disease course may have less severe disease and therefore be more likely to benefit from the effects of smoking cessation. There remains an important gap in our current knowledge in that all of the randomized evidence to support the effect between smoking cessation on the rate of lung function decline and symptoms is based on those individuals with mild to moderate disease. As to whether smoking cessation confers the same benefits among severely impaired individuals remains unknown. Furthermore, our sensitivity analyses were concerning in that individuals who were most likely to have moderate to severe disease did not have a decreased risk of exacerbations associated with duration of smoking cessation. Our study, however, cannot address this particular concern.
This study had several strengths. First, we studied patients from multiple centers, minimizing the chance that the patterns of diagnosis or treatment by any single physician or group of clinicians exerted undue influence on our results. Second, the cohort was drawn from a complete primary care clinic population, reducing the likelihood of selection bias, such as is often found in randomized trials. Third, we had excellent reporting of smoking status and the ability to follow patients continuously in the VA system.
Still, this study had some potential limitations. First, some degree of ascertainment bias is likely present, as we were unable to assess clinic visits and hospital admissions to non-VA facilities. Second, we recognize that our definition of COPD did not include spirometric assessment and thereby allows for both potential misclassification of outcome and cohort definitions. However, we were interested in an entire population of clinic patients because many individuals are unaware that they may have COPD. Third, our assessment of exposure was performed only once. This may have led to under-reporting of tobacco consumption because of social desirability.34
In addition, some patients may have stopped or re-started smoking in the interval follow-up period, and previous studies have shown that the duration of abstinence is associated with the risk of recidivism, although after 6–12 months, the rate of permanent smoking abstinence plateaus.35
The early relapse rate may in part explain the effects noted in those who had quit for less than 1 year. Finally, we did not have any biological confirmation of smoking status, such as with cotinine or carbon monoxide measurements.
COPD exacerbations are an important cause of morbidity among patients with COPD. Recent strategies have focused on ways to decrease the rate of COPD exacerbations, primarily through pharmacological therapy or interventions. From a public health perspective, smoking cessation is an effective and cost-saving strategy, yet there are many payers of health care who do not pay for or only pay for very limited smoking cessation programs.36,37
Access to smoking cessation programs is relatively easy, with a number of quit lines and other telephone-based smoking cessation programs that do not necessarily require clinician referrals. Our data suggest that smoking cessation reduces the risk of COPD exacerbations. Greater efforts are needed to promote and facilitate access to smoking cessation programs and to understand the biologic changes that occur after successful smoking cessation.