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Smoking cessation and the risk of hospitalization for pneumonia
Respiratory Medicine (2012) 106, 1055e1062
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/rmed
Smoking cessation and the risk of hospitalization for pneumonia Laura M. Cecere a,b,*, Emily C. Williams a,c, Haili Sun a, Chris L. Bryson a,d, Brendan J. Clark e, Katharine A. Bradley a,c,d,f, David H. Au a,b a
Health Services Research and Development (HSR&D) Northwest Center of Excellence, Department of Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA b Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA c Department of Health Services, University of Washington, Seattle, WA, USA d Department of Medicine, Division of General Internal Medicine, University of Washington, Seattle, WA, USA e Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Aurora, CO, USA f Group Health Research Institute, Seattle, WA, USA Received 9 December 2011; accepted 24 March 2012 Available online 25 April 2012
KEYWORDS Pneumonia; Smoking cessation; COPD
Summary Background: Smoking increases the risk of hospitalization for pneumonia, yet it is unknown if smoking cessation changes this risk. We sought to determine if smoking cessation and the duration of abstinence from tobacco reduce the risk of pneumonia hospitalization. Methods: We performed secondary analysis of data collected from male United States Veterans participating in a randomized trial. We used Cox proportional-hazard models to estimate risk of hospitalization for pneumonia within one year of enrollment. We adjusted for confounders, including: demographics, comorbidity, alcohol use, prior pneumonia, inhaled corticosteroid use, and intensity of tobacco exposure. Among a restricted cohort excluding never smokers, we assessed for effect modification by a diagnosis of chronic obstructive pulmonary disease (COPD). Results: Of the 25,235 participants, we identified 6720 current, 13,625 former, and 4890 never smokers. Compared to current smokers, never smokers had a decreased (adjusted HR 0.48, 95% CI 0.31e0.74), while former smokers had no difference in (adjusted HR 0.83, 95% CI 0.63e1.09) risk of hospitalization for pneumonia. Among participants without COPD, former smokers had a lower risk of hospitalization (adjusted HR 0.65, 95% CI 0.45e0.95). However, this lower risk
Abbreviation: ACQUIP, Ambulatory Care Quality Improvement Project; ACSC, Ambulatory care sensitive condition; AUDIT-C, Alcohol Use Disorders Identification Test Consumption; COPD, Chronic obstructive pulmonary disease; CHF, Congestive heart failure; CI, Confidence interval; CVA, Cerebrovascular accident; DM, Diabetes mellitus; GIMC, General internal medicine clinics; HR, Hazard ratio; ICD-9, International Classification of Diseases 9th Edition; ICS, Inhaled corticosteroids; MI, Myocardial infarction; VA, Department of Veterans Affairs. * Corresponding author. Health Services Research and Development, VA Puget Sound Health Care System, 1100 Olive Way, Suite 1400, Seattle, WA 98101, USA. Tel.: þ1 206 277 4191; fax: þ1 206 768 5343. E-mail address: [email protected] (L.M. Cecere). 0954-6111/$ - see front matter Published by Elsevier Ltd. doi:10.1016/j.rmed.2012.03.018
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L.M. Cecere et al. was isolated to those who quit tobacco more than 10 years previously (adjusted HR 0.62, 95% CI 0.41e0.93). Among those with COPD, there was no difference in risk with smoking cessation or duration of remaining tobacco-free. Conclusions: Tobacco cessation is likely important in reducing hospital admissions for pneumonia, but its benefit depends on duration of smoking cessation and is likely attenuated in the presence of COPD. Published by Elsevier Ltd.
Introduction In the United States, pneumonia is responsible for more than 1 million hospitalizations each year, resulting in annual healthcare costs of more than 10 billion dollars.1 Despite its designation as an ambulatory care sensitive condition (ACSC),2 or one for which hospitalization is potentially preventable, rates of admission for bacterial pneumonia have increased over time, particularly among older adults.3,4 Efforts to date to reduce hospital admissions for pneumonia have concentrated largely on early diagnosis and appropriate outpatient treatment, as well as primary prevention with the use of the influenza and 23-valent pneumococcal vaccines in at-risk populations.5 Despite the efficacy of these vaccines in preventing influenza6 and invasive pneumococcal disease,7,8 respectively, controversy remains about their effectiveness against developing severe pneumonia requiring hospitalization.9 Attempts to eradicate preventable conditions known to increase the risk of pneumonia and pneumonia-related hospitalizations, such as chronic obstructive pulmonary disease (COPD),10e17 may be important in decreasing the burden of illness due to pneumonia in the future.3 Smoking is the leading cause of COPD,18 and is itself a strong predictor of pneumonia,10,11,16,19 need for hospitalization12,13,15 and resulting mortality.14,20,21 While a few studies suggest that smoking cessation may be associated with a lower risk of developing pneumonia19,22 no study has examined its effect on rates of hospitalization for the condition. We sought to determine if smoking cessation and the duration of abstinence of tobacco were associated with a lower risk of hospitalization for bacterial pneumonia among a large cohort of United States Veterans. Due to the strong association between COPD and poor clinical outcomes among patients with pneumonia,12e15,23,24 we also assessed whether or not this risk was modified by a self-reported history of a physician diagnosis of COPD.
Briefly, participants in ACQUIP received care at one of seven Department of Veterans Affairs (VA) general internal medicine clinics (GIMC) across the United States. Eligible patients were required to have a valid mailing address, be assigned a primary care provider, and have been seen at least once in the past year with a follow-up visit scheduled. For this analysis, we included all male patients enrolled in ACQUIP between March 1997 and December 1998 who returned the health inventory checklist described below and had complete ascertainment of their alcohol use and smoking status. The intervention consisted of collecting information about targeted health conditions from patient questionnaires, physiologic data from the medical record, and ratings of patient health and satisfaction and then providing this information to clinicians before each primary care visit. This intervention had no effect on improving patient health status or satisfaction with care,25 and we included participants in both arms of the study in this analysis. We excluded women because they made up only 5% of the study population. The human subjects committees at the University of Washington and all other participating sites approved the ACQUIP study protocol. The Institutional Review Boards of the University of Washington and VA Puget Sound approved the analyses presented here (VA MIRB #01308).
Data collection Participants in ACQUIP completed mailed surveys, including a health inventory checklist containing questions about chronic medical conditions and current and prior tobacco exposure. Survey data were merged with hospital and pharmacy records extracted from the VA electronic medical record system and Medicare database. Collected data included International Classification of Diseases 9th Edition (ICD-9) diagnoses for all inpatient and outpatient visits through December 1999 and all outpatient prescriptions obtained from a VA facility. The date of enrollment, or index date, was defined as the day the health inventory checklist was processed.
Methods
Outcome and exposures of interest
Study setting and population
Our primary outcome of interest for this study was risk of first hospitalization for pneumonia occurring within one year of enrollment. We identified all hospitalizations with a primary ICD-9 discharge diagnosis of bacterial pneumonia as defined by the Agency for Healthcare Research and Quality,2 including: 481, 482.2, 482.30, 482.31, 482.32, 482.39, 482.9, 483.0, 483.1, 483.8, 485, and 486.
We performed secondary analysis of data collected for the Ambulatory Care Quality Improvement Project (ACQUIP), a multi-center randomized trial to improve patient health and satisfaction. The study population, methods and results of this study have been described previously in detail.25
Smoking cessation and pneumonia hospitalization Using the health inventory checklist, we ascertained whether patients were current, former or never smokers as of the index date. Among those with a history of tobacco use, we determined the average number of cigarettes smoked daily in 10-cigarette increments up to 40 cigarettes per day. We grouped former smokers based upon their self-reported time since quitting smoking into the following categories: less than 1 year, 1e5 years, 6e10 years or more than 10 years since last cigarette use.
Covariates Using the survey data, we identified demographic information for all participants as of the index date, including: age, race, marital status and highest level of education. We used the score on the self-reported Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire to assess alcohol use and misuse, categorizing patients into four groups: no past use (AUDIT-C score of 0), low-level use (AUDIT-C score of 1e3), mild-moderate alcohol misuse (AUDIT-C 4e7) and severe alcohol misuse (AUDIT-C 8e12).26e31 In addition, we identified the presence of seven specific comorbid illnesses, including: prior myocardial infarction (MI), diabetes mellitus (DM), history of cerebrovascular accident (CVA), congestive heart failure (CHF), malignancy, COPD and prior pneumonia. Due to the increased risk of pneumonia among users of inhaled corticosteroids (ICS),32 we identified participants receiving a prescription for an ICS in the year prior to enrollment using pharmacy data.
Statistical analysis We utilized Cox proportional-hazard models to estimate the risk of first hospitalization for pneumonia associated with smoking status and length of smoking cessation.33 We followed patients until their first hospitalization for pneumonia, and censored for death, end of follow-up, or at one year post-enrollment. We assessed the relationship between subsequent hospitalization for pneumonia and both smoking status (entire cohort) and duration of abstinence from tobacco (including only those participants with a history of tobacco exposure) after adjusting for all the covariates listed above. In addition, we adjusted for the average number of cigarettes smoked per day in the models estimating associations of the time since quitting tobacco. Lastly, we used stratified models to examine how the relationship between smoking status and time since quitting tobacco was modified by the presence or absence of self-reported physician diagnosed COPD in a restricted cohort including only former and current smokers. We tested the proportional hazards assumption graphically and via Schoenfeld residuals, and found it to be valid for all final models, with the exception of the adjusted models restricted to patients with COPD. In this case, the addition of prior MI as a covariate caused a violation of the proportional hazards assumption, and therefore it was omitted from the final adjusted model. All statistical analyses were performed using Stata-10 statistical software (College Station, TX).
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Results Study population Of the 62,487 patients mailed the initial ACQUIP health checklist questionnaires, 36,821 patients (59%) responded. On average, these respondents were older (63 vs. 59 years) and had a higher prevalence of comorbid conditions including coronary artery disease, COPD, chronic heart failure, depression, diabetes and hypertension. However, after stratifying by age, the prevalence of these chronic conditions among responders and non-responders was similar. Of the 36,821 respondents, we identified 25,235 men (69%) who met eligibility criteria for this study. Of these we identified 6720 (26.6%) current smokers, 13,625 (54.0%) former smokers, and 4890 (19.4%) never smokers. Of the former smokers, the majority (n Z 8,760, 64.3%) reported quitting more than 10 years prior to enrollment. Current smokers were younger, more likely to be of black race, less likely to be married, and less educated than either former or never smokers (Table 1). Former smokers were more likely to have had a previous MI or CVA, report a history of prior pneumonia, be treated with an ICS, and to carry a diagnosis of DM, CHF, or malignancy than either current or never smokers. Former smokers were more likely than never smokers, but less likely than current smokers, to have a self-reported physician diagnosis of COPD. However, when examined by duration of smoking cessation, the proportion of former smokers who had quit within the past five years who had a self-reported diagnosis of COPD was similar to that of current smokers. On average, both former and current smokers reported consuming about a pack per day of cigarettes. Current smokers were more likely to report either mild-moderate or severe alcohol misuse compared to former and never smokers.
Risk of hospitalization for pneumonia and smoking status During the year following enrollment, we identified 359 hospital admissions for pneumonia, occurring at a median of 190 days (range 1e365 days). The overall incidence of admissions for pneumonia among the cohort was 14.6 per 1000 person-years. Among former and never smokers, the incidence of pneumonia was much higher among the 5074 participants with a self-reported diagnosis of COPD than among the 15,266 subjects without such a diagnosis (32.6 hospitalizations per 1000 person/years vs. 10.8 hospitalizations per 1000 person/years, respectively). In adjusted analyses and in comparison to current smokers, never smokers were at decreased risk of hospitalization for pneumonia (Table 2). Former smokers had a decreased point estimate of risk of hospitalization that did not reach statistical significance. Similarly, among all participants, we found no difference in risk of hospitalization for pneumonia among former smokers with varying lengths of abstinence from tobacco when compared to current smokers (Table 2; p-value for linear trend Z 0.07).
1058 Table 1
L.M. Cecere et al. Characteristics of participants by smoking status and duration of reported abstinence. Current smokers
Former smokers
Never smokers
All former smokers
By duration of abstinence Quit <1 yr
Quit 1e5 yrs Quit 6e10 yrs Quit >10 yrs
N Z 6720
N Z 13,625
N Z 1053
N Z 1998
N Z 1814
N Z 8760
N Z 4890
N (%)
N (%)
N (%)
N (%)
N (%)
N (%)
N (%)
a
Age (years) <50 50e59 60e69 70e79 80 Racea White Black Other Married Educationa
1950 1814 1848 997 102
(29) (27) (28) (15) (1)
1341 2155 4471 4883 759
(10) (16) (33) (36) (5)
244 273 334 186 16
(23) (26) (32) (18) (1)
348 440 690 473 47
(17) (22) (35) (24) (2)
222 372 653 507 58
(12) (21) (36) (28) (3)
527 1070 2794 3717 638
(6) (12) (32) (42) (7)
933 812 1253 1492 391
(19) (17) (26) (30) (8)
4691 1544 321 2920
(70) (23) (5) (43)
10,380 1998 758 8579
(76) (15) (6) (63)
719 250 54 520
(68) (24) (5) (49)
1428 389 123 1105
(71) (19) (6) (55)
1351 294 107 1110
(74) (16) (6) (61)
6882 1065 474 5844
(79) (12) (5) (67)
3355 947 432 2775
(69) (19) (9) (57)
1912 (28) 4003 (60) 670 (10)
4062 (30) 7314 (54) 1929 (14)
1156 1102 705 465 597 1935 924 495 18.9
2944 3303 1546 1299 1820 3139 2006 1173 20.6
(17) (16) (10) (7) (9) (29) (14) (7) (10.4)
257 (24) 644 (61) 126 (12)
(22) 214 (24) 189 (11) 111 (10) 97 (13) 110 (23) 310 (15) 165 (9) 127 (11.4) 20.7
(20) (18) (11) (9) (10) (29) (16) (12) (11.1)
574 (29) 1132 (57) 248 (12)
494 (27) 1061 (58) 224 (12)
2737 (31) 4477 (51) 1331 (15)
1046 (21) 2557 (52) 1172 (24)
450 438 261 206 265 616 308 234 21.4
417 441 199 182 231 466 255 176 22.3
1863 2235 975 814 1214 1747 1278 636 20.1
634 1092 441 309 506 574 444 180 N/A
(23) (22) (13) (10) (13) (31) (15) (12) (11.2)
(23) (24) (11) (10) (13) (26) (14) (10) (11.2)
(21) (26) (11) (9) (14) (20) (15) (7) (11.5)
(13) (22) (9) (6) (10) (12) (9) (4)
2501 (37) 1808 (27) 1500 (22)
6634 (49) 4392 (32) 2128 (16)
434 (41) 364 (35) 185 (18)
1008 (50) 588 (29) 314 (16)
877 (48) 606 (33) 272 (15)
4315 (49) 2834 (32) 1357 (15)
2488 (51) 1636 (33) 612 (13)
911 (14)
471 (3)
70 (7)
88 (4)
59 (3)
254 (3)
154 (3)
Some column totals do not add to 100% due to missing values; Abbreviations: MI Z Myocardial infarction; CVA Z Cerebrovascular accident; CHF Z Congestive heart failure; COPD Z chronic obstructive pulmonary disease; ICS Z Inhaled corticosteroid. a
Stratification by self-reported physician diagnosis of COPD Among former and current smokers who did not endorse having a physician diagnosis of COPD, we found a significantly lower risk of hospitalization among former smokers when compared to current tobacco users after adjustment for age, demographics, alcohol use/misuse, non-pulmonary comorbid illness, history of prior pneumonia, use of ICS, and intensity of tobacco exposure (cigarettes/day) (Table 3). Furthermore, among former smokers, we found the lower risk to be isolated to those who quit tobacco more than 10 years previously. In contrast, among former and current smokers with a self-reported physician diagnosis of COPD, we found no difference in risk of hospitalization dependent on smoking status or on time since quitting tobacco when compared to current smokers (Table 3).
Discussion In a large cohort of more than 25,000 Veterans, we found smoking cessation was an important predictor of the risk of pneumonia, but that risk was dependent on the duration of cessation as well as whether patients had recognized COPD. These findings are important as they suggest that smoking cessation could be beneficial in reducing future hospitalizations for pneumonia, but that in order to be effective, quitting smoking likely needs to occur early in life. Furthermore, these results suggests that as clinicians discuss the importance of smoking cessation that they may include the concept that benefits to lung health may be most substantial prior to developing lung disease, such as COPD. To our knowledge, no previous study has assessed the relationship between smoking cessation and hospitalization
Smoking cessation and pneumonia hospitalization Table 2
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Risk of hospitalization for pneumonia by smoking status and duration of abstinence.
Tobacco exposure Smoking status Current Former Never Duration of smoking cessation Current Quit <1 year Quit 1e5 years Quit 6e10 years Quit >10 years
Total (N )
Admissions (N )
Person-years
Rate (per 1000 person-years)
Adjusted hazard ratio (95% CI)
6720 13,625 4890
89 232 38
6557 13,241 4825
13.6 17.5 7.9
1.00a 0.83 (0.63e1.09) 0.48 (0.31e0.74)
6720 1053 1998 1814 8760
89 15 38 31 148
6557 1020 1938 1763 8520
13.6 14.7 19.6 17.6 17.4
1.00b 0.93 (0.52e1.66) 0.95 (0.63e1.42) 0.79 (0.50e1.26) 0.77 (0.57e1.04)
Values in bold indicate p-value<0.05. a Adjusted for age, race, marital status, education level, alcohol use, previous myocardial infarction, diabetes mellitus, history of cerebrovascular accident, congestive heart failure, malignancy, prior pneumonia, use of ICS, and diagnosis of COPD. b Adjusted for same demographics and comorbid illnesses, with additional adjustment made for cigarettes per day consumed (p-value for linear trend Z 0.07).
for pneumonia. However, two prior studies suggest smoking cessation to be associated with a reduced risk of developing pneumonia in the first place. In a population based caseecontrol study, Almirall et al. found the odds of developing pneumonia was reduced by 50% after 5 years of smoking cessation.19 Similarly, Baik et al. found former
smokers who quit smoking less than ten years prior had a 1.5 times higher risk, while those who had quit for ten or more years had no difference in risk, of developing pneumonia when compared to never smokers.22 Based on these studies, we expected to find a similar reduction in risk of hospitalization for pneumonia among all former smokers,
Table 3 Risk of hospitalization for pneumonia by smoking status and duration of abstinence, stratified by self-reported physician diagnosis of chronic obstructive pulmonary disease (COPD). Tobacco exposure
Total (N )
Admissions (N )
Person-years
Rate (per 1000 person-years)
Adjusted hazard ratio (95% CI)
49 113
4694 10,247
10.4 11.0
Referenta 0.65 (0.45, 0.95)
49 5 14 16 78
4694 727 1350 1315 6855
10.4 6.9 10.4 12.2 11.4
Referenta,b 0.64 (0.25, 1.64) 0.71 (0.38, 1.35) 0.77 (0.41, 1.47) 0.62 (0.41, 0.93)
1935 3139
40 118
1863 2990
21.5 39.5
Referentc 1.04 (0.70e1.54)
1935 310 616 466 1747
40 10 24 15 69
1863 292 587 448 1663
21.5 34.2 40.9 33.5 41.5
Referentc,d 1.24 (0.59e2.58) 1.23 (0.72e2.10) 0.83 (0.42e1.61) 0.99 (0.64e1.53)
No self-reported diagnosis of COPDa Smoking status Current 4785 Former 10,481 Duration of smoking cessation Current 4785 Quit <1 year 743 Quit 1e5 years 1381 Quit 6e10 years 1347 Quit >10 years 7010 Self-reported diagnosis of COPDa Smoking status Current Former Duration of smoking cessation Current Quit <1 year Quit 1e5 years Quit 6e10 years Quit >10 years
Values in bold indicate p-value <0.05. a Adjusted for age, race, marital status, education level, alcohol use, previous myocardial infarction, diabetes mellitus, history of cerebrovascular accident, congestive heart failure, malignancy, prior pneumonia, use of ICS, and average cigarettes per day. b p-value for linear trend Z 0.03. c Adjusted for same covariates listed above, with the exception of myocardial infarction, which was omitted from the model due to violation of proportional hazard assumptions. d p-value for linear trend Z 0.75.
1060 however this was not the case. Our patient population has a high prevalence of COPD, a finding that is consistent with previous studies showing a higher occurrence of COPD among United States Veterans than the general population.34 This is likely due primarily to high rates of tobacco smoking within this group, but age, exposure to passive tobacco smoke and occupational exposures are also risk factors for COPD,34,35 which may help explain the 12% of never smokers with self-reported COPD in this cohort. We hypothesize that differences between the results of our study and those previously published could be due to this high prevalence of COPD within our population, which will have driven our findings for our nonstratified analyses toward the null. This is supported by the fact that we did find a similar reduction to these other studies in risk among former smokers without a selfreported diagnosis of COPD. There are several possible explanations for our finding that ex-smokers without COPD have reduced risk of hospitalization for pneumonia compared to current smokers, whereas among patients with self-reported COPD this association is not observed. First, there are several biologic mechanisms thought to result in increased susceptibility to respiratory infection among smokers. These include a number of alterations to the host immune system, ranging from impaired ciliary function36 to depressed T-cell activity and natural killer cell function.37,38 Although many of these changes are likely reversible over time with smoking cessation, the immune dysfunction that occurs with smoking tobacco may be less reversible among patients with COPD.39 Second, patients who are able to achieve smoking cessation are also likely to achieve other healthy behaviors, such as reducing alcohol intake and following up with primary care physicians, which could result in earlier diagnosis and treatment and a subsequent reduction in their risk of hospitalization. COPD has been associated with the development of pneumonia severe enough to result in hospitalization,12e15 need for mechanical ventilation23 and death,14,23,24 and smoking cessation alone, or in combination with other healthy behaviors, may not be sufficient to reduce the incidence of hospitalization among this patient group. The majority of the estimated 1 in 5 adult tobacco users in the United States40 began smoking at an early age,41 and the incidence of tobacco use is higher among adolescents than older adults.40 Patients who are young and have not yet had undesirable health consequences from smoking may be reluctant to attempt smoking cessation. There is evidence that smoking cessation interventions that incorporate “gain-framed” messages, or highlight the benefits of abstinence from tobacco, may be more successful than those that are “loss-framed,” or emphasize the costs of continued smoking.42,43 Our results suggest that clinicians providing counseling about the benefits of smoking cessation can emphasize not only that smoking cessation reduces the risk of common tobacco-related lung diseases, such as COPD and lung cancer, but also educate patients about the importance of quitting early in life, when other adverse health outcomes, such as hospitalization for pneumonia, may be still modifiable. This study has some potential limitations. First, we relied upon self-report to determine current smoking status
L.M. Cecere et al. and the duration of abstinence among former smokers, which could result in potential misclassification of exposure status. Due to social desirability, participants may have under-reported current tobacco use or over-estimated their duration of abstinence, which could have resulted in biasing the study toward the null. Second, we could not account for the duration of tobacco exposure. However, as most patients begin smoking at around the same time and at a young age, adjustment for duration of use, in addition to age and average intensity of tobacco exposure, would likely not significantly change our findings. Third, we relied upon self-report of a physician diagnosis, rather than spirometry, to identify patients with COPD, which could result in misclassification. However, the high prevalence of COPD within our population is similar to that found in previous studies of United States Veterans. Fourth, our findings may not generalize to women, who are less likely to be hospitalized, less likely to require intensive care admission and to have a lower pneumonia-related mortality than men.44 Lastly, although the intervention had no effect on improving patient’s health status, and is therefore unlikely to have an effect on our outcome of interest, our study participants did tend to be older, white men, with high rates of comorbid COPD, which could affect the generalizability of our results. 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. In conclusion, we found that smoking cessation is associated with a reduction in the risk of hospitalization for pneumonia, but only among patients without a diagnosis of COPD, and then only among patients who quit smoking more than 10 years previously. These findings give clinicians additional important information to provide to patients about the benefits of early smoking cessation and emphasizes the advantages of smoking cessation prior to the development of lung disease.
Funding source This study was supported by a Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) grant [IAC 05-206-1]. Dr. Cecere is supported by a VA HSR&D fellowship [TPM 61037]. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs.
Conflict of interest statement Drs. Au and Bryson are co-investigators on a grant from Giliad Sciences for work which is unrelated to this
Smoking cessation and pneumonia hospitalization manuscript. Dr. Au is a research consultant for Bosch LLC. Drs. Cecere, Williams, Sun, Clark, and Bradley have no potential conflicts of interest to disclose.
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1061 17. Mannino DM, Davis KJ, Kiri VA. Chronic obstructive pulmonary disease and hospitalizations for pneumonia in a US cohort. Respir Med 2009;103:224e9. 18. Rabe K, Hurd S, Anzueto A, Barnes P, Buist S, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007;176: 532e55. 19. Almirall J, Gonza ´lez CA, Balanzo ´ X, Bolı´bar I. Proportion of community-acquired pneumonia cases attributable to tobacco smoking. Chest 1999;116:375e9. 20. Doll R, Peto R. Mortality in relation to smoking: 20 years’ observations on male British doctors. Br Med J 1976;2: 1525e36. 21. Rogot E, Murray JL. Smoking and causes of death among U.S. veterans: 16 years of observation. Public Health Rep 1980;95: 213e22. 22. Baik I, Curhan GC, Rimm EB, Bendich A, Willett WC, Fawzi WW. A prospective study of age and lifestyle factors in relation to community-acquired pneumonia in US men and women. Arch Intern Med 2000;160:3082e8. 23. Rello J, Rodriguez A, Torres A, Roig J, Sole-Violan J, GarnachoMontero J, et al. Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia. Eur Respir J 2006;27:1210e6. 24. Restrepo MI, Mortensen EM, Pugh JA, Anzueto A. COPD is associated with increased mortality in patients with community-acquired pneumonia. Eur Respir J 2006;28: 346e51. 25. Fihn SD, McDonell MB, Diehr P, Anderson SM, Bradley KA, Au DH, et al. Effects of sustained audit/feedback on selfreported health status of primary care patients. Am J Med 2004;116:241e8. 26. Chew RB, Bryson CL, Au DH, Maciejewski ML, Bradley KA. Are smoking and alcohol misuse associated with subsequent hospitalizations for ambulatory care sensitive conditions? J Behav Health Serv Res 2011;38:3e15. 27. Bryson CL, Au DH, Sun H, Williams EC, Kivlahan DR, Bradley KA. Alcohol screening scores and medication nonadherence. Ann Intern Med 2008;149:795e804. 28. Au DH, Kivlahan DR, Bryson CL, Blough D, Bradley KA. Alcohol screening scores and risk of hospitalizations for GI conditions in men. Alcohol Clin Exp Res 2007;31:443e51. 29. Bradley KA, Maynard C, Kivlahan DR, McDonell MB, Fihn SDInvestigators ACQIP. The relationship between alcohol screening questionnaires and mortality among male veteran outpatients. J Stud Alcohol 2001;62:826e33. 30. Harris AH, Bryson CL, Sun H, Blough D, Bradley KA. Alcohol screening scores predict risk of subsequent fractures. Subst Use Misuse 2009;44:1055e69. 31. Bridevaux IP, Bradley KA, Bryson CL, McDonell MB, Fihn SD. Alcohol screening results in elderly male veterans: association with health status and mortality. J Am Geriatr Soc 2004;52: 1510e7. 32. Ernst P, Gonzalez AV, Brassard P, Suissa S. Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia. Am J Respir Crit Care Med 2007;176:162e6. 33. Hosmer DW, Lemeshow S, May S. Applied survival analysis: regression modeling of time-to-event data. 2nd ed. Hoboken, N.J.: Wiley-Interscience; 2008. 34. Murphy DE, Chaudhry Z, Almoosa KF, Panos RJ. High prevalence of chronic obstructive pulmonary disease among veterans in the urban midwest. Mil Med 2011;176:552e60. 35. Lamprecht B, McBurnie MA, Vollmer WM, Gudmundsson G, Welte T, Nizankowska-Mogilnicka E, et al. COPD in never smokers: results from the population-based burden of obstructive lung disease study. Chest 2011;139:752e63.
1062 36. Dye JA, Adler KB. Effects of cigarette smoke on epithelial cells of the respiratory tract. Thorax 1994;49:825e34. 37. Johnson JD, Houchens DP, Kluwe WM, Craig DK, Fisher GL. Effects of mainstream and environmental tobacco smoke on the immune system in animals and humans: a review. Crit Rev Toxicol 1990;20:369e95. 38. Holt PG. Immune and inflammatory function in cigarette smokers. Thorax 1987;42:241e9. 39. Willemse BW, Postma DS, Timens W, ten Hacken NH. The impact of smoking cessation on respiratory symptoms, lung function, airway hyperresponsiveness and inflammation. Eur Respir J 2004;23:464e76. 40. Center for Disease Control and Prevention(CDC). Vital signs: current cigarette smoking among adults aged >or Z18 years e United States. MMWR Morb Mortal Wkly Rep 2009;2010(59): 1135e40.
L.M. Cecere et al. 41. Elders MJ, Perry CL, Eriksen MP, Giovino GA. The report of the Surgeon General: preventing tobacco use among young people. Am J Public Health 1994;84:543e7. 42. Toll BA, O’Malley SS, Katulak NA, Wu R, Dubin JA, Latimer A, et al. Comparing gain- and loss-framed messages for smoking cessation with sustained-release bupropion: a randomized controlled trial. Psychol Addict Behav 2007;21:534e44. 43. Toll BA, Martino S, Latimer A, Salovey P, O’Malley S, CarlinMenter S, et al. Randomized trial: Quitline specialist training in gain-framed vs standard-care messages for smoking cessation. J Natl Cancer Inst 2010;102:96e106. 44. Kaplan V, Angus DC, Griffin MF, Clermont G, Scott Watson R, Linde-Zwirble WT. Hospitalized community-acquired pneumonia in the elderly: age- and sex-related patterns of care and outcome in the United States. Am J Respir Crit Care Med 2002; 165:766e72.
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Smoking cessation and the risk of hospitalization for pneumonia Laura M. Cecere a,b,*, Emily C. Williams a,c, Haili Sun a, Chris L. Bryson a,d, Brendan J. Clark e, Katharine A. Bradley a,c,d,f, David H. Au a,b a
Health Services Research and Development (HSR&D) Northwest Center of Excellence, Department of Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA b Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA c Department of Health Services, University of Washington, Seattle, WA, USA d Department of Medicine, Division of General Internal Medicine, University of Washington, Seattle, WA, USA e Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Aurora, CO, USA f Group Health Research Institute, Seattle, WA, USA Received 9 December 2011; accepted 24 March 2012 Available online 25 April 2012
KEYWORDS Pneumonia; Smoking cessation; COPD
Summary Background: Smoking increases the risk of hospitalization for pneumonia, yet it is unknown if smoking cessation changes this risk. We sought to determine if smoking cessation and the duration of abstinence from tobacco reduce the risk of pneumonia hospitalization. Methods: We performed secondary analysis of data collected from male United States Veterans participating in a randomized trial. We used Cox proportional-hazard models to estimate risk of hospitalization for pneumonia within one year of enrollment. We adjusted for confounders, including: demographics, comorbidity, alcohol use, prior pneumonia, inhaled corticosteroid use, and intensity of tobacco exposure. Among a restricted cohort excluding never smokers, we assessed for effect modification by a diagnosis of chronic obstructive pulmonary disease (COPD). Results: Of the 25,235 participants, we identified 6720 current, 13,625 former, and 4890 never smokers. Compared to current smokers, never smokers had a decreased (adjusted HR 0.48, 95% CI 0.31e0.74), while former smokers had no difference in (adjusted HR 0.83, 95% CI 0.63e1.09) risk of hospitalization for pneumonia. Among participants without COPD, former smokers had a lower risk of hospitalization (adjusted HR 0.65, 95% CI 0.45e0.95). However, this lower risk
Abbreviation: ACQUIP, Ambulatory Care Quality Improvement Project; ACSC, Ambulatory care sensitive condition; AUDIT-C, Alcohol Use Disorders Identification Test Consumption; COPD, Chronic obstructive pulmonary disease; CHF, Congestive heart failure; CI, Confidence interval; CVA, Cerebrovascular accident; DM, Diabetes mellitus; GIMC, General internal medicine clinics; HR, Hazard ratio; ICD-9, International Classification of Diseases 9th Edition; ICS, Inhaled corticosteroids; MI, Myocardial infarction; VA, Department of Veterans Affairs. * Corresponding author. Health Services Research and Development, VA Puget Sound Health Care System, 1100 Olive Way, Suite 1400, Seattle, WA 98101, USA. Tel.: þ1 206 277 4191; fax: þ1 206 768 5343. E-mail address: [email protected] (L.M. Cecere). 0954-6111/$ - see front matter Published by Elsevier Ltd. doi:10.1016/j.rmed.2012.03.018
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L.M. Cecere et al. was isolated to those who quit tobacco more than 10 years previously (adjusted HR 0.62, 95% CI 0.41e0.93). Among those with COPD, there was no difference in risk with smoking cessation or duration of remaining tobacco-free. Conclusions: Tobacco cessation is likely important in reducing hospital admissions for pneumonia, but its benefit depends on duration of smoking cessation and is likely attenuated in the presence of COPD. Published by Elsevier Ltd.
Introduction In the United States, pneumonia is responsible for more than 1 million hospitalizations each year, resulting in annual healthcare costs of more than 10 billion dollars.1 Despite its designation as an ambulatory care sensitive condition (ACSC),2 or one for which hospitalization is potentially preventable, rates of admission for bacterial pneumonia have increased over time, particularly among older adults.3,4 Efforts to date to reduce hospital admissions for pneumonia have concentrated largely on early diagnosis and appropriate outpatient treatment, as well as primary prevention with the use of the influenza and 23-valent pneumococcal vaccines in at-risk populations.5 Despite the efficacy of these vaccines in preventing influenza6 and invasive pneumococcal disease,7,8 respectively, controversy remains about their effectiveness against developing severe pneumonia requiring hospitalization.9 Attempts to eradicate preventable conditions known to increase the risk of pneumonia and pneumonia-related hospitalizations, such as chronic obstructive pulmonary disease (COPD),10e17 may be important in decreasing the burden of illness due to pneumonia in the future.3 Smoking is the leading cause of COPD,18 and is itself a strong predictor of pneumonia,10,11,16,19 need for hospitalization12,13,15 and resulting mortality.14,20,21 While a few studies suggest that smoking cessation may be associated with a lower risk of developing pneumonia19,22 no study has examined its effect on rates of hospitalization for the condition. We sought to determine if smoking cessation and the duration of abstinence of tobacco were associated with a lower risk of hospitalization for bacterial pneumonia among a large cohort of United States Veterans. Due to the strong association between COPD and poor clinical outcomes among patients with pneumonia,12e15,23,24 we also assessed whether or not this risk was modified by a self-reported history of a physician diagnosis of COPD.
Briefly, participants in ACQUIP received care at one of seven Department of Veterans Affairs (VA) general internal medicine clinics (GIMC) across the United States. Eligible patients were required to have a valid mailing address, be assigned a primary care provider, and have been seen at least once in the past year with a follow-up visit scheduled. For this analysis, we included all male patients enrolled in ACQUIP between March 1997 and December 1998 who returned the health inventory checklist described below and had complete ascertainment of their alcohol use and smoking status. The intervention consisted of collecting information about targeted health conditions from patient questionnaires, physiologic data from the medical record, and ratings of patient health and satisfaction and then providing this information to clinicians before each primary care visit. This intervention had no effect on improving patient health status or satisfaction with care,25 and we included participants in both arms of the study in this analysis. We excluded women because they made up only 5% of the study population. The human subjects committees at the University of Washington and all other participating sites approved the ACQUIP study protocol. The Institutional Review Boards of the University of Washington and VA Puget Sound approved the analyses presented here (VA MIRB #01308).
Data collection Participants in ACQUIP completed mailed surveys, including a health inventory checklist containing questions about chronic medical conditions and current and prior tobacco exposure. Survey data were merged with hospital and pharmacy records extracted from the VA electronic medical record system and Medicare database. Collected data included International Classification of Diseases 9th Edition (ICD-9) diagnoses for all inpatient and outpatient visits through December 1999 and all outpatient prescriptions obtained from a VA facility. The date of enrollment, or index date, was defined as the day the health inventory checklist was processed.
Methods
Outcome and exposures of interest
Study setting and population
Our primary outcome of interest for this study was risk of first hospitalization for pneumonia occurring within one year of enrollment. We identified all hospitalizations with a primary ICD-9 discharge diagnosis of bacterial pneumonia as defined by the Agency for Healthcare Research and Quality,2 including: 481, 482.2, 482.30, 482.31, 482.32, 482.39, 482.9, 483.0, 483.1, 483.8, 485, and 486.
We performed secondary analysis of data collected for the Ambulatory Care Quality Improvement Project (ACQUIP), a multi-center randomized trial to improve patient health and satisfaction. The study population, methods and results of this study have been described previously in detail.25
Smoking cessation and pneumonia hospitalization Using the health inventory checklist, we ascertained whether patients were current, former or never smokers as of the index date. Among those with a history of tobacco use, we determined the average number of cigarettes smoked daily in 10-cigarette increments up to 40 cigarettes per day. We grouped former smokers based upon their self-reported time since quitting smoking into the following categories: less than 1 year, 1e5 years, 6e10 years or more than 10 years since last cigarette use.
Covariates Using the survey data, we identified demographic information for all participants as of the index date, including: age, race, marital status and highest level of education. We used the score on the self-reported Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire to assess alcohol use and misuse, categorizing patients into four groups: no past use (AUDIT-C score of 0), low-level use (AUDIT-C score of 1e3), mild-moderate alcohol misuse (AUDIT-C 4e7) and severe alcohol misuse (AUDIT-C 8e12).26e31 In addition, we identified the presence of seven specific comorbid illnesses, including: prior myocardial infarction (MI), diabetes mellitus (DM), history of cerebrovascular accident (CVA), congestive heart failure (CHF), malignancy, COPD and prior pneumonia. Due to the increased risk of pneumonia among users of inhaled corticosteroids (ICS),32 we identified participants receiving a prescription for an ICS in the year prior to enrollment using pharmacy data.
Statistical analysis We utilized Cox proportional-hazard models to estimate the risk of first hospitalization for pneumonia associated with smoking status and length of smoking cessation.33 We followed patients until their first hospitalization for pneumonia, and censored for death, end of follow-up, or at one year post-enrollment. We assessed the relationship between subsequent hospitalization for pneumonia and both smoking status (entire cohort) and duration of abstinence from tobacco (including only those participants with a history of tobacco exposure) after adjusting for all the covariates listed above. In addition, we adjusted for the average number of cigarettes smoked per day in the models estimating associations of the time since quitting tobacco. Lastly, we used stratified models to examine how the relationship between smoking status and time since quitting tobacco was modified by the presence or absence of self-reported physician diagnosed COPD in a restricted cohort including only former and current smokers. We tested the proportional hazards assumption graphically and via Schoenfeld residuals, and found it to be valid for all final models, with the exception of the adjusted models restricted to patients with COPD. In this case, the addition of prior MI as a covariate caused a violation of the proportional hazards assumption, and therefore it was omitted from the final adjusted model. All statistical analyses were performed using Stata-10 statistical software (College Station, TX).
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Results Study population Of the 62,487 patients mailed the initial ACQUIP health checklist questionnaires, 36,821 patients (59%) responded. On average, these respondents were older (63 vs. 59 years) and had a higher prevalence of comorbid conditions including coronary artery disease, COPD, chronic heart failure, depression, diabetes and hypertension. However, after stratifying by age, the prevalence of these chronic conditions among responders and non-responders was similar. Of the 36,821 respondents, we identified 25,235 men (69%) who met eligibility criteria for this study. Of these we identified 6720 (26.6%) current smokers, 13,625 (54.0%) former smokers, and 4890 (19.4%) never smokers. Of the former smokers, the majority (n Z 8,760, 64.3%) reported quitting more than 10 years prior to enrollment. Current smokers were younger, more likely to be of black race, less likely to be married, and less educated than either former or never smokers (Table 1). Former smokers were more likely to have had a previous MI or CVA, report a history of prior pneumonia, be treated with an ICS, and to carry a diagnosis of DM, CHF, or malignancy than either current or never smokers. Former smokers were more likely than never smokers, but less likely than current smokers, to have a self-reported physician diagnosis of COPD. However, when examined by duration of smoking cessation, the proportion of former smokers who had quit within the past five years who had a self-reported diagnosis of COPD was similar to that of current smokers. On average, both former and current smokers reported consuming about a pack per day of cigarettes. Current smokers were more likely to report either mild-moderate or severe alcohol misuse compared to former and never smokers.
Risk of hospitalization for pneumonia and smoking status During the year following enrollment, we identified 359 hospital admissions for pneumonia, occurring at a median of 190 days (range 1e365 days). The overall incidence of admissions for pneumonia among the cohort was 14.6 per 1000 person-years. Among former and never smokers, the incidence of pneumonia was much higher among the 5074 participants with a self-reported diagnosis of COPD than among the 15,266 subjects without such a diagnosis (32.6 hospitalizations per 1000 person/years vs. 10.8 hospitalizations per 1000 person/years, respectively). In adjusted analyses and in comparison to current smokers, never smokers were at decreased risk of hospitalization for pneumonia (Table 2). Former smokers had a decreased point estimate of risk of hospitalization that did not reach statistical significance. Similarly, among all participants, we found no difference in risk of hospitalization for pneumonia among former smokers with varying lengths of abstinence from tobacco when compared to current smokers (Table 2; p-value for linear trend Z 0.07).
1058 Table 1
L.M. Cecere et al. Characteristics of participants by smoking status and duration of reported abstinence. Current smokers
Former smokers
Never smokers
All former smokers
By duration of abstinence Quit <1 yr
Quit 1e5 yrs Quit 6e10 yrs Quit >10 yrs
N Z 6720
N Z 13,625
N Z 1053
N Z 1998
N Z 1814
N Z 8760
N Z 4890
N (%)
N (%)
N (%)
N (%)
N (%)
N (%)
N (%)
a
Age (years) <50 50e59 60e69 70e79 80 Racea White Black Other Married Educationa
1950 1814 1848 997 102
(29) (27) (28) (15) (1)
1341 2155 4471 4883 759
(10) (16) (33) (36) (5)
244 273 334 186 16
(23) (26) (32) (18) (1)
348 440 690 473 47
(17) (22) (35) (24) (2)
222 372 653 507 58
(12) (21) (36) (28) (3)
527 1070 2794 3717 638
(6) (12) (32) (42) (7)
933 812 1253 1492 391
(19) (17) (26) (30) (8)
4691 1544 321 2920
(70) (23) (5) (43)
10,380 1998 758 8579
(76) (15) (6) (63)
719 250 54 520
(68) (24) (5) (49)
1428 389 123 1105
(71) (19) (6) (55)
1351 294 107 1110
(74) (16) (6) (61)
6882 1065 474 5844
(79) (12) (5) (67)
3355 947 432 2775
(69) (19) (9) (57)
1912 (28) 4003 (60) 670 (10)
4062 (30) 7314 (54) 1929 (14)
1156 1102 705 465 597 1935 924 495 18.9
2944 3303 1546 1299 1820 3139 2006 1173 20.6
(17) (16) (10) (7) (9) (29) (14) (7) (10.4)
257 (24) 644 (61) 126 (12)
(22) 214 (24) 189 (11) 111 (10) 97 (13) 110 (23) 310 (15) 165 (9) 127 (11.4) 20.7
(20) (18) (11) (9) (10) (29) (16) (12) (11.1)
574 (29) 1132 (57) 248 (12)
494 (27) 1061 (58) 224 (12)
2737 (31) 4477 (51) 1331 (15)
1046 (21) 2557 (52) 1172 (24)
450 438 261 206 265 616 308 234 21.4
417 441 199 182 231 466 255 176 22.3
1863 2235 975 814 1214 1747 1278 636 20.1
634 1092 441 309 506 574 444 180 N/A
(23) (22) (13) (10) (13) (31) (15) (12) (11.2)
(23) (24) (11) (10) (13) (26) (14) (10) (11.2)
(21) (26) (11) (9) (14) (20) (15) (7) (11.5)
(13) (22) (9) (6) (10) (12) (9) (4)
2501 (37) 1808 (27) 1500 (22)
6634 (49) 4392 (32) 2128 (16)
434 (41) 364 (35) 185 (18)
1008 (50) 588 (29) 314 (16)
877 (48) 606 (33) 272 (15)
4315 (49) 2834 (32) 1357 (15)
2488 (51) 1636 (33) 612 (13)
911 (14)
471 (3)
70 (7)
88 (4)
59 (3)
254 (3)
154 (3)
Some column totals do not add to 100% due to missing values; Abbreviations: MI Z Myocardial infarction; CVA Z Cerebrovascular accident; CHF Z Congestive heart failure; COPD Z chronic obstructive pulmonary disease; ICS Z Inhaled corticosteroid. a
Stratification by self-reported physician diagnosis of COPD Among former and current smokers who did not endorse having a physician diagnosis of COPD, we found a significantly lower risk of hospitalization among former smokers when compared to current tobacco users after adjustment for age, demographics, alcohol use/misuse, non-pulmonary comorbid illness, history of prior pneumonia, use of ICS, and intensity of tobacco exposure (cigarettes/day) (Table 3). Furthermore, among former smokers, we found the lower risk to be isolated to those who quit tobacco more than 10 years previously. In contrast, among former and current smokers with a self-reported physician diagnosis of COPD, we found no difference in risk of hospitalization dependent on smoking status or on time since quitting tobacco when compared to current smokers (Table 3).
Discussion In a large cohort of more than 25,000 Veterans, we found smoking cessation was an important predictor of the risk of pneumonia, but that risk was dependent on the duration of cessation as well as whether patients had recognized COPD. These findings are important as they suggest that smoking cessation could be beneficial in reducing future hospitalizations for pneumonia, but that in order to be effective, quitting smoking likely needs to occur early in life. Furthermore, these results suggests that as clinicians discuss the importance of smoking cessation that they may include the concept that benefits to lung health may be most substantial prior to developing lung disease, such as COPD. To our knowledge, no previous study has assessed the relationship between smoking cessation and hospitalization
Smoking cessation and pneumonia hospitalization Table 2
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Risk of hospitalization for pneumonia by smoking status and duration of abstinence.
Tobacco exposure Smoking status Current Former Never Duration of smoking cessation Current Quit <1 year Quit 1e5 years Quit 6e10 years Quit >10 years
Total (N )
Admissions (N )
Person-years
Rate (per 1000 person-years)
Adjusted hazard ratio (95% CI)
6720 13,625 4890
89 232 38
6557 13,241 4825
13.6 17.5 7.9
1.00a 0.83 (0.63e1.09) 0.48 (0.31e0.74)
6720 1053 1998 1814 8760
89 15 38 31 148
6557 1020 1938 1763 8520
13.6 14.7 19.6 17.6 17.4
1.00b 0.93 (0.52e1.66) 0.95 (0.63e1.42) 0.79 (0.50e1.26) 0.77 (0.57e1.04)
Values in bold indicate p-value<0.05. a Adjusted for age, race, marital status, education level, alcohol use, previous myocardial infarction, diabetes mellitus, history of cerebrovascular accident, congestive heart failure, malignancy, prior pneumonia, use of ICS, and diagnosis of COPD. b Adjusted for same demographics and comorbid illnesses, with additional adjustment made for cigarettes per day consumed (p-value for linear trend Z 0.07).
for pneumonia. However, two prior studies suggest smoking cessation to be associated with a reduced risk of developing pneumonia in the first place. In a population based caseecontrol study, Almirall et al. found the odds of developing pneumonia was reduced by 50% after 5 years of smoking cessation.19 Similarly, Baik et al. found former
smokers who quit smoking less than ten years prior had a 1.5 times higher risk, while those who had quit for ten or more years had no difference in risk, of developing pneumonia when compared to never smokers.22 Based on these studies, we expected to find a similar reduction in risk of hospitalization for pneumonia among all former smokers,
Table 3 Risk of hospitalization for pneumonia by smoking status and duration of abstinence, stratified by self-reported physician diagnosis of chronic obstructive pulmonary disease (COPD). Tobacco exposure
Total (N )
Admissions (N )
Person-years
Rate (per 1000 person-years)
Adjusted hazard ratio (95% CI)
49 113
4694 10,247
10.4 11.0
Referenta 0.65 (0.45, 0.95)
49 5 14 16 78
4694 727 1350 1315 6855
10.4 6.9 10.4 12.2 11.4
Referenta,b 0.64 (0.25, 1.64) 0.71 (0.38, 1.35) 0.77 (0.41, 1.47) 0.62 (0.41, 0.93)
1935 3139
40 118
1863 2990
21.5 39.5
Referentc 1.04 (0.70e1.54)
1935 310 616 466 1747
40 10 24 15 69
1863 292 587 448 1663
21.5 34.2 40.9 33.5 41.5
Referentc,d 1.24 (0.59e2.58) 1.23 (0.72e2.10) 0.83 (0.42e1.61) 0.99 (0.64e1.53)
No self-reported diagnosis of COPDa Smoking status Current 4785 Former 10,481 Duration of smoking cessation Current 4785 Quit <1 year 743 Quit 1e5 years 1381 Quit 6e10 years 1347 Quit >10 years 7010 Self-reported diagnosis of COPDa Smoking status Current Former Duration of smoking cessation Current Quit <1 year Quit 1e5 years Quit 6e10 years Quit >10 years
Values in bold indicate p-value <0.05. a Adjusted for age, race, marital status, education level, alcohol use, previous myocardial infarction, diabetes mellitus, history of cerebrovascular accident, congestive heart failure, malignancy, prior pneumonia, use of ICS, and average cigarettes per day. b p-value for linear trend Z 0.03. c Adjusted for same covariates listed above, with the exception of myocardial infarction, which was omitted from the model due to violation of proportional hazard assumptions. d p-value for linear trend Z 0.75.
1060 however this was not the case. Our patient population has a high prevalence of COPD, a finding that is consistent with previous studies showing a higher occurrence of COPD among United States Veterans than the general population.34 This is likely due primarily to high rates of tobacco smoking within this group, but age, exposure to passive tobacco smoke and occupational exposures are also risk factors for COPD,34,35 which may help explain the 12% of never smokers with self-reported COPD in this cohort. We hypothesize that differences between the results of our study and those previously published could be due to this high prevalence of COPD within our population, which will have driven our findings for our nonstratified analyses toward the null. This is supported by the fact that we did find a similar reduction to these other studies in risk among former smokers without a selfreported diagnosis of COPD. There are several possible explanations for our finding that ex-smokers without COPD have reduced risk of hospitalization for pneumonia compared to current smokers, whereas among patients with self-reported COPD this association is not observed. First, there are several biologic mechanisms thought to result in increased susceptibility to respiratory infection among smokers. These include a number of alterations to the host immune system, ranging from impaired ciliary function36 to depressed T-cell activity and natural killer cell function.37,38 Although many of these changes are likely reversible over time with smoking cessation, the immune dysfunction that occurs with smoking tobacco may be less reversible among patients with COPD.39 Second, patients who are able to achieve smoking cessation are also likely to achieve other healthy behaviors, such as reducing alcohol intake and following up with primary care physicians, which could result in earlier diagnosis and treatment and a subsequent reduction in their risk of hospitalization. COPD has been associated with the development of pneumonia severe enough to result in hospitalization,12e15 need for mechanical ventilation23 and death,14,23,24 and smoking cessation alone, or in combination with other healthy behaviors, may not be sufficient to reduce the incidence of hospitalization among this patient group. The majority of the estimated 1 in 5 adult tobacco users in the United States40 began smoking at an early age,41 and the incidence of tobacco use is higher among adolescents than older adults.40 Patients who are young and have not yet had undesirable health consequences from smoking may be reluctant to attempt smoking cessation. There is evidence that smoking cessation interventions that incorporate “gain-framed” messages, or highlight the benefits of abstinence from tobacco, may be more successful than those that are “loss-framed,” or emphasize the costs of continued smoking.42,43 Our results suggest that clinicians providing counseling about the benefits of smoking cessation can emphasize not only that smoking cessation reduces the risk of common tobacco-related lung diseases, such as COPD and lung cancer, but also educate patients about the importance of quitting early in life, when other adverse health outcomes, such as hospitalization for pneumonia, may be still modifiable. This study has some potential limitations. First, we relied upon self-report to determine current smoking status
L.M. Cecere et al. and the duration of abstinence among former smokers, which could result in potential misclassification of exposure status. Due to social desirability, participants may have under-reported current tobacco use or over-estimated their duration of abstinence, which could have resulted in biasing the study toward the null. Second, we could not account for the duration of tobacco exposure. However, as most patients begin smoking at around the same time and at a young age, adjustment for duration of use, in addition to age and average intensity of tobacco exposure, would likely not significantly change our findings. Third, we relied upon self-report of a physician diagnosis, rather than spirometry, to identify patients with COPD, which could result in misclassification. However, the high prevalence of COPD within our population is similar to that found in previous studies of United States Veterans. Fourth, our findings may not generalize to women, who are less likely to be hospitalized, less likely to require intensive care admission and to have a lower pneumonia-related mortality than men.44 Lastly, although the intervention had no effect on improving patient’s health status, and is therefore unlikely to have an effect on our outcome of interest, our study participants did tend to be older, white men, with high rates of comorbid COPD, which could affect the generalizability of our results. 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. In conclusion, we found that smoking cessation is associated with a reduction in the risk of hospitalization for pneumonia, but only among patients without a diagnosis of COPD, and then only among patients who quit smoking more than 10 years previously. These findings give clinicians additional important information to provide to patients about the benefits of early smoking cessation and emphasizes the advantages of smoking cessation prior to the development of lung disease.
Funding source This study was supported by a Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) grant [IAC 05-206-1]. Dr. Cecere is supported by a VA HSR&D fellowship [TPM 61037]. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs.
Conflict of interest statement Drs. Au and Bryson are co-investigators on a grant from Giliad Sciences for work which is unrelated to this
Smoking cessation and pneumonia hospitalization manuscript. Dr. Au is a research consultant for Bosch LLC. Drs. Cecere, Williams, Sun, Clark, and Bradley have no potential conflicts of interest to disclose.
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