Tobacco Smoking Increases the Risk for Death From Pneumococcal Pneumonia

doi:10.1378/chest.13-2853

CHEST

Volume 146, Issue 4, October 2014, Pages 1029-1037

https://doi.org/10.1378/chest.13-2853 Get rights and content

BACKGROUND

Active smoking increases the risk of developing community-acquired pneumonia (CAP) and invasive pneumococcal disease, although its impact on mortality in pneumococcal CAP outcomes remains unclear. The aim of this study was to investigate the influence of current smoking status on pneumococcal CAP mortality.

METHODS

We performed a multicenter, prospective, observational cohort study in 4,288 hospitalized patients with CAP. The study group consisted of 892 patients with pneumococcal CAP: 204 current smokers (22.8%), 387 nonsmokers (43.4%), and 301 exsmokers (33.7%).

RESULTS

Mortality at 30 days was 3.9%: 4.9% in current smokers vs 4.3% in nonsmokers and 2.6% in exsmokers. Current smokers with CAP were younger (51 years vs 74 years), with more alcohol abuse and fewer cardiac, renal, and asthma diseases. Current smokers had lower CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) scores, although 40% had severe sepsis at diagnosis. Current smoking was an independent risk factor (OR, 5.0; 95% CI, 1.8-13.5; P = .001) for 30-day mortality of pneumococcal CAP after adjusting for age (OR, 1.06; P = .001), liver disease (OR, 4.5), sepsis (OR, 2.3), antibiotic adherence to guidelines, and first antibiotic dose given < 6 h. The independent risk effect of current smokers remained when compared only with nonsmokers (OR, 4.0; 95% CI, 1.3-12.6; P = .015) or to exsmokers (OR, 3.9; 95% CI, 1.09-4.95; P = .02).

CONCLUSIONS

Current smokers with pneumococcal CAP often develop severe sepsis and require hospitalization at a younger age, despite fewer comorbid conditions. Smoking increases the risk of 30-day mortality independently of tobacco-related comorbidity, age, and comorbid conditions. Current smokers should be actively targeted for preventive strategies.

Section snippets

Design and Study Population

The current study is a secondary analysis, and the whole prospective cohort has been published.²⁸ In brief, inclusion criteria were adults aged > 18 years with a new radiographic infiltrate compatible with the presence of acute pneumonia and at least two signs or symptoms of CAP. Exclusion criteria were admission within the previous 15 days, solid organ transplantation, hematologic malignancies, immunosuppressive treatment and/or chronic corticosteroid treatment (≥ 20 mg/d), and HIV infection.

General Characteristics

We recruited 4,374 patients with CAP in the whole cohort study; 86 were excluded due to missing data. A total of 913 patients had pneumococcal CAP (21.3%), of whom 83 had mixed etiology (pneumococcus-involved mixed etiology) and 21 lost to follow-up were excluded. The study group comprised 892 patients with pneumococcal CAP (Table 1). Main patient characteristics, habits, vaccination status, comorbid conditions, sepsis status, and CURB-65 score are shown in Table 2. Of these patients, 204 were

Discussion

The main findings of our study are the following:

Current smokers developed sepsis and require hospitalization for pneumococcal CAP at a younger age than noncurrent smokers.
Active smoking is an independent mortality risk factor (OR, 5.0) in patients with pneumococcal CAP after adjusting for age, influenza and pneumococcal vaccination, comorbidities (alcohol-related, heart, kidney, cerebrovascular, and neoplastic diseases), initial severity measured by CURB-65 score, severe sepsis,

Acknowledgments

Author contributions: S. B., R. M., and A. T. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. S. B. served as principal author. S. B., R. M., and A. T. contributed to the study design; S. B., R. M., A. T., S. R., R. Z., A. C., J. A., L. B., J. J. M.-V., I. A., F. R. d. C., J. R., L. M., and J. R.-M contributed to data acquisition; S. B., R. M., and A. T. contributed to data analysis and interpretation;

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On the other hand, more severe and extremely severe cases seem to have been included in 2016 and 2017 than in 2012–2015 according to the severity index using A-DROP, probably due to the inclusion of more elderly patients who had confusion and/or dehydration in 2016 and 2017 and aging in Japan may leads to increased severity of pneumococcal pneumonia patients. In addition to the severity index using A-DROP, various items have been reported as independent risk factors for mortality in patients with pneumococcal pneumonia, including male sex [20], old age [4,20], a poor ECOG performance status [18], cerebrovascular disease [28], chronic liver disease [19], diabetes mellitus [4], bacteremia [18,28], and the requirement for invasive mechanical ventilation [4]. Similar to previous reports, the presence of some comorbid diseases, coexistence of IPD, invasive mechanical ventilation, and a low BMI were identified as risk factors for mortality in this study.
Pneumococcal pneumonia has a high morbidity and mortality in adults, especially those ≥65 years old. In the past decade, pneumococcal vaccination programs have been initiated worldwide, however, few data concerning mortality changes are available in pneumococcal pneumonia patients and there are no reports clarifying these current changes in Japan.
Japanese patients ≥65 years old hospitalized with pneumococcal pneumonia between April 2012 and March 2018 were analyzed using the Diagnostic Procedure Combination database. In-hospital mortality was evaluated, and the odds ratios for this outcome in each fiscal year compared with that in 2012 was analyzed using multivariable logistic regression models.
Between 2012 and 2017, data of 47,375 pneumococcal pneumonia patients ≥65 years old were extracted. The incidence per 1000 person-years for in-hospital mortality was 60.4 in 2012, 56.8 in 2013, 63.2 in 2014, 56.1 in 2015, 73.0 in 2016, and 67.4 in 2017 and the odds ratios for in-hospital mortality in 2013, 2014, 2015, 2016, and 2017 compared with that in 2012 were 1.00, 1.05, 1.04, 1.06, and 0.98, respectively. There were no significant differences between 2012 and each year from 2013 to 2017. Low BMI; low ADL score; high A-DROP score; comorbid malignancy and heart failure; the coexistence of invasive pneumococcal infection; and the use of invasive mechanical ventilation were independent risk factors for in-hospital mortality.
There were no changes in in-hospital mortality in pneumococcal pneumonia patients between 2012 or each year from 2013 to 2017 and further epidemiological observations are necessary.
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Patients who underwent elective colorectal, pancreatic, gastric, or hepatic procedures were identified in the 2017 ACS NSQIP dataset. The primary outcome was 30-day death or serious morbidity (DSM). Secondary outcomes included pulmonary complications, wound complications, and readmission. Multivariable logistic regression was used to evaluate the association between smoking and these outcomes.
A total of 46,921 patients were identified, of whom 7,671 (16.3%) were smokers. Smoking was associated with DSM (23.2% vs. 20.4%, OR 1.15 [1.08–1.23]), wound complications (13.0% vs. 10.4%, OR 1.24 [1.14–1.34]), pulmonary complications (4.9% vs 2.9%, OR 1.93 [1.70–2.20]), and unplanned readmission (12.6% vs. 11%, OR 1.14 [95% CI 1.06–1.23]).
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Clinical conditions associated with an increased risk of community-acquired pneumonia include history of pneumonia (odds ratio [OR] <6·25); chronic cardiovascular diseases (OR <3·20); cerebrovascular disease, stroke, and dementia (OR <2·68); neurological or psychiatric conditions (OR <3·20); chronic respiratory diseases, including chronic obstructive pulmonary disorder (COPD), bronchitis, or asthma (OR <2·17); dysphagia (adjusted OR [aOR] from 2·10 to 11·90); diabetes (aOR <1·33); cancer (aOR <1·42); and chronic liver disease (aOR <1·87) or renal disease (aOR <1·78).16,17 Several lifestyle factors are associated with an increased risk of community-acquired pneumonia, namely history of alcohol abuse or alcoholism (OR <2·91), being underweight (OR <2·20), living with more than ten people (OR <2·20), current smoking status (aOR <2·00), former smoking status (aOR <1·04), and regular contact with children (OR <1·48).16–19 Finally, clinical conditions and therapies leading to an immunocompromised state are crucial determinants for community-acquired pneumonia.20
Community-acquired pneumonia is not usually considered a high-priority problem by the public, although it is responsible for substantial mortality, with a third of patients dying within 1 year after being discharged from hospital for pneumoniae. Although up to 18% of patients with community-acquired pneumonia who were hospitalised (admitted to hospital and treated there) have at least one risk factor for immunosuppression worldwide, strong evidence on community-acquired pneumonia management in this population is scarce. Several features of clinical management for community-acquired pneumonia should be addressed to reduce mortality, morbidity, and complications related to community-acquired pneumonia in patients who are immunocompetent and patients who are immunocompromised. These features include rapid diagnosis, microbiological investigation, prevention and management of complications (eg, respiratory failure, sepsis, and multiorgan failure), empirical antibiotic therapy in accordance with patient's risk factors and local microbiological epidemiology, individualised antibiotic therapy according to microbiological data, appropriate outcomes for therapeutic switch from parenteral to oral antibiotics, discharge planning, and long-term follow-up. This Seminar offers an updated view on community-acquired pneumonia in adults, with suggestions for clinical and translational research.
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Community-acquired pneumonia (CAP) is a frequently occurring disease linked to high mortality and morbidity. Previous studies indicated that the administration of antibiotics within 4 hrs of admission can improve key patient outcomes associated with CAP, such as mortality and time to clinical stability. However, the results have been heterogeneous and may not be applicable to all healthcare settings. Therefore, we designed a cohort study to estimate the impact of timely antibiotic administration on outcomes in patients admitted with CAP.
The impact of antibiotic administration within 4 hrs of admission and other covariates were estimated for 30-day mortality, stability within 72 hrs, 30-day readmission and time to discharge, using multivariable regression models. Sensitivity analyses were performed on a subset of patients with the most severe CAP and a propensity score matched cohort.
In total, 2264 patients were included. Of these, 273 (12.1%) died within 30 days of admission, 1277 (56.4%) were alive and stable within 72 hrs and 334 (14.8%) were discharged alive and readmitted within 30 days. Median length of hospital stay was 5 days (interquartile range 3–8). In all models, the administration of antibiotics within 4 hrs of admission had no significant effect on the outcomes. The adjusted odds ratios (OR) derived from the multivariable models for 30-day mortality, stability within 72 hrs and 30-day readmission were 1.01 (95% confidence interval (CI) 0.76; 1.33), 0.88 (95% CI 0.74; 1.05) and 1.05 (95% CI 0.82; 1.34). The adjusted hazard ratio (HR) for time to discharge was 1.00 (95% CI 0.91; 1.10).
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FUNDING/SUPPORT: This study was supported by the Centro de investigación en red de enfermedades respiratorias, an initiative of the Instituto de Salud Carlos III [Fis Grant PI 041150]; Sociedad Española de Neumología y Cirugía torácica (SEPAR) and PII (SEPAR Research Programme) in respiratory infections [Grant 2007]; and a grant from the Ministry of Health of the Autonomous Community of Valencia [2007/0059].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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CHEST

Original Research: Chest InfectionsTobacco Smoking Increases the Risk for Death From Pneumococcal Pneumonia

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

Section snippets

Design and Study Population

General Characteristics

Discussion

Acknowledgments

J Autoimmun

J Allergy Clin Immunol

Chest

Clin Microbiol Infect

Chest

Chest

Chest

Neuron

Prev Med

Respir Med

Immunological effects of tobacco smoking in “healthy” smokers

COPD

Cigarette smoking and innate immunity

Inflamm Res

Inhibition by cigarette smoke of nuclear factor-κB-dependent response to bacteria in the airway

Am J Respir Cell Mol Biol

Threshold of biologic responses of the small airway epithelium to low levels of tobacco smoke

Am J Respir Crit Care Med

Exposure to cigarette smoke inhibits the pulmonary T-cell response to influenza virus and Mycobacterium tuberculosis

Infect Immun

Tobacco use increases susceptibility to bacterial infection

Tob Induc Dis

Risk factors for community-acquired pneumonia in adults: a population-based case-control study

Eur Respir J

Community-Acquired Pneumonia in Catalan Countries (PACAP) Study Group. New evidence of risk factors for community-acquired pneumonia: a population-based study

Eur Respir J

A prospective study of age and lifestyle factors in relation to community-acquired pneumonia in US men and women

Arch Intern Med

Active Bacterial Core Surveillance Team. Cigarette smoking and invasive pneumococcal disease

N Engl J Med

Risk factors for sporadic community-acquired Legionnaires' disease. A 3-year national case-control study

Public Health

Smoking and the outcome of infection

J Intern Med

Tobacco associated mortality in Mumbai (Bombay) India. Results of the Bombay Cohort Study

Int J Epidemiol

Original Research: Chest Infections
Tobacco Smoking Increases the Risk for Death From Pneumococcal Pneumonia