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epithelial barrier integrity&#44; alveolar macrophages that recognize and phagocytize invading microorganisms&#41;&#46; Any failure of these mechanisms may result in microorganisms spreading to the bronchial tree&#44; triggering community-acquired pneumonia &#40;CAP&#41;&#44; which remains a major cause of morbidity and mortality in developed countries&#46; In the general adult population&#44; the annual incidence of CAP varies between 1&#46;6 and 13&#46;4 cases per 1000 inhabitants&#44; with a hospitalization rate of between 22 and 51&#37; and a mortality rate of 3&#37;&#8211;24&#37;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> that has not changed in recent years&#44; despite the preventive measures undertaken&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Smoking and Pneumonia</span><p id="par0015" class="elsevierStylePara elsevierViewall">The most important risk factor for CAP is age&#46; So much so&#44; that the incidence triples or quadruples when age is &#62;65 years&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The reason is unclear&#44; but several factors may be involved&#44; related to immune senescence due to weakness &#40;innate and adaptive&#41; of the immune system&#44; increased asymptomatic aspirations in this age group&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> or the convergence of other risk factors &#40;RF&#41; that do not acquire statistical significance in younger people&#44; but that take center stage in older age groups&#44; possibly due to an additive effect&#46; One of these factors may be tobacco smoking&#44; the main RF for COPD&#44; which in turn is one of the main RFs for CAP&#46; Thus&#44; it is often difficult to determine the specific weight of smoking in the development of CAP&#44; especially considering that smoking is associated with lower socioeconomic status&#44; poor diet&#44; increased alcohol consumption&#44; and reduced physical activity&#44; that are also RFs for respiratory infection&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Nevertheless&#44; enough studies using statistical analysis with logistic regression models are now available to allow the differentiation of any confounding factors&#44; showing that tobacco smoking in itself increases the risk of pneumonia&#46; In this regard&#44; a population-based study<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> was published that demonstrated an increased risk of CAP in smokers that was also directly related to the duration of tobacco consumption and the number of cigarettes consumed&#46; Concurrently&#44; it has been shown that this risk disappears when smokers quit&#46; In fact&#44; after 5 years&#44; the risk decreases by 50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Moreover&#44; if we consider that one of the criteria for causality between two factors is dose-response&#44; the increase in risk associated with an increase in intensity of consumption and the overall amount of tobacco consumed further reinforces the notion that tobacco smoking is a direct causal agent of CAP&#46; On the other hand&#44; we know that tobacco smoking causes morphological changes in the epithelium of the bronchial mucosa&#44; with loss of cilia&#44; mucous gland hypertrophy and increased goblet cells that may favor the presence and spread of microbes in the bronchial tree&#46; An inflammatory reaction is produced in the airway causing macrophage and neutrophil activation that releases proteases&#46; Oxidative stress and cytokine release are triggered&#44; leading to both innate and adaptive immune response&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;14</span></a> This may in turn make the bronchial mucosa epithelium more sensitive to the inflammatory aggression of the infection itself&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#8211;17</span></a> Moreover&#44; it is now known that tobacco smoking inhibits some of the key functions of the innate and adaptive response&#44; including the response of two Toll-like receptors &#40;TLR2&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> nuclear factor kappaB &#40;NF-&#954;B&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> CD4-lymphocyte proliferation &#40;LTCD4&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;19</span></a> maturation of dendritic cells&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and opsonization and phagocytosis capacities&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Thus&#44; tobacco smoking can alter immunity against infection&#44; affecting the modulation of intra- and intercellular signaling of epithelium and immune cells&#44; and suppressing the activation of important elements of the innate and adaptive immune response&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;21</span></a> The fact that tobacco smoking increases susceptibility to bacterial infection is well established&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Passive Smoking and Pneumonia</span><p id="par0020" class="elsevierStylePara elsevierViewall">Passive smoking is considered a major epidemiological problem&#46; In 2004&#44; an international study including 192 countries found that 40&#37; of children&#44; 33&#37; of male non-smokers and 35&#37; of female non-smokers&#44; were passive smokers&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> There were wide geographical variations that could be explained by the different stages of the tobacco smoking epidemic in the country surveyed&#44; because passive smoking is directly related to active smoking rates&#46; In the year 2005&#44; prevalence data in Spain estimated that about 50&#37; of adults were exposed to second-hand smoke&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Later&#44; as in most developed countries&#44; legislation was introduced to regulate tobacco smoking in public places&#46; This has reduced exposure to tobacco smoke by approximately 20&#37;&#8211;25&#37;&#44; due to falling consumption in public places and in the workplace&#44; but not at home&#46; Accordingly&#44; in recent years there has been growing interest in understanding the effect of passive tobacco smoking and some studies suggest that it could also involve a higher risk of respiratory infections in both the children of smoking parents&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> and in adults&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> Allowing smoking in the home has also been shown to be an important predictor of health loss in elderly people with CAP&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> In fact&#44; lesions in the respiratory epithelium&#44; connective tissue and vascular endothelium of the lung caused by tobacco smoke can occur even at low smoke concentrations&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> supporting the notion that exposure to tobacco smoke could be an important risk factor for CAP development in passive smokers&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Two separate case-controlled&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> population-based studies have also demonstrated that passive smoking is a risk factor for developing pneumococcal bacteremia in immunocompetent adults&#44; resulting in an odds ratio &#40;OR&#41; of 2&#46;6 and attributable risk &#40;AR&#41; of 31&#37; in subjects aged &#60;65 years&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;33</span></a> and OR 2&#46;2 and AR 13&#37; in those over 65 years of age&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;32</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Smoking and Pneumococcal Pneumonia</span><p id="par0030" class="elsevierStylePara elsevierViewall">The most common causative organism of CAP&#44; regardless of care level and severity&#44; is <span class="elsevierStyleItalic">Streptococcus pneumoniae</span>&#46; This has also been shown to be the agent most frequently linked to smoking&#44; especially in patients with COPD&#46; An <span class="elsevierStyleItalic">in vitro</span> study has shown increased adherence of <span class="elsevierStyleItalic">S&#46; pneumoniae</span> to the epithelial cells in the oral cavity of smokers&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> persisting for up to three years after smoking cessation&#46; This may produce greater oropharyngeal colonization and lead to greater chance of developing CAP&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Smoking has also been related with invasive pneumococcal disease &#40;IPD&#41;&#44; which in approximately 80&#37; of cases is due to pneumonia&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> This association was reported in a study by Pastor et al&#46; in 1995&#44; with an OR of 2&#46;6 in smokers between 24 and 64 years of age and OR of 2&#46;2 in smokers older than 65 years&#46; Attributable risk &#40;AR&#41; was 31&#37; in the first group and 13&#37; in the second group&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Another population-based&#44; case-controlled study<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> also highlighted that smoking is the largest independent RF for IPD in immunocompetent adults&#44; with an OR&#61;4&#46;1 in current smokers &#40;AR 51&#37;&#41;&#46; Furthermore&#44; there is a dose-response effect&#44; and smoking cessation dramatically reduces the risk after 10 years&#44; when it becomes the same as that of nonsmokers&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The special relationship of active smoking with pneumococcus has been demonstrated by some studies that have shown tobacco-induced changes in the clearance and phagocytosis of <span class="elsevierStyleItalic">S&#46; pneumoniae</span> in the lungs&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> and inhibition of the anti-pneumococcal activity of some innate immunity antimicrobial peptides&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38</span></a> Thus&#44; tobacco smoking impairs immunity to infection&#44; especially against some microorganisms&#44; including <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#44; and it seems well established that active smoking increases the risk of pneumonia&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">However&#44; the information as to whether active smokers have a worse CAP prognosis is not so clear&#46; Three longitudinal studies<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">39&#8211;41</span></a> involving large patient cohorts found higher mortality in smokers with pneumonia&#44; while two metaanalyses<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;43</span></a> found that tobacco smoking did not affect prognosis&#46; Two large retrospective series that studied CAP mortality in relation to tobacco smoking have shown contradictory results&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#44;45</span></a> Finally&#44; a recent study showed that tobacco smoking was an independent risk factor for septic shock in pneumococcal pneumonia&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> and another epidemiological study concluded that smoking was an independent determinant of mortality in bacteremic CAP caused by <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> Considering all these data&#44; we can conclude that there is evidence to suggest worse prognosis of pneumococcal pneumonia in active smokers&#44; while the picture is not so clear if we consider overall CAP&#44; independent of the etiology&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Smoking and <span class="elsevierStyleItalic">Legionella pneumophila</span> Pneumonia</span><p id="par0050" class="elsevierStylePara elsevierViewall">Less frequent&#44; but not less important&#44; is CAP due to <span class="elsevierStyleItalic">Legionella pneumophila</span>&#46; Its incidence varies according to published series&#58; some report sporadic cases while in others it is the second or third most common etiologic agent&#46; This depends on epidemiological factors&#44; the completeness of the diagnostic method used&#44; and the severity of CAP&#44; among other factors&#46; In population-based studies&#44; <span class="elsevierStyleItalic">L&#46; pneumophila</span> represents 1&#37;&#8211;3&#37; of diagnosed microorganisms&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> This type of CAP usually affects young individuals&#44; often without underlying disease&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> Smoking is the most important risk factor in these subjects&#44; as the risk may be increased by 121&#37; for each pack of cigarettes consumed daily&#44; with OR of 3&#46;48&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> and as much as 7&#46;49 if analyzed in people without comorbidities&#46; This increased risk is attributed to the difficulty in eradicating the microorganism from the bronchial tree&#44; due to the deterioration of the respiratory mucosa and impaired cilia caused by tobacco smoking that&#44; depending on the individual&#39;s immune status&#44; facilitates entry into and subsequent invasion of the alveolar macrophages&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Smoking and Other Risk Factors of Pneumonia Acquired in the Community</span><p id="par0055" class="elsevierStylePara elsevierViewall">Tobacco smoking may also favor the presence of diseases which are in turn known risk factors of CAP&#44; including&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Periodontal diseases directly related to the development of CAP&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> Poorer oral hygiene has been shown to potentially lead to increased respiratory infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">52&#44;53</span></a> Additionally&#44; smokers show higher subgingival bacterial colonization than non-smokers&#44; which is directly related to the number of cigarettes smoked by day&#46; Accordingly&#44; smokers of fewer than 10 cigarettes&#47;day present periodontitis between 2&#46;5 and 6 times more often than non-smokers &#40;OR 2&#46;79&#41;&#44; while OR is 5&#46;88 for those smoking &#62;30 cigarettes&#47;day&#59; OR decreases dramatically if the habit is quit and can reach OR 1&#46;15 after 11 years&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Viral upper respiratory tract infections&#46; Upper respiratory tract infections &#40;URTI&#41; are a risk factor of CAP&#44; independent of other related factors&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;7</span></a> and smoking independently influences the presence of prior viral infection&#46; Blake et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> observed in a cohort of soldiers diagnosed with URTI that 22&#46;7&#37; were smokers&#44; <span class="elsevierStyleItalic">vs</span> 16&#37; non-smokers &#40;RR&#58; 1&#46;5&#41;&#46; Increased susceptibility to experimental viral infection has also been observed in smokers&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a></p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Prevention</span><p id="par0070" class="elsevierStylePara elsevierViewall">At present there is enough scientific evidence to show that active tobacco smoking is an important risk factor for CAP<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;28&#44;29&#44;33</span></a>&#59; it has a direct and independent effect on the risk of CAP&#44; but it may also act indirectly causing chronic bronchitis or COPD which&#44; in turn&#44; are well recognized risk factors for CAP&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;33</span></a> Therefore&#44; one of the main ways of preventing CAP is to intervene in the smoking habit&#44; advising its cessation&#44; which may reduce the risk of CAP by 50&#37; after five years&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Furthermore&#44; a reduction of 14&#37; in IPD has been observed every year<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> and&#44; after 10 years&#44; the risk of IPD can reach the same level as that of non-smokers&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">On the other hand&#44; pneumococcal vaccine is concomitantly recommended&#46; In fact&#44; the American scientific societies propose tobacco cessation combined with pneumococcal vaccine in patients hospitalized for CAP&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> and further recommend the pneumococcal vaccine for active smokers in the population aged between 19 and 64 years&#44; regardless of the presence of comorbidities&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> This recommendation is even more relevant for active smokers&#44; in whom lower rates of influenza and pneumococcal immunization have been observed compared to former smokers and non-smokers&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">At present&#44; two types of vaccine are available&#58; the 23-valent polysaccharide vaccine and 13-valent conjugated vaccine&#46; The former has been used in Spain since 1999&#44; and protective effect has been found in studies not designed to assess its effectiveness&#44;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;60</span></a> while clinical trials to test its efficacy against IPD do not establish such an effect&#44; and effectiveness on CAP in general cannot be estimated&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a> Therefore&#44; pneumococcal immunization with the 13-valente conjugate vaccine&#44; authorized for adults in Europe since October 2011 and in Spain since July 2012&#44; has been recently recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> The main advantage over the former is that&#44; being conjugated&#44; it is capable of inducing a T-dependent immune response that provides a better immune response and generates immune memory&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> Additionally&#44; it has been described to generate IgA responses in mucosa&#44; reducing nasopharyngeal colonization by serotypes represented in the vaccine&#44; thus breaking the infectious cycle and producing group immunity&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a> Furthermore&#44; the serotype coverage of the 13-valent conjugate vaccine reaches up to 82&#37; of CAP-producing agents in healthy adults&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">65</span></a> Therefore&#44; it seems clear that the smoking population should be considered as a target for pneumococcal vaccination strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicts of Interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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          "identificador" => "xres342972"
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          "titulo" => "Palabras clave"
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          "identificador" => "sec0005"
          "titulo" => "Smoking and Pneumonia"
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          "identificador" => "sec0010"
          "titulo" => "Passive Smoking and Pneumonia"
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        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Smoking and Pneumococcal Pneumonia"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Smoking and Legionella pneumophila Pneumonia"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Smoking and Other Risk Factors of Pneumonia Acquired in the Community"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Prevention"
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        10 => array:2 [
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          "titulo" => "Conflicts of Interest"
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          "titulo" => "References"
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    "fechaRecibido" => "2013-09-20"
    "fechaAceptado" => "2013-11-19"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec324609"
          "palabras" => array:4 [
            0 => "Smoking"
            1 => "Community-acquired pneumonia"
            2 => "Risk factors"
            3 => "Prevention"
          ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:4 [
            0 => "Tabaquismo"
            1 => "Neumon&#237;a adquirida en la comunidad"
            2 => "Factores de riesgo"
            3 => "Prevenci&#243;n"
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection&#44; even in passive smokers&#46; This relationship also shows a dose-response effect&#44; since the risk reduces spectacularly 10 years after giving up smoking&#44; returning to the level of non-smokers&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Streptococcus pneumoniae</span> is the causative microorganism responsible for community-acquired pneumonia &#40;CAP&#41; most frequently associated with smoking&#44; particularly in invasive pneumococcal disease and septic shock&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">It is not clear how it acts on the progress of pneumonia&#44; but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In CAP caused by <span class="elsevierStyleItalic">Legionella pneumophila</span>&#44; it has also been observed that smoking is the most important risk factor&#44; with the risk rising 121&#37; for each pack of cigarettes smoked a day&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Tobacco use may also favor diseases that are also known risk factors for CAP&#44; such as periodontal disease and upper respiratory viral infections&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">By way of prevention&#44; while giving up smoking should always be proposed&#44; the use of the pneumococcal vaccine is also recommended&#44; regardless of the presence of other comorbidities&#46;</p>"
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        "titulo" => "Resumen"
        "resumen" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En estudios recientes ha quedando quedado perfectamente establecido que el tabaco incrementa la susceptibilidad a la infecci&#243;n bacteriana pulmonar&#44; incluso en fumadores pasivos&#46; Este efecto muestra tambi&#233;n dosis-respuesta&#44; ya que disminuye espectacularmente el riesgo 10 a&#241;os despu&#233;s de abandonar el h&#225;bito tab&#225;quico&#44; situ&#225;ndose a niveles de no fumadores&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Streptococcus pneumoniae</span> es el microorganismo causante de neumon&#237;a adquirida en la comunidad &#40;NAC&#41; que m&#225;s se ha relacionado con el tabaquismo&#44; especialmente en situaciones de enfermedad neumoc&#243;cica invasiva y shock s&#233;ptico&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Su influencia sobre la evoluci&#243;n de la neumon&#237;a no parece clara&#44; aunque existen evidencias que sugieren un peor pron&#243;stico de la neumon&#237;a neumoc&#243;cica&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">En NAC causadas por <span class="elsevierStyleItalic">Legionella pneumophila</span> tambi&#233;n se ha observado que el h&#225;bito tab&#225;quico es el factor de riesgo m&#225;s remarcable&#44; ya que puede suponer un aumento del riesgo del 121&#37; por cada paquete diario de cigarrillos consumidos&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Por otro lado&#44; el consumo de tabaco puede tambi&#233;n favorecer la presencia de enfermedades que a su vez son factores de riesgo conocidos de NAC&#44; como enfermedades periodontales e infecciones v&#237;ricas de la v&#237;a a&#233;rea superior&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Como medida preventiva&#44; si bien cabe proponer el abandono del tabaco&#44; tambi&#233;n es recomendable la vacuna neumoc&#243;cica&#44; independientemente de la presencia de comorbilidad&#46;</p>"
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    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Almirall J&#44; Blanquer J&#44; Bello S&#46; Neumon&#237;a adquirida en la comunidad en fumadores&#46; Arch Bronconeumol&#46; 2014&#59;50&#58;250&#8211;254&#46;</p>"
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    ]
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            2 => array:3 [
              "identificador" => "bib0015"
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                  "contribucion" => array:1 [
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                          "etal" => false
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                            3 => "I&#46; Bolibar"
                          ]
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                      ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1999"
                        "volumen" => "116"
                        "paginaInicial" => "375"
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Journal Information
Vol. 50. Issue 6.
Pages 250-254 (June 2014)
Visits
37316
Vol. 50. Issue 6.
Pages 250-254 (June 2014)
Review
Full text access
Community-Acquired Pneumonia Among Smokers
Neumonía adquirida en la comunidad en fumadores
Visits
37316
Jordi Almiralla,
Corresponding author
jalmirall@csdm.cat

Corresponding author.
, José Blanquerb, Salvador Belloc
a Servicio de Cuidados Intensivos, Hospital de Mataró, Universitat Autónoma de Barcelona, CIBERES, Barcelona, Spain
b Cuidados Intensivos Respiratorios, Hospital Clínico Universitario, INCLIVA, Valencia, Spain
c Servicio de Neumología, Hospital Universitario Miguel Servet, CIBERES, Zaragoza, Spain
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Abstract

Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection, even in passive smokers. This relationship also shows a dose-response effect, since the risk reduces spectacularly 10 years after giving up smoking, returning to the level of non-smokers.

Streptococcus pneumoniae is the causative microorganism responsible for community-acquired pneumonia (CAP) most frequently associated with smoking, particularly in invasive pneumococcal disease and septic shock.

It is not clear how it acts on the progress of pneumonia, but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse.

In CAP caused by Legionella pneumophila, it has also been observed that smoking is the most important risk factor, with the risk rising 121% for each pack of cigarettes smoked a day.

Tobacco use may also favor diseases that are also known risk factors for CAP, such as periodontal disease and upper respiratory viral infections.

By way of prevention, while giving up smoking should always be proposed, the use of the pneumococcal vaccine is also recommended, regardless of the presence of other comorbidities.

Keywords:
Smoking
Community-acquired pneumonia
Risk factors
Prevention
Resumen

En estudios recientes ha quedando quedado perfectamente establecido que el tabaco incrementa la susceptibilidad a la infección bacteriana pulmonar, incluso en fumadores pasivos. Este efecto muestra también dosis-respuesta, ya que disminuye espectacularmente el riesgo 10 años después de abandonar el hábito tabáquico, situándose a niveles de no fumadores.

Streptococcus pneumoniae es el microorganismo causante de neumonía adquirida en la comunidad (NAC) que más se ha relacionado con el tabaquismo, especialmente en situaciones de enfermedad neumocócica invasiva y shock séptico.

Su influencia sobre la evolución de la neumonía no parece clara, aunque existen evidencias que sugieren un peor pronóstico de la neumonía neumocócica.

En NAC causadas por Legionella pneumophila también se ha observado que el hábito tabáquico es el factor de riesgo más remarcable, ya que puede suponer un aumento del riesgo del 121% por cada paquete diario de cigarrillos consumidos.

Por otro lado, el consumo de tabaco puede también favorecer la presencia de enfermedades que a su vez son factores de riesgo conocidos de NAC, como enfermedades periodontales e infecciones víricas de la vía aérea superior.

Como medida preventiva, si bien cabe proponer el abandono del tabaco, también es recomendable la vacuna neumocócica, independientemente de la presencia de comorbilidad.

Palabras clave:
Tabaquismo
Neumonía adquirida en la comunidad
Factores de riesgo
Prevención
Full Text

The adverse effects of tobacco smoking make it one of the most important risk factors for major chronic cardiovascular and respiratory diseases. In some of these, tobacco use may worsen prognosis, while for others there is a clear causal relationship.

Chronic obstructive pulmonary disease (COPD) and lung cancer are among the most common smoking-related diseases, but there is also evidence linking smoking with diseases such as asthma, interstitial and allergic diseases, and pulmonary infections.1 Indeed, the airway is constantly exposed to microorganisms, but the healthy lung has sufficient defense mechanisms to prevent microbial invasion (effective mucociliary clearance, epithelial barrier integrity, alveolar macrophages that recognize and phagocytize invading microorganisms). Any failure of these mechanisms may result in microorganisms spreading to the bronchial tree, triggering community-acquired pneumonia (CAP), which remains a major cause of morbidity and mortality in developed countries. In the general adult population, the annual incidence of CAP varies between 1.6 and 13.4 cases per 1000 inhabitants, with a hospitalization rate of between 22 and 51% and a mortality rate of 3%–24%2–4 that has not changed in recent years, despite the preventive measures undertaken.5

Smoking and Pneumonia

The most important risk factor for CAP is age. So much so, that the incidence triples or quadruples when age is >65 years.2 The reason is unclear, but several factors may be involved, related to immune senescence due to weakness (innate and adaptive) of the immune system, increased asymptomatic aspirations in this age group,6 or the convergence of other risk factors (RF) that do not acquire statistical significance in younger people, but that take center stage in older age groups, possibly due to an additive effect. One of these factors may be tobacco smoking, the main RF for COPD, which in turn is one of the main RFs for CAP. Thus, it is often difficult to determine the specific weight of smoking in the development of CAP, especially considering that smoking is associated with lower socioeconomic status, poor diet, increased alcohol consumption, and reduced physical activity, that are also RFs for respiratory infection.7 Nevertheless, enough studies using statistical analysis with logistic regression models are now available to allow the differentiation of any confounding factors, showing that tobacco smoking in itself increases the risk of pneumonia. In this regard, a population-based study2,3 was published that demonstrated an increased risk of CAP in smokers that was also directly related to the duration of tobacco consumption and the number of cigarettes consumed. Concurrently, it has been shown that this risk disappears when smokers quit. In fact, after 5 years, the risk decreases by 50%.3 Moreover, if we consider that one of the criteria for causality between two factors is dose-response, the increase in risk associated with an increase in intensity of consumption and the overall amount of tobacco consumed further reinforces the notion that tobacco smoking is a direct causal agent of CAP. On the other hand, we know that tobacco smoking causes morphological changes in the epithelium of the bronchial mucosa, with loss of cilia, mucous gland hypertrophy and increased goblet cells that may favor the presence and spread of microbes in the bronchial tree. An inflammatory reaction is produced in the airway causing macrophage and neutrophil activation that releases proteases. Oxidative stress and cytokine release are triggered, leading to both innate and adaptive immune response.8–14 This may in turn make the bronchial mucosa epithelium more sensitive to the inflammatory aggression of the infection itself.15–17 Moreover, it is now known that tobacco smoking inhibits some of the key functions of the innate and adaptive response, including the response of two Toll-like receptors (TLR2),18 nuclear factor kappaB (NF-κB),8 CD4-lymphocyte proliferation (LTCD4),12,19 maturation of dendritic cells,10 and opsonization and phagocytosis capacities.20 Thus, tobacco smoking can alter immunity against infection, affecting the modulation of intra- and intercellular signaling of epithelium and immune cells, and suppressing the activation of important elements of the innate and adaptive immune response.17,21 The fact that tobacco smoking increases susceptibility to bacterial infection is well established.22,23

Passive Smoking and Pneumonia

Passive smoking is considered a major epidemiological problem. In 2004, an international study including 192 countries found that 40% of children, 33% of male non-smokers and 35% of female non-smokers, were passive smokers.24 There were wide geographical variations that could be explained by the different stages of the tobacco smoking epidemic in the country surveyed, because passive smoking is directly related to active smoking rates. In the year 2005, prevalence data in Spain estimated that about 50% of adults were exposed to second-hand smoke.25 Later, as in most developed countries, legislation was introduced to regulate tobacco smoking in public places. This has reduced exposure to tobacco smoke by approximately 20%–25%, due to falling consumption in public places and in the workplace, but not at home. Accordingly, in recent years there has been growing interest in understanding the effect of passive tobacco smoking and some studies suggest that it could also involve a higher risk of respiratory infections in both the children of smoking parents,26,27 and in adults.28,29 Allowing smoking in the home has also been shown to be an important predictor of health loss in elderly people with CAP.30 In fact, lesions in the respiratory epithelium, connective tissue and vascular endothelium of the lung caused by tobacco smoke can occur even at low smoke concentrations,31 supporting the notion that exposure to tobacco smoke could be an important risk factor for CAP development in passive smokers.

Two separate case-controlled,32 population-based studies have also demonstrated that passive smoking is a risk factor for developing pneumococcal bacteremia in immunocompetent adults, resulting in an odds ratio (OR) of 2.6 and attributable risk (AR) of 31% in subjects aged <65 years,28,33 and OR 2.2 and AR 13% in those over 65 years of age.28,32

Smoking and Pneumococcal Pneumonia

The most common causative organism of CAP, regardless of care level and severity, is Streptococcus pneumoniae. This has also been shown to be the agent most frequently linked to smoking, especially in patients with COPD. An in vitro study has shown increased adherence of S. pneumoniae to the epithelial cells in the oral cavity of smokers,34 persisting for up to three years after smoking cessation. This may produce greater oropharyngeal colonization and lead to greater chance of developing CAP.

Smoking has also been related with invasive pneumococcal disease (IPD), which in approximately 80% of cases is due to pneumonia.35 This association was reported in a study by Pastor et al. in 1995, with an OR of 2.6 in smokers between 24 and 64 years of age and OR of 2.2 in smokers older than 65 years. Attributable risk (AR) was 31% in the first group and 13% in the second group.3 Another population-based, case-controlled study28 also highlighted that smoking is the largest independent RF for IPD in immunocompetent adults, with an OR=4.1 in current smokers (AR 51%). Furthermore, there is a dose-response effect, and smoking cessation dramatically reduces the risk after 10 years, when it becomes the same as that of nonsmokers.

The special relationship of active smoking with pneumococcus has been demonstrated by some studies that have shown tobacco-induced changes in the clearance and phagocytosis of S. pneumoniae in the lungs,36 and inhibition of the anti-pneumococcal activity of some innate immunity antimicrobial peptides.37,38 Thus, tobacco smoking impairs immunity to infection, especially against some microorganisms, including S. pneumoniae, and it seems well established that active smoking increases the risk of pneumonia.

However, the information as to whether active smokers have a worse CAP prognosis is not so clear. Three longitudinal studies39–41 involving large patient cohorts found higher mortality in smokers with pneumonia, while two metaanalyses42,43 found that tobacco smoking did not affect prognosis. Two large retrospective series that studied CAP mortality in relation to tobacco smoking have shown contradictory results.44,45 Finally, a recent study showed that tobacco smoking was an independent risk factor for septic shock in pneumococcal pneumonia,46 and another epidemiological study concluded that smoking was an independent determinant of mortality in bacteremic CAP caused by S. pneumoniae.47 Considering all these data, we can conclude that there is evidence to suggest worse prognosis of pneumococcal pneumonia in active smokers, while the picture is not so clear if we consider overall CAP, independent of the etiology.

Smoking and Legionella pneumophila Pneumonia

Less frequent, but not less important, is CAP due to Legionella pneumophila. Its incidence varies according to published series: some report sporadic cases while in others it is the second or third most common etiologic agent. This depends on epidemiological factors, the completeness of the diagnostic method used, and the severity of CAP, among other factors. In population-based studies, L. pneumophila represents 1%–3% of diagnosed microorganisms.48 This type of CAP usually affects young individuals, often without underlying disease.49 Smoking is the most important risk factor in these subjects, as the risk may be increased by 121% for each pack of cigarettes consumed daily, with OR of 3.48,50 and as much as 7.49 if analyzed in people without comorbidities. This increased risk is attributed to the difficulty in eradicating the microorganism from the bronchial tree, due to the deterioration of the respiratory mucosa and impaired cilia caused by tobacco smoking that, depending on the individual's immune status, facilitates entry into and subsequent invasion of the alveolar macrophages.

Smoking and Other Risk Factors of Pneumonia Acquired in the Community

Tobacco smoking may also favor the presence of diseases which are in turn known risk factors of CAP, including:

  • -

    Periodontal diseases directly related to the development of CAP.51 Poorer oral hygiene has been shown to potentially lead to increased respiratory infection.52,53 Additionally, smokers show higher subgingival bacterial colonization than non-smokers, which is directly related to the number of cigarettes smoked by day. Accordingly, smokers of fewer than 10 cigarettes/day present periodontitis between 2.5 and 6 times more often than non-smokers (OR 2.79), while OR is 5.88 for those smoking >30 cigarettes/day; OR decreases dramatically if the habit is quit and can reach OR 1.15 after 11 years.54

  • -

    Viral upper respiratory tract infections. Upper respiratory tract infections (URTI) are a risk factor of CAP, independent of other related factors,2,7 and smoking independently influences the presence of prior viral infection. Blake et al.55 observed in a cohort of soldiers diagnosed with URTI that 22.7% were smokers, vs 16% non-smokers (RR: 1.5). Increased susceptibility to experimental viral infection has also been observed in smokers.56

Prevention

At present there is enough scientific evidence to show that active tobacco smoking is an important risk factor for CAP26,28,29,33; it has a direct and independent effect on the risk of CAP, but it may also act indirectly causing chronic bronchitis or COPD which, in turn, are well recognized risk factors for CAP.7,33 Therefore, one of the main ways of preventing CAP is to intervene in the smoking habit, advising its cessation, which may reduce the risk of CAP by 50% after five years.3 Furthermore, a reduction of 14% in IPD has been observed every year28 and, after 10 years, the risk of IPD can reach the same level as that of non-smokers.

On the other hand, pneumococcal vaccine is concomitantly recommended. In fact, the American scientific societies propose tobacco cessation combined with pneumococcal vaccine in patients hospitalized for CAP,57 and further recommend the pneumococcal vaccine for active smokers in the population aged between 19 and 64 years, regardless of the presence of comorbidities.58 This recommendation is even more relevant for active smokers, in whom lower rates of influenza and pneumococcal immunization have been observed compared to former smokers and non-smokers.59

At present, two types of vaccine are available: the 23-valent polysaccharide vaccine and 13-valent conjugated vaccine. The former has been used in Spain since 1999, and protective effect has been found in studies not designed to assess its effectiveness,7,60 while clinical trials to test its efficacy against IPD do not establish such an effect, and effectiveness on CAP in general cannot be estimated.61 Therefore, pneumococcal immunization with the 13-valente conjugate vaccine, authorized for adults in Europe since October 2011 and in Spain since July 2012, has been recently recommended.62 The main advantage over the former is that, being conjugated, it is capable of inducing a T-dependent immune response that provides a better immune response and generates immune memory.63 Additionally, it has been described to generate IgA responses in mucosa, reducing nasopharyngeal colonization by serotypes represented in the vaccine, thus breaking the infectious cycle and producing group immunity.64 Furthermore, the serotype coverage of the 13-valent conjugate vaccine reaches up to 82% of CAP-producing agents in healthy adults.65 Therefore, it seems clear that the smoking population should be considered as a target for pneumococcal vaccination strategies.66

Conflicts of Interest

The authors declare no conflicts of interest.

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Please cite this article as: Almirall J, Blanquer J, Bello S. Neumonía adquirida en la comunidad en fumadores. Arch Bronconeumol. 2014;50:250–254.

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