Editorial
What's Next in Pneumonia?
¿Qué nos depara el futuro de la neumonía?
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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "208" "paginaFinal" => "210" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Catia Cilloniz, Antoni Torres" "autores" => array:2 [ 0 => array:3 [ "nombre" => "Catia" "apellidos" => "Cilloniz" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 1 => array:4 [ "nombre" => "Antoni" "apellidos" => "Torres" "email" => array:1 [ 0 => "atorres@clinic.cat" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Pneumology, Hospital Clinic of Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "August Pi i Sunyer Biomedical Research Institute – IDIBAPS, University of Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Biomedical Research Networking Centers in Respiratory Diseases (Ciberes), Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Qué nos depara el futuro de la neumonía?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pneumonia remains the leading infectious cause of death for all ages worldwide.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">1</span></a> Due to the progressively aging population globally, the proportion of very old patients (VOP<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>80 years) hospitalized with pneumonia continues to rise; similarly, the proportion of VOP requiring treatment in intensive care units (ICU) is increasing.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">2</span></a> VOP are at a high risk of pneumonia due to multiple chronic comorbidities, immunosenescence, malnutrition, frailty and polypharmacy. This same group also faces a higher likelihood of severe pneumonia and mortality.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">3</span></a> Conversely, pneumonia disproportionately affects children under five years old. In 2019, the respiratory disease claimed the lives of 672,000 children aged less than five years.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">1</span></a> This means that a child who has not even turned five years old will die every 47<span class="elsevierStyleHsp" style=""></span>s due to pneumonia.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">1</span></a> No doubt remains that pneumonia is a major burden on global health. Yet, despite that, there are still several challenges and controversies related to critical aspects of pneumonia management and prevention.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Early-risk severity stratification and appropriate antimicrobial therapy have been well-established to be integral components in improving pneumonia outcomes. However, there are no risk stratification tools to guide management of pneumonia in VOP and children requiring intensive care. The most widely used severity scores, like PSI and CURB65, perform well in predicting 30-day mortality; however, these same scores fall short when it comes to predicting the need for ICU admission. The first upcoming challenge in pneumonia will be to continue research that demonstrates the usefulness of severity scores in predicting which patients would benefit from more aggressive treatments and ICU care.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Additionally, early identification of pneumonia-causing microorganisms is essential in implementing adequate antimicrobial therapy. Indeed, a patient's prognosis could benefit significantly from adequate microbial treatment.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">4</span></a> However, we can only identify the microbial cause of pneumonia in approximately 50% of cases. While a detection of specific pathogens such as respiratory viruses have improved via the application of molecular techniques,<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">5</span></a> more must be done. The lack of standardization of these techniques limits their full integration in clinical practice. Additionally, result interpretation can be ambiguous with respect to pathogen detection and colonization/infection determination. As the current COVID-19 pandemic has demonstrated, the role of molecular tests in detecting pathogens, including emergent viruses like severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2), is becoming more pivotal.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the coming years, a second challenge of pneumonia research will be to evaluate the usefulness, applicability and standardization of molecular testing in detecting pneumonia pathogens and related resistance to improve and personalize the management and care for patients with community-acquired pneumonia (CAP). Currently, <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> and influenza virus are the most common causes of pneumonia. Although multidrug-resistant (MDR) pathogens present in a lower proportion in CAP, especially in severe cases, the impact of such microbes on clinical outcomes is huge.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">5,6</span></a> It will therefore be important to continue research also on the utility of scores that predict patients at risk of drug-resistant microorganisms like PES pathogens (<span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>, extended-spectrum β-lactamase-producing <span class="elsevierStyleItalic">Enterobacterales</span>, and methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span>) that recently have emerged as causes of CAP.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In the last ten years, scores assessing the potential risk of MDR pathogens in patients with CAP have come into development.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">8–11</span></a> However, the scores present a higher variability on the assigned weight to each variable investigated, and variability in the thresholds for patients at risk of MDR pathogens is present. Interestingly, the PES score<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">7</span></a> has showed a high negative predictive value (98%), making it possibly an important tool to rule out patients with CAP who do not need antibiotic coverage against PES pathogens. However, future studies are needed to support the therapeutic clinical decision-making processes, especially as it relates to cases caused by MDR pathogens others than PES microorganism. For example, carbapenem-resistant <span class="elsevierStyleItalic">Enterobacterales</span> or <span class="elsevierStyleItalic">Acinetobacter baumanni</span> are MDR pathogens that are associated with higher morbidity and mortality despite low frequency of such microorganisms in this series of patients.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">12–14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">At the same time, mounting evidence supports considering the immunological profile of patients with CAP as a useful tool in assessing severity and prognosis in pneumonia.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">15,16</span></a> Researchers have found that the lymphopenic CAP (L-CAP) phenotype was associated to increased severity, mortality and a dysregulated immunological response in patients with CAP.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">15,17</span></a> In patients with CAP and sepsis, lymphopenia was also reported to be associated with an increased risk of ICU admission and 30-day mortality.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">18</span></a> The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-lymphocyte ratio have also shown to be simple to use and extremely good markers of severity in pneumonia.<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">19,20</span></a> NLR integrates two types of immune responses to infection (neutrophilia and lymphopenia), making it a substantial prognostic marker in pneumonia.<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">19,21,22</span></a> Importantly, these markers are easily obtainable at hospital admission; clinicians should therefore implement them in clinical practice.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Recent studies have also explored the application of machine learning algorithms to support clinical decisions related to CAP.<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">23–25</span></a> It is the latest interesting approach in managing pneumonia. However, validations of the algorithms developed are necessary to implement such a tool in the future.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Continuing, due to the difficulty posed in determining microbial etiology, antibiotic therapy for pneumonia must be empirical.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">4</span></a> Controversy concerning what empirical antibiotic therapy is the most adequate for pneumonia, especially in severe cases, very old and/or immunocompromised patients, is present, though. Similarly, there has yet to be an established consensus on the optimal duration of antibiotic therapy in cases of pneumonia. Compounding this is the added, continuous debate about what indications are adequate for corticosteroid use, especially in light of the recent impact of corticosteroids in patients with severe COVID-19.<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">26,27</span></a> Lastly, despite great efforts made by an expert panel to develop clinical guidelines, there are still gaps in the quality and quantity of studies on which the guidelines are based. The majority of studies are observational, and there are few randomized controlled trials (RCT). Also, most studies have focused on non-severe pneumonia and in immunocompetent individuals. As a result of such study characteristics, information regarding the very old population is limited and thereby places a cap on generalizations. Studies undertaken in the future will need to consider different antibiotic regimens, newer antibiotics and antibiotic therapy duration, especially in those patients who are critically ill, very old or immunocompromised. Furthermore, prospective studies will need to provide a better characterization of patients with pneumonia who could stand to benefit from corticosteroids as adjunctive therapy. New data of this nature would address existing disparities in these important issues on pneumonia.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Of note, we would like to reiterate that pneumonia is a preventable disease with well-known risk factors.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">4,28–30</span></a> Effective vaccines such as <span class="elsevierStyleItalic">Haemophilus influenzae</span> type b, <span class="elsevierStyleItalic">pneumococcal</span> and influenza vaccine could reduce the burden of pneumonia on the most vulnerable populations globally. For example, pneumococcal conjugate vaccines (PCVs) have significantly reduced pneumococcal disease worldwide.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">31</span></a> However, there are limitations in serotype coverage by PCV13 vaccine due to the evolution and emergence of new pneumococcal serotypes.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">32</span></a> Developing new formulation of PCV vaccines—such as the 20-valent PCV (PCV20) that contains the capsular polysaccharide conjugates of serotypes present in the PCV13 plus 7 new serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F)<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">33</span></a> and the 15-valent PCV (PCV15) that contain scapsular polysaccharide conjugates of serotypes present in the PCV13 plus serotypes 22F and 33F<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">34</span></a>—are essential to reduce the burden of pneumococcal disease. However, while European vaccination programs are well-established for children and adults,<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">35</span></a> vaccination coverage remains suboptimal among the adult population. Low- and middle-income countries experience low vaccination coverage. According to the World Health Organization, approximately 19 million children aged<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>1 year have not received basic vaccines, including the pneumococcal vaccination.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">36</span></a> In the next, few years, routine vaccination programs for children and adults will require a boost in support and uptake worldwide.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Finally, it is vital to remark the importance of preventing aspiration pneumonia. This type of pneumonia remains poorly recognized, even though it has increased especially among very old, frail patients and is a cause of severe disease.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">37</span></a> Studies focusing on preventive strategies for modifiable risk factors, such as oropharynx colonization, modifying gastric pH and dysphagia, are necessary to reduce their prevalence.</p><p id="par0055" class="elsevierStylePara elsevierViewall">This all stated, we believe that governments must invest more in clinical research on pneumonia and strengthen investigation teams as they strive to pursue high-quality evidence related to different aspects of pneumonia. Although the COVID-19 pandemic has placed great pressure on health systems across the globe, governmental actions of such a magnitude would serve to create specific, national strategies to control pneumonia and improve vaccine uptake, risk factors, diagnosis and treatment of pneumonia. Only through developing concrete approaches and bettering the quantity and quality of scientific evidence on pneumonia will we be able to reduce the high burden of pneumonia and avoid deaths of the most vulnerable populations.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:37 [ 0 => array:3 [ "identificador" => "bib0190" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 2 | 11 |
| 2024 October | 82 | 20 | 102 |
| 2024 September | 82 | 43 | 125 |
| 2024 August | 110 | 47 | 157 |
| 2024 July | 82 | 24 | 106 |
| 2024 June | 85 | 33 | 118 |
| 2024 May | 126 | 32 | 158 |
| 2024 April | 78 | 33 | 111 |
| 2024 March | 64 | 31 | 95 |
| 2024 February | 75 | 50 | 125 |
| 2024 January | 119 | 62 | 181 |
| 2023 December | 70 | 45 | 115 |
| 2023 November | 84 | 31 | 115 |
| 2023 October | 111 | 37 | 148 |
| 2023 September | 82 | 33 | 115 |
| 2023 August | 72 | 39 | 111 |
| 2023 July | 92 | 46 | 138 |
| 2023 June | 99 | 22 | 121 |
| 2023 May | 101 | 23 | 124 |
| 2023 April | 95 | 33 | 128 |
| 2023 March | 145 | 27 | 172 |
| 2023 February | 120 | 24 | 144 |
| 2023 January | 99 | 39 | 138 |
| 2022 December | 135 | 34 | 169 |
| 2022 November | 115 | 42 | 157 |
| 2022 October | 120 | 46 | 166 |
| 2022 September | 104 | 32 | 136 |
| 2022 August | 115 | 50 | 165 |
| 2022 July | 148 | 48 | 196 |
| 2022 June | 126 | 39 | 165 |
| 2022 May | 149 | 42 | 191 |
| 2022 April | 471 | 120 | 591 |
| 2022 March | 370 | 87 | 457 |
| 2022 February | 2 | 0 | 2 |
| 2022 January | 1 | 2 | 3 |
| 2021 December | 2 | 4 | 6 |
| 2021 October | 1 | 0 | 1 |
| 2021 September | 2 | 4 | 6 |
| 2021 August | 0 | 2 | 2 |
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