PMC:4801059 / 1620-6125 JSONTXT

{"project":"MyTest","denotations":[{"id":"26884414-25714161-29787762","span":{"begin":1081,"end":1082},"obj":"25714161"},{"id":"26884414-26172429-29787763","span":{"begin":1260,"end":1261},"obj":"26172429"},{"id":"26884414-23326226-29787764","span":{"begin":1844,"end":1846},"obj":"23326226"},{"id":"26884414-9180184-29787765","span":{"begin":3033,"end":3035},"obj":"9180184"},{"id":"26884414-15166819-29787766","span":{"begin":3761,"end":3763},"obj":"15166819"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"INTRODUCTION\nPneumonia is the leading cause of death in children \u003c5 years worldwide, which is responsible for one million deaths each year [1]. The burden is greatest in developing countries, at an estimated 0.22 episodes per child-year, but remains a major public health concern even among developed countries where there are an estimated 0.015 episodes per child-year [2]. In the USA, pneumonia is the second only to newborn infant births as the most common reason for hospital admissions (36 cases per 10 000 persons [3]) and causes nearly 50 000 deaths each year [4].\nA wide range of viral, bacterial and fungal agents can cause pneumonia when aspirated into the lungs. The Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study identified viruses as the most commonly identified etiologic agent in children and adults hospitalized with pneumonia. An etiologic agent was detected in 81% of 2222 children \u003c18 years of age: 66% had one or more viral pathogens, 8% one or more bacterial pathogens and 7% both bacterial and viral pathogens [5]. Among 2259 adults, an etiologic agent was detected in 38%: 23% had one or more viral pathogens, 11% one or more bacterial pathogens and 3% both bacterial and viral pathogens [6]. However, virtually all these serious pneumonia cases were treated with antibiotics, as secondary bacterial infection can complicate lower respiratory viral infection. Therefore, even in cases determined to be pneumonia solely of viral etiology, bacterial interactions of virus and bacteria may play some role. \nExplanatory Box 1. Challenges in determining the etiology of pneumonia Even in countries where pneumonia surveillance is routinely conducted such as the USA, no information on microbial etiology is recorded for approximately 65–85% of hospitalized pneumonia cases [11, 12]. Severely ill patients often are not included in surveillance, organisms on the causal pathway may have been cleared by the time that the patient presents clinically or prior to testing because of rapid treatment with antibiotics when pneumonia is suspected, and autopsies are infrequently done on the elderly. To optimally determine etiology, direct sampling via bronchoalveolar lavage is required, but usually detection of causal agents is conducted on blood, sputum and urine because of ease of collection, ethical issues and costs. Bacteremia is observed in only 7%–13% of adult pneumonia cases and 1–5% in child pneumonia cases, sputum can potentially be contaminated by bacteria in the URT and is difficult to obtain from children, and blood and urine antigen assays require further validation or are limited to adults and specific to only a few pathogens (e.g. Streptococcus pneumoniae and Legionella species) (reviewed by Murdoch et al. [13]). Although modern molecular biologic techniques make it feasible to conduct untargeted screens for all bacterial, viral and fungal species present, it is still difficult to distinguish between infection, colonization or contamination [14]. Continued efforts are needed to develop more accurate methods to determine the etiology of pneumonia, and thus maximize treatment and prevention efforts. The large proportion of pneumonia cases without a detected pathogen underscores the limitations of current surveillance and detection methods and how they frame our understanding of pneumonia etiology (Box 1). EPIC study results suggest we may not be detecting the full panel of pathogens in cases we currently define as viral pneumonia nor considering the potential role of bacteria on the pathogenic potential of viruses. Bacterial causes of pneumonia are associated with more severe clinical symptoms and increasing antibiotic resistance complicates treatment [2, 7–10], making bacterial causes of pneumonia a major concern.\nIn this review, we examine two hypotheses that argue the etiology of bacterial pneumonia is a consequence of ecologic selection influenced by the interaction of respiratory viruses and bacteria within the host: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial carriage structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We begin by describing the normal processes of bacterial selection in the upper and LRTs and then present evidence on how these processes can potentially be altered by respiratory viruses."}

{"project":"2_test","denotations":[{"id":"26884414-25714161-29787762","span":{"begin":1081,"end":1082},"obj":"25714161"},{"id":"26884414-26172429-29787763","span":{"begin":1260,"end":1261},"obj":"26172429"},{"id":"26884414-23326226-29787764","span":{"begin":1844,"end":1846},"obj":"23326226"},{"id":"26884414-9180184-29787765","span":{"begin":3033,"end":3035},"obj":"9180184"},{"id":"26884414-15166819-29787766","span":{"begin":3761,"end":3763},"obj":"15166819"}],"text":"INTRODUCTION\nPneumonia is the leading cause of death in children \u003c5 years worldwide, which is responsible for one million deaths each year [1]. The burden is greatest in developing countries, at an estimated 0.22 episodes per child-year, but remains a major public health concern even among developed countries where there are an estimated 0.015 episodes per child-year [2]. In the USA, pneumonia is the second only to newborn infant births as the most common reason for hospital admissions (36 cases per 10 000 persons [3]) and causes nearly 50 000 deaths each year [4].\nA wide range of viral, bacterial and fungal agents can cause pneumonia when aspirated into the lungs. The Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study identified viruses as the most commonly identified etiologic agent in children and adults hospitalized with pneumonia. An etiologic agent was detected in 81% of 2222 children \u003c18 years of age: 66% had one or more viral pathogens, 8% one or more bacterial pathogens and 7% both bacterial and viral pathogens [5]. Among 2259 adults, an etiologic agent was detected in 38%: 23% had one or more viral pathogens, 11% one or more bacterial pathogens and 3% both bacterial and viral pathogens [6]. However, virtually all these serious pneumonia cases were treated with antibiotics, as secondary bacterial infection can complicate lower respiratory viral infection. Therefore, even in cases determined to be pneumonia solely of viral etiology, bacterial interactions of virus and bacteria may play some role. \nExplanatory Box 1. Challenges in determining the etiology of pneumonia Even in countries where pneumonia surveillance is routinely conducted such as the USA, no information on microbial etiology is recorded for approximately 65–85% of hospitalized pneumonia cases [11, 12]. Severely ill patients often are not included in surveillance, organisms on the causal pathway may have been cleared by the time that the patient presents clinically or prior to testing because of rapid treatment with antibiotics when pneumonia is suspected, and autopsies are infrequently done on the elderly. To optimally determine etiology, direct sampling via bronchoalveolar lavage is required, but usually detection of causal agents is conducted on blood, sputum and urine because of ease of collection, ethical issues and costs. Bacteremia is observed in only 7%–13% of adult pneumonia cases and 1–5% in child pneumonia cases, sputum can potentially be contaminated by bacteria in the URT and is difficult to obtain from children, and blood and urine antigen assays require further validation or are limited to adults and specific to only a few pathogens (e.g. Streptococcus pneumoniae and Legionella species) (reviewed by Murdoch et al. [13]). Although modern molecular biologic techniques make it feasible to conduct untargeted screens for all bacterial, viral and fungal species present, it is still difficult to distinguish between infection, colonization or contamination [14]. Continued efforts are needed to develop more accurate methods to determine the etiology of pneumonia, and thus maximize treatment and prevention efforts. The large proportion of pneumonia cases without a detected pathogen underscores the limitations of current surveillance and detection methods and how they frame our understanding of pneumonia etiology (Box 1). EPIC study results suggest we may not be detecting the full panel of pathogens in cases we currently define as viral pneumonia nor considering the potential role of bacteria on the pathogenic potential of viruses. Bacterial causes of pneumonia are associated with more severe clinical symptoms and increasing antibiotic resistance complicates treatment [2, 7–10], making bacterial causes of pneumonia a major concern.\nIn this review, we examine two hypotheses that argue the etiology of bacterial pneumonia is a consequence of ecologic selection influenced by the interaction of respiratory viruses and bacteria within the host: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial carriage structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We begin by describing the normal processes of bacterial selection in the upper and LRTs and then present evidence on how these processes can potentially be altered by respiratory viruses."}