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Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention
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Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2016) | Viewed by 166002

Special Issue Editor

Prof. Dr. Susanna Esposito

E-Mail Website
Guest Editor
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
Interests: respiratory tract infections; emerging infections; vaccines; antibiotic therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pneumonia remains a frequent cause of morbidity and mortality worldwide, even in industrialized countries. Over the last five years, several international guidelines have been updated with new evidence concerning the incidence, etiology and management of pneumonia, but there are still some major problems in standardization. The definition of pneumonia varies widely worldwide depending on whether chest radiography is used or not; furthermore, although chest radiography is still the main means of confirming a clinical suspicion of pneumonia in everyday practice, its diagnostic accuracy is limited by significant intra- and inter-observer differences in interpreting plain chest radiographs. Moreover, in terms of therapy, the first-line antimicrobial approach varies from country to country, and there is no clear consensus concerning second-line treatment. Furthermore, preventive possibilities using vaccines appeared able to decrease pneumonia incidence, but recommendations on vaccines use are different from country to country. The main aim of this Special Issue is to consider the available data concerning the pathogenesis, diagnosis, treatment and prevention of pneumonia in children and adults, highlighting results coming from recent researches that appear associated with cost-effectiveness benefits in patients’ management.

Prof. Dr. Susanna Esposito
Guest Editor

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Keywords

  • antibiotic therapy
  • CAP
  • lower respiratory tract infection
  • molecular diagnostics
  • pneumonia
  • prevention
  • pulmonology
  • respiratory infection
  • vaccines
  • VAP

Published Papers (17 papers)

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Research

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850 KiB  
Article
Genomic Loads and Genotypes of Respiratory Syncytial Virus: Viral Factors during Lower Respiratory Tract Infection in Chilean Hospitalized Infants
by Yazmín Espinosa, Camila San Martín, Alejandro A. Torres, Mauricio J. Farfán, Juan P. Torres, Vasanthi Avadhanula, Pedro A. Piedra and Lorena I. Tapia
Int. J. Mol. Sci. 2017, 18(3), 654; https://doi.org/10.3390/ijms18030654 - 21 Mar 2017
Cited by 22 | Viewed by 5221
Abstract
The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity [...] Read more.
The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Article
Factors That Negatively Affect the Prognosis of Pediatric Community-Acquired Pneumonia in District Hospital in Tanzania
by Serena Caggiano, Nicola Ullmann, Elisa De Vitis, Marzia Trivelli, Chiara Mariani, Maria Podagrosi, Fabiana Ursitti, Chiara Bertolaso, Carolina Putotto, Marta Unolt, Andrea Pietravalle, Paola Pansa, Kajoro Mphayokulela, Maria Incoronata Lemmo, Michael Mkwambe, Joseph Kazaura, Marzia Duse, Francesco Nieddu, Chiara Azzari and Renato Cutrera
Int. J. Mol. Sci. 2017, 18(3), 623; https://doi.org/10.3390/ijms18030623 - 13 Mar 2017
Cited by 17 | Viewed by 5451
Abstract
Community-acquired pneumonia (CAP) is still the most important cause of death in countries with scarce resources. All children (33 months ± 35 DS) discharged from the Pediatric Unit of Itigi Hospital, Tanzania, with a diagnosis of CAP from August 2014 to April 2015 [...] Read more.
Community-acquired pneumonia (CAP) is still the most important cause of death in countries with scarce resources. All children (33 months ± 35 DS) discharged from the Pediatric Unit of Itigi Hospital, Tanzania, with a diagnosis of CAP from August 2014 to April 2015 were enrolled. Clinical data were gathered. Dried blood spot (DBS) samples for quantitative real-time polymerase chain reaction (PCR) for bacterial detection were collected in all 100 children included. Twenty-four percent of patients were identified with severe CAP and 11% died. Surprisingly, 54% of patients were admitted with a wrong diagnosis, which increased complications, the need for antibiotics and chest X-rays, and the length of hospitalization. Comorbidity, found in 32% of children, significantly increased severity, complications, deaths, need for chest X-rays, and oxygen therapy. Malnourished children (29%) required more antibiotics. Microbiologically, Streptococcus pneumonia (S. p.), Haemophilus influenza type b (Hib) and Staphylococcus aureus (S. a.) were the bacteria more frequently isolated. Seventy-five percent of patients had mono-infection. Etiology was not correlated with severity, complications, deaths, oxygen demand, or duration of hospitalization. Our study highlights that difficult diagnoses and comorbidities negatively affect clinical evolution. S. p. and Hib still play a large role; thus, implementation of current vaccine strategies is needed. DBS is a simple and efficient diagnostic method for bacterial identification in countries with scarce resources. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Article
Exhaled Breath Metabolomics for the Diagnosis of Pneumonia in Intubated and Mechanically-Ventilated Intensive Care Unit (ICU)-Patients
by Pouline M. P. Van Oort, Sanne De Bruin, Hans Weda, Hugo H. Knobel, Marcus J. Schultz, Lieuwe D. Bos and On Behalf of the MARS Consortium
Int. J. Mol. Sci. 2017, 18(2), 449; https://doi.org/10.3390/ijms18020449 - 19 Feb 2017
Cited by 47 | Viewed by 7200
Abstract
The diagnosis of hospital-acquired pneumonia remains challenging. We hypothesized that analysis of volatile organic compounds (VOCs) in exhaled breath could be used to diagnose pneumonia or the presence of pathogens in the respiratory tract in intubated and mechanically-ventilated intensive care unit patients. In [...] Read more.
The diagnosis of hospital-acquired pneumonia remains challenging. We hypothesized that analysis of volatile organic compounds (VOCs) in exhaled breath could be used to diagnose pneumonia or the presence of pathogens in the respiratory tract in intubated and mechanically-ventilated intensive care unit patients. In this prospective, single-centre, cross-sectional cohort study breath from mechanically ventilated patients was analysed using gas chromatography-mass spectrometry. Potentially relevant VOCs were selected with a p-value < 0.05 and an area under the receiver operating characteristics curve (AUROC) above 0.7. These VOCs were used for principal component analysis and partial least square discriminant analysis (PLS-DA). AUROC was used as a measure of accuracy. Ninety-three patients were included in the study. Twelve of 145 identified VOCs were significantly altered in patients with pneumonia compared to controls. In colonized patients, 52 VOCs were significantly different. Partial least square discriminant analysis classified patients with modest accuracy (AUROC: 0.73 (95% confidence interval (CI): 0.57–0.88) after leave-one-out cross-validation). For determining the colonization status of patients, the model had an AUROC of 0.69 (95% CI: 0.57–0.82) after leave-one-out cross-validation. To conclude, exhaled breath analysis can be used to discriminate pneumonia from controls with a modest to good accuracy. Furthermore breath profiling could be used to predict the presence and absence of pathogens in the respiratory tract. These findings need to be validated externally. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Article
Unexpectedly Higher Morbidity and Mortality of Hospitalized Elderly Patients Associated with Rhinovirus Compared with Influenza Virus Respiratory Tract Infection
by Ivan F. N. Hung, Anna Jinxia Zhang, Kelvin K. W. To, Jasper F. W. Chan, Shawn H. S. Zhu, Ricky Zhang, Tuen-Ching Chan, Kwok-Hung Chan and Kwok-Yung Yuen
Int. J. Mol. Sci. 2017, 18(2), 259; https://doi.org/10.3390/ijms18020259 - 26 Jan 2017
Cited by 27 | Viewed by 7769
Abstract
Rhinovirus is a common cause of upper and lower respiratory tract infections in adults, especially among the elderly and immunocompromised. Nevertheless, its clinical characteristics and mortality risks have not been well described. A retrospective analysis on a prospective cohort was conducted in a [...] Read more.
Rhinovirus is a common cause of upper and lower respiratory tract infections in adults, especially among the elderly and immunocompromised. Nevertheless, its clinical characteristics and mortality risks have not been well described. A retrospective analysis on a prospective cohort was conducted in a single teaching hospital center over a one-year period. We compared adult patients hospitalized for pneumonia caused by rhinovirus infection with those hospitalized for influenza infection during the same period. All recruited patients were followed up for at least 3 months up to 15 months. Independent risk factors associated with mortality for rhinovirus infection were identified. Between 1 March 2014 and 28 February 2015, a total of 1946 patients were consecutively included for analysis. Of these, 728 patients were hospitalized for rhinovirus infection and 1218 patients were hospitalized for influenza infection. Significantly more rhinovirus patients were elderly home residents and had chronic lung diseases (p < 0.001), whereas more influenza patients had previous stroke (p = 0.02); otherwise, there were no differences in the Charlson comorbidity indexes between the two groups. More patients in the rhinovirus group developed pneumonia complications (p = 0.03), required oxygen therapy, and had a longer hospitalization period (p < 0.001), whereas more patients in the influenza virus group presented with fever (p < 0.001) and upper respiratory tract symptoms of cough and sore throat (p < 0.001), and developed cardiovascular complications (p < 0.001). The 30-day (p < 0.05), 90-day (p < 0.01), and 1-year (p < 0.01) mortality rate was significantly higher in the rhinovirus group than the influenza virus group. Intensive care unit admission (odds ratio (OR): 9.56; 95% confidence interval (C.I.) 2.17–42.18), elderly home residents (OR: 2.60; 95% C.I. 1.56–4.33), requirement of oxygen therapy during hospitalization (OR: 2.62; 95% C.I. 1.62–4.24), and hemoglobin level <13.3 g/dL upon admission (OR: 2.43; 95% C.I. 1.16–5.12) were independent risk factors associated with 1-year mortality in patients hospitalized for rhinovirus infection. Rhinovirus infection in the adults was associated with significantly higher mortality and longer hospitalization when compared with influenza virus infection. Institutionalized older adults were particularly at risk. More stringent infection control among health care workers in elderly homes could lower the infection rate before an effective vaccine and antiviral become available. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Article
Pneumococcal Colonization in the Familial Context and Implications for Anti-Pneumococcal Immunization in Adults: Results from the BINOCOLO Project in Sicily
by Fabio Tramuto, Emanuele Amodio, Giuseppe Calamusa, Vincenzo Restivo, Claudio Costantino, Francesco Vitale and On behalf of the BINOCOLO Group
Int. J. Mol. Sci. 2017, 18(1), 105; https://doi.org/10.3390/ijms18010105 - 06 Jan 2017
Cited by 7 | Viewed by 4921
Abstract
The spread of Streptococcus pneumoniae within families has been scarcely investigated so far. This feasibility study aimed to estimate the prevalence of pneumococcal carriage in school-aged children and co-habiting relatives and to explore the potential link between the family environment and the sharing [...] Read more.
The spread of Streptococcus pneumoniae within families has been scarcely investigated so far. This feasibility study aimed to estimate the prevalence of pneumococcal carriage in school-aged children and co-habiting relatives and to explore the potential link between the family environment and the sharing of pneumococcal serotypes covered by the vaccine. Oropharyngeal samples of 146 subjects belonging to 36 different family groups were molecularly tested for pneumococcal detection and serotyping. The overall prevalence of pneumococcal carriage was 65.8% (n = 96/146), whereas it was higher among schoolchildren (77.8%, n = 28/36); subjects of seven years of age had the highest odds of being colonized (odds ratio, OR = 5.176; p = 0.145). Pneumococcal serotypes included in the 13-valent conjugate vaccine formulation were largely detected in the study population and multiple serotypes colonization was considerable. Factors relating to a close proximity among people at the family level were statistically associated with pneumococcal carriage (OR = 2.121; p = 0.049), as well as active smoking habit with a clear dose-response effect (ORs = 1.017–3.326). About half of family clusters evidenced similar patterns of carried pneumococcal serotypes and the odds of sustaining a high level of intrafamilial sharing increased with household size (ORs = 1.083–5.000). This study highlighted the potential role played by the family environment in sustaining both the circulation and horizontal transmission of pneumococcus. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Review

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722 KiB  
Review
Immunological Features of Respiratory Syncytial Virus-Caused Pneumonia—Implications for Vaccine Design
by Emma Rey-Jurado and Alexis M. Kalergis
Int. J. Mol. Sci. 2017, 18(3), 556; https://doi.org/10.3390/ijms18030556 - 04 Mar 2017
Cited by 27 | Viewed by 8077
Abstract
The human respiratory syncytial virus (hRSV) is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently [...] Read more.
The human respiratory syncytial virus (hRSV) is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. Upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hRSV. Further, T cell immunity plays an important role for virus clearance. Based on animal studies, it is thought that the host immune response to hRSV is based on a biased T helper (Th)-2 and Th17 T cell responses with the recruitment of T cells, neutrophils and eosinophils to the lung, causing inflammation and tissue damage. In contrast, human immunity against RSV has been shown to be more complex with no definitive T cell polarization profile. Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. However, such treatment involves several injections at a significantly high cost. For these reasons, intense research has been focused on finding novel vaccines or therapies to prevent hRSV infection in the population. Here, we comprehensively review the recent literature relative to the immunological features during hRSV infection, as well as the new insights into preventing the disease caused by this virus. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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666 KiB  
Review
The Impacts of Cellular Senescence in Elderly Pneumonia and in Age-Related Lung Diseases That Increase the Risk of Respiratory Infections
by Shigehisa Yanagi, Hironobu Tsubouchi, Ayako Miura, Ayako Matsuo, Nobuhiro Matsumoto and Masamitsu Nakazato
Int. J. Mol. Sci. 2017, 18(3), 503; https://doi.org/10.3390/ijms18030503 - 25 Feb 2017
Cited by 44 | Viewed by 8890
Abstract
Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly [...] Read more.
Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP). These properties are beneficial if the sequence of senescence–clearance–regeneration is transient in manner. However, persisting senescent cell accumulation and excessive SASP might induce sustained low-grade inflammation and disruption of normal tissue microenvironments in aged tissue. Emerging evidence indicates that cellular senescence is a key component in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which are known to be age-related and increase the risk of pneumonia. In addition to their structural collapses, COPD and IPF might increase the vulnerability to pathogen insults through SASP. Here, we discuss the current advances in understanding of the impacts of cellular senescence in elderly pneumonia and in these chronic lung disorders that heighten the risk of respiratory infections. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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223 KiB  
Review
Biomarkers in Pediatric Community-Acquired Pneumonia
by Nicola Principi and Susanna Esposito
Int. J. Mol. Sci. 2017, 18(2), 447; https://doi.org/10.3390/ijms18020447 - 19 Feb 2017
Cited by 66 | Viewed by 9111
Abstract
Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and [...] Read more.
Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and prediction of disease severity are critical for effectively managing individuals with CAP. To solve questionable cases, several biomarkers indicating the etiology and severity of CAP have been studied. Unfortunately, only a few studies have examined the roles of these biomarkers in pediatric practice. The main aim of this paper is to detail current knowledge regarding the use of biomarkers to diagnose and treat CAP in children, analyzing the most recently published relevant studies. Despite several attempts, the etiologic diagnosis of pediatric CAP and the estimation of the potential outcome remain unsolved problems in most cases. Among traditional biomarkers, procalcitonin (PCT) appears to be the most effective for both selecting bacterial cases and evaluating the severity. However, a precise cut-off separating bacterial from viral and mild from severe cases has not been defined. The three-host protein assay based on C-reactive protein (CRP), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), plasma interferon-γ protein-10 (IP-10), and micro-array-based whole genome expression arrays might offer more advantages in comparison with former biomarkers. However, further studies are needed before the routine use of those presently in development can be recommended. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
224 KiB  
Review
Pneumonia, Acute Respiratory Distress Syndrome, and Early Immune-Modulator Therapy
by Kyung-Yil Lee
Int. J. Mol. Sci. 2017, 18(2), 388; https://doi.org/10.3390/ijms18020388 - 11 Feb 2017
Cited by 93 | Viewed by 9869
Abstract
Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved [...] Read more.
Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Review
Combined Use of Delamanid and Bedaquiline to Treat Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: A Systematic Review
by Giovanni Battista Migliori, Emanuele Pontali, Giovanni Sotgiu, Rosella Centis, Lia D’Ambrosio, Simon Tiberi, Marina Tadolini and Susanna Esposito
Int. J. Mol. Sci. 2017, 18(2), 341; https://doi.org/10.3390/ijms18020341 - 07 Feb 2017
Cited by 47 | Viewed by 8281
Abstract
The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on lack of evidence, recommends their use under specific conditions and not in combination. No systematic review has yet [...] Read more.
The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on lack of evidence, recommends their use under specific conditions and not in combination. No systematic review has yet evaluated the efficacy, safety, and tolerability of delamanid and bedaquiline used in combination. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of delamanid and bedaquiline-containing regimens in individuals with pulmonary/extrapulmonary disease, which were bacteriologically confirmed as M/XDR-TB. We used PubMed to identify any relevant manuscripts in English up to the 23 December 2016, excluding editorials and reviews. Three out of 75 manuscripts retrieved satisfied the inclusion criteria, whilst 72 were excluded for dealing with only one drug (three studies), being recommendations (one study) or identifying need for their use (one study), focusing on drug resistance aspects (six studies) or being generic reviews/other studies (61 papers). The studies retrieved reported two XDR-TB cases observed for six months and achieving consistent sputum smear and culture conversion. Case 2 experienced a short break of bedaquiline, which was re-started after introducing verapamil. After a transient and symptom-free increase of the QT interval from week 5 to 17, it then decreased below the 500 ms threshold. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Review
Recurrent Pneumonia in Children: A Reasoned Diagnostic Approach and a Single Centre Experience
by Silvia Montella, Adele Corcione and Francesca Santamaria
Int. J. Mol. Sci. 2017, 18(2), 296; https://doi.org/10.3390/ijms18020296 - 29 Jan 2017
Cited by 29 | Viewed by 12310
Abstract
Recurrent pneumonia (RP), i.e., at least two episodes of pneumonia in one year or three episodes ever with intercritical radiographic clearing of densities, occurs in 7.7%–9% of children with community-acquired pneumonia. In RP, the challenge is to discriminate between children with self-limiting or [...] Read more.
Recurrent pneumonia (RP), i.e., at least two episodes of pneumonia in one year or three episodes ever with intercritical radiographic clearing of densities, occurs in 7.7%–9% of children with community-acquired pneumonia. In RP, the challenge is to discriminate between children with self-limiting or minor problems, that do not require a diagnostic work-up, and those with an underlying disease. The aim of the current review is to discuss a reasoned diagnostic approach to RP in childhood. Particular emphasis has been placed on which children should undergo a diagnostic work-up and which tests should be performed. A pediatric case series is also presented, in order to document a single centre experience of RP. A management algorithm for the approach to children with RP, based on the evidence from a literature review, is proposed. Like all algorithms, it is not meant to replace clinical judgment, but it should drive physicians to adopt a systematic approach to pediatric RP and provide a useful guide to the clinician. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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1362 KiB  
Review
Lung Infections in Systemic Rheumatic Disease: Focus on Opportunistic Infections
by Manuela Di Franco, Bruno Lucchino, Martina Spaziante, Cristina Iannuccelli, Guido Valesini and Giancarlo Iaiani
Int. J. Mol. Sci. 2017, 18(2), 293; https://doi.org/10.3390/ijms18020293 - 29 Jan 2017
Cited by 28 | Viewed by 5582
Abstract
Systemic rheumatic diseases have significant morbidity and mortality, due in large part to concurrent infections. The lung has been reported among the most frequent sites of infection in patients with rheumatic disease, who are susceptible to developing pneumonia sustained both by common pathogens [...] Read more.
Systemic rheumatic diseases have significant morbidity and mortality, due in large part to concurrent infections. The lung has been reported among the most frequent sites of infection in patients with rheumatic disease, who are susceptible to developing pneumonia sustained both by common pathogens and by opportunistic microorganisms. Patients with rheumatic disease show a peculiar vulnerability to infectious complications. This is due in part to intrinsic disease-related immune dysregulation and in part to the immunosuppressive treatments. Several therapeutic agents have been associated to a wide spectrum of infections, complicating the management of rheumatic diseases. This review discusses the most frequent pulmonary infections encountered in rheumatic diseases, focusing on opportunistic agents, consequent diagnostic challenges and appropriate therapeutic strategies. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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401 KiB  
Review
Radiation-Induced Organizing Pneumonia: A Characteristic Disease that Requires Symptom-Oriented Management
by Keisuke Otani, Yuji Seo and Kazuhiko Ogawa
Int. J. Mol. Sci. 2017, 18(2), 281; https://doi.org/10.3390/ijms18020281 - 27 Jan 2017
Cited by 14 | Viewed by 6033
Abstract
Radiation-induced organizing pneumonia (RIOP) is an inflammatory lung disease that is occasionally observed after irradiation to the breast. It is a type of secondary organizing pneumonia that is characterized by infiltrates outside the irradiated volume that are sometimes migratory. Corticosteroids work acutely, but [...] Read more.
Radiation-induced organizing pneumonia (RIOP) is an inflammatory lung disease that is occasionally observed after irradiation to the breast. It is a type of secondary organizing pneumonia that is characterized by infiltrates outside the irradiated volume that are sometimes migratory. Corticosteroids work acutely, but relapse of pneumonia is often experienced. Management of RIOP should simply be symptom-oriented, and the use of corticosteroids should be limited to severe symptoms from the perspective not only of cost-effectiveness but also of cancer treatment. Once steroid therapy is started, it takes a long time to stop it due to frequent relapses. We review RIOP from the perspective of its diagnosis, epidemiology, molecular pathogenesis, and patient management. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Review
Current Concepts of ARDS: A Narrative Review
by Michele Umbrello, Paolo Formenti, Luca Bolgiaghi and Davide Chiumello
Int. J. Mol. Sci. 2017, 18(1), 64; https://doi.org/10.3390/ijms18010064 - 29 Dec 2016
Cited by 100 | Viewed by 23376
Abstract
Acute respiratory distress syndrome (ARDS) is characterized by the acute onset of pulmonary edema of non-cardiogenic origin, along with bilateral pulmonary infiltrates and reduction in respiratory system compliance. The hallmark of the syndrome is refractory hypoxemia. Despite its first description dates back in [...] Read more.
Acute respiratory distress syndrome (ARDS) is characterized by the acute onset of pulmonary edema of non-cardiogenic origin, along with bilateral pulmonary infiltrates and reduction in respiratory system compliance. The hallmark of the syndrome is refractory hypoxemia. Despite its first description dates back in the late 1970s, a new definition has recently been proposed. However, the definition remains based on clinical characteristic. In the present review, the diagnostic workup and the pathophysiology of the syndrome will be presented. Therapeutic approaches to ARDS, including lung protective ventilation, prone positioning, neuromuscular blockade, inhaled vasodilators, corticosteroids and recruitment manoeuvres will be reviewed. We will underline how a holistic framework of respiratory and hemodynamic support should be provided to patients with ARDS, aiming to ensure adequate gas exchange by promoting lung recruitment while minimizing the risk of ventilator-induced lung injury. To do so, lung recruitability should be considered, as well as the avoidance of lung overstress by monitoring transpulmonary pressure or airway driving pressure. In the most severe cases, neuromuscular blockade, prone positioning, and extra-corporeal life support (alone or in combination) should be taken into account. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Review
Prevention of Community-Acquired Pneumonia with Available Pneumococcal Vaccines
by Nicola Principi and Susanna Esposito
Int. J. Mol. Sci. 2017, 18(1), 30; https://doi.org/10.3390/ijms18010030 - 25 Dec 2016
Cited by 22 | Viewed by 6180
Abstract
Community-acquired pneumonia (CAP) places a considerable burden on society. A substantial number of pediatric and adult CAP cases are due to Streptococcus pneumoniae, but fortunately there are effective vaccines available that have a significant impact on CAP-related medical, social, and economic problems. The [...] Read more.
Community-acquired pneumonia (CAP) places a considerable burden on society. A substantial number of pediatric and adult CAP cases are due to Streptococcus pneumoniae, but fortunately there are effective vaccines available that have a significant impact on CAP-related medical, social, and economic problems. The main aim of this paper is to evaluate the published evidence concerning the impact of pneumococcal vaccines on the prevention of CAP in children and adults. Available data indicate that pneumococcal conjugate vaccines (PCVs) are effective in children, reducing all-cause CAP cases and bacteremic and nonbacteremic CAP cases. Moreover, at least for PCV7 and PCV13, vaccination of children is effective in reducing the incidence of CAP among adults. Recently use of PCV13 in adults alone or in combination with the pneumococcal polysaccharide vaccine has been suggested and further studies can better define its effectiveness in this group of subjects. The only relevant problem for PCV13 is the risk of a second replacement phenomenon, which might significantly reduce its real efficacy in clinical practice. Protein-based pneumococcal vaccines might be a possible solution to this problem. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Review
Microbial Etiology of Pneumonia: Epidemiology, Diagnosis and Resistance Patterns
by Catia Cilloniz, Ignacio Martin-Loeches, Carolina Garcia-Vidal, Alicia San Jose and Antoni Torres
Int. J. Mol. Sci. 2016, 17(12), 2120; https://doi.org/10.3390/ijms17122120 - 16 Dec 2016
Cited by 146 | Viewed by 30109
Abstract
Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity. Despite advances in antimicrobial therapies, microbiological diagnostic tests and prevention measures, pneumonia remains the main cause of death from infectious disease in the world. An important reason [...] Read more.
Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity. Despite advances in antimicrobial therapies, microbiological diagnostic tests and prevention measures, pneumonia remains the main cause of death from infectious disease in the world. An important reason for the increased global mortality is the impact of pneumonia on chronic diseases, along with the increasing age of the population and the virulence factors of the causative microorganism. The increasing number of multidrug-resistant bacteria, difficult-to-treat microorganisms, and the emergence of new pathogens are a major problem for clinicians when deciding antimicrobial therapy. A key factor for managing and effectively guiding appropriate antimicrobial therapy is an understanding of the role of the different causative microorganisms in the etiology of pneumonia, since it has been shown that the adequacy of initial antimicrobial therapy is a key factor for prognosis in pneumonia. Furthermore, broad-spectrum antibiotic therapies are sometimes given until microbiological results are available and de-escalation cannot be performed quickly. This review provides an overview of microbial etiology, resistance patterns, epidemiology and microbial diagnosis of pneumonia. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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Review
Lung Involvement in Children with Hereditary Autoinflammatory Disorders
by Giusyda Tarantino, Susanna Esposito, Laura Andreozzi, Benedetta Bracci, Francesca D’Errico and Donato Rigante
Int. J. Mol. Sci. 2016, 17(12), 2111; https://doi.org/10.3390/ijms17122111 - 15 Dec 2016
Cited by 21 | Viewed by 5214
Abstract
Short-lived systemic inflammatory reactions arising from disrupted rules in the innate immune system are the operating platforms of hereditary autoinflammatory disorders (HAIDs). Multiple organs may be involved and aseptic inflammation leading to disease-specific phenotypes defines most HAIDs. Lungs are infrequently involved in children [...] Read more.
Short-lived systemic inflammatory reactions arising from disrupted rules in the innate immune system are the operating platforms of hereditary autoinflammatory disorders (HAIDs). Multiple organs may be involved and aseptic inflammation leading to disease-specific phenotypes defines most HAIDs. Lungs are infrequently involved in children with HAIDs: the most common pulmonary manifestation is pleuritis in familial Mediterranean fever (FMF) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), respectively caused by mutations in the MEFV and TNFRSF1A genes, while interstitial lung disease can be observed in STING-associated vasculopathy with onset in infancy (SAVI), caused by mutations in the TMEM173 gene. The specific pleuropulmonary diseases may range from sub-clinical abnormalities during inflammatory flares of FMF and TRAPS to a severe life-threatening disorder in children with SAVI. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
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