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{{Bacterial pneumonia}} | {{Bacterial pneumonia}} | ||
'''Editor-In-Chief:''' [[User:C Michael Gibson|C. Michael Gibson, M.S., M.D.]] [Mailto:charlesmichaelgibson@gmail.com| <nowiki>[1]</nowiki>]; '''Associate Editor(s)-in-Chief:''' [[User:AroojNaz|Arooj Naz, M.B.B.S]] | |||
=Overview= | |||
Due to increasing [[antibiotic resistance]] and emerging organisms, it is important that the approaches to diagnosing [[pneumonia]] continue to advance. Currently, the host factors predisposing one to pneumonia are being studied in detail.<ref name="pmid29546996">{{cite journal| author=Dela Cruz CS, Wunderink RG, Christiani DC, Cormier SA, Crothers K, Doerschuk CM | display-authors=etal| title=Future Research Directions in Pneumonia. NHLBI Working Group Report. | journal=Am J Respir Crit Care Med | year= 2018 | volume= 198 | issue= 2 | pages= 256-263 | pmid=29546996 | doi=10.1164/rccm.201801-0139WS | pmc=6058989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29546996 }} </ref> Host directed therapeutic approaches against pneumonia infection may prove to be very advantageous. These include: | |||
#Host Susceptibility | |||
#Host Response to Pneumonia | |||
#Host Consequences | |||
Host susceptibility takes into consideration the [[age]], [[Genetics|genetic factors]], exposures, acute and [[chronic diseases]]. The genetic factors being focused on right now include variants in the NGR1, [[PAK6]], MATN1 and [[FER (gene)|FER]] genes. The host response take into account Immune resistance and repair mechanisms. Host consequences refer to the development of [[complications]] and exacerbation of existing [[Chronic|chronic conditions]]. | |||
=Host Susceptibility= | |||
Factors that determine host susceptibility include [[age]], [[Genetics|genetic factors]], exposures, [[acute diseases]] and [[chronic diseases]] that allow [[pneumonia]] to develop.<ref name="pmid29546996">{{cite journal| author=Dela Cruz CS, Wunderink RG, Christiani DC, Cormier SA, Crothers K, Doerschuk CM | display-authors=etal| title=Future Research Directions in Pneumonia. NHLBI Working Group Report. | journal=Am J Respir Crit Care Med | year= 2018 | volume= 198 | issue= 2 | pages= 256-263 | pmid=29546996 | doi=10.1164/rccm.201801-0139WS | pmc=6058989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29546996 }} </ref> | |||
*'''Age:''' Increased susceptibility to pneumonia and related mortality is more pronounced at the extremes of age in paediatric and geriatric populations | |||
*'''Genetic factors:''' A few links to gene variants have emerged and studying them further may help determine ways to prevent the occurrence of pneumonia. Through meta-analysis studied, potentially interesting gene variants have been found in ''[[NGR1]]'' (P = 6.3 × 10-8), ''[[PAK6]]'' (P = 3.3 × 10-7), and near ''[[MATN1]]'' (P = 2.8 × 10-7).<ref name="pmid27508494">{{cite journal| author=Hayden LP, Cho MH, McDonald MN, Crapo JD, Beaty TH, Silverman EK | display-authors=etal| title=Susceptibility to Childhood Pneumonia: A Genome-Wide Analysis. | journal=Am J Respir Cell Mol Biol | year= 2017 | volume= 56 | issue= 1 | pages= 20-28 | pmid=27508494 | doi=10.1165/rcmb.2016-0101OC | pmc=5248961 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27508494 }} </ref> Variants have also been studied in the ''[[FER (gene)|FER]]'' gene that may reduce [[Sepsis|sepsis realted death]] in cases of pneumonia<ref name="pmid25533491">{{cite journal| author=Rautanen A, Mills TC, Gordon AC, Hutton P, Steffens M, Nuamah R | display-authors=etal| title=Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study. | journal=Lancet Respir Med | year= 2015 | volume= 3 | issue= 1 | pages= 53-60 | pmid=25533491 | doi=10.1016/S2213-2600(14)70290-5 | pmc=4314768 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25533491 }} </ref> | |||
*'''Exposures:''' [[Cigarette smoke]], [[alcohol abuse]] and [[air pollution]] can greatly exacerbate pneumonia and promote the development of disease | |||
*'''Acute conditions:''' Pneumonia in itself is considered an acute disease but the presence of acute diseases such as a [[Influenza infection|viral influenza infection]], can predispose an individual to the development of pneumonia, The relationship between acute conditions and the development of pneumonia are being studied in detail | |||
*'''Chronic diseases:''' Chronic diseases predispose to pneumonia due to structural changes that develop over time. These include [[COPD]], [[diabetes]], [[cancer]] and [[obesity]] as well as many others | |||
=Host Response to Pneumonia= | |||
Factors that affect host response include a hosts immune resistance and repair mechanisms.<ref name="pmid29546996">{{cite journal| author=Dela Cruz CS, Wunderink RG, Christiani DC, Cormier SA, Crothers K, Doerschuk CM | display-authors=etal| title=Future Research Directions in Pneumonia. NHLBI Working Group Report. | journal=Am J Respir Crit Care Med | year= 2018 | volume= 198 | issue= 2 | pages= 256-263 | pmid=29546996 | doi=10.1164/rccm.201801-0139WS | pmc=6058989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29546996 }} </ref> | |||
*'''Immune resistance:''' microbes enter the respiratory system and are encountered by [[epithelial cells]], [[macrophages]] and [[dendritic cells]]. The response provided by these cells can help determine the progression and outcome of the disease. The function of [[B cells]] and [[T cells]], [[NF-κB]] and [[cytokines]] in preventing pneumonia and contributing to immunity are being further studied<ref name="pmid29767563">{{cite journal| author=Quinton LJ, Walkey AJ, Mizgerd JP| title=Integrative Physiology of Pneumonia. | journal=Physiol Rev | year= 2018 | volume= 98 | issue= 3 | pages= 1417-1464 | pmid=29767563 | doi=10.1152/physrev.00032.2017 | pmc=6088146 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29767563 }} </ref><ref name="pmid25148693">{{cite journal| author=Quinton LJ, Mizgerd JP| title=Dynamics of lung defense in pneumonia: resistance, resilience, and remodeling. | journal=Annu Rev Physiol | year= 2015 | volume= 77 | issue= | pages= 407-30 | pmid=25148693 | doi=10.1146/annurev-physiol-021014-071937 | pmc=4366440 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25148693 }} </ref> | |||
*'''Repair mechanisms:''' Response from macrophages and epithelial cells may be responsible for lung defences but these are still misunderstood and require further investigation. Studied are being done to develop methods that can predict disease outcomes according to host response measures | |||
<br /> | |||
=Host Consequences= | |||
Host consequences refer to the development of complications and exacerbation of existing chronic conditions.<ref name="pmid29546996">{{cite journal| author=Dela Cruz CS, Wunderink RG, Christiani DC, Cormier SA, Crothers K, Doerschuk CM | display-authors=etal| title=Future Research Directions in Pneumonia. NHLBI Working Group Report. | journal=Am J Respir Crit Care Med | year= 2018 | volume= 198 | issue= 2 | pages= 256-263 | pmid=29546996 | doi=10.1164/rccm.201801-0139WS | pmc=6058989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29546996 }} </ref> | |||
#'''Development of complications:''' Development of [[complications]] and acceleration of pre-existing conditions may be seen. Metastatic infection can evolve to include the [[pleura]], [[bone]], [[joints]], [[brain]], [[heart valves]], and the [[myocardium]] resulting in structural changes and remodelling<ref name="pmid28614669">{{cite journal| author=Reyes LF, Restrepo MI, Hinojosa CA, Soni NJ, Anzueto A, Babu BL | display-authors=etal| title=Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling. | journal=Am J Respir Crit Care Med | year= 2017 | volume= 196 | issue= 5 | pages= 609-620 | pmid=28614669 | doi=10.1164/rccm.201701-0104OC | pmc=5620668 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28614669 }}</ref> | |||
#'''Exacerbation of existing chronic conditions:''' After a pneumonia infection, the risk of developing or further progression of chronic conditions is worrisome. These include [[cardiovascular diseases]] such as [[myocardial infarction]] and the [[Stroke|risk of stroke]]. [[Biomarkers]] such as [[cytokines]] are found to be increased at the time of diagnosis and often times have found to be abnormally elevated at the time of discharge, even after the pneumonia had been succesfully treated<ref name="pmid18369199">{{cite journal| author=Yende S, D'Angelo G, Kellum JA, Weissfeld L, Fine J, Welch RD | display-authors=etal| title=Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis. | journal=Am J Respir Crit Care Med | year= 2008 | volume= 177 | issue= 11 | pages= 1242-7 | pmid=18369199 | doi=10.1164/rccm.200712-1777OC | pmc=2720087 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18369199 }}</ref> | |||
==References== | ==References== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S
Overview
Due to increasing antibiotic resistance and emerging organisms, it is important that the approaches to diagnosing pneumonia continue to advance. Currently, the host factors predisposing one to pneumonia are being studied in detail.[1] Host directed therapeutic approaches against pneumonia infection may prove to be very advantageous. These include:
- Host Susceptibility
- Host Response to Pneumonia
- Host Consequences
Host susceptibility takes into consideration the age, genetic factors, exposures, acute and chronic diseases. The genetic factors being focused on right now include variants in the NGR1, PAK6, MATN1 and FER genes. The host response take into account Immune resistance and repair mechanisms. Host consequences refer to the development of complications and exacerbation of existing chronic conditions.
Host Susceptibility
Factors that determine host susceptibility include age, genetic factors, exposures, acute diseases and chronic diseases that allow pneumonia to develop.[1]
- Age: Increased susceptibility to pneumonia and related mortality is more pronounced at the extremes of age in paediatric and geriatric populations
- Genetic factors: A few links to gene variants have emerged and studying them further may help determine ways to prevent the occurrence of pneumonia. Through meta-analysis studied, potentially interesting gene variants have been found in NGR1 (P = 6.3 × 10-8), PAK6 (P = 3.3 × 10-7), and near MATN1 (P = 2.8 × 10-7).[2] Variants have also been studied in the FER gene that may reduce sepsis realted death in cases of pneumonia[3]
- Exposures: Cigarette smoke, alcohol abuse and air pollution can greatly exacerbate pneumonia and promote the development of disease
- Acute conditions: Pneumonia in itself is considered an acute disease but the presence of acute diseases such as a viral influenza infection, can predispose an individual to the development of pneumonia, The relationship between acute conditions and the development of pneumonia are being studied in detail
- Chronic diseases: Chronic diseases predispose to pneumonia due to structural changes that develop over time. These include COPD, diabetes, cancer and obesity as well as many others
Host Response to Pneumonia
Factors that affect host response include a hosts immune resistance and repair mechanisms.[1]
- Immune resistance: microbes enter the respiratory system and are encountered by epithelial cells, macrophages and dendritic cells. The response provided by these cells can help determine the progression and outcome of the disease. The function of B cells and T cells, NF-κB and cytokines in preventing pneumonia and contributing to immunity are being further studied[4][5]
- Repair mechanisms: Response from macrophages and epithelial cells may be responsible for lung defences but these are still misunderstood and require further investigation. Studied are being done to develop methods that can predict disease outcomes according to host response measures
Host Consequences
Host consequences refer to the development of complications and exacerbation of existing chronic conditions.[1]
- Development of complications: Development of complications and acceleration of pre-existing conditions may be seen. Metastatic infection can evolve to include the pleura, bone, joints, brain, heart valves, and the myocardium resulting in structural changes and remodelling[6]
- Exacerbation of existing chronic conditions: After a pneumonia infection, the risk of developing or further progression of chronic conditions is worrisome. These include cardiovascular diseases such as myocardial infarction and the risk of stroke. Biomarkers such as cytokines are found to be increased at the time of diagnosis and often times have found to be abnormally elevated at the time of discharge, even after the pneumonia had been succesfully treated[7]
References
- ↑ 1.0 1.1 1.2 1.3 Dela Cruz CS, Wunderink RG, Christiani DC, Cormier SA, Crothers K, Doerschuk CM; et al. (2018). "Future Research Directions in Pneumonia. NHLBI Working Group Report". Am J Respir Crit Care Med. 198 (2): 256–263. doi:10.1164/rccm.201801-0139WS. PMC 6058989. PMID 29546996.
- ↑ Hayden LP, Cho MH, McDonald MN, Crapo JD, Beaty TH, Silverman EK; et al. (2017). "Susceptibility to Childhood Pneumonia: A Genome-Wide Analysis". Am J Respir Cell Mol Biol. 56 (1): 20–28. doi:10.1165/rcmb.2016-0101OC. PMC 5248961. PMID 27508494.
- ↑ Rautanen A, Mills TC, Gordon AC, Hutton P, Steffens M, Nuamah R; et al. (2015). "Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study". Lancet Respir Med. 3 (1): 53–60. doi:10.1016/S2213-2600(14)70290-5. PMC 4314768. PMID 25533491.
- ↑ Quinton LJ, Walkey AJ, Mizgerd JP (2018). "Integrative Physiology of Pneumonia". Physiol Rev. 98 (3): 1417–1464. doi:10.1152/physrev.00032.2017. PMC 6088146. PMID 29767563.
- ↑ Quinton LJ, Mizgerd JP (2015). "Dynamics of lung defense in pneumonia: resistance, resilience, and remodeling". Annu Rev Physiol. 77: 407–30. doi:10.1146/annurev-physiol-021014-071937. PMC 4366440. PMID 25148693.
- ↑ Reyes LF, Restrepo MI, Hinojosa CA, Soni NJ, Anzueto A, Babu BL; et al. (2017). "Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling". Am J Respir Crit Care Med. 196 (5): 609–620. doi:10.1164/rccm.201701-0104OC. PMC 5620668. PMID 28614669.
- ↑ Yende S, D'Angelo G, Kellum JA, Weissfeld L, Fine J, Welch RD; et al. (2008). "Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis". Am J Respir Crit Care Med. 177 (11): 1242–7. doi:10.1164/rccm.200712-1777OC. PMC 2720087. PMID 18369199.