질병관리본부학술연구용역사업최종결과보고서 과제명 수행기관 / 연구책임자 발주부서 - 1 -

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2 질병관리본부학술연구용역사업최종결과보고서 과제명 수행기관 / 연구책임자 발주부서 - 1 -

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4 최종결과보고서요약문 - 3 -

5 Summary β - 4 -

6 학술연구용역과제연구결과

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9 연구목표 진행상황 달성도 (%)

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13 μ μ μ

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18 Sample_name Sample_type Sex Age Bact. Cx. 1 Diagnosis Radio Sx and jsign 13ADV_01 Nasopharyng M 0 Some γ -Streptococcus Pneumonia Perihilar consolidation in fever, cough, sputum right 13ADV_02 Nasopharyng F 5 Few γ Pneumonia No active lung fever -Streptococcus disease 13ADV_03 Nasopharyng M 2 Normal Acute No active lung fever respiratory tract microbiota tonsillopharyng itis disease 13ADV_04 Nasopharyng F 3 Few α -Streptococcus Bronchitis No active lung disease fever, poor oral intake 13ADV_05 Sputum F 52 No growth Pneumonia, aggravation of dyspnea S/P lung transplantation bilaterla pleural effusion 13ADV_06 Sputum M 71 Few H. influenzae Mycoplasma pneumonia Bilateral peribronchial fever, cough, rhinorrhea infiltration, R/O bilateral pleural effusion 13ADV_07 Nasopharyng F 5 NT Acute No active lung fever tonsillopharyng itis disease 13ADV_08 Nasopharyng M 1 No growth Pneumonia No active lung fever, cough disease 13CRV_01 Sputum F 66 Few S. maltophilia Pneumonia, Acute myeloid pneumonia in the Rt. lower lung cough, sputum, fever leukemia 13CRV_02 Nasopharyng M 0 Few α -Streptococcus Bronchiolitis No active lung disease cough, sputum, rhinorrhea, wheezing 13CRV_03 Sputum F 8 Many α -Streptococcus Pneumonia patchy consolidation/g cough, sputum GO at both lungs 13CRV_04 Sputum F 80 Few γ Pneumonia Increased dyspnea,

19 13CRV_05 13CRV_06 Nasopharyng Nasopharyng -Streptococcus M 0 Many S. aureus M 0 Few α -Streptococcus 13CRV_07 Sputum F 8 Many α 13CRV_08 Sputum F 66 Few S. -Streptococcus maltophilia 13IFV_01 Sputum F 33 13IFV_02 Sputum F 80 Many A. 13IFV_03 Nasopharyng baumannii F 77 Normal respiratory tract microbiota 13IFV_04 VTM M 3 Normal respiratory tract microbiota 13IFV_05 VTM M 6 Predominant org. α -Streptococcus Bronchitis Bronchiolitis Pneumonia Pneumonia, Acute myeloid leukemia Pneumonia, acute pulmonary edema Influenza Croup Pneumonia 13IFV_06 VTM M 1 No growth Leftpulmonarya rteryjunctionste nosis 13IFV_07 VTM M 4 No growth Pneumonia 13IFV_08 VTM F 4 Few α Pneumonia -Streptococcus 13IFV_09 VTM M 1 No growth Croup bronchovascular bundle thickening. Increased amount of bilateral pleural effusion(rt>lt). Diffuse GGO at both lungs No active lung disease No active lung disease patchy consolidation/g GO at both lungs pneumonia in the Rt. lower lung Aggravation of haziness in BLLZ, R/O pleural effusion or pneumonia No active lung disease cough, sputum cough, poor oral intake cough, sputum, rhinorrhea, wheezing cough, sputum cough, sputum, fever fever, cough, poor oral inta다 fever, sputum 13IFV_10 VTM M 8 Few α -Streptococcus 13IFV_11 Nasopharyng M 0 Many α -Streptococcus Mycoplasma pneumonia Pneumonia Bilateral perihilar infiltrations fever, cough, sputum, rhinorrhea

20 13IFV_12 VTM F 1 No growth Croup 13IFV_13 VTM M 2 Few α Pneumonia -Streptococcus 13IFV_14 VTM M 2 1 Many Streptococcus Nephrotic syndrome pneumoniae 13IFV_15 VTM F 3 No growth Croup 13IFV_16 VTM F 2 1 Few Pneumonia Haemophilus influenzae 13IFV_17 Nasopharyng M 2 Predominant org. α -Streptococcus Bronchitis No active lung disease 13IFV_18 Sputum F 45 Normal Asthma No remarkable respiratory parenchymal tract lesion in both microbiota lung 13IFV_19 Sputum F 73 Normal Influenza No active lung respiratory disease tract microbiota 13IFV_20 Sputum M 50 Normal Pneumonia focal respiratory consolidation tract in LLLF, r/o microbiota pneumonia 13IFV_21 Sputum M 65 Many α Pneumonia No active lung -Streptococcus disease 13IFV_22 Nasopharyng F 73 Normal Influenza No active lung respiratory disease tract microbiota 13IFV_23 Sputum F 32 Normal Preterm labor small amount of respiratory without left pleural tract delivery effusion microbiota 13IFV_24 Sputum M 75 Predominant pneumonia, No active lung org. γ drug eruption disease -Streptococcus 13IFV_25 Sputum F 78 No growth Pneumonia Newly developed GGO and consolidation win RML, LLL 13IFV_26 Nasopharyng F 5 13IFV_27 Sputum F 80 Many A. Pneumonia, Aggravation of baumannii acute haziness in pulmonary BLLZ, R/O edema pleural effusion or pneumonia 13IFV_28 Sputum F 80 Many A. Pneumonia, Aggravation of baumannii acute haziness in fever, poor oral intake fever, cough, dyspnea, wheezing fever, sputum, rhinorrhea myalgia, fever, cough fever, cough, sputum fever, sputum, rhinorrhea fever cough,sputu m cough, sputum, dyspnea fever, cough, poor oral inta다 fever, cough, poor oral

21 pulmonary edema BLLZ, R/O pleural effusion or pneumonia 13IFV_29 Nasopharyng F 2 NT Influenza Slightly increased bilateral perihilar infiltration 13IFV_30 Nasopharyng F 0 Many α Pneumonia, Increased -Streptococcus Bronchiolitis perihilar infiltration in bilateral lung field 13IFV_31 Nasopharyng F 0 Many α Pneumonia, Increased -Streptococcus Bronchiolitis perihilar infiltration in bilateral lung field 13IFV_32 Nasopharyng M 0 Few α Bronchiolitis No active lung -Streptococcus disease 13IFV_33 Nasopharyng F 3 Normal Pneumonia Mild bilateral respiratory perihilar GGO tract microbiota 13IFV_34 Sputum F 39 Few Pneumonia, No active lung Staphylococcus Asthma disease sp. 13IFV_35 Sputum M 86 Few α Pneumonia No active lung -Streptococcus disease 13IFV_36 Sputum M 86 Few α Pneumonia No active lung -Streptococcus disease 13MPV_01 Nasopharyng F 2 Few γ Pneumonia Peribronchial -Streptococcus hazziness in both lungs 13MPV_02 Nasopharyng M 0 Few α Human Multifocal patch -Streptococcus metapneumovi GGO/consolidati rus on at both pneumonia lungs 13MPV_03 Nasopharyng F 0 Few α Human Bilateral perihilar -Streptococcus metapneumovi infiltration rus pneumonia 13MPV_04 Nasopharyng M 5 NT Bronchitis Mild bilateral perihilar infiltration with GGO 13MPV_05 Nasopharyng F 2 13MPV_06 Nasopharyng M 5 Few α Human Increased -Streptococcus metapneumovi opacity in the rus RMLZ and pneumonia bilateral perihilar inta다 fever fever, cough, wheezing fever, cough, wheezing fever, cough, wheezing fever, cough, diarrhea, wheezing dyspnea, wheezing dyspnea dyspnea fever, cough, sputum, rhinorrhea, vomiting, wheezing fever, cough, sputum, rhinorrhea, wheezing fever, cough fever fever, cough, sputum

22 13MPV_07 sputum M 75 Few α -Streptococcus Pneumonia 13MPV_08 Nasopharyng F 4 Few S. Human pneumoniae metapneumovi rus pneumonia 13MPV_09 Nasopharyng F 1 Some H. Human influenzae metapneumovi rus pneumonia 13PIV_01 F 0 Some α Bronchiolitis -Streptococcus 13PIV_02 M 1 Few α Pneumonia -Streptococcus 13PIV_03 VTM F 2 No growth Pneumonia 13PIV_04 VTM F 0 No growth Bronchiolitis infiltration Increased reticulonodular opacity in bilateral lower lung field Pneumonia with basal atelectasis, LLL Increased GGO/consolidati on in bilateral perihilar area No active lung disease Increased GGO/consolidati on in Rt lung cough, sputum fever, cough, rhinorrhea cough, sputum, rhinorrhea, wheezing fever 13PIV_05 VTM F 1 1 Many Streptococcusp neumoniae Bronchiolitis 13PIV_06 VTM F 1 1 Some Pneumonia Gram negative rod Moraxella sp. 13PIV_07 VTM M 2 No growth Pneumonia 13PIV_08 VTM M 0 Few α -Streptococcus 13PIV_09 VTM F 4 Few α -Streptococcus 13PIV_10 VTM M 1 Few α -Streptococcus Bronchiolitis Pneumonia Pneumonia Bronchitis 13PIV_11 VTM M 1 No growth Bronchiolitis 13PIV_12 F 0 Few S. pneumoniae Bronchiolitis 13PIV_13 VTM M 0 No growth Bronchiolitis Bilateral perihilar infiltrations fever, cough, wheezing 13PIV_14 M 0 No growth Bronchiolitis Slightly aggravated bilateral perihilar infiltration 13PIV_15 M 1 Few α Pneumonia peribronchial -Streptococcus consolidation at both lung fields cough, sputum, rhinorrhea, wheezing fever, cough, sputum, rhinorrha,

23 13PIV_16 VTM F CFU Pneumonia Staphylococcus sp. 13PIV_17 VTM F 0 No growth Pneumonia diarrhea 13PIV_18 VTM F 0 Few α -Streptococcus Acute bronchitis d/t parainfluenza virus 13PIV_19 VTM M 1 No growth Pneumonia 13PIV_20 VTM M 1 No growth Croup 13PIV_21 Nasopharyng M 0 NT Pneumonia Patchy GGO in BUL 13PIV_22 Sputum M 58 Many K. Pneumonia Increased pneumoniae diffuse opacity & some S. in RUL maltophilia 13PIV_23 M 1 No growth Pneumonia Increased opacity at Lt. retrocardiac area, r/o pneumonic consolidation 13RHV_01 Nasopharyng F 6 No growth Pneumonia Patchy GGO in LMLF 13RHV_02 Nasopharyng F 1 No growth Bronchiolitis No active lung disease 13RHV_03 Sputum F 67 Many S. Pneumonia, consolidation in aureus septic shock both lungs 13RHV_04 Nasopharyng M 0 Many α Pneumonia, remained -Streptococcus Acute consolidation in tonsillopharyng LLL itis 13RHV_05 Nasopharyng M 0 No growth Pneumonia Bilateral perihilar infiltration with patchy consolidations and overaeration in BLL 13RHV_06 Nasopharyng F 1 No growth Bronchiolitis No active lung disease 13RHV_07 Nasopharyng M 0 Few α Bronchiolitis No active lung -Streptococcus disease 13RHV_08 Nasopharyng M 0 Few α Bronchiolitis No active lung -Streptococcus disease 13RHV_09 Nasopharyng M 0 Few γ Bronchiolitis No active lung -Streptococcus diseas 13RHV_10 Nasopharyng M 0 Few α Bronchiolitis No active lung -Streptococcus disease fever, cough dyspnea, mental change fever, cough, sputum, rhinorrhea cough, wheezing, respiratory diffidulty fever, cough, wheezing mental change fever cough, respiratory difficulty, wheezing fever, cough, wheezing cough, wheezing cough, wheezing cough, wheezing cough, wheezing

24 13RHV_11 Sputum M 58 Normal respiratory tract microbiota Chronic obstructive pulmonary disease No active lung disease 13RHV_12 Nasopharyng M 3 No growth Asthma Bilateral perihilar infiltration 13RHV_13 Nasopharyng M 1 Some CNS Pneumonia consolidation in right lung and bilateral perihilar infiltration 13RHV_14 Sputum F 67 Many S. Pneumonia, consolidation in aureus septic shock both lungs 13RHV_15 Nasopharyng M 0 Many α Pneumonia, remained -Streptococcus Acute consolidation in tonsillopharyng LLL itis 13RHV_16 VTM M 2 No growth Bronchitis 13RSV_01 Nasopharyng F 1 Few S. Bronchiolitis Mild pneumoniae peribronchial infiltration in Rt. lung 13RSV_02 Nasopharyng F 2 Some H. Bronchitis No active lung influenzae disease 13RSV_03 Sputum F 2 Few α Mycoplasma Aggravated -Streptococcus pneumonia patchy consolidations in bilateral perihilar area 13RSV_04 Nasopharyng M 0 Many γ Pneumonia, Increased -Streptococcus respiratory opacity in RLLF syncytial virus 13RSV_05 Nasopharyng M 0 Few α Acute No active lung -Streptococcus bronchiolitis disease due to respiratory syncytial virus 13RSV_06 Nasopharyng M 1 No growth Bronchiolitis Bilateral perihilar infiltration 13RSV_07 Nasopharyng M 1 Few α -Streptococcus Acute bronchiolitis due to respiratory syncytial virus Bilateral peribronchial infiltration 13RSV_08 Nasopharyng M 1 Few γ COPD (stage Nodular opacity -Streptococcus III) in RLLF 13RSV_09 Nasopharyng F 0 No growth Bronchiolitis Bilateral perihilar infiltration 13RSV_10 Nasopharyng F 0 Few γ Acute No active lung -Streptococcus bronchiolitis disease due to cough, sputum, dyspnea fever, cough, wheezing cough, sputum, lethargy mental change fever fever, cough, wheezing cough, poor oral intake fever fever, cough, wheezing cough, rhinorrhea, wheezing fever, cough, sputum, wheezing fever, cough, sputum, wheezing fever, cough, chilling cough, sputum, rhinorrhea, wheezing cough, sputum, rhinorrhea,

25 respiratory syncytial virus 13RSV_11 Nasopharyng F 0 No growth Acute No active lung bronchiolitis disease due to respiratory syncytial virus 13RSV_12 Nasopharyng F 0 No growth Pneumonia, No active lung respiratory disease syncytial virus 13RSV_13 Nasopharyng F 3 No growth Asthma Mild bilateral perihilar infiltration 13RSV_14 VTM M 0 Pneumonia wheezing fever, cough, wheezing cough, sputum, rhinorrhea, fever, poor oral intake fever, cough, sputum, wheezing 13RSV_15 VTM M 3 Some α Pneumonia -Streptococcus 13RSV_16 VTM M 1 Few α -Streptococcus Mycoplasma pneumonia 13RSV_17 Nasopharyng M 2 Normal respiratory tract Pneumonia No active lung disease fever, poor oral intake, vomiting microbiota 13RSV_18 Nasopharyng M 0 Many S. aureus Bronchitis No active lung disease cough, poor oral intake 13RSV_19 Sputum F 62 Normal respiratory tract Status asthmaticus, s/p RUL No active lung disease cough, sputum, dyspnea microbiota lobectomy 13RSV_20 Nasopharyng F 0 NT Pneumonia No active lung fever disease 13RSV_21 Nasopharyng M 2 Predominant org. α Bronchitis No active lung disease fever, poor oral intake -Streptococcus 13RSV_22 Nasopharyng M 0 Few α -Streptococcus Bronchiolitis No active lung disease fever, cough, wheezing 13RSV_23 Nasopharyng M 2 Few α -Streptococcus Pneumonia No active lung disease cough, vomiting 13RSV_24 Nasopharyng M 1 Few α -Streptococcus Pneumonia Incresed bilateral peribronchial markings cough, fever, respiratory difficulty, wheezing 13RSV_25 Sputum F 75 Many α -Streptococcus Pneumonia increased reticular fever, cough, sputum opacity in RLL 13RSV_26 Nasopharyng F 0 No growth Pneumonia Bilateral perihilar infiltration fever, cough, sputum, wheezing 13RSV_27 Nasopharyng F 2 Few α -Streptococcus Pneumonia, respiratory Patchy GGO in LLL fever, cough, wheezing syncytial virus 13RSV_28 Nasopharyng M 0 NT Pneumonia, No active lung cough

26 respiratory disease syncytial virus 13RSV_29 Nasopharyng F 2 Few α -Streptococcus Mycoplasma pneumonia No active lung disease 13RSV_30 Sputum F 2 Few α Mycoplasma No active lung -Streptococcus pneumonia disease 13RSV_31 Nasopharyng M 0 Many γ Pneumonia, Increased -Streptococcus respiratory opacity in RLLF syncytial virus 13RSV_32 Sputum F 71 Many γ Pneumonia pulmonary -Streptococcus edema 13RSV_33 Nasopharyng M 0 No growth Pneumonia, No active lung respiratory disease syncytial virus 13RSV_34 Nasopharyng F 0 Few α Pneumonia, Bilateral perihilar -Streptococcus respiratory infiltration with syncytial virus bronchial wall thickening 13RSV_35 Nasopharyng M 1 Few α Pneumonia, Bilateral perihilar -Streptococcus respiratory infiltration with syncytial virus bronchial wall thickening 13RSV_36 Nasopharyng F 0 NT Bronchiolitis No active lung disease 13RSV_37 Nasopharyng F 1 Many γ Mycoplasma Bronchial wall -Streptococcus pneumonia thickening in the bilateral perihilar area 13RSV_38 Nasopharyng M 0 Few α Acute No active lung -Streptococcus bronchiolitis disease due to respiratory syncytial virus 13RSV_39 Nasopharyng M 2 Few γ Pneumonia Bronchial wall -Streptococcus thickening in both lungs 13RSV_40 Sputum F 36 Normal Bronchiolitis Bronchiolitis respiratory obliterans obliterance tract causing the microbiota air-trapping in the bilateral lungs 13RSV_41 Nasopharyng M 0 Few Bacillus Pneumonia right perihilar sp infiltration 13RSV_42 Nasopharyng M 1 Many S. Pneumonia, Bilateral perihilar pneumoniae respiratory infiltration with syncytial virus bronchial wall thickening fever fever fever, cough, wheezing cough, sputum, dyspnea, drowsy mental status cough, rhinorrhea fever, cough, sputum, rhinorrhea fever, cough, sputum, rhinorrhea cough, sputum, rhinorrhea fever, cough, rhinorrhea cough, sputum, rhinorrhea, wheezing fever, cough, vomiting cough fever, cough fever, cough, rhinorrhea, wheezing

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30 그림 3. 바이러스메타지놈내의바이러스군집구성요약 표 5. 바이러스메타지놈에서확인된 7종바이러스외 other viruses & phages virus name reads Torque teno virus 1306 Choristoneura occidentalis granulovirus 755 WU Polyomavirus 539 Simbu virus segment L 472 Iodobacteriophage phiplpe 130 Shamonda virus segment S 90 Herpesvirus 36 Erwinia phage 31 Burkholderia phage 30 Propionibacterium phage 29 Chlamydia phage 26 Pseudomonas phage 25 Stenotrophomonas phage S1 22 Bocavirus 22 Propionibacterium phage PA6 18 Murine osteosarcoma virus 17 Streptococcus phage Haemophilus phage HP2 16 Staphylococcus phage SAP Stenotrophomonas phage 15 Circovirus-like genome RW-E 13 Enterobacteria phage P1 13 Propionibacterium phage PA

31 Actinomyces phage Av-1 10 Enterococcus phage phifl3a 10 Streptococcus phage 8 Bdellovibrio phage phimh2k 6 Rhodococcus phage REQ2 6 Ostreococcus tauri virus 1 5 Mycobacterium phage 5 Pseudomonas phage vb_paes_pmg1 5 Small anellovirus 4 Salmonella phage vb_soss_oslo 4 Staphylococcus phage SAP-26 4 Amsacta moorei entomopoxvirus 3 Ectocarpus siliculosus virus 1 3 Paramecium bursaria Chlorella virus FR483 3 Bordetella phage BIP-1 3 Enterobacteria phage RB16 3 Escherichia phage vb_ecop_g7c 3 Lactococcus phage Lactococcus phage TP Roseobacter phage SIO1 3 Synechococcus phage 3 Xanthomonas phage OP2 3 Enterovirus 2 Avian sapelovirus 2 Emiliania huxleyi virus 2 Melanoplus sanguinipes entomopoxvirus 2 Oryctes rhinoceros 2 Brochothrix phage BL3 2 Burkholderia phage 2 Lactobacillus phage LP65 2 Listeria phage A006 2 Micromonas sp. RCC1109 virus MpV1 2 Roseophage 1 Astrovirus 1 Rotavirus 1 Abelson murine leukemia virus 1 Acanthamoeba polyphaga mimivirus 1 Camelpox virus 1 Cotesia congregata virus 1 Deerpox virus W Lumpy skin disease virus NI Marseillevirus 1 Megavirus chiliensis 1 Reticuloendotheliosis virus

32 Sinorhizobium phage PBC5 1 Spodoptera litura nucleopolyhedrovirus II 1 Squirrel monkey retrovirus 1 Taterapox virus 1 Woolly monkey sarcoma virus 1 Yoka poxvirus 1 Bacillus prophage phbc6a52 1 Microbacterium phage Min1 1 Tsukamurella phage TPA2 1 Xanthomonas phage Cf1c

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48 β Genome size 2,220,021bp GC ratio 42.06% Number of plasmids 0 Number of contigs 175 Number of scaffolds 156 Number of rrna genes 2 Number of trna genes 37 Number of ORFs 2,441 Method Illumina_MiSeq_PE_250 Method reads Method coverage

COG Description Genes % J Translation, ribosomal structure and biogenesis 146 10.06% K Transcription 60 4.14% L Replication, recombination and repair 109 7.

49 COG Description Genes % J Translation, ribosomal structure and biogenesis % K Transcription % L Replication, recombination and repair % D Cell cycle control, cell division, chromosome % partitioning O Posttranslational modification, protein turnover, % chaperones M Cell wall/membrane/envelope biogenesis % N Cell motility % P Inorganic ion transport and metabolism % T Signal transduction mechanisms % C Energy production and conversion % G Carbohydrate transport and metabolism % E Amino acid transport and metabolism % F Nucleotide transport and metabolism % H Coenzyme transport and metabolism % I Lipid transport and metabolism % Q Secondary metabolites biosynthesis, transport and % catabolism R General function prediction only % S Function unknown % Total %

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¼Û±âÇõ 223 Table 1. Results of FEV 1.0, Methacholine Challenge Test, and Exercise Provocation Test in Eight Patients Who Performed PFT Pts Tests 1 2 3 4 5 6 7 8 FEV 1.0 (%pred) 66.6 88.8 120 101 90.5 95.4 91.6