PMID- 35713619
OWN - NLM
STAT- MEDLINE
DCOM- 20221103
LR  - 20230502
IS  - 2325-6621 (Electronic)
IS  - 2329-6933 (Print)
IS  - 2325-6621 (Linking)
VI  - 19
IP  - 11
DP  - 2022 Nov
TI  - Acute Pulmonary Exacerbation Phenotypes in Patients with Cystic Fibrosis.
PG  - 1818-1826
LID - 10.1513/AnnalsATS.202111-1266OC [doi]
AB  - Rationale: The etiology of cystic fibrosis (CF) pulmonary exacerbations (PEx) is 
      likely multifactorial with viral, bacterial, and non-infectious pathways 
      contributing. Objectives: To determine whether viral infection status and CRP 
      (C-reactive protein) can classify subphenotypes of PEx that differ in outcomes 
      and biomarker profiles. Methods: Patients were recruited at time of admission for 
      a PEx. Nasal swabs and sputum samples were collected and processed using the 
      respiratory panel of the FilmArray multiplex polymerase chain reaction (PCR). 
      Serum and plasma biomarkers were measured. PEx were classified using serum CRP 
      and viral PCR: "pauci-inflammatory" if CRP < 5 mg/L, "non-viral with systemic 
      inflammation" if CRP ⩾ 5 mg/L and no viral infection detected by PCR and "viral 
      with systemic inflammation" if CRP ⩾ 5 mg/L and viral infection detected by PCR. 
      Results: Discovery cohort (n = 59) subphenotype frequencies were 1) 
      pauci-inflammatory (37%); 2) non-viral with systemic inflammation (41%); and 3) 
      viral with systemic inflammation (22%). Immunoglobulin G, immunoglobulin M, 
      interleukin-10, interleukin-13, serum calprotectin, and CRP levels differed 
      across phenotypes. Reduction from baseline in forced expiratory volume in 1 
      second as percent predicted (FEV(1)pp) at onset of exacerbation differed between 
      non-viral with systemic inflammation and viral with systemic inflammation 
      (-6.73 +/- 1.78 vs. -13.5 +/- 2.32%; P = 0.025). Non-viral with systemic inflammation 
      PEx had a trend toward longer duration of intravenous antibiotics versus 
      pauci-inflammation (18.1 +/- 1.17 vs. 14.8 +/- 1.19 days, P = 0.057). There were no 
      differences in percent with lung function recovery to <10% of baseline FEV(1)pp. 
      Similar results were seen in local and external validation cohorts comparing a 
      pauci-inflammatory to viral/non-viral inflammatory exacerbation phenotypes. 
      Conclusions: Subphenotypes of CF PEx exist with differences in biomarker profile, 
      clinical presentation, and outcomes.
FAU - Carter, Suzanne C
AU  - Carter SC
AD  - National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University 
      Hospital, Dublin, Ireland.
AD  - University College Dublin School of Medicine, Dublin, Ireland.
FAU - Franciosi, Alessandro N
AU  - Franciosi AN
AUID- ORCID: 0000-0002-4241-8718
AD  - Department of Medicine, University of British Columbia, Vancouver, British 
      Columbia, Canada.
FAU - O'Shea, Kate M
AU  - O'Shea KM
AD  - University College Dublin School of Medicine, Dublin, Ireland.
FAU - O'Carroll, Orla M
AU  - O'Carroll OM
AD  - National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University 
      Hospital, Dublin, Ireland.
FAU - Sharma, Ashutosh
AU  - Sharma A
AD  - Department of Medicine, University of British Columbia, Vancouver, British 
      Columbia, Canada.
FAU - Bell, Aoife
AU  - Bell A
AD  - University College Dublin School of Medicine, Dublin, Ireland.
FAU - Keogan, Brian
AU  - Keogan B
AD  - National Virus Reference Laboratory, University College Dublin, Dublin, Ireland.
FAU - O'Reilly, Paul
AU  - O'Reilly P
AD  - National Virus Reference Laboratory, University College Dublin, Dublin, Ireland.
FAU - Coughlan, Suzie
AU  - Coughlan S
AD  - National Virus Reference Laboratory, University College Dublin, Dublin, Ireland.
FAU - Law, Sheonagh M
AU  - Law SM
AD  - Centre for Inflammation Research, University of Edinburgh, Edinburgh, Scotland.
FAU - Gray, Robert D
AU  - Gray RD
AD  - Centre for Inflammation Research, University of Edinburgh, Edinburgh, Scotland.
FAU - Hisert, Katherine B
AU  - Hisert KB
AD  - Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, 
      National Jewish Health, Denver, Colorado.
AD  - University of Washington, Seattle, Washington; and.
FAU - Singh, Pradeep K
AU  - Singh PK
AD  - University of Washington, Seattle, Washington; and.
FAU - Cooke, Gordon
AU  - Cooke G
AD  - University College Dublin School of Medicine, Dublin, Ireland.
AD  - Technological University Dublin, Dublin, Ireland.
FAU - Grogan, Brenda
AU  - Grogan B
AD  - National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University 
      Hospital, Dublin, Ireland.
FAU - De Gascun, Cillian F
AU  - De Gascun CF
AD  - National Virus Reference Laboratory, University College Dublin, Dublin, Ireland.
FAU - Gallagher, Charles G
AU  - Gallagher CG
AD  - National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University 
      Hospital, Dublin, Ireland.
AD  - University College Dublin School of Medicine, Dublin, Ireland.
FAU - Nicholson, Trevor T
AU  - Nicholson TT
AUID- ORCID: 0000-0003-3187-1493
AD  - National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University 
      Hospital, Dublin, Ireland.
FAU - Quon, Bradley S
AU  - Quon BS
AD  - Department of Medicine, University of British Columbia, Vancouver, British 
      Columbia, Canada.
FAU - McKone, Edward F
AU  - McKone EF
AUID- ORCID: 0000-0002-5455-8208
AD  - National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University 
      Hospital, Dublin, Ireland.
AD  - University College Dublin School of Medicine, Dublin, Ireland.
LA  - eng
GR  - SCAF/16/02/CSO_/Chief Scientist Office/United Kingdom
GR  - 201,246/Z/16/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Am Thorac Soc
JT  - Annals of the American Thoracic Society
JID - 101600811
RN  - 9007-41-4 (C-Reactive Protein)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Biomarkers)
SB  - IM
CIN - Ann Am Thorac Soc. 2022 Nov;19(11):1799-1801. PMID: 36318079
MH  - Humans
MH  - *Cystic Fibrosis
MH  - Lung
MH  - C-Reactive Protein/metabolism
MH  - Anti-Bacterial Agents/therapeutic use
MH  - Biomarkers
MH  - Inflammation/drug therapy
MH  - Phenotype
MH  - Disease Progression
PMC - PMC9667812
OTO - NOTNLM
OT  - cystic fibrosis
OT  - exacerbation
OT  - pauci-inflammatory
OT  - phenotype
OT  - viral infection
EDAT- 2022/06/18 06:00
MHDA- 2022/11/04 06:00
PMCR- 2023/05/01
CRDT- 2022/06/17 10:43
PHST- 2022/06/18 06:00 [pubmed]
PHST- 2022/11/04 06:00 [medline]
PHST- 2022/06/17 10:43 [entrez]
PHST- 2023/05/01 00:00 [pmc-release]
AID - 10.1513/AnnalsATS.202111-1266OC [doi]
PST - ppublish
SO  - Ann Am Thorac Soc. 2022 Nov;19(11):1818-1826. doi: 
      10.1513/AnnalsATS.202111-1266OC.