Evidence map›Paper›PMID 35451201›Full record

ArticlePediatric pulmonology2022

DNA sequencing analysis of cystic fibrosis transmembrane conductance regulator gene identifies cystic fibrosis-associated variants in the Severe Asthma Research Program.

Manuel E Izquierdo, Chad R Marion, Wendy C Moore, Karen S Raraigh, Jennifer L Taylor-Cousar, Gary R Cutting, E Ampleford, Gregory A Hawkins, Joe Zein, M Castro and 12 more

Open access · greenAbstract readLetter
In one paragraph

Article in Pediatric pulmonology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Article
  3. Asthma and respiratory comorbidities.The Journal of allergy and clinical immunology · 2025
    Review
  4. CFTR heterozygosity in severe asthma with recurrent airway infections: a retrospective review.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2022
    Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 14 institutions in 1 country.

Manuel E IzquierdoWake Forest Baptist Medical Center, Winston Salem, North Carolina, USA.
Chad R MarionDepartment of Internal Medicine, Wake Forest University, Winston Salem, North Carolina, USA.ORCID 0000-0002-7923-0890
Wendy C MooreWake Forest Sch of Med, Winston-Salem, North Carolina, USA.
Karen S RaraighJohns Hopkins, Baltimore, Maryland, USA.ORCID 0000-0001-6730-6854
Jennifer L Taylor-CousarDepartment of Medicine and Pediatrics, National Jewish Health, Denver, Colorado, USA.ORCID 0000-0002-5436-9722
Gary R CuttingInstitute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, USA.ORCID 0000-0002-8250-8590
E AmplefordDepartment of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Gregory A HawkinsCenter for Precision Medicine, Wake Forest Baptist Health, Winston Salem, North Carolina, USA.
Joe ZeinDepartments of Inflammation and Immunity, Cleveland Clinic, Cleveland, Ohio, USA.
M CastroPulmonary Critical Care & Sleep Medicine, University of Kansas, Kansas City, Missouri, USA.ORCID 0000-0001-6328-8994
Loren C DenlingerDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Serpil C ErzurumCleveland Clinic Foundation, Cleveland, Ohio, USA.
John V FahyPulmonary and Critical Care Medicine, University of California At San Francisco, San Francisco, California, USA.ORCID 0000-0001-5427-9308
Elliot IsraelBrigham and Womens Hospital, Boston, Massachusetts, USA.
Nizar N JarjourUniversity of Wisconsin Hospitals & Clinics, Madison, Wisconsin, USA.
David MaugerPennsylvania State University, Pennsylvania, USA.
Bruce D LevyBrigham and Womens Hospital, Boston, Massachusetts, USA.
Sally E WenzelMedicine PACCM, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Prescott WoodruffDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Eugene R BleeckerDepartment of Medicine, University of Arizona, Tucson, Arizona, USA.
Deborah A MeyersDepartment of Genetics, Genomics, and Precision Medicine, University of Arizona, Tucson, Arizona, USA.
Victor E OrtegaMayo Clinic, Scottsdale, Arizona, USA.
Wake Forest University · USAtrium Health Wake Forest Baptist · USBrigham and Women's Hospital · USCleveland Clinic · USJohns Hopkins University · USUniversity of Arizona · USUniversity of California, San Francisco · USMayo Clinic in Arizona · USNational Jewish Health · USPennsylvania State University · USUniversity of Kansas · USUniversity of Pittsburgh · USUniversity of Wisconsin–Madison · USUW Health University Hospital · US

Funding

Rapid saliva antigen test for SARS-CoV-2 detectionU01HL146002 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ARONICA, MARK A, CASTRO, MARIO · 2019 to 2023
$17.3M
Severe Asthma Research ProjectR01HL069174 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WENZEL, SALLY E · 2001 to 2010
$9.2M
Clinical Coordinating Center for the Severe Asthma Research Program (SARP)U10HL109086 · NHLBI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI MAUGER, DAVID T. · 2011 to 2017
$8.1M
Severe Asthma From Respiratory InfectionsR01HL069116 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI BUSSE, WILLIAM W. · 2001 to 2010
$7.6M
Non-coding RNA structure change in Chronic Obstructive Pulmonary DiseaseR01HL111527 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Alain T Laederach, Kevin M Weeks · 2012 to 2026
$6.6M
Genotype-Phenotype Interactions in Severe AsthmaR01HL069167 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BLEECKER, EUGENE ROLAND · 2001 to 2010
$5.5M
Redox Determinants of Severe AsthmaR01HL069170 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI ERZURUM, SERPIL C. · 2001 to 2010
$5.1M
AMSA: ALXR/FBR Mediated Signaling in Severe AsthmaU10HL109172 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ISRAEL, ELLIOT, LEVY, BRUCE D · 2011 to 2016
$4.2M
Airway redox biochemistry as a deteriminant of asthma phenotype during adolescen*U10HL109250 · NHLBI · UNIVERSITY OF VIRGINIA · PI ERZURUM, SERPIL C., GASTON, BENJAMIN · 2011 to 2016
$4.2M
Clinical and Molecular Phenotypes of Severe AsthmaU10HL109146 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FAHY, JOHN V · 2011 to 2016
$4.0M
Implications and Stability of Clinical and Molecular Phenotypes of Severe AsthmaU10HL109152 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WENZEL, SALLY E · 2011 to 2016
$3.9M
Stability of Severe Asthma Phenotypes: Impact of ExacerbationsU10HL109168 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI JARJOUR, NIZAR N · 2011 to 2016
$3.9M
NHLBI NIH HHS R01 HL069116NHLBI NIH HHS R01 HL069167NHLBI NIH HHS R01 HL069170NHLBI NIH HHS R01 HL069174NHLBI NIH HHS R01 HL111527NHLBI NIH HHS R01 HL142992NHLBI NIH HHS U01 HL146002NHLBI NIH HHS U10 HL109086NHLBI NIH HHS U10 HL109146NHLBI NIH HHS U10 HL109152NHLBI NIH HHS U10 HL109164NHLBI NIH HHS U10 HL109168NHLBI NIH HHS U10 HL109172NHLBI NIH HHS U10 HL109250NHLBI NIH HHS U10 HL109257
6 · The paper itself

Abstract

backgroundHeterozygote carriers of potentially pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have increased asthma risk. However, the frequency and impact of CFTR variation among individuals with asthma is unknown.

objectiveTo determine whether potentially pathogenic CFTR variants associate with disease severity and whether individuals with two potentially pathogenic variants exist in a severe asthma-enriched cohort.

methodsWe analyzed sequencing data spanning a 190.5Kb region of CFTR in participants from the Severe Asthma Research Program (SARP1-3). Potentially pathogenic, rare CFTR variants (frequency < 0.05) were classified as CF-causing or of varying clinical consequences (VVCC) (CFTR2. org). Regression-based models tested for association between CFTR genotypes (0-2 potentially pathogenic variants) and severity outcomes.

resultsOf 1401 participants, 9.5% (134) had one potentially pathogenic variant, occurring more frequently in non-Hispanic white (NHW, 10.1% [84 of 831]) compared to African American individuals (AA, 5.2% [22 of 426]). We found ≥2 potentially pathogenic CFTR variants in 1.4% (19); 0.5% (4) of NHW and 2.8% (12) of AA. Potentially pathogenic CFTR variant genotypes (≥1 or ≥2 variants) were not cumulatively associated with lung function or exacerbations. In NHW, we found three F508del compound heterozygotes with F508del and a VVCC (two 5 T; TG12[c.1210-11 T > G] and one Arg1070Trp) and a homozygote for the VVCC, 5 T; TG12.

conclusionsWe found potentially pathogenic CFTR variants within a severe asthma-enriched cohort, including three compound heterozygote genotypes variably associated with CF in NHW individuals. These findings provide the rationale for CFTR sequencing and phenotyping of CF-related traits in individuals with severe asthma.

Indexed as

AsthmaCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHumansMutationSequence Analysis, DNACFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorAsthmaCF-Asthma OverlapCFTRcystic fibrosisheterozygote carriers

Identifiers

PMID35451201
PMCPMC9443928
OpenAlexW4224212299

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.