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Proof of Concept: Very Rapid Tidal Breathing Nasal Nitric Oxide Sampling Discriminates Primary Ciliary Dyskinesia from Healthy Subjects

Introduction Nasal nitric oxide (nNO) is extremely low in individuals with primary ciliary dyskinesia (PCD) and is recommended as part of early workup. We investigated whether tidal breathing sampling for a few seconds was as discriminative between PCD and healthy controls (HC) as conventional tidal...

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Published in:Lung 2019-04, Vol.197 (2), p.209-216
Main Authors: Holgersen, Mathias G., Marthin, June K., Nielsen, Kim G.
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description Introduction Nasal nitric oxide (nNO) is extremely low in individuals with primary ciliary dyskinesia (PCD) and is recommended as part of early workup. We investigated whether tidal breathing sampling for a few seconds was as discriminative between PCD and healthy controls (HC) as conventional tidal breathing sampling (cTB-nNO) for 20–30 s. Methods We performed very rapid sampling of tidal breathing (vrTB-nNO) for 2, 4 and 6 s, respectively. Vacuum sampling with applied negative pressure (vrTB-nNO vac ; negative pressure was applied by pinching the sampling tube) for
doi_str_mv 10.1007/s00408-019-00202-x
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We investigated whether tidal breathing sampling for a few seconds was as discriminative between PCD and healthy controls (HC) as conventional tidal breathing sampling (cTB-nNO) for 20–30 s. Methods We performed very rapid sampling of tidal breathing (vrTB-nNO) for 2, 4 and 6 s, respectively. Vacuum sampling with applied negative pressure (vrTB-nNO vac ; negative pressure was applied by pinching the sampling tube) for &lt; 2 s resulted in enhanced suction of nasal air during measurement. Feasibility, success rate, discriminatory capacity, repeatability and agreement were assessed for all four sampling modalities. Results We included 13 patients with PCD, median (IQR) age of 21.8 (12.2–27.7) years and 17 HC, 25.3 (14.5–33.4) years. Measurements were highly feasible (96.7% success rate). Measured NO values with vrTB-nNO modalities differed significantly from TB-nNO measurements (HC: p  &lt; 0.001, PCD: p  &lt; 0.05). All modalities showed excellent discrimination. The vacuum method gave remarkably high values of nNO in both groups (1865 vs. 86 ppb), but retained excellent discrimination. vrTB-nNO 4sec , vrTB-nNO 6sec and vrTB-nNO vac showed identical specificity to cTB-nNO (all: 1.0, 95% CI 0.77–1.0). Conclusion vrTB-nNO sampling requires only a few seconds of probe-in-nose time, is feasible, and provides excellent discrimination between PCD and HC. Rapid TB-nNO sampling needs standardisation and further investigations in infants, young children and patients referred for PCD workup.</description><identifier>ISSN: 0341-2040</identifier><identifier>EISSN: 1432-1750</identifier><identifier>DOI: 10.1007/s00408-019-00202-x</identifier><identifier>PMID: 30762092</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adolescent ; Adult ; Aged ; Airway Biology ; Biomarkers - metabolism ; Breath Tests ; Breathing ; Case-Control Studies ; Child ; Children ; Ciliary Motility Disorders - diagnosis ; Ciliary Motility Disorders - metabolism ; Ciliary Motility Disorders - physiopathology ; Diagnosis ; Feasibility Studies ; Female ; Humans ; Infants ; Male ; Medicine ; Medicine &amp; Public Health ; Middle Aged ; Movement disorders ; Nitric oxide ; Nitric Oxide - metabolism ; Nose ; Patients ; Pneumology/Respiratory System ; Predictive Value of Tests ; Pressure ; Primary ciliary dyskinesia ; Proof of Concept Study ; Reproducibility of Results ; Respiration ; Risk factors ; Sampling ; Suction ; Time Factors ; Vacuum ; Young Adult</subject><ispartof>Lung, 2019-04, Vol.197 (2), p.209-216</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>COPYRIGHT 2019 Springer</rights><rights>Lung is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-dd814b20713137540f159f701651389cb8e738aaef016f092fbed0a6ed7d44f63</citedby><cites>FETCH-LOGICAL-c511t-dd814b20713137540f159f701651389cb8e738aaef016f092fbed0a6ed7d44f63</cites><orcidid>0000-0001-9944-6253 ; 0000-0002-4420-3091 ; 0000-0001-5906-9449</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30762092$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Holgersen, Mathias G.</creatorcontrib><creatorcontrib>Marthin, June K.</creatorcontrib><creatorcontrib>Nielsen, Kim G.</creatorcontrib><title>Proof of Concept: Very Rapid Tidal Breathing Nasal Nitric Oxide Sampling Discriminates Primary Ciliary Dyskinesia from Healthy Subjects</title><title>Lung</title><addtitle>Lung</addtitle><addtitle>Lung</addtitle><description>Introduction Nasal nitric oxide (nNO) is extremely low in individuals with primary ciliary dyskinesia (PCD) and is recommended as part of early workup. We investigated whether tidal breathing sampling for a few seconds was as discriminative between PCD and healthy controls (HC) as conventional tidal breathing sampling (cTB-nNO) for 20–30 s. Methods We performed very rapid sampling of tidal breathing (vrTB-nNO) for 2, 4 and 6 s, respectively. Vacuum sampling with applied negative pressure (vrTB-nNO vac ; negative pressure was applied by pinching the sampling tube) for &lt; 2 s resulted in enhanced suction of nasal air during measurement. Feasibility, success rate, discriminatory capacity, repeatability and agreement were assessed for all four sampling modalities. Results We included 13 patients with PCD, median (IQR) age of 21.8 (12.2–27.7) years and 17 HC, 25.3 (14.5–33.4) years. Measurements were highly feasible (96.7% success rate). Measured NO values with vrTB-nNO modalities differed significantly from TB-nNO measurements (HC: p  &lt; 0.001, PCD: p  &lt; 0.05). All modalities showed excellent discrimination. The vacuum method gave remarkably high values of nNO in both groups (1865 vs. 86 ppb), but retained excellent discrimination. vrTB-nNO 4sec , vrTB-nNO 6sec and vrTB-nNO vac showed identical specificity to cTB-nNO (all: 1.0, 95% CI 0.77–1.0). Conclusion vrTB-nNO sampling requires only a few seconds of probe-in-nose time, is feasible, and provides excellent discrimination between PCD and HC. Rapid TB-nNO sampling needs standardisation and further investigations in infants, young children and patients referred for PCD workup.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Airway Biology</subject><subject>Biomarkers - metabolism</subject><subject>Breath Tests</subject><subject>Breathing</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Children</subject><subject>Ciliary Motility Disorders - diagnosis</subject><subject>Ciliary Motility Disorders - metabolism</subject><subject>Ciliary Motility Disorders - physiopathology</subject><subject>Diagnosis</subject><subject>Feasibility Studies</subject><subject>Female</subject><subject>Humans</subject><subject>Infants</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Middle Aged</subject><subject>Movement disorders</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nose</subject><subject>Patients</subject><subject>Pneumology/Respiratory System</subject><subject>Predictive Value of Tests</subject><subject>Pressure</subject><subject>Primary ciliary dyskinesia</subject><subject>Proof of Concept Study</subject><subject>Reproducibility of Results</subject><subject>Respiration</subject><subject>Risk factors</subject><subject>Sampling</subject><subject>Suction</subject><subject>Time Factors</subject><subject>Vacuum</subject><subject>Young Adult</subject><issn>0341-2040</issn><issn>1432-1750</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kttu1DAQhi0EokvhBbhAlpAQNylj5-CEu7IFilS1FS3cWt5kvOslsVM7kXafgNfG2xRK0QrZ8mH8zWg88xPyksERAxDvAkAGZQKsSgA48GTziMxYlvKEiRwekxmkGUt4hA7IsxDWAEwULH9KDlIQBYeKz8jPS--cpnHOna2xH97T7-i39KvqTUOvTaNa-sGjGlbGLum5CvF-bgZvanqxMQ3SK9X17e7txITam85YNWCgl_GoYpy5ac1uP9mGH8ZiMIpq7zp6iqodVlt6NS7WWA_hOXmiVRvwxd1-SL59-ng9P03OLj5_mR-fJXXO2JA0TcmyBQfBUpaKPAPN8koLYEXO0rKqFyWKtFQKdTTp-EO9wAZUgY1oskwX6SF5O8XtvbsZMQyyi3lj2yqLbgySc1YIEdcqoq__Qddu9DZmJzkrgcdMiuKeWqoWpbHaDV7Vu6DyOC_TMoudEpFK9lBLtOhV6yxqE80P-KM9fBwNdqbe6_DmL4fVbXWDa8fBOBsegnwCa-9C8KhlP7VKMpA7WclJVjLKSt7KSm6i06u7UoyLDps_Lr91FIF0AkJ8skv097X6T9hfqi3VkQ</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Holgersen, Mathias G.</creator><creator>Marthin, June K.</creator><creator>Nielsen, Kim G.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9944-6253</orcidid><orcidid>https://orcid.org/0000-0002-4420-3091</orcidid><orcidid>https://orcid.org/0000-0001-5906-9449</orcidid></search><sort><creationdate>20190401</creationdate><title>Proof of Concept: Very Rapid Tidal Breathing Nasal Nitric Oxide Sampling Discriminates Primary Ciliary Dyskinesia from Healthy Subjects</title><author>Holgersen, Mathias G. ; 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Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Lung</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Holgersen, Mathias G.</au><au>Marthin, June K.</au><au>Nielsen, Kim G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proof of Concept: Very Rapid Tidal Breathing Nasal Nitric Oxide Sampling Discriminates Primary Ciliary Dyskinesia from Healthy Subjects</atitle><jtitle>Lung</jtitle><stitle>Lung</stitle><addtitle>Lung</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>197</volume><issue>2</issue><spage>209</spage><epage>216</epage><pages>209-216</pages><issn>0341-2040</issn><eissn>1432-1750</eissn><abstract>Introduction Nasal nitric oxide (nNO) is extremely low in individuals with primary ciliary dyskinesia (PCD) and is recommended as part of early workup. We investigated whether tidal breathing sampling for a few seconds was as discriminative between PCD and healthy controls (HC) as conventional tidal breathing sampling (cTB-nNO) for 20–30 s. Methods We performed very rapid sampling of tidal breathing (vrTB-nNO) for 2, 4 and 6 s, respectively. Vacuum sampling with applied negative pressure (vrTB-nNO vac ; negative pressure was applied by pinching the sampling tube) for &lt; 2 s resulted in enhanced suction of nasal air during measurement. Feasibility, success rate, discriminatory capacity, repeatability and agreement were assessed for all four sampling modalities. Results We included 13 patients with PCD, median (IQR) age of 21.8 (12.2–27.7) years and 17 HC, 25.3 (14.5–33.4) years. Measurements were highly feasible (96.7% success rate). Measured NO values with vrTB-nNO modalities differed significantly from TB-nNO measurements (HC: p  &lt; 0.001, PCD: p  &lt; 0.05). All modalities showed excellent discrimination. 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subjects Adolescent
Adult
Aged
Airway Biology
Biomarkers - metabolism
Breath Tests
Breathing
Case-Control Studies
Child
Children
Ciliary Motility Disorders - diagnosis
Ciliary Motility Disorders - metabolism
Ciliary Motility Disorders - physiopathology
Diagnosis
Feasibility Studies
Female
Humans
Infants
Male
Medicine
Medicine & Public Health
Middle Aged
Movement disorders
Nitric oxide
Nitric Oxide - metabolism
Nose
Patients
Pneumology/Respiratory System
Predictive Value of Tests
Pressure
Primary ciliary dyskinesia
Proof of Concept Study
Reproducibility of Results
Respiration
Risk factors
Sampling
Suction
Time Factors
Vacuum
Young Adult
title Proof of Concept: Very Rapid Tidal Breathing Nasal Nitric Oxide Sampling Discriminates Primary Ciliary Dyskinesia from Healthy Subjects
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