{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:35:44Z","timestamp":1781710544917,"version":"3.54.5"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Onset of wheeze is the endpoint often used in the determination of a positive bronchial challenge test (BCT) in young children who cannot perform spirometry. We sought to assess several clinical endpoints at the time of a positive BCT in young children with recurrent wheeze compared to findings in school\u2010aged children with asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Positive BCT was defined in: (1) preschool children (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a022) as either persistent cough, wheeze, fall in oxygen saturation (SpO\n                      <jats:sub>2<\/jats:sub>\n                      ) of \u22655%, or \u226550% increase in respiratory rate (RR) from baseline; and (2) school\u2010aged children (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a022) as the concentration of methacholine (MCh) required to elicit a 20% decline in FEV\n                      <jats:sub>1<\/jats:sub>\n                      (PC\n                      <jats:sub>20<\/jats:sub>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All preschool children (mean age 3.4\u00a0years) had a positive BCT (median provocative MCh concentration 1.25\u00a0mg\/ml [IQR, 0.62, 1.25]). Twenty (91%) school\u2010aged children (mean age 11.3\u00a0years) had a positive BCT (median PC\n                      <jats:sub>20<\/jats:sub>\n                      1.25\u00a0mg\/ml [IQR, 0.55, 2.5]). At the time of the positive BCT, the mean fall in SpO\n                      <jats:sub>2<\/jats:sub>\n                      (6.9% vs. 3.8%;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.001) and the mean % increase in RR (61% vs. 22%;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.001) were greater among preschool\u2010aged than among school\u2010aged children. A minority of children developed wheeze at time of positive BCT (23% preschool\u2010 vs. 15% school\u2010aged children;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.5).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The use of wheeze as an endpoint for BCT in preschool children is unreliable, as it rarely occurs. The use of clinical endpoints, such as \u226525% increase in RR or fall in SpO\n                      <jats:sub>2<\/jats:sub>\n                      of \u22653%, captured all of our positive BCT in preschool children, while minimizing undue respiratory distress.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.13767","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T09:54:53Z","timestamp":1649152493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Wheeze is an unreliable endpoint for bronchial methacholine challenges in preschool children"],"prefix":"10.1111","volume":"33","author":[{"given":"Lora","family":"Stewart","sequence":"first","affiliation":[{"name":"Divisions of Allergy\u2010Clinical Immunology and Clinical Pharmacology National Jewish Health  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Miyazawa","sequence":"additional","affiliation":[{"name":"Divisions of Allergy\u2010Clinical Immunology and Clinical Pharmacology National Jewish Health  Denver Colorado USA"},{"name":"Department of Pediatrics National Jewish Health  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronina","family":"Covar","sequence":"additional","affiliation":[{"name":"Divisions of Allergy\u2010Clinical Immunology and Clinical Pharmacology National Jewish Health  Denver Colorado USA"},{"name":"Department of Pediatrics National Jewish Health  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Mjaanes","sequence":"additional","affiliation":[{"name":"Divisions of Allergy\u2010Clinical Immunology and Clinical Pharmacology National Jewish Health  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed","family":"Shimamoto","sequence":"additional","affiliation":[{"name":"Divisions of Allergy\u2010Clinical Immunology and Clinical Pharmacology National Jewish Health  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Gleason","sequence":"additional","affiliation":[{"name":"Divisions of Allergy\u2010Clinical Immunology and Clinical Pharmacology National Jewish Health  Denver Colorado USA"},{"name":"Department of Pediatrics National Jewish Health  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Peroni","sequence":"additional","affiliation":[{"name":"Section of Pediatrics Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Spahn","sequence":"additional","affiliation":[{"name":"Divisions of Allergy\u2010Clinical Immunology and Clinical Pharmacology National Jewish Health  Denver Colorado USA"},{"name":"Department of Pediatrics National Jewish Health  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5209-9733","authenticated-orcid":false,"given":"Pasquale","family":"Comberiati","sequence":"additional","affiliation":[{"name":"Section of Pediatrics Department of Clinical and Experimental Medicine University of Pisa  Pisa 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