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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Evidence reviews for bronchial challenge test with mannitol - NCBI Bookshelf</title>
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<meta name="citation_keywords" content="Bronchial Provocation Tests">
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<meta name="citation_keywords" content="Mannitol">
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class="bkr_bib"><h1 id="_NBK611960_"><span itemprop="name">Evidence reviews for bronchial challenge test with mannitol</span></h1><div class="subtitle">Asthma: diagnosis, monitoring and chronic asthma management (update)</div><p><b>Evidence review I</b></p><p><i>NICE Guideline, No. 245</i></p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2024 Nov</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-6622-6</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © BTS, NICE and SIGN 2024.</div></div><div class="bkr_clear"></div></div><div id="niceng245er9.s1"><h2 id="_niceng245er9_s1_">1. Bronchial challenge testing with mannitol</h2><div id="niceng245er9.s1.1"><h3>1.1. Review question</h3><p>In people under investigation for asthma, what is the diagnostic test accuracy and clinical and cost-effectiveness of bronchial challenge testing (indirect) with mannitol?</p><div id="niceng245er9.s1.1.1"><h4>1.1.1. Introduction</h4><p>Bronchial hyper-responsiveness (BHR) is a key characteristic of asthma, and measurement of this via bronchial challenge testing should be helpful in making the diagnosis. Bronchial challenge tests are most often performed using histamine or methacholine which both act directly on airway smooth muscle. Mannitol acts indirectly by causing the release of endogenous mediators which in turn stimulate airway smooth muscle, and it has been suggested that this is a better method of diagnostic testing for BHR since it is a closer mimic of the pathophysiological process of asthma. This review was therefore performed to explore the value of mannitol bronchial challenge as a test for asthma.</p></div><div id="niceng245er9.s1.1.2"><h4>1.1.2. Summary of the protocol</h4><p>For full details see the review protocol in <a href="#niceng245er9.appa">Appendix A</a>.</p><p>No test-and-treat evidence was found so only the diagnostic accuracy evidence was reported.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng245er9tab1"><a href="/books/NBK611960/table/niceng245er9.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img" rid-ob="figobniceng245er9tab1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng245er9.tab1"><a href="/books/NBK611960/table/niceng245er9.tab1/?report=objectonly" target="object" rid-ob="figobniceng245er9tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">PICO characteristics of diagnostic accuracy review question. </p></div></div></div><div id="niceng245er9.s1.1.3"><h4>1.1.3. Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>. Methods specific to this review question are described in the review protocol in <a href="#niceng245er9.appa">appendix A</a> and the <a href="/books/NBK611960/bin/NG245-methods.pdf">methods</a> document.</p><p>Declarations of interest were recorded according to <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE’s conflicts of interest policy</a>.</p></div><div id="niceng245er9.s1.1.4"><h4>1.1.4. Diagnostic evidence</h4><div id="niceng245er9.s1.1.4.1"><h5>1.1.4.1. Included studies</h5><p>Two cross-sectional studies were included in the review; (<a class="bibr" href="#niceng245er9.s1.ref1" rid="niceng245er9.s1.ref1">Anderson, et al., 2009</a>; <a class="bibr" href="#niceng245er9.s1.ref4" rid="niceng245er9.s1.ref4">Porpodis, et al., 2017</a>) these are summarised in <a href="/books/NBK611960/table/niceng245er9.tab2/?report=objectonly" target="object" rid-ob="figobniceng245er9tab2">Table 2</a> below. Evidence from these studies is summarised in the clinical evidence summary below in <a href="/books/NBK611960/table/niceng245er9.tab3/?report=objectonly" target="object" rid-ob="figobniceng245er9tab3">Table 3</a> and references in <a href="#niceng245er9.s1.rl.r1">1.3</a> References. The assessment of the evidence quality was conducted with emphasis on test sensitivity and specificity as this was identified by the committee as the primary measure in guiding decision-making. The committee set clinical decision thresholds as sensitivity: upper= 90% and lower= 10%, specificity: upper= 80% and lower= 50%. Values above the upper threshold indicated a test would be recommended and values below the lower threshold indicated a test is of no clinical use.</p><p>See also the study selection flow chart in <a href="#niceng245er9.appc">Appendix C</a>, sensitivity and specificity forest plots in <a href="#niceng245er9.appe">Appendix E</a>, and study evidence tables in <a href="#niceng245er9.appd">Appendix D</a>.</p></div><div id="niceng245er9.s1.1.4.2"><h5>1.1.4.2. Excluded studie</h5><p>See the excluded studies list in <a href="#niceng245er9.apph">Appendix H</a>.</p></div></div><div id="niceng245er9.s1.1.5"><h4>1.1.5. Summary of studies included in the diagnostic evidence</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng245er9tab2"><a href="/books/NBK611960/table/niceng245er9.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img" rid-ob="figobniceng245er9tab2"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng245er9.tab2"><a href="/books/NBK611960/table/niceng245er9.tab2/?report=objectonly" target="object" rid-ob="figobniceng245er9tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of studies included in the evidence review. </p></div></div><p>See <a href="#niceng245er9.appd">Appendix D</a> for full evidence tables.</p></div><div id="niceng245er9.s1.1.6"><h4>1.1.6. Summary of the diagnostic evidence</h4><p>The assessment of the evidence quality was conducted with emphasis on test sensitivity and specificity as this was identified by the committee as the primary measure in guiding decision-making. The committee set clinical decision thresholds as sensitivity: upper= 90% and lower= 10%, specificity: upper= 80% and lower= 50%. Values above the upper threshold indicated a test would be recommended and values below the lower threshold indicated a test is of no clinical use.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng245er9tab3"><a href="/books/NBK611960/table/niceng245er9.tab3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img" rid-ob="figobniceng245er9tab3"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng245er9.tab3"><a href="/books/NBK611960/table/niceng245er9.tab3/?report=objectonly" target="object" rid-ob="figobniceng245er9tab3">Table 3</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: bronchial challenge with mannitol vs clinician diagnosis of asthma in non-smoking adolescents/adults. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng245er9tab4"><a href="/books/NBK611960/table/niceng245er9.tab4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img" rid-ob="figobniceng245er9tab4"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng245er9.tab4"><a href="/books/NBK611960/table/niceng245er9.tab4/?report=objectonly" target="object" rid-ob="figobniceng245er9tab4">Table 4</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: bronchial challenge with mannitol vs clinician diagnosis of asthma in adolescents/adults with mixed smoking status. </p></div></div></div><div id="niceng245er9.s1.1.7"><h4>1.1.7. Economic evidence</h4><div id="niceng245er9.s1.1.7.1"><h5>1.1.7.1. Included studies</h5><p>No health economic studies were included.</p></div><div id="niceng245er9.s1.1.7.2"><h5>1.1.7.2. Excluded studies</h5><p>No relevant health economic studies were excluded due to assessment of limited applicability or methodological limitations.</p><p>See also the health economic study selection flow chart in <a href="#niceng245er9.appf">Appendix F</a>.</p></div></div><div id="niceng245er9.s1.1.8"><h4>1.1.8. Summary of included economic evidence</h4><p>None.</p></div><div id="niceng245er9.s1.1.9"><h4>1.1.9. Economic model</h4><p>A health economic model was conducted focusing on sequences and combinations of diagnostic tests. This is reported in Evidence review 1.11.</p></div><div id="niceng245er9.s1.1.10"><h4>1.1.10. Unit costs</h4><p>Relevant unit costs are provided below to aid consideration of cost effectiveness.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng245er9tab5"><a href="/books/NBK611960/table/niceng245er9.tab5/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img" rid-ob="figobniceng245er9tab5"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng245er9.tab5"><a href="/books/NBK611960/table/niceng245er9.tab5/?report=objectonly" target="object" rid-ob="figobniceng245er9tab5">Table 5</a></h4><p class="float-caption no_bottom_margin">Cost of a bronchial challenge test. </p></div></div></div><div id="niceng245er9.s1.1.11"><h4>1.1.11. Evidence statements</h4><div id="niceng245er9.s1.1.11.1"><h5>Economic</h5><ul><li class="half_rhythm"><div>No relevant economic evaluations were identified.</div></li></ul></div></div></div><div id="niceng245er9.s1.2"><h3>1.2. The committee’s discussion and interpretation of the evidence</h3><div id="niceng245er9.s1.2.1"><h4>1.2.1. The outcomes that matter most</h4><div id="niceng245er9.s1.2.1.1"><h5>Test and treat studies</h5><p>The outcomes considered for this review were: severe asthma exacerbations, mortality, quality of life, asthma control, hospital admissions, reliever/rescue medication use, lung function (change in FEV1 or morning PEF – average over at least 7 days for morning PEF), adverse events (linear growth, pneumonia frequency, adrenal insufficiency, bone mineral density), inflammatory markers; exhaled nitric oxide (continuous outcome at ≥8 weeks). For the purpose of decision making, all outcomes were considered equally important and were therefore rated as critical by the committee. No relevant evidence was identified for any of the outcomes.</p></div><div id="niceng245er9.s1.2.1.2"><h5>Diagnostic accuracy</h5><p>The committee considered the diagnostic measures of sensitivity and specificity of the index test for diagnosing asthma as well as the positive and negative predictive values where these were reported by the studies. Clinical decision thresholds were set by the committee as sensitivity/specificity 0.9 and 0.8 above which a test would be recommended and 0.1 and 0.5 below which a test is of no clinical use. The committee were interested in establishing whether there was an optimal cut-off value of bronchial challenge testing with mannitol with sufficiently high sensitivity and specificity to be useful in making a diagnosis of asthma, but also in whether there are separate cut-off values which could usefully help either rule in or rule out an asthma diagnosis.</p></div></div><div id="niceng245er9.s1.2.2"><h4>1.2.2. The quality of the evidence</h4><div id="niceng245er9.s1.2.2.1"><h5>Test and treat studies</h5><p>No relevant clinical studies were identified comparing the clinical effectiveness of diagnosis of asthma based on bronchial challenge with mannitol.</p></div><div id="niceng245er9.s1.2.2.2"><h5>Diagnostic accuracy</h5><p>Two cross-sectional studies were included in this review. One study was conducted in non-smoking participants, with the other containing a mixture of smoking and non-smoking participants. Both studies used the same cut-off, with a reduction in FEV<sub>1</sub> of ≥15% from baseline or ≥10% with consecutive doses using a provocative dose <635 mg being considered diagnostic of asthma.</p><p>Evidence ranged from moderate-very low-quality. All evidence was downgraded by at least one increment due to risk of bias arising from an unclear method of participant selection, with further downgrading due to an unclear blinding procedure in one of the studies. Additionally, the evidence in adolescents/adults with mixed smoking status’ was downgraded due to indirectness. Finally, imprecision was seen across both specificity estimates due to the 95%CI overlapping the upper threshold for decision-making.</p></div></div><div id="niceng245er9.s1.2.3"><h4>1.2.3. Benefits and harms</h4><p>Moderate-low-quality evidence in non-smoking adolescents/adults reported a sensitivity of 0.56 and a specificity of 0.75, neither of which met the decision-making threshold. Very low-quality evidence in people with mixed smoking status reported a sensitivity of 0.64 and a specificity of 0.95, with the latter meeting the threshold for decision-making. Whilst interpreting the evidence, the committee acknowledged the limitations in the quality of evidence, and also noted the relatively small number of participants (n=88) contributing to study in which high specificity was found.</p><p>Although the evidence is limited the committee agreed that mannitol was of potential value in the diagnosis of asthma because it shows good specificity without losing too much sensitivity. However, it would need to be used in conjunction with other tests since it is not accurate enough on its own. The diagnostic accuracy of mannitol in combination with other diagnostic tests was investigated in a separate review (1.11) in this guideline.</p></div><div id="niceng245er9.s1.2.4"><h4>1.2.4. Cost effectiveness and resource use</h4><p>No relevant published health economic analyses were identified for this review question. The cost of a bronchial challenge test was presented to aid committee consideration of cost effectiveness. The cost was estimated to reach £179.49 as the test is provided only in secondary care.</p><p>The committee considered bronchial challenge test with mannitol alongside or in combination with a variety of tests for asthma within a diagnostic algorithm in adults and children (see evidence review 1.11. Although potentially accurate, the committee agreed that the evidence was lacking and therefore recommended methacholine instead. This is also in line with current practice where methacholine is generally preferred.</p></div><div id="niceng245er9.s1.2.5"><h4>1.2.5. Other factors the committee took into account</h4><p>One factor that was considered when discussing the evidence was the risk of adverse side effects occurring during bronchial challenge testing with mannitol. This was initially raised as a point of concern by the lay members of the committee due to theoretical danger of deliberately restricting the airways. However, this concern was alleviated by the clinicians on the committee. It was explained that bronchial challenge tests only aim to achieve a reduction in FEV<sub>1</sub> of 15%, which in most individuals is not an uncomfortable level of bronchoconstriction. In very few cases a greater fall in FEV<sub>1</sub> of up to 40% may occur, but bronchial challenge tests are always followed by a rapid-acting bronchodilator to restore the functionality of the airway, thus limiting any discomfort experienced. Furthermore, bronchial challenge tests are conducted in secondary care where specialist input and facilities are available should any severe adverse events occur. Given the low likelihood of adverse events, combined with the safe testing environment, the committee agreed that the benefits of bronchial challenge testing with mannitol strongly outweighed the risks.</p><p>A second factor that was considered was the relatively easy access to and use of mannitol as a provocative agent. Unlike methacholine, mannitol requires no preparation and can be stored for longer, which was considered to be significant advantages.</p></div><div id="niceng245er9.s1.2.6"><h4>1.2.6. Recommendations supported by this evidence review</h4><p>Recommendations 1.2.4 and 1.2.9.</p></div></div><div id="niceng245er9.s1.rl.r1"><h3>1.3. References</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="niceng245er9.s1.ref1">Anderson
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SD, Charlton
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B, Weiler
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JM, et al. (2009) Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma
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<em>Respiratory Research</em>
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10: 4. [<a href="/pmc/articles/PMC2644668/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2644668</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19161635" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19161635</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng245er9.s1.ref2">National Institute for Health and Care Excellence. Developing NICE guidelines: the manual. . London. National Institute for Health and Care Excellence, 2014. Available from: <a href="http://www.nice.org.uk/article/PMG20/chapter/1%20Introduction%20and%20overview" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">http://www<wbr style="display:inline-block"></wbr>​.nice.org.uk<wbr style="display:inline-block"></wbr>​/article/PMG20/chapter<wbr style="display:inline-block"></wbr>​/1%20Introduction%20and%20overview</a> [<a href="https://pubmed.ncbi.nlm.nih.gov/26677490" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26677490</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng245er9.s1.ref3">NHS England. 2021/22 National Cost Collection data. 2022. Available from: <a href="https://www.england.nhs.uk/costing-in-the-nhs/national-cost-collection/" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.england.nhs<wbr style="display:inline-block"></wbr>​.uk/costing-in-the-nhs<wbr style="display:inline-block"></wbr>​/national-cost-collection/</a> Last accessed: 26/02/2024.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng245er9.s1.ref4">Porpodis
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K, Domvri
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K, Kontakiotis
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T, et al. (2017) Comparison of diagnostic validity of mannitol and methacholine challenges and relationship to clinical status and airway inflammation in steroid-naive asthmatic patients
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<em>The Journal of asthma : official journal of the Association for the Care of Asthma</em>
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54 (5): 520–529.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/27686218" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27686218</span></a>]</div></p></li></ul></div></div><div id="appendixesappgroup1"><h2 id="_appendixesappgroup1_">Appendices</h2><div id="niceng245er9.appa"><h3>Appendix A. Review protocols</h3><p id="niceng245er9.appa.et1"><a href="/books/NBK611960/bin/niceng245er9-appa-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Review protocol for bronchial challenge testing with mannitol for the diagnosis of asthma</a><span class="small"> (PDF, 240K)</span></p><p id="niceng245er9.appa.et2"><a href="/books/NBK611960/bin/niceng245er9-appa-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Health economic review protocol</a><span class="small"> (PDF, 133K)</span></p></div><div id="niceng245er9.appb"><h3>Appendix B. Literature search strategies</h3><p id="niceng245er9.appb.et1"><a href="/books/NBK611960/bin/niceng245er9-appb-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">B.1. Clinical search literature search strategy</a><span class="small"> (PDF, 199K)</span></p><p id="niceng245er9.appb.et2"><a href="/books/NBK611960/bin/niceng245er9-appb-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">B.2. Health economic literature search strategy</a><span class="small"> (PDF, 170K)</span></p></div><div id="niceng245er9.appc"><h3>Appendix C. Diagnostic evidence study selection</h3><p id="niceng245er9.appc.et1"><a href="/books/NBK611960/bin/niceng245er9-appc-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Figure 1. Flow chart of clinical study selection for the review of diagnostic test accuracy of bronchial challenge test with mannitol</a><span class="small"> (PDF, 98K)</span></p></div><div id="niceng245er9.appd"><h3>Appendix D. Diagnostic evidence</h3><p id="niceng245er9.appd.et1"><a href="/books/NBK611960/bin/niceng245er9-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (153K)</span></p></div><div id="niceng245er9.appe"><h3>Appendix E. Forest plots</h3><p id="niceng245er9.appe.et1"><a href="/books/NBK611960/bin/niceng245er9-appe-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">E.1. Coupled sensitivity and specificity forest plots</a><span class="small"> (PDF, 93K)</span></p></div><div id="niceng245er9.appf"><h3>Appendix F. Economic evidence study selection</h3><p id="niceng245er9.appf.et1"><a href="/books/NBK611960/bin/niceng245er9-appf-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Figure 4. Flow chart of health economic study selection for the guideline</a><span class="small"> (PDF, 148K)</span></p></div><div id="niceng245er9.appg"><h3>Appendix G. Economic evidence tables</h3><p>None.</p></div><div id="niceng245er9.apph"><h3>Appendix H. Excluded studies</h3><div id="niceng245er9.apph.s1"><h4>H.1. Clinical studies</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng245er9apphtab1"><a href="/books/NBK611960/table/niceng245er9.apph.tab1/?report=objectonly" target="object" title="Table 9" class="img_link icnblk_img" rid-ob="figobniceng245er9apphtab1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng245er9.apph.tab1"><a href="/books/NBK611960/table/niceng245er9.apph.tab1/?report=objectonly" target="object" rid-ob="figobniceng245er9apphtab1">Table 9</a></h4><p class="float-caption no_bottom_margin">Studies excluded from the clinical review. </p></div></div></div><div id="niceng245er9.apph.s2"><h4>H.2. Health Economic studies</h4><p>Published health economic studies that met the inclusion criteria (relevant population, comparators, economic study design, published 2006 or later and not from non-OECD country or USA) but that were excluded following appraisal of applicability and methodological quality are listed below. See the health economic protocol for more details.</p><p>None.</p></div></div></div></div><div class="fm-sec"><div><p>Final</p></div><div><p>BTS/NICE/SIGN collaborative guideline NG245</p><p>Developed by BTS, NICE and SIGN</p></div><div><p><b>Disclaimer</b>: The recommendations in this collaborative guideline represent the view of BTS, NICE and SIGN, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>This collaborative guideline covers health and care in England and Scotland. Decisions on how they apply in other UK countries are made by ministers in the <a href="http://wales.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a> and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. This collaborative guideline is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © BTS, NICE and SIGN 2024.</div><div class="small"><span class="label">Bookshelf ID: NBK611960</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/39937940" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">39937940</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobniceng245er9tab1"><div id="niceng245er9.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">PICO characteristics of diagnostic accuracy review question</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK611960/table/niceng245er9.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng245er9.tab1_lrgtbl__"><table><tbody><tr><th id="hd_b_niceng245er9.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_niceng245er9.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inclusion:
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<ul><li class="half_rhythm"><div>Adolescents/adults (≥12 years) with suspected asthma (presenting with respiratory symptoms).</div></li></ul>
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Stratified by smoking status:
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<ul><li class="half_rhythm"><div>Smokers</div></li><li class="half_rhythm"><div>Non-smokers</div></li><li class="half_rhythm"><div>Mixed populations</div></li></ul>
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Exclusion:
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<ul><li class="half_rhythm"><div>Children under 11 years as mannitol is not licenced in this population.</div></li><li class="half_rhythm"><div>People on steroid medication (washout period minimum of 4 weeks for inclusion)</div></li></ul></td></tr><tr><th id="hd_b_niceng245er9.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Target condition</th><td headers="hd_b_niceng245er9.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Asthma</td></tr><tr><th id="hd_b_niceng245er9.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Index test</th><td headers="hd_b_niceng245er9.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Mannitol</div></li></ul></td></tr><tr><th id="hd_b_niceng245er9.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference standard</th><td headers="hd_b_niceng245er9.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>Physician diagnosis of asthma based on symptoms plus an objective test from any one of the following:
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<ul><li class="half_rhythm"><div>peak flow variability (cut-off value of more than 20% variability as indication of a positive test);</div></li><li class="half_rhythm"><div>bronchodilator reversibility (cut-off value of an improvement in FEV1 of more than or equal to 12%, and an increase in volume of more than or equal to 200mls as indication of a positive test);</div></li><li class="half_rhythm"><div>bronchial hyper-responsiveness (histamine or methacholine challenge test, cut-off value of PC20 less than or equal to 8mg/ml as indication of a positive test)</div></li><li class="half_rhythm"><div>FeNO</div></li></ul></p>
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<p>Where no evidence is available using the cut-off values specified above, evidence will be included from studies using a reference standard of physician diagnosis with an objective test using an alternative threshold.</p>
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<p>Where no evidence is available from studies using physician diagnosis and an objective test, evidence will be included from studies using physician diagnosis based on symptoms alone, or patient report of a previous physician diagnosis.</p></td></tr><tr><th id="hd_b_niceng245er9.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Statistical measures</th><td headers="hd_b_niceng245er9.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Sensitivity: thresholds: upper 90, lower 10</div></li><li class="half_rhythm"><div>Specificity: thresholds: upper 80, lower 50</div></li><li class="half_rhythm"><div>Raw data to calculate 2x2 tables to calculate sensitivity and specificity</div></li><li class="half_rhythm"><div>Negative predictive value (NPV), Positive predictive value (PPV)</div></li></ul></td></tr><tr><th id="hd_b_niceng245er9.tab1_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design</th><td headers="hd_b_niceng245er9.tab1_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Cross sectional studies</div></li><li class="half_rhythm"><div>Cohort studies</div></li></ul></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng245er9tab2"><div id="niceng245er9.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of studies included in the evidence review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK611960/table/niceng245er9.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng245er9.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_niceng245er9.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_niceng245er9.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Population</th><th id="hd_h_niceng245er9.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Target condition</th><th id="hd_h_niceng245er9.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Index test</th><th id="hd_h_niceng245er9.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Reference standard</th><th id="hd_h_niceng245er9.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_niceng245er9.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anderson 2009(<a class="bibr" href="#niceng245er9.s1.ref1" rid="niceng245er9.s1.ref1">Anderson, et al., 2009</a>)</td><td headers="hd_h_niceng245er9.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>N=375 people with signs and symptoms suggestive of asthma without a firm diagnosis of asthma or non-asthma.</p>
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<p>Age, mean (SD): 24.3 (10.2) years. Range 6-50 years</p>
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<p>USA</p>
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</td><td headers="hd_h_niceng245er9.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Asthma</td><td headers="hd_h_niceng245er9.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Mannitol test expressed as PD15 (dose of mannitol that caused a reduction in FEV<sub>1</sub> of 15% from baseline, or 10% fall between consecutive doses)</p>
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<p>Maximum cumulative dose: 635 mg</p>
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</td><td headers="hd_h_niceng245er9.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diagnosis of asthma by a respiratory physician based on data from exercise challenge, examination, skin tests and FEV<sub>1</sub> reversibility</td><td headers="hd_h_niceng245er9.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Prospective cross-sectional study</p>
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<p>ICS use: 4-week washout</p>
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<p>Smoking status: Smokers excluded</p>
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</td></tr><tr><td headers="hd_h_niceng245er9.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Porpodis 2017(<a class="bibr" href="#niceng245er9.s1.ref4" rid="niceng245er9.s1.ref4">Porpodis, et al., 2017</a>)</td><td headers="hd_h_niceng245er9.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>N=88 people with asthma related symptoms in the past month visiting an asthma clinic for asthma diagnosis</p>
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<p>Age, mean (SD): 38.56 (16.73) years</p>
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<p>Greece</p>
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</td><td headers="hd_h_niceng245er9.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Asthma</td><td headers="hd_h_niceng245er9.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Mannitol test expressed as PD15 (dose of mannitol that caused a reduction in FEV<sub>1</sub> of 15% from baseline, or 10% fall between consecutive doses)</p>
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<p>Maximum cumulative dose: 635 mg</p>
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</td><td headers="hd_h_niceng245er9.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Asthma diagnosis according to GINA guidelines: combination of at least a ≥12% (and ≥200 mL) increase in baseline FEV1 after albuterol, along with new symptoms of coughing, wheezing, or shortness of breath over the past month</td><td headers="hd_h_niceng245er9.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Prospective cross-sectional study</p>
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<p>ICS use: Treatment naïve</p>
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<p>Smoking status: 15% current smokers</p>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng245er9tab3"><div id="niceng245er9.tab3" class="table"><h3><span class="label">Table 3</span><span class="title">Clinical evidence summary: bronchial challenge with mannitol vs clinician diagnosis of asthma in non-smoking adolescents/adults</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK611960/table/niceng245er9.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng245er9.tab3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Studies</th><th id="hd_h_niceng245er9.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">N</th><th id="hd_h_niceng245er9.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Risk of bias</th><th id="hd_h_niceng245er9.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Inconsistency</th><th id="hd_h_niceng245er9.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Indirectness</th><th id="hd_h_niceng245er9.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Imprecision</th><th id="hd_h_niceng245er9.tab3_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Effect size (95%CI)</th><th id="hd_h_niceng245er9.tab3_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Quality</th></tr></thead><tbody><tr><th headers="hd_h_niceng245er9.tab3_1_1_1_1 hd_h_niceng245er9.tab3_1_1_1_2 hd_h_niceng245er9.tab3_1_1_1_3 hd_h_niceng245er9.tab3_1_1_1_4 hd_h_niceng245er9.tab3_1_1_1_5 hd_h_niceng245er9.tab3_1_1_1_6 hd_h_niceng245er9.tab3_1_1_1_7 hd_h_niceng245er9.tab3_1_1_1_8" id="hd_b_niceng245er9.tab3_1_1_1_1" colspan="8" rowspan="1" style="text-align:left;vertical-align:top;">Mannitol (PD15 or 10% between consecutive doses) vs clinician diagnosis with exercise challenge, history, examination, skin test and bronchodilator reversibility data</th></tr><tr><td headers="hd_h_niceng245er9.tab3_1_1_1_1 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">1 cross-sectional study</td><td headers="hd_h_niceng245er9.tab3_1_1_1_2 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">375</td><td headers="hd_h_niceng245er9.tab3_1_1_1_3 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>1</sup></td><td headers="hd_h_niceng245er9.tab3_1_1_1_4 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not serious</td><td headers="hd_h_niceng245er9.tab3_1_1_1_5 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not serious</td><td headers="hd_h_niceng245er9.tab3_1_1_1_6 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not serious</td><td headers="hd_h_niceng245er9.tab3_1_1_1_7 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sensitivity= 0.56 (0.49-0.62)</td><td headers="hd_h_niceng245er9.tab3_1_1_1_8 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MODERATE</td></tr><tr><td headers="hd_h_niceng245er9.tab3_1_1_1_3 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>1</sup></td><td headers="hd_h_niceng245er9.tab3_1_1_1_4 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not serious</td><td headers="hd_h_niceng245er9.tab3_1_1_1_5 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not serious</td><td headers="hd_h_niceng245er9.tab3_1_1_1_6 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>2</sup></td><td headers="hd_h_niceng245er9.tab3_1_1_1_7 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Specificity= 0.75 (0.67-0.82)</td><td headers="hd_h_niceng245er9.tab3_1_1_1_8 hd_b_niceng245er9.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">LOW</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="niceng245er9.tab3_1"><p class="no_margin">Downgraded by one increment due to concerns arising from the method of participant selection (method not reported)</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="niceng245er9.tab3_2"><p class="no_margin">Downgraded by one increment due to the 95%CI overlapping the threshold corresponding to ‘high specificity’ (80%)</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng245er9tab4"><div id="niceng245er9.tab4" class="table"><h3><span class="label">Table 4</span><span class="title">Clinical evidence summary: bronchial challenge with mannitol vs clinician diagnosis of asthma in adolescents/adults with mixed smoking status</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK611960/table/niceng245er9.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng245er9.tab4_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Studies</th><th id="hd_h_niceng245er9.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">N</th><th id="hd_h_niceng245er9.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Risk of bias</th><th id="hd_h_niceng245er9.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Inconsistency</th><th id="hd_h_niceng245er9.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Indirectness</th><th id="hd_h_niceng245er9.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Imprecision</th><th id="hd_h_niceng245er9.tab4_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Effect size (95%CI)</th><th id="hd_h_niceng245er9.tab4_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Quality</th></tr></thead><tbody><tr><th headers="hd_h_niceng245er9.tab4_1_1_1_1 hd_h_niceng245er9.tab4_1_1_1_2 hd_h_niceng245er9.tab4_1_1_1_3 hd_h_niceng245er9.tab4_1_1_1_4 hd_h_niceng245er9.tab4_1_1_1_5 hd_h_niceng245er9.tab4_1_1_1_6 hd_h_niceng245er9.tab4_1_1_1_7 hd_h_niceng245er9.tab4_1_1_1_8" id="hd_b_niceng245er9.tab4_1_1_1_1" colspan="8" rowspan="1" style="text-align:left;vertical-align:top;">Mannitol (PD15 or 10% between consecutive doses) vs clinician diagnosis with bronchodilator reversibility and symptom monitoring over one-month</th></tr><tr><td headers="hd_h_niceng245er9.tab4_1_1_1_1 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">1 cross-sectional study</td><td headers="hd_h_niceng245er9.tab4_1_1_1_2 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">88</td><td headers="hd_h_niceng245er9.tab4_1_1_1_3 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>1</sup></td><td headers="hd_h_niceng245er9.tab4_1_1_1_4 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not serious</td><td headers="hd_h_niceng245er9.tab4_1_1_1_5 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>2</sup></td><td headers="hd_h_niceng245er9.tab4_1_1_1_6 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not serious</td><td headers="hd_h_niceng245er9.tab4_1_1_1_7 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sensitivity= 0.64 (0.52-0.76)</td><td headers="hd_h_niceng245er9.tab4_1_1_1_8 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><td headers="hd_h_niceng245er9.tab4_1_1_1_3 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>1</sup></td><td headers="hd_h_niceng245er9.tab4_1_1_1_4 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not serious</td><td headers="hd_h_niceng245er9.tab4_1_1_1_5 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>2</sup></td><td headers="hd_h_niceng245er9.tab4_1_1_1_6 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>3</sup></td><td headers="hd_h_niceng245er9.tab4_1_1_1_7 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Specificity= 0.95 (0.76-1.00)</td><td headers="hd_h_niceng245er9.tab4_1_1_1_8 hd_b_niceng245er9.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="niceng245er9.tab4_1"><p class="no_margin">Downgraded by two increments due to concerns arising from the method of participant selection (method not reported) and the interpretation of the index test and reference standard (unclear if blinded)</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="niceng245er9.tab4_2"><p class="no_margin">Downgraded by one increment due to population (contains a mixture of smoking and non-smoking participants) indirectness</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="niceng245er9.tab4_3"><p class="no_margin">Downgraded by one increment due to the 95%CI overlapping the threshold corresponding to ‘high specificity’ (80%)</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng245er9tab5"><div id="niceng245er9.tab5" class="table"><h3><span class="label">Table 5</span><span class="title">Cost of a bronchial challenge test</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK611960/table/niceng245er9.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng245er9.tab5_lrgtbl__"><table><thead><tr><th id="hd_h_niceng245er9.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Resource</th><th id="hd_h_niceng245er9.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Unit costs</th><th id="hd_h_niceng245er9.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Source</th></tr></thead><tbody><tr><td headers="hd_h_niceng245er9.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Bronchial challenge test with mannitol</td><td headers="hd_h_niceng245er9.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">£179.49</td><td headers="hd_h_niceng245er9.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">National Cost Collection 2021-22 – DZ36Z(<a class="bibr" href="#niceng245er9.s1.ref3" rid="niceng245er9.s1.ref3">NHS England, 2022</a>)</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng245er9apphtab1"><div id="niceng245er9.apph.tab1" class="table"><h3><span class="label">Table 9</span><span class="title">Studies excluded from the clinical review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK611960/table/niceng245er9.apph.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng245er9.apph.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_niceng245er9.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_niceng245er9.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Code [Reason]</th></tr></thead><tbody><tr><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Backer, Vibeke; Sverrild, Asger; Porsbjerg, Celeste (2014) FENO and AHR mannitol in patients referred to an out-of-hospital asthma clinic: a real-life study. The Journal of asthma : official journal of the Association for the Care of Asthma
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51(4): 411–6
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[<a href="https://pubmed.ncbi.nlm.nih.gov/24450977" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24450977</span></a>]
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</td><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>- Reference standard not relevant to this review protocol</p>
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<p>
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<i>Reference standard was an objective test (FeNO) without clinician diagnosis</i>
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</p>
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</td></tr><tr><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Barben, Juerg, Kuehni, Claudia E, Strippoli, Marie-Pierre F
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et al. (2011) Mannitol dry powder challenge in comparison with exercise testing in children. Pediatric pulmonology
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46(9): 842–8
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[<a href="https://pubmed.ncbi.nlm.nih.gov/21465681" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21465681</span></a>]
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</td><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>- Population not relevant to this review protocol</p>
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<p>
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<i>>10% of population receiving ICS and no appropriate washout period included</i>
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</p>
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</td></tr><tr><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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de Menezes, M.B., Ferraz, E., Brannan, J.D.
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et al. (2018) The efficacy and safety of mannitol challenge in a workplace setting for assessing asthma prevalence. Journal of Asthma
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55(12): 1278–1285 [<a href="https://pubmed.ncbi.nlm.nih.gov/29300533" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29300533</span></a>]
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</td><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>- Study aiming to diagnose a condition other than asthma</p>
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<p>
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<i>Occupational asthma is outside scope of this guideline</i>
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</p>
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</td></tr><tr><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Georas, Steve, Ransom, Nicole, Hillman, Sara
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et al. (2019) The leaky lung test: a pilot study using inhaled mannitol to measure airway barrier function in asthma. The Journal of asthma : official journal of the Association for the Care of Asthma
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56(12): 1257–1265
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[<a href="/pmc/articles/PMC6522330/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6522330</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30444143" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30444143</span></a>]
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</td><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>- Population not relevant to this review protocol</p>
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<p>
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<i>Study contains people already diagnosed with asthma</i>
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</p>
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</td></tr><tr><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Kernen, Philipp, Steveling-Klein, Esther H, Saccilotto, Ramon T
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et al. (2019) The sensitivity and specificity of the mannitol bronchial challenge test to identify asthma in different populations: a systematic review. Swiss medical weekly
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149: w20100 [<a href="https://pubmed.ncbi.nlm.nih.gov/31476241" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31476241</span></a>]
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</td><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Knag
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Pedersen, Signe, Ustrup, Amalie
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S, Baarnes, Camilla B
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et al. (2020) Usefulness of mannitol challenge testing for diagnosing asthma in everyday clinical practice. The Journal of asthma : official journal of the Association for the Care of Asthma
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57(6): 663–669
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[<a href="https://pubmed.ncbi.nlm.nih.gov/30990094" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30990094</span></a>]
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</td><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>- Reference standard not relevant to this review protocol</p>
|
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<p>
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<i>Clinician diagnosis included bronchial challenge with mannitol</i>
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</p>
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</td></tr><tr><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Porsbjerg, C, Rasmussen, L, Thomsen, S F
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|
et al. (2007) Response to mannitol in asymptomatic subjects with airway hyper-responsiveness to methacholine. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
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37(1): 22–8
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[<a href="https://pubmed.ncbi.nlm.nih.gov/17210038" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17210038</span></a>]
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</td><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>- Population not relevant to this review protocol</p>
|
|
<p>
|
|
<i>Study included participants not presenting with respiratory symptoms</i>
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</p>
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</td></tr><tr><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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White, Elisha C, de Klerk, Nicholas, Hantos, Zoltan
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et al. (2017) Mannitol challenge testing for asthma in a community cohort of young adults. Respirology (Carlton, Vic.)
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22(4): 678–683
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[<a href="https://pubmed.ncbi.nlm.nih.gov/27917572" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27917572</span></a>]
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</td><td headers="hd_h_niceng245er9.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>- Population not relevant to this review protocol</p>
|
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<p>
|
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<i>Study included participants already diagnosed with asthma</i>
|
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</p>
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</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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