Corticosteroids/β2-agonists in Hair in Asthmatic Patients (CorticHair)

Asthma Clinical Trial

— CorticHair  

Official title:

Therapeutic Drug Monitoring of Corticosteroids/β2-agonists in Hair in Asthmatic Patients: an Open-label Feasibility Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03691961
• Other study ID #: 2017047F
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 20, 2018
• Est. completion date: July 20, 2023

Study information

• Verified date: August 2022
• Source: Hopital Foch
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This feasibility study will be open-label with two dose groups: patients receiving budesonide/formoterol Turbuhaler® at a total daily dose [400 to 800 µg[ (group 1) and patients receiving a total daily dose ≥800 µg/day (group 2) to investigate whether there is a relationship between dose and hair concentration. The objective of this feasibility study is to determine if the product administered to the patient is detectable and quantifiable in hair in order to have a mean to monitor adherence to the treatment. This study does not in any way evaluate the efficacy or safety of the medicinal product, which will be used in accordance with its marketing authorization.

Description:

Asthma affects 3-10% of the European population and is a heterogeneous disease in its clinical manifestations and also in its response to treatment. Since therapy is often started at young age and given over many years, with adjustments made on disease control, long-term adherence and efficacy are particular concerns. Adherence to inhaled controller medications is a major challenge to obtain disease control and to avoid serious asthma flare-ups or unnecessary treatment stepping up. In addition to adherence concerns, poor asthma control may also be the consequence of a poor inhalation technique and the resulting insufficient drug exposure. To overcome adherence issues, patients are encouraged to self-manage their disease and the use of new technologies such as inhaler reminders, electronic devices and/or smartphone applications may be helpful. Although there is a margin to improve and monitor adherence, assessing the efficiency of the inhalation technique in daily routine and its consequences in terms of drug exposure is much harder. The traditional monitoring of pharmacological therapies involves therapeutic drug monitoring, i.e. the measure of drug concentration in plasma. But drugs concentration in plasma most only reflect the quantity of drug in the body in the last 24-48 hrs only. Hence, therapeutic drug monitoring is not used for inhaled asthma treatments, in part because of the limited interest in assessing only a 24-48 hrs exposure and of the very low plasma concentrations which are very challenging to measure. Since drugs present in the bloodstream also reach and stay in the forming hair where their concentrations can be measured and interpreted as an overall chronic exposure, hair analysis could become a valuable tool in the monitoring of inhaled asthma treatments, with the use of very specific mass spectrometry techniques and of the most sensitive last-generation mass spectrometers.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: July 20, 2023
• Est. primary completion date: July 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedure
• Outpatients with asthma, of either gender, aged =18 and <50 years at visit 1
• Controlled or partly controlled asthma according to the Global Initiative for Asthma (GINA) guideline
• Receiving a constant daily dose =400 µg budesonide of budesonide/formoterol Turbuhaler® for more than 2 months
• No treatment step-down is planned in the 3 next months
• ACQ (Asthma Control Questionnaire) score = 1.50
• Patient with healthcare insurance

Exclusion Criteria:

• Pregnant women or women wishing to become pregnant in the next 3 months
• Patients with body mass index (BMI) <18 or >30
• Patients with known kidney or liver disease (creatinine clearance < 60 mL/min/1.73 m² or alanine aminotransferase (ALAT) > 5N)
• Smokers or former smokers < 3 years
• Patients with simultaneous asthma and chronic obstructive pulmonary disease (COPD) (or defined as having asthma-COPD overlap syndrome)
• Other budesonide- or formoterol-containing drugs (e.g Foradil®, Rhinocort®, Mikicort®, Entocort®…)
• CYP3A4 inducers (systemic corticosteroid, rifampicin, phenobarbital, carbamazepine…)
• CYP3A4 inhibitors (macrolides, azole antifungals, valproic acid, amiodarone, fluoxetine)
• Hair treatment (coloration, bleaching, perming…)
• Hairless patients, hair implants or hair extensions
• Length of hair from the vertex posterior region < 5 cm or planning to cut hair from this region shorter than 5 cm in the next 4 months
• Patient deprived of liberty by judicial or administrative decision
• Major protected by law

Related Conditions & MeSH terms

• Asthma

Intervention

Other:
• Hair sampling
After 4 months of treatment, a strand of hair from the vertex posterior region of the scalp about the width of a thin pencil and with a length equal to or greater than 3 cm will be cut.

Diagnostic Test:
• Hair's drug concentrations
The hair's concentrations of budesonide/formoterol is analysed with mass spectrometry.

Locations

Country	Name	City	State
France	Foch Hospital	Suresnes

Sponsors (1)

Lead Sponsor	Collaborator
Hopital Foch

Country where clinical trial is conducted

France, 

References & Publications (102)

Al-Jahdali H, Ahmed A, Al-Harbi A, Khan M, Baharoon S, Bin Salih S, Halwani R, Al-Muhsen S. Improper inhaler technique is associated with poor asthma control and frequent emergency department visits. Allergy Asthma Clin Immunol. 2013 Mar 6;9(1):8. doi: 10.1186/1710-1492-9-8. — View Citation

Alonso L, Fuchs E. The hair cycle. J Cell Sci. 2006 Feb 1;119(Pt 3):391-3. Review. — View Citation

Alvarez JC, Abe E, Etting I, Le Guen M, Devillier P, Grassin-Delyle S. Quantification of remifentanil and propofol in human plasma: a LC-MS/MS assay validated according to the EMA guideline. Bioanalysis. 2015;7(13):1675-84. doi: 10.4155/bio.15.89. — View Citation

Alvarez JC, Charbit B, Grassin-Delyle S, Demolis JL, Funck-Brentano C, Abe E. Human plasma quantification of droperidol and ondansetron used in preventing postoperative nausea and vomiting with a LC/ESI/MS/MS method. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Jan 15;879(2):186-90. doi: 10.1016/j.jchromb.2010.12.001. Epub 2010 Dec 16. — View Citation

Auchus RJ. Steroid assays and endocrinology: best practices for basic scientists. Endocrinology. 2014 Jun;155(6):2049-51. doi: 10.1210/en.2014-7534. — View Citation

Baque CS, Zhou J, Gu W, Collaudin C, Kravtchenko S, Kempf JY, Saint-Léger D. Relationships between hair growth rate and morphological parameters of human straight hair: a same law above ethnical origins? Int J Cosmet Sci. 2012 Apr;34(2):111-6. doi: 10.1111/j.1468-2494.2011.00687.x. Epub 2011 Oct 21. — View Citation

Baxi SM, Greenblatt RM, Bacchetti P, Jin C, French AL, Keller MJ, Augenbraun MH, Gange SJ, Liu C, Mack WJ, Gandhi M; Women's Interagency HIV Study (WIHS). Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients. PLoS One. 2015 Jun 8;10(6):e0129100. doi: 10.1371/journal.pone.0129100. eCollection 2015. — View Citation

Bévalot F, Gaillard Y, Lhermitte MA, Pépin G. Analysis of corticosteroids in hair by liquid chromatography-electrospray ionization mass spectrometry. J Chromatogr B Biomed Sci Appl. 2000 Apr 14;740(2):227-36. — View Citation

Borges NC, Astigarraga RB, Sverdloff CE, Borges BC, Paiva TR, Galvinas PR, Moreno RA. Budesonide quantification by HPLC coupled to atmospheric pressure photoionization (APPI) tandem mass spectrometry. Application to a comparative systemic bioavailability of two budesonide formulations in healthy volunteers. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Feb 1;879(3-4):236-42. doi: 10.1016/j.jchromb.2010.12.003. Epub 2010 Dec 13. — View Citation

Buscher BA, Jägfeldt H, Sandman H, Brust-van Schaik R, van Schaik F, Brüll LP. The determination of budesonide and fluticasone in human sputum samples collected from COPD patients using LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Jan 1;880(1):6-11. doi: 10.1016/j.jchromb.2011.10.029. Epub 2011 Nov 16. — View Citation

Capron A, Antunes MV, Wagner SC, Mattevi VS, Vieira N, Leite R, Reginato F, Capra M, Fogliatto L, Wallemacq P, Linden R. First report of imatinib measurement in hair: Method development and preliminary evaluation of the relation between hair and plasma concentrations with therapeutic response in chronic myeloid leukemia. Clin Chim Acta. 2016 Jan 30;453:42-7. doi: 10.1016/j.cca.2015.11.032. Epub 2015 Dec 3. — View Citation

Chalmers GW, Macleod KJ, Little SA, Thomson LJ, McSharry CP, Thomson NC. Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma. Thorax. 2002 Mar;57(3):226-30. — View Citation

Chèze, M. and Gaulier, J.-M. (2014). Chapter 8 - Drugs Involved in Drug-Facilitated Crimes (DFC): Analytical Aspects: 2-Hair A2 - Kintz, Pascal. Toxicological Aspects of Drug-Facilitated Crimes. Oxford, Academic Press: 181-222.

Choi HI, Choi GI, Kim EK, Choi YJ, Sohn KC, Lee Y, Kim CD, Yoon TJ, Sohn HJ, Han SH, Kim S, Lee JH, Lee YH. Hair greying is associated with active hair growth. Br J Dermatol. 2011 Dec;165(6):1183-9. doi: 10.1111/j.1365-2133.2011.10625.x. — View Citation

Cirimele V, Kintz P, Dumestre V, Goullé JP, Ludes B. Identification of ten corticosteroids in human hair by liquid chromatography-ionspray mass spectrometry. Forensic Sci Int. 2000 Jan 10;107(1-3):381-8. — View Citation

Cirimele V, Tracqui A, Kintz P, Ludes B. First identification of prednisone in human hair by liquid chromatography-ionspray mass spectrometry. J Anal Toxicol. 1999 May-Jun;23(3):225-6. — View Citation

Cochrane MG, Bala MV, Downs KE, Mauskopf J, Ben-Joseph RH. Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique. Chest. 2000 Feb;117(2):542-50. Review. — View Citation

Cone EJ. Mechanisms of drug incorporation into hair. Ther Drug Monit. 1996 Aug;18(4):438-43. — View Citation

Cooper GA, Kronstrand R, Kintz P; Society of Hair Testing. Society of Hair Testing guidelines for drug testing in hair. Forensic Sci Int. 2012 May 10;218(1-3):20-4. doi: 10.1016/j.forsciint.2011.10.024. Epub 2011 Nov 15. — View Citation

Cuypers E, Flinders B, Bosman IJ, Lusthof KJ, Van Asten AC, Tytgat J, Heeren RMA. Hydrogen peroxide reactions on cocaine in hair using imaging mass spectrometry. Forensic Sci Int. 2014 Sep;242:103-110. doi: 10.1016/j.forsciint.2014.06.035. Epub 2014 Jul 7. — View Citation

Dalby C, Polanowski T, Larsson T, Borgström L, Edsbäcker S, Harrison TW. The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial. Respir Res. 2009 Oct 31;10:104. doi: 10.1186/1465-9921-10-104. — View Citation

DAVIS BK. Phases of the hair-growth cycle. Nature. 1962 May 19;194:694. — View Citation

Deventer K, Mikulcíková P, Van Hoecke H, Van Eenoo P, Delbeke FT. Detection of budesonide in human urine after inhalation by liquid chromatography-mass spectrometry. J Pharm Biomed Anal. 2006 Oct 11;42(4):474-9. Epub 2006 Jul 12. — View Citation

Deventer K, Pozo OJ, Delbeke FT, Van Eenoo P. Quantitative detection of inhaled formoterol in human urine and relevance to doping control analysis. Drug Test Anal. 2012 Jun;4(6):449-54. doi: 10.1002/dta.418. Epub 2012 Mar 22. — View Citation

Dimova H, Wang Y, Pommery S, Moellmann H, Hochhaus G. SPE/RIA vs LC/MS for measurement of low levels of budesonide in plasma. Biomed Chromatogr. 2003 Jan;17(1):14-20. — View Citation

Duvivier WF, Peeters RJ, van Beek TA, Nielen MW. Evidence based decontamination protocols for the removal of external ?9-tetrahydrocannabinol (THC) from contaminated hair. Forensic Sci Int. 2016 Feb;259:110-8. doi: 10.1016/j.forsciint.2015.12.014. Epub 2015 Dec 19. — View Citation

Fabresse N, Grassin-Delyle S, Etting I, Alvarez JC. Detection and quantification of 12 anabolic steroids and analogs in human whole blood and 20 in hair using LC-HRMS/MS: application to real cases. Int J Legal Med. 2017 Jul;131(4):989-999. doi: 10.1007/s00414-017-1552-3. Epub 2017 Feb 24. — View Citation

Fabresse, N. (2015). Mise au point et validation d'une méthode de dosage des anabolisants stéroïdiens dans le sang et les cheveux par spectrométrie de masse haute résolution Orbitrap Application à deux cas médico-légaux, http://www.sudoc.fr/188207155: 93.

FDA.

Foster JM, Usherwood T, Smith L, Sawyer SM, Xuan W, Rand CS, Reddel HK. Inhaler reminders improve adherence with controller treatment in primary care patients with asthma. J Allergy Clin Immunol. 2014 Dec;134(6):1260-1268.e3. doi: 10.1016/j.jaci.2014.05.041. Epub 2014 Jul 22. — View Citation

Gaillard Y, Vayssette F, Pépin G. Compared interest between hair analysis and urinalysis in doping controls. Results for amphetamines, corticosteroids and anabolic steroids in racing cyclists. Forensic Sci Int. 2000 Jan 10;107(1-3):361-79. — View Citation

Gamble J, Stevenson M, McClean E, Heaney LG. The prevalence of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2009 Nov 1;180(9):817-22. doi: 10.1164/rccm.200902-0166OC. Epub 2009 Jul 30. — View Citation

Gandhi M, Ameli N, Bacchetti P, Anastos K, Gange SJ, Minkoff H, Young M, Milam J, Cohen MH, Sharp GB, Huang Y, Greenblatt RM. Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy. Clin Infect Dis. 2011 May;52(10):1267-75. doi: 10.1093/cid/cir131. — View Citation

Gandhi M, Greenblatt RM, Bacchetti P, Jin C, Huang Y, Anastos K, Cohen M, Dehovitz JA, Sharp GB, Gange SJ, Liu C, Hanson SC, Aouizerat B; Women's Interagency HIV Study. A single-nucleotide polymorphism in CYP2B6 leads to >3-fold increases in efavirenz concentrations in plasma and hair among HIV-infected women. J Infect Dis. 2012 Nov;206(9):1453-61. doi: 10.1093/infdis/jis508. Epub 2012 Aug 20. — View Citation

Grassin Delyle S, Abe E, Batisse A, Tremey B, Fischler M, Devillier P, Alvarez JC. A validated assay for the quantitative analysis of tranexamic acid in human serum by liquid chromatography coupled with electrospray ionization mass spectrometry. Clin Chim Acta. 2010 Mar;411(5-6):438-43. doi: 10.1016/j.cca.2010.01.005. Epub 2010 Jan 11. — View Citation

Grassin Delyle S, Abe E, Devillier P, Alvarez JC. Determination of rimonabant in human plasma and hair by liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Sep 1;872(1-2):115-20. doi: 10.1016/j.jchromb.2008.07.041. Epub 2008 Aug 5. — View Citation

Handelsman DJ, Wartofsky L. Requirement for mass spectrometry sex steroid assays in the Journal of Clinical Endocrinology and Metabolism. J Clin Endocrinol Metab. 2013 Oct;98(10):3971-3. doi: 10.1210/jc.2013-3375. — View Citation

He G, Lu J, Wang X, Xu Y, Wu Y, Dong Y, Shen L, He Z, Zhao J, Yuan H. An improved liquid chromatography-tandem mass spectrometric method to quantify formoterol in human urine. J Chromatogr Sci. 2014 Sep;52(8):848-51. doi: 10.1093/chromsci/bmt127. Epub 2013 Sep 12. — View Citation

Hoelzle C, Scheufler F, Uhl M, Sachs H, Thieme D. Application of discriminant analysis to differentiate between incorporation of cocaine and its congeners into hair and contamination. Forensic Sci Int. 2008 Mar 21;176(1):13-8. Epub 2007 Dec 11. — View Citation

Josefsson M, Sabanovic A. Sample preparation on polymeric solid phase extraction sorbents for liquid chromatographic-tandem mass spectrometric analysis of human whole blood--a study on a number of beta-agonists and beta-antagonists. J Chromatogr A. 2006 Jul 7;1120(1-2):1-12. Epub 2006 Apr 4. — View Citation

Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999 Oct;14(4):902-7. — View Citation

Juniper EF, Svensson K, Mörk AC, Ståhl E. Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir Med. 2005 May;99(5):553-8. Epub 2004 Nov 26. — View Citation

Jurado C, Kintz P, Menéndez M, Repetto M. Influence of the cosmetic treatment of hair on drug testing. Int J Legal Med. 1997;110(3):159-63. — View Citation

Kintz P, Alvarez JC, Deveaux M, Dumestre V, Gaillard Y, Gaulier JM. Conflicting hair testing results can have an impact in courts: interpretation of single exposure to zolpidem. J Anal Toxicol. 2014 Jun;38(5):304-5. doi: 10.1093/jat/bku014. Epub 2014 Mar 11. — View Citation

Kintz P, Cirimele V, Ludes B. Pharmacological criteria that can affect the detection of doping agents in hair. Forensic Sci Int. 2000 Jan 10;107(1-3):325-34. — View Citation

Kintz P, Dumestre-Toulet V, Jamey C, Cirimele V, Ludes B. Doping control for beta-adrenergic compounds through hair analysis. J Forensic Sci. 2000 Jan;45(1):170-4. — View Citation

Kintz P. Value of the concept of minimal detectable dosage in human hair. Forensic Sci Int. 2012 May 10;218(1-3):28-30. doi: 10.1016/j.forsciint.2011.10.018. Epub 2011 Oct 20. Review. — View Citation

Kronkvist K, Gustavsson M, Wendel AK, Jaegfeldt H. Automated sample preparation for the determination of budesonide in plasma samples by liquid chromatography and tandem mass spectrometry. J Chromatogr A. 1998 Oct 9;823(1-2):401-9. — View Citation

Kronstrand R, Ahlner J, Dizdar N, Larson G. Quantitative analysis of desmethylselegiline, methamphetamine, and amphetamine in hair and plasma from Parkinson patients on long-term selegiline medication. J Anal Toxicol. 2003 Apr;27(3):135-41. — View Citation

Kronstrand R, Roman M, Hedman M, Ahlner J, Dizdar N. Dose-hair concentration relationship and pigmentation effects in patients on low-dose clozapine. Forensic Sci Med Pathol. 2007 Jun;3(2):107-14. doi: 10.1007/s12024-007-0010-9. Epub 2007 May 9. — View Citation

LeBeau MA, Montgomery MA, Brewer JD. The role of variations in growth rate and sample collection on interpreting results of segmental analyses of hair. Forensic Sci Int. 2011 Jul 15;210(1-3):110-6. doi: 10.1016/j.forsciint.2011.02.015. Epub 2011 Mar 6. — View Citation

Lee KM, Kim HJ, Son J, Park JH, Kwon OS, Lee J. Simple quantitation of formoterol and 11-nor-?(9)-tetrahydrocannabinol-9-carboxylic acid in human urine by liquid chromatography-tandem mass spectrometry in doping control. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Sep 15;967:8-12. doi: 10.1016/j.jchromb.2014.07.009. Epub 2014 Jul 14. — View Citation

Lemaire-Hurtel, A.-S., Durand-Maugard, C., Berquin, P., Antonios, M., Hary, L., Andrejak, M., Masson, H., Manaouil, C., Abe, E. and Alvarez, J.-C. (2010).

Li N, Tattam B, Brow KF, Seale JP. Quantification of epimeric budesonide and fluticasone propionate in human plasma by liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 2001 Sep 25;761(2):177-85. — View Citation

Li YN, Tattam B, Brown KF, Seale JP. Determination of epimers 22R and 22S of budesonide in human plasma by high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. J Chromatogr B Biomed Appl. 1996 Aug 30;683(2):259-68. — View Citation

Lindberg C, Blomqvist A, Paulson J. Determination of (22R,S)budesonide in human plasma by automated liquid chromatography/thermospray mass spectrometry. Biol Mass Spectrom. 1992 Nov;21(11):525-33. — View Citation

Liu AY, Yang Q, Huang Y, Bacchetti P, Anderson PL, Jin C, Goggin K, Stojanovski K, Grant R, Buchbinder SP, Greenblatt RM, Gandhi M. Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP). PLoS One. 2014 Jan 8;9(1):e83736. doi: 10.1371/journal.pone.0083736. eCollection 2014. — View Citation

Loussouarn G, Lozano I, Panhard S, Collaudin C, El Rawadi C, Genain G. Diversity in human hair growth, diameter, colour and shape. An in vivo study on young adults from 24 different ethnic groups observed in the five continents. Eur J Dermatol. 2016 Apr 1;26(2):144-54. doi: 10.1684/ejd.2015.2726. — View Citation

Lu Y, Sun Z, Zhang Y, Chen X, Zhong D. Simultaneous quantification of 22R and 22S epimers of budesonide in human plasma by ultra-high-performance liquid chromatography-tandem mass spectrometry: application in a stereoselective pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Mar 15;921-922:27-34. doi: 10.1016/j.jchromb.2013.01.015. Epub 2013 Jan 28. — View Citation

Mancebo, M., Grassin-Delyle, S., Essid, A., Bataille, J., Guérard, P., Delyle, A. G. and Alvarez, J.-C. (2011).

Mascher DG, Zech K, Nave R, Kubesch KM, Mascher HJ. Ultra-sensitive determination of Formoterol in human serum by high performance liquid chromatography and electrospray tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Jan 2;830(1):25-34. Epub 2005 Nov 7. — View Citation

Mazzarino M, de la Torre X, Fiacco I, Pompei C, Calabrese F, Botrè F. A simplified procedure for the analysis of formoterol in human urine by liquid chromatography-electrospray tandem mass spectrometry: application to the characterization of the metabolic profile and stability of formoterol in urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Jul 15;931:75-83. doi: 10.1016/j.jchromb.2013.05.021. Epub 2013 May 28. — View Citation

Millar SE. Molecular mechanisms regulating hair follicle development. J Invest Dermatol. 2002 Feb;118(2):216-25. Review. — View Citation

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. — View Citation

Miller-Larsson A, Mattsson H, Hjertberg E, Dahlbäck M, Tunek A, Brattsand R. Reversible fatty acid conjugation of budesonide. Novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab Dispos. 1998 Jul;26(7):623-30. — View Citation

Miramont S, Alvarez JC, Bourgogne E, Chéron G. [Passive cocaine inhalation by a 25-month-old child]. Arch Pediatr. 2013 Jun;20(6):654-6. doi: 10.1016/j.arcped.2013.03.006. Epub 2013 Apr 19. French. — View Citation

Mortimer KJ, Harrison TW, Tang Y, Wu K, Lewis S, Sahasranaman S, Hochhaus G, Tattersfield AE. Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma. Br J Clin Pharmacol. 2006 Oct;62(4):412-9. — View Citation

Nilsson K, Andersson M, Beck O. Phospholipid removal combined with a semi-automated 96-well SPE application for determination of budesonide in human plasma with LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Nov 1;970:31-5. doi: 10.1016/j.jchromb.2014.08.035. Epub 2014 Sep 6. — View Citation

Noppe G, de Rijke YB, Dorst K, van den Akker EL, van Rossum EF. LC-MS/MS-based method for long-term steroid profiling in human scalp hair. Clin Endocrinol (Oxf). 2015 Aug;83(2):162-6. doi: 10.1111/cen.12781. Epub 2015 Apr 27. — View Citation

Pecoraro, V. and Astore, I. P. L. (1990). Measurements of hair growth under physiological conditions. Hair and Hair Diseases. C. E. Orfanos and R. Happle. Berlin, Heidelberg, Springer Berlin Heidelberg: 237-254.

Pötsch L. A discourse on human hair fibers and reflections on the conservation of drug molecules. Int J Legal Med. 1996;108(6):285-93. Review. — View Citation

Pragst F, Balikova MA. State of the art in hair analysis for detection of drug and alcohol abuse. Clin Chim Acta. 2006 Aug;370(1-2):17-49. Epub 2006 Mar 6. Review. — View Citation

Pritchett JS, Phinney KW. Influence of chemical straightening on the stability of drugs of abuse in hair. J Anal Toxicol. 2015 Jan-Feb;39(1):13-6. doi: 10.1093/jat/bku106. Epub 2014 Oct 8. — View Citation

Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Eur Respir J. 1993 Mar;6 Suppl 16:5-40. doi: 10.1183/09041950.005s1693. — View Citation

Ray A, Raundhal M, Oriss TB, Ray P, Wenzel SE. Current concepts of severe asthma. J Clin Invest. 2016 Jul 1;126(7):2394-403. doi: 10.1172/JCI84144. Epub 2016 Jul 1. Review. — View Citation

Ribot M, Polito A, Grassin-Delyle S, Annane D, Alvarez JC. Human plasma quantification of fludrocortisone using liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry after low-dosage administration. Clin Chim Acta. 2013 May;420:109-13. doi: 10.1016/j.cca.2012.11.026. Epub 2012 Dec 7. — View Citation

Ricard F, Abe E, Duverneuil-Mayer C, Charlier P, de la Grandmaison G, Alvarez JC. Measurement of atropine and scopolamine in hair by LC-MS/MS after Datura stramonium chronic exposure. Forensic Sci Int. 2012 Nov 30;223(1-3):256-60. doi: 10.1016/j.forsciint.2012.09.015. Epub 2012 Oct 22. — View Citation

Roberts JK, Cook SF, Stockmann C, Rollins DE, Wilkins DG, Sherwin CM. A Population Pharmacokinetic Analysis of Dextroamphetamine in the Plasma and Hair of Healthy Adults. Clin Drug Investig. 2015 Oct;35(10):633-43. doi: 10.1007/s40261-015-0323-5. — View Citation

Röhrich J, Zörntlein S, Pötsch L, Skopp G, Becker J. Effect of the shampoo Ultra Clean on drug concentrations in human hair. Int J Legal Med. 2000;113(2):102-6. — View Citation

Rollins DE, Wilkins DG, Krueger GG, Augsburger MP, Mizuno A, O'Neal C, Borges CR, Slawson MH. The effect of hair color on the incorporation of codeine into human hair. J Anal Toxicol. 2003 Nov-Dec;27(8):545-51. — View Citation

Salomone A, Tsanaclis L, Agius R, Kintz P, Baumgartner MR. European guidelines for workplace drug and alcohol testing in hair. Drug Test Anal. 2016 Oct;8(10):996-1004. doi: 10.1002/dta.1999. Epub 2016 Jul 12. — View Citation

Sardela VF, Deventer K, Pereira HM, de Aquino Neto FR, Van Eenoo P. Development and validation of a ultra high performance liquid chromatography-tandem mass spectrometric method for the direct detection of formoterol in human urine. J Pharm Biomed Anal. 2012 Nov;70:471-5. doi: 10.1016/j.jpba.2012.06.042. Epub 2012 Jul 7. — View Citation

Shen HH, Du XF, Ying SM. [Comparison of Chinese guideline for asthma managment and prevention (2016 update) and global initiative for asthma (2017 update)]. Zhonghua Jie He He Hu Xi Za Zhi. 2018 Mar 12;41(3):166-168. doi: 10.3760/cma.j.issn.1001-0939.2018.03.003. Chinese. — View Citation

Skopp G, Pötsch L, Moeller MR. On cosmetically treated hair--aspects and pitfalls of interpretation. Forensic Sci Int. 1997 Jan 17;84(1-3):43-52. — View Citation

Streel B, Cahay B, Klinkenberg R. Using total error concept for the validation of a liquid chromatography-tandem mass spectrometry method for the determination of budesonide epimers in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Aug 1;877(23):2290-300. doi: 10.1016/j.jchromb.2009.02.004. Epub 2009 Feb 11. — View Citation

Sullivan SD, Rasouliyan L, Russo PA, Kamath T, Chipps BE; TENOR Study Group. Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma. Allergy. 2007 Feb;62(2):126-33. — View Citation

Szeitz A, Manji J, Riggs KW, Thamboo A, Javer AR. Validated assay for the simultaneous determination of cortisol and budesonide in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2014 Mar;90:198-206. doi: 10.1016/j.jpba.2013.12.006. Epub 2013 Dec 16. — View Citation

Taylor RL, Grebe SK, Singh RJ. Quantitative, highly sensitive liquid chromatography-tandem mass spectrometry method for detection of synthetic corticosteroids. Clin Chem. 2004 Dec;50(12):2345-52. Epub 2004 Oct 14. — View Citation

Thevis M, Opfermann G, Schänzer W. Liquid chromatography/electrospray ionization tandem mass spectrometric screening and confirmation methods for beta2-agonists in human or equine urine. J Mass Spectrom. 2003 Nov;38(11):1197-206. — View Citation

Thomas A, Geyer H, Schänzer W, Crone C, Kellmann M, Moehring T, Thevis M. Sensitive determination of prohibited drugs in dried blood spots (DBS) for doping controls by means of a benchtop quadrupole/Orbitrap mass spectrometer. Anal Bioanal Chem. 2012 May;403(5):1279-89. doi: 10.1007/s00216-011-5655-2. Epub 2012 Jan 10. — View Citation

Thorsson L, Edsbäcker S, Conradson TB. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J. 1994 Oct;7(10):1839-44. — View Citation

Tosi A, Misciali C, Piraccini BM, Peluso AM, Bardazzi F. Drug-induced hair loss and hair growth. Incidence, management and avoidance. Drug Saf. 1994 Apr;10(4):310-7. Review. — View Citation

Tsanaclis L, Nutt J, Bagley K, Bevan S, Wicks J. Differentiation between consumption and external contamination when testing for cocaine and cannabis in hair samples. Drug Test Anal. 2014 Jun;6 Suppl 1:37-41. doi: 10.1002/dta.1623. — View Citation

van den Brink KI, Boorsma M, Staal-van den Brekel AJ, Edsbäcker S, Wouters EF, Thorsson L. Evidence of the in vivo esterification of budesonide in human airways. Br J Clin Pharmacol. 2008 Jul;66(1):27-35. doi: 10.1111/j.1365-2125.2008.03164.x. Epub 2008 Apr 1. — View Citation

Van Neste D. Thickness, medullation and growth rate of female scalp hair are subject to significant variation according to pigmentation and scalp location during ageing. Eur J Dermatol. 2004 Jan-Feb;14(1):28-32. — View Citation

Van Neste D. Why care about linear hair growth rates (LHGR)? a study using in vivo imaging and computer assisted image analysis after manual processing (CAIAMP) in unaffected male controls and men with male pattern hair loss (MPHL). Eur J Dermatol. 2014 Sep-Oct;24(5):568-76. doi: 10.1684/ejd.2014.2428. — View Citation

Van Neste DJ, Rushton DH. Gender differences in scalp hair growth rates are maintained but reduced in pattern hair loss compared to controls. Skin Res Technol. 2016 Aug;22(3):363-9. doi: 10.1111/srt.12274. Epub 2015 Nov 3. — View Citation

van Zyl GU, van Mens TE, McIlleron H, Zeier M, Nachega JB, Decloedt E, Malavazzi C, Smith P, Huang Y, van der Merwe L, Gandhi M, Maartens G. Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting. J Acquir Immune Defic Syndr. 2011 Apr;56(4):333-9. doi: 10.1097/QAI.0b013e31820dc0cc. — View Citation

Wang Y, Tang Y, Moellmann H, Hochhaus G. Simultaneous quantification of budesonide and its two metabolites, 6beta-hydroxybudesonide and 16alpha-hydroxyprednisolone, in human plasma by liquid chromatography negative electrospray ionization tandem mass spectrometry. Biomed Chromatogr. 2003 Mar-Apr;17(2-3):158-64. — View Citation

Wenzel SE. Complex phenotypes in asthma: current definitions. Pulm Pharmacol Ther. 2013 Dec;26(6):710-5. doi: 10.1016/j.pupt.2013.07.003. Epub 2013 Jul 20. — View Citation

Williams J, Patsalos PN, Mei Z, Schapel G, Wilson JF, Richens A. Relation between dosage of carbamazepine and concentration in hair and plasma samples from a compliant inpatient epileptic population. Ther Drug Monit. 2001 Feb;23(1):15-20. — View Citation

Yegles M, Marson Y, Wennig R. Influence of bleaching on stability of benzodiazepines in hair. Forensic Sci Int. 2000 Jan 10;107(1-3):87-92. — View Citation

* Note: There are 102 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Budesonide/formoterol hair concentrations (active substance and metabolites)	After 4 months of treatment, the hair's concentrations of budesonide/formoterol is analyzed with mass spectrometry.	4 months
Secondary	Budesonide/formoterol concentration in three 1-cm hair segments (active substance and metabolites)	After 4 months of treatment, the concentrations of budesonide/formoterol in three 1-cm hair segments is analyzed with mass spectrometry.	4 months
Secondary	Budesonide/formoterol hair's concentration compared to the daily observance.	Patient cumulative dose is estimated from daily observance recorded by the patient in the observance record.	4 months
Secondary	Correlation between budesonide/formoterol hair concentrations, forced expiratory volume in 1 second (FEV1), and asthma control questionnaire (ACQ)	FEV1 (measured according to a standardized spirometry technique), and ACQ (patients with a score below 1.0 will have adequately controlled asthma and above 1.0 their asthma will not be well controlled) are collected at the inclusion visit and the 4 months visit	4 months