AMP-BPT and His-BPT for Assessment of Asthma

NCT02318043 | Completed

• 1 other identifier: GWJ
• Study Type: interventional
• Target: 84
• Locations: 0 countries
• Sites: N/A

Brief Summary

Adenosine monophosphate (AMP) may reflect airway inflammation and hyperresponsiveness, but relationship between AMP and histamine (His, a conventional stimulus) bronchial provocation test (BPT) in asthma is not fully elucidated. The investigators aimed to compare both BPTs and determine their usefulness in reflecting changes of asthmatic symptoms. BPTs were performed in cross-over fashion, at 2-4day intervals. Cumulative doses eliciting 20% FEV1fall (PD20FEV1), diagnostic performance and adverse events were compared. Patients with PD20FEV1 lower than geometric mean were defined as responders, otherwise poor responders. Patients with uncontrolled and partly controlled asthma, who maintained their original inhaled corticosteroids therapy, underwent reassessment of airway responsiveness and asthmatic symptoms 3 and 6 months after.

Conditions

Asthma

Keywords

adenosine monophosphate; histamine; bronchial provocation test; asthma symptom score; asthma control

Outcome Measures

Primary Outcomes (2)

• Cumulative dose eliciting 20% fall in FEV1 (PD20FEV1)

  Cumulative dose eliciting 20% fall in FEV1 (PD20FEV1), reported as

  up to 12 months (Jan 2007 to Dec 2007)

• Asthma symptom score as proposed by Hoggs et al

  Asthma symptom score recorded within 1 week, with the highest possible score of 42 for the whole week

  up to 12 months (Jan 2007 to Dec 2007)

Secondary Outcomes (9)

• Baseline spirometry (FVC, FEV1, FEV1/FVC, MMEF, PEF)

  up to 12 months (Jan 2007 to Dec 2007)

• Maximal decrease in FVC following bronchial provocation (expressed as percentage)

  up to 12 months (Jan 2007 to Dec 2007)

• Maximal decrease in FEV1 following bronchial provocation (expressed as percentage)

  up to 12 months (Jan 2007 to Dec 2007)

• Maximal decrease in MMEF following bronchial provocation (expressed as percentage)

  up to 12 months (Jan 2007 to Dec 2007)

• Maximal decrease in PEF following bronchial provocation (expressed as percentage)

  up to 12 months (Jan 2007 to Dec 2007)

Other Outcomes (1)

• incidence of adverse events of both BPTs

  up to 12 months (Jan 2007 to Dec 2007)

Study Arms (2)

AMP-BPT

ACTIVE COMPARATOR

Methods of AMP-BPT, by applying dosimeters, resembled that reported previously \[see references 21-25\]. Briefly, dilutions were delivered via nebulizers (output: 160 μl/min) using automated APS pro system (JAEGER, Hochburg, Germany). Inhalation challenge with normal saline served as control step. Challenge steps were proceeded if FEV1 fall \<15% and restored to \<10% within 1 minute. Subsequent inhalation challenges were performed at 1-minute intervals, and ceased when FEV1 fell by ≥20%. Salbutamol was administered via spacer (Volumatic, Allen \& Hanbury's, UK). Spirometry was reexamined at minutes 3, 5, 10 and thereafter, to ensure safety, before discharge.

Drug: inhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg)

His-BPT

ACTIVE COMPARATOR

Methods of His-BPT, by applying dosimeters, resembled that reported previously \[see references 21-25\]. Briefly, dilutions were delivered via nebulizers (output: 160 μl/min) using automated APS pro system (JAEGER, Hochburg, Germany). Inhalation challenge with normal saline served as control step. Challenge steps were proceeded if FEV1 fall \<15% and restored to \<10% within 1 minute. Subsequent inhalation challenges were performed at 1-minute intervals, and ceased when FEV1 fell by ≥20%. Salbutamol was administered via spacer (Volumatic, Allen \& Hanbury's, UK). Spirometry was reexamined at minutes 3, 5, 10 and thereafter, to ensure safety, before discharge.

Drug: inhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg)

Interventions

inhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg) DRUG

Patients with uncontrolled and partly controlled asthma, following accomplishment of study 1, were invited to participate in observational study (study 2), which sought to determine usefulness of both BPTs in reflecting improvement of asthmatic symptoms following 3 and 6 months of moderate-dose ICSs treatment (400\~800μg budesonide or equivalent). Patient continued to administer their original ICS during follow-up. During two follow-up visits (3 months apart), AMP-BPT, His-BPT and Hogg's symptom scores were reassessed.

AMP-BPT; His-BPT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged 18\~65 years;
• nil respiratory infection within 3 weeks;
• normal chest radiography;
• baseline FEV1\>60% predicted;
• withdrawn from, if any, oral leukotriene modifiers, corticosteroid or anti-histamine for 5 days, oral xanthenes or long-acting bronchodilators for 2 days, inhaled corticosteroids (ICSs) for 24 hours, and salbutamol for 6 hours

You may not qualify if:

• FEV1 fall ≥20% following saline inhalation;
• other chronic lower respiratory diseases (i.e. COPD);
• severe systemic diseases (i.e. uncontrolled hypertension, malignancy);
• limited understanding.
• For healthy subjects, they had to be aged 18\~65 years and had nil respiratory infection within 3 weeks, systemic diseases and had normal lung function.

Sponsors & Collaborators

• Guangzhou Institute of Respiratory Disease: lead

Related Publications (25)

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  PMID: 12629006 BACKGROUND

• Hanania NA. Targeting airway inflammation in asthma: current and future therapies. Chest. 2008 Apr;133(4):989-98. doi: 10.1378/chest.07-0829.

  PMID: 18398119 BACKGROUND

• Leuppi JD. Bronchoprovocation tests in asthma: direct versus indirect challenges. Curr Opin Pulm Med. 2014 Jan;20(1):31-6. doi: 10.1097/MCP.0000000000000009.

  PMID: 24275928 BACKGROUND

• Janssens T, Verleden G, De Peuter S, Petersen S, Van den Bergh O. Predicting asthma treatment outcome at diagnosis: the role of symptom perception during a histamine challenge test. J Asthma. 2012 Apr;49(3):230-6. doi: 10.3109/02770903.2012.656864. Epub 2012 Feb 9.

  PMID: 22316110 BACKGROUND

• Dor A, Liebhart J, Malolepszy J. [Comparison of exercise and histamine provocation tests in patients with bronchial asthma]. Pneumonol Alergol Pol. 1999;67(1-2):22-7. Polish.

  PMID: 10481521 BACKGROUND

• Driver AG, Kukoly CA, Ali S, Mustafa SJ. Adenosine in bronchoalveolar lavage fluid in asthma. Am Rev Respir Dis. 1993 Jul;148(1):91-7. doi: 10.1164/ajrccm/148.1.91.

  PMID: 8317821 BACKGROUND

• Ali S, Mustafa SJ, Driver AG, Metzger WJ. Release of adenosine in bronchoalveolar lavage fluid following allergen bronchial provocation in allergic rabbits. Am Rev Respir Dis 1991;143:A417

  BACKGROUND

• Polosa R, Ng WH, Crimi N, Vancheri C, Holgate ST, Church MK, Mistretta A. Release of mast-cell-derived mediators after endobronchial adenosine challenge in asthma. Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 1):624-9. doi: 10.1164/ajrccm/151.3_Pt_1.624.

  PMID: 7881647 BACKGROUND

• van den Berge M, Kerstjens HA, Meijer RJ, de Reus DM, Koeter GH, Kauffman HF, Postma DS. Corticosteroid-induced improvement in the PC20 of adenosine monophosphate is more closely associated with reduction in airway inflammation than improvement in the PC20 of methacholine. Am J Respir Crit Care Med. 2001 Oct 1;164(7):1127-32. doi: 10.1164/ajrccm.164.7.2102135.

  PMID: 11673197 BACKGROUND

• De Meer G, Heederik D, Postma DS. Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV(1). Am J Respir Crit Care Med. 2002 Feb 1;165(3):327-31. doi: 10.1164/ajrccm.165.3.2104066.

  PMID: 11818315 BACKGROUND

• Suh DI, Lee JK, Kim CK, Koh YY. Bronchial hyperresponsiveness to methacholine and adenosine 5'-monophosphate, and the presence and degree of atopy in young children with asthma. Clin Exp Allergy. 2011 Mar;41(3):338-45. doi: 10.1111/j.1365-2222.2010.03664.x. Epub 2011 Jan 24.

  PMID: 21255136 BACKGROUND

• Suh DI, Lee JK, Kim CK, Koh YY. Methacholine and adenosine 5'-monophosphate (AMP) responsiveness, and the presence and degree of atopy in children with asthma. Pediatr Allergy Immunol. 2011 Feb;22(1 Pt 2):e101-6. doi: 10.1111/j.1399-3038.2010.01110.x.

  PMID: 21342276 BACKGROUND

• Kim CK, Choi SJ, Lee JK, Suh DI, Koh YY. Bronchial hyperresponsiveness to methacholine and adenosine monophosphate and the degree of atopy in children with allergic rhinitis. Ann Allergy Asthma Immunol. 2011 Jan;106(1):36-41. doi: 10.1016/j.anai.2010.10.019.

  PMID: 21195943 BACKGROUND

• The Respiratory Society of the Chinese Medical Association. Guidelines for lung function testing (Part 3): Histamine and methacholine bronchial provocation test. Zhonghua Jie He He Hu Xi Za Zhi 2014; 37:566-71

  BACKGROUND

• O'Byrne P, Bateman ED, Bousquet JD. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Updated 2006. Available at http://www.ginasthma.org/Guidelines/guidelines-resources.html Latest accessed: Sep 20, 2014

  BACKGROUND

• Hogg JC, James AL, Pare PD. Evidence for inflammation in asthma. Am Rev Respir Dis. 1991 Mar;143(3 Pt 2):S39-42. doi: 10.1164/ajrccm/143.3_Pt_2.S39. No abstract available.

  PMID: 2003688 BACKGROUND

• 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. doi: 10.1183/09031936.05.00034805. No abstract available.

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• Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, 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. General considerations for lung function testing. Eur Respir J. 2005 Jul;26(1):153-61. doi: 10.1183/09031936.05.00034505. No abstract available.

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• Guan W, Zheng J, Gao Y, Jiang C, An J, Yu X, Liu W. Leukotriene D4 bronchial provocation test: methodology and diagnostic value. Curr Med Res Opin. 2012 May;28(5):797-803. doi: 10.1185/03007995.2012.678936. Epub 2012 May 3.

  PMID: 22435894 BACKGROUND

• Guan W, Zheng J, Gao Y, Jiang C, Xie Y, An J, Yu X, Liu W, Zhong N. Leukotriene D4 and methacholine bronchial provocation tests for identifying leukotriene-responsiveness subtypes. J Allergy Clin Immunol. 2013 Feb;131(2):332-8.e1-4. doi: 10.1016/j.jaci.2012.08.020. Epub 2012 Oct 4.

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• Guan WJ, Zheng JP, Gao Y, Jiang CY, Shi X, Xie YQ, Liu QX, Jiang M, An JY, Yu XX, Liu WT, Zhong LP, Wu ZP, Zhong NS. Impulse oscillometry for leukotriene D4 inhalation challenge in asthma. Respir Care. 2013 Dec;58(12):2120-6. doi: 10.4187/respcare.02417. Epub 2013 May 28.

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MeSH Terms

Conditions

Asthma

Interventions

Fluticasone; Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 7, 2014
• First Posted: December 17, 2014
• Study Start: January 1, 2007
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: December 17, 2014

Record last verified: 2014-12