Mechanism(s)of Airflow Limitation in Moderate-severe Persistent Asthma

Официальное название

Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers

Обзор

The purpose of this study is to evaluate the site and mechanisms responsible for expiratory airflow limitation in chronic, treated, non-smoking, stable asthmatics with moderate to severe persistent expiratory airflow obstruction. Treatment will include inhaled corticosteroids and long acting beta2agonists and long acting muscarinic antagonists. We are interested in determining whether the large and/or small airways are the predominant site of airflow limitation. We are also interested in determining whether intrinsic small airways obstruction and/or loss of lung elastic recoil is responsible for expiratory airflow limitation and to what extent may be attributed to loss of lung elastic recoil vs decreased airway conductance in peripheral airways. We are also interested to evaluate the role of varying doses of inhaled corticosteroids to suppress large and small airway inflammation using exhaled nitric oxide as surrogate markers of inflammation. For comparison purposes, spirometry and measurements of exhaled nitric oxide will also be obtained if possible during a naturally occurring exacerbation of asthma. High resolution thin section CT of the lung will also be obtained. Analysis will evaluate integrity of the lung parenchyma as to absence and or presence of emphysema and extent of emphysema using voxel quantification. We will also investigate optical coherence tomography to detect clinically unsuspected emphysema. We will also obtain autopsy material when available in asthmatics who expire. Will also measure serum periostin as a marker of inflammation by collaborating with Genetech in San Francisco.

Подробное описание

Results will be evaluated during exacerbation and when stable following treatment.

Вмешательства

• Препарат budesonide/formoterol
  2 inhalations 2X/daily in treated arm/group. No placebo group
• Препарат fluticasone/salmeterol
  fluticasone 100ug/salmeterol 50ug, 1 inhalation bid noplacebo fluticasone 250ug/salmeterol 50ug, 1 inhalations bid no placebo Spiriva handihaler daily or respihaler 2 inhalations daily no placebo group
• Препарат mometasone/formoterol
  200/5 mcg two puffs bid 100/5 mcg two puffs bid Breo Ellipta once daily Spiriva capsule handihaler once daily or Spiriva respihaler 2 in no placebo group
• Препарат Prednisone
  0-15 mg daily as needed

Первичные конечные точки

• use exhaled nitric oxide as a surrogate marker of large airway vs small airway/lung inflammation following various doses of inhaled corticosteroids [Срок оценки: 20-60 days]
• determine site of airflow limitation, whether predominantly large and /or small airways using expiratory flow volume curves obtained before and after asthmatics breathe a 80% helium-20% oxygen gas mixture [Срок оценки: 20-60 days]
• investigate the mechanisms that limit expiratory airflow: intrinsic airway obstruction vs loss of lung elastic recoil [Срок оценки: 20-60 days]
• determine the extent of asthma and distribution of emphysema [Срок оценки: within 10 days following death or explanted lung if lung transplant obtained]

Вторичные конечные точки (3)

• dynamic hyperinflation [Срок оценки: 20-60 days]
• Evaluate large and small airways and lung parenchyma in autopsied or transplanted lung in asthmatics and look for unsuspected emphysema [Срок оценки: June 2018]
• Optical Coherence Tomography [Срок оценки: June 2015]

Критерии участия

Критерии включения

• Current non-smoking (<10 pack yr smoking history)
• Stable, treated asthmatics
• Age 12-95 yr
• post 180ug albuterol by MDI: FEV 1/FVC < 70% and FEV 1 <80% predicted

Критерии исключения

• Pregnancy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 1 центр

• Arthur F Gelb Medical Corporation — Lakewood

Публикации

• Gelb AF, Zamel N. Unsuspected pseudophysiologic emphysema in chronic persistent asthma. Am J Respir Crit Care Med. 2000 Nov;162(5):1778-82. doi: 10.1164/ajrccm.162.5.2001037. PMID 11069812
• Gelb AF, Licuanan J, Shinar CM, Zamel N. Unsuspected loss of lung elastic recoil in chronic persistent asthma. Chest. 2002 Mar;121(3):715-21. doi: 10.1378/chest.121.3.715. PMID 11888951
• Gelb AF, Gutierrez CA, Weisman IM, Newsom R, Taylor CF, Zamel N. Simplified detection of dynamic hyperinflation. Chest. 2004 Dec;126(6):1855-60. doi: 10.1378/chest.126.6.1855. PMID 15596684
• Gelb AF, Flynn Taylor C, Shinar CM, Gutierrez C, Zamel N. Role of spirometry and exhaled nitric oxide to predict exacerbations in treated asthmatics. Chest. 2006 Jun;129(6):1492-9. doi: 10.1378/chest.129.6.1492. PMID 16778266
• Gelb AF, Taylor CF, Nussbaum E, Gutierrez C, Schein A, Shinar CM, Schein MJ, Epstein JD, Zamel N. Alveolar and airway sites of nitric oxide inflammation in treated asthma. Am J Respir Crit Care Med. 2004 Oct 1;170(7):737-41. doi: 10.1164/rccm.200403-408OC. Epub 2004 Jun 30. PMID 15229098
• Gelb AF, Zamel N, Krishnan A. Physiologic similarities and differences between asthma and chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2008 Jan;14(1):24-30. doi: 10.1097/MCP.0b013e3282f197df. PMID 18043272
• Gelb AF, Moridzadeh R, Singh DH, Fraser C, George SC. In moderate-to-severe asthma patients monitoring exhaled nitric oxide during exacerbation is not a good predictor of spirometric response to oral corticosteroid. J Allergy Clin Immunol. 2012 Jun;129(6):1491-8. doi: 10.1016/j.jaci.2012.03.036. Epub 2012 May 2. PMID 22560478
• Gelb AF, Yamamoto A, Mauad T, Kollin J, Schein MJ, Nadel JA. Unsuspected mild emphysema in nonsmoking patients with chronic asthma with persistent airway obstruction. J Allergy Clin Immunol. 2014 Jan;133(1):263-5.e1-3. doi: 10.1016/j.jaci.2013.09.045. Epub 2013 Nov 28. No abstract available. PMID 24290280

Идентификаторы

NCT: NCT00576069 · 20070934

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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