Small Airway Involvement in Patients With Chronic Hypersensitivity Pneumonitis

NCT02523833 | Completed

• 1 other identifier: SDC 3966/13/091
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Hypersensitivity pneumonitis (HP) is a syndrome with variable clinical presentation in which lung inflammation is caused by inhalation of specific organic antigens or low molecular weight particles in previously sensitized individuals. Systemic symptoms may or may not be present. Chronic HP represents the final stage of the disease, caused by prolonged exposure to a particular antigen, leading to pulmonary fibrosis. In chronic HP, pulmonary function tests (PFTs) commonly present a restrictive ventilatory pattern, with decreased diffusion of carbon monoxide (DLCO). Some patients can also have obstructive disorders with expiratory flow limitation, due to obstruction of the small airways typically caused by bronchiolar involvement in this pathology. However, PFTs are relatively insensitive for detecting small airway involvement when there is concomitant interstitial fibrosis. First, conventional PFTs may be normal in patients with small airway involvement, since they contribute to less than 30% of the total airway resistance. In addition, damage to the small airways in HP is generally occurring parallel to areas of focal fibrosis - even when small airways are involved, these regions can be completely ignored, since they are excluded from ventilation. In summary, traditional PFTs are not sufficiently sensitive to detect diffuse small airway involvement in these diseases. In these cases, other functional tests, such as forced oscillation technique (FOT) and high resolution computer tomography (HRCT) scans of the chest with expired studies, could be used for this purpose. This will be a cross-sectional study, which will include the following evaluations in 28 patients with HP recruited from our clinic: \- Clinical variables: (A) demographic and anthropometric data; (B) Clinical data: Onset of symptoms and time of diagnosis C) Dyspnea score: D) Smoking: \* Current or former smoker \* Smoking history (number of cigarettes smoked per day and for how long);

• Spirometry with forced and slow maneuvers before and after bronchodilator (salbutamol);
• Plethysmography to measure lung volumes;
• Diffusion capacity of carbon monoxide (DLCO);
• High-resolution chest CT with expiratory scans;
• Six-minute walk test;
• Cardio-respiratory test using a maximal incremental treadmill.
• Forced oscillation technique (FOT).

Conditions

Hypersensitivity Pneumonitis; Airway Disease Small

Outcome Measures

Primary Outcomes (1)

• Pletismography - forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC) < 0.7, residual volume (VR) and VR/total lung capacity (TLC) values and changes with salbutamol

  Percentage of VEF1/FVC \< 0.7, residual volume (VR) \>120% predicted and VR/total lung capacity (TLC)\>.45 values and changes with salbutamol

  One day visit

Secondary Outcomes (2)

• Air trapping in expiratory chest CT scans

  One day visit

• Reactance and impedance of small airways through forced oscillation technique

  One day visit

Other Outcomes (1)

• Maximal cardiopulmonary exercise testing

  One day visit

Study Arms (1)

Chronic HP patients

OTHER

Chronic hypersensitivity pneumonitis patients - use of salbutamol

Drug: Salbutamol

Interventions

Salbutamol DRUG

Salbutamol after spirometry, plethysmography and forced oscillation technique.

Also known as: Aerolin

Chronic HP patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of chronic hypersensitivity pneumonitis confirmed by:
• patients with known exposure to antigen, tomographic criteria and absence of other diagnoses;
• confirmation with histology obtained by transthoracic biopsy, surgical biopsy or bronchoalveolar lavage with lymphocytosis above 30%;
• Age between 18 to 75 years;
• Clinically stable (no exacerbations or hospitalizations related to the underlying disease) for at least 6 weeks;
• Compliance with signing an informed consent for participation in the project.

You may not qualify if:

• Patients with FEV1 and / or DLCO \<30% predicted;
• Patients using supplemental oxygen;
• Previous diagnosis of asthma or COPD;
• Pregnant women;
• Musculoskeletal disorders that limit exercise;
• Another medical condition that might interfere with the execution of tests;
• Current or past smoking history with tobacco intake greater than 30 pack-years;
• Severe heart disease functional class New York Heart Association (NYHA) III-IV) and / or decompensated hear failure.

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead

Study Sites (1)

Olívia Meira Dias

São Paulo, 05409002, Brazil

Location

Related Publications (7)

• Dellaca RL, Duffy N, Pompilio PP, Aliverti A, Koulouris NG, Pedotti A, Calverley PM. Expiratory flow limitation detected by forced oscillation and negative expiratory pressure. Eur Respir J. 2007 Feb;29(2):363-74. doi: 10.1183/09031936.00038006. Epub 2006 Nov 1.

  PMID: 17079262 BACKGROUND

• Dellaca RL, Santus P, Aliverti A, Stevenson N, Centanni S, Macklem PT, Pedotti A, Calverley PM. Detection of expiratory flow limitation in COPD using the forced oscillation technique. Eur Respir J. 2004 Feb;23(2):232-40. doi: 10.1183/09031936.04.00046804.

  PMID: 14979497 BACKGROUND

• Lacasse Y, Selman M, Costabel U, Dalphin JC, Ando M, Morell F, Erkinjuntti-Pekkanen R, Muller N, Colby TV, Schuyler M, Cormier Y; HP Study Group. Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2003 Oct 15;168(8):952-8. doi: 10.1164/rccm.200301-137OC. Epub 2003 Jul 3.

  PMID: 12842854 RESULT

• Selman M, Pardo A, Barrera L, Estrada A, Watson SR, Wilson K, Aziz N, Kaminski N, Zlotnik A. Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2006 Jan 15;173(2):188-98. doi: 10.1164/rccm.200504-644OC. Epub 2005 Sep 15.

  PMID: 16166619 RESULT

• Lynch DA, Newell JD, Logan PM, King TE Jr, Muller NL. Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis? AJR Am J Roentgenol. 1995 Oct;165(4):807-11. doi: 10.2214/ajr.165.4.7676971.

  PMID: 7676971 RESULT

• Silva CI, Muller NL, Lynch DA, Curran-Everett D, Brown KK, Lee KS, Chung MP, Churg A. Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology. 2008 Jan;246(1):288-97. doi: 10.1148/radiol.2453061881.

  PMID: 18096541 RESULT

• Buschman DL, Gamsu G, Waldron JA Jr, Klein JS, King TE Jr. Chronic hypersensitivity pneumonitis: use of CT in diagnosis. AJR Am J Roentgenol. 1992 Nov;159(5):957-60. doi: 10.2214/ajr.159.5.1414806.

  PMID: 1414806 RESULT

MeSH Terms

Conditions

Alveolitis, Extrinsic Allergic

Interventions

Albuterol

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Officials

• Carlos Roberto R de Carvalho, MD, PhD

  Heart Institute (InCor)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical doctor

Study Record Dates

• First Submitted: August 9, 2015
• First Posted: August 14, 2015
• Study Start: September 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: November 20, 2017
• Last Updated: May 2, 2018

Record last verified: 2018-05

Locations

BR (1)