General Risk Factors and Inflammatory Determinants in Older Patients With Asthma (GRANDMA)

A cross-sectional study in asthma patients to determine if a late age of onset asthma (start symptoms >18 years old), is associated with more persistent airway/systemic inflammation, worse asthma control, more co-morbidity, a different microbiome and poorer quality of life despite the use of optimized asthma therapy.

Study Overview

• Status: Completed
• Conditions: Asthma; Childhood Asthma; Late-Onset Asthma
• Intervention / Treatment: Procedure: Sputum induction; Procedure: Blood sample

Detailed Description

For ages, asthma has been considered a disease for children and young adults. However, nowadays 30% of all asthma patients is over 50 years old. Asthma in the elderly is generally more severe and approximately 50% of all deaths drom asthma occur in this age group. With rapid aging of the global population, the burden of asthma in the elderly will further increase.

Asthma is a heterogeneous disease and the question is whether asthma in the elderly can be considered the same disease as asthma in children and young adults. The pathophysiology and risk factors of asthma in the elderly are still not completely understood. Good characterization of asthma in the elderly requires clinical phenotyping as well as a thorough analysis of the underlying cellular and molecular mechanisms. It is hypothesized that in older asthma patients, a late age of onset (start asthma symptoms >18 years) is associated with more persistent airway/systemic inflammation, worse asthma control, more co-morbidity and poorer quality of life despite the use of optimized asthma therapy.

• Study Type: Observational
• Enrollment (Actual): 90

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3045PM
      • Franciscus Gasthuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The aim is to enrol 30 patients with early onset asthma (age of onset < 18 years) and 30 patients with late onset asthma (age of onset > 18 years); all with a smoking history of < 10 PY. Both groups consist of 15 older asthma patients (> 50 years) and 15 younger asthma patients (< 50 years); per age group 15 healthy controls serve as comparison (no asthma). Asthma diagnosis is based on presence of typical clinical symptoms, reversible airway obstruction (+12% improvement in FEV1 after bronchodilator) or bronchial hyperreactivity (PC20 < 8 mg/ml) or a FeNO > 50 ppb. All asthma patients have GINA step 4-5 medication (high dose ICS/LABA) and are not adequately controlled (ACQ > 0,75)

Description

Inclusion Criteria Asthma patients:

• Age between 18-80 years
• Smoking history of < 10 packyears (PY)
• Willing and able to comply with the study protocol
• Asthma diagnosis is based on presence of typical clinical symptoms, reversible airway obstruction (+12% improvement in forced expiratory volume at one second (FEV1) after bronchodilator) or bronchial hyperreactivity (PC20 < 8 mg/ml) or a (fractional exhaled nitric oxide) FeNO > 50 ppb. - All asthma patients have (Global Initiative for Asthma ) GINA step 4-5 medication (high dose ICS/LABA).
• Asthma control questionaire (ACQ) > 0,75
• Written informed consent.

Inclusion Criteria Healthy controls:\Inclusion criteria healthy control:

• Written informed consent
• Age between 18-80 years.

Exclusion Criteria:

• Smoking history of > 10 PY
• Age < 18 years or > 80 years
• Not able to speak or write Dutch language.
• Not able to perform lung function test/sputum induction
• ACQ < 0,75

• Other diseases which could influence pulmonary function and/or the immune system such as: o A possible infection of the upper- or lower respiratory tract 4 weeks prior to the collection of materials;

  • Chronic obstructive pulmonary disorder (COPD) in the medical history;
  • Auto-immune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), myasthenia gravis or Goodpasture's syndrome;
  • Malignancies;
  • Inherited or acquired immunodeficiency
  • Pregnancy;

Exclusion criteria healthy controls:

• Asthma, as defined earlier (page 13);
• An abnormal spirometry with a forced vital capacity (FVC) or FEV1 below the 80% of the predicted value
• A liaison with the coordinating or principal investigator, which could likely influence the decision to participate in this study voluntarily (in concordance with the World Meteorological Organization (WMO) -article 5);

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Early onset asthma; Sputum induction according to the European Respiratory Society (ERS) protocol. A blood sample of 100ml will be taken.	Procedure: Sputum induction; Sputum induction according to the ERS protocol; Procedure: Blood sample; A blood sample of 100ml will be taken.
Late onset asthma; Sputum induction according to the ERS protocol. A blood sample of 100ml will be taken.	Procedure: Sputum induction; Sputum induction according to the ERS protocol; Procedure: Blood sample; A blood sample of 100ml will be taken.
No pulmonary disease; Sputum induction according to the ERS protocol. A blood sample of 100ml will be taken.	Procedure: Sputum induction; Sputum induction according to the ERS protocol; Procedure: Blood sample; A blood sample of 100ml will be taken.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in number and activation status of inflammatory cells in sputum and blood	To compare the differences in number and activation status of inflammatory cells in sputum and blood of different subgroups of asthmatics.)	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interleukin cell type 2 (ILC2) correlation and disease phenotype	To find correlations between ILC2 numbers and characteristics and immunological and clinical disease phenotype. -	1 month
Hair cortisol	Detection of cortisol levels in hair, to determine a possible method to check Inhaled corticosteroid (ICS) adherence.	1 month
Inflammatory profile	To measure physiological factors (lung function, activity level) and relate them to inflammatory profile.	1 month
Selfmanagement / coping strategies	To investigate the relationship between duration and onset of asthma and self-management/coping strategies of patients.	1 month
The effect of aging on inflammation, physiology, psychology and co-morbidities in asthma.	The effect of aging on inflammation, physiology, psychology and co-morbidities in asthma.	1 month
Detection of different microbiome subgroups of asthmatics and compare with controls.	Detection of microflora/microbiome pattern in sputum and faeces in different subgroups of asthmatics and compare with controls.	1 month

Collaborators and Investigators

• Sponsor: Gerdien Tramper
• Investigators: Principal Investigator: GM de Boer, MD, Franciscus Gasthuis Rotterdam; Principal Investigator: GJ Braunstahl, MD, PhD, Franciscus Gasthuis Rotterdam; Principal Investigator: GA Tramper, MD, PhD, Franciscus Gasthuis Rotterdam

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 8, 2017
• Primary Completion (ACTUAL): August 31, 2019
• Study Completion (ACTUAL): December 31, 2019

Study Registration Dates

• First Submitted: September 8, 2017
• First Submitted That Met QC Criteria: September 8, 2017
• First Posted (ACTUAL): September 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 14, 2020
• Last Update Submitted That Met QC Criteria: August 13, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: asthma; inflammation; microbiome; comorbidity; age of onset
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: GRANDMA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No