Clinical trial NCT03278561: General Risk Factors and Inflammatory Determinants in Older Patients With Asthma
Official title: General Risk Factors and Inflammatory Determinants in Older Patients With Asthma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Late-Onset Asthma
Childhood Asthma
Keywords: asthma
age of onset
inflammation
comorbidity
microbiome
Lead sponsor: Franciscus Gasthuis
Sponsor class: OTHER
First posted: 2017-09-11
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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)

Brief summary: 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.

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.

Eligibility criteria: 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);

Primary outcomes:
measure: Differences in number and activation status of inflammatory cells in sputum and blood
timeFrame: 1 month
Secondary outcomes:
measure: Interleukin cell type 2 (ILC2) correlation and disease phenotype
timeFrame: 1 month
measure: Hair cortisol
timeFrame: 1 month
measure: Inflammatory profile
timeFrame: 1 month
measure: Selfmanagement / coping strategies
timeFrame: 1 month
measure: The effect of aging on inflammation, physiology, psychology and co-morbidities in asthma.
timeFrame: 1 month
measure: Detection of different microbiome subgroups of asthmatics and compare with controls.
timeFrame: 1 month
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis
state: Zuid-Holland
Study officials:
affiliation: Franciscus Gasthuis Rotterdam
name: GM de Boer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Franciscus Gasthuis Rotterdam
name: GJ Braunstahl, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Franciscus Gasthuis Rotterdam
name: GA Tramper, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: