A retrospective and prospective observational study of asthma designed to determine real-world and molecular description of asthma according to treatment and type 2 biology

REGAIN is a retrospective and prospective asthma cohort study designed to determine real-world molecular description of asthma according to treatment and type 2 biology. The researchers will enroll 5 pre-specified groups of participants with asthma of specific interest for mechanistic analyses according to clinically determined type 2 inflammatory endotype and response to therapy with inhaled steroids and other inhaled controllers with or without asthma biologics. This study is conducted at asthma specialty programs at Mount Sinai National Jewish Health Respiratory Institute in New York and National Jewish Health, Denver, Colorado, USA. Participants with asthma meeting specific inclusion criteria were identified and enrolled by screening electronic medical records from pulmonary and allergy specialty programs. Targeted populations included 5 categories of asthma patients as outlined in Table 1 including the following: (1) patients with type 2 asthma with symptom control at time of enrollment (ACT > 20) on standard Global Initiative For Asthma (GINA) step therapy (n=200) (2) asthma managed on stable biological therapy (n=200), (3) type 2 asthma with prior treatment with at least 2 biological therapies, (n=60), (4) likely type 2 low asthma patients (n=200), (5) asthma patients scheduled to be started de novo on biological therapies (n=120), and (6) healthy participants (n=400). Healthy participants were recruited in New York and Denver by community advertising. An optional study component employing a mobile phone application, use of digital inhaler monitors, and home digital peak flow will contribute data regarding medication use and lung function in the community and collect environmental data impacting asthma using geolocation data.

Inclusion Criteria for Asthma Participants:

• Age >18

• Clinical diagnosis of asthma verified by a specialist physician (allergist or pulmonologist) and one or more of the following:

  • Historical variability of airflow limitation via classic reversibility criteria (> 12%, 200 ml within past 10 years).
  • Historical methacholine challenge with PC20 < 8 mg/ml (within past 10 years).
  • FEV1 variability, between two clinic visits, of 20% within the past 5 years either with improvement according to appropriate therapy or decrease in lung function upon withdrawal or decrease of therapy.
  • Elevated FeNO > 50 ppb at least once historically (within past 10 years).
  • < 10 pack per year personal tobacco use and not a current smoker of cigarettes or other inhalational tobacco (e-cigarette, marijuana or other inhalational drug use).
  • At least partial response of presenting symptoms to GINA Step 1-4 asthma treatment (ICS or ICS/LABA as determined by study physician investigators)

Exclusion criteria for Asthma Participants:

• >10 pack per year tobacco, current smoker of cigarettes, e-cigarettes or other inhalational drug use.
• Clinically significant lung disease based on imaging or clinical history other than asthma as determined by an allergist or pulmonologist
• Currently pregnant or breastfeeding
• Anemia with hemoglobin level ˂9 mg/dl at the time of study enrollment

Inclusion Criteria for Healthy Controls:

• Age > 18
• No current smoking (quit > 6 months previously) confirmed by serum cotinine level < 1 ng/ml
• < 10 pack year tobacco history
• No current respiratory symptoms (cough wheeze, dyspnea)
• No current lung disease or other significant medical comorbidity (see exclusion criteria below)

Exclusion Criteria for Healthy Controls:

• Age < 18
• Diagnosis of asthma, COPD, emphysema, bronchiectasis or other significant lung disease
• Treatment or a history of malignancy currently or within the past 5 years, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin
• Treatment of inflammatory disease or autoimmune disease such as lupus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis or others
• Treatment with immune modulating medications for a health condition including any of the following (systemic glucocorticoids, sirolimus, tacrolimus, anti-TNF abatacept, azathioprine, methotrexate, cyclosporine, cyclophosphamide, immunoglobulin, mycophenolate, rituximab, plaquenil or others)
• Treatment with anti-IL5, anti-IgE and anti-IL4 receptor alpha for non-asthma indications
• Vaccination within 4 weeks
• History of clinically significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, gastrointestinal, uncontrolled diabetes, uncontrolled infectious disease, HIV infection, cerebrovascular, or other significant medical illness or disorder which in the judgment of the investigator could impact the participant as a healthy control
• Serum cotinine > 1 ng/ml

Specific groups of asthma patients as outlined and healthy volunteers

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Specify Other Time FrameAfter last participant completes the study and publication.

Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose.

To achieve aims in the approved proposal. Specify Other Mechanism Please email requests for access to linda.rogers@mssm.edu or Emanuele.deRinaldis@sanofi.com