Personalized Treatment Algorithms for Difficult-to-treat Asthma

With this study investigators will conduct study visits to determine and quantify known molecular, genetic, genomic, epigenetics, immunologic, and exposure biomarkers that will help elucidate molecular disease endotype within the difficult-to-treat phenotype. This information will be used along with clinical, psychosocial, and adherence data to develop a personalized treatment plan. Following the personalized treatment plan, study clinicians will prescribe the medications through a home delivery or routine pharmacy depending on the family's preference and covered by the participant's health insurance. Investigators will track disease outcome metrics including exacerbations, symptom-free days, and asthma symptom scores to determine the effectiveness of this personalized approach.

• Cholecalciferol (Drug), also known as Vitamin D: Oral administration
• antihistamine (Drug), also known as cetirizine, loratadine: Oral administration
• Azithromycin (Drug), also known as Zithromax: Oral administration
• emollient cream (Drug): Topical
• Fluticasone Propionate (Drug), also known as Flonase Nasal Spray: Nasal spray
• Asthma Controller Medication (Drug), also known as Mometasone/Formoterol, Fluticasone/Salmeterol, Mometasone Furoate, Fluticasone, Beclomethasone, Budesonide/Formoterol, Tiotropium: Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.

Primary outcomes

• Change in Composite Asthma Severity Index (CASI) [Baseline to 12 months]: CASI was measured by questionnaire and is a severity score of symptom burden, exacerbations, healthcare utilization, lung function and dose of inhaled corticosteroids. The change in CASI score was calculated between V1 (Baseline), V2 (Guideline Care - before intervention), and V3 (12 Months). \[The CASI score has a minimum value = 0, maximum value = 20, a higher score indicates greater asthma severity\]

Secondary outcomes

• Asthma Control Test (ACT) [Baseline to 12 months]: ACT was measured by questionnaire, assessing frequency of reported asthma symptoms, rescue medication use, the effect of asthma on daily functioning, and overall asthma control. The change in ACT score was calculated between V1 (Baseline), V2 (Guideline Care - before intervention), and V3 (12 Months). \[The ACT score has a minimum value = 5, maximum value = 25, a score 19 indicates well-controlled asthma\]
• Pulmonary Function Measured by Spirometry: Forced Expiratory Volume in 1 Second (FEV1) / Forced Vital Capacity (FVC) [Baseline to 12 months]: FEV1 is air volume exhaled in 1 second during spirometry. Forced vital capacity is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. The change in FEV1/FVC was calculated between V1 (Baseline), V2 (Guideline Care - before intervention), and V3 (12 Months). This will be used as a measurement in asthma severity. \[A lower FEV1/FVC ratio indicates more severe asthma\]
• Adherence of Asthma Controller Medication [Baseline to 12 months]: Adherence was measured using the Propeller Health Inhaler monitor and web-based software management platform that tracks adherence of asthma medications. The change in adherence was calculated between V1 (baseline) to V3 (12 Months).

Sex: All, ages: 6 Years to 17 Years

Inclusion Criteria:

* History of provider-diagnosed asthma
* Meets one of the following definition for NAEPP guidelines uncontrolled moderate persistent asthma or severe persistent asthma in the past 12 months:

  * NAEPP step 3-4 with one of the following criteria in the past 12 months:

    * Two Asthma Control Test (ACT) scores <20
    * 1 Urgent Care or Emergency Department visit or hospitalization for asthma
    * >2 prednisone bursts
  * NAEPP step 5-6
* Current health insurance coverage at enrollment. This will be verified at V1 at the registration desk. If the family loses insurance during the study, the patient will be referred to the pulmonary social worker and financial office for assistance
* Reside at a primary home on average 5 out of 7 days a week.
* Primary home is within a 40 mile radius of Cincinnati Children's Base location or PI's discretion.

Exclusion Criteria:

* Received biologic therapy 6 months prior to enrollment
* Received systemic steroids 6 weeks prior to enrollment
* Active chronic disease apart from asthma or allergic disease
* Co-morbid lung disease
* Dependence on immunosuppressive drugs for a condition other than asthma
* Participant is pregnant
* Has a severe bleeding disorder
* Has significant developmental disability
* Share a bedroom with a currently enrolled Breath Warriors study participant

Participant flow

Outcome results

• Change in Composite Asthma Severity Index (CASI) (Primary), Median, score on a scale: Personalized Treatment 5 (5 to 6) (p 0.52)
• Asthma Control Test (ACT) (Secondary), Median, score on a scale: Personalized Treatment 23.0 (20.0 to 23.0) (p 0.45)
• Pulmonary Function Measured by Spirometry: Forced Expiratory Volume in 1 Second (FEV1) / Forced Vital Capacity (FVC) (Secondary), Median, Ratio: Personalized Treatment 0.81 (0.76 to 0.86) (p 0.27)
• Adherence of Asthma Controller Medication (Secondary), Median, percentage of medication taken: Personalized Treatment 42 (21 to 57) (p 0.17)

Adverse events

Time frame: 1 year

Serious adverse events by term

Other adverse events by term

• Results publication: Guilbert TW, Biagini JM, Ramsey RR, Keidel K, Curtsinger K, Kroner JW, Durrani SR, Stevens M, Pilipenko V, Martin LJ, Kercsmar CM, Hommel K, Hershey GKK. Treatment by biomarker-informed endotype vs guideline care in children with difficult-to-treat asthma. Ann Allergy Asthma Immunol. 2022 May;128(5):535-543.e6. doi: 10.1016/j.anai.2022.01.030. Epub 2022 Feb 3. PMID 35123074

• Study Protocol and Statistical Analysis Plan (PDF, 2019-03-19)

• Theresa Guilbert, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
• Gurjit K Khurana Hershey, MD, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati