sinusitis, OSA, VCD
• GERD - acid and non-acid reflux
• Environmental control
• Alternative diagnoses
• Incorporate objective measures into management
• Written action plan
blood eos < 200/µl)
2020/11/14
12
Clinical Features of Asthmatics with “High” and “Low” IL-13
Gene Signatures
2020/11/14
13
Woodruff, et al. AJRCCM 2009;ቤተ መጻሕፍቲ ባይዱ180:388-395
• Cluster 4: early onset, atopic, severe obstruction with some reversibility (FEV1: 57% to 76% pred), high healthcare utilization
• Cluster 5: early onset, severe obstruction, 66%
Th2 “high” vs. “low” signature results in different clinical characteristics and
response to ICS
2020/11/14
14
Woodruff et al Am J Respir Crit Care Med 180:3888-95, 2009
Th2
IL -13
IL-5
Th1
IgE
2020/11/14
Eosinophils
5
Severe Asthma • Definition
• Phenotypes - Pathologic/Clinical • Therapeutic Options
2020/11/14
6
Inflammation and Remodeling in Asthma
• Review medication technique
2020/11/14
8
Severe Asthma Clusters
2020/11/14
9
Moore et al. AJRCCM 2010;181:315-323
Asthma Clusters
• Cluster 1: early onset, atopic, nl lung fxn < 2 controllers, minimal healthcare utilization
2020/11/14
3
Allergic Asthma: Pathways
2020/11/14
4
Generation of Allergic Adaptive Immune Responses
APC
CD86 CD28
CD80
MHC II TCR
T Lymphocyte
B-cell
IL-4
Mast Cell
2020/11/14
7
Courtesy of Marllyn Glassberg, MD
Approach to Management/Contributing Factors/Co-Morbid Conditions
• Examine for concomitant medical disorders, i.e.
哮喘免疫表型
Asthma
• Asthma is clinically defined as a syndrome with episodic wheezing, shortness of breath, cough and sputum production
• The constant features are airway irritability (hyperresponsiveness) and inflammation
2020/11/14
2
Asthma: Epidemiology
• Between 150-300 million patients worldwide • 15-25 million in the U.S. • Most common chronic disease of childhood • Over 500,000 E.R. visits per year • 25,000 ICU admissions • 5-6,000 deaths in U.S. • On the increase
atopic; less reversibility ( FEV1: 43% to 58%), high
he20a20l/t1h1/14care utilization
10 Moore et al. AJRCCM 2010;181:315-323
Asthma Phenotypes: Heterogeneous Disease
Occupational
Aspirin
Exercise
Me2n02s0e/11s/14
11
Pathological Phenotypes
• Eosinophilic/TH2 (IL-4, IL-5 and IL-13) • Non-eosinophilic (sputum eos < 2%, or peripheral
Clinical: Fixed obstruction Obese Adult onset Exacerbation prone Treatment resistant
Pathologic: Eosinophilic Non-eosinophilic Pauci-granulocytic
Triggers:
• Cluster 2: early onset, atopic, > 2 controllers, nl lung fxn, significant health care utilization
• Cluster 3: adult onset, obese woman with low lung fxn, high medication requirement and healthcare utilization