Severe uncontrolled asthma patient : discussion for trigger factors

1. SEVERE ASTHMA UPDATE
& CASE DISCUSSION
Sheng-Yeh Shen M.D.
Department of Chest Medicine
MacKay Memorial Hospital, Taipei Campus
3 Jun 2020

4. Br J Gen Pract 2016; DOI: 10.3399/bjgp16X687001

10. GINA statement of add-on
controllers

11. GINA statement of add-on
controllers

12. Nordic consensus statement on the systematic assessment and management of possible severe
asthma in adults
EUROPEAN CLINICAL RESPIRATORY JOURNAL, 2018 VOL. 5, 1

13. EUROPEAN CLINICAL RESPIRATORY JOURNAL, 2018 VOL. 5, 1440868
https://doi.org/10.1080/20018525.2018.1440868

15. EUROPEAN CLINICAL RESPIRATORY JOURNAL, 2018 VOL. 5, 144

16. Case Sharing :
Asthma with Comorbidity

17. Basic Information
• 21-year-old man
• BH 172cm, BW 100Kg (2014 75Kg)
• Non-smoker
• No home pet
• Occupation – university student
• Medical History –
asthma in the age of 2 by pediatric OPD record
juvenile rheumatoid arthritis diagnosed in 2014

18. Record in MMH AIR clinic
• 2014/12/17 PM 06:57:25
【Ｓ】
lower back pain in AM with both knee pain for 3 years, VAS/VRS: 5/10
both knee pain but swelling(-), oral ulcer(+) sometime, genital ulcer (-), Uveitis (-)
fever(-), erythema(-), active arthritis(-)
【Ｏ】
C3 86mg/dL (79 -152), C4 16 mg/dL (16 -38)
Anti-cyclic citrullinated peptides (Anti-CCP) 0.90
RF Negative
Antinuclear Factor Negative
Anti-ds-DNA Negative
ENA Screening Negative
ANCA-Perinuclear Negative
ANCA-Cytoplasmic Negative

19. Q1.What kind of comorbidity will you think the
patient have according to the available information ?
1. Chronic rhinosinusitis
2. GERD
3. OSA
4. Anxiety and depression
5. All of above

20. Clinical Course of Juvenile RA

22. Clinical Course of GERD

23. Record in GI clinic
• 2014/3/1 AM 10:18:46
【Ｓ】
Abdominal fullness , easy diarrhea after eating
refer from Ped due to possible of PUD
103/02/15 BW: 75Kg, 173cm, HC 59.8cm,
abdominal girth 102.5cm => 103.2cm
Overgrowth syndrome?
103/01/24
【SERUM/PLASMA】
Glucose AC 91 mg/dL, Uric Acid H 9.0 mg/dL,
LDL- Cholesterol 127 mg/dL, HDL- Cholesterol 51 mg/dL
AFP 1.73 ng/mL
103/01/24 abd echo mild fatty liver

24. Clinical Course of ADHD ?

25. Record in MMH Psychiatric clinic - 1
• 2014/5/19 PM 05:28:22
【Ｓ】
Senior high school Gr1 his family knew his visit
but come alone,
live with parents, elder brother
tense relationship of parents.
C.C. : stressful at school.
P. I. : tremor and nervous in the classroom

26. Record in MMH Psychiatric clinic - 2
• P’t deny conflict with teacher.
• Sleepy in the class after taking antihistamine
【Ｏ】
poor sleep, tea+
suggest DC after noon.
【Ａ】
31400 Attention deficit disorder
30000 Anxiety state
【P】
sleep hygiene education

27. Summary by MMH endocrinologist
• 2015/3/16 PM 01:14:53 16 Y/o
• 【Ｓ】79Kg
Bechet disease was diagnosed by ped. AIR Dr.
Ankylosing spondylitis was highly suspected by AIR Dr.
Senior high school Gr 2
headache off & on, abdominal distension and persistent diarrhea
mild cough with sputum and rhinorrhea , persistent multiple oral ulcers
*ADHD was suspected by psychiatrist at his young age.
104/02/16 FREE-T4: 1.39 ng/dL, TSH: 1.92 μIU/mL
Lupus Anticoagulant: Positive, Protein C: H 143.4%,
Rheumatoid Factor: <20.0 IU/mL

28. Clinical Course of OSA

29. Record in MMH Sleep Clinic
• 2015/8/14 PM 04:04:03 17 Y/o
【Ｓ】night cough while lying down, snoring, dyspnea at night 4-5 times
Sleep Features:
Snores or mouth breathing nightly: Y
Apnea or increased work of breathing: unknown
Restless or wakes at night: Y, 4-5 times
Restless legs or cramps: Y
Headache on waking: Y, dizziness occasionally
Sleep Timing: Bed time:22:00 Sleep time: 24:00 Wake time:7:00, difficult to get up
Daytime symptoms : moderate Sleepiness
【Ｏ】Weight: 84kg, Friedman palate position: II
Tonsils size: 4, Body mass index: < 40

30. Clinical Course of Asthma

31. Record in MMH Pediatric clinic
• 2015/3/25 PM 03:08:07 16 Y/o
【Ｓ】79Kg
fever since yesterday
chest pain aggravated with headache,
polyps noted over left uvula,
abdominal pain and heart burn sensation
aggravated, esp. after oral Aspirin
cough, rhinorrhea, and wheezing,
profound sputum

32. Initial treatment of Asthma (16 Y/o)
• Methylprednisolone 4mg 2T BID
Budesonide HFA (DUASMA) 1PF BID
Bambuterol 10mg 0.5T QHS
additional medication for RA
METHOTREXATE 2.5mg 7T QD x 3D

33. First Visit in MMH Chest clinic
• 2015/7/31 PM 04:19:14 17 Y/o
【Ｓ】Productive cough for yellow sputum for 3 weeks,
sore throat, chest tightness, dyspnea, wheezing heard by himself,
night cough (++)
Tx from AIR OPD
Ultracet (ACT 325 /tramado), Etoricoxib 60mg (Arcoxia)
【Ｏ】
Cons: clear & alert
Throat: swelling and erythematous (+)
Chest: wheezing (++)
• Tx: Symbicort 2PF BID, Prednisolone 15mg QD

34. Laboratory and Exam Data

35. Chest Images

36. Upper GI Endoscopy
• ESOPHAGUS Ulcer, GERD LA Class A
• STOMACH superficial Gastritis
• Helicobacter pyroli test (Clo test) : Positive

37. 2015, 8/19

38. PFT 2016/12/14

39. 20150516 20170311 20190412 20190816
WBC/Eos(%) 8300/2.7 7500/4.9 7900/5.5 9900/1.7
Xolair

40. Allergen Test

41. PSG

44. Q2. Which phenotype fits this patient ?
1. Eosinophilic asthma
2. Neutrophilic asthma
3. Mixed type
4. Could not figure out because of the limited
information

45. Acute Severe Asthma in Adolescent and Adult Patients: Current Perspectives onAssessment and Management
J. Clin. Med. 2019, 8, 1283

46. Q3. Which treatment will you
prescribe for this patient ?
1. ICS/LABA
2. ICS/LABA/LAMA
3. Only LTRA (Singulair)
4. Anti-IgE Ab (Xolair)
5. Anti-IL5 Ab (Nucala, Fasenra)

47. Omalizumab for severe asthma: toward personalized treatment based on biomarker profile and clinical history
Journal of Asthma and Allergy 2018:11 53–61

48. His course of asthma treatment in
2019
• Symbicort DPI + Spiriva MSI + Singulair + nasal
steroid from NTUH & MMH
• Xolair biweekly 300mg SC since 2019 May
• Poor inhaler & Xolair compliance in Jul & Aug
• 2019 Sep – Oct monthly Xolair 300mg

49. ACT 2017, 7/27  2019, 6/20
33152=14  34553=20

50. J Allergy Clin Immunol
2019;144:1-12.
Attempts to phenotype and endotype asthma
using
cluster analysis have identified 4 consistent
clusters
(1) early-onset allergic asthma
(2) early-onset moderate-to-severe remodeled
asthma
(3) late-onset non-allergic eosinophilic asthma

51. Phenotypes and endotypes of adult
asthma
 These phenotypes are likely driven by different
underlying biologic processes and are
suggestive of endotypes that in the future will
be identifiable by using specific tests and
treated uniquely in the clinic.
 Being able to identify patients within each
cluster using biomarkers and clinical
symptoms moves us closer to the goal of
precision medicine by allowing clinicians to
use the right biologic for the right patient.

54. Severe Uncontrolled
Asthma : Experience of
anti-IL5 Treatment

55. Case Sharing Content
 Part I. Two Cases Discussion
1. 48-year-old woman, mixed phenotype
2. 35-year-old woman, presented with eosinophilic pneumonia
 Part II. Different Area, Different Race, Different Treatment Pattern
- Comparing Patients in Taipei and Taitung MacKay Memorial Hospital

56. PATIENT 1. HYPEREOSINOPHILIC
SYNDROME
48F，153cm, 51Kg BMI 21.8
Former smoker: less than 1 PPD for about 10 years, quit for 2 years
Occupation: Office (import Toluene C6H5CH3) for 15 years
Home pet: a poodle for 7 years
residence: New Taipei City Company: Taipei City

57. CLINICAL COURSE
 2015 Nov and 2016 Feb:
asthma with AE and acute respiratory failure s/p intubation and MV
support
 Treatment as GINA guideline: step-up to 5 in 6 months (2016 Mar~Sep)
Symbicort DPI 2 pf BID
Singulair 10mg QHS
Theophylline 125mg BID
Spiriva 1 pf BID
Methylprednisolone 4mg TID

58. ACUTE HYPERCAPNIC
RESPIRATORY FAILURE IN ER

59. IN ICU

61. LAB PROFILES

62. XOLAIR DOSE WITH 2WK-
INTERVAL: 450MG

63. 2016/2/2
4
2016/5/
6
2016/9/
2
2016/10/
21
2016/11/
18

64. PFT FEV1/FVC FEV1 (L) Reversibility
of FEV1
RV/TLC
(predicted)
VC/TLC PEFR
Before/
After BD
2016/6/24 51% 51% (1.21L) 36% (440mL) 47% (34%) 85/106 3.8/4.83
L/sec
2016/11/4 49% 47% (1.16L) 17% (200mL) 42% (34%) 81/93 3.39/4.3
L/sec

65. STEP-DOWN OF TREATMENT
AFTER XOLAIR
Symbicort DPI 2 pf BID
Singulair 10mg QHS
Theophylline 125mg BID
Spiriva 1 pf BID
Methylprednisolone 4mg TID

66. CLINICAL EFFICACY:
ACT SCORE
5/6 11/18
2 4
2 4
3 4
2 5
3 4
1
2
2
1

67. DISCUSSION
 What is the most possible factor to cause persistent
eosinophilia ?
 Could the patient fit the diagnosis of occupational asthma
(Toluene) ?
 What ‘s the next treatment option for the patient ?
 Is it possible the patient in the early stage of Churg-
Strauss syndrome (eosinophilic granulomatosis with
polyangiitis) ?
Allergic stage Eosinophilic stage  Vasculitic stage
 Dx criteria: Asthma, eosinophilia, mononeuropathy or
polyneuropathy, pulmonary infiltrates, sinus problems,
extravascular eosinophils by biopsy

68. Asthma Controlled ?

69. HER STORY WENT ON AND ON …
2017 Mar – severe AE of asthma, ER visit and
admission to the ward
Upper GI endoscopic Diagnosis : GERD LA Class
A, superficial gastritis (suspect OCS related)

70. AE s/p
IV
systemi
c
steroid
EOSINOPHIL %

71. PFT AFTER XOLAIR TREATMENT
FOR 18 MONTHS

72. MONTHLY NUCALA 100MG SC
SINCE 2019 APRIL
2019 4/12 5/10 6/21 7/12
ACT 33333=15 34424=17
2018/11/02 7/12
Eosinphil count 6200 x 19.4% 1203 132.6 3900 x 3.4%

73. PATIENT 2. EOSINOPHILIC
PNEUMONIA
35F，158cm, 68Kg BMI 27.2
Former smoker: less than 1 PPD for 9 years, quit for 1 year
Occupation: housekeeper
Home pet: no home pet
Residence: Taipei City

74. CLINICAL COURSE
 2018 Jan 17 ~ Jan 29 Chest Ward in Taipei MacKay Memorial
Hospital
Eosinophilic pneumonia, asthma with acute exacerbation,
allergic rhinitis
 Chest OPD follow up 2018 Feb 5
Symbicort DPI 2 PF BID
Methylprednisolone 4mg 3T BID
Fluticasone (Avamys) Nasal Spray 2PF QD

77. LABORATORY DATA IN MMH ER

78. BAL BY BRONCHOSCOPY
【體液】
Cytospin for BAL
Count 100 cell
NEUT 8
Eosin 40
Baso 0
Mono 0
Lymphocyte 35
Other cells 17
TB PCR Test 結果 : Negative

79. LABORATORY DATA IN THE WARD
項目名稱 結果值 單位 參考值
IgE 250 IU/mL <100
P-ANCA(MPO) 0.1 IU/mL <3.5(-),3.5-5(+/-),>5(+)
C-ANCA(PR3)) 0.4 IU/mL <2(-),2-3(+/-),>3(+)
Cryptococcus Negative Negative
Aspergillus Ag 0.13 <0.50 (Galactomannan)
Rheumatoid Factor <10 IU/mL <14
Antinuclear Factor Negative <40X+
C3 148 mg/dL 79 - 152
C4 36 mg/dL 16 - 38

83. Case Sharing Content
 Part II. Different Area, Different Race, Different Treatment Pattern
- Comparing Patients in Taipei and Taitung MacKay Memorial Hospital

84. Severe Asthma with Xolair
Treatment in MMH
 Total cases: 26
 Male: female  7:19 (26.9:73.1)
 Age: mean=57.1, sd= 14.3
37
79

85. BMI
 Mean: 25
Male
Female 3

86. smoking
 Never: Ever: Current = 13:5:8
Gender/smoking Never Ever Current
male 2 (28.6%) 3 (42.8%) 2 (28.6%)
Female 11 (57.9%) 2 (10.5%) 6 (31.6%)

87. Lung function before Xolair
 Obstruction  post FEV1/post FVC
 < 60 : 10
 > 60: 15 (1 patients: no post data)
 Bronchodilator test (post-pre FEV1 > 200ml and 12%)
 Positive: 4
 Negative: 21 (1 patients: no post data)

88. ACT score
用藥前
ACT
ACT1 ACT2 ACT3

89. Obesity and smoking
 Case 2 & case 15
 BMI = 39.1, Ever smoker (age:41)
 BMI = 33.9, Current smoker (age:42)
ACT
0 1 2 3
Non-
smoker
BMI=33.
0
Age=40

90. Lung function after Xolair Treatment
 Total: 26 patients
 Only 16 patients follow up lung function after using xolair
 Mean: 11.7 months f/u
 Min: 3 months, max: 33 months

91. IgE level
 Min: 56.4, max: 4400
 30~1300

92. Comorbidity
 慢性鼻炎: 21 (21/26=80.8%)
 GERD : 10 (10/26=38.5%)

93. Summary of anti-IgE Treatment
 IgE level
 Not a good biomarker for evaluating anti-IgE response
 Most patients had comorbidity of chronic rhinitis
 Easier to get cold
 Omalizaumab  decrease rate of cold/rhinovirus infection
 Many patients had GERD
 Obesity and smoking seems be poor response factors for
anti-IgE Ab

94. Severe Asthma Patients with
Nucala Treatment in Taipei
MMH

95. Severe Asthma Patients with
Nucala Treatment in Taitung
MMH