Asthma management phenotype based approach
-
Upload
gamal-agmy -
Category
Health & Medicine
-
view
1.027 -
download
0
Transcript of Asthma management phenotype based approach
![Page 1: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/1.jpg)
![Page 2: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/2.jpg)
Asthma Management
Phenotypes based approach
Gamal Rabie Agmy, MD, FCCP Professor of chest Diseases, Assiut university
![Page 3: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/3.jpg)
Asthma is a heterogeneous disease, usually
characterized by chronic airway inflammation.
It is defined by the history of respiratory
symptoms such as wheeze, shortness of breath,
chest tightness and cough that vary over time
and in intensity, together with variable expiratory
airflow limitation.
Definition of asthma
NEW!
GINA 2014
![Page 4: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/4.jpg)
• Increased probability that symptoms are due to asthma if:
– More than one type of symptom (wheeze, shortness of breath, cough, chest tightness)
– Symptoms often worse at night or in the early morning
– Symptoms vary over time and in intensity
– Symptoms are triggered by viral infections, exercise, allergen exposure, changes in weather, laughter, irritants such as car exhaust fumes, smoke, or strong smells
• Decreased probability that symptoms are due to asthma if:
– Isolated cough with no other respiratory symptoms
– Chronic production of sputum
– Shortness of breath associated with dizziness, light-headedness or peripheral tingling
– Chest pain
– Exercise-induced dyspnea with noisy inspiration (stridor)
Diagnosis of asthma – symptoms
GINA 2014
![Page 5: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/5.jpg)
• Confirm presence of airflow limitation
– Document that FEV1/FVC is reduced (at least once, when FEV1 is low)
– FEV1/ FVC ratio is normally >0.75 – 0.80 in healthy adults, and >0.90 in children
• Confirm variation in lung function is greater than in healthy individuals
– The greater the variation, or the more times variation is seen, the greater probability that the diagnosis is asthma
– Excessive bronchodilator reversibility (adults: increase in FEV1 >12% and >200mL; children: increase >12% predicted)
– Excessive diurnal variability from 1-2 weeks’ twice-daily PEF monitoring (daily amplitude x 100/daily mean, averaged)
– Significant increase in FEV1 or PEF after 4 weeks of controller treatment
– If initial testing is negative:
• Repeat when patient is symptomatic, or after withholding bronchodilators
• Refer for additional tests (especially children ≤5 years, or the elderly)
Diagnosis of asthma – variable airflow
limitation
GINA 2014, Box 1-2
![Page 6: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/6.jpg)
© Global Initiative for Asthma
Time (seconds)
Volume
Note: Each FEV1 represents the highest of
three reproducible measurements
Typical spirometric tracings
FEV1
1 2 3 4 5
Normal
Asthma
(after BD)
Asthma
(before BD)
Flow
Volume
Normal
Asthma
(after BD)
Asthma
(before BD)
GINA 2014
![Page 7: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/7.jpg)
• Physical examination in people with asthma
– Often normal
– The most frequent finding is wheezing on auscultation, especially on
forced expiration
• Wheezing is also found in other conditions, for example:
– Respiratory infections
– COPD
– Upper airway dysfunction
– Endobronchial obstruction
– Inhaled foreign body
• Wheezing may be absent during severe asthma exacerbations (‘silent
chest’)
Diagnosis of asthma – physical examination
GINA 2014
![Page 8: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/8.jpg)
GINA 2014, Box 1-1 © Global Initiative for Asthma
NEW!
![Page 9: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/9.jpg)
Asthma Pathology
Asthma is a chronic inflammatory disease associated with airway
hyperresponsiveness (AHR), short-term consequences…
Airway obstruction
and symptoms by:
Bronchoconstriction
Mucus plugs
Mucosal edema Inflammatory cell
infiltration/activation
Remodelling:
Increased vascularity
Epithelial cell disruption
Increased airway smooth
muscle mass
(hyperplasia)
Reticular basement membrane thickening
…and long-term consequences
Bousquet J et al. Am J Respir Crit Care Med 2000;161:1720–1745;
Beckett PA et al. Thorax 2003;58:163–174
![Page 10: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/10.jpg)
![Page 11: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/11.jpg)
Asthma Inflammation
![Page 12: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/12.jpg)
Asthma Timeline
![Page 13: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/13.jpg)
![Page 14: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/14.jpg)
![Page 15: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/15.jpg)
![Page 16: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/16.jpg)
◙ For revealing the complexity and the
heterogeneity of this disease, asthma patients
were grouped into subtypes called phenotypes.
◙ Term ‘phenotype’ describes subtypes of
asthma focused on ‘clinically observable
characteristics’ of a disease.
![Page 17: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/17.jpg)
![Page 18: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/18.jpg)
![Page 19: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/19.jpg)
![Page 20: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/20.jpg)
Therefore, there are many ‘definitions’ for asthma phenotypes,
many of which are related to differences in symptoms and
severity rather than to differences in underlying mechanisms. but
this kind of subtyping does little to help understand prognosis
and target therapy.
When a link can be made between clinical characteristics and
molecular pathways, the term endotype can be introduced
to describe distinct subtypes with a defining etiology and
consistent pathobiologic mechanisms.
![Page 21: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/21.jpg)
The definition of a true phenotype (or endotype)
requires an underlying pathobiology with
identifiable biomarkers and genetics .
Gene-expression profiling allows definition of
expression signatures to characterize patient
subgroups, predict response to treatment, and
offer novel therapies.
![Page 22: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/22.jpg)
Asthma Endotypes: categories
1. TH2-associated asthma
– Allergic asthma
– Early-onset allergic asthma
– Late-onset persistent eosinophilic asthma
– Aspirin exacerbated airway disease (AERD)
– Exercise induced asthma
2. Non Th2-associated asthma
– Obesity-related asthma
– Neutrophilic asthma
– Smoking asthma
![Page 23: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/23.jpg)
Asthma Endotypes: categories
![Page 24: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/24.jpg)
Asthma Endotypes: categories
1. TH2-associated asthma
– Allergic asthma
– Early-onset allergic asthma
– Late-onset persistent eosinophilic asthma
– Aspirin exacerbated airway disease (AERD)
– Exercise induced asthma
2. Non Th2-associated asthma
– Obesity-related asthma
– Neutrophilic asthma
– Smoking asthma
![Page 25: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/25.jpg)
TH2-associated asthma
Allergic asthma (Virus induced asthma)
![Page 26: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/26.jpg)
![Page 27: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/27.jpg)
![Page 28: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/28.jpg)
![Page 29: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/29.jpg)
![Page 30: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/30.jpg)
![Page 31: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/31.jpg)
![Page 32: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/32.jpg)
![Page 33: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/33.jpg)
Asthma Phenotypes: categories
1. TH2-associated asthma
– Allergic asthma
– Early-onset allergic asthma
– Late-onset persistent eosinophilic asthma
– Aspirin exacerbated airway disease (AERD)
– Exercise induced asthma
2. Non Th2-associated asthma
– Obesity-related asthma
– Neutrophilic asthma
– Smoking asthma
![Page 34: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/34.jpg)
TH2-associated asthma
Early-onset allergic asthma
• Clinical characteristics :
– This group of asthmatic patients developed their
disease in childhood, and maintained their symptoms
into adulthood. . The majority of early-onset allergic
asthma is mild but that an increasing complexity of
immune processes leads to greater severity.
– Most people with asthma are likely to have this
phenotype.
– Positive skin prick tests, specific IgE antibodies in
serum, eosinophilia in the peripheral blood.
![Page 35: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/35.jpg)
TH2-associated asthma
Early-onset allergic asthma
• Genetics:
– Early-onset allergic patients commonly have a family
history of asthma, suggesting a genetic component.
– Several Th2 cytokine SNPs
– Higher numbers of mutations in TH2-related genes
(IL4, IL13, IL4Rα ) associated with greater severity of
disease.
• Biomarkers:
– Positive SPT, elevated IgE/elevated FeNO
– Th2 cytokines IL-4 ,IL-5 , IL-9, IL-13, and periostin
measured in sputum, BAL, serum and bronchial
biopsies.
![Page 36: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/36.jpg)
TH2-associated asthma
Early-onset allergic asthma
• Treatment responses:
– Corticosteroid-responsive.
– Th2 Targeted therapy:
– Anti IgE (omalizumab)in Severe allergic asthma.
– Anti–IL-13( lebrikizumab) in Allergic asthma with
dominant IL-13 activation . Surrogate marker
predicting better response is high circulating levels of
periostin.
– Inhaled IL-4Rα antagonist. Surrogate marker
predicting better response is IL-4 receptor a
polymorphism.
![Page 37: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/37.jpg)
Asthma Phenotypes: categories
1. TH2-associated asthma
– Allergic asthma
– Early-onset allergic asthma
– Late-onset persistent eosinophilic asthma
– Aspirin exacerbated airway disease (AERD)
– Exercise induced asthma
2. Non Th2-associated asthma
– Obesity-related asthma
– Neutrophilic asthma
– Smoking asthma
![Page 38: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/38.jpg)
TH2-associated asthma
Late-onset persistent eosinophilic asthma
• Clinical characteristics:
– The majority of this group develops disease in adult
life, often in the late 20s to 40s.
– Severe from onset, Severe exacerbations with
persistent sputum eosinophilia (>2%), despite
corticosteroid therapy.
– less clinical allergic responses( non atopic) than
early-onset asthma.
– It is often associated with sinus disease.
![Page 39: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/39.jpg)
TH2-associated asthma
Late-onset persistent eosinophilic asthma
• Genetics:
– Few patients in this group have a family history of
asthma.
– little is known regarding the genetics of adult onset
persistent asthma.
![Page 40: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/40.jpg)
TH2-associated asthma
Late-onset persistent eosinophilic asthma
• Biomarkers:
– Lung eosinophilia. Persistent sputum eosinophilia (≥2%)
– The lack of clinical allergy in this phenotype suggests that
the TH2 process differs from and is probably more
complex than the one associated with the early-onset
allergic phenotype but the presence of IL-13 and IL-5 in
the lower airways confirm Th2 pathway.
– Some individuals show sputum neutrophilia intermixed
with their eosinophilic process. This mixed inflammatory
process implies that there are interactions of additional
immune pathways with TH2 immunity, including
activation of pathways related to IL-33 and IL-17 .
– Elevations in FeNO
![Page 41: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/41.jpg)
TH2-associated asthma
Late-onset persistent eosinophilic asthma
• Treatment responses:
– persistent eosinophilia in late-onset disease inspite of
ICS implies that the TH2 process in this type of asthma is
refractory to corticosteroids but high systemic doses of
corticosteroids are generally able to overcome this
refractoriness in late-onset asthma.
– IL-5 targeted therapy may show much better efficacy in
this endotype, compared in early-onset allergic asthma
patients, as IL-5 dependent eosinophilia may be more
important in this potential endotype. (decreasing
exacerbations and systemic corticosteroid requirements)
– IL-4 and IL-13 targeted therapy pathway.
![Page 42: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/42.jpg)
Asthma Phenotypes: categories
1. TH2-associated asthma
– Allergic asthma
– Early-onset allergic asthma
– Late-onset persistent eosinophilic asthma
– Aspirin exacerbated airway disease (AERD)
– Exercise induced asthma
2. Non Th2-associated asthma
– Obesity-related asthma
– Neutrophilic asthma
– Smoking asthma
![Page 43: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/43.jpg)
TH2-associated asthma
Aspirin exacerbated airway disease (AERD)
• AERD is probably a subendotype or a similar endotype.
It is an acquired condition on top of an intrinsic or less
frequently allergic asthma and thus, despite its peculiar
sensitivity to NSAIDs, still has major overlap with these
conditions.
• Clinical characteristics :
– AERD is frequently progressive severe asthma starts
late in life and is associated with eosinophilia and
sinus disease Polyposis.
– Response to aspirin challenge
![Page 44: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/44.jpg)
• Genetics :
– LT-related gene polymorphisms.
– Gene-expression study identified upregulation of
periostin a potent regulator of fibrosis and
collagen deposition has also been identified in
polyps of and in airway epithelial cells of patients
with AIA.
– Overexpression of periostin has been associated
with accelerated cell growth and
angiogenesis(subtype).
• Biomarkers:
– high cysteinyl leukotriene level.
TH2-associated asthma
Aspirin exacerbated airway disease (AERD)
![Page 45: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/45.jpg)
• Treatment responses :
– Many patients require systemic corticosteroids to
control their sinusitis and asthma.
– Leukotriene modifiers especially 5-LO inhibitors
can have a robust impact on the AERD subset.
– Downregulation of periostin after treatment of
asthmatic patients with corticosteroids suggests that
normalization of periostin expression is a part of the
therapeutic effects of corticosteroids. This opens a
possibility of specifically targeting periostin in future
therapies for nasal polyps and asthma
TH2-associated asthma
Aspirin exacerbated airway disease (AERD)
![Page 46: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/46.jpg)
TH2-associated asthma
Aspirin exacerbated airway disease (AERD)
![Page 47: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/47.jpg)
Asthma Phenotypes: categories
1. TH2-associated asthma
– Allergic asthma
– Early-onset allergic asthma
– Late-onset persistent eosinophilic asthma
– Aspirin exacerbated airway disease (AERD)
– Exercise induced asthma
2. Non Th2-associated asthma
– Obesity-related asthma
– Neutrophilic asthma
– Smoking asthma
![Page 48: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/48.jpg)
• Clinical characteristics:
– Exercise induced asthma refers to asthma whose
symptoms are experienced primarily after exercise.
EIA is a milder form of TH2 asthma.
– Consistent with a relationship to TH2 processes, EIA
common in atopic athletes and high percentages of
eosinophils and mast cells and their mediators .
• Biomarkers:
– Th2 cytokines and cysteinyl leukotriene
• Genetics:
– No distinct genetic factors .
TH2-associated asthma
Exercise induced asthma
![Page 49: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/49.jpg)
Slide 49
Benefits of LTRAs in Activity-Induced Asthma
• Leukotrienes are important mediators of exercise-triggered
asthma episodes.1
• Both the LTRA montelukast and the LABA salmeterol
provide benefit in terms of chronic symptom control.2,3
– Montelukast may provide better bronchoprotection against
exercise-triggered asthma.4,5
– SABA rescue therapy may be more effective postexercise.2
Slide 49
LTRAs=leukotriene receptor antagonists; LABA=long-acting β-agonist; SABA=short-acting β-agonist.
1. O’Byrne PM. Am J Respir Crit Care Med. 2000;161:S68–S72. 2. Storms W et al. Respir Med. 2004;98:1051–1062. 3. Wilson AM et al.
Chest. 2001;119(4):1021–1026. 4. Villaran C et al. J Allergy Clin Immunol. 1999;104(3, pt 1):547–553. 5. Edelman JM et al. Ann Intern Med. 2000;
132(2):97–104.
![Page 50: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/50.jpg)
TH2-associated asthma
Exercise induced asthma
Ann Allergy Asthma Immunol 2010
![Page 51: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/51.jpg)
Slide 51
Study Design1
E=exercise challenge.
1. Fogel RB et al. Ann Allergy Asthma Immunol. 2010;104:511–517.
(n=78) Montelukast 5 mg + placebo for salmeterol
Salmeterol 50 µg twice daily + placebo for montelukast
(154) Fluticasone
100 µg twice daily
–4
Week
6 10 0 4
Active Treatment Run-In Active Treatment Washout
E
Fluticasone
100 µg twice daily
(n=76) Salmeterol 50 µg twice daily + placebo for montelukast
Montelukast 5 mg + placebo for salmeterol
E E
Slide 51
![Page 52: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/52.jpg)
Efficacy End Points1
Minutes Postchallenge This article was published in the Annals of Allergy, Asthma & Immunology, 104, Fogel RB, Rosario N, Aristizabal G, et al, Ef fect of montelukast or
salmeterol added to inhaled f luticasone on exercise-induced bronchoconstriction in children, 511–517, ©2010 American College of Allergy, Asthma &
Immunology.
AUC0–20 min=area under the curve for the f irst 20 minutes af ter exercise; FEV1=forced expiratory volume in 1 second.
1. Fogel RB et al. Ann Allergy Asthma Immunol. 2010;104:511–517.
Slide 52
Mean
Perc
en
tag
e C
han
ge
Fro
m P
rech
all
en
ge
0 5 10 15 20 25 30 35 50
End of exercise, start of spirometry
–30
–20
–10
0
10
Exerc
ise C
halle
nge
β-agonist use 1st 2nd
Return to within 5% of the preexercise baseline FEV1
20
Time to recovery to within 5% of the preexercise baseline FEV1
AUC0–20 min
Max % fall in FEV1
Slide 52
![Page 53: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/53.jpg)
Montelukast Provided Better Bronchoprotection After Exercise Than Salmeterol1
Mean
± S
D M
axim
um
%
Fall
in
FE
V1
Slide 53
SD=standard deviation; FEV1=forced expiratory volume in 1 second; LS=least squares. aOn a background of inhaled f luticasone.
1. Fogel RB et al. Ann Allergy Asthma Immunol. 2010;104:511–517.
Maximum % Fall in FEV1 (Primary End Point)
Slide 53
LS mean difference:
–3.3% (P=0.009)
Salmeterola
(n=144)
–10.6 ± 12.2
–13.8 ± 12.5
–20
0
–10
–15
–5
Montelukasta
(n=144)
![Page 54: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/54.jpg)
Montelukast Maintained Bronchoprotective Effects After Exercise Challenge1
Mean
± S
E %
Ch
an
ge
Fro
m P
rech
all
en
ge
This article was published in the Annals of Allergy, Asthma & Immunology, 104, Fogel RB, Rosario N, Aristizabal G, et al, Ef fect of montelukast or
salmeterol added to inhaled f luticasone on exercise-induced bronchoconstriction in children, 511–517, ©2010 American College of Allergy, Asthma &
Immunology.
FEV1=forced expiratory volume in 1 second; SE=standard error.
1. Fogel RB et al. Ann Allergy Asthma Immunol. 2010;104:511–517.
Minutes Postchallenge
Pre-
challenge 0 5 10 15 20 25 30 35 50
Montelukast (n=144)
Salmeterol (n=144)
–15
–10
–5
0
10
5
Short-acting β-agonist rescue
Change in FEV1 Over Time
Slide 54
![Page 55: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/55.jpg)
Montelukast Reduced the Extent and Duration of Bronchoconstriction1
Slide 55
AUC0–20 min=area under the curve for the f irst 20 minutes af ter exercise; FEV1=forced expiratory volume in 1 second; LS=least squares; SD=standard deviation.
1. Fogel RB et al. Ann Allergy Asthma Immunol. 2010;104:511–517.
AUC0–20 min for FEV1 Following Exercise Challenge
Mean
± S
D A
UC
0–
20
min
,
% •
min
Salmeterol (n=144)
0
Montelukast (n=144)
LS mean difference:
–52.7% (P=0.006)
116.0
168.8
250
100
50
150
Slide 55
200
![Page 56: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/56.jpg)
Montelukast Reduced the Time to Recovery1
M
ed
ian
Tim
e, m
in
Slide 56
FEV1=forced expiratory volume in 1 second; LS=least squares.
1. Fogel RB et al. Ann Allergy Asthma Immunol. 2010;104:511–517.
Time to Recovery to Within 5% of Preexercise FEV1
Salmeterol (n=142)
Montelukast (n=141)
LS Mean Difference: 1.3
(P=0.04)
Slide 56
0
5.9
11.1
14
6
2
10
4
8
12
![Page 57: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/57.jpg)
Children Remained More Responsive to SABA Rescue With Montelukast1
Slide 57
SABA=short-acting β-agonist; FEV1=forced expiratory volume in 1 second; LS=least squares.
1. Fogel RB et al. Ann Allergy Asthma Immunol. 2010;104:511–517.
Average % Change in FEV1 Following First SABA Use
Slide 57
Avera
ge %
Ch
an
ge i
n F
EV
1
Fro
m P
reexerc
ise B
aseli
ne
Salmeterol (n=144)
0
Montelukast (n=144)
LS mean difference:
3.8% (P<0.001)
6.5
2.7
8
4
2
6
10
![Page 58: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/58.jpg)
Slide 58
Summary and Conclusions
• In a study of children aged 6 to 14 years receiving an ICS
for the treatment of persistent asthma (N=154):
– Montelukast provided superior bronchoprotection
compared with LABA therapy.
– Children remained more responsive to SABA rescue while
on montelukast compared with LABA therapy.
• Montelukast + an ICS may provide better protection against
exercise-triggered asthma than a LABA + an ICS.
ICS=inhaled corticosteroid; LABA=long-acting β-agonist; SABA=short-acting β-agonist.
1. Fogel RB et al. Ann Allergy Asthma Immunol. 2010;104:511–517.
Slide 58
![Page 59: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/59.jpg)
Montelukast Activity-Induced Asthma Study (6–14 years)
Summary
Adapted from Kemp JP et al J Pediatr 1998;133(3):424-428; Data on file, MSD.
Clinical Benefits
Reduced the Extent of EIB
Reduced the Duration of EIB
Reduced the Recovery Time From EIB
Tolerability
As Placebo
![Page 60: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/60.jpg)
Asthma Phenotypes: categories
1. TH2-associated asthma
– Allergic asthma
– Early-onset allergic asthma
– Late-onset persistent eosinophilic asthma
– Aspirin exacerbated airway disease (AERD)
– Exercise induced asthma
2. Non Th2-associated asthma
– Obesity-related asthma
– Neutrophilic asthma
– Smoking asthma
![Page 61: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/61.jpg)
• Whether obesity is a driving component in asthma
development or a mere confounder or comorbidity of its
presence remains controversial.
• It is likely that obesity differentially impacts asthma that
develops early in life, as compared to later in life, being a
more prominent independent contributor in later onset
disease.
• So a distinct obesity-related asthma phenotype seems to
occur only in non-TH2 asthma.
Non TH2-associated asthma
Obesity related Asthma
![Page 62: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/62.jpg)
• Clinical characteristics:
– Patients in this group are commonly women, obese,
late onset (mid-40s), less allergic (obesity is neither a
risk factor for atopy nor a risk factor for allergic
asthma).with a high burden of symptoms.
• Biomarkers:
– High expression of non Th2 mediators such as tumor
necrosis factor (TNF)-a, IL-6 .
– Hormones of obesity, such as adiponectin, leptin,
and resistin either alone or in association with
increased oxidative stress.
– Elevations in an endogenous inhibitor of iNOS,
asymmetric dimethyl arginine (ADMA).
– lower amounts of FeNO, fewer eosinophils.
Non TH2-associated asthma
Obesity related Asthma
![Page 63: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/63.jpg)
• Treatment responses:
– Patients of this subgroup usually respond poorly to
corticosteroids.
– Bariatric surgery induced weight loss was associated
with profound improvements in lung function and
symptoms in obese asthma.
– However, the effect of weight loss on bronchial hyper
responsiveness was only shown in late-onset,
nonallergic (non-Th2) asthma patient, consistent with
late onset obese asthma being a separate endotype.
This is further supported by the increase in ADMA in
association with worsening severity and control in
late onset obese asthma only.
Non TH2-associated asthma
Obesity related Asthma
![Page 64: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/64.jpg)
Asthma Phenotypes: categories
1. TH2-associated asthma
– Allergic asthma
– Early-onset allergic asthma
– Late-onset persistent eosinophilic asthma
– Aspirin exacerbated airway disease (AERD)
– Exercise induced asthma
2. Non Th2-associated asthma
– Obesity-related asthma
– Neutrophilic asthma
– Smoking asthma
![Page 65: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/65.jpg)
• Smoking has a complex relationship with asthma. It is
associated with deteriorating lung function and
resistance to corticosteroids.
• Smoking asthma has been associated with neutrophilia
in lung tissue.
• It is unknown if smoking asthma is a subtype of
neutrophilic asthma or an independent endotype . Since
not all smoking asthma is accompanied by neutrophilia,
it is more likely that there is only a partial overlap
between neutrophilic asthma and smoking asthma.
Non TH2-associated asthma
Smoking asthma
![Page 66: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/66.jpg)
• Some reports have suggested that smoking is
associated with elevated total IgE and that active
smoking may increase the risk of sensitization to
workplace allergens.
• However, little is understood regarding the role of
genetics, biomarkers or pathobiology.
• FeNO levels are decreased by smoking and could help
to differentiate asthmatic subjects from non-asthmatic
subjects.
• Treatment responses
– Quitting smoking
– Restoration of HDAC 2 nuclear recruitment with
theophylline.
Non TH2-associated asthma
Smoking asthma
![Page 67: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/67.jpg)
Non TH2-associated asthma
Smoking asthma
Rationale for Targeting Leukotrienes in Patients With Asthma Who Smoke
![Page 68: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/68.jpg)
Slide 68
Does Smoking Affect Leukotriene Production
in Subjects Without Asthma?
LTE4=leukotriene E4.
1. Fauler J et al. Eur J Clin Invest. 1997;27:43–47.
Correlation of LTE4 Excretion With Cigarette Smoking1
No. of Cigarettes Smoked Per Day
Uri
na
ry E
xc
reti
on
of
LT
E4,
nm
ol/
mo
l c
rea
tin
ine
1
10
20 30 40 50 60 70 80
100
0
(r=0.92, P<0.001)
(n=30)
![Page 69: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/69.jpg)
Does Smoking Affect Leukotriene Production
in Patients With Asthma?
Slide 69
LTE4=leukotriene E4.
1. Gaki E et al. Respir Med. 2007;101:826–832.
LTE4/Creatinine Concentration Ratios in Smoking and Nonsmoking Asthma
Patients1 LT
E4/C
rea
tin
ine
, p
g/m
g
300
250
200
150
100
50
0
P<0.0001
Asthma
Smoking
(n=20)
Nonsmoking
(n=20)
![Page 70: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/70.jpg)
Effect of Montelukast for treatment of asthma in cigarette
smokers
Slide 70
J Allergy Clin Immunol 2013
![Page 71: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/71.jpg)
Study Goal and Design
Montelukast 10 mg once daily (n=347)
Fluticasone propionate 250 µg twice daily (n=336)
Placebo (n=336)
Single-blind
placebo
run-in period Washout
Day –31 Day –21 Day 1 Day 30 Day 90 Day 180
Period I Period II
Goal: To evaluate the effect of montelukast vs placebo (primary) and
medium-dose fluticasone (secondary) in asthma patients who smoke
Slide 71
![Page 72: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/72.jpg)
Key Inclusion/Exclusion Criteria
• Inclusion
– Male or female, aged 18 to 55 years
– History of chronic asthma ≥1 year
– Evidence of reversible airway obstruction (increase in FEV1 ≥12%
following
β-agonist administration)
– Cigarette smoker of 0.5 to 2 packs per day (≤30 pack-year history)
– Weekly average ≥2 puffs/day β-agonist during run-in period
Slide 72
FEV1=forced expiratory volume in 1 second; COPD=chronic obstructive pulmonary disease.
![Page 73: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/73.jpg)
Key Inclusion/Exclusion Criteria
• Exclusion
– History of COPD
– History of intubation for asthma, acute asthma therapy in an
emergency department/urgent care/office setting within 1 month,
or hospitalization for asthma within 3 months of the beginning of
run-in
– Any active, acute, or chronic pulmonary disorder (other than
asthma), or active, clinically significant sinus infection
– Unresolved signs and symptoms of upper respiratory tract
infection within 3 weeks
of the beginning of run-in
– Prohibited medications (prior to screening visit)
Slide 73
FEV1=forced expiratory volume in 1 second; COPD=chronic obstructive pulmonary disease.
![Page 74: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/74.jpg)
Primary and Secondary Efficacy
End Points
• Primary
– Percentage of asthma-control days, defined as a day
with none of the following:
♦ Unscheduled visit for asthma care to an office,
emergency department, or hospital setting
♦ Use of >2 puffs of β-agonist
♦ Use of other asthma rescue medication
♦ Nocturnal awakenings
• Secondary
– Average change from baseline in mean daytime
symptom score
– Change from baseline in average AM peak expiratory
flow rate
Slide 74
![Page 75: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/75.jpg)
Tertiary Efficacy End Points
• Changes in lung function
– FEV1
– PM PEFR
• Changes in parameters of asthma control
– Average daily number of β-agonist puffs
– Average nighttime symptom score
– Asthma-free daysa
– Asthma attacks/time to first attackb
– Discontinuations due to asthma
• Other
– Eosinophil count FEV1=forced expiratory volume in 1 second; PEFR=peak expiratory f low rate.
aAsthma-free day def ined as a day with no unscheduled visit for asthma care to an of f ice, emergency department, or hospital setting; no use of
β-agonist; no use of other rescue medication; and no nocturnal awakening. bAsthma attack def ined as the occurrence of an unscheduled visit to the doctor’s office or emergency department, hospitalization, or treatment
with oral, intravenous, or intramuscular corticosteroids.
Slide 75
![Page 76: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/76.jpg)
Safety Profile End Points
• Clinical Adverse Experiences
– Overall adverse experiences (primary)
– Serious adverse experiences
– Drug-related adverse experiences
– Discontinuations due to adverse experiences
Slide 76
![Page 77: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/77.jpg)
Significant improvements in the mean percentage
of days with asthma control in both groups
Slide 77 J Allergy Clin Immunol 2013;
![Page 78: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/78.jpg)
Patients with a smoking history of >11 pack years
tended to show more benefit with montelukast
Slide 78 J Allergy Clin Immunol 2013;
![Page 79: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/79.jpg)
Key Conclusion
• Evidence suggests that corticosteroids have reduced efficacy for
treatment of asthma in smokers. Because smoking induces cysteinyl
leukotriene production, treatment with Singulair might be helpful in
this population.
• Both montelukast and fluticasone were superior to placebo in this
population; the difference between the 2 treatments was not
statistically significant.
• Patients with a smoking history of less than 11 pack years tended to
show more benefit with fluticasone, whereas those with a smoking
history of greater than 11 pack years tended to show more benefit
with montelukast
Slide 80
![Page 80: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/80.jpg)
© Global Initiative for Asthma
GINA Global Strategy for Asthma
Management and Prevention 2014
This slide set is restricted for academic and educational purposes
only. Use of the slide set, or of individual slides, for commercial or
promotional purposes requires approval from GINA.
Assessment of asthma
![Page 81: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/81.jpg)
© Global Initiative for Asthma
GINA assessment of asthma control
GINA 2014, Box 2-2A
![Page 82: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/82.jpg)
© Global Initiative for Asthma
GINA assessment of asthma control
GINA 2014, Box 2-2B
![Page 83: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/83.jpg)
© Global Initiative for Asthma
Assessment of risk factors for poor asthma outcomes
Risk factors for exacerbations include:
• Ever intubated for asthma
• Uncontrolled asthma symptoms
• Having ≥1 exacerbation in last 12 months
• Low FEV1 (measure lung function at start of treatment, at 3-6 months
to assess personal best, and periodically thereafter)
• Incorrect inhaler technique and/or poor adherence
• Smoking
• Obesity, pregnancy, blood eosinophilia
GINA 2014, Box 2-2B
Risk factors for exacerbations include:
• Ever intubated for asthma
• Uncontrolled asthma symptoms
• Having ≥1 exacerbation in last 12 months
• Low FEV1 (measure lung function at start of treatment, at 3-6 months
to assess personal best, and periodically thereafter)
• Incorrect inhaler technique and/or poor adherence
• Smoking
• Obesity, pregnancy, blood eosinophilia
Risk factors for fixed airflow limitation include:
• No ICS treatment, smoking, occupational exposure, mucus
hypersecretion, blood eosinophilia
Risk factors for exacerbations include:
• Ever intubated for asthma
• Uncontrolled asthma symptoms
• Having ≥1 exacerbation in last 12 months
• Low FEV1 (measure lung function at start of treatment, at 3-6 months
to assess personal best, and periodically thereafter)
• Incorrect inhaler technique and/or poor adherence
• Smoking
• Obesity, pregnancy, blood eosinophilia
Risk factors for fixed airflow limitation include:
• No ICS treatment, smoking, occupational exposure, mucus
hypersecretion, blood eosinophilia
Risk factors for medication side-effects include:
• Frequent oral steroids, high dose/potent ICS, P450 inhibitors
![Page 84: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/84.jpg)
© Global Initiative for Asthma
How?
Asthma severity is assessed retrospectively from the level of
treatment required to control symptoms and exacerbations
When?
Assess asthma severity after patient has been on controller
treatment for several months
Severity is not static – it may change over months or years, or as
different treatments become available
Categories of asthma severity
Mild asthma: well-controlled with Steps 1 or 2 (as-needed SABA or
low dose ICS)
Moderate asthma: well-controlled with Step 3 (low-dose ICS/LABA)
Severe asthma: requires Step 4/5 (moderate or high dose
ICS/LABA ± add-on), or remains uncontrolled despite this treatment
Assessing asthma severity
GINA 2014
![Page 85: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/85.jpg)
© Global Initiative for Asthma
GINA Global Strategy for Asthma
Management and Prevention 2014
This slide set is restricted for academic and educational purposes
only. Use of the slide set, or of individual slides, for commercial or
promotional purposes requires approval from GINA.
Treating asthma to control
symptoms and minimize risk
![Page 86: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/86.jpg)
© Global Initiative for Asthma
Choosing between controller options – population-level decisions
Choosing between treatment options at a population level
e.g. national formularies, health maintenance organisations, national guidelines
The ‘preferred treatment’ at each step is based on:
Efficacy
Effectiveness
Safety
Availability and cost at the population level
based on group mean data for symptoms, exacerbations
and lung function (from RCTs, pragmatic studies and
observational data)
NEW!
GINA 2014, Box 3-3 (1/2) Provided by H Reddel
![Page 87: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/87.jpg)
© Global Initiative for Asthma
Start controller treatment early
For best outcomes, initiate controller treatment as early as possible
after making the diagnosis of asthma
Indications for regular low-dose ICS - any of:
Asthma symptoms more than twice a month
Waking due to asthma more than once a month
Any asthma symptoms plus any risk factors for exacerbations
Consider starting at a higher step if:
Troublesome asthma symptoms on most days
Waking from asthma once or more a week, especially if any risk
factors for exacerbations
If initial asthma presentation is with an exacerbation:
Give a short course of oral steroids and start regular controller
treatment (e.g. high dose ICS or medium dose ICS/LABA, then step
down)
Initial controller treatment for adults, adolescents and children 6–11 years
GINA 2014, Box 3-4 (1/2)
NEW!
![Page 88: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/88.jpg)
© Global Initiative for Asthma
Step 1 – as-needed inhaled short-acting beta2-agonist (SABA)
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
GINA 2014, Box 3-5, Step 1
![Page 89: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/89.jpg)
© Global Initiative for Asthma
Step 2 – low-dose controller + as-needed inhaled SABA
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
GINA 2014, Box 3-5, Step 2
![Page 90: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/90.jpg)
© Global Initiative for Asthma
Step 3 – one or two controllers + as-needed inhaled reliever
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
GINA 2014, Box 3-5, Step 3
![Page 91: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/91.jpg)
© Global Initiative for Asthma
Step 4 – two or more controllers + as-needed inhaled reliever
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
GINA 2014, Box 3-5, Step 4
![Page 92: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/92.jpg)
© Global Initiative for Asthma
Step 5 – higher level care and/or add-on treatment
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
GINA 2014, Box 3-5, Step 5
![Page 93: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/93.jpg)
© Global Initiative for Asthma
Low, medium and high dose inhaled corticosteroids
Adults and adolescents (≥12 years)
This is not a table of equivalence, but of estimated clinical comparability
Most of the clinical benefit from ICS is seen at low doses
High doses are arbitrary, but for most ICS are those that, with prolonged use,
are associated with increased risk of systemic side-effects
Inhaled corticosteroid Total daily dose (mcg)
Low Medium High
Beclometasone dipropionate (CFC) 200–500 >500–1000 >1000
Beclometasone dipropionate (HFA) 100–200 >200–400 >400
Budesonide (DPI) 200–400 >400–800 >800
Ciclesonide (HFA) 80–160 >160–320 >320
Fluticasone propionate (DPI or HFA) 100–250 >250–500 >500
Mometasone furoate 110–220 >220–440 >440
Triamcinolone acetonide 400–1000 >1000–2000 >2000
GINA 2014, Box 3-6 (1/2)
![Page 94: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/94.jpg)
© Global Initiative for Asthma
Low, medium and high dose inhaled corticosteroids
Children 6–11 years
This is not a table of equivalence, but of estimated clinical comparability
Most of the clinical benefit from ICS is seen at low doses
High doses are arbitrary, but for most ICS are those that, with prolonged use, are
associated with increased risk of systemic side-effects
Inhaled corticosteroid Total daily dose (mcg)
Low Medium High
Beclometasone dipropionate (CFC) 100–200 >200–400 >400
Beclometasone dipropionate (HFA) 50–100 >100–200 >200
Budesonide (DPI) 100–200 >200–400 >400
Budesonide (nebules) 250–500 >500–1000 >1000
Ciclesonide (HFA) 80 >80–160 >160
Fluticasone propionate (DPI) 100–200 >200–400 >400
Fluticasone propionate (HFA) 100–200 >200–500 >500
Mometasone furoate 110 ≥220–<440 ≥440
Triamcinolone acetonide 400–800 >800–1200 >1200
GINA 2014, Box 3-6 (2/2)
![Page 95: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/95.jpg)
Levels of Asthma Control
Characteristic Controlled
(All of the following)
Partly controlled (Any present in any week)
Uncontrolled
Daytime symptoms None (2 or less /
week)
More than
twice / week
3 or more
features of
partly
controlled
asthma present in
any week
Limitations of
activities None Any
Nocturnal
symptoms /
awakening
None Any
Need for rescue /
“reliever” treatment
None (2 or less /
week)
More than
twice / week
Lung function
(PEF or FEV1) Normal
< 80% predicted or
personal best (if
known) on any day
Exacerbation None One or more / year 1 in any week
![Page 96: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/96.jpg)
© Global Initiative for Asthma
How often should asthma be reviewed?
1-3 months after treatment started, then every 3-12 months
During pregnancy, every 4-6 weeks
After an exacerbation, within 1 week
Stepping up asthma treatment
Sustained step-up, for at least 2-3 months if asthma poorly controlled
• Important: first check for common causes (symptoms not due to asthma, incorrect inhaler technique, poor adherence)
Short-term step-up, for 1-2 weeks, e.g. with viral infection or allergen
• May be initiated by patient with written asthma action plan
Day-to-day adjustment
• For patients prescribed low-dose ICS/formoterol maintenance and reliever regimen*
Stepping down asthma treatment
Consider step-down after good control maintained for 3 months
Find each patient’s minimum effective dose, that controls both symptoms and exacerbations
Reviewing response and adjusting treatment
GINA 2014
*Approved only for low dose beclometasone/formoterol and low dose budesonide/formoterol
![Page 97: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/97.jpg)
The underline cause of Asthma is the
inflammation…
Does the ICS based therapy is enough?
![Page 98: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/98.jpg)
Airway Inflammation Persisted
Despite Corticosteroid Use
ICS=inhaled corticosteroids; OCS ± ICS=received oral corticosteroids with or without ICS
Adapted from Louis R et al Am J Respir Crit Care Med 2000;161:9-16.
20,000
10,000
1,000
100
10
1
Eosinophil 103/g sputum
Control group
Mild to moderate
ICS low-dose (n=10)
ICS high-dose
(n=15)
OCS (n=10)
OCS ± ICS (n=7)
Severe asthma
p<0.01
p<0.001
p<0.001
p<0.01
In a clinical study of 74 patients
![Page 99: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/99.jpg)
Leukotrienes
Other inflammatory mediators
This slide is an artistic rendition.
Adapted from Holgate ST, Peters-Golden M J Allergy Clin Immunol 2003;111(1 suppl):S1-S4; Holgate ST et al J Allergy Clin Immunol 2003;111(1 suppl):S18-S36; Henderson WR Jr et al Am J Respir Crit Care Med 2002;165:108-116; Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):S37-S42; Varner AE, Lemanske RF Jr. In Asthma and Rhinitis. Oxford, UK: Blackwell Science, 2000:1172-1185.
No Inflammation Inflammation Asthma
Leukotrienes: Important in Early Asthma
and Throughout the Disease
![Page 100: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/100.jpg)
block
steroid- sensitive mediators
blocks the
effects of CysLTs
Inhaled steroids Montelukast
Montelukast Combined with a Steroid
Affects the Dual Pathways of Inflammation
The slide represents an artistic rendition.
Adapted from Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):S37-S42; Bisgaard H Allergy
2001;56(suppl 66):7-11.
Steroid-sensitive
mediators play a key role
in asthmatic inflammation
CysLTs play a key role in asthmatic
inflammation
Steroids do NOT inhibit CysLT formation in the airways of asthmatic patients
DUAL PATHWAY
Dual Pathways of Inflammation
![Page 101: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/101.jpg)
SGA 2003-W-6701-SS
Downloaded from – www.singulair.ae Slide 102
Budesonide Turbuhaler 400–1600 µg qd
+ montelukast (n=326)
Budesonide Turbuhaler 400–1600 µg qd
+ placebo
(n=313)
qd = once daily
Inhaled short-acting beta2 agonists were permitted as needed.
Adapted from Vaquerizo MJ et al Thorax 2003;58:204-211.
CASIOPEA Study
Design
Period I
Weeks
Period II
Budesonide
Turbuhaler 400–1600 µg/day
V1
–2
V2
0
V2
4
V2
8
V5
16
![Page 102: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/102.jpg)
SGA 2003-W-6701-SS
Downloaded from – www.singulair.ae Slide 103
FEV1 = forced expiratory volume in one second
Adapted from Vaquerizo MJ et al Thorax 2003;58:204-211.
• Non-smoking asthmatic patients 18–70 years of age
• Prior treatment with a clinically stable dose of ICS
equivalent to budesonide 400–1600 µg/day
• FEV1 55% of predicted
• Reversible airway obstruction (12% increase
from baseline)
• Minimum total daytime asthma symptom score
of 64 (of possible 336)
• 1 puff/day of beta2 agonist
CASIOPEA Study
Inclusion Criteria
![Page 103: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/103.jpg)
SGA 2003-W-6701-SS
Downloaded from – www.singulair.ae Slide 104
Adapted from Vaquerizo MJ et al Thorax 2003;58:204-211.
CASIOPEA Study
Montelukast + Budesonide
Significantly Reduced Asthma-Exacerbation Days
4.8
3.1
Budesonide +
placebo
(n=308)
Montelukast +
budesonide
(n=317)
Median
percentage
of asthma-
exacerbation
days
5
4
3
2
1
0
35% p=0.03
![Page 104: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/104.jpg)
SGA 2003-W-6701-SS
Downloaded from – www.singulair.ae Slide 105
Adapted from Vaquerizo MJ et al Thorax 2003;58:204-211.
CASIOPEA Study
Montelukast + Budesonide
Significantly Increased Asthma-Free Days
42.3
66.1
Budesonide +
placebo
(n=308)
Montelukast +
budesonide
(n=317)
Median
percentage
of asthma-
free days
70
60
50
40
30
56% p=0.001
![Page 105: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/105.jpg)
SGA 2003-W-6701-SS
Downloaded from – www.singulair.ae Slide 106
*The percentage of patients who awoke during the night because of asthma
Adapted from Vaquerizo MJ et al Thorax 2003;58:204-211.
CASIOPEA Study
Montelukast + Budesonide
Significantly Reduced Nocturnal Awakenings
25.6
Least square
mean % of
patients
with nocturnal
awakenings*
35
30
25
20
32.2
20% p=0.01
Budesonide +
placebo
(n=308)
Montelukast +
budesonide
(n=317)
![Page 106: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/106.jpg)
SGA 2003-W-6701-SS
Downloaded from – www.singulair.ae Slide 107
*p = 0.05 vs. budesonide alone
Adapted from Vaquerizo MJ et al Thorax 2003;58:204-211.
CASIOPEA Study
Montelukast + Budesonide
Significantly Reduced Beta2-Agonist Use*
% change
from
baseline in
beta2-agonist
use
30
20
10
0
–10
–20
–30
–40
First 7 days in active treatment
Budesonide + placebo (n=313)
Montelukast + budesonide (n=326)
Basal 1 2 3 4 5 6 7
A more rapid onset of action
than budesonide + placebo
![Page 107: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/107.jpg)
SGA 2003-W-6701-SS
Downloaded from – www.singulair.ae Slide 108
CASIOPEA Study
Montelukast + Budesonide
Significantly Increased AM PEFR*
Tertiary endpoint: Morning PEFR
Mean adjusted by center and stratum
*p = 0.05 vs. budesonide alone
Adapted from Vaquerizo MJ et al Thorax 2003;58:204-21.
11.3
16.86
Budesonide + placebo (n=308)
Montelukast + budesonide
(n=317)
20
15
10
5
0
49% p=0.05
Least square
mean change
in morning
PEFR
(L/min)
![Page 108: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/108.jpg)
Key Conclusion
SINGULAIR in combination with ICS represents an
essential tool to better treat the inflammation.
This approach has also proven to provide high
efficacy on asthma symptoms.
The efficacy of the SINGULAIR/ICS approach on
symptoms results from its superior efficacy on
inflammation, the underlying cause of asthma.
![Page 109: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/109.jpg)
110
Epidemiologic Links between Allergic Rhinitis and Asthma
Many Patients with Asthma Have
Allergic Rhinitis
Adapted f rom Bousquet J et al J Allergy Clin Immunol 2001;108(suppl 5):S147–S334; Sibbald B, Rink E Thorax 1991;46:895–901; Leynaert B
et al J Allergy Clin Immunol 1999;104:301–304; Brydon MJ Asthma J 1996:29–32.
Up to 80%
of all asthmatic patients have allergic rhinitis
All asthmatic patients
![Page 110: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/110.jpg)
111
One Airway, One Disease
Allergic Rhinitis and Asthma Share Common
Inflammatory Cells and Mediators
Adapted f rom Casale TB et al Clin Rev Allergy Immunol 2001;21:27–49; Kay AB N Engl J Med 2001;344:30–37.
Early-phase
response
Late-phase
response T cells
Inflammatory
mediators
Allergen
Cytokines
Preformed Mediators Cysteinyl leukotrienes
Prostaglandins
Platelet-activating factor
Eosinophils
Membrane-bound
IgE
Mast
cell
![Page 111: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/111.jpg)
Drug Asthma AR
Asthma and AR
ICS – –
LABAs – –
Intranasal steroids
– –
Antihistamines
– –
Montelukast
Major Therapies At-A-Glance
ICS=inhaled corticosteroids; LABAs=long-acting beta2-agonists
Adapted f rom Flovent® prescribing information, GlaxoWellcome, Research Triangle Park, NC, 2000; Pulmicort Turbuhaler® prescribing
information, AstraZeneca, Wilmington, DE, 2003; Advair Diskus® prescribing information, GlaxoWellcome, Research Triangle Park, NC, 2004;
Serevent® prescribing information, GlaxoWellcome, Research Triangle Park, NC, 2000; Zyrtec® prescribing information, Pf izer Labs, New York,
NY, 2004; Allegra-D® prescribing information, Aventis Pharmaceuticals, Kansas City, MO, 2004; Flonase® prescribing information,
GlaxoWellcome, Research Triangle Park, NC, 2000; Beconase AQ® prescribing information, GlaxoWellcome, Research Triangle Park, NC, 2002.
![Page 112: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/112.jpg)
COMPACT Study Design
Adapted f rom Price DB et al Thorax 2003;58:211–216.
Budesonide
400 µg
twice daily
Montelukast 10 mg once daily +
Budesonide 400 µg twice daily (n=448)
0 4 16
Period I
Run-in (4 weeks)
Single-blind
Period II
Active treatment (12 weeks)
Double-blind
1 8 12
Budesonide 800 µg twice daily +
Oral placebo montelukast (n=441)
Weeks
![Page 113: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/113.jpg)
Subanalysis of Asthma Patients with Concomitant Allergic Rhinitis in COMPACT
Montelukast Provided Greater Improvements in Morning PEF in Asthma Patients with Concomitant Allergic Rhinitis
50
40
30
20
10
0
Change
from
baseline
(L/min, LS
meanSEM)
0 4 8 12 0 4 8 12
Montelukast (n=433)*
Budesonide (n=425)**
p<0.03
p=0.36
Weeks Weeks
Montelukast (n=216)*
Budesonide (n=184)**
*Montelukast 10 mg once daily + budesonide 400 µg twice daily; **Budesonide 800 µg twice daily
Adapted f rom Price DB et al. Presentation at the World Allergy Organization Biannual Meeting, September 2003, Vancouver, British Columbia,
Canada.
50
40
30
20
10
0
![Page 114: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/114.jpg)
Proposed pathophysiologic mechanisms
of asthma exacerbated by sinusitis
Spread of inflammatory mediators and
chemotactic factors to lower airways triggers
sinobronchial reflex mechanism.
Stimulation of autonomic nervous system
causes acute bronchial hyperresponsiveness.
Bronchoconstrictive reflexes originating in
extrathoracic airway receptors are stimulated.
![Page 115: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/115.jpg)
Proposed pathophysiologic mechanisms
of asthma exacerbated by sinusitis
Reversible partial beta-adrenergic blockade is enhanced.
Nasal congestion causes mouth-breathing, which leads to increased loss of water and heat in lower airways.
Depressed nitric oxide concentration promotes acute bronchial hyperresponsiveness.
![Page 116: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/116.jpg)
Why isn’t his asthma getting
better????
![Page 117: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/117.jpg)
Poor asthma control? - then look up the nose. The importance of co-morbid rhinitis in patients with asthma
Scadding G. and Walker S.
The Royal National Throat, Nose and Ear Hospital, London, UK,Primary Care Respiratory Journal 21(2):222-228 2012
![Page 118: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/118.jpg)
Review the patient after 2–4 weeks
Improved
Continue or step-
down treatment for >1 month
Review diagnosis
Review compliance Query infections or other causes
Add or
increase INS dose
Rhinorrhea:
Add ipratropium
In preferred order - INS - H1 blockers or LTRA
Failure
Blockage: Add
decongestant or oral corticosteroid
If failure: refer to a specialist
ARIA Update 2008: INSs Are the Preferred
First-Line Therapy for Moderate/Severe PER1
Moderate/Severe Persistent
ARIA = Allergic Rhinitis and its Impact on Asthma; INS = intranasal corticosteroid; PER = persistent allergic rhinitis;
LTRA = leukotriene receptor antagonist. 1. Bousquet J et al. Allergy. 2008;63(suppl 86):8–160.
![Page 119: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/119.jpg)
Characteristics of an Ideal INS : balancing efficacy, safety and preference
Rapid onset of action
High efficacy against all nasal symptoms
Once daily dosing schedule
Acceptable to patients
With low or absent local / systemic side-effects
Clin Exp All Rev 2002(2):32-37
![Page 120: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/120.jpg)
Share Your Patient Concerns …..
![Page 121: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/121.jpg)
122
NASONEX Rapid Onset of Action: Significant Total Symptom Relief Within Hours of a Single Dose in Patients With SAR
*P<0.05 vs placebo.
Berkowitz et al. Allergy Asthma Proc. 1999;20:167.
-8
-6
-4
-2
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Hours after dosing
Mean
ch
an
ge f
rom
baselin
e
in t
ota
l sym
pto
m s
co
re
* * * * * * * *
NASONEX® 200 μg (n=119)
Placebo (n=116)
Change in Total Symptoms
5 hrs
![Page 122: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/122.jpg)
123
Primary
Endpoint
70
60
40
50
0
30
20
10
Days
1–15
Days
16–30
Days
31–45
Days
46–60
Days
61–75
Days
76–90
Endpoint*
Me
an
re
du
cti
on
fro
m
ba
se
lin
e in
AM
/PM
TN
SS
, %
MFNS
Placebo
a
a
a a
a a a
aP<0.01 vs placebo.
*Endpoint was defined as the last patient visit or last diary interval for which the patient had non-missing data. Baseline values were MFNS = 7.0 and placebo = 7.1. MFNS = mometasone furoate nasal spray; PAR = perennial allergic rhinitis; TNSS = total nasal symptom score. 1. Mandl M et al. Ann Allergy Asthma Immunol. 1997;79:370–378.
MFNS in Adolescents/Adults With PAR:
Efficacy Results – TNSS1
![Page 123: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/123.jpg)
124
Ch
an
ge
in
na
sa
l c
on
ge
sti
on
fro
m b
as
eli
ne
, %
-60
-50
-40
-30
-20
-10
0
Days
1–15
Days
16–30
Days
31–45
Days
46–60
Days
61–75
Days
76–90 Endpoint* Baseline
Placebo (n=184)
MFNS 200 µg once daily (n=181)
40%
33%
aP<0.05 vs placebo.
*Endpoint was defined as the last patient visit or last diary interval for which the patient had non-missing data. MFNS = mometasone furoate nasal spray; PAR = perennial allergic rhinitis .
1. Mandl M et al. Ann Allergy Asthma Immunol. 1997;79:370–378.
MFNS in Adolescents/Adults With PAR:
Efficacy Results – Nasal Congestion1
a
a
a
a a
a
a
![Page 124: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/124.jpg)
0
10
20
30
40
50
60
Flunisolide Triamcinolone Beclomethasone Budesonide FP Fluticasone
furoate
Ciclesonide MF
INS Systemic Bioavailability1,a
aDifferences in safety between INSs are more theoretical than evidence-based, with the greatest concern being systemic
exposure and effects on adrenal function and growth in children. INS = intranasal corticosteroid; FP = fluticasone propionate; MF = mometasone furoate. 1. Derendorf H et al. Allergy. 2008;63:1292–1300.
<0.1%
Bio
ava
ila
bil
ity,
%
![Page 125: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/125.jpg)
126
1-Year Therapy With MFNS Did Not Induce
Nasal Atrophy in Patients With PAR1,a
Nasal Biopsies Before MFNS Treatment After 12 Months of Treatment With
MFNS 200 µg/d
Disruption of epithelium
Eosinophil infiltration
Epithelium intact
No eosinophil infiltration
aThe clinical relevance of these data in the treatment of allergic rhinitis is not known.
MFNS = mometasone furoate nasal spray; PAR = perennial allergic rhinitis. 1. Minshall E et al. Otolaryngol Head Neck Surg. 1998;118:648–654.
![Page 126: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/126.jpg)
127
MFNS: Effect on Serum Cortisol in Children
2–5 Years of Age Following 42 Days of Treatment1 S
eru
m c
ort
iso
l
(μg
/dL
– R
IA)
0
2
4
6
8
10
12
14
16
Mean serum cortisol concentration-time profile on Day 42 in children with AR
MFNS 100 μg once
daily (n=26)
Placebo once daily
(n=26)
6:00 AM 10:00 AM 2:00 PM 6:00 PM 10:00 PM 2:00 AM 6:00 AM
MFNS = mometasone furoate nasal spray; AR = allergic rhinitis; RIA = radioimmunoassay. 1. Cutler DL et al. Pediatr Asthma Allergy Immunol. 2006;19:146–153.
![Page 127: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/127.jpg)
Wheezing in
Children
![Page 128: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/128.jpg)
Adventitious Airway Sounds
Snoring
Stridor
Wheezing
Crepitations
![Page 129: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/129.jpg)
Airway Diameter
![Page 130: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/130.jpg)
Cause of Wheezing
Not from obstruction of small airways –
Surface area too large
From increased intrathoracic pressure +
decreased large airway pressure =
vibration of airway wall in large airways
(Generations 1-5)
![Page 131: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/131.jpg)
Wheezing
Sign of lower (intra-thoracic) airway
obstruction
Small airways
![Page 132: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/132.jpg)
Air Trapping
Hyperinflated chest
Barrel shaped
Loss of cardiac dullness
Liver pushed down
Hoover sign
![Page 133: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/133.jpg)
Hoover Sign
Normal diagphragm movement
Hyperinflation = diaphragm flattened
Diaphragm contraction = paradoxical
inward movement of lower interrcostal
area during inspiration
![Page 134: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/134.jpg)
Acute Wheezing
Asthma
Bronchiolitis
Foreign body
![Page 135: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/135.jpg)
Bronchiolitis
136
![Page 136: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/136.jpg)
What Is Bronchiolitis?
Bronchiolitis is acute inflammation of the airways, characterised by wheeze
Bronchiolitis can result from a viral infection
Respiratory Syncytial Virus (RSV) may be responsible for up to 90% of bronchiolitis cases in young children
Hall CB, McCarthy CA. In: Principles and Practice of Infectious Diseases 2000:1782-1801;
Panitch HB et al. Clin Chest Med 1993;14:715-731
137
![Page 137: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/137.jpg)
RSV Is a Common Virus Causing
Bronchiolitis in Children
In a clinical study in Argentina, RSV was the most common virus isolated from a sample of children aged <5 years with acute lower respiratory infection
0.7% 6.5% 6.8% 7.8%
78.2%
RSV
Adenovirus
Parainfluenza
Influenza A
Influenza B
Carballal G et al. J Med Virol 2001;64:167-174
138
New viruses (Human
Metapneumovirus,
Bocca, Corona)
![Page 138: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/138.jpg)
Chronic Wheezing
Thriving child – Happy wheezer
Child failing to thrive - Causes
![Page 139: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/139.jpg)
Exclude other conditions
Structural problems: bronchoscopy
URTD : Polysomnography,
Esophageal disease: Barium swallow, pH probes, scopes and gram
Primary ciliary dyskinesia: nasal ciliary motility, Exhaled NO, EM, saccharine test
TB: mantoux, induced sputum/ gastric lavage/ BAL = Culture, microscopy & PCR
Bronchiectasis: HRCT scan, BAL
CF: sweat test, nasal potentials, genotypes
Systemic immune deficiency: Ig subtypes, lymphocytes & neutrophil function, HIV
Cardiovascular disease: echo, angiography
![Page 140: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/140.jpg)
WHEEZING PHENOTYPES 12 Longitudinal birth cohorts
Original Tucson Group (Taussig L et al 1985)
Persistent
Atopic
Non Atopic
Transient
![Page 141: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/141.jpg)
TRANSIENT WHEEZERS Commonest form of wheeze
Decrease lung function at birth
No airway hyper-responsiveness
Non Atopic
No immune responses to viruses
Resolves by 3 years
– Wheeze in first year – better outcome
– Wheeze 2-3 year – worse outcome due to maturity of immune system
Affected by : Teenage pregnancy & smoking
Male gender
Day care- infections
![Page 142: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/142.jpg)
STRUCTURAL CONSIDERATIONS
Lung Growth: Fetal 8 years
Affected by:
Temperature & O2 tension
Nutrition & Smoking
Functional disorders eg CDH
Prematurity
Growth factors-Gene repair
Drugs (B2 agonist/ C/S)
Risk factors for COPD Mx: antioxidant, retinoids,MMPI
![Page 143: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/143.jpg)
PERSISTENT NON
ATOPIC WHEEZER
Lung function abnormal at birth and
reduced in later life
Non Atopic
Airway hyper-responsiveness
Peak flow variability
RSV induced wheeze due to alteration
in airway tone
BETTER OUTCOME THAN ATOPIC
PERSISTENT WHEEZERS
![Page 144: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/144.jpg)
OUTCOME OF INFANT WHEEZING
Low birth weight
Pregnancy smoking
Male Sex
Affluence
Atopy
Low maternal age (first born)
Infant wheeze
With viral infection alone With various precipitants
Remission in 80%
?? COPD in adults
Persistent asthma (with or without
evidence of atopy) in 50-60%
![Page 145: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/145.jpg)
Asthma in Pre-School
Children
146
![Page 146: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/146.jpg)
The Various Marches That Set Up Asthma
Asthma
![Page 147: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/147.jpg)
The Atopic March
![Page 148: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/148.jpg)
Wheezing Phenotypes
• Tuscon:
- Transient early wheezing
- Persistent early-onset wheezing
- Late-onset wheezing (Martinez FD, 1995)
• ERS Task-Force:
- Viral induced wheeze
- Multi-trigger wheeze (Brand PLP, 2008)
![Page 149: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/149.jpg)
Outcome of wheeze in infancy
Martinez FD, et al. N Engl J Med 1995; 332: 133-138
![Page 150: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/150.jpg)
Causes of Recurrent Wheezing in Infancy
Asthma
Multiple trigger wheeze
Episodic viral wheeze
Other
causes
![Page 151: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/151.jpg)
Viruses and Asthma
Atopy
Asthma
Rhinovirus
RSV
Genes
Influenza
![Page 152: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/152.jpg)
Features Suggestive of Asthma
• Wheezing more than 1x/ month (Evidence C)
• Activity-induced cough or wheeze (Evidence A)
• Cough at night (Evidence A)
• Absence of seasonal variation (Evidence B)
• Symptoms persisting after the age of 3 years (Evidence A)
• Symptoms worsening with certain exposures (Evidence B)
• Colds repeatedly going to the chest (Evidence B)
• Response to a bronchodilator (Evidence B)
• Response to a 10-day oral steroid course (Evidence B)
• Concomitant rhinitis, eczema or food allergies (Evidence B)
• Family history of allergy (Evidence B)
• Response to a bronchodilators in children under 5 (FEV>12%, PEFR> (FEV>12%, PEF>20% of pre-bronchodilators PEF) (Evidence A)
• Diurnal variation of PEF >20% with twice daily readings (Evidence A)
![Page 153: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/153.jpg)
Asthma Prediction Index
Major Criteria
Family history of
asthma
Positive history of
atopic eczema
Positive SPT
Minor Criteria
Eosinophilia > 4%
Positive history of
allergic rhinitis
Wheeze without
viral infections
Asthma = 1 Major or 2 Minor
Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD.
A clinical index to def ine risk of asthma in young children with recurrent wheezing.
Am J Respir Crit Care Med. 2000;162(4 Pt 1):1403-6.
![Page 154: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/154.jpg)
56% Asthmatic Children in Pretoria Atopic
Figure 1. Inhalant Allergens. % of positive tests
(Only 28 of 50 patients positive)
27%
21%9%2%5%
12%
19%5%
Bermuda grass
Grass mix
Tree mix
Cat epithelium
Dog dander
HDM
Cockroach
Horse
![Page 155: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/155.jpg)
TREATING
WHEEZES
![Page 156: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/156.jpg)
Treatment Options Pre-school Wheeze
Montelukast 7 - 14 days
Episodic wheeze
ICS or
LTRA
Multiple trigger wheeze
Mild
ICS + LABA
Persistent asthma
Moderate/Severe
Wheeze
If not responding – Stop Treatment and Review diagnosis
![Page 157: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/157.jpg)
© Global Initiative for Asthma
GINA Global Strategy for Asthma
Management and Prevention 2014
This slide set is restricted for academic and educational purposes
only. Use of the slide set, or of individual slides, for commercial or
promotional purposes requires approval from GINA.
Diagnosis and management
of asthma in children
5 years and younger
GINA 2014
![Page 158: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/158.jpg)
© Global Initiative for Asthma
Features suggesting asthma in children ≤5 years
Feature Characteristics suggesting asthma
Cough Recurrent or persistent non-productive cough that may be worse at
night or accompanied by some wheezing and breathing difficulties.
Cough occurring with exercise, laughing, crying or exposure to
tobacco smoke in the absence of an apparent respiratory infection
Wheezing Recurrent wheezing, including during sleep or with triggers such as
activity, laughing, crying or exposure to tobacco smoke or air pollution
Difficult or heavy
breathing or
shortness of breath
Occurring with exercise, laughing, or crying
Reduced activity Not running, playing or laughing at the same intensity as other
children; tires earlier during walks (wants to be carried)
Past or family history Other allergic disease (atopic dermatitis or allergic rhinitis)
Asthma in first-degree relatives
Therapeutic trial with
low dose ICS and
as-needed SABA
Clinical improvement during 2–3 months of controller treatment and
worsening when treatment is stopped
GINA 2014, Box 6-2
![Page 159: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/159.jpg)
© Global Initiative for Asthma
Common differential diagnoses of asthma in children ≤5 years
Condition Typical features
Recurrent viral respiratory
infections
Mainly cough, runny congested nose for <10 days; wheeze
usually mild; no symptoms between infections
Gastroesophageal reflux Cough when feeding; recurrent chest infections; vomits easily
especially after large feeds; poor response to asthma
medications
Foreign body aspiration Episode of abrupt severe cough and/or stridor during eating or
play; recurrent chest infections and cough; focal lung signs
Tracheomalacia or
bronchomalacia
Noisy breathing when crying or eating, or during URTIs; harsh
cough; inspiratory or expiratory retraction; symptoms often
present since birth; poor response to asthma treatment
Tuberculosis Persistent noisy respirations and cough; fever unresponsive to
normal antibiotics; enlarged lymph nodes; poor response to BD
or ICS; contact with someone with TB
Congenital heart disease Cardiac murmur; cyanosis when eating; failure to thrive;
tachycardia; tachypnea or hepatomegaly; poor response to
asthma medications
GINA 2014, Box 6-3 (1/2)
![Page 160: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/160.jpg)
© Global Initiative for Asthma
Common differential diagnoses of asthma in children ≤5 years (continued)
Condition Typical features
Cystic fibrosis Cough starting shortly after birth; recurrent chest infections;
failure to thrive (malabsorption); loose greasy bulky stools
Primary ciliary dyskinesia Cough and recurrent mild chest infections; chronic ear infections
and purulent nasal discharge; poor response to asthma
medications; situs inversus (in ~50% children with this condition)
Vascular ring Respirations often persistently noisy; poor response to asthma
medications
Bronchopulmonary
dysplasia
Infant born prematurely; very low birth weight; needed prolonged
mechanical ventilation or supplemental oxygen; difficulty with
breathing present from birth
Immune deficiency Recurrent fever and infections (including non-respiratory); failure
to thrive
GINA 2014, Box 6-3 (2/2)
![Page 161: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/161.jpg)
© Global Initiative for Asthma
GINA assessment of asthma control in children ≤5 years
GINA 2014, Box 6-4 (1/2)
![Page 162: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/162.jpg)
© Global Initiative for Asthma
Risk factors for poor asthma outcomes in children ≤5 years
Risk factors for exacerbations in the next few months
• Uncontrolled asthma symptoms
• One or more severe exacerbation in previous year
• The start of the child’s usual ‘flare-up’ season (especially if autumn/fall)
• Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens (e.g.
house dust mite, cockroach, pets, mold), especially in combination with viral infection
• Major psychological or socio-economic problems for child or family
• Poor adherence with controller medication, or incorrect inhaler technique
GINA 2014, Box 6-4B
Risk factors for exacerbations in the next few months
• Uncontrolled asthma symptoms
• One or more severe exacerbation in previous year
• The start of the child’s usual ‘flare-up’ season (especially if autumn/fall)
• Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens (e.g.
house dust mite, cockroach, pets, mold), especially in combination with viral infection
• Major psychological or socio-economic problems for child or family
• Poor adherence with controller medication, or incorrect inhaler technique
Risk factors for fixed airflow limitation
• Severe asthma with several hospitalizations
• History of bronchiolitis
Risk factors for exacerbations in the next few months
• Uncontrolled asthma symptoms
• One or more severe exacerbation in previous year
• The start of the child’s usual ‘flare-up’ season (especially if autumn/fall)
• Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens (e.g.
house dust mite, cockroach, pets, mold), especially in combination with viral infection
• Major psychological or socio-economic problems for child or family
• Poor adherence with controller medication, or incorrect inhaler technique
Risk factors for fixed airflow limitation
• Severe asthma with several hospitalizations
• History of bronchiolitis
Risk factors for medication side-effects
• Systemic: Frequent courses of OCS; high-dose and/or potent ICS
• Local: moderate/high-dose or potent ICS; incorrect inhaler technique; failure to protect
skin or eyes when using ICS by nebulizer or spacer with face mask
![Page 163: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/163.jpg)
© Global Initiative for Asthma
Control-based asthma management cycle in children ≤5 years
GINA 2014, Box 6-5
![Page 164: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/164.jpg)
© Global Initiative for Asthma
Stepwise approach to control symptoms and reduce risk (children ≤5 years)
GINA 2014, Box 6-5
![Page 165: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/165.jpg)
© Global Initiative for Asthma
Stepwise approach – pharmacotherapy (children ≤5 years)
© Global Initiative for Asthma GINA 2014, Box 6-5
![Page 166: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/166.jpg)
© Global Initiative for Asthma
Assess asthma control
Symptom control, future risk, comorbidities
Self-management
Education, inhaler skills, written asthma action plan, adherence
Regular review
Assess response, adverse events, establish minimal effective treatment
Other
(Where relevant): environmental control for smoke, allergens, indoor or
outdoor air pollution
Stepwise approach – key issues (children ≤5 years)
GINA 2014, Box 6-5
![Page 167: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/167.jpg)
© Global Initiative for Asthma
Step 1 (children ≤5 years) – as-needed inhaled SABA
© Global Initiative for Asthma GINA 2014, Box 6-5
![Page 168: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/168.jpg)
© Global Initiative for Asthma
Preferred option: as-needed inhaled SABA
Provide inhaled SABA to all children who experience wheezing
episodes
Not effective in all children
Other options
Oral bronchodilator therapy is not recommended (slower onset of
action, more side-effects)
For children with intermittent viral-induced wheeze and no interval
symptoms, if as-needed SABA is not sufficient, consider intermittent
ICS. Because of the risk of side-effects, this should only be
considered if the physician is confident that the treatment will be
used appropriately.
Step 1 (children ≤5 years) – as-needed inhaled SABA
GINA 2014
![Page 169: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/169.jpg)
© Global Initiative for Asthma
Step 2 (children ≤5 years) – initial controller + as-needed SABA
© Global Initiative for Asthma GINA 2014, Box 6-5
![Page 170: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/170.jpg)
© Global Initiative for Asthma
Indication
Child with symptom pattern consistent with asthma, and symptoms not
well-controlled, or ≥3 exacerbations per year
May also be used as a diagnostic trial for children with frequent
wheezing episodes
Preferred option: regular daily low dose ICS + as-needed inhaled SABA
Give for ≥3 months to establish effectiveness, and review response
Other options depend on symptom pattern
(Persistent asthma) – regular leukotriene receptor antagonist (LTRA)
leads to modest reduction in symptoms and need for OCS compared
with placebo
(Intermittent viral-induced wheeze) – regular LTRA improves some
outcomes but does not reduce risk of exacerbations
(Frequent viral-induced wheeze with interval symptoms) – consider
episodic or as-needed ICS, but give a trial of regular ICS first
Step 2 (children ≤5 years) – initial controller + as-needed SABA
GINA 2014
![Page 171: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/171.jpg)
© Global Initiative for Asthma
Step 3 (children ≤5 years) – medium dose ICS + as-needed inhaled SABA
© Global Initiative for Asthma GINA 2014, Box 6-5
![Page 172: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/172.jpg)
© Global Initiative for Asthma
Indication
Asthma diagnosis, and symptoms not well-controlled on low dose
ICS
First check symptoms are due to asthma, and check adherence,
inhaler technique and environmental exposures
Preferred option: medium dose ICS with as-needed inhaled SABA
Review response after 3 months
Other options
Consider adding LTRA to low dose ICS (based on data from older
children)
Step 3 (children ≤5 years) – medium dose ICS + as-needed inhaled SABA
GINA 2014
![Page 173: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/173.jpg)
© Global Initiative for Asthma
Step 4 (children ≤5 years) – refer for expert assessment
© Global Initiative for Asthma GINA 2014, Box 6-5
![Page 174: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/174.jpg)
© Global Initiative for Asthma
Indication
Asthma diagnosis, and symptoms not well-controlled on medium
dose ICS
First check symptoms are due to asthma, and check adherence,
inhaler technique and environmental exposures
Preferred option: continue controller treatment and refer for
expert assessment
Other options (preferably with specialist advice)
Higher dose ICS and/or more frequent dosing (for a few weeks)
Add LTRA, theophylline or low dose OCS (for a few weeks only)
Add intermittent ICS to regular daily ICS if exacerbations are the
main problem
ICS/LABA not recommended in this age group
Step 4 (children ≤5 years) – refer for expert assessment
GINA 2014
![Page 175: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/175.jpg)
© Global Initiative for Asthma
This is not a table of equivalence
A low daily dose is defined as the dose that has not been associated
with clinically adverse effects in trials that included measures of safety
‘Low dose’ inhaled corticosteroids (mcg/day) for children ≤5 years
GINA 2014, Box 6-6
Inhaled corticosteroid Low daily dose (mcg)
Beclometasone dipropionate (HFA) 100
Budesonide (pMDI + spacer) 200
Budesonide (nebulizer) 500
Fluticasone propionate (HFA) 100
Ciclesonide 160
Mometasone furoate Not studied below age 4 years
Triamcinolone acetonide Not studied in this age group
GINA 2014, Box 6-6
![Page 176: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/176.jpg)
© Global Initiative for Asthma
Choosing an inhaler device for children ≤5 years
GINA 2014, Box 6-6
Age Preferred device Alternate device
0–3 years Pressurized metered dose
inhaler plus dedicated spacer
with face mask
Nebulizer with face mask
4–5 years
Pressurized metered dose
inhaler plus dedicated spacer
with mouthpiece
Pressurized metered dose
inhaler plus dedicated spacer
with face mask, or nebulizer
with mouthpiece or face mask
GINA 2014, Box 6-7
![Page 177: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/177.jpg)
© Global Initiative for Asthma
Initial assessment of acute asthma exacerbations in children ≤5 years
Symptoms Mild Severe*
Altered consciousness No Agitated, confused or drowsy
Oximetry on
presentation (SaO2)**
>95% <92%
Speech† Sentences Words
Pulse rate <100 beats/min >200 beats/min (0–3 years)
>180 beats/min (4–5 years)
Central cyanosis Absent Likely to be present
Wheeze intensity Variable Chest may be quiet
*Any of these features indicates a severe exacerbation
**Oximetry before treatment with oxygen or bronchodilator † Take into account the child’s normal developmental capability
GINA 2014, Box 6-8
![Page 178: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/178.jpg)
© Global Initiative for Asthma
Indications for immediate transfer to hospital for children ≤5 years
GINA 2014, Box 6-9
*Normal respiratory rates (breaths/minute): 0-2 months: <60; 2-12 months: <50; 1-5 yrs: <40
Transfer immediately to hospital if ANY of the following are present:
Features of severe exacerbation at initial or subsequent assessment
Child is unable to speak or drink
Cyanosis Subcostal retraction
Oxygen saturation <92% when breathing room air
Silent chest on auscultation
Lack of response to initial bronchodilator treatment
Lack of response to 6 puffs of inhaled SABA (2 separate puffs, repeated
3 times) over 1-2 hours
Persisting tachypnea* despite 3 administrations of inhaled SABA, even if the
child shows other clinical signs of improvement
Unable to be managed at home
Social environment that impairs delivery of acute treatment
Parent/carer unable to manage child at home
![Page 179: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/179.jpg)
© Global Initiative for Asthma
Initial management of asthma exacerbations in children ≤5 years
Therapy Dose and administration
Supplemental
oxygen
24% delivered by face mask (usually 1L/min) to maintain
oxygen saturation 94-98%
Inhaled SABA 2–6 puffs of salbutamol by spacer, or 2.5mg by nebulizer, every
20 min for first hour, then reassess severity. If symptoms
persist or recur, give an additional 2-3 puffs per hour. Admit to
hospital if >10 puffs required in 3-4 hours.
Systemic
corticosteroids
Give initial dose of oral prednisolone (1-2mg/kg up to maximum
of 20mg for children <2 years; 30 mg for 2-5 years)
GINA 2014, Box 6-10
Therapy Dose and administration
Supplemental
oxygen
24% delivered by face mask (usually 1L/min) to maintain
oxygen saturation 94-98%
Inhaled SABA 2–6 puffs of salbutamol by spacer, or 2.5mg by nebulizer, every
20 min for first hour, then reassess severity. If symptoms
persist or recur, give an additional 2-3 puffs per hour. Admit to
hospital if >10 puffs required in 3-4 hours.
Systemic
corticosteroids
Give initial dose of oral prednisolone (1-2mg/kg up to maximum
of 20mg for children <2 years; 30 mg for 2-5 years)
Additional options in the first hour of treatment
Ipratropium
bromide
For moderate/severe exacerbations, give 2 puffs of
ipratropium bromide 80mcg (or 250mcg by nebulizer) every
20 minutes for one hour only
Magnesium
sulfate
Consider nebulized isotonic MgSO4 (150mg) 3 doses in first
hour for children ≥2 years with severe exacerbation
![Page 180: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/180.jpg)
Case 1
A 45-year-old man complains of nasal blockage and loss
of smell and taste. He is an asthmatic who has been well
controlled on ICS and LABA therapy. His past history is
significant for chronic rhinosinusitis and one previous hospital admission for asthma with intubation and
mechanical ventilation.
He was told following that admission that he was allergic
to Aspirin, which he had taken for a back pain. On physical examination his lungs are clear of wheeze.
![Page 181: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/181.jpg)
The findings on nasal examination are seen
in this Figure
![Page 182: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/182.jpg)
A. Leukotriene receptor antagonist.
B. A 3-week course of prednisone.
C. Inhaled topical nasal corticosteroid.
D. Allergen immunotherapy to relevant antigens.
E. Aspirin desensitization program.
The most appropriate treatment at this time is:
![Page 183: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/183.jpg)
A. Leukotriene receptor antagonist.
B. A 3-week course of prednisone.
C. Inhaled topical nasal corticosteroid.
D. Allergen immunotherapy to relevant antigens.
E. Aspirin desensitization program.
The most appropriate treatment at this time is:
![Page 184: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/184.jpg)
The patient under discussion has asthma and nasal
polyposis. The aim of therapy for nasal polyps is to restore
nasal patency, and this may return lost taste and smell and
restore sinus drainage.
Topical corticosteroids have been the drugs of choice for
many years as they have been shown to reduce the size of
small polyps and prevent or delay the recurrence of nasal
polyps after surgery. Oral corticosteroids are also very
effective for nasal polyps and in severe cases are preferred
for 3 weeks followed by prolonged topical therapy.
Oral and not topical corticosteroids are usually effective for
anosmia and therefore are preferred in this patient, making
option B correct and C incorrect. When corticosteroids are
not effective, surgery is unavoidable.
![Page 185: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/185.jpg)
Having both asthma and nasal polyposis places a patient up
to a 40% risk of having or developing aspirin sensitivity,
otherwise known as aspirin intolerant asthma (AIA).
Nasal polyps are smooth gelatinous semitranslucent
structures that seem to be outgrowths of the nasal mucosa.
Most polyps arise from the ethmoid sinus and histologically
are a mass of edema fluid with an abundance of eosinophils
and other inflammatory cells such as mast cells,
lymphocytes, and neutrophils. Nasal polyposis is an non-
IgE mediated inflammatory condition and is often
associated with nonallergic rhinitis, aspirin sensitivity, and
nonallergic asthma.
Atopy is no more prevalent in patients with nasal polyps
than in the general population; therefore, option D would not
be an appropriate step in this patient.
![Page 186: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/186.jpg)
Most patients with AIA have a long history of
perennial rhinitis, which begins in the third decade,
often after a viral illness. Over months to years
nasal polyps develop followed by the appearance
of moderately severe to severe asthma and aspirin
sensitivity.
After ingestion of aspirin or a nonsteroidal
antiinflammatory drug (NSAID), an acute asthma
exacerbation occurs, often accompanied by
rhinorrhea, periorbital edema, conjunctival
congestion, and occasionally flushing of the face.
![Page 187: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/187.jpg)
Evidence suggests that by inhibiting the
cyclooxygenase (COX) pathway, aspirin and
NSAIDS divert arachadonic metabolism to the
lipoxygenase pathway which is involved in the
pathogenesis of this syndrome. Leukotriene
pathway modifiers such as the receptor
antagonists have shown to be effective
Leukotriene pathway pathway which is involved in the
pathogenesis of this syndrome. Leukotriene pathway
modifiers such as the receptor antagonists have shown to
be effective for asthma but not nasal polyps; therefore,
option A is not correct
![Page 188: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/188.jpg)
Aspirin desensitization is done by giving small increasing
oral doses of aspirin over 2 to 3 days and then a daily dose
after a refractory period is reached. The asthma is improved
and the nasal inflammatory disease responds the best. This
procedure is ideal in those patients who have just had
surgical polypectomy, as it has been shown to delay the
recurrence of polyps for an average of 6 years.
It would not improve nasal patentcy in this patient;
therefore, option E is not correct. The addition of
nedocromil sodium is incorrect because there is no need to
“step up” her asthma therapy at this time.
![Page 189: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/189.jpg)
oMr Samir a lifelong heavy smoker and asthmatic, the seventy year old Mr Samir is wheezing most days and always is short of breath. He is on regular combivent, beclomethasone 200mcg bd and intermittant salbutamol.
Case 2
![Page 190: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/190.jpg)
oThe most likely diagnosis is Uncontrolled
Asthma.
but The COPD element should not be neglected in this patient with a high smoking index (old age and heavy smoker). It definitely has a share in his symptoms and airflow limitation.
What is the likely diagnosis?
![Page 191: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/191.jpg)
![Page 192: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/192.jpg)
A 46 year old man comes to your clinic for management of
his asthma. He takes high-dose inhaled corticosteroids
and a long-acting beta agonist, along with a leukotriene
inhibitor. His adherence and technique are perfect.
He still has symptoms of cough, wheezing, and chest
tightness that bother him most days and nights each
week. He is using albuterol daily. The symptoms persist
when he goes on vacation out of state.
Sputum culture is negative. IgE level is 3,600 ng/mL. His
primary doctor obtained imaging and a chest CT, which
are shown.
Case 3
![Page 193: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/193.jpg)
![Page 194: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/194.jpg)
What should be the next step? A. Schedule spirometry for next week to
guide step-up therapy.
B. Start omalizumab injections every 2
weeks.
C. Sweat chloride testing.
D. Skin testing for reactivity to Aspergillus
fumigatus.
E. HIV test.
![Page 195: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/195.jpg)
What should be the next step? A. Schedule spirometry for next week to
guide step-up therapy.
B. Start omalizumab injections every 2
weeks.
C. Sweat chloride testing.
D. Skin testing for reactivity to Aspergillus
fumigatus.
E. HIV test.
![Page 196: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/196.jpg)
Allergic bronchopulmonary aspergillosis (ABPA) is an
ongoing hypersensitivity reaction in response to
bronchial colonization by Aspergillus, and is a common
cause of poorly controlled asthma. Cystic fibrosis
patients are also often affected. Bronchial obstruction
by mucus and chronic inflammation can lead to
bronchiectasis and lung fibrosis with irreversible loss
of lung function.
Clinical features: Cough productive of sputum, frequent
"bronchitis"; often with dyspnea and wheezing.
![Page 197: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/197.jpg)
Diagnosis:
By constellation of symptoms and objective
findings. "Classic" ABPA would include the
following:
Asthma history Immediate reactivity on skin prick with Aspergillus
antigens
Precipitating serum antibodies to A. fumigatus Serum total IgE concentration >1,000 ng/mL
Peripheral blood eosinophilia >500/mm3 Lung opacities on chest x-ray or chest HRCT
Central bronchiectasis present on chest CT
Elevated specific serum IgE and IgG to A. fumigatus
![Page 198: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/198.jpg)
A skin test is the best first test, as it
is considered 100% sensitive (i.e., a
negative test rules out the condition).
A serum IgE < 1,000 or negative
precipitating antibodies also rule out
ABPA with high confidence.
![Page 199: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/199.jpg)
Case 4
Your internal medicine colleague asks you about
a patient she is about to discharge home after a
hospitalization for asthma exacerbation. The
patient, takes a beta-blocker for coronary artery
disease and hypertension. Your colleague is
considering stopping the beta-blocker to avoid
any contribution to future asthma exacerbations,
but wants your opinion first.
![Page 200: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/200.jpg)
What do you recommend?
A. Stop the beta blocker.
B. Continue the beta blocker.
C. Stop the beta blocker; order a stress test.
D. Continue the beta blocker; order an
echocardiogram.
![Page 201: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/201.jpg)
Case 5
o Yusuf is 4 years old. He has had a persistant cough for
weeks that wakes him at night. “Every cold goes to his
chest” This is the fifth consultation for cough in the last
year. Only once has a wheeze been documented. His
father is known asthmatic.
1- What is the likely diagnosis? 2- What treatment would you give?
![Page 202: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/202.jpg)
Self-fulfilling: Infant Wheezing
Phenotypes
• Never (51%)
• Transient (20%) – Wheeze 0-3, not at age 6
• Persistent (14%) – Wheeze 0-3 still present
age 6
• Late onset (15%) – Wheeze after age 3
![Page 203: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/203.jpg)
Diagnosing Asthma in Young
Children – Asthma Predictive
Index
• > 4 episodes/yr of wheezing lasting more than 1 day affecting sleep in a child with one MAJOR or two MINOR criteria
• Major criteria
– Parent with asthma
– Physician diagnosed
atopic dermatitis
• Minor criteria
– Physician diagnosed
allergic rhinitis
– Eosinophilia (>4%)
– Wheezing apart from
colds
1Adapted from Castro-Rodriquez JA, et al. AJRCCM 2000; 162: 1403
![Page 204: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/204.jpg)
Modified Asthma Predictive Index (API)
![Page 205: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/205.jpg)
Cough-variant asthma
Cough-variant asthma presents as dry
cough at night. It worsens with exercise
(EIA) and nonspecific triggers (cold air).
Cough-variant asthma responds to asthma
therapy with ICS.
Cough-variant asthma is diagnosed with
pulmonary function testing (PFTs) with
response to bronchodilator. The most
common cause of chronic cough in children
is cough-variant asthma.
![Page 206: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/206.jpg)
1- What is the likely diagnosis?
The likely diagnosis is Bronchial Asthma (childhood asthma): - Family history. - Symtoms (cough mainly at night, every cold goes to the chest). - Signs: chest wheeze.
![Page 207: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/207.jpg)
Treatmnt
![Page 208: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/208.jpg)
Severe asthma - differential diagnosis and management
![Page 209: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/209.jpg)
Case 7 oA 30-year-old G2P1 pregnant woman at 15 weeks gestation presents to an outpatient clinic with worsening dyspnea over the preceding two weeks. Her past medical history is significant for asthma diagnosed in childhood, seasonal allergies, and gastroesophageal reflux disease (GERD) during her previous pregnancy. She notes that her asthma symptoms had been well-controlled on inhaled Budesonide/formoterol (160mcg/4.5mcg), Salbutamol MDI as needed, and a nasal steroid spray prior to pregnancy. However, she discontinued all of her medications when she learned that she was pregnant for fear that they might harm her baby.
![Page 210: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/210.jpg)
oAt today’s visit she feels that she is unable to take a deep breath. She also describes one to two episodes of wheezing daily and night time cough two to three times per week. Warm air, dust, and exposure to cats seem to exacerbate her symptoms. oOn physical exam, the patient is in no acute distress. The lungs are clear to auscultation bilaterally.
1- Is the patient controlled?
2- Is asthma medications safe in pregnancy?
3- Treatment needed?
![Page 211: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/211.jpg)
1- Is the patient controlled?
NO…… Breathlessness. Frequent nocturnal symptoms
(cough and wheezes).
![Page 212: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/212.jpg)
2- Is asthma medications safe in pregnancy?
Yes, There is little evidence suggesting that medications used to treat asthma may harm the fetus. AND also Pregnant patients with asthma should be advised that the greater risk for their babies lies in poorly controlled asthma and most modern asthma medications are safe.
For this reason, using medications to obtain optimal asthma control is justified.
![Page 213: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/213.jpg)
3- Treatment needed?
Asthma control was already achieved on this treatment: o Inhaled Budesonide/formoterol (160mcg/4.5mcg). o Salbutamol MDI as needed. o Nasal steroid spray. o It may be repeated with reassurance about the safety of the medications and regular follow up to assess asthma control.
![Page 214: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/214.jpg)
![Page 215: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/215.jpg)
![Page 216: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/216.jpg)
![Page 217: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/217.jpg)
![Page 218: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/218.jpg)
o Sandra is 60 years old and has had asthma for 4 years. She
has attended today as she has a cough, She is short of breath
and getting disturbed nights.
o She is currently on regular salbutamol and beclomethasone 200mcg 2
puffs bd.
Discuss your therapeutic options?
Case 8
![Page 219: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/219.jpg)
current medications: (medium dose ICS + rapid acting B₂ agonist as reliever) Therapeutic options: STEP UP the actual treatment: Add long acting B₂ agonist with ICS in a single inhaler. (+/-) sustained release theophylline or leukotriene modifier.
![Page 220: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/220.jpg)
o A 22 years old male patient, non smoker, comes to
primary care clinic complaining of chronic cough for the
last 3 months, mainly at night, together with occasional
exertional dyspnea and chest wheezes.
o 1- How will you approach this case?
o 2- What is the basic functional assessment to be
proposed?
Case 9
![Page 221: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/221.jpg)
1- How will you approach this case?
o A young patient with symptoms suggestive of airway
obstruction.
(bronchial asthma??)
Proper medical history is essential: - Family or past history of allergic diseases. - Risk factors and exposure to exacerbating factors. - detailed history concerning the pattern of symptoms.
Physical examination: (CHEST WHEEZES??)
- Order for functional assessment
![Page 222: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/222.jpg)
2- What is the basic functional assessment to be proposed?
Spirometry before and after B₂ agonist to demostrate airway obstruction and to assess the reversibility.
![Page 223: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/223.jpg)
o A 23 years old female patient with known bronchial asthma
since childhood experiences almost daily symptoms, her
sleep is disturbed because of asthma three times a week,
and she is not able to perform regular exercise. She’s been
prescribed daily ICS for six months and uses Salbutamol for
breakthrough wheezing, chest tightness and breathlessness.
oWhat are the management options?
Case 10
![Page 224: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/224.jpg)
What are the management options?
o The patient is uncontrolled on her current treatment
Daily symptoms
Nocturnal symptoms>3 times/week
Limitations of activities
So……Stepping up…
Add long acting B₂ agonist to ICS.
Add leukotriene modifier.
+/- Sustained release theophylline.
Pattern of
uncontrolled
asthma
![Page 225: Asthma management phenotype based approach](https://reader030.fdocuments.net/reader030/viewer/2022032616/55a516901a28abdc7f8b4688/html5/thumbnails/225.jpg)