This document discusses various asthma phenotypes or endotypes that have been identified based on differences in clinical characteristics, biomarkers and treatment responses. The two main endotypes discussed are TH2-high asthma and non-TH2 asthma. TH2-high asthma includes early-onset allergic asthma, late-onset eosinophilic asthma and exercise-induced asthma. It is characterized by eosinophilia, TH2 biomarkers and good response to corticosteroids and anti-TH2 targeted therapies. Non-TH2 asthma includes obesity-related asthma, neutrophilic asthma and smoking asthma. It has fewer clinical allergies and TH2 biomarkers, and poorer responses to corticosteroids. Distinct clinical features, genetics,

2. Asthma Updates
Gamal Rabie Agmy, MD, FCCP
Professor of chest Diseases, Assiut university

3. Definition of Asthma

A chronic inflammatory disorder of the airways

Many cells and cellular elements play a role

Chronic inflammation is associated with airway
hyperresponsiveness that leads to recurrent
episodes of wheezing, breathlessness, chest
tightness, and coughing

Widespread, variable, and often reversible
airflow limitation

4. Asthma Inflammation: Cells and Mediators
Source: Peter J. Barnes, MD

5. Mechanisms: Asthma Inflammation
Source: Peter J. Barnes, MD

6. Asthma Inflammation: Cells and Mediators
Source: Peter J. Barnes, MD

7. Asthma Pathobiology
Smooth Muscle
Dysfunction
•
•
•
•
Bronchoconstriction
Bronchial Hyperreactivity
Hypertrophy/Hyperplasia
Inflammatory Mediator
Release
Airway
Inflammation
• Inflammatory Cell
Infiltration/Activation
• Mucosal Edema
• Cellular Proliferation
• Epithelial Damage
• Basement Membrane
Thickening
Symptoms/Exacerbations

8. Pathology of Asthma

9. Factors that Exacerbate Asthma






Allergens
Respiratory infections
Exercise and hyperventilation
Weather changes
Sulfur dioxide
Food, additives, drugs

10. Factors that Influence Asthma
Development and Expression
Host Factors
 Genetic
- Atopy
- Airway
hyperresponsiveness
 Gender
 Obesity
Environmental Factors
 Indoor allergens
 Outdoor allergens
 Occupational sensitizers
 Tobacco smoke
 Air Pollution
 Respiratory Infections
 Diet

11. Is it Asthma?

Recurrent episodes of wheezing

Troublesome cough at night

Cough or wheeze after exercise

Cough, wheeze or chest tightness
after exposure to airborne allergens or
pollutants

Colds “go to the chest” or take more
than 10 days to clear

12. 90% of the asthma problem is not seen:
The inflammation!!!
Bronchospasm= 10%

13. Symptoms
When this disappears…
Have we eliminated this?
Underlying
disease

14. Levels of Asthma Control
Characteristic
Controlled
Partly controlled
(All of the following)
(Any present in any week)
Daytime symptoms
None (2 or less /
week)
More than
twice / 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
Uncontrolled
3 or more
features of
partly
controlled
asthma
present in
any week
1 in any week

21. Estimate Comparative Daily Dosages for
Inhaled Glucocorticosteroids by Age
Drug
Low Daily Dose (g)
> 5 y Age < 5 y
Medium Daily Dose (g)
> 5 y Age < 5 y
Beclomethasone
200-500
100-200
>500-1000
>200-400
Budesonide
200-600
100-200
600-1000
>200-400
Budesonide-Neb
Inhalation Suspension
Ciclesonide
250-500
80 – 160
High Daily Dose (g)
> 5 y Age < 5 y
>1000
>1000
>500-1000
80-160
>160-320
>160-320
>400
>400
>1000
>320-1280
>320
Flunisolide
500-1000
500-750
>1000-2000
>750-1250
>2000
>1250
Fluticasone
100-250
100-200
>250-500
>200-500
>500
>500
Mometasone furoate
200-400
100-200
> 400-800
>200-400
400-1000
400-800
>1000-2000
>800-1200
Triamcinolone acetonide
>800-1200
>2000
>400
>1200

23. 
Asthma is a complex disease or a syndrome that includes
several disease variants.

The term asthma, like „arthritis‟, equates to a definition of
grouped clinical and physiological characteristics. These
characteristics could identify syndromes, phenotypes or even
multiple diseases rather than a single disease.

24. 
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.

27. 
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.

28. 
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.

29. 
By The study of wenzel ,et al 2013 Combining clinical, statistical
and molecular approaches two broad emerging “endotypes” have
been defined.

Traditionally asthma has been thought to be a Th2-associated
disease. There is strong evidence supporting a TH2-high phenotype
in up to 50% of people with asthma of any severity, yet 50% show
no evidence for this immune process.

30. These patients are characterized by atopy, eosinophilic
inflammation and favorable response to corticosteroids.

Early-onset allergic asthma

Late-onset persistent eosinophilic asthma

Exercise induced asthma

31. 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 .

32. 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.

33. 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.
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. .

34. 
Inhaled IL-4Rα antagonist . Surrogate marker predicting
better response is IL-4 receptor a polymorphism.

35. 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 earlyonset asthma.

It is often associated with sinus disease.

36. Genetics:


Few patients in this group have a family history of asthma.
little is known regarding the genetics of adult onset persistent
asthma.

37. 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 IL17 .

Elevations in FeNO

38. 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)

L-4 and IL-13 targeted therapy pathway.

39. 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

40. 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.

41. 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

42. 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 .

43. Biomarkers:

Th2 cytokines and cysteinyl leukotriene
Genetics:

No distinct genetic factors .
Treatment responses:

Leukotriene modifiers high LTE4/FENO ratio is Surrogate
marker predicting better response.

IL-9 targeted therapy has been shown effective on patients of
this group, which implies that Th2 immunity is involved in the
pathophysiology of EIA.

44. The lack of efficacy of Th2 targeted therapy suggests that a
subgroup of asthma develops in the absence of Th2 immunity .
Little is understood about the non Th2 asthma and its related
molecular elements.

Obesity-related asthma

Neutrophilic asthma

Smoking asthma

45. 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.

,

..

46. 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.

47. 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.

48. 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.

49. Clinical characteristics and biomarkers:

It remains controversial whether neutrophilia is an independent driving
component, a synergistic factor with eosinophilia or just a consequence of
corticosteroid therapy.

Still unclear whether this represents a unique form of asthma or just a
different stage of severity or persistent bacterial colonization or infection of
the airways on the background of a previously eosinophilic asthma.

Airway pathophysiology in neutrophilic asthma is characterized by (fixed)
airflow limitation
measured by CT) .
more trapping of air, thicker airway walls (as

50. 
Novel mechanisms implicated in the pathogenesis of
noneosinophilic asthma involve the activation of innate immune
responses with a possible role of bacteria, viruses.

Neutrophilia can also co-exist with eosinophilia, and this identifies
the people with the most severe asthma and emphasizes the
complexity of the immunobiology of severe asthma in which
multiple different innate and adaptive immune pathways and cells
may have roles.


Impaired nuclear recruitment of histone deacetylase (HDAC).
The role of TH17 immunity

51. Biomarkers:

IL-8, IL-17A, LTB4, and possibly IL-32.

IL-1 and TNF-α pathways are upregulated and associated with
neutrophilic inflammation in a sputum gene-expression study.

low levels of FeNO.

52. Treatment responses:


Corticosteroids are less effective in patients of this subgroup.
Macrolide antibiotics may have some efficacy on neutrophilic
asthma, By modulating the innate immune response in the
lung, by reducing the expression of neutrophilic markers .

Restoration of HDAC 2 nuclear recruitment with theophylline.

Anti-TNF-α responsive( infliximab )

The efficacy of IL-17 targeted therapy in this subtype of
asthma awaits evidence from ongoing clinical trials.

53. 
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.


54. 
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.

55. The intensity of the colors represents the range of severity; the relative sizes
of the subcircles suggest relative proportions of affected individuals

56. Lötvall et al.2011 proposed endotyping asthma into six classes
depending on several parameters used to define an endotype.

Aspirin sensitive asthma

Allergic asthma (adults)

Severe late-onset hypereosinophilic

ABPM

API-positive preschool wheezer

Asthma in cross country skiers

57. Lotvall J et al JACI 2011

58. Agache,etal 2o12

61. The principle of personalized or individualized medicine is to
'bring the right drug to the right patient at the right dose', such
that therapeutic efficacy is maximized and the side effects are
kept to a minimum.

62. 
The consideration of disease endotypes in treatment design
should be able to bridge the present era of treating asthma
based on family history, patient characteristics and laboratory
test, to the future era of personalized medicine where
treatment scheme will be based on individual biological data
such as genomic, proteomic and metabolic profiles.

63. Asthmatic Granulomatosis
A Novel Disease with Asthmatic and
Granulomatous Features
This study present video-assisted thoracoscopic biopsy
findings from 10 patients, previously diagnosed with severe
asthma and meeting criteria for asthma. Pathobiologically,
these patients have evidence for asthmatic small airway
inflammation and infrequent nonnecrotizing granulomas with
interstitial inflammation. This distinct pathobiology in addition
to their response to cytotoxic agents suggests that these
patients represent a newly described disease, which we term
asthmatic granulomatosis.
Sally E. Wenzel1, Catherine A. Vitari1, Manisha Shende2, Diane C. Strollo3,
Allyson Larkin4, and Samuel A. Yousem5
Am J Respir Crit Care Med Vol 186, Iss. 6, pp 501–507, Sep 15, 2012

64. The Asthma–Chronic Obstructive
Pulmonary Disease Overlap
Syndrome (ACOS)

65. ACOS
The Spanish COPD guidelines propose
four COPD phenotypes that determine
differential treatment: nonexacerbator
with emphysema or chronic bronchitis,
mixed COPD–asthma, exacerbator with
emphysema and exacerbator with
chronic bronchitis

66. ACOS
The mixed COPD–asthma phenotype was
defined as an airflow obstruction that is not
completely reversible accompanied by
symptoms or signs of an increased
reversibility of the obstruction.[7] In other
guidelines, these patients are described as
'patients with COPD and prominent asthmatic
component' or as asthma that complicates
COPD.

67. ACOS
*Two major criteria (FEV1 >15% and >400 ml
after bronchodilator or sputum eosinophils or
history of asthma) and
*Two minor criteria (elevated total IgE or
history of atopy or FEV1 >12% and >200 ml
after bronchodilator) are recommended.

68. ACOS
*Asthma with partially reversible airflow obstruction
– that is, based on change in FEV1 with
bronchodilators – with or without emphysema or
reduced carbon monoxide diffusing capacity (DLco)
to <80% predicted;
*COPD with emphysema accompanied by
reversible or partially reversible airflow obstruction,
with or without environmental allergies or reduced
DLco.

69. ACOS
The following major criteria for ACOS:
a physician diagnosis of asthma and COPD in the
same patient, history or evidence of atopy, for
example, hay fever, elevated total IgE, age 40 years
or
more,
smoking
>10
pack-years,
postbronchodilator FEV1 <80% predicted and
FEV1/FVC <70%.
Minor criteria:
A ≥15% increase in FEV1 or ≥12% and ≥200 ml
increase in FEV1 postbronchodilator treatment with
albuterol .

70. Lessons learnt from
studies of asthma deaths
Many deaths from asthma are preventable – 88-92% of attacks requiring
hospitalisation develop over 6 hours
Factors include:
• inadequate objective monitoring
• failure to refer earlier for specialist advice
• inadequate treatment with steroids
B

Keep patients who have had near fatal asthma or brittle asthma
under specialist supervision indefinitely

71
Health care professionals must be aware that patients with severe
asthma and one or more adverse psychosocial factors are at risk of
death
Respiratory specialist should follow up patients admitted with
severe asthma for at least a year after admission
Management of acute asthma. Thorax 2012

71. Levels of severity of
acute asthma exacerbations
Near fatal asthma
72
Raised PaCO2 and/or requiring mechanical ventilation with raised
inflation pressures
Management of acute asthma. Thorax 2012

72. Levels of severity of
acute asthma exacerbations
Near fatal asthma
Life threatening
asthma
73
Raised PaCO2 and/or requiring mechanical ventilation with
raised inflation pressures
Any one of the following in a patient with severe asthma:
• Altered conscious level
• Exhaustion
• Arrythmias
• Hypotension
• Cyanosis
• Silent chest
• Poor respiratory effort
• PEF <33% best or
predicted
• SpO2 <92%
• PaO2 <8 kPa
• “normal” PaCO2
(4.6–6.0 kPa)
Management of acute asthma. Thorax 2003; 58 (Suppl I): i1-i92

73. Levels of severity of
acute asthma exacerbations
Near fatal asthma
Raised PaCO2 and/or requiring mechanical ventilation with raised
inflation pressures
Life threatening
asthma
Any one of the following in a patient with severe asthma:
PEF <33% best or •
silent chest •
dysrhythmia •
predicted
cyanosis •
hypotension •
SpO2 <92% • feeble respiratory •
exhaustion •
PaO2 <8 kPa •
effort
confusion •
normal PaCO2 (4.6-6.0 kPa) •
bradycardia •
coma •
Acute severe
asthma
74
Any one of:
• PEF 33-50% best or predicted
• respiratory rate 25/min
• heart rate 110/min
• inability to complete sentences
in one breath
Management of acute asthma. Thorax 2003; 58 (Suppl I): i1-i92

74. Levels of severity of
acute asthma exacerbations
Near fatal asthma
Raised PaCO2 and/or requiring mechanical ventilation with raised
inflation pressures
Life threatening
asthma
Any one of the following in a patient with severe asthma:
PEF <33% best or •
silent chest •
dysrhythmia •
predicted
cyanosis •
hypotension •
SpO2 <92% • feeble respiratory •
exhaustion •
PaO2 <8 kPa •
effort
confusion •
normal PaCO2 (4.6-60 kPa) •
bradycardia •
coma •
Acute severe
asthma
Any one of:
inability to complete sentences •
in one breath
Moderate asthma
exacerbation
75
PEF 33-50% best or predicted
respiratory rate 25/min
heart rate 110/min
•
•
•
• Increasing symptoms
• No features of acute severe
• PEF >50-75% best or predicted
asthma
Management of acute asthma. Thorax 2012

75. Levels of severity of
acute asthma exacerbations
Near fatal asthma
Raised PaCO2 and/or requiring mechanical ventilation with raised
inflation pressures
Life threatening
asthma
Any one of the following in a patient with severe asthma:
PEF <33% best or •
silent chest •
dysrhythmia •
predicted
cyanosis •
hypotension •
SpO2 <92% • feeble respiratory •
exhaustion •
PaO2 <8 kPa •
effort
confusion •
normal PaCO2 (4.6-6.0 kPa) •
bradycardia •
coma •
Acute severe
asthma
Any one of:
inability to complete sentences •
in one breath
Moderate asthma
exacerbation
Brittle asthma
PEF 33-50% best or predicted
respiratory rate 25/min
heart rate 110/min
Increasing symptoms
PEF >50-75% best or predicted
No features of acute severe
asthma
•
• Type 1: wide PEF variability (>40% diurnal variation for >50% of
•
76
•
•
•
•
•
the time over a period >150 days) despite intense therapy
Type 2: sudden severe attacks on a background of apparently
well-controlled asthma
Management of acute asthma. Thorax 2012

76. Initial assessment – the role of
symptoms, signs and measurements
Clinical features
77
Clinical features can identify some patients with severe asthma,
eg severe breathlessness (including too breathless to complete
sentences in one breath), tachypnea, tachycardia, silent chest,
cyanosis, accessory muscle use, altered consciousness or
collapse.
None of these singly or together is specific. Their absence does not
exclude a severe attack.
Management of acute asthma. Thorax 2012

77. Initial assessment – the role of
symptoms, signs and measurements
Clinical features
PEF or FEV1
78
Clinical features, symptoms and respiratory and cardiovascular signs
helpful in recognising severe asthma, but none specific, and their absence
does not exclude a severe attack
Measurements of airway caliber improve recognition of the
degree of severity, the appropriateness or intensity of therapy, and
decisions about management in hospital or at home.
PEF or FEV1 are useful and valid measures of airway caliber. PEF is
more convenient in the acute situation.
PEF expressed as a percentage of the patient‟s previous best value
is most useful clinically. PEF as a percentage of predicted gives
a rough guide in the absence of a known previous best value.
Different peak flow meters give different readings. Where possible
the same or similar type of peak flow meter should be used.
Management of acute asthma. Thorax 2003; 58 (Suppl I): i1-i92

78. Initial assessment – the role of
symptoms, signs and measurements
Clinical features
Clinical features, symptoms and respiratory and cardiovascular signs
helpful in recognising severe asthma, but none specific, and their absence
does not exclude a severe attack
PEF or FEV1
Measurements of airway calibre improve recognition of severity and guide
hospital or at home management decisions. PEF is more convenient and
cheaper than FEV1. PEF as % previous best value or % predicted most
useful
Pulse oximetry Measure oxygen saturation (SpO2) with a pulse oximeter to
determine the adequacy of oxygen therapy and the need for arterial
blood gas (ABG) measurement. The aim of oxygen therapy is to
maintain SpO2 94-98%.
79
Management of acute asthma. Thorax 2012

79. Initial assessment – the role of
symptoms, signs and measurements
Clinical features
Clinical features, symptoms and respiratory and cardiovascular signs
helpful in recognising severe asthma, but none specific, and their absence
does not exclude a severe attack
PEF or FEV1
Measurements of airway calibre improve recognition of severity and guide
hospital or at home management decisions. PEF is more convenient and
cheaper than FEV1. PEF as % previous best value or % predicted most
useful
Pulse oximetry
Necessary to determine adequacy of oxygen therapy and need for arterial
blood gas measurement. Aim of oxygen therapy is to maintain SpO 2 92%
Blood gases
(ABG)
80
Measure oxygen saturation (SpO2) with a pulse oximeter to
determine the adequacy of oxygen therapy and the need for arterial
blood gas (ABG) measurement. The aim of oxygen therapy is to
maintain SpO2 94-98%.
Management of acute asthma. Thorax 2003; 58 (Suppl I): i1-i92

80. Initial assessment – the role of
symptoms, signs and measurements
Clinical features
Clinical features, symptoms and respiratory and cardiovascular signs
helpful in recognising severe asthma, but none specific, and their absence
does not exclude a severe attack
PEF or FEV1
Measurements of airway calibre improve recognition of severity and guide
hospital or at home management decisions. PEF is more convenient and
cheaper than FEV1. PEF as % previous best value or % predicted most
useful
Pulse oximetry
Necessary to determine adequacy of oxygen therapy and need for arterial
blood gas measurement. Aim of oxygen therapy is to maintain SpO 2 92%
Blood gases
(ABG)
Necessary for patients with SpO2 <92% or other features of life threatening
asthma
Chest X-ray Not routinely recommended in patients in the absence of:
• suspected pneumomediastinum or • failure to respond to treatment
pneumothorax
satisfactorily
• suspected consolidation
• requirement for ventilation
• life threatening asthma
81
Management of acute asthma. Thorax 2003; 58 (Suppl I): i1-i92

81. Initial assessment – the role of
symptoms, signs and measurements
Clinical features
PEF or FEV1
Measurements of airway calibre improve recognition of severity and guide
hospital or at home management decisions. PEF is more convenient and
cheaper than FEV1. PEF as % previous best value or % predicted most
useful
Pulse oximetry
Necessary to determine adequacy of oxygen therapy and need for arterial
blood gas measurement. Aim of oxygen therapy is to maintain SpO 2 92%
Blood gases
(ABG)
Necessary for patients with SpO2 <92% or other features of life threatening
asthma
Chest X-ray
Not routinely recommended in patients in the absence of:
suspected pneumomediastinum or •
failure to respond to treatment •
pneumothorax
satisfactorily
suspected consolidation •
requirement for ventilation •
life threatening asthma •
Systolic paradox
82
Clinical features, symptoms and respiratory and cardiovascular signs
helpful in recognising severe asthma, but none specific, and their absence
does not exclude a severe attack
Abandoned as an indicator of the severity of an attack
Management of acute asthma. Thorax 2012

82. Radiographic Signs of Pneumomediastinum
Subcutaneous emphysema
Thymic sail sign
Pneumoprecardium
Ring around the artery sign
Tubular artery sign
Double bronchial wall sign
Continuous diaphragm sign
Extrapleural sign
Air in the pulmonary ligament

87. Not all wheezing is asthma
Wheezing occurrences in children:
- single episode in 30% to 50% of children before 5 yr of age
- 40% who wheeze before 3 yr of age continue at 6 yr (“persistent
wheezers”)
- 50% of infants who wheeze once will wheeze again within
several months

88. Childhood asthma phenotypes:
- transient early wheezers - wheeze sometime during first year of
life; risk factors include prematurity, history of parental smoking
during pregnancy, and passive exposure to tobacco smoke; such
patients do not respond to inhaled bronchodilators or inhaled
corticosteroids (ICS); wheezing tends to remit as child’s airway
gets larger (between ages 2-3 yr)
- nonatopic wheezers - 0 to 6 yr of age; wheeze associated
exclusively with viral infection; usually no eczema or family
history; wheezing tends to remit by 6 yr of age
- atopic wheezers - past 5 yr of age, allergic - have positive blood
and skin testing to inhalant allergens; tend to present within 2 to
3 yr of age, and continue to wheeze; wheezing not related to URTI

90. A 2012 study described 2 "new" phenotypes
for young children with wheezing:
1-"boys atopic multiple-trigger" and
2-"girls
nonatopic
uncontrolled
wheeze". JACI, 2012.

91. Diagnosing Asthma in Young
Children – Asthma Predictive
Index
• Major criteria
– Parent with asthma
• > 4 episodes/yr of
– Physician diagnosed
wheezing lasting
atopic dermatitis
more than 1 day
affecting sleep in a
• Minor criteria
child with one MAJOR
– Physician diagnosed
or two MINOR criteria
allergic rhinitis
– Eosinophilia (>4%)
– Wheezing apart from
colds
1Adapted
from Castro-Rodriquez JA, et al. AJRCCM 2000; 162: 1403

93. Cough-variant asthma
Chronic, persistent cough - without wheezing - may be the only
manifestation of asthma. More than 60% bronchial obstruction is
needed to produce wheezing - asthma can occur without wheezing spirometry is required for diagnosis.
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.

94. 95