Medicine,

1. ASTHMA
dr. nderitu
1

2. Outline of presentation
• Definition of Asthma
• Epidemiology
• Pathophysiology
• Clinical manifestations
• complications
• investigations
• Management
2

3. Asthma
• a chronic inflammatory disorder of the airways in
which many cells & cellular elements play a role
– mast cells
–Eosinophils
– T-lymphocytes
–Macrophages
– neutrophils & epithelial cells
3

4. Asthma
• The key components of definition include:
–presence of airway inflammation
–Airway hyper-responsiveness
–Recurrent episodes of symptoms of wheezing,
breathlessness, chest tightness & coughing
– Reversible airways obstruction
4

5. Classification of asthma
• Asthma can be classified according to the
underlying pattern of airway inflammation with
the presence or absence of eosinophils in the
airways
• Extrinsic asthma
– when an allergen is thought to be the cause of
their asthma
– This is more common in children with a history
of atopy, where triggers, such as dust mite,
cause IgE production
5

6. Classification of asthma
• Intrinsic asthma
–develops in adulthood, with symptoms
triggered by non-allergenic factors such as a
viral infection, irritants which cause epithelial
damage and mucosal inflammation, emotional
upset
6

7. Classification of asthma
• The National Asthma Education & Prevention
Program has classified chronic asthma as:
–Intermittent
–Mild persistent
–Moderate persistent
–Severe persistent
• classification is based on severity, which is
determined by symptoms & lung function tests
7

8. Intermittent asthma
• considered intermittent if without treatment any of
the following are true
–Symptoms (difficulty breathing, wheezing, chest
tightness & coughing)
• Occur <2 days a week
• Do not interfere with normal activities
–Night-time symptoms occur on <2 days a month
– Lung function: Normal FEV1 (FEV1>80)
8

9. Mild persistent asthma
• considered mild persistent if without treatment
any of the following are true:
–Symptoms occur on >2 days a week
–Attacks interfere with daily activities (minor
limitation)
–Night time symptoms occur 3-4x a month
– Lung function test: FEV1 ≥ 80
9

10. Moderate persistent asthma
• considered moderate persistent if without
treatment any of the following are true:
–Symptoms occur daily
–Symptoms interfere with daily activities
(Some limitation)
–Night time symptoms occur >1 time a week
–Lung function tests : abnormal (FEV1 60-
80%)
10

11. Severe persistent asthma
• Asthma is considered severe persistent if without
treatment any of the following are true:
–Symptoms occur throughout each day
–Severely limit daily physical activities
–Night-time symptoms occur often, sometimes
every night
–Lung function : abnormal (FEV1 < 60)
11

12. Forms of Asthma
• Exercise-Induced Asthma
–a type of asthma triggered by exercise or
physical exertion
–Shortness of breath, wheezing, or chest
tightness usually occur during or shortly after
vigorous exercise & resolve within 30-60
minutes
• Occupational Asthma
–results from workplace triggers
12

13. Forms of Asthma
• Nocturnal Asthma
– Worsening of asthma during sleep
– occurs between midnight and 8 AM.
– decrease in epinephrine & increase histamine levels during
night time may predispose nocturnal asthma during sleep
• Allergic asthma
– It’s associated with allergic encounter and usually higher
in childhood asthma.
– The allergens are air borne and evoke the asthmatic
response through the classic allergic pathway.
13

14. Forms of Asthma
• acute severe asthma (Status asthmaticus)
–an acute exacerbation of asthma that remains
unresponsive to initial treatment with
bronchodilators
–can vary from a mild form to a severe form with
bronchospasm, airway inflammation, and mucus
plugging that can cause difficulty breathing,
carbon dioxide retention, hypoxemia, and
respiratory failure
14

15. Epidemiology
• the 14th most important disorder in the world in
terms of the extent & duration of disability
• global disease that affects persons of all ages and
either sex
• 14% of the world’s children experience asthma
symptoms.
• 8.6% of young adults (aged 18-45) experience
asthma symptoms
(Global asthma
report, 2014) 15

16. Epidemiology
• affects ~ 334 million people worldwide
• the most common chronic disease of childhood
• The burden of asthma is greatest for children
aged 10-14 and the elderly aged 75-79
(Global asthma report, 2014)
16

17. Epidemiology– kenya
• about 10% of the Kenyan population have
asthma
• more prevalent in urban as opposed to rural
areas
17

18. Triggering agents & risk factors for Asthma
• Genetic Predisposition
• Epidemiologic studies strongly support the concept of
a genetic predisposition plus environmental interaction
to the development of asthma
• Genetic factors account for 60% -80% of the
susceptibility
– However, asthma is not a simple single gene
inherited disease.
– It is likely that multiple genes interact in complex
ways to influence the expression of asthma
18

19. Triggering agents & risk factors for Asthma
• Genetic Predisposition
• presence of asthma in a parent is a strong risk
factor for the development of asthma in a child.
–This risk increases when a family history of
atopy is also present.
• 50% of asthma can be attributed to atopy &
atopic asthma is more common in children than
adults
19

20. Triggering agents & risk factors for Asthma
• Respiratory infection
– Respiratory syncytial virus (RSV), rhinovirus, influenza,
parainfluenza, Mycoplasma pneumonia, Chlamydia
• Allergens
– Airborne pollens (grass, trees, weeds), house dust mites,
animal dander, cockroaches, fungal spores
• Environment
– Cold air, fog, ozone, sulfur dioxide, nitrogen dioxide,
tobacco smoke, wood smoke
• Emotion
– Anxiety, stress
20

21. Triggering agents & risk factors for Asthma
• Exercise particularly in cold, dry climate
– causes water & heat loss from the airways, triggering mediator
release from mast cells
• Drugs & preservatives
– Aspirin, NSAIDs, sulfites, benzalkonium chloride,
nonselective β-blockers
• Occupational stimuli
– Bakers (flour dust)
– farmers (hay mold)
– printers (arabic gum)
– chemical workers (azo dyes, anthraquinone, ethylenediamine,
toluene diisocyanates, polyvinyl chloride)
– plastics, rubber & wood workers
21

22. Triggering agents for Asthma
• Diet
• The role of dietary factors is controversial.
– Observational studies have shown that diets low in
antioxidants such as vitamin C and vitamin A,
magnesium , omega-3 polyunsaturated fats (fish oil)
are associated with an increased risk of asthma
– however, interventional studies with supplementary
diets have not supported an important role for these
dietary factors.
22

23. Triggering agents & risk factors for Asthma
• Obesity
• Asthma occurs more frequently in obese people
(body mass index >30 kg/m2)
• Although mechanical factors may contribute, it
may also be linked to the proinflammatory
adipokines & reduced anti-inflammatory
adipokines that are released from fat stores
23

24. Pathophysiology
• Asthma is characterized by
 inflammation
 airway hyper-responsiveness
airway obstruction
24

25. Pathophysiology
• inhaled antigen induce a type 2 T-helper CD4+
(TH2) response
• presentation of antigens to T lymphocytes causes
activation of the TH2 type response
• production of antigen-specific IgE & pro-
inflammatory cytokines and chemokines that recruit
and activate eosinophils, neutrophils, and alveolar
macrophages
25

26. Pathophysiology
• Further exposure to the antigen results in cross-
linking of cell-bound IgE in mast cells and
basophils
• causing the release or generation of inflammatory
mediators such as histamine, leukotrienes
26

27. Pathophysiology
• Activation & degranulation of mast cells
results in an early phase response that involves
an acute bronchoconstriction that usually lasts
~1h after allergen exposure
• In the late phase response, activated airway
cells release inflammatory cytokines &
chemokines, recruiting inflammatory cells into
the lungs
27

28. Pathophysiology
• late phase response occurs 4-6 hours after the
initial allergen challenge & results in a less
intense bronchoconstriction as well as increased
airway hyper-responsiveness & airway
inflammation
28

29. Pathophysiology
• Airway Inflammation &Hyper-responsiveness
– inflammatory mediators such as histamine,
leukotrienes, and bradykinin , generated during mast
cell degranulation can increase vascular permeability,
leading to airway edema & increased mucus
production
– Eosinophilic infiltration of the airways is a hallmark
of asthma, and activated eosinophils can cause
bronchoconstriction & AHR
29

30. Pathophysiology
• Airway Obstruction
–manifests itself as symptoms such as chest
tightness, cough, and wheezing
–caused by multiple factors including airway
smooth muscle constriction, airway edema,
mucus hypersecretion & airway remodeling
–airway obstruction in asthma has generally been
considered reversible
30

31. Pathophysiology
• Although airway obstruction in asthma has generally
been considered reversible, some asthmatics have an
irreversible or fixed obstruction
• Airway remodeling
– The process that produces the structural airway
changes leading to this fixed obstruction
– characterized by airway epithelial damage,
subepithelial fibrosis, airway smooth muscle
hypertrophy & hyperplasia, increased mucus
production
31

32. Pathophysiology
• Airway remodeling may be caused by:
–repetitive injury to the airways
–an abnormal injury-repair cycle of dysfunctional
epithelial cells
–in response to the chronic inflammatory process
32

33. 33

34. Clinical Presentation of Chronic
Asthma
• General
– Asthma severity ranges from normal pulmonary
function & symptoms only with acute exacerbations
to significantly decreased pulmonary function with
continuous symptoms
• Symptoms
– dyspnea, cough, wheezing & chest tightness
– symptoms may be continual, episodic, seasonal, or
occur in association with known triggers
– Symptoms may occur more often at night, early in
the morning, or with exercise
34

35. Clinical Presentation of Acute Asthma
• General
–Acute asthma can present rapidly (within 3-
6hr) but more commonly, deterioration occurs
over several hours, days, or even weeks
–gradual deterioration over several days
followed by a more rapid deterioration over
2-3 days
35

36. Clinical Presentation of Acute Asthma
• Symptoms
• The patient usually presents with complaints of
dyspnea, cough, shortness of breath, and chest
tightness.
• Because of their inability to breathe, patients are
generally anxious and may be agitated
• In severe acute asthma, patients may be unable to
communicate in complete sentences.
• Mental status changes may indicate impending
respiratory failure
36

37. Clinical Presentation of Acute Asthma
• Signs
–Tachypnea
–Tachycardia
–Cyansosis
–Bradycardia & absence of wheezing may
indicate impending respiratory failure
37

38. Possible Complications
• Decreased ability to exercise and take part in other
activities
• Lack of sleep due to nighttime symptoms
• Permanent changes in the function of the lungs
• Persistent cough
• Trouble breathing that requires breathing assistance
(ventilator)
• Death
38

39. Investigations
• Take a detailed medical history
– the clinical history is the most important element in
the diagnosis of asthma.
– Is there recurrent or episodic wheeze, cough, chest
tightness or shortness of breath?
– Are the symptoms particularly troublesome at
night or early morning?
– Are the symptoms triggered by factors such as dust,
cold exposure, strong smells or exercise?
– Is there a consistent response to asthma specific
treatment?
39

40. Investigations
• Lung Function Tests (Spirometry)
FEV1 <80%
FEV1/FVC <70%
≥12% (at least 200 mL) improvement in FEV1 15
min after an inhaled bronchodilator (short-acting
β2-agonist) demonstrates a reversible obstruction
in some patients 2- 3-weeks course of oral
corticosteroids may be necessary to demonstrate
reversibility in airway obstruction (prednisone or
prednisolone 30–40 mg daily)
40

41. Investigations
• ≥ 15% reduction in FEV1 after an exercise test is
diagnostic for exercise-induced asthma
• When spirometry is equivocal, ≥ 20% decrease in
FEV1 after the administration of methacholine is
diagnostic for asthma
• Total serum IgE & specific IgE to inhaled allergens
may be measured in some patients
41

42. Investigations: Pulmonary function Test
• bronchodilators should be stopped before the test
– 6 h for short-acting β2-agonists, such as albuterol
–8 h for ipratropium
–12-36 h for theophylline
– 24 h for long-acting β2-agonists, such as
salmeterol & formoterol
42

43. Management of chronic asthma
• Therapy for chronic asthma is directed at:
–suppressing the underlying inflammatory
response
–normalizing pulmonary function
43

44. Management of chronic asthma
• Goal of therapy
– Achieve & maintain control of symptoms
– Prevent asthma exacerbations
– Maintain lung function as close to normal as
possible
– Maintain normal level of activity including exercise
– provide optimal pharmacotherapy with minimal or
no adverse effects
– Prevent development of irreversible airflow
limitation
– meet patients’ and families’ expectations of &
satisfaction with asthma care
44

45. Management of chronic asthma
• Nonpharmacologic Therapy
• Pharmacological therapy
45

46. Nonpharmacologic Therapy
• Risk factor avoidance
–Patients who smoke should be strongly
encouraged to quit cigarette smoking
–Patients sensitive to specific allergens should be
educated on ways to avoid them
–Control of outdoor trigger factors
–Control of Indoor triggers factors
46

47. Pharmacologic Therapy
• β2-Adrenergic Agonists
• Corticosteroids
• Anticholinergics
• Leukotriene Modifiers
• Mast cell stabilizers
• Methylxanthines
• monoclonal anti-IgE antibody
47

48. β2-Agonists Adrenergic Agonists
• Mechanism of action
– relax airway smooth muscle by directly
stimulating β2-adrenergic receptors
– decrease mast cell degranulation & histamine
release
– increase mucociliary clearance
• Inhalation, oral, and injectable dosage forms are
available
• the inhalation dosage forms are most commonly
used.
48

49. β2-Agonists Adrenergic Agonists
• significantly better Bronchodilating activity in
acute asthma than theophylline or anticholinergic
agents
• Oral β2-agonists
– should not be used in acute asthma b/c of a
delayed onset of action compared to the inhaled
route
–have more systemic effects & generally should
be avoided
49

50. Inhaled short-acting β2-agonists
• Albuterol (salbutamol)
–most commonly used
• pirbuterol and terbutaline
• Non-selective β2-agonists
–Metaproterenol
• equally potent when given in equivalent doses
50

51. Inhaled short-acting β2-agonists
• the most effective agents for reversing acute
airway obstruction caused by bronchoconstriction
• the drugs of choice for treating acute severe asthma
and symptoms of chronic asthma
• have an onset of action of 5 minutes and a duration
of action of 4-6 hours
• Adverse effects
–tachycardia, tremor, hypokalemia
51

52. 52

53. 53

54. Long-Acting Inhaled β2-agonists
• Salmeterol & formoterol
– long-acting inhaled β2-agonists
– provide up to 12 hours of bronchodilation after a
single dose
– approved for the chronic prevention of asthma
symptoms.
• Salmeterolis a partial agonist with an onset of action
of ~ 30 minutes. Because of this delayed onset of
action, patients should be cautioned not to use
salmeterol as a quick relief medication
• Formoterol is a full agonist that has an onset of action
similar to that of albuterol
54

55. Long-Acting Inhaled β2-agonists
• indicated for add on therapy for asthma not
controlled on low to medium doses of inhaled
corticosteroids
• Addition of a long-acting inhaled β2-agonist to
inhaled corticosteroid therapy also reduces the
amount of inhaled corticosteroids necessary
for asthma control
55

56. Long-Acting Inhaled β2-agonists
• Combined therapy with a long-acting inhaled β2-agonist
and an inhaled corticosteroid is also superior to the
combination of a leukotriene modifier or theophylline
with an inhaled corticosteroid
• Although both formoterol & salmeterol are effective as
add-on therapy for moderate persistent asthma, neither
agent should be used as monotherapy for chronic asthma.
56

57. Long-Acting Inhaled β2-agonists
• Patients treated with salmeterol alone are at
greater risk of worsening asthma than those treated
with inhaled corticosteroids
• Salmeterol is also available in a fixed ratio
combination product containing fluticasone
–increasing patient adherence due to the
decreased number of inhalations
57

58. Corticosteroids
• the most potent anti-inflammatory agents
available for the treatment of asthma
• Pharmacological effects
– decrease airway inflammation
– decrease AHR
– decrease mucus production
– upregulation of β2-adrenergic receptors
• are available in inhaled, oral & injectable dosage
forms
58

59. Inhaled Corticosteroids
• the most comprehensive control of the inflammatory
process and are the cornerstone of therapy in persistent
asthma
• more effective than cromolyn, leukotriene modifiers,
nedocromil, and theophylline in reducing markers of
inflammation and AHR, improving lung function
• Advantage: the targeted delivery of drug to the lungs,
which decreases the risk of systemic adverse effects
59

60. Inhaled Corticosteroids
• effective when given twice daily
• May also be effective when given once daily
for mild asthma
60

61. 61

62. Systemic Corticosteroids
• are effective as both long-term control & rescue
medications
• due to the potential for serious adverse effects, it
should only be used for long-term control of
asthma in patients who have failed other
therapies
• attenuate the inflammatory response & increase
the response to β2-agonists
62

63. Systemic Corticosteroids
• onset of effects is delayed & a clinical response may
not be seen for 4-12 hours
– hence, should be started early in the course of acute
exacerbations or worsening asthma
• In general, the duration of therapy ranges from 3 days
for mild exacerbations to 14 days for severe
exacerbations
• not necessary to taper the systemic steroid dose in
patients receiving short bursts of systemic
corticosteroid therapy, as the adrenal suppression that
occurs is transient and rapidly reversible
63

64. 64

65. 65

66. Anticholinergics
• Ipratropium bromide
– act by inhibiting the effects of Ach on M3
receptors in the airways
– only protect against cholinergic-mediated
bronchoconstriction
– not as effective as β2-agonists in asthma
– is the most commonly used anticholinergic for
treating bronchoconstriction
– available as an MDI and solution for nebulization
66

67. Anticholinergics
• Ipratropium bromide
–has an onset of action of ~30 minutes
–duration of action of 4-8 hours
–The addition of ipratropium bromide to inhaled
β2-agonist therapy in acute severe asthma
improves pulmonary function & decreases
hospitalization
• combination should be considered first-line
therapy in severe exacerbations
67

68. Leukotriene Modifiers
• inhibit 5-lipoxygenase (zileuton)
• competitively antagonize the effects of leukotriene
D4 (montelukast and zafirlukast)
• improve FEV1 & decrease asthma symptomss &
exacerbations
• Less effective than low doses of inhaled
corticosteroids
68

69. Leukotriene Modifiers
• Zileuton
• use is uncommon due to:
– the need for dosing four times a day
– potential drug interactions(inhibits the CYP-450 &
has been shown to decrease the clearance of
theophylline, R-warfarin & propranolol)
– the potential for hepatotoxicity (need for frequent
monitoring of liver enzymes)
69

70. Leukotriene Modifiers
• zafirlukast & montelukast
– well tolerated and dosed twice and once a day,
respectively
– Significant increases in hepatic enzymes have been
reported in postmarketing studies for zafirlukast
but not montelukast
– Zafirlukast also inhibits the CYP2C9 & CYP3A4
isoenzymes and may increase prothrombin times
in patients receiving warfarin
70

71. Mast cell stabilizers: Cromolyn & Nedocromil
• inhaled anti-inflammatory agents that block both
the early- and late-phase response
• alternative therapies to inhaled corticosteroids for
the treatment of mild persistent asthma
• less effective than low doses of inhaled
corticosteroids
• not as effective as albuterol for prophylaxis of
exercise-induced asthma
• given by inhalation prophylactically to patients
with exercise-induced or allergen-induced asthma
71

72. Mast cell stabilizers: Cromolyn & Nedocromil
• MOA: inhibit histamine release from mast cells,
reduce airway hyper-responsiveness, and block
the early and late responses to allergens
• ineffective once symptoms have occurred.
• the safest of all anti-asthmatic drugs but the least
effective
72

73. Methylxanthines
• Theophylline
–an alternative to inhaled corticosteroids for the
treatment of mild persistent asthma
–limited efficacy compared to inhaled
corticosteroids
– a narrow therapeutic index with life-threatening
toxicity
73

74. Theophylline : MOA
• causes bronchodilation through inhibition of
phosphodiesterase III
• have anti-inflammatory due to activation of histone
deacetylases 2 which are reduced in severe asthma
& COPD
–Activation of histone deacetylase-2 leads to
switching off of activated inflammatory genes,
which in turn may contribute to reversal of
glucocorticoid resistance by theophylline
74

75. Methylxanthines
• Theophylline
– Target serum conc. 5-15 mg/L
– not problematic at serum conc <15 mg/L
– increased risk of adverse effects outweighs the increase in
bronchodilation in most patients >15 mg/L
• Adverse effects: at higher concentrations
– cardiac arrhythmias (due to adenosine antagonist effect)
– Seizures
– toxic encephalopathy
– death
75

76. Methylxanthines
• Aminophylline
–a compound of the bronchodilator theophylline
with ethylenediamine
–The ethylenediamine improves solubility
–less potent & shorter-acting than Theophylline
–Mechanism of action: similar to Theophylline
–Dose: 6-7 mg/kg IV infused over 20 minutes
76

77. monoclonal anti-IgE antibody
• Omalizumab
– a recombinant humanized monoclonal anti-IgE
antibody that inhibits binding of IgE to receptors on
mast cells & basophils
– resulting in the inhibition of mediator release &
attenuation of the early & late-phase allergic
response
77

78. Omalizumab
• may be a treatment option for moderate to severe
persistent asthmatics
– 12 years of age or older whose asthma is not
controlled by inhaled corticosteroids
– who have a positive skin test to perennial allergens
• dose: 150-375mg SC every 2-4weeks
• Adverse effects:
– bruising, redness, pain, stinging, itching & burning
78

79. 79
Figure: Stepwise approach to asthma therapy according to the severity of asthma
ICS-- inhaled corticosteroids
LABA---long-acting β2-agonist
OCS---oral corticosteroid
Long-term control
For quick relief of
symptoms

80. 80

81. 81

82. 82

83. management of severe acute asthma
• Status asthmaticus is an acute severe asthma
attack that does not improve with usual doses of
inhaled bronchodilators and steroids.
• Patients have severe dyspnea that has developed
over hours to days
• Frequently, these individuals have a previous
history of endotracheal intubation & mechanical
ventilation, frequent emergency department visits
& previous use of systemic corticosteroids
83

84. Signs & symptoms of Status asthmaticus
• Hypoxemia
• tachypnea
• tachycardia
• often tachypneic and may have trouble speaking
• wheezing
– may be absent when airflow is severely reduced
• Agitation, drowsiness, and confusion
• Rapid treatment is the key to preventing
cardiopulmonary arrest
84

85. management of severe acute asthma
• Goal of therapy
• correct significant hypoxemia
• Rapidly reverse airflow obstruction
• reduce the likelihood of recurrent severe airflow
obstruction
85

86. management of severe acute asthma
• Treatment approach
–use of oxygen for the rapid reversal of
hypoxemia
– a short-acting β2-agonist to reverse airway
constriction
–a systemic corticosteroid to attenuate the
inflammatory response
86

87. management of severe acute asthma
• Immedate oxygen administration to maintain
saturations >90%
• The repetitive or continuous administration of a
selective short-acting β2-agonist is the most
effective means of rapidly reversing airflow
obstruction
• Nebulized albuterol may be given:
– intermittently at a dose of 0.1 mg/kg per
nebulization up to 5.0 mg every 10–15 minutes,
or
– it can be administered continuously at a dose of
0.5 mg/kg/h to a maximum of 20–30 mg/h
87

88. management of severe acute asthma
• IV β-agonists should be considered in patients with
severe bronchospasm unresponsive to inhaled
bronchodilators
– Terbutaline is given as a bolus or loading dose of
10 mcg/kg followed by a continuous infusion of
0.5–5 mcg/kg/min
– The HR & BP should be monitored closely,
because excessive tachycardia may occur in
patients receiving either inhaled or IV β2-agonist
therapy
88

89. management of severe acute asthma
• Epinephrine
– can be given SC or IM, 0.5mg in adults in
refractory situations
• E.g bronchoconstriction resistant to
selective β 2-agonists
89

90. management of severe acute asthma
• Immediate administration of systemic corticosteroids
is critical to the early management of life-threatening
status asthmaticus
• Although oral systemic corticosteroids are generally
recommended, consideration should be given to IV
steroid administration in critically ill patients
secondary to frequent intolerance of enterally
administered medications
• A dose of 2 mg/kg/d of methylprednisolone is
generally prescribed for the critical care setting.
90

91. management of severe acute asthma
• Fluid replacement
– patients may become dehydrated as a result
of increased RR & decreased oral intake
–assess fluid status & provide appropriate
corrections with IV normal saline
91

92. Management of Exercise-induced asthma
• EIA typically begins after exercise has ended
& resolves spontaneously within 30 min
• can generally be prevented by inhalation of a
short-acting β2-agonist or mast cell stabilizer
before starting the exercise
• If β2-agonists are not effective or if exercise-
induced asthma is associated with severe
symptoms, the patient has more severe asthma
than is recognized and requires controller
therapy 92

93. Management of Exercise-induced asthma
• short-acting β-2 agonists (e.g. albuterol)
–are the preferred agents
– Taken 10 minutes before exercise
–can prevent the airways from contracting & help
control exercise-induced asthma.
• cromolyn sodium
–may be useful when taken 15-20 minutes before
exercise
93

94. Management of Refractory Asthma
• most patients with asthma are easily controlled
with appropriate medication
• a small proportion of patients (approximately 5–
10% of asthmatics) are difficult to control despite
maximal inhaled therapy
• The most common reason for poor control of
asthma is noncompliance with medication,
particularly ICS
94

95. Management of Refractory Asthma
• check compliance & the correct use of inhalers to
identify and eliminate any underlying triggers
• Low doses of Theophylline may be helpful in some
patients
• Most of these patients will require maintenance
treatment with oral corticosteroids
• In some patients with allergic asthma,
omalizumab is effective, particularly when there
are frequent exacerbations
95

96. Special considerations of asthma
management
• Aspirin-Sensitive Asthma
–Aspirin inhibits the enzyme COX, which
normally converts arachidonic acid to
bronchodilatory prostaglandins
–When this pathway is blocked, an alternative
reaction predominates, leading to an increase in
production of bronchoconstrictor leukotrienes
96

97. Special considerations of asthma management
• Aspirin-Sensitive Asthma
–The primary treatment is avoidance of NSAIDs
–All nonselective COX inhibitors should be
avoided
–selective COX2 inhibitors are safe to use when
an anti-inflammatory analgesic is needed
–responds to usual therapy with ICS
–Leukotriene modifiers can blunt the response to
NSAIDs
97

98. Special considerations of asthma management
• Asthma in the Elderly
• principles of management are the same as in
other asthmatics
• but side effects of therapy may be a problem,
including muscle tremor with β2-agonists &
more systemic side effects with ICS.
98

99. Special considerations of asthma management
• Pregnancy
–poor control may have adverse effects on
fetal development
–SABA, ICS, and theophylline are safe
–less safety information about LABA,
antileukotrienes, and anti-IgE.
– If an OCS is needed, it is better to use
prednisone rather than prednisolone
99

100. Special considerations of asthma management:
Cigarette Smoking
• Smoking asthmatics
– have more severe disease
– more frequent hospital admissions
– a faster decline in lung function
– a higher risk of death from asthma than nonsmoking
asthmatics
• smoking interferes with the anti-inflammatory actions
of corticosteroids by reducing HDAC2, necessitating
higher doses for asthma control
• Smoking cessation improves lung function & reduces
the steroid resistance
100

101. Special considerations of asthma management
• Surgery
–If asthma is well controlled, there is no
contraindication to general anesthesia &
intubation
–Patients with FEV1 <80% should also be given a
boost of OCS prior to surgery
–High-maintenance doses of corticosteroids may
be a contraindication to surgery b/c of increased
risks of infection & delayed wound healing.
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