1.
Asthma &Allergic Rhinitis=
Allergic rhinobronchitis =
United Airway Disease =
One Airway Disease =
Linked Airway Disease
Gamal Rabie Agmy, MD, FCCP
Professor of chest Diseases, Assiut university

2.
Definition of allergic rhinitis
“Rhinitis is defined as an inflammation of the lining of the nose and
is characterised by nasal symptoms including anterior or posterior
rhinorrhoea, sneezing, nasal blockage and/or itching of the
nose…It is often associated with ocular symptoms.”
Definition of asthma
“Asthma is a common and chronic inflammatory condition of the
airways that is complex and characterized by variable and
recurring symptoms, airflow obstruction, bronchial
hyperresponsiveness, and an underlying inflammation” 2
1 Guidelines for the Diagnosis and Management of Asthma Expert Panel Report 3 . 2007
2. National Asthma Education and Prevention Program Expert Panel Report 3:Guidelines for the Diagnosis and Management of Asthma. 2007
SAR, seasonalallergic rhinitis
PAR,perennialallergic rhinitis

3.
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

4.
Link between Asthma and
Rhinitis
 Allergic rhinitis (AR) and asthma affect
the upper and lower respiratory tracts,
respectively.
 Both are characterized by inflammation
of the respiratory mucosa and involve
similar inflammatory cells and
mediators.

5.
Link between Asthma and
Rhinitis
 Upper and lower airways form a continuous
respiratory tract
 Many inflammatory changes of allergic
rhinitis are similar to those of allergic
asthma
 The anatomical and immunological link
between the lung and nose means that
inflammation in one organ influences
symptoms in the other

6.
Epidemiologic Links between Allergic Rhinitis and Asthma
Many Patients with Asthma Have
Allergic Rhinitis
Up to 88%
of all asthmatic patients have allergic rhinitis
BMJ 2002; 324 doi: http://dx.doi.org/10.1136/bmj.324.7334.403 (Published 16 February 2002) Cite this as: BMJ 2002;324:403

7.
8
Epidemiologic Links between Allergic Rhinitis and Asthma
Many Patients with Asthma Have
Allergic Rhinitis
Adapted from 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

8.
Coexistence of Asthma and
Rhinitis
88%
50%
Percentage of Patients with Co-existing Conditions
0%
20%
40%
60%
80%
100%
Asthma patients Rhinitis patients
%patients
88% 50%
BMJ 2002; 324 doi: http://dx.doi.org/10.1136/bmj.324.7334.403 (Published 16 February 2002) Cite this as: BMJ 2002;324:403

9.
Allergic Rhinitis
Epidemiologic Links betweenAllergic Rhinitis and Asthma
Allergic Rhinitis and Asthma Have Similar
Prevalence Patterns
Study of worldwide prevalence of atopic diseases in 463,801 children 13–14 years of
age. Children self-reported symptoms over 12 months using questionnaires.
UK
Australia
Canada
Brazil
USA
South Africa
Germany
France
Argentina
Algeria
China
Russia
0 5 10 15 20 25 30 35 40
% prevalence
UK
Australia
Canada
Brazil
USA
South Africa
Germany
France
Argentina
Algeria
China
Russia
0 5 10 15 20 25 30 35 40
% prevalence
Asthma
Adapted from the International Study of Asthma and Allergies in Childhood (ISAAC) Steering CommitteeLancet 1998;351:1225–1232.

10.
Adapted from National Institutes of Health Global Initiative for Asthma:Global Strategy for Asthma Managementand Prevention:A Pocket Guide for Physicians
and Nurses. Publication No.95-3659B.Bethesda,MD: National Institutes of Health,1998;BousquetJ et al J AllergyClin Immunol 2001;108(suppl 5):S148–S149.
One Airway, One Disease
BothAsthma and Allergic Rhinitis Are InflammatoryConditions
 Asthma is fundamentally a disease of inflammation
 Inflammation of the lower airways causes
bronchoconstriction and airway hyperresponsiveness,
resulting in asthma symptoms
 Allergic rhinitis is an IgE-mediated inflammatory disorder
 Inflammation of the nasal membranes in response to
allergen exposure results in nasal symptoms
IgE=immunoglobulin E

11.
One Airway, One Disease
BothAsthma and Allergic Rhinitis Are Inflammatory
Conditions
 In AR, one distinction is heavy
vascularization of the nasal passages,
which may lead to severe nasal
obstruction.
 In asthma, the presence of smooth
muscle from the trachea to the
bronchioles can result in characteristic
bronchoconstriction
Robert A. Nathan, MD. Management of Patients with Allergic Rhinitis and Asthma: Literature Review.2009

12.
14
One Airway, One Disease
Allergic Rhinitis and Asthma Share Common
Inflammatory Cells and Mediators
Adapted from 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

13.
Promotes
eosinophil and
other cell migration
and infiltration
Nasal
mucosa
Allergic
inflammatory
response
• Nasalinflammation
• Nasalobstruction
• Difficulty breathing
• Tinnitus
Late-Phase InflammatoryResponse
(4–24 hours)
Histaminic
response
• Sneezing
• Itchy, watery eyes
• Rhinorrhoea
• Nasal congestion
Histamine binds to
H1 receptors
Early-Phase InflammatoryResponse
(minutes-1 hour)
Allergic Rhinitis
Leukotriene C4
Prostaglandin D2
Tryptase
HISTAMINE
CYTOKINES
IL-1
IL-3
IL-4
IL-5
IL-6
IL-13
TNF-
CHEMOKINES
IL-8
Eotaxin
RANTES
ADHESION MOLECULES
P-selectin
ICAM
Allergen

14.
Allergic Rhinitis and Asthma Share a Similar Inflammatory
Process and Occur in the Mucosa
Eos=eosinophils;neut=neutrophils;MC=mastcells;Ly=lymphocytes;MP=macrophages
Adapted from Bousquet J et al J Allergy Clin Immunol 2001;108(suppl 5):S148–S149.
Eosinophil infiltration
Allergic rhinitis Asthma
Nasal mucosa Bronchial mucosa

15.
Asthma Inflammation

16.
The underline cause of Asthma is the
inflammation…
Does the ICS based therapy is enough?

17.
Clinical Links betweenAllergic Rhinitis and Asthma
Many Patients withAsthma Have NasalInflammation
Eosinophil counts in the nasal mucosa
Study of whether nasal mucosal inflammation exists in asthma regardless of the presence of allergic rhinitis in atopic
subjects 20 to 66 years of age
Bars represent median values.
Adapted from Gaga M et al Clin Exp Allergy 2000;20:663–669.
18
16
14
12
10
8
6
4
2
0
Eosinophils/
field of
nasal biopsy
Rhinitis No rhinitis Control
(n=9) (n=8) (n=10)
p<0.001
p<0.001
Asthmatic

18.
Clinical Links betweenAllergic Rhinitis and Asthma
Inflammatory Changes in the Nasal and
Bronchial Mucosa Are Correlated
Study of whethernasalmucosalinflammation existsin asthma regardlessof the presence ofallergic
rhinitis in atopic subjects 20 to 66 years of age
Adapted from Gaga M et al Clin Exp Allergy 2000;20:663–669.
40
35
30
25
20
15
10
5
0
Asthmatic
nasal
mucosa
eosinophils
0
r=0.851, p<0.001
Asthmatic bronchial mucosa eosinophils
5 10 15 20 25 30
(n=17)

19.
One Airway, One Disease
Symptoms Correlate with the Early- and Late-Phase
Responsesin Allergic Rhinitis and Asthma
FEV1=forced expiratory volume in one second
Adapted from Varner AE, Lemanske RF Jr. In: Asthma and Rhinitis. 2nd ed. Oxford: Blackwell Science, 2000:1172–1185; Togias A J
Allergy Clin Immunol 2000;105(6 pt 2):S599–S604.
(Asthma)
Score for nasal
symptoms
Sneezing
Nasal pruritus
Congestion
Rhinorrhea
Time post-challenge (hours)
1Antigen
challenge
3–4 8–12 24
Immediate (early) phase Late phase
FEV1
(% change)
Time (hours)
0
50
100
1 10 240 2 3 4 5 6 7 8 9
Upper
Airways
Lower
Airways
(Allergic
rhinitis)

20.
22
Congestion and Inflammation:
Adverse Clinical Impact in Upper Respiratory Disease
Allergic rhinitis
Nasal polyps
Sleep disturbance,
including sleep-
disordered breathing
Rhinosinusitis (acute and chronic)
Asthma with AR
Congestion
Inflammation
Common cold

21.
23
Burden of Allergic Rhinitis in
US and Europe: 2005
0
10
20
30
40
50
60
70
US Europe France Germany Italy Spain UK
Prevalence
Diagnosed
Drug-treated
Source: Decision Resources Report.
Patients(Millions)

22.
24
Congestion and Other Symptoms of
Allergic Rhinitis Impair Learning in
Pediatric Patients
40
44
48
52
56
60
Mean Composite Learning Scores
in Children 10-12 Years of Age At 2 Weeks
Vuurman et al. Ann Allergy. 1993;71:121.
Children with
Allergic Rhinitis
(n=12)
Meancompositelearning
Scoreat2weeks(%)
Healthy
Children (n=13)
P=0.007

23.
25
Prevalence of Allergic Rhinitis worldwide
• AR is estimated to affect over 500 million people worldwide1
– Prevalence is increasing in most countries of the world, particularly
in areas with low or medium levels of prevalence
– Prevalence may be plateauing or even decreasing in the highest
prevalence areas
• What about EGYPT?
AR = allergic rhinitis;
1. Bousquet J et al. Allergy. 2008;63(suppl 86):8–160; 2. Bauchau V et al. Eur Respir J. 2004;24:758–764; 3. Executive summary: adult. Allergies in America: a landmark survey of nasal
allergy sufferers. http://www.mmcpub.com/scsaia/AdultSummary.pdf. ccessed February 2011; 4. Ait-Khaled N et al. Allergy. 2009;64:123–148.

24.
Allergies In the Middle East
AIME survey, 2011

25.
Impact of allergic rhinitis on lung
function
 Both AR and asthma have airflow
limitation as the main functional
consequence
 The forced expiratory volume in 1
second (FEV1), a measurement of
exhaled volume during the first second
of a forced expiratory maneuver, may be
impaired in approximately 5% of patients
with AR who report only nasal
symptoms.

26.
How Allergic rhinitis affects
asthma
 Allergic rhinitis may promote or exacerbate
asthma through several physiologic mechanisms
that link the disorders.
 These include :
1- The vagal (rhinobronchial) reflex, which causes
nasal stimulation to induce bronchoconstriction.
2- Systemic release of mediators and cytokines.
3- Postnasal drip and resulting irritation.
4- The need for oral respiration caused by nasal
obstruction, which causes dry, cold air to
penetrate into the bronchi and promote bronchial
hyperreactivity

27.
Mechanisms of pathologic relationships between upper and lower airways
Fig.
Copyright© 2010 Southern Me1.20Reproduced with permission from Meltzer EO.Allergy Asthma
Proc2005;26:336-340.
dical Association.Published by LippincottWilliams & Wilkins. 29

28.
Other 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.

29.
Other Proposed pathophysiologic mechanisms of
asthma exacerbated by sinusitis
Reversible partial beta-adrenergic blockade
is enhanced.
Depressed nitric oxide concentration
promotes acute bronchial
hyperresponsiveness.

30.
Epidemiologic Links betweenAllergic Rhinitis and Asthma
Allergic Rhinitis Is a Risk Factor for Asthma
Allergic rhinitis increased the risk of asthma about threefold 1
23-yearfollow-up of first-yearcollegestudents undergoing allergy testing;data basedon738 individuals
(69% male)with average age of 40 years
1. Celine Bergeron and Qutayba Hamid. Relationship between Asthma and Rhinitis: Epidemiologic, Pathophysiologic, and Therapeutic
Aspects Allergy Asthma Clinical Immunol.2005
Adapted from Settipane RJ et al Allergy Proc 1994;15:21–25.
12
10
8
6
4
2
0
% of
patients who
developed
asthma
10.5
Allergic rhinitis
at baseline
(n=162)
3.6
No allergic rhinitis
at baseline
(n=528)
p<0.002

31.
Post Hoc Resource Use Analysis of IMPACT
Allergic Rhinitis Increased the Risk of Asthma Attacks
Post hoc analysis of medical resource use/asthma attacks in asthmatic patients with and without concomitant allergic rhinitis over
52 weeks
Adapted from Bousquet J et al Clin Exp Allergy 2005;35:723–727.
25
20
15
10
0
% of
patients
21.3
Patients with asthma
+ allergic rhinitis
(n=893)
17.1
Patients
with asthma
(n=597)
p=0.046

32.
Allergic Rhinitis Worsens Asthma
Allergic Rhinitis Doubled the Risk of ER Visits in Patients
with Asthma
Post hoc analysis of medical resource use/asthma attacks in asthmatic patients with and without concomitant allergic rhinitis over
52 weeks
ER=emergency room
Adapted from Bousquet J et al Clin Exp Allergy 2005;35:723–727.
% of
patients
Patients with asthma
+ allergic rhinitis
(n=893)
Patients
with asthma
(n=597)
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
p=0.029
1.7
3.6

33.
Retrospective Cohort Study of UK Mediplus Database
Allergic Rhinitis Increased the Number of Prescriptions
for Rescue Therapy (SABA) in Patientswith Asthma
Analysis of health-care resource use in adults 16 to 55 years of age with asthma and allergic rhinitis in general practice in the UK
SABA=short-acting beta2-agonists
Adapted from Price D et al Clin Exp Allergy 2005;35:282–287.
Patients with asthma
+ allergic rhinitis
(n=4611)
Patients with asthma
(n=22,692)
3.3
3.2
3.1
3.0
2.9
2.8
2.7
2.6
2.5
2.4
0
Annual
prescriptions
per patient
3.2
2.7
p<0.0001

34.
Treating Rhinitis May Help
Asthma
 The key to successful therapy for rhinitis
and asthma is the prevention or
suppression of inflammation
 Treatment of rhinitis has been shown to be
beneficial to the lower airways
 Treating inflammation in the upper airways
indirectly improves asthma symptoms and
decreases bronchial hyperreactivity

35.
Classification of allergic rhinitis
Intermittent symptoms
 <4 days per week
 Or <4 consecutive weeks
Mild
All of the following
 Normal sleep
 Normal daily activities, sport,
leisure
 Normal work and school
 No troublesome symptoms
Persistent symptoms
 >4 days per week
 And >4 consecutive weeks
Moderate/Severe
One or more items
 Abnormal sleep
 Impairment of daily activities,
sport, leisure
 Problems caused at work
or school
 Troublesome symptoms
Reference:
1. ARIA 2007

36.
© Global Initiative for Asthma
GINA assessment of symptom control
A. Symptom control
In the past 4 weeks, has the patient had:
Well-
controlled
Partly
controlled
Uncontrolled
• Daytime asthma symptoms more
than twice a week? Yes No
None of
these
1-2 of
these
3-4 of
these
• Any night waking due to asthma? Yes No
• Reliever needed for symptoms*
more than twice a week? Yes No
• Any activity limitation due to asthma? Yes No
B. Risk factors for poor asthma outcomes
• Assess risk factors at diagnosis and periodically
• Measure FEV1 at start of treatment, after 3 to 6 months of treatment to record the patient’s
personal best, then periodically for ongoing risk assessment
ASSESS PATIENT’S RISKS FOR:
• Exacerbations
• Fixed airflow limitation
• Medication side-effects
GINA 2015 Box 2-2B (1/4)
Level of asthma symptom control

37.
ARIA Guidelines:
Recommendations for
Management of Allergic
Rhinitis
2012

38.
© Global Initiative for Asthma
Step 1 – as-needed inhaled short-acting
beta2-agonist (SABA)
GINA 2015, Box 3-5, Step 1 (4/8)
PREFERRED
CONTROLLER
CHOICE
Other
controller
options
RELIEVER
STEP 1 STEP 2
STEP 3
STEP 4
STEP 5
Low dose ICS
Consider low
dose ICS
Leukotriene receptor antagonists (LTRA)
Low dose theophylline*
Med/high dose ICS
Low dose ICS+LTRA
(or + theoph*)
As-needed short-acting beta2-agonist (SABA) As-needed SABA or
low dose ICS/formoterol**
Low dose
ICS/LABA*
Med/high
ICS/LABA
Refer for
add-on
treatment
e.g.
anti-IgE
*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
# Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of
exacerbations; it is not indicated in children <18 years.
Add tiotropium#
High dose ICS
+ LTRA
(or + theoph*)
Add
tiotropium#
Add low
dose OCS

39.
One Airway, One Disease
ARIA and IPAG Guidelines Recommend
a Combined Approach to Managing Asthmaand Allergic Rhinitis
 Patients with allergic rhinitis should be
evaluated for asthma
 Patients with asthma should be evaluated for
allergic rhinitis
 A strategy should combine the treatment of
upper and lower airways in terms of efficacy
and tolerability
ARIA=Allergic Rhinitis and its Impacton Asthma;IPAG=InternationalPrimary Care AirwaysGroups
Adaptedfrom Bousquet J et al J Allergy Clin Immunol2001;108(suppl 5):S147–S334;International
Primary Care Airways Group,Los Angeles,California,USA,MCR Vision, 2005.

40.
Shared Epidemiological Findings of Allergic Rhinitis and Asthma
Summary
Several epidemiological findings suggests the link between
asthma and allergic rhinitis as well as the worsening effect of
allergic rhinitis on asthma:
 AR coexists in the majority of asthma patients
 Asthma patients with concomitant AR experience more
asthma attacks and use more resources to control their
asthma than patients with asthma alone.
 Asthma patients with concomitant AR experience worse
quality of life (physical functioning) than patients with AR alone
during the pollen season.

41.
TH2-associated asthma
Aspirin exacerbated airway disease (AERD)

42.
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.

43.
The findings on nasal examination are seen
in this Figure

44.
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:

45.
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:

46.
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.

47.
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.

48.
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.

49.
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

50.
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.

51.
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

52.
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?

53.
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

54.
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.

55.
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.

56.
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.

57.
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

58.
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.

59.
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.

60.
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.

61.
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?

62.
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

63.
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

64.
Modified Asthma Predictive Index (API)

65.
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.

66.
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.

67.
Treatment

68.
Severe asthma - differential diagnosis and management

69.
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.

70.
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?

71.
1- Is the patient controlled?
NO……
 Breathlessness.
 Frequent nocturnal symptoms
(cough and wheezes).

72.
2- Is asthma medicationssafe 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.

73.
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.

74.
Case 8
A 48-year-old postmenopausal woman has a 15-year
history of asthma. Her asthma is triggered by aspirin,
cigarette smoke, and upper respiratory tract infections. Six
months ago, after an upper respiratory tract infection, she
had an asthma exacerbation with peak expiratory flow rate
(PEFR) values of 45% of her personal best, with
continuous asthma symptoms, which were treated with a
10-day course of oral corticosteroids. Her PEFR improved
to 80% of her personal best and she was able to taper
and discontinue oral corticosteroids without a decrease in
her PEFR values or worsening of her asthma symptoms.
Now, 6 months later, she feels at her baseline with
minimal asthma symptoms when she exercises. She
denies nocturnal asthma symptoms.

75.
Case 8
On physical examination, she is free of wheeze, even with
forced inspiratory and expiratory efforts. Her spirometry
shows an FEV1 level that is 90% of predicted. Her current
medical regimen for treatment of asthma includes the
following: salmeterol by metered-dose inhaler (MDI), 2
puffs bid; fluticasone propionate by MDI, 250 μg, 2 puffs
bid; montelukast, 10 mg qhs; and salbutamol by MDI, 2
puffs prn, rescue for shortness of breath.

76.
The best treatment recommendation for her currently is to:
A. Continue her current medical regimen.
B. Discontinue montelukast.
C. Discontinue salmeterol.
D. Decrease fluticasone propionate dose to 125 μg, 2
puffs bid.
E. Add nedocromil sodium by MDI, 2 puffs qid

77.
The best treatment recommendation for her currently is to:
A. Continue her current medical regimen.
B. Discontinue montelukast.
C. Discontinue salmeterol.
D. Decrease fluticasone propionate dose to 125 μg, 2
puffs bid.
E. Add nedocromil sodium by MDI, 2 puffs qid

78.
All of the following statements concerning the
natural history of asthma are true EXCEPT:
A. The age-related decline in FEV1 is greater for
asthmatic than non-asthmatic adults.
B. Most adult asthmatics do not experience complete
asthma remission.
C. Regular use of inhaled corticosteroids is associated
with reduced asthma mortality.
D. Delayed introduction of inhaled corticosteroids
reduces the likelihood that FEV1 will normalize with
therapy.
E. The risk of a fatal asthma episode is greatest for
asthmatics with severe disease and fixed airflow
obstruction.
Case 9

79.
All of the following statements concerning the
natural history of asthma are true EXCEPT:
A. The age-related decline in FEV1 is greater for
asthmatic than non-asthmatic adults.
B. Most adult asthmatics do not experience complete
asthma remission.
C. Regular use of inhaled corticosteroids is associated
with reduced asthma mortality.
D. Delayed introduction of inhaled corticosteroids
reduces the likelihood that FEV1 will normalize with
therapy.
E. The risk of a fatal asthma episode is greatest for
asthmatics with severe disease and fixed airflow
obstruction.
Case 9

80.
The greatest risk of a fatal outcome in asthma appears to be in those
patients who demonstrate the highest degrees of airway
hyperresponsiveness and FEV1 lability, rather than in those with severe but
fixed airflow obstruction. In one study, the relative risk of death from asthma
was seven times higher for patients who demonstrated a 50% or greater
increase in FEV1 in response to bronchodilator, compared to those whose
FEV1 improved by less than 25%. While this observation might seem
somewhat contrary to expectations, it emphasizes that the most important
result of poor asthma control is the persistence of excessive airway lability,
with its attendant risk of asthma exacerbation. Persisting FEV1 lability is
most common among smokers and those with persistent atopic asthma.
Other documented risk factors for asthma mortality include age > 40 years,
smoking, and blood eosinophilia. Middle-aged and older adults with asthma
rarely achieve complete remission. The remission rate in adults is also
substantially lower than in children (10% to 15% vs over 50%). In a 25-year
study of adult asthma, remission, which was defined as becoming
asymptomatic with normal FEV1 and normal airway responsiveness, was
noted in only 20 of 190 subjects (10.5%).

81.
In this study, remission was associated with milder asthma and younger age at
first diagnosis, together with male gender and less initial airway
hyperresponsiveness. Control of asthma symptoms, FEV1, and airway
hyperresponsiveness also appears to be influenced by the timing of the
introduction of inhaled corticosteroids (ICS). Several trials have shown that
FEV1 is much less likely to normalize if the institution of ICS is delayed
following the initial diagnosis of asthma. Similar to the situation in COPD,
several longitudinal studies have demonstrated a more rapid age-related
decline in FEV1 in adult asthmatics compared to the nonasthmatic population,
and this is further compounded by smoking. There are few long-term studies of
the effects of treatment on the natural history of asthma. However, a recent
study of asthmatics aged 5 to 44 years has clearly demonstrated a dose-
dependent reduction in asthma mortality with increasing use of ICS, in that the
death rate from asthma was reduced by approximately 50% with the use of 6 or
more canisters of ICS during a 12-month period, compared to patients who
used smaller amounts of ICS

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