Asthma Masqueraders

4. Educational aims:
•Not all people who report respiratory symptoms have
asthma.
•COUGH, WHEEZING (AND other respiratory noises), and dyspnea
are common respiratory symptoms that potentially have an
extensive differential diagnosis.
•The diagnosis of asthma should be documented by
variable lung function, airway hyperresponsiveness and
inflammation

5. Hallmarks of asthma
Overview of differential diagnosis
Distinguishing asthma from COPD
Distinguishing asthma from VCD
Distinguishing asthma from cardiac asthma
Less common and uncommon
masqueraders

6. .A chronic inflammatory disorder of the airways
.Many cells and cellular elements play a role
.Chronic inflammation is associated with airway hyper
responsiveness that leads to recurrent episodes of
• wheezing
• breathlessness
• chest tightness
• and coughing
particularly at night or in the early morning
• Widespread, variable, and often reversible airflow obstruction

7. The distinguishing characteristic of asthma :
•is the response to bronchodilator or
corticosteroids when the patient is symptomatic.
•For patients who are old enough to perform a
pulmonary function test, substantial improvement of
airway obstruction from an aerosol bronchodilator or
a short course of reasonably high-dose systemic
corticosteroid, 2mg/kg twice daily to a maximum of
40 mg twice daily
WEINBERGER, ABU-HASAN :Pesudo-asthma: W hen Cough, Wheezing, and
Dyspnea Are Not Asthma .PEDIATRICS Volume120, Number 4, October 2007

8. •symptoms within 5 to 7 days of optimal medication and
•Pulmonary function after a maximum of 10 days
Argues against asthma as the etiology,
Provided that the patient has taken the medication.
WEINBERGER, ABU-HASAN :Pesudo-asthma: W hen Cough, Wheezing, and
Dyspnea Are Not Asthma .PEDIATRICS Volume120, Number 4, October 2007

9. MISDIAGNOSIS OF NON-ASTHMATIC CONDITIONS AS
UNCONTROLLED ASTHMA HAS BEEN REPORTED TO BE AS HIGH
AS 12–30%

10. So, the evaluation should start with:
• Careful history with emphasis on asthma symptoms
including dyspnoea (and relation to exercise), cough,
wheezing, chest tightness and nocturnal awakenings.
• In addition, information should be obtained on
exacerbating triggers, environmental or occupational factors
and comorbidities that may be contributing.
• Children and adults should be evaluated for other conditions
that may mimic or be associated with asthma

11. •1) Rhinosinusitis/(adults) nasal polyps
•2) Psychological factors: personality trait, symptom
perception, anxiety, depression
•3) Vocal cord dysfunction
•4) Obesity
•5) Smoking/smoking related disease
•6) Obstructive sleep apnoea
•7) Hyperventilation syndrome
•8) Hormonal influences: premenstrual, menarche, menopause,
thyroid disorders
•9) Gastro-oesophageal reflux disease (symptomatic)
•10) Drugs: aspirin, non-steroidal anti-inflammatory drugs
(NSAIDs),b-adrenergic blockers, angiotensinconverting
enzyme inhibitors
ERS/ATS GUIDELINES ON SEVERE ASTHMA |
K.F. CHUNG ET AL, 2014

12. Children
1. Bronchiolitis
2. Recurrent (micro)aspiration, reflux, swallowing
dysfunction
3. Prematurity and related lung disease
4. Cystic fibrosis
5. Congenital or acquired immune deficiency
6. Primary ciliary dyskinesia
7. Tracheobronchomalacia
8. ERS/ATS GUIDELINES ON SEVERE ASTHMA | K.F. CHUNG ET AL, 2014

13. 9.Carcinoid or other tumour
10.Mediastinal mass/enlarged lymph node
11.Congenital heart disease
12.Interstitial lung disease
13.Connective tissue disease
14.Central airways obstruction/compression
15.Foreign body
16.Congenital malformations including vascular ring
17.habit-cough syndrome
18.Exercise-induced supraventricular tachycardia
19.Exercise-induced laryngomalacia
ERS/ATS GUIDELINES ON SEVERE ASTHMA | K.F. CHUNG ET AL, 2014

14. 1. Dysfunctional breathlessness/vocal cord
dysfunction(VCD)
2. Chronic obstructive pulmonary disease(COPD)
3. Hyperventilation with panic attacks
4. Bronchiolitis obliterans
5. Congestive heart failure
6. Adverse drug reaction (e.g. angiotensin-
converting enzyme inhibitors)
7. Bronchiectasis/cystic fibrosis
8. Hypersensitivity pneumonitis
ERS/ATS GUIDELINES ON SEVERE ASTHMA |
K.F. CHUNG ET AL, 2014

15. 9.Hypereosinophilic syndromes
10.Pulmonary embolus
11.Herpetic tracheobronchitis
12.Endobronchial lesion/foreign body (e.g. amyloid, carcinoid, tracheal
stricture)
13.Allergic bronchopulmonary aspergillosis
14.Acquired tracheobronchomalacia
15.Churg–Strauss syndrome
16. Pulmonary migraine(Pulmonary migraine consists of combined
recurrent asthma; cough with thick mucoid sputum; lower back pain
radiating to the shoulder; subtotal or total atelectasis of a segment or
lobe; focal headache, occasionally, nausea with vomiting)due to
Spastic narrowing of the bronchi is postulated—along with retained
mucous secretions, smooth muscle hypertrophy, and thickened
bronchial walls . Cerebral and abdominal vascular migraine episodes
are believed to accompany pulmonary migraine.{Tucker GF Jr.
Pulmonary migraine. Ann Otol Rhinol Laryngol. Sep-Oct 1977;86(5 Pt
1):671-6}
17.Reactive airways dysfunction syndrome

18. • Vocal cord dysfunction (VCD) is the intermittent, abnormal
adduction of the vocal cords during respiration
resulting in variable upper airway obstruction. The variable
airway obstruction classically affects the inspiratory phase of
respiration but the expiratory phase can be affected as well.
• VCD frequently co-exists with asthma and complicates
effective care and management when not recognized as a
separate entity(refractory asthma).
• The cord function is reversed in that the vocal folds Adduct on
inspiration versus Abduct
• Leads to tightness or spasm in the larynx
• Inspiratory wheeze evident

20. • One type occurs spontaneously,
with the patient experiencing dyspnea and inspiratory
stridor (often described as “wheezing”) at various and
often unpredictable times. Whether this is a panic- or
anxiety-induced reaction is speculative.
• The other phenotype is a reaction that occurs only
with exercise,
which is commonly seen in adolescent athletes during
competitive aerobic activities. Typically transient and
relieved spontaneously with a period of rest,

21. • FIGURE 5
Flow-volume loops obtained before and when symptomatic for 2 patterns of vocal cord
dysfunction syndrome. A, Preexercise flow-volume loop with the midinspiratory and
midexpiratory flows approximately equal and the postexercise loop exhibiting the typical
flattening of the inspiratory portion of the flow-volume loop in a 15-year-old girl with
exercise-induced inspiratory stridor that had been described as “wheezing” by previous
Physicians.This indicates reversible upper airway obstruction that was then
confirmed by visualizing adduction of the vocal cords on inspiration with flexible laryngoscopy. B, Flow-
volume loops from a 15-year-old girl with a history of repeated episodes of sudden-onset severe
dyspnea. She had spontaneous onset of severe dyspnea
during our initial evaluation with marked compromise of both inspiration and expiration
illustrated by the spirometric tracing. Flexible laryngoscopy demonstrated the vocal
cords and false vocal cords to be severely adducted, leaving only an2-mm opening for
air movement except when talking.

22. • The gold standard for the diagnosis of VCD is by direct
observation of the vocal cords with videolaryngostroboscopy (VLS). The
variable nature of VCD can limit the diagnostic value of VLS and other
direct observational approaches if symptoms are not present at the
time of the study.
• Anterior portions of the vocal folds are ADDucted
• Only a small area of opening at the
Posterior aspect of the vocal folds
• Diamond shaped ‘CHINK’
• May be evident on both inhalation
and exhalation
Benninger et al ,Vocal cord dysfunction and
asthma: Current Opinion in Pulmonary
Medicine2011(17:45–49)

23. • intermittent shortness of breath
• wheezing,
• stridor,
• or cough, which may be interpreted as
• worsening asthma control given their nonspecific nature
and can lead to unnecessary increases in asthma therapy.
• Difficulty with inspiratory phase
• Throat tightening > bronchial/ chest
• Dysphonia during/following an attack
• Abrupt onset and resolution
• Little or NO response to medical treatment (inhalers,
bronchodilators)
.
Benninger et al ,Vocal cord dysfunction and asthma:
Current Opinion in Pulmonary Medicine201117:45–49

24. The concept of a hyper-responsive larynx, similar to the
hyper-responsive airway in asthma, has been the focus of
recent studies and may help explain the high prevalence
of VCD seen in asthmatics.
The larynx is highly innervated with sensory and motor
nerve fibers which are:
thought to become hyperexcitable by intrinsic or extrinsic
stimuli resulting in hyperfunctional glottic movement,
cough and other laryngeal sensations
Benninger et al ,Vocal cord dysfunction and asthma: Current Opinion in Pulmonary
Medicine2011 17:45–49

26. VCD ASTHMA
FEV1/FVC
FEV1
Normal
Normal
Low
Low
Flow volume loop Flattening of the inspiratory
limb
affection of the expiratory
limb
Precipitators (triggers) Exercise, extreme temperatures Exercise, extreme temp.
temperatur,.. irritants,,
emotional stressors ,allergens,
Number of triggers Usually one Usually multiple
Breathing obstruction Laryngeal area Chest area
location
Timing of breathing Stridor on Wheezing on
noises inspiration exhalation

27. VCD ASTHMA
Pattern of dyspneic event Sudden onset and
relatively rapid
cessation
More gradual onset , longer
recovery period
Nocturnal awakening
with symptoms
Rarely Almost always
Response to broncho- dilators
and/or systemic
corticosteroids
No response Good response

28. • Speech therapy
The mainstays of treatment for vocal cord dysfunction (VCD) involve teaching the
patient vocal cord relaxation techniques and breathing exercises. These procedures
have been very successful and are used concomitantly with psychological support in
difficult cases
• Psychotherapy
• The role of the psychiatrist is to implement cognitive behavior psychotherapy or
general psychotherapy based upon evaluation of psychiatric and/or personality
disorders.
• Helium-oxygen therapy in the emergent treatment of acute VCD.
• Anticholinergic agent
Inhaled ipratropium may be helpful treatment in patients with exercise-
induced VCD
Benninger et al ,Vocal cord dysfunction and asthma: Current Opinion in Pulmonary
Medicine201117:45–49
Deckert J, Deckert L. Vocal cord dysfunction. Am Fam Physician. Jan 15 2010;81(2):156-9

30. • Asthma and chronic obstructive pulmonary
disease (COPD) are both characterized by airway obstruction, which is
variable and reversible in asthma but is progressive and largely
irreversible in COPD
• In both diseases,
-there is chronic inflammation of the respiratory tract, which is mediated by
the increased expression of multiple inflammatory proteins,
including cytokines, chemokines, adhesion
molecules, inflammatory enzymes and receptors
• In both diseases there are acute episodes
or exacerbations, when the intensity of this
inflammation increases.
P.J. Barnes ,
Similarities and differences in Inflammatory Mechanisms of Asthma
andCOPD :Breathe| March 2011| Volume 7| No 3

31. Despite the similarity of some clinical features of asthma and COPD,
• there are marked differences in the pattern of inflammation that occurs in the
respiratory tract
• different mediators produced, distinct consequences of inflammation and
differing responses to therapy.
In addition, the inflammation seen in asthma is mainly located in the larger
conducting airways, although small
airways may also be involved in more severe
disease
• P.J. Barnes ,
• Similarities and differences in Inflamatory Mechanisms of Asthma andCOPD :Breathe| March
2011| Volume 7| No 3

32. P.J. Barnes ,
Similarities and differences in Inflamatory Mechanisms of Asthma andCOPD
:Breathe| March 2011| Volume 7| No 3

33. Clinical criteria ASTHMA COPD
Age of onset any age elderly smokers
Classic
symptoms
Episodic wheezing,
cough, dyspnea and
chest tightness
dyspnea on
exertion
Relation of sx to
respiratory Cycle
exhalation >
inhalation
exhalation >
inhalation
Tilles SA, Nelson HS Current Review of
asthma. Current Medicine, 2003

34. Comparison of Asthma and COPD
criteria ASTHMA COPD
Chest radiology Hyperinflation in acute
attack
Hyperinflation and
hyperlucency
PFTs reversible
Obstruction
Increased
volumes,
normal or
increased DLCO
irreversible
obstruction
Increased
volumes,
,
decreased DLCO
Tilles SA, Nelson HS Current Review of
asthma. Current Medicine, 2003

35. Comparison of Asthma and COPD
Pathological criteria ASTHMA COPD
inflammatory
cells
Eosinophils
Neutrophils
Mast cells
CD4+ T cells
Th2
Neutrophils
Macrophages
Th2 ,CD8+ T cells
Structural
changes
Airway sm muscle +++
All airways
No Parenchymal change
Epithelial shedding
Fibrosis + (subepithelial)
Mucous secretion +
Airway sm muscle +
Peripheral airways
Parenchymal destruction
Epithelial metaplasia
Fibrosis ++
(peribronchiolar)
Mucous secretion +++
Tzortzaki EG, et al J Allergy 2011; 2011:843543

36. Comparison of Asthma and COPD
Response to treatment ASTHMA COPD
Response to
Corticosteroids
Response to
bronchodilators
good
good modest
Poor
good modest
Tilles SA, Nelson HS Current Review of
asthma. Current Medicine, 2003

37. Figure 1 Inflammatory and immune cells involved in
asthma
P.J. Barnes ,
Similarities and differences in Inflamatory Mechanisms of Asthma
andCOPD :Breathe| March 2011| Volume 7| No 3

38. Figure 2
Inflammatory and immune cells involved in chronic obstructive
pulmonarydisease (COPD)
P.J. Barnes ,
Similarities and differences in Inflamatory Mechanisms of
Asthma andCOPD :Breathe| March 2011| Volume 7| No 3

39. Figure 3
Contrasting histopathology of asthma and chronic obstructive pulmonarydisease (COPD).
small airway from a patient who died from asthma and a similar sized airway from a patient
with severe COPD are shown. There is an infiltration with inflammatory cells in both diseases.
The airway smooth muscle (ASM) layer is thickened in asthma but only to a minimal degree in
COPD. The basement membrane (BM) is thickened in asthma due to collagen deposition
(subepithelial fibrosis) but not in COPD, whereas in COPD collagen is deposited mainly around
the airway (peribronchiolar fibrosis). The alveolar attachments are intact in asthma, but
disrupted in COPD as a result of emphysema. Images courtesy of J. Hogg (Vancouver, Canada).
P.J. Barnes ,
Similarities and differences in Inflamatory Mechanisms of Asthma andCOPD
:Breathe| March 2011| Volume 7| No 3

40. Although the inflammatory and immune
mechanisms of asthma and COPD described
above are markedly different, there are several
situations where they become more similar and
the distinction between asthma and COPD
becomes blurred as in table
P.J. Barnes ,
Similarities and differences in Inflamatory
Mechanisms of Asthma andCOPD :Breathe|
March 2011| Volume 7| No 3

41. Table Comparison between asthma and chronic obstructive pulmonary
disease (COPD) inflammation patterns

42. The Asthma–Chronic Obstructive
Pulmonary Disease Overlap
Syndrome
• Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is a
commonly encountered yet loosely defined clinical entity. ACOS accounts for
approximately 15–25% of the obstructive airway diseases and patients experience worse
outcomes compared with asthma or COPD alone.
Patients with ACOS have the
• combined risk factors of smoking and atopy, are generally younger than patients with
COPD and experience acute exacerbations with higher frequency and greater severity
than lone COPD
major criteria for ACOS:
1.A physician diagnosis of asthma and COPD in the same patient, history or evidence of atopy,
for example, hay fever, elevated total IgE
2.Age 40 years or more, smoking >10 pack-years,
3.postbronchodilator FEV1 <80% predicted and FEV1/FVC <70%. A ≥15% increase in
• FEV1 ≥12% and ≥200 ml increase in FEV1 postbronchodilator treatment with albuterol
would be a minor criteria.
Louie et al Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) Expert Rev Clin
Pharmacol. 2013;6(2):197-219

43. Cardiac asthma as a common masquerader of asthma
• Congestive heart failure causes engorged pulmonary vessels and
interstitial pulmonary edema, which reduce lung compliance and
contribute to the sensation of dyspnea and wheezing. Cardiac
asthma is characterized by wheezing secondary to bronchospasm
in congestive heart failure, and it is related to paroxysmal
nocturnal dyspnea and nocturnal coughing
Characterstic features:
Dysnea on exertion,PND
Rales
Early night symptoms
Gallop rhythm and S3
CXR and Echocardiography are diagnostic
Asthma Differential Diagnoses -emedicine.medscape.com/article/296301- differential

44. • Tracheal and bronchial lesions (central airway obstruction)
A variety of airway tumors are reported to manifest with symptoms similar
to those of asthma. These tumors include endobronchial carcinoid and
mucoepidermoid tumors when causing partial airway obstruction
• Foreign bodies
Foreign body aspiration may cause not only localized wheezing but also
generalized wheezing. Wheezing occurs in toddlers as well as in adults.
As described in one patient, foreign body aspiration may necessitate
bronchoscopic retrieval before the patient even recalls the inciting event,
and as many as 25% of patients may never recall the event.
Asthma Differential Diagnoses -
emedicine.medscape.com/article/296301-
differential

45. • Sinus disease
Sinus disease and post nasal drip , especially in children,
is associated with bronchial asthma and wheezing.
• Gastroesophageal reflux
Cough, recurrent bronchitis, pneumonia, wheezing, and
asthma are associated with gastroesophageal reflux
(GER).The incidence of GER in patients with asthma
ranges from 38% in patients with only asthma
symptoms to 48% in patients with recurrent
pneumonia
Asthma Differential Diagnoses -
emedicine.medscape.com/article/296301-
differential

46. • Other conditions and factors
Other extrinsic conditions, such as
lymphadenopathy from Hodgkin lymphoma of
the upper mediastinum, can contribute to
asthma. In addition, aspirin or NSAID
hypersensitivity and reactive airways
dysfunction syndrome may be mistaken for
asthma. Misdiagnoses as refractory bronchial
asthma has resulted in inappropriate long-term
treatment with corticosteroids.
Asthma Differential Diagnoses -emedicine.medscape.com/article/296301- differential

47. Less Common Asthma Masqueraders
Habit-Cough Syndrome
Habit-cough syndrome is common in children
It is a troublesome disorder that
commonly is treated as asthma that often results in a
great deal of morbidity and ineffective treatment and yet
is readily curable rapidly with suggestion therapy with a simple behavioral technique.
The classical presentation of habit-cough syndrome
1. is that of a harsh, barking, repetitive cough that occurs several times per minute
for hours
2. the complete absence of cough once the patientis asleep.
3. a high incidence of abdominal
pain and irritable bowel syndrome in many of the children with habit-cough syndrome,
In considering treatment and discussing the issue with the family, it is
important not to refer to this as a psychogenic cough
WEINBERGER, ABU-HASAN :Pesudo-asthma: W hen Cough, Wheezing, and
Dyspnea Are Not Asthma .PEDIATRICS Volume120, Number 4, October 2007

48. Tracheomalacia
• Malacia = “softness”
Normal intrathoracic trachea dilates somewhat with inspiration and narrows with expiration
• Inadequate rigidity of the tracheal or main-stem bronchial cartilage results in tracheal
collapse, which causes cough by at least 2 mechanisms
1. Collapse of the trachea or main-stem
bronchi during increased intrathoracic pressure as in
vigorous exhalation or coughing can cause the anterior
and posterior walls to come into contact, which results in
an irritable focus that stimulates further cough.
2.In addition, when secretions are present in the airway, the
airway collapse prevents normal airway clearance of
secretions. The secretions then act as a continued stimulus for a nonproductive cough.
• Types:
• Tracheomalacia - trachea
• Bronchomalacia - one or both of the main-stem bronchi
• Tracheobronchomalacia - both
WEINBERGER, ABU-HASAN :Pesudo-asthma: W hen Cough, Wheezing, and
Dyspnea Are Not Asthma .PEDIATRICS Volume120, Number 4, October 2007

49. Causes of tracheomalacia
• Congenital disease: (also called primary): consequence of the inadequate
maturity of tracheobronchial cartilage
– Polychondritis
– Chondromalacia
– Mucopolysaccharidoses: Hunter syndrome and Hurler syndrome
– Idiopathic “giant trachea” or Mounier- Kuhn syndrome
– Acquired Tracheomalacia:
• Posttraumatic
– Post-intubation
– Post-tracheostomy
• Emphysema
• Chronic infection/bronchitis
• Chronic inflammation
– Relapsing polychondritis
• Chronic external compression of the trachea
– Malignancy
– Benign tumors
– Cysts
– Abscesses
– Aortic aneurysm
• Vascular rings, previously undiagnosed in childhood
WEINBERGER, ABU-HASAN :Pesudo-asthma: W hen Cough, Wheezing, and
Dyspnea Are Not Asthma .PEDIATRICS Volume120, Number 4, October 2007
Less Common Asthma
Masqueraders

50. Direct visualization by bronchoscopy is the gold
standard to document a narrowing of at least
50% in the sagittal diameter in expiration
– Mild : obstruction during expiration is to one
half of the lumen
– Moderate : obstruction reaches three quarters
of the lumen
– Severe : the posterior wall touches the
anterior wall
Nuutinen J. Acquired tracheobronchomalacia: a clinical study with bronchological correlations.
Ann Clin Res 1977;9:350–355

51. FIGURE
Bronchomalacia of the right upper lobe (A) and the right main stem (B). Depending on
the degree of obstruction caused by the malacia, either cough or expiratory monophonic
wheezing may be heard. Obstruction occurs on expiration with positive intrathoracic
pressure during expiration while negative intrathoracic pressure during inspiration
opens the airway. Complete airway obstruction during expiration can result in lobar
emphysema from persistent hyperinflation of the lobe distal to the malacia. Decreased
clearing of secretions distal to the malacia may be associated with purulent bacterial
bronchitis.

52. Other Rare Causes of Chronic Cough which masquerades asthma
There are some particularly unusual causes of
chronic cough that were misdiagnosed as asthma. Although unlikely to be encountered
frequently, awareness of these entities can encourage additional investigation when
the pattern of symptoms and response to
treatment is not consistent with asthma. A uvula that
was in contact with the epiglottis
was cause of along standing .
FIGURE
Tonsils (the lateral masses in the image) impinging on the epiglottis in a 3-year-old girl
caused chronic cough that initially was treated unsuccessfully as asthma. A tonsillectomy
cured her cough
WEINBERGER, ABU-HASAN :Pesudo-asthma: W hen Cough, Wheezing, and
Dyspnea Are Not Asthma .PEDIATRICS Volume120, Number 4, October 2007

53. • Reactive Airways Dysfunction Syndrome or RADS is a term
proposed by Stuart M. Brooks M.D. and colleagues in 198. To
describe an asthma-like syndrome developing after a single
exposure to high levels of an irritating vapor, fume, or smoke. It
involves coughing, wheezing, and dysnea.
• It can also manifest in adults with exposure to high levels of
chlorine, ammonia, acetic acid or sulphur dioxide, creating
symptoms like asthma.[6] The severity of these symptoms can be
mild to fatal, and can even create long-term airway damage
depending on the amount of exposure and the concentration of
chlorine. Some experts classify RADS as occupational asthma.
Those with exposure to highly irritating substances should receive
treatment to mitigate harmful effects
Aslan et al 2008 . "The Effect of Nebulized NaHCO3 Treatment on 'RADS' Due to Chlorine Gas Inhalation". Inhalation Toxicology: Vol. 18, Number 11

54. Often, the term "reactive airway disease" is used
when asthma is suspected, but not yet
confirmed.
Reactive airway disease in children is a general
term that doesn't indicate a specific diagnosis. It
may be used to describe a history of coughing,
wheezing or shortness of breath triggered by
infection. These signs and symptoms may or
may not be caused by asthma.

55. HOME MESSAGE
• Not all people who report respiratory symptoms have asthma
• COUGH, WHEEZING (AND other respiratory noises), and dyspnea are
common respiratory symptoms that potentially have an extensive
differential diagnosis.
• The distinguishing characteristic of asthma :
- is the response to bronchodilator orcorticosteroids when the patient is
symptomatic
-Improvement of airway obstruction from an aerosol bronchodilator
or a short course of systemic corticosteroid which is documented by PFTs.
Argues against asthma as
the etiology, Provided that the patient has taken the medication