Understanding Allergic

Reactions

Samuel Gubernick, DO

FAAAAI, FACAAI, FAAP

Allergy

• Von Pirquet

– Coined the term

“Allergy” in 1906

• Derived from Greek

word “allos” meaning

changed or altered

state and “ergon”

meaning reaction

• Reaction may be host

protective or injurious

Hypersensitivity Classification

• Gell and Coombs

– Developed classification of hypersensitivity

reactions (1963)

• Type I Hypersensitivity- IgE mediated

• Type II Hypersensitivity- Antibody mediated

• Type III Hypersensitivity- Immune complex

• Type IV Hypersensitivity- Cell mediated

Stages in Symptomatic Allergic Rhinitis

and Asthma

Subsequent

Allergen

Exposures

Initial AllergenExposure

DelayedSymptoms

NaiveAirway

SensitizedAirway

ImmediateSymptoms

Late-PhaseResponse

Early-PhaseResponse

Cellular Participants

in the Allergic Response

• APCs

• Helper T lymphocytes

(TH0, TH2 subclasses)

• B lymphocytes

• Mast cells

• Airway epithelial cells

• Eosinophils

T-Cell Differentiation During Sensitization

IL-2, IL-3, IL-4, IL-5, IL-9IL-10, IL-13, GM-CSF

APC

TH0 Cell

TH2 Cell

MHC II CD4

IL-4Antigen

IgE Antibodies in Allergic Inflammation

Allergen

B Cell

IL-4

Plasma Cell

IgEAntibodies

Mast Cell

AllergenExposure

ActivatedMast Cell

Preformed in Granules

– Preformed mediators

• Histamine

• Tryptase & Chymase

• Heparin

• Condroitin sulfate

• Carboxypeptidase A

• Cathepsin G

• Acid hydrolase

• TNF-a, VPF, VEGF

Newly Generated

– Newly synthesized lipids

• PGD2

• LTC4

• LTB4

• PAF

– Cytokines

• IL-3, 4, 5, 6, 8, 10, 13, 16

• TNF-a

• MIP-1a

• RANTES

• GM-CSF

• b-FGF

• SCF

• TGF-b

• VEGF

• MCP

Immediate allergic reaction

• Triggered when allergens bridge IgE-FceRI

units on mast cell surface

– Histamine, leukotrienes, PGD2, tryptase,

cytokines & other mediators released

– Peak of allergic symptoms within 30 minutes

• Mast cell major cause of anaphylaxis

Late-phase allergic reaction

Mast cell action amplifies this reaction: role of TNF-a & other cytokines and mediators

Recruitment of other inflammatory cells: lymphocytes, monocytes/macrophages, eosinophils, and basophils (as early as 1 hour)

Cytokines and chemokines released by TH2

cells, monocytes, eosinophils

Release of mediators from basophils:

histamine, leukotrienes and cytokines

Symptoms peak in three to eight hours

Early and Late Phase Response

Summary of Allergic Response

Mast Cells

Subsequent AllergenExposures

NaiveAirway

SensitizedAirway

Late-PhaseResponse

Early-PhaseResponse

Initial AllergenExposure

TH2 Cells

AirwayEpithelial

Cells

InflammationAirway DamageHyperresponsiveness

CytokineRelease

Leukocyte Influx:EosinophilsT LymphocytesBasophilsNeutrophils

SensitizedTH2 Cells

SensitizedMast Cells

Definition of Allergic Rhinitis

• Inflammation of the membranes lining the nose

• Characterized by one or more of the following:

– congestion

– itching

– sneezing

– rhinorrhea

– postnasal drainage

• IgE-mediated reaction to a specific aeroallergen

Types of Rhinitis

• I. Allergic rhinitis

– A. Perennial

– B. Seasonal

– C. Episodic

• II. Nonallergic rhinitis

– A. Vasomotor rhinitis

– B. Gustatory rhinitis

– C. Infectious

• 1. Acute

• 2. Chronic

– D. NARES

• III. Occupational rhinitis

– A. Caused by protein and

chemical allergens, IgE-

mediated

– B. Caused by chemical

respiratory sensitizers,

immune mechanism

uncertain

– C. Work-aggravated rhinitis

Types of Rhinitis - continued

• IV. Other rhinitis syndromes

• A. Hormonally induced– 1. Pregnancy rhinitis

– 2. Menstrual cycle related

– 3. Thyroid

• B. Drug-induced– 1. Rhinitis medicamentosa

– 2. Oral contraceptives

– 3. Antihypertensives, other CV

– 4. Aspirin/NSAIDs

– 5. Other drugs

• C. Atrophic rhinitis

– D. Rhinitis associated with inflammatory-immunologic diseases

• 1. Granulomatous infections

• 2. Wegener graulomatosis

• 3. Sarcoidosis

• 4. Midline granuloma

• 5. Churg-Strauss

• 6. Relapsing polychondritis

• 7. Amyloidosis

Conditions that may mimic

symptoms of rhinitis

• A. Nasal polyps

• B. Structural/mechanical

– 1. Deviated septum

– 2. Adenoidal hypertrophy

– 3. Trauma

– 4. Foreign bodies

– 5. Nasal tumors

– 6. Choanal atresia

– 7. Cleft palate

– 8. Pharnygonasal reflux

– 9. Acromegaly

• C. CSF rhinorrhea

• D. Ciliary dyskinesia

Comorbid Conditions

• Asthma– Allergic rhinitis occurs in over 75% of asthmatic patients

– 15% of patients with AR have asthma

– “One airway, one disease”

• Allergic Conjunctivitis

• Nasal polyposis

• Eustachian tube dysfunction & otitis media

• Rhinosinusitis

• Atopic dermatitis

• Lymphoid hypertrophy / obstructive sleep apnea

Allergens

• Seasonal

– Tree pollen

– Grass pollen

– Weed pollen

– Mold spores

• Perennial

– House-dust mites

– Animal dander• Dogs, cats

• Mice and rats

– Cockroaches

– Mold spores

– Occupational

allergens

House Dust Mites

• Dermatophagoides pteronyssiunus

• Dermatophagoides farinae

• Blomia tropicalis

• Live in bedding, upholstered furniture,

stuffed animals and carpet.

• Feed on human skin scales.

• Grow best in relative humidity above

50-70%.

House Dust Mite Control

• Encase mattress, box-springs and pillows

• Wash bedding weekly at 130° F

• Remove stuffed animals

• Reduce humidity

• Second line – remove carpeting and upholstered

furniture, HEPA vacuum

• Air filters not effective

Cockroach Allergen

• Blattella germanica most common in U.S. inner cities

• Allergens found in cockroach feces and typically carried on larger particles (>10µM)

• Prevalence of sensitivity to cockroach:

– 18.1% in general population

– 33.2% in asthmatics

Allergen avoidance - Cockroach

• Eradicate cockroaches with appropriate gel-type,

non-volatile, insecticides

• Eliminate dampness

• Seal cracks and crevices in floors and ceilings

• Removal of food and water sources

• Thorough cleaning of all surfaces including floors,

cabinets, appliances, and fabrics to remove

allergen

Exposure to A alternata in US Homes is

Associated with Active Asthma

Association Between Spore Peaks and

Asthma Hospitalizations

Salvaggio et al. JACI. 48:96,

1971

•First documented by Salvaggio 1971

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Mold Avoidance

• Avoid barns, hay, raking leaves, and mowing grass

• Proper building maintenance, dehumidification, air

conditioning, and increased ventilation are helpful

• Ensure dry indoor conditions - mold growth indoors

can be inhibited by reducing moisture and humidity

• Use bleach, ammonia, etc to remove mold from

bathrooms and other wet spaces

• Humidifiers and vaporizers increase indoor humidity

and can become contaminated with mold

Cat and Dog Allergens

• Particles that carry cat and dog allergens can be small

(2-10μm), become airborne with minimal disturbance and

remain airborne for hours.

• Travel on particles that are passively transferred.

• Are ubiquitous in public buildings and moderate exposure

in communities with domestic cat ownership is

unavoidable.

• Homes with pets have allergen levels ~100x higher than

homes without

Pet allergen avoidance

• Remove pets from home is best

• Keep the pet outside at all times

• Keep pets out of bedroom

• Vacuum carpets, mattresses and upholstery

• Air cleaners

• Wash pet regularly

Cat Allergen in Home Declines

Slowly After Pet Removal

Fel d 1 content in the dust from homes after removal of a cat

Wood et al JACI 83:730,1989

Pollen allergen avoidance

• Remain indoors with windows closed at peak pollen times

• Trees release pollen early in the morning around dawn

and counts near the source will be highest in the morning.

Urban counts will increase as the pollen travels toward the

area and usually peaks at the middle of the day. Avoid the

outdoors between 5 a.m. and 10 a.m - when counts are

the highest. Pollen counts decrease by late afternoon.

• Wear sunglasses

• Use air-conditioning, where possible

• Install car pollen filter

Vasomotor Rhinitis

• Vasomotor rhinitis

– Perennial

– Nasal congestion and post-nasal drip

– Mechanism unknown - vascular and/or neurological

dysfunction of nasal mucosa ?

– Females predominance, 40-60 years

– Triggers

• change in temperature, humidity, barometric pressure

• Irritants - perfume, tobacco smoke, paint, ammonia

• emotional stress

Test results alone

do not make a diagnosis

• Correlation of allergy test results with the

patient’s history and physical exam, the

environmental history, the disease process, and

a thorough knowledge of all relevant allergens in

a specific location is essential in making an

appropriate diagnosis.

• Bottom line – interpret allergy testing in light of

the clinical setting.

• Therefore, the practice of “remote allergy” or

diagnosis by testing alone is not acceptable.

Total IgE

• Over 25% of patients with allergic rhinitis have

normal total IgE levels.

• Up to 20% of nonallergic patients have elevated

total IgE levels.

• Therefore, total serum IgE is not a good

screening test for allergy.

Chronic cough

How is cough produced?

• Cough receptors stimulated

• A signal is sent to brain/cough center

• A signal is sent back to respiratory tract

• Starts with deep inhalation and then a

forced exhalation with closed

glottis/windpipe. Air gushes out at a high

speed of 300 miles/hour

Is it really important to know

• Character

• Timing

• Presence or absence of sputum production

• Associated complications

Children are not little adults!

Frequent Throat Clearing

• When can it be abnormal?

• Abnormal if waking you up at night

• Causes: Habit, Anxiety, Allergies, Sinus

Disease, Reflux

History

• Triggers: Talking, laughter, walking, running, strong smells, perfumes

• Timing: Daytime vs nighttime

• Relationship with meals

• Preceding Events:

Viral URI, Recent Immigration from a developing country, foreign travel

• Analysis of cough sound: Pediatric vs Adult

• Review of systems is very important

Analysis of Cough Character

Cough Character Potential Etiology

Barking or brassy Croup, tracheomalacia,

habit cough

Cough productive of

casts

Plastic bronchitis

Honking Psychogenic

Paroxysmal (with or

without whoop)

Pertussis/Parapertussis

Staccato Chlamydia in infants

Physical Examination

• Thick, yellow postnasal drip visible in

oropharynx: think chronic sinusitis

• Look into ears to rule out wax impaction

and other causes (Arnold’s Nerve)

• Look at nails for clubbing (CF, etc.)

• Check for thyroid masses

• Look for signs of atopy

Most Common Causes of

Chronic Cough

• The following account for >90% of causes

in a non-smoker who is not on an ACEI

– Upper Airway Cough Syndrome

– Asthma

– Reflux Disease

– Non-asthmatic Eosinophilic Bronchitis/ NAEB

(? Uncommon in the US)

Four basic steps for evaluating

chronic cough

• Stop ACE-inhibitor (1-3 months)

• Stop Smoking (1 month)

• Chest XR

• Spirometry/PFT (Pre- and Post)

Common Pitfalls

• Failure to consider common

extrapulmonary causes

• Insufficient dose of medication or duration

of therapy

Classification based on

duration of cough

• Acute cough lasting < 3 weeks

• Sub-acute cough lasting 3-8 weeks

• Chronic cough lasting > 8 weeks

Causes of acute cough

• Common cold

• Acute bronchitis

• Allergic rhinitis

• Acute bacterial sinusitis

• Pertussis

• COPD/Emphysema exacerbation

Post-Viral Cough

• A very common form of nonspecific cough

• Usually dry

• Due to increased cough receptor sensitivity

• NOT cough variant asthma

• May respond to albuterol or inhaled steroids

• Children in daycare – 6-12 URIs per year

Bordetella Pertussis

• Pertussis vaccine is about 80% effective

• Last DPT given at approximately 5 yo

• Immunity wanes 3 years post vaccination and

children susceptible within 5-10 years

• Characteristic “Whoop” is absent in teens and

adults

• Teens/adults not seriously ill and serve as

reservoirs for the disease

Red Book 26th ed American Academy of Pediatrics

Pertussis

When to suspect & Whom to treat?

• Suspect and treat if a clear cut history of exposure

• Suspect and treat if cough and vomiting (?)

• Erythromycin is the drug of choice; however, unless administered early, it does not alter the course of the disease

Causes of sub-acute cough

Sub-acute cough: 3-8 weeks duration

• Post-infectious

• Pertussis

• Sub-acute bacterial sinusitis

• Asthma

• Allergic rhinitis

Foreign Body Aspiration

• Most children with foreign body aspiration

present within 24 hrs

• 20% present > 1 week after the incident

• Nonobstructive or partially obstructive can

go unnoticed

• Foods – 80% , Peanuts, hot dogs, hard

candy most commonly removed

• Bilateral is rare but can occur

Causes of chronic cough

• Postnasal drip syndromes (PNDS)

(1) Allergic rhinitis

(2) Nonallergic rhinitis

(3) Chronic bacterial sinusitis

• Asthma

• GERD

• Eosinophilic bronchitis

• Chronic bronchitis

• ACE-inhibitor induced cough

Strategies in Cough

• “Anatomic-diagnostic” protocol

• Full investigation for common causes in all patients

• Empiric trials of therapy without routine investigation

The Anatomic Diagnostic

Protocol

• By Richard Irwin, et al (1981)

• Prospective study

• Not randomized or blinded (limitation)

• Offers framework for many of the

published diagnostic algorithms

• Success Rates of 84-98%

Irwin RS et al. Am Rev Respir Dis. 1981;123: 413-417

Upper Airway Cough

Syndrome/ Postnasal Drip

• Dry up / stop the mucus:

(1) Dexbrompheniramine

(2) Decongestants

(3) Steroid nose sprays

(4) Antihistamine nose sprays

(5) Ipratropium (0.06%) nose spray

• Liquify the mucus:

(1) Sinus rinse

(2) Guaiafenesin

Treat the cause, use combinations!

How important is sinus imaging

• Consider in cough patients with postnasal

drip unresponsive to treatment

• Consider in cough patients who are

smokers

• Sinus XRay vs Sinus CT

• Sinus: Limited vs Full CT

Sinusitis in children

• Paranasal sinuses

– Maxillary and Ethmoid sinuses are present at

birth

– Sphenoid and Frontal sinuses are

radiographically present by 5-6 yrs of age

Reflux Disease

• Cough and hoarseness are the major complaints.

• Heartburn, sour taste and regurgitation are unusual.

• Silent reflux in 50-75% cases

• H2-blocker alone may fail

• Remember: Diet, Weight reduction, etc…

The Clinical History of Reflux

• Diurnal variation– Cough on lying down - positional

– Decrease when asleep

– Wakes without cough

– Cough on rising

• With food– The act of eating

– Types of food

– Post prandial

Laryngopharyngeal Reflux

• Increasing incidence

• Hoarse voice

• Transient aphonia

• Globus (sensation of a lump in the throat)

• Persistent throat clearing

• Tickle in the throat or sticky sensation

Laryngopharyngeal Reflux

Pseudosulcus vocalis

Posterior commissure hypertrophy

Vocal fold edema

Ventricular obliteration

Koufman Score

If RFS >7, 95% PPV for LPR

Reflux Tests

• Laryngoscopy

• 24-hour Esophageal pH monitor

• Multichannel Intraluminal Impedance and manometry

• Bravo pH Probe

• EGD

• Barium Swallow

• Motility studies

• Aeriflux

24-hour esophageal pH monitoring

• Positive predictive value: 89%

• Negative predictive value: <100%

• Inconvenient for patients, ? interpretation of results in the diagnosis of cough

• Explore a temporal relationship between reflux and cough (keep a cough diary)

• Useful if therapeutic trial fails

Airway pH Measurement

• Aeriflux measures acid in the airway not in the

esophagus

• Collection system condenses exhaled breath

• Volatile acids from the airway are captured during this

condensation process

• If acids are exhaled at a time when coughing is

occurring, a direct relationship between reflux and cough

is established

Sleep apnea and GERD

• The phreno-esophageal ligament (PEL) connects the diaphragm to the LES.

• During the sleep apnea syndrome, there is increased respiratory effort by the diaphragm.

• This extra effort is transmitted to the LES by the PEL.

• This further leads to opening of LES and possibly reflux.

Is GERD as a cause of chronic

cough being overdiagnosed?

• Depending on flexible laryngoscopy to detect changes of LPR can lead to over-and under-diagnosis

• Acid versus non-acid reflux

• Role of barium swallow

• Role of EGD

• Multichannel Intraluminal Impedance and manometry

Reflux Disease- Management

• Diet and Lifestyle

• Weight reduction

• Treating sleep apnea

• H2 blockers

• PPI

• Properistaltic agents

• Avoid excessive exercise

Methacholine Challenge test

In a setting of adult chronic cough patients:

• Positive predictive value: 60-88%

• Negative predictive value: 100%

Asthma and Cough

• Bronchial inflammation causes vagal stimulation

• Asthma (and eosinophilic inflammation) ruled

out if MCT negative and no response to

prednisone 30 mg po qd for 2 weeks

• Consider adding leukotriene modifiers if

inadequate/no response to inhaled steroids

Asthma Eosinophilic

bronchitis

• Sputum eosinophilia

• Airway hyperresponsiveness

• Treatment is inhaled or oral steroids

• Sputum eosinophilia

• No airway hyperresponsiveness

• Treatment is inhaled or oral steroids

• Natural history unclear

• Initially reported in 1989

Eosinophilic bronchitis

How can physiologic alterations in

severe asthma promote reflux?

• Increase in transient LES relaxation

• LES hypotonia

• Esophageal dysmotility (due to autonomic

dysfunction in asthma)

• Asthma meds can increase LES dysfunction

(theophylline, oral beta agonists)

• Hyperinflation in asthma reduces crural

diaphragmatic support to the LES

Psychogenic/Habit cough

• More common in the childhood/teenage years

• Characteristically does not occur while sleeping

• Honking or barking cough may be diagnostically

helpful in kids, not in adults

• Rule out all possible causes first

• Treatment: Patient education, breathing

exercises

Irwin RS Chest 1998;114(suppl): 133S-181S

J Commun Disord 1988 Sep;21(5):393-400

How common is lung cancer in

chronic cough?

• Very rare (0 to 2%)

• CXR has a negative predictive value of

>95%, and a positive predictive value of

30 to 40%

Chest 1998;114(2):133s-181s

Treatment of Unexplained Cough

• Rule out all possible causes first

• Team approach- Allergy, Pulmonology, Otolaryngology, Gastroenterology, Speech Therapy, Behavioral Counseling

• Think outside the box- use lidocaine via nebulizer, nedocromil inhaler, baclofen, neurontin, Bromfenex, manage chronic pain, weight reduction, rule out sleep apnea

• Don’t give up too soon!

Work-up for chronic cough

• CXR

• Limited sinus CT

• Spirometry

• Methacholine challenge test

• Allergy skin tests

• Environmental control

• R/O occupational exposures

• Chest CT

• Neck CT

• Rhinolaryngoscopy

• Bronchoscopy

• 24-hour esophageal pH monitor

• EGD

• Barium swallow, etc.

Individualize the approach

Be cost-effective

Tips About Work-up

• Sinus XR can be false negative (consider limited CT sinus)

• CXR can be false negative (10%) in Interstitial Lung Disease (consider HRCT Chest)

• OK to get second opinion from another Radiologist if in doubt

• Just because a patient has seen ENT, don’t assume sinusitis is ruled out!

Therapeutic trials: When to expect a

response?

• Smoking cessation: up to 4 weeks

• ACE-inhibitor discontinuation: up to 4 weeks

• Postnasal drip syndromes: up to 2-3 weeks

• Asthma: up to 6-8 weeks

• GERD: up to 8-12 weeks

• Eosinophilic bronchitis: up to 3-4 weeks

Don’t give up too soon

What is the clinical utility of

flexible bronchoscopy

• Adds little to the diagnosis of chronic cough in

the context of normal CXR or HRCT Chest

• Useful to detect and assess endobronchial

lesions (tumors, foreign bodies)

• Always get a HRCT Chest before bronchoscopy

• If you are checking a HRCT Chest: include the

neck

Barnes TW, et al. Chest 2004;126:268-272

Cough Suppressant Therapy

Site of action Drugs

Mucocilliary clearance Guaiafenesin, Ipratropium

(Not tiotropium/spiriva)

Afferent limb of cough

reflex

Moguisteine,

Levodropropizine (Not

available in the US)

Centrally acting Codeine,

Dextromethorphan

Efferent limb Baclofen (GABA agonist)

reflux cough resistant for

PPI and ACEI cough

When to use cough suppressants

and expectorants?

Very rarely

• Some available over the counter

• Incurable lung cancer

• Codine, dextromethorphan (Delsym), TessalonPerles, Tussionex

• Guaiafenesin: ? decreases cough receptor sensitivity, loosens the mucus. Trial with 1200 mg twice daily for adults.

Nonpharmacologic Airway

Clearance Therapies

• Assisted techniques - Chest physiotherapy,

manually assisted cough, autogenic drainage,

respiratory muscle strength training

• Devices - Positive Expiratory Pressure,

Oscillatory Devices, Mechanical insufflation-

exsufflation, electrical stimulation of respiratory

muscles

• Beneficial in the short-term; long-term efficacy

and outcomes are unknown

Zebras to watch for

• “Clinically silent” suppurative airway disease

• Congestive heart failure

• Cancer: bronchogenic, esophageal, metastasis

• Cystic fibrosis

• Interstitial lung disease

• Foreign bodies

• Pneumonia, recurrent aspiration, pharyngeal dysfunction

• Sarcoidosis

Zebras to watch for, continued

• Pressure from an intrathoracic mass

• Primary ciliary dyskinesia (infertility)

• Lingual thyroid (hypothyroidism)

• Sleep apnea

• Vocal cord dysfunction (can cause post-viral cough)

• Pulmonary tuberculosis

• Bronchiectasis

• Chronic tonsillar enlargement

Vocal Cord Dysfunction

Vocal Cord Dysfunction

• Paradoxical vocal cord motion (PVCM)– Episodic laryngeal dyskinesia, VCM

– Vocal cord adduction during inspiration/expiration causing a functional extrathoracic airway obstruction.

– Symptoms include: wheeze, cough, dyspnea

– More common than is appreciated, diagnosis frequently not considered.

– Often confused with asthma and misdiagnosed.

– Much morbidity caused from misdiagnosis.• Newman et al studied 95 patients with proven PVCM

• Asthma was misdiagnosed an avg. 4.8 years, 28% intubated

Prevalence• General population is unknown.

– O’Connel et al, 164 patients

– Up to 20% of females who underwent rhinolaryngoscopy for any reason had PVCM.

• National Jewish Center, 1994, multiple patients diagnosed with refractory asthma:

– 10% had PVCM alone.

– 30% had PVCM with coexistent asthma.

• Patients diagnosed with PVCM:

– 56% had coexistent asthma.

• Because PVCM is common among asthmatics and presents with symptoms similar to those seen in patients with only asthma, it is commonly overlooked and not included in the differential.

Demographics

• In children under age 18:

– 2 studies at different institutions found:

• Average presenting age: 14.6 (range 9.0 – 18.0)

• 82-86% of patients female.

• Similarities among patients included: organized

sports, social stressors, exercised-induced

symptoms.

– Powell et al found strong association with GERD.

• Laryngospasm likely secondary to reflux irritation

but cause- effect relationship has not yet been

established

Demographics cont’d

• All age groups:– Average age at diagnosis 30 years (range 22-34)

– 70-98% of patients were female, Caucasian

• Documented psychological risk factors:– Medical profession, overweight, stress, anxiety,

childhood abuse, psychiatric illness.

– Increased incidence during wartime.

• Documented physiological risk factors:– Asthma, brainstem abnormalities, CF, GERD

Clinical Presentation

• Wide variety of symptoms including: – Cough

– Inspiratory/expiratory wheeze

– Dyspnea with/without exertion

– Stridor

– Hoarseness

– Chest tightness

– Reflux

• Study evaluating 90 patients with PVCM– Cough was the most common symptom - up to 77%

Clinical Presentation cont’d

• History significant for frequent, episodic attacks leading to SOB and multiple ER visits.

• Previous diagnoses include asthma, refractory asthma, exercise-induced bronchospasm, COPD, anaphylaxis.

• Children with PVCM have increased incidence of anxiety disorder compared to asthmatics.– Anxiety precedes respiratory symptoms in PVCM

– Anxiety follows respiratory symptoms in asthmatics.

Physical Exam

• Classical finding on laryngoscopic exam is inspiratory anterior vocal cord closure with posterior chinking.

• This obstruction decreases laminar airflow through the glottis and produces an inspiratory wheeze or stridorous sound similar to that heard in asthmatics.

• Differs from paralysis:– PVCM show normal cord movement during

phonation.

• Differs from laryngospasm: – Laryngospasm shows adduction throughout the

entire cord length without posterior chinking.

Posterior chinking

Other Physical Exam Findings

• Wheezing originates over the larynx and is less evident over the rest of the lung fields.

• Tachypnea with neck extension and constant contraction of the anterior neck muscles.

• Patients with or without concurrent asthma are often hypoxic and therefore may appear cyanotic during exacerbations.

• Spirometry with flow-volume loops have been used to support the diagnosis of PVCM in symptomatic patients.

• Flow-volume loops of patients with PVCM often show flattening of the inspiratory curve, or a decrease in maximal inspiratory flow during acute attacks, and are normal while asymptomatic.

PCVM

PFT studies cont’d

• Inspiratory blunting is sensitive for symptomatic patients with PVCM but is not specific for VCD and may be produced by most types of extrathoracic airway obstruction.

• Parker et al evaluated 26 patients with PVCM– exercise flow-volume loops indicated the upper

airway as a cause for symptoms in 74%

– 62% showed inspiratory flow limitation

• Primary use of PFT’s is to eliminate asthma from the differential diagnosis.

PFT studies cont’d

• Expiratory adduction and obstruction has been

shown by laryngoscopy in these patients without

evidence of expiratory flow-volume abnormalities.

– Mechanism unknown, pursed-lip exhalation

suspected

• Elevates soft palate to posterior nasopharyngeal wall

• Closes nasopharyngeal airway, increases resistance

• Creates sufficient back pressure to open vocal cords

and therefore shows no expiratory flow loop defect

Diagnosis• Difficult due to its episodic nature and presentation.

• Criteria for diagnosis:– Laryngoscopic confirmed adduction of vocal cords during

inspiration, early expiration, or both inspiration and expiration with evidence of posterior glottic chinking.

• adduction occurring during only the last half of expiration is not pathologic

– PVCM cannot be ruled out when asymptomatic.• if the patient is asymptomatic, negative laryngoscopic findings do

not exclude the diagnosis

– Absence of gagging or coughing during laryngoscopy• must not confuse PVCM with vocal cord motion produced by a

laryngoscope induced gag reflex

Treatment of VCD

• Acute treatment

– Heliox 70/30

– CPAP

– IPPV

– Benzodiazepines

– Panting exercises

– Reassurance

• Long term management

– Biofeedback training

– Supportive

psychotherapy

– Speech therapy

– Hypnotherapy

– Panting exercises