KMA Annual Meeting 2010 - Allergy - Wheeze, Crackle, POP: When its not Asthma/COPD

KY Society of Allergy, Asthma & Clinical Immunology
2010 KMA Annual Meeting
Sept 22, 2010

Wheeze, Crackle, Pop: When it’s not
Asthma/COPD
Rodney J. Folz, MD, PhD
Chief, Division of Pulmonary, Critical Care and
Sleep Disorders Medicine
University of Louisville School of Medicine

Uof L Division of Pulmonary, Critical Care, and Sleep Disorders Medicine

Disclosures
• Funding From:
• NIH
• American Heart Association
• Pfizer
• Merck
• Boehringer Ingelheim
• BioMarcks
• GlaxoSmithKline
• Cystic Fibrosis Foundation


Case 1
• 60 yo WF referred for 2nd opinion • Allergic rhinits
with chronic cough, asthma, and mild – Significantly improved with allergy shots
bronchiectasis. and medications

• CC • Mild asthma dx 15 years ago
– Well controlled, improved with allergy
– chronic cough
shots and ICS/LABA.
• Waxed and waned
• Minimally productive
• Mild recurrent sinusitis
– Normal sinus CT
– recurrent pneumonia every couple of
years, bronchitis over 34 yrs • Allergies:
– allergic rhinosinusitis and placed on – PCN, Sulfa, Ceftin, flagyl
immunotherapy – Lactose intolerant
– Ink, cats, dust, mold allergies
– bronchoscopy 6 years ago


Case 1
• Meds:
– montelukast
– ICS/LABA
– Albuterol
• FH: +recurrent bronchitis (mother)
• SH:
– Homemaker
– hobbies: print makeup with some exposure to solvents acetones/solvents
• PE: + bibasilar expiratory crackles


Adult Combined Skin Tests


Case 1

Mild obstruction


Typical Flow‐Volume Curve
Normal vs severe obstruction

Patient

Normal Severe obstruction


Case 1
• Findings:
– Coarse lung markings
within the base
– Prominent right
cardiophrenic fat pad


Case 1
• Findings:
– Scattered parenchymal
abnormalities
– Mild left base
bronchiectasis


Case 1

• Immunoglobulin levels • Fungal serologies: neg
– IGG 1180 • A1AT: 170
– IGA 152
– IGM 100
– IGE 246 (High)
• CBC, CMP, TSH, UA normal


What would you do at this point?

Active Diagnoses: DDx for Bronchiectasis
• Allergic rhinosinusitis • Pneumonia, recurrent
• Acquired airway obstruction (foreign
• Asthma / cough body, TB, airway adenoma, amyloid,
• Prior pneumonia ABPA, impaction, etc)
• Congenital airway obstruction
• Recurrent bronchitis – mild (bronchial cyst, sequestration,
• Mild bronchiectasis • Immuno deficiencies
• Chronic granulomatous disease
• Ciliary defects
• Recurrent aspiration
• Inhalation toxic fumes/dusts
• Cystic fibrosis


Pilocarpine Iontophoresis ‐ “Sweat Chloride”


CFTR Genotyping


Overview of Cystic Fibrosis
• Most common “lethal” genetic disease in Caucasian
population
– 1:3,300 Caucasian
– 1:29 Carriers mutant CFTR gene (more in other countries
e.g. N Ireland, Australia)
• Lower incidence in other populations
– 1:9,500 Hispanic
– 1:15,300 African‐American
– 1:32,100 Asian
• ~30,000 patients in U.S.
• Close to 50% of those with CF are now adults


History and Epidemiology
• 1938: “Cystic Fibrosis of the Pancreas” described by
Andersen
• 1950’s: Excessive salt loss in sweat recognized in heat
wave by di Sant’Agnese
• 1980’s: Specific ion transport abnormalities
described (Boucher, Knowles, others)
• 1989: CFTR cloned by Collins, Tsui groups
• 1990’s: New treatment strategies, gene therapy
• 2000’s: Pathophysiology, gene modifiers, standards
of care, quality improvement, novel treaments


Median Survival

CFF registry data

Adult with CF are increasing

CFF registry report 2007

Frequency histogram for age at
diagnosis for those >40 years

Median age at
diagnosis = 13
years

Rodman et al., AJRCCM 171:621-626, 2005


CF Genetics
• Monogenetic, autosomal
recessive
• Carriers are asymptomatic
• Affected gene
– Cystic Fibrosis Transmembrane
conductance Regulator” or CFTR.
• >1600 individual CFTR
mutations identified
• The ΔF508 mutation accounts
for 2/3 of CF alleles worldwide


CFTR Function

MSD - Membrane spanning domain
NBD - Nucleotide binding domain
R - Regulatory domain


CF Mutation Frequency


The Diagnosis of CF
• 71% diagnosed in 1st year of life
• 8% diagnosed after age 10
• 2% have Non Classic CF, which may not be
recognized until adulthood

• Diagnosis requires both:
– 1 or more typical phenotypic features and
– evidence of CFTR malfunction


With permission: N Eng J Med 347; 439-442: 2002

Overview: diagnostic criteria contd..

Laboratory evidence of CFTR dysfunction.
Elevated sweat chloride (>60 mmol/L)
Mutations in CFTR on both alleles
Characteristic bioelectric abnormalities
nasal PCD – research
Immunoreactive trypsinogen (IRT)
newborn screening


UofL / Kosair Cystic Fibrosis Center
PEDIATRIC PROGRAM ADULT PROGRAM
502‐629‐8830 502‐852‐5841
• Nemr Eid, MD • Rodney Folz, MD, PhD
– Pediatric Program Director – Adult Program Director

• Martha Eddy, RN • Kay Burris, RN
– Peds CF coordinator – Adult CF coordinator
• 502‐629‐7455 (office) • 502‐852‐1080 (office)
• 502‐629‐7540 (fax) • 502‐852‐1359 (fax)
• Dietitian • Dietitian
• Social Worker • Social Worker
• Respiratory Therapists • Respiratory Therapists


Case #2
• CC:
– 35 yo WF c/o referred for wheezing and cough, much worse following
“exposure” to noxious fumes.
• PMH:
– Asthma, 15+ years
– Recurrent hoarseness, SOA
– Multiple chemical sensitivities to fumes, odors, fragrances.
– MVR
– Recurrent URIs dating back 15+ years
– Tobacco use, 1‐2 ppd for 15 years. Significant second hand tobacco smoke
exposure as a child.
• FHx: CAD, DM, HTN, COPD, asthma


Case #2
• HPI:
– In USOH and claims while at a grocery store parking lot
was exposed to strong fumes from an acetic acid container
spill nearby.
– Examined in ED. CXR nl. ABG: pH 7.42, pCO2 38, pO2 102
– 10 days later underwent spirometry testing:
• 19% (610 ml) improvement in FVC
• 10% (260 ml) improvement in FEV1
– Had several “asthma exacerbations” treated with
ICS/LABA, oral corticosteroids.
– 6 months later underwent Challenge testing.


Spirometry pre and post albuerol MCh Case Studies

Post Bronchodilator
1. Is this asthma?
2. Is this RADs?


Several Questions
• Is this asthma?
• Is this RADs?


Exposures known to cause RADS


Minimally acceptable criteria ‐
Spirometry
• Have the patient assume the correct posture.
• Attach the nose clip, place mouthpiece in mouth and instruct patient to
close lips around the mouthpiece and breathe quietly.
• Instruct the patient to inhale completely and rapidly with little or no pause
(< 1 sec) at TLC.
• Instruct patient to exhale maximally until no more air can be expelled.
• Repeat instructions as necessary, coaching vigorously during the
expiratory maneuver.
• Repeat for a minimum of 3 acceptable maneuvers, no more than 8 are
usually required.
• Check test repeatability and perform more maneuvers as necessary.


Between maneuver repeatability
criteria for spirometry
• After a minimum of 3 acceptable FVC maneuvers have been
obtained:
– The 2 largest FVCs are within 0.15 liters of each other.
– The 2 largest FEV1s are within 0.15 liters of each other.
• If both of these criteria are not met, continue testing until
– Both of criteria are met with additional acceptable maneuvers, OR
– A total of 8 maneuvers have been performed, OR
– The patient cannot or should not continue.


MCh Case Studies


Spirometry did not meet ATS standards

Pre Post


Should we order MCh Challenge Testing?
Questions:
1. Is this a positive Mch challenge test?
2. Does this patient have bronchial hyperreactivity?
3. Does this patient have asthma or RADS?

80%

baseline diluent MCh 1 mg/dl Albuterol #1 Albuterol #2


Asthma: Four Domains
1. Symptoms • No one domain is essential for
2. Variable airway obstruction the diagnosis.
3. Airway hyperresponsiveness • Primary care mostly uses
4. Airway inflammation symptoms to diagnose asthma
can lead to incorrect diagnoses
• Increasing awareness of different
asthma phenotypes and
associated response to
treatments.


Measurements of
Bronchial Hyperresponsiveness (BHR)
1. Methacholine Challenge Testing (MCT)
2. Exercise Induced Bronchoconstriction (EIB)
3. Challenge testing can also be performed at specialized centers using:
• Allergens
• Histamine
• Drugs
• cold air
• occupational sensitizers
• Eucapneic hyperventilation


MCT indications
• When asthma is a serious • Determine relative risk of
possibility and traditional developing asthma
methods unable to establish • Response to therapy
the diagnosis. • Clinical research trials
– Wheezing, chest tightness,
dyspnea, cough following:
• Cold air exposure
• Exercise
• URI
• Work place exposure
• Allergen exposure


Contraindications for MCT


Technician Training Qualifications
• Be familiar with this guideline and • Know when to stop further
knowledgeable about specific test testing
procedures
• Be proficient in the
• Be capable of managing the administration of inhaled
equipment including set‐up, bronchodilators and evaluation of
verification of proper function, the response to them
maintenance, and cleaning
• 4 days of hands on training
• Be proficient at spirometry
• Minimum of 20 supervised tests
• Know the contraindications to
MCT

• Be familiar with safety and
emergency procedures


Safety Considerations ‐ Patients
• Patient • 700 histamine challenge
• 20% cough, chest tightness, or
– Acute bronchospasm flushing
– Hypoxia • Delayed effects are rare
– V/Q mismatch • No deaths
• 1000 COPD patients ‐ MCT
• 25% cough
• 21% dyspnea
• However, there have been
• 10% wheezing
fatalities reported with
• 6% dizziness
– antigen challenge
• 2% headache – distilled water challenge.
• 2/3 no symptoms


Safety Considerations ‐ Technician
• Technician English Wright Nebulizer
– Minimize exposure to aerosol
– 2 exchanges per hour
– Extra precautions or
avoidance in technicians with
asthma.
– Use of HEPA cleaner.

DeVilbiss model 646 nebulizer


Safety Considerations
• Technician English Wright Nebulizer

– Survey of 600 allergy
specialists:
• 20% report symptoms
• 2 cases of asthma in
nurses who use MCh

DeVilbiss model 646 nebulizer


Factors that influence MCT results
• Excellent sensitivity • BHR is also seen in:
• Mediocre positive • COPD – tobacco induced
• CHF
predictive value
• CF
• Bronchitis
• Allergic rhinitis
• Sarcoidosis
• Bronchiectasis
• Siblings of asthmatics


Environmental factors that enhance bronchial hyper‐
responsiveness and their duration of effect


Agents that decrease bronchial hyper‐responsiveness
and their duration of effect


MCh Dosing Protocols
2 Methods
• 2 min tidal breathing • 5 breath dosimeter
– Recommended by the – Standardized by NIAID
Canadian Thoracic – Uses quadrupling doses
Society. of MCh
– Uses doubling doses of • 0.0625, 0.25, 1, 4, 16
MCh mg/dl
• 0.03, 0.06, 0.125, 0.25, – Perform 5 inhalations
0.5, 1, 2, 4, 8, 16 mg/dl from FRC
– Perform 2 minutes of
tidal breathing from FRC


Advantages / Disadvantages
• 2 min tidal breathing • 5 breath dosimeter
– Allows more precise steps – Quicker method
– More commonly used by – Reduced MCh exposure to
clinical research protocols. technician
– May shorten overall time by
starting at 1 mg/ml if no
history of asthma
– May omit next dose if < 5%
drop in FEV1


Interpretation strategies
• Factors to consider when interpreting PC20
– Pretest probability of asthma
– Presence or degree of baseline airway obstruction
– Quality of patient’s spirometry maneuvers
– Symptoms reported by patient at end‐of‐test
– Degree of recovery after bronchodilator


Interpretation Strategies
Categorical Method Decision analysis


MCh Case Studies
• EH
• 65 yo WF
• 20 py
• Referred for
– chronic cough
• Normal PFTs
• BMI 29

• BH
• 60 yo WF
• Never smoke
• Referred for
– chronic cough and dyspnea
• Normal spirometry
• BMI 32


MCh Case Studies
• EC
• 63 WF
• Never smoke
• Referred for:
– SOB, DOE
• BMI 33

• PH
• 43 WF
• Never smoke
• Referred for:
– Sarcoidosis, cough
• BMI 33


Methacholine challenge
Poor QualityStudy:
1. Started at 1 mg/dl MCh.
2. Constricted with first dose albuterol.
3. Second dose albuterol had opposite effect.

80%

baseline diluent MCh 1 mg/dl Albuterol #1 Albuterol #2


Case Presentation
Does this patient have Exercise-
Induced Bronchoconstriction (EIB)?
14 minutes treadmill
Heart rate 200 bpm

14 yo WF presents with:
Intermittent cough a/w exercise
Intermittent chest tightness a/w exercise
Seasonal allergies
Otherwise completely healthy
Antihistamines and Singulair not helpful


EIB ‐ Indications
1. Evaluation of breathlessness during or after exertion
2. When EIB would impair a person (with a history
suggestive of asthma) to perform demanding work
1. Lifeguard
2. Firefighter
3. military or police

3. Determine effectiveness and optimal dosages of
medications used to treat EIB
4. Evaluate effects of antiinflammatory therapy


EIB ‐ Mechanism
• The major factors that determine the severity of EIB are:
• the pulmonary ventilation reached and sustained
• water content and temperature of inspired air
• The stimulus for airway narrowing is
• Rapid loss of water
• The mechanisms involved are:
• Thermal and /or osmotic effects of dehydration and cooling
• Stimulates release of inflammatory mediators
» Histamine
» cysteinyl leukotrienes)


EIB ‐ Contraindications


EIB – patient prep
• Wear comfortable clothes and gym shoes
• Light meal
• Avoid vigorous exercise for > 4 hours
– Prior exercise exerts protective effect.
– 50% of EIB are refractory to second challenge with 60
minutes.


Treadmill versus Cycle Ergometers


Exercise Challenge Testing Protocol
• Patient breathes dry air in air conditioned room.
• Target 4‐6 minutes of near‐maximum exercise, total duration
6‐8 minutes.
• Advance exercise to reach 80‐90 Max HR in 2‐3 minutes. (220
– age).
• Alternatively target work rate in watts
» (53.8 X FEV1) – 11.07

• Valid test requires:
• Exercise intensity sustained for 4‐6 min
• Reach target HR within 4 minutes
• Monitor HR, O2 Sats, EKG


Assessing Response
• FEV1 is primary outcome variable.
• Assess at 5 min, 10 min, 20 or 30 min.
• Decrease from baseline FEV1 of 10% is a generally
accepted as an abnormal response.
• A fall of 15% appears more diagnostic of EIB.
• Healthy subjects generally increase FEV1.
• Nadir FEV1 occurs most often within 5‐10 minutes.


Case Presentation
• 14 yo WF presents with:
• Intermittent cough
• Intermittent chest tightness 14 minutes treadmill
Heart rate 200 bpm
• Seasonal allergies
• O/W completely healthy
• Antihistamines and Singulair not helpful


EIB therapeutic options
• Improve control of underlying concomitant asthma.
• Patient education.
• Improve cardiovascular fitness.
• Breath through scarf or mask to warm/humidify air.
• Prophylactic SABA
• Prophylactic mast cell stabilizers.
• Antileukotriene agents
• Diet enriched with omega‐3 fatty acids


Thank you for your attention


KMA Annual Meeting 2010 - Allergy - Wheeze, Crackle, POP: When its not Asthma/COPD

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