Term
| Know the flow-volume loop patterns for fixed and variable obstruction, both extra and intra thoracic. |
|
Definition
Fixed (regardless of location) looks like an old-fashioned TV screen (square with rounded corners)
Variable extra thoracic obstruction: Looks like a sail on a sailboat (expiratory flow is much greater than insp flow). This is the pattern seen in vocal cord dysfunction.
Variable intrathoracic obstruction: looks like an iceberg (Exp flow is much less than insp flos) |
|
|
Term
COPD Risk and Smoking Cessation:
What is the effect of stopping smoking at age 45 vs 65? |
|
Definition
Stopping at 45 results in mild COPD (delayed onset of FEV1 meeting criteria for disability) vs stopping at 65 (which greatly reduces the time for FEV1 to progress from disability to death).
Note: smoking regularly causes the steepest drop in FEV1. |
|
|
Term
1. What is the spirometric definition of airflow obstruction?
2. What are the ATS criteria for a "positive bronchodilator response"? |
|
Definition
1. FEV1:FVC < lower limit of normal
OR
FEV1:FVC < 0.7
2. Change in FEV1 of 12% or more and 200 ml or more |
|
|
Term
1. Know the relationships of lung volumes: TLC, IC, FRC, VC, IRV, TV, ERV, RV
2. Know how these volumes are altered in obstructive vs restrictive lung diseases. |
|
Definition
1. TLC = IC + FRC
TLC = IRV + TV + ERV + RV
TLC = VC + RV
2. Obstruction: TLC, FRC and RV are increased.
3. Restriction: TLC, FRC, RV and VC are decreased. |
|
|
Term
Which enzymes do NSAIDs and ASA inhibit?
Know the effects of LTE4 in the airway of an asthmatic |
|
Definition
Cyclooxygenases (COX-1 and COX-2). The degree of sensitivity to NSAIDs is proportional to the concentration of NSAID required to inhibit COX-1 in vitro.
Bronchoconstriction, vasodilation, mucus secretion, eosinophil chemotaxis |
|
|
Term
COX inhibitors
1. Which drugs are weak inhibitors?
2. Do the highly selective COX-2 inhibitors cause sx in AERD patients? |
|
Definition
1. Acetaminophen and salsalate. In small doses, they can be given with little chance of adverse rxn. In high doses, respiratory rxns have been reported.
2. No (Rofexoxib, celecoxib) |
|
|
Term
| What are the clinical benefits of ASA desensitization? |
|
Definition
Reduction in:
1. asthma/resp disease
2. recurrence of polyps/need for sinus surgery
3. hospitalizations for asthma
4. need for systemic steroids
5. anosmia (olfaction improves) |
|
|
Term
AERD vs urticaria/angioedema
1. Do these have the same mechanism?
2. Does desensitization for CIU work? |
|
Definition
1. No
2. No, desensitization for CIU is "impossible to sustain" |
|
|
Term
Know the agents administered in direct and indirect bronchial challenges
Know which challenge agents are considered to be "selective" |
|
Definition
Direct: Methacholine, histamine, prostaglandins, leukotrienes
(Direct agents act directly on airway smooth muscle receptors.)
Indirect: Exercise, Eucapnic Voluntary Hyperpnea/Hyperventilation, Cold Air Hyperventilation, Distilled water, Hypertonic saline, Mannitol, Adenosine monophosphate, Bradykinin, Propranolol
(Indirect stimuli act thru release of mediators from inflammatory cells, mostly mast cells).
Selective agents include allergens, occupational sensitizers, ASA, NSAIDs, ?food additives |
|
|
Term
| Bronchial challenges can be used to... |
|
Definition
1. Clarify dx of asthma
2. Quantify severity of asthma
3. Determine/compare utility of controller meds
4. Determine/compare duration of action of drugs
5. Understand mechanisms of asthma
6. assess airway reactivity
7. Evaluate for occupational asthma |
|
|
Term
Know the benefits and risks for using methacholine vs histamine in bronchial challenge.
Should you dilute methacholine in normal saline or phosphate-buffered saline? |
|
Definition
Methacholine and histamine are nearly equipotent.
Methacholine-obtained measurements seems to be more reproducible. However, methacholine can be assoc with prolonged bronchoconstriction.
Methacholine is preferred b/c it has less side effects. Histamine causes headache, flushing, tachycardia, hoarseness. At high concentrations, histamine precipitates out of solution. Also, tachyphylaxis occurs with repeated histamine challenges. Histamine inhalation reduces airway responsiveness to other stimuli, like exercise and acetylcholine.
Use normal saline (methacholine is unstable when diluted in phosphate-buffered saline) |
|
|
Term
| What cutoff for FEV1 should be used as a contraindication to performing bronchial challenge with histamine or methacholine? |
|
Definition
|
|
Term
Which factors enhance bronchial responsiveness to histamine or methacholine?
Which factors lessen the response to histamine or methacholine? |
|
Definition
1. Enhance: recent exposure to allergen, occupational agent, ozone/pollutants and recent viral resp infxn
Reduce: Avoidance of allergens, occup agents; bronchodilators (beta agonists, theo), antihistamines, anticholinergics, regular steroid use, previous histamine inhalation (tachyphylaxis) |
|
|
Term
Mannitol Bronchial Challenge
Know the procedure |
|
Definition
Available as pre-packaged capsules and DPI (Osmohaler RS01). Start with empty capsule, measure FEV1 twice 1 minute after each dose, starting with empty capsule< until there is a 15% fall in FEV1 or a cumulative dose of 635mg of mannitol has been inhaled.
Assess recovery 10 minutes after beta agonist administration. |
|
|
Term
Mannitol Bronchial Challenge
1. What is a positive test?
2. What does a positive test predict?
3. What does a negative test tell you? |
|
Definition
1. Positive test = FEV1 falls at least 15% at a cumulative dose of 635mg of mannitol.
2. Predicts who is likely to be an ICS responder
3. Tells you that inflammation is probably not present...either asthma is very mild or well controlled. For the patient already on ICS, it also can help guide ICS taper. |
|
|
Term
| 1. What are the effect of beta agonists, nedocromil, cromolyn, montelukast, fexofenadine, loratadine on mannitol challenge? |
|
Definition
| All reduce responsiveness to mannitol. Mannitol inhalation is assoc with release of prostaglandins and leukotrienes; this release can be inhibited by beta agonists and cromolyn |
|
|
Term
What is a :
1. Normal PC20
2. Borderline PC20
3. Positive PC20
Are the cutpoints the same in kids? |
|
Definition
1. PC20 > 16 mg/ml
2. PC20 btwn 4 and 16 mg/ml
3. PC 20 below 4 mg/ml (3-4 mg/ml is the standard cutoff)
Yes, the cutpoints are the same for kids and adults. |
|
|
Term
| When is the best time to do bronchoprovocation? |
|
Definition
| During periods of active symptoms or current exposures (such as to allergen, occupational agents) otherwise, it is difficult to interpret a negative methacholine challenge. |
|
|
Term
| To which agents do patients with COPD have increased responsiveness: direct or indirect agents? |
|
Definition
|
|
Term
| What is the impact of baseline airway obstruction on the interpretation of a positive methacholine challenge |
|
Definition
| Airway hyperresponsivenss is highly correlated with degree of obstruction (FEV1 reduction), so it is hard to interpret a positive challenge when patient is obstructed at baseline. |
|
|
Term
| How long should a patient exhale for a spirometric test to be considered valid? |
|
Definition
| 6 seconds (less than 6 seconds is considered invalid) |
|
|
Term
| Which causes of occupational asthma are best assessed with bronchial challenge? |
|
Definition
| Diisocyanates and plicatic acid (Western Rd Cedar) |
|
|
Term
| Which causes of occupational asthma are best assessed with bronchial challenge? |
|
Definition
| Diisocyanates and plicatic acid (Western Rd Cedar) |
|
|
Term
| Indications for bronchial challenge with allergen |
|
Definition
Mostly used as a research tool.
1. Clarify role of a specific allergen in asthma
2. Assessment of allergic reactivity when skin tests cannot be performed
3. Comparisons for other standardized procedures (like skin tests, in vitro tests)
4. To determine mechanisms, such as mediators released
5. Determination of new or provocative allergens in pulm disease
6. Evaluation of treatment modalities (medications, immunotherapy) and blocking agents
7. convince patient of cause and effect relationship |
|
|
Term
Does a negative methacholine challenge rule out EIB?
What is the preferred method to assess for EIB? |
|
Definition
No
Exercise challenge is preferred. |
|
|
Term
1. How do the tidal breath and TLC inhalation methods compare?
2. What is the effect of using TLC inhalation during bronchial challenge? (i.e. why is the tidal breath method preferred?) |
|
Definition
1. They are about the same in persons with mild, moderate or severe airways hyperresponsiveness. However, TLC method causes bronchoprotection in asthmatics with very mild AHR and can therefore yield false negative result.
2. Bronchoprotection |
|
|
Term
| Know the relationship between severity of airways hyperresponsiveness and severity of asthma |
|
Definition
| Low PD20 does not equate with severe asthma. |
|
|
Term
Which agents are more specific for differentiating asthma from COPD/other causes of chronic airflow obstruction, direct or indirect stimuli?
Which stimuli, direct or indirect, correlate better with airway eosinophilia? |
|
Definition
Indirect stimuli
Indirect challenges correlate better with airway eosinophilia and imrpove more with anti-inflam therapy. |
|
|
Term
| What is the mechanism of bronchoconstriction in bronchial challenges using hyperventilation? |
|
Definition
| Osmotic challenge (excessive drying of the airway) just like in exercise challenge/EIB and hypertonic saline challenge. |
|
|
Term
| What is the mechanism of bronchoconstriction in adenosine (AMP) challenge? in mannitol challenge? |
|
Definition
AMP: non-osmotic release of mast cell mediators
Mannitol: osmotic challenge |
|
|
Term
True or false: direct challenges have a high negative predictive value.
What are the causes for false negative and false positive challenges? |
|
Definition
True. Direct challenges have high sensitivity. They rule out asthma with reasonable certainty. False negative methacholine challenges are seen in:
-elite athletes
-use of bronchodilators, inc meds with anticholinergic effects, like antidepressants, antipsychotics
-lack of current exposures or symptoms
-inhalation of methacholine by TLC breathing method
False positives:
-normal (5-15% of normal pop)
-rhinitis (20-40% of rhinitics)
- mild, subclinical or latent asthma |
|
|
Term
| Does methacholine challenge predict response to asthma therapy in persons with isolated cough and nl lung fxn? |
|
Definition
No. You can see normal methacholine challenge in persons with eosinophilic bronchitis, a common cause of cough and a condition in which corticosteroids are effective.
Therefore, in someone with isolated cough and normal lung function, a diagnostic trial of ICS or oral steroids is reasonable to do before doing a bronchial challenge. |
|
|
Term
| True or false: in contrast to the direct stimuli, indirect stimuli are highly specific but not very sensitive. |
|
Definition
True. Indirect stimuli confirm asthma dx but do not exclude dx of asthma.
Indirect challenges are valuable in the investigation of EIB. |
|
|
Term
| What is the role of methacholine challenge in occupational asthma? |
|
Definition
1. To confirm that person has asthma
2. To follow airway hyperresponsiveness to assess adequacy of environmental control
3. To assess for disability or impairment. |
|
|
Term
How long should the following meds be withheld prior to bronchial challenge? and for which type of challenge?
1. SABAs
2. LABAs
3. Ipratropium
4. Tiotropium |
|
Definition
1. SABA: 6-8 hrs prior to any challenge
2. LABA: 24 hours prior to any challenge
3. Ipratropium: 8 hrs prior to methachol
4. Tio: at least 48 hrs prior to methacholine |
|
|
Term
| What is the relevance of airway hyperresponsiveness (AHR) in terms of asthma prognosis? |
|
Definition
| AHR in infancy and childhood is correlated with persistence and severity of asthma in adulthood. |
|
|
