Asthma and Allergic Disease Flashcards
According to GINA guidelines for adults and adolescents, what is the preferred initial therapy for infrequent asthma symptoms and no risk factors for exacerbations?
ICS-formoterol PRN
According to GINA guidelines for adults and adolescents, what is the preferred initial therapy for asthma symptoms or need for reliever 2x/mos or more?
Low dose ICS + SABA PRN
OR
ICS-formoterol PRN
According to GINA guidelines for adults and adolescents, what is the preferred initial therapy for troublesome asthma symptoms?
low dose ICS-LABA maintenance and reliever OR maintenance only low dose ICS-LABA OR Medium dose daily ICS
According to GINA guidelines for adults and adolescents, what is the preferred initial therapy for severe initial presentation or acute exacerbation?
Regular controller with high dose ICS or medium dose ICA-LABA
Consider course of oral steroids
According to GINA guidelines for children 6-11, what is the preferred initial therapy for infrequent symptoms less than 2x/mos?
as needed SABA
OR
ICS whenever SABA is taken
According to GINA guidelines for children 6-11, what is the preferred initial therapy for asthma symptoms or reliever use 2x/mos or more?
low dose ICS + SABA PRN
According to GINA guidelines for children 6-11, what is the preferred initial therapy for troublesome symptoms most days?
Low dose ICS-LABA + SABA PRN
OR
Medium dose ICS + SABA PRN
According to GINA guidelines for children 6-11, what is the preferred initial therapy for severe asthma symptoms?
Medium dose ICS-LABA
3 elements of severe asthma definition as per CTS statement
1) Asthma diagnosis confirmed by history and objective measures
2) Treatment needed = high dose ICS and second controller for previous year/oral steroids>50% in last year (asthma either uncontrolled despite these or needing the above for prevention of loss of control)
3) Environmental factors, comorbidities, adherence and inhaler technique addressed before labelling as severe asthma
Criteria for uncontrolled asthma
1) CTS asthma control criteria ACQ >1.5 or ACT or cACTn >20
2) Frequent (>2) exacerbation needing oral steroids
3) 1 or more severe exacerbation needing ICU or mechanical ventilation
4) FEV1 <80% with low ratio
CTS asthma control criteria (9)
1) Daytime sx < 4 days per week
2) Nighttime sx <1 night per week
3) Physical activity = normal
4) Exacerbations = mild, infrequent
5) Absence from work or school due to asthma: none
6) Need for SABA < 4 doses per week
7) PEF or FEV1 >90% of personal best
8) PEF diurnal variation <10-15%
9) Sputum eosinophils <2-3%
Uses for FeNO
1) Diagnose eosinophilic airway inflammation
2) Predict steroid responsiveness
3) Monitor treatment
4) Indicate non adherence to steroid therapy
3 isoforms for nitric oxidate synthetase (NOS)
1) Neuronal (nNOS)
2) Inducible (iNOS)
3) Endothelial (eNOS)
Upregulators for iNOS
TNF-alpha IL-1 beta IFN gamma IL-4 IL-13
FeNO levels in adults and children below which implies no eosinophilic airway inflammation and non responsiveness to steroids
Adults: <25 ppb
Children <20 ppb
What is considered a significant change in FeNO between visits?
Delta of 10% (values <50) and delta of 20% (>50)
What are the lower cutoffs for FeNO?
20 and 25 (>12yrs)
What are the upper cutoffs for FeNO?
35 and 50 (>12 yrs)
If an asthma patient as FeNO <20 and symptoms, how do you treat?
May not benefit from steroids and implies non-eosinophilic inflammation. Look for other cause
If an asthma patient as FeNO <20 and no symptoms, how do you treat?
can wean ICS and repeat FeNO after 4 weeks
If an asthma patient as FeNO <50 (or children >35) and symptoms, how do you treat?
check adherence and inhaler technique, assess for allergen exposure, may need to increased ICS
If an asthma patient as FeNO >50 and no symptoms, how do you treat?
no change in ICS, may relapse on weaning
If an asthma patient as FeNO 20-35 and no symptoms, how do you treat?
no changes in treatment
If an asthma patient as FeNO 20-35 and symptoms, how do you treat?
assess allergen exposure, check adherence, consider increasing ICS
Causes of normal FeNO in asthma (4)
1) Adequately treated with steroids - no sx
2) Technical faults - constant expiratory flow not maintained
3) Smoking can cause lower FeNO levels
4) Non eosinophilic asthma (steroid resistant)
Asthma, 3 cytokines targeted for treatment.
IL-4, IL-5, IL-13 (Th2 cell)
What has been demonstrated as indirect evidence of inflammation in asthmatics?
Elevated eNO
Lowered pH of lung condensate
Peripheral blood eosinophilia
General acceptance for asthma as an inflammatory dx due to:
- Evidence for steroid effectiveness
- Reversibility of BHR (bronchial hyper-reactivity) with prolonged allergen avoidance
Allergens assoc w/ Asthma
Mostly indoor-perennial or outdoor allergens with a long season
Dust mites = ++ important cause of sensitization
Perennial indoor allergens = associated with more severe asthma
Pollen allergies - generally assoc w/ less severe asthma
Molds may play a role - Alternaria and Aspergillus (ABPA) implicated
Factors implicating allergen deposition into lungs
Aerodynamic size affects both speed at which particles fall and deposition in the lungs
Particles <5um reach the alveoli needed to reach alveoli
Larger particles → bronchi; may cause allergy more effectively → carry more allergen
Mold spores (ie Aspergillus) = different than other particles - firm outer surface does not release protein rapidly, allergens often not expressed until spores germinate
Relationship with Asthma and IgE
Increased risk of acute asthma seen w/ both total serum IgE OR allergen specific IgE > 10 IU/ml
Interaction Btw Viral Infection & Allergic Responses in Children w Acute Asthma Episode
Viral illness = precipitant of asthma episodes
Children <3 yrs - essentially any virus can lead acute episode of asthma or bronchiolitis
(Major RF for wheeze in this population is small lung size at birth)
Children >3yo: Rhinovirus = main virus assoc with acute
episodes, AND the children are highly allergic (↑IgE)
Rhinovirus provoked wheezing stronger RF for subsequent wheezing by 6 years than RSV induced wheezing
Relationship between Rhinovirus and Asthma (mechanism)
Rhinovirus causes ↑ blood & nasal eosinophils, ↑ exhaled NO, ↓ exhaled pH
Response is more marked in asthmatic individuals with high IgE (>200IU/mL)
Unclear if asthma response 2° to viral infiltration of lungs OR events in nose trigger events in the lung e.g. cytokine/cell mediated effects
Studies suggest viral infections in atopic children initiate an atopy-dependent cascade that then amplifies and sustains airway inflammation –>exacerbation/loss of control
What can an Allergen challenge in an Allergic subject produce?
FEV1 ↓↓s w/n 15-min of allergy challenge Late responses include: - Eosinophil infiltration, - prolonged BHR -Mast cell release --> histamine, Platelet activating factor (PAF); IL-5
Mechanism of Treatment with Monoclonal Antibodies to IgE in Asthma
Monoclonal antibodies to the antigenic site on human IgE that binds to the receptor for IgE (FcεRI)
- only binds to free IgE that is not bound to mast cell or basophil → major benefit in some children
Changes in the lungs of children with asthma
Acellular infiltrate
Excess mucus production
Collagen deposition
Irritability of smooth muscle
The mechanism of this response involves a cascade of leukotrienes, prostaglandins, cytokines and chemokines → potential targets for therapy.
Key points regarding immunology and asthma (from Kendig chapter)
1) Treatment of asthma in children >3yrs focus = long-term anti-inflammatory Rx
2) Majority of those allergic = allergic to some allergen within their home (contributes to both sensitization AND asthma)
3) Viral infections = important in provoking wheezing exacerbation
4) Elevated IgE = strong assoc w/ asthma (These have been assoc w/ ↑specific AND total IgE.)
5) Targeted therapy (anti-inflammatories, allergen avoidance or immunotherapy, future tx directed at altering immune response)
Definition of Asthma
Asthma is a disease characterized by an increased responsiveness of the trachea and bronchi to various stimuli and manifested by a widespread narrowing of the airways that changes in severity either spontaneously or as a result of therapy
Characterized by variable, reversible obstruction of airflow, which may
improve spontaneously or after specific therapy
Characteristics of asthma in infancy
It most commonly presents in infancy with a viral RTI that causes lower airway inflammation with consequent wheezing and coughing known as bronchiolitis
Association of Rhinovirus and Asthma
Less commonly the cause of the initial episode may be even more likely associated with subsequent recurrent wheezing.
If a parent has asthma, chances of child having it
~25%
Pathology features of asthma
Increased thickness of reticular basement membrane and increased eosinophil density
1) Eosinophilia
2) Mucous plugs
3) Mucosal Edema
4) Mast cells
5) Thickened basement membrane (type 4 collagen deposition)
2 groups of early childhood asthma
1) non-atopic intermittent viral respiratory infection
2) chronic atopic asthma
Characteristics of non-atopic intermittent viral respiratory infection-induced asthma group
Predominates in infants and children.
Show no evidence of airway inflammation in children with a history of intermittent non-atopic asthma during their symptom-free periods.
Symptomatic preschool age non-atopic asthmatic children have predominantly noneosinophilic airway inflammation .
Characteristics of chronic atopic asthma group
More commonly in older children and adults.
Airway inflammation seems to persist in patients with atopic asthma, even when they are asymptomatic.
Eosinophilic airway inflammation characteristic of atopic children with asthma
Major cause of asthma exacerbations
Viral infections
Appear to be the major RF for the large increase in hospital admissions for asthma that occurs in the fall months.
The smaller airways in the young child are also more easily obstructed by inflammation associated with a viral respiratory infection, which is a likely contributing factor to increased hospitalization
Which group is more likely to have persistent symptoms over time?
Most preschool-age children with asthma remit or greatly improve by school age, those with evidence for atopy (i.e., the predisposition to make IgE antibody to major inhalants) are most likely to continue having a substantial frequency of asthmatic symptoms
Clinical presentation of asthma
Expiratory wheezing, and dyspnea.
Wheezing, is defined as musical, continuous sounds that originate from oscillations in narrowed airways.
Recurring lower respiratory symptoms consisting of cough, labored breathing, and expiratory wheezing are consistent with a diagnosis of asthma.
Clinical presentation of acute asthma exacerbation
Labored breathing with intercostal and suprasternal and substernal retractions may be present.
Physical findings:
- Polyphonic expiratory wheezing as a manifestation of diffusely narrowed small airways.
- Coarse crackles can be present from mucous in the larger airways.
- Hypoxemia from V/Q mismatching in early course of acute asthma with decreased PCO2 resulting from the increased hypoxic ventilatory drive.
- A rising PCO2 is an indication of impending respiratory failure.
CXR: atelectasis, peribronchial thickening
Diagnoses to consider when cough, wheeze or laboured breathing in the preschool age child is not consistent with asthma
Aspiration syndromes Bronchomalacia BPD PBB Compression of the airway from aberrant vessels CF FB in airway or esophagus PCD Pertussis Tracheal polyps Tracheomalacia VCD
Three distinct clinical patterns of asthma that can be seen in childhood
Intermittent (most common in preschool)
Chronic
Seasonal allergic.
Characteristics of Intermittent Asthma pattern
- Symptoms occur exclusively following viral RTI, these children are completely free from symptoms during the intercurrent periods.
- The major contributors to the high hospitalization rate in this age group
- an absence of specific IgE to major inhalant allergens is generally predictive of a viral respiratory infection– induced pattern
- Exam normal in between episodes
Characteristics of Chronic Asthma pattern
- Associated with persistent symptoms
- These children have daily or near daily symptoms of asthma, even between exacerbations.
- Have evidence for specific IgE to inhalant allergens.
2 components of asthma treatment
measures used to stop acute asthma symptoms, and maintenance medication to prevent attacks.
2 medications that are used for exacerbations
Bronchodilators and systemic corticosteroids are the major medications used for acute symptoms.
β2-adrenergic bronchodilator, provides rapid airway smooth muscle relaxation, which relief the bronchospastic component of the airway obstruction but have no effect on the progression of the process that results from inflammation.
Additional options for acute asthma exacerbation after SABA and steroids
Theophylline, magnesium and IV beta agonists
Systemic corticosteroids are potent anti-inflammatory agents for asthma and have long been recognized as effective for treating acute exacerbations.
Studies demonstrated that earlier aggressive systemic corticosteroids in children with an acute exacerbation decrease urgent medical care and hospitalization.
