Chapt. 7: Asthma Flashcards
Common but complex clinical syndrome affecting people of all ages, characterized by variable airflow obstruction, bronchial hyperresponsiveness and airway inflammation, and manifesting as differing phenotypes.
Asthma
Burden of disease of asthma?
Affects 300million individuals of all ages worldwide, comprising 1-18% of the population in different countries
Are fundamental to the definition of asthma, but are rarely measured in primary care?
Airway inflammation and Bronchial Hyperresponsiveness
Used to demonstrate the presence and reversibility of airflow obstruction, and patient-held peak expiratory flow (PEF) meters can be used to show variable airflow obstruction over a period of time (eg. 2-4 weeks)
Spirometry
The principal mechanism of asthma and the main treatment target.
Airway inflammation
Typical features of airway inflammation in asthma?
Increased eosinophils, mast cells, and lymphocytes and predominance of type 2 helper T lymphocytes (Th2 cells).
What is produced by Th2 cells?
IL-3, IL-4, IL-5, IL-13 and GM-CSF
What phenotype of asthma exhibits only few inflammatory cells?
pauci-granulocytic phenotype
What characterizes asthma?
Structural changes in the airway that may precede the development of asthma, including epithelial damage, subepithelial fibrosis, increased airway vasculature, and increased smooth muscle mass.
Mucous hypersecretion is associated with what?
With an increase in the number of secretory glands and goblet cells
What is the prevalence of asthma?
3-5% in developing countries to >20% in developed countries, affecting people of all ages
Allergic type asthma is frequently accompanied by what other manifestations of allergy?
Allergic rhinitis and atopic dermatitis
Of asthma sufferers, what percentage of patients have their first episode of wheezing before 6 years of age?
95%
Adult onset asthma, which is more common in women, is associated with what? (3)
More persistent airflow obstruction, a lack of association with atopy, a worse prognosis.
Asthma common male or female?
Asthma is more common in boys than girls, but more common in women than men, the gender switch occurring in adolescence.
How many people die from asthma each year?
250000 deaths each year, accounting for 1 in every 250 deaths worldwide
What is the incidence of adult onset asthma?
4.6 cases per 1000 person-years in females and 3.6 in males
What is often used to define asthma?
Wheezing at any time in the previous 12 months
Chronic inflammation in asthma is accompanied by structural changes referred to as what?
Remodeling
At least what proportion of patients with asthma have features of allergy, consituting allergic or extrinsic asthma, usually accompanied by elevated levels of circulating IgE, and usually beginning in childhood?
Two thirds
What is the dominant abnormality in asthma?
Airway inflammation, occuring even in the earliest stages
What are the airway inflammatory cells?
Lymphocytes, plasma cells, mast cells and macrophages, typically associated with eosinophils.
What other cells are seen in asthmatic patients who are also smokers?
Neutrophils
What is exhibited by the cells in allergic asthma?
Th2 profile of cytoking secretion, characterized by production if IL-4, IL-5, IL-9, GM-CSF and IL-1
Structural alterations in the lungs are termed?
Airway remodeling. Characteristically involves airway wall thickening in large and small airways, involving all airway wall components. The epithelium is hyperplastic and injured.
Describe the basement membrane in asthmatic patients.
It is thickened by subepithelial fibrosis, with hyperplasia and hypertrophy of mucus-secreting cells. The airway walls have increased vascularity and smooth muscle hypertrophy or hyperplasia. Stiffness and loss of elasticity of the parenchyma occurs, contributing to air trapping and hyperinflation.
Identified as an asthma-susceptibility gene, with a polymorphism associated with early-life measures of lung function.
ADAM33
Refers to the relationship between genetic variation and drug response, with research focused on the B2-adrenoreceptor encoded by the gene ADRB2.
Pharmacogenetics
These processes result from modifications of DNA structure without a change in the sequence in response to environmental exposures, and may be passed between generations.
Epigenetic processes
Refers to the observable characteristics of an individual or group resulting from interaction of its genotype with its environment.
Phenotype
What defines the different phenotypes in asthma?
Clinical features
Pattern of inflammation
Pulmonary function
Triggers or on comorbidity
A subtype defined by distinct functional or pathophysiologic mechanisms, and addresses etiology and pathophysiology?
Endotype
What are some associated comorbidities with asthma?
Rhinitis, sinusitis, GERD, obstructive sleep apnea, hormonal disorders, and psychological disturbances.
Phenotypes of Asthma based on Airway inflammation (3)?
Eosinophilic
Neutrophilic
Pauci-granulocytic
What are the phenotypes of asthma based on clinical features? (5)
Mild, moderate, or severe asthma Exacerbation-prone Treatment-resistant Early-onset or late-onset asthma Asthma in the elderly
What are the phenotypes of asthma based on pulmonary function? (3)
With a component of fixed airway obstruction
With marked/rapid fluctuations of airway caliber
With marked hyperinflation
What are the phenotypes of asthma based on triggers? (7)
Allergic or non-allergic asthma Aspirin or NSAIDs Occupational allergens or irritants Hormones: premenstrual and menopausal asthma Exercise or cold air-induced asthma Asthma in high level athlete Asthma in the smoker
What are the phenotypes of asthma based on comorbid conditions? (5)
Rhinitis/rhinosinusitis, nasal polyps, and aspirin intolerance
Psychological disturbances (eg. depression, anxiety disorders)
With dysfunctional breathing (hyperventilation syndrome, vocal cord dysfunction)
With associated COPD
Asthma in the obese
What are the 4 wheezing phenotypes? (According to the Tucson Children’s Respiratory Study)
- Never (51%)
- Transient early (20%), with onset of wheezing before age 3 years and wheezing resolved by age 6
- Persistent (14%), with onset of wheezing before age 3 years with continued wheezing at age 6
- Late onset (15%), with onset of wheezing between 3 and 6 years of age.
Most prevalent type of wheezing?
Early transient wheezing
Of children who wheeze in the first 3 years, _____ have resolution of their symptoms by 6 years of age.
60%
Is transient wheezing associated with maternal smoking during pregnancy?
Yes.
What proportion of adolescents who are transient wheezers continue to wheeze?
Less than one quarter
What type of wheezing is associated with the first episode of wheezing occurring before the age of 1 year?
Non-atopic persistent wheezing, representing 20% of wheezy children under 3 years of age.
What are the pulmonary changes seen in children with non-atopic persistent wheezing?
Lower level of prebronchodilator lung function and enhanced airway reactivity.
In 20% of children who wheeze during the first 3 years, what are the findings?
IgE-associated atopic persistent wheezing.
What are the risk factors for wheezing?
Male gender, parental asthma, atopic dermatitis, eosinophilia at 9 months, and history of wheezing with infections.
What is the pattern of lung function in children with wheezing?
normal lung function in infancy but reduced lung function at age 6 years
What are the potential risk factors for the development of asthma?
Personal or family history of asthma and allergy
Exposure to airborne allergens
Tobacco smoke or other polluntants
Past respiratory infections
What are the PE findings in asthmatic patients during an exacerbation?
Wheezes heard with auscultation, with prolonged expiratory time.
Preferred method to measure airway obstruction in asthma.
Spirometry
Definition of airway obstruction during spirometry
A ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of <0.7
An absolute measure of the volume of air exhaled in the first second of forced expiration
FEV1
Indicates presence of airway obstruction.
Reduced percent predicted FEV1 with a low FEV1/FVC ratio
Definition of reversibility in asthma
An increase in FEV1 of 12% or more with at least a 200ml change after a bronchodilator or following 4 weeks of anti-inflammatory treatment with ICS
What is the lower limit of normal in spirometry?
5th percentile. because these values are not always proportional to the percent of predicted value.
What are most commonly used to predict normal values of spirometry?
Fixed-ratio lower limit of normal for FEV1/FVC (70%) and percent of predicted FEV1
How to diagnose asthma in adults?
Symptoms of episodic breathlessness, wheezing, cough, chest tightness, phlegm production (one or more)
PLUS
Increase in FEV1 after a bronchodilator or after a course of controlled therapy >=12% (and a minimum of >=200ml)
OR
Increase in PEF after a bronchodilator or after a course of controller therapy of 60L/min (minimum >=20%, based on multiple daily readings)
OR
Metacholine PC20 <4 mg/mL (4-16 mg/mL is borderline)
OR
Decrease in FEV1 after excercise challenge >=10-15%
FEV1: forced expiratory volume in 1 second; FVC forced vital capacity; PC20: provocative concentration that induces a 20% fall in FEV1; PEF: peak expiratory flow
What test can be used to demonstrate peak flow variability over a period of time (e.g. 2 weeks) to support the diagnosis of asthma?
Domiciliary morning and night monitoring
What is the classic monitoring pattern seen in untreated asthmatic patients?
“saw-tooth” pattern with significant diurnal variability (lower values on morning readings)
How to calculate for diurnal variability for asthmatic patients? (lower values on morning readings)
Highest PEF of the day minus the lowest PEF reading divided by the mean of the day’s highest and lowest readings, and averaged over a 1 to 2 week period.
What is the average diurnal variability?
> 10%, and the greater the variation, the greater the support for diagnosis
Provides an objective test of the constriction thresholds or ‘twitchiness’ of the airways.
Bronchial provocation test
How to perform bronchial provocation test?
Patients inhale (usually via a nebulizer) increasing concentrations or cumulative doses of a bronchoconstrictor, and spirometry is repeated until a 20% reduction in baseline FEV1 is observed. The lower the concentration or dose required, the more hyperreactive the airways. These are highly sensitive.
What is the most common bronchial challenge test?
Metacholine inhalational test. Measures the provocative concentration of metacholine inducing a 20% fall i FEV1 (PC20). Test is sensitive but not specific.
In what other conditions may metacholine inhalational test be positive?
Rhinitis
COPD
In what conditions may have a false-negative metacholine inhalational test?
Regular use of ICS
Although total IgE levels suggest an atopic status, they do not help to establish a diagnosis of asthma and are of limited clinical value. True or false?
True.
What are other non-invasive assessments of airway inflammation that are helpful in cases of diagnostic difficulty?
Induced sputum analysis
Measurement of fractional nitric oxide concentration in exhaled breath (FeNO).
What is upregulated in asthmatic inflammation?
Production of NO by airway epithelial cells which is driven by inducible NO synthase, and is upregulated in asthmatic inflammation, while production of iNOS is decreased by corticosteroid therapy.
What test may help to detect eosinophilic inflammation assess the likelihood of steroid responsiveness, contribute to the monitoring of corticosteroid needs, and detect non-adherence?
FeNO
Role of imaging studies in the diagnosis or follow-up of asthma?
Can be used to investigate diagnostic difficulties when they arise such as allergic bronchopulmonary aspergillosis, COPD (emphysema), and interstitial diseases.
Findings on HRCT in severe asthma patients
Lung hyperinflation
Mosaic perfusion pattern at full inspiration (reflecting ventilation-perfusion inequalities)
Increased airway wall thickness
What is work-related asthma?
Broad term indicating asthma worsened by the workplace. It encompasses “occupational asthma” anmd “work-exacerbated asthma”.
What is occupational asthma?
Asthma caused by a specific workplace agent
What is work-exacerbated asthma?
Asthma is worsened by stimuli at the workplace
Common citation of the definition of occupational asthma?
Characterized by airway inflammation, variable airflow limitation, and airway hyperresponsiveness due to causes and conditions attributable to a particular occupational environment and not to stimuli encountered outside the workplace.
What percentage of all cases of adult-onset asthma are attributable to workplace exposures?
17.6%
What are the common causes of adult-onset asthma?
Laboratory animals
Wheat flour
Dental health apprentices exposed to latex gloves
What is the pathophysiology in the majority of adult onset asthma?
IgE-dependent mechanism
What are some HMW agents which can cause adult-onset asthma?
Cereals (flour): wheat, rye, barley, buckwheat
Latex: gloves
Animals: mice, rats, cows, seafood
Enzymes: alpha-amylase, maxatase, alcalase, papain, bromelain, pancreatin
What are some LMW agents which can cause adult-onset asthma?
Isocyanates Metals Biocides Persulfate salts Acid anhydrides Reactive dyes Acrylates Wood dusts
Treatment of occupational asthma?
Early removal of sensitizing factor may allow full resolution.
How to confirm diagnosis of occupational asthma?
serial measures of airway responsiveness and PEF, or specific bronchoprovocation tests performed
What is the presentation of asthma in elderly patients?
May show mostly a combined neutrophilic and eosinophilic inflammatory pattern with more severe airway obstruction and physiologic features related to aging of the lung.
What are some conditions which may mimic asthma?
Vocal cord dysfunction Hyperventilation syndrome Upper airways diseases Deconditioning Obesity-related symptoms Pulmonary embolism OSA Airway neoplasms