This document provides an overview of asthma including its definition, epidemiology, risk factors, pathogenesis, clinical features, diagnosis, status asthmaticus, and treatment. Asthma is a heterogeneous disease characterized by airway inflammation and affects approximately 300 million people worldwide. Key risk factors include atopy, genetic predisposition, infections, obesity, and air pollution. Clinical features include symptoms of wheezing, coughing, and shortness of breath. Diagnosis involves assessing symptoms and lung function tests. Treatment involves inhaled corticosteroids and bronchodilators, with status asthmaticus defined as an acute exacerbation not responding to standard treatment and requiring more intensive interventions.
3. “a heterogeneous disease, usually
characterized by airway inflammation. It is
defined by the presence of respiratory
symptoms such as wheeze, shortness of
breath, chest tightness and cough that vary
over time and in intensity, together with
variable expiratory airflow limitation.”
4. affects approximately 300 million people
worldwide (Harrisons 19E)
can present at any age, with a peak age of 3
years.
In childhood, M:F ration is 2: 1
By adulthood the sex ratio has equalized
7. Atopy
allergic rhinitis (80%)
atopic dermatitis (eczema)
Genetic predisposition
Determines severity, is polygenic
Novel genes: ADAM-33, and DPP-10
Infections
Atypical bacteria, such as Mycoplasma and
Chlamydophila
8. Obesity
BMI> 30 kg/m2
more difficult to control
Others
Air pollution
Cold air
In utero exposure to environmental tobacco
smoke
Pharmacologic agents (ẞ blockers)
11. >1 sx (wheeze, shortness of breath, cough,
chest tightness)
Symptoms often worse at night or in the
early morning
Symptoms vary over time and in intensity
Symptoms are triggered by viral infections
(colds), exercise, allergen exposure, changes
in weather, laughter, or irritants
12. Isolated cough
Chronic production of sputum
SOB associated with dizziness, light-
headedness or peripheral tingling (paresthesia)
Chest pain
Exercise-induced dyspnea with noisy
inspiration.
13.
14.
15.
16. Allergic asthma:
starts in past and/or family history of allergic disease such
as eczema, allergic rhinitis, or food or drug allergy.
Examination of the induced sputum reveals eosinophilic
airway inflammation
Respond well (ICS) treatment.
Non-allergic asthma:
Sputum neutrophilic, eosinophilic or contain only a few
inflammatory cells
Respond less well to ICS.
17. Late-onset asthma
particularly women
non-allergic
require higher doses of ICS or are refractory to corticosteroid
treatment.
Asthma with fixed airflow limitation:
some patients with long-standing asthma develop fixed airflow
limitation that is thought to be due to airway wall remodeling.
Asthma with obesity:
obese patients have prominent respiratory symptoms
little eosinophilic airway inflammation.
18.
19. • classically present with a history of episodes of coughing,
chest tightness, shortness of breath, and wheezing
onset of symptoms with specific triggers
Family history
Social history
home characteristics, smoking, workplace or
school characteristics, educational level, social
support, non-adherence of asthma medications,
and illicit drug use.
20. Prodromal symptoms may precede an attack
Itching under the chin
discomfort b/n scapula
unexplained fear.
21. Hyperexpansion of the thorax
Wheezing during normal breathing
Prolonged phase of forced exhalation
Increased nasal secretion, mucosal swelling,
and/or nasal polyps
Atopic dermatitis/eczema
22. Lung function tests
Spirometry
▪ forced expiratory volume in 1 second (FEV1)
▪ FEV1/FVC <0.7 generally defines obstruction.
▪ peak expiratory flow (PEF)
▪ Reversibility
▪ increase in FEV1 of ≥12% or >200 mL after inhalation of a short-
acting bronchodilator
Flow volume loop
23.
24. Provocation studies airway hyperresponsiveness
Metacholine/ histamine challenge
A 20 % reduction in FEV1
Exhaled NO – to measure air way inflammation
Total serum IgE and specific IgE to inhaled allergens
Skin prick test to common inhalant allergens
25. Airway Hyperresponsiveness
Methacholine or histamine challenge
Laboratory tests: not usually helpful
Blood eosinophilia
Sputum eosinophilia
Serum IgE levels
Chest X-ray: usually normal, may show hyperinflated lungs
Exhaled nitric oxide (FENO)
Allergy skin testing
27. Condition Characteristics
COPD Airway obstruction is less reversible; typically seen in older patients
with smoking history
Vocal cord
dysfunction
Abrupt onset and end of symptoms; monophonic wheeze; more
common in younger patients; confirm with laryngoscopy or flow-
volume loop
Heart failure Dyspnea and often wheezing; crackles on auscultation; limited
response to asthma therapy; cardiomegaly; edema
Bronchiectasis Cough productive of large amount of purulent sputum; rhonchi and
crackles are common; may have wheezing and clubbing; confirmed by
CT imaging
ABPA Recurrent infiltrates on chest radiograph; eosinophilia; positive skin
testing to Aspergillus antigens, high IgE levels
Mechanical
obstruction
More localized wheezing; if central in location, flow-volume loop may
provide a clue
Eosinophilic
granulomatosis
with polyangiitis
Autoimmune small-vessel vasculitis presents with peripheral
eosinophilia, lung symptoms similar to asthma
28.
29.
30.
31. ẞ2-Agonists
Relax airway smooth-muscle cells
No effects on inflammatory cells
SABAs: 3–6 h
Salbutamole- useful in preventing EIA if taken prior to
exercise
LABAs: >12h
salmeterol and formoterol (Important to use ICS when LABAs
are given
Anticholinergics
prevent cholinergic nerve-induced bronchoconstriction and
mucus secretion. once- daily tiotropium bromide
Theophylline- Side Effects
32. Inhaled corticosteroids (ICSs)
Most effective controllers for asthma
Anti-inflammatory
↑expression of β2-receptors
Reduce AHR
First-line therapy for patients with persistent asthma
Local side effects
hoarseness (dysphonia)
oral candidiasis
Antileukotrienes, Cromones, Anti-IgE
33. Intermittent Persistent
Components of
Severity
Mild Moderate Severe
Symptoms ≤2 days/week >2 days/week but
not daily
Daily Throughout the day
Nighttime
awakenings
≤2 ×/month 3-4 ×/month >1 ×/week but not
nightly
Often 7 ×/week
SABA use for
symptom control
≤2 days/week >2 days/week but
not more than 1
×/d
Daily Several times a day
Lung function FEV1 ≥80% of
predicted
FEV1/FVC normal
FEV1 ≥80% of
predicted
FEV1/FVC normal
FEV1 ≥60% but
<80% of predicted
FEV1 <60% of
predicted
Exacerbations 0-1/year >2/year >2/year >2/year
36. Formerly known as status asthmaticus
Acute exacerbation of asthma that does not
respond to standard treatment
(Bronchodilators, inhalers, steroids)
Medical emergency
37. 50% due to URTIs
Non adherence
NSAID exposure in ASA-allergic patients
Allergen exposure
Irritant inhalation
38. Chest tightness, wheezing, use of accessory
muscles and dyspnea that are often not or
poorly relieved by their usual reliever inhaler
breathless that they are unable to complete
sentences
cyanotic
39. General appearance:
alteration of consciousness
fatigue
upright posture
diaphoresis
Respiratory system
tachypnea (>30min)
use of accessory muscles for breathing
reduced respiratory excursion
diffuse expiratory wheezing
Cyanotic
40. Cardiovascular system
Tachycardia (>120/min)
pulsus paradoxus
SPIROMETRY
PEFR< 120L/MIN
FEV1< 1L
Arterial blood gas analysis
hypercapnia or normal
CXR:
over inflated lung
41. Cardiac arrest
Respiratory failure or arrest
Hypoxemia with hypoxic ischemic central
nervous system (CNS) injury
Pneumothorax or pneumomediastinum
Toxicity from medications
42. Good prognosis if appropriate therapy is administered.
…unless a complicating illness such as
CHF
COPDis present
A delay in initiating treatment is probably the worst
prognostic factor
43.
44. High concentration of oxygen + High doses of SABA
Severely ill patients with impending respiratory failure, IV
β2-agonists
Nebulized anticholinergic- if unsatisfactory response to
β2-agonists
patients who are refractory to inhaled therapies, a slow
infusion of aminophylline
Magnesium sulfate given intravenously or by nebulizer
with inhaled β2-agonists
Prophylactic intubation for impending respiratory failure,
when the PCO2 is normal or rises.
Patients with respiratory failure necessary to intubate
45. These patients may benefit from an
anesthetic such as halothane if they have not
responded to conventional bronchodilators.
Sedatives are C/I depress ventilation.
Antibiotics not required unless there are signs
of pneumonia.
47. Harrison’s principles of internal medicine 19th
e/o
Global asthma initiative for asthma
Review article Chapter 14: Acute severe
asthma(status asthmaticus)
Review article [Status asthmaticus]
Hinweis der Redaktion
A rise in asthma mortality seen in several countries during the 1960s was associated with increased use of short-acting inhaled β2-adrenergic agonists (as rescue therapy), but there is now compelling evidence that the more widespread use of inhaled corticosteroids (ICS) in patients with persis- tent asthma is responsible for the decrease in mortality in recent years. Major risk factors for asthma deaths are poorly controlled disease with frequent use of bronchodilator inhalers, lack of or poor compliance with ICS therapy, and previous admissions to hospital with near-fatal asthma.
AHR is the characteristic physiologic abnormality of asthma and describes the excessive bronchoconstrictor response to multiple inhaled triggers that would have no effect on nor- mal airways.
Atopy refers to the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis (eczema). Atopy is typically associated with heightened immune responses to common allergens, especially inhaled allergens and food allergens.
Genetic screens with classical linkage analysis and single-nucleotide polymorphisms of various candidate genes indicate that asthma is polygenic, with each gene identified having a small effect that is often not replicated in different populations. This observation suggests that the interaction of many genes is important, and these may differ in different populations. The most consistent findings have been associa- tions with polymorphisms of genes on chromosome 5q, including the T helper 2 (TH2) cells interleukin (IL)-4, IL-5, IL-9, and IL-13, which are associated with atopy.
exposure to microbial diversity appears to protect against asthma by shifting Th cells to a Th1 instead of a predominantly Th2 phenotype
Th1 cells tend to generate responses against intracellular parasites such as bacteria and viruses, Th2 cells produce immune responses against helminths and other extracellular parasites
Dendritic cells are specialized macrophage-like cells in the airway epithelium, which are the major antigen-presenting cells. Dendritic cells take up allergens, process them to peptides, and migrate to local lymph nodes where they pres- ent the allergenic peptides to uncommitted T lymphocytes to program the production of allergen-specific T cells. Immature dendritic cells in the respiratory tract promote TH2 cell differentiation and require cyto- kines, such as IL-12 and tumor necrosis factor α (TNF-α), to promote the normally preponderant TH1 response.
Allergen inhalation results in a marked increase in activated eosinophils in the airways at the time of the late reaction. Eosinophils are linked to the development of AHR through the release of basic proteins and oxygen-derived free radicals.
Smooth muscle
Inflammatory media- tors may modulate the ion channels that serve to regulate the resting membrane potential of airway smooth-muscle cells, thus altering the level of excitability of these cells.
VAsculAr resPonses There is increased airway mucosal blood flow in asthma, which may contribute to airway narrowing. There is an increase in the number of blood vessels in asthmatic airways as a result of angiogenesis in response to growth factors, particularly vascular endothelial growth factor. Microvascular leakage from postcapillary venules in response to inflammatory mediators is observed in asthma, resulting in airway edema and plasma exudation into the airway lumen.
mucus hyPersecretion Increased mucus secretion contributes to the viscid mucous plugs that occlude asthmatic airways, particularly in fatal asthma. There is hyperplasia of submucosal glands that are con- fined to large airways and of increased numbers of epithelial goblet cells. IL-13 induces mucus hypersecretion in experimental models of asthma.
fibrosis In all asthmatic patients, the basement membrane is appar- ently thickened due to subepithelial fibrosis with deposition of types III and V collagen below the true basement membrane and is associated with eosinophil infiltration, presumably through the release of profibrotic mediators such as transforming growth factor-β.
Non-allergic asthma:
Sputum neutrophilic, eosinophilic or contain only a few inflammatory cells (paucigranulocytic). Patients with non-allergic asthma often respond less well to ICS.
Between attacks and exacerbations, spirometry can be normal in patients with suspected asthma
Flow-volume loops show reduced peak flow and reduced maximum expiratory flow. Further lung function tests are rarely necessary, but whole-body plethysmog- raphy shows increased airway resistance and may show increased total lung capacity and residual volume. Gas diffusion is usually normal, but there may be a small increase in gas transfer in some patients.
Spirometry and flow-volume loop in asthmatic compared to nor- mal subject. There is a reduction in forced expiratory volume in 1 second (FEV1) but less reduction in forced vital capacity (FVC), giving a reduced FEV1/FVC ratio (<70%). The flow-volume loop shows reduced peak expiratory flow and a typical scalloped appearance indicating widespread airflow obstruction.
Inflammatory cells express small numbers of β2- receptors, but these are rapidly downregulated with β2-agonist acti- vation so that, in contrast to corticosteroids, there are no effects on inflammatory cells in the airways and there is no reduction in AHR.
Increased use of SABA indicates that asthma is not controlled. They are also useful in preventing EIA if taken prior to exercise. SABAs are used in high doses by nebulizer or via a metered- dose inhaler with a spacer. Long-acting β2-agonists (LABAs) include salmeterol and formoterol, both of which have a duration of action over 12 h and are given twice daily by inhalation; indacaterol is given once daily. LABAs have replaced the regular use of SABAs, but LABAs should not be given in the absence of ICS therapy because they do not control the underlying inflammation. They do, however, improve asthma control and reduce exacerbations when added to ICS, which allows asthma to be controlled at lower doses of corticosteroids. This observation has led to the widespread use of fixed-combination inhalers that contain a corticosteroid and a LABA, which have proved to be highly effective in the control of asthma.
Stepwise approach to asthma therapy according to the severity of asthma and ability to control symptoms. ICS, inhaled corticosteroids; LABA, long-acting β2-agonist; OCS, oral corti- costeroid.
A high concentration of oxygen should be given by face mask to achieve oxygen saturation of >90%. The mainstay of treatment are high doses of SABA given either by nebulizer or via a metered-dose inhaler with a spacer. In severely ill patients with impending respira- tory failure, IV β2-agonists may be given. A nebulized anticholinergic may be added if there is not a satisfactory response to β2-agonists alone, as there are additive effects. In patients who are refractory to inhaled therapies, a slow infusion of aminophylline may be effec- tive, but it is important to monitor blood levels, especially if patients have already been treated with oral theophylline. Magnesium sulfate given intravenously or by nebulizer is effective when added to inhaled β2-agonists, and is relatively well tolerated but is not routinely recommended. Prophylactic intubation may be indicated for impending respiratory failure, when the PCO2 is normal or rises. For patients with respiratory failure, it is necessary to intubate and institute ventilation. These patients may benefit from an anesthetic such as halothane if they have not responded to conventional bronchodilators. Sedatives should never be given because they may depress ventilation. Antibiotics should not be used routinely unless there are signs of pneumonia.