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introduction
the case of...
causes and risk factors
pathophysiology
signs and symptoms
investigations
differential diagnosis
treatments
consequences and course
resources and references
topic development

Asthma

last authored: Dec 2012, David LaPierre
last reviewed:

Introduction

Asthma is a chronic inflammatory disorder of the airways, causing recurrent episodes of wheezing, breathlessness, chest tightness, and cough. It usually is associated with airway hyperresponsiveness.

Incidence is highest in children, in whom it is the most common chronic disease in developed countries. Up to 7% of the US is thought to have asthma.

Asthma can be life-threatening. Mortality can be reduced dramatically with effective medication and lifestyle prevention, but there are still 300-500 deaths per year in Canada.

Medication adherence is very important, and also very challenging. Unfortunately, both patients and health care professionals frequently do not work together to ensure maximal treatment.

The Case of...

a simple case introducing clincial presentation and calling for a differential diagnosis to get students thinking.

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Causes and Risk Factors

Cause of asthma remains unknown, but appears polygenic and multifactorial. Episodes usually in paroxysms, usually associated with a trigger.

Enviromental allergens include air pollution, passive smoking, molds, dust mites, cockroaches, pets, and other agents. The eradication of mold and increased home ventilation can improve asthma symptoms and reduce medication use (Burr et al, 2007).

Occupational exposures are also very important.

Symptoms can also be triggered by cold air or exercise.

Infections, such as viral respiratory tract infections can cause bronchospasm, even without a diagnosis of asthma. As a result, they can cause significant exacerbations of asthma.

Genetic factors include polymorphisms in the beta-adrenergic receptor gene. This leads to diminished beta-agonist responsiveness regarding medication.

Atopy is strongly linked to asthma, and between 30%-80% of people with asthma also have allergic rhinitis and/or eczema (atopic dermatitis). Obesity also appears linked to higher rates of asthma. Diet can also be important.

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Pathophysiology

Asthma is an obstructive disease associated with widespread but variable bronchoconstriction and airflow limitation. This is due to hyperresponsiveness to a variety of stimuli which normally would have little or no effect.

Antigenic stimulation causes mast cell degranulation and leukocyte activation, resulting in inflammation. Eosinophils, mast cells, macrophages, T cells, neutrophils, and epithelial cells are all involved.

T_H2 CD4+ cells are prominent in the asthmatic mielieu, secreting IL-4 and other cytokines promoting allergic inflammation and stimulating B cell production of IgE and other antibodies. There is evidence that deregulation of T_H2 inhibition by interferon-gamma, and downregulation of the transcription factor T-bet, may be important.

Chronic airway remodeling also occurs with poorly managed asthma. Bronchial smooth muscle hyperplasia and hypertrophy and deposition of collagen, potentially mediated by mast cell release of growth factors and proteases, can increase the constrictive effects of inflammation.

Mucus collects in airways, and lungs become overinflated with mucus plugs. Goblet cell metaplasia and hypertrophy of bronchial musculature and submucosal mucus glands occurs due to increased function. The basement membranes can also thicken.

Chronic asthma can lead to irreversible airflow limitation, rendering bronchodilators less efficient.

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Signs and Symptoms

Asthma has a wide spectrum of predisposing factors and clinical presentations, making uniform classification difficult. One set of categories includes intermittent, persistently mild, persistently moderate, and severe persistent asthma, based on frequency and severity. Interference with activity, nighttime symptoms.

All that wheezes is not asthma.

Typically, asthma is divided into extrinsic asthma, initiated by a type I hypersensitivity to atopic, occupational, or other extrinsic antigens, and intrinsic asthma, initiated by nonimmune mechanisms, including aspirin, pulmonary infections, stress, cold, and exercise.

Diagnosis requires documentation of hyperactivity and reversibility of airflow limitation, either by history or with spirometry.

history
physical exam

History

Symptoms that suggest asthma include:

worsen with triggers, ie allergens, irritants, or infection
most severe at night or in the early morning
episodic attacks of severe dyspnea, coughing, wheezing, and chest tightness
responsiveness to medication
worsening with laughing or playing

Paroxysmal nocturnal dyspnea can also be caused by asthma, thought to be due to decreased vital capacity, decreased body temperature, decreased endogenous vasodilators and increased exposure to bed allergens.

Exercise-induced asthma can cause dyspnea greater than expected with exertion, with symptoms worst 15-30 minutes after exercise cessation.

Other flags to watch for include:

absenteeism from school
encounters with health care providers (GP, ED, admissions, ICU)

Attacks can last up to several hours, but in some people, asthma can persist at low levels all the time. Many people are asymptomatic between attacks.

Past medical history

seasonal allergies
excema

Family history

asthma (how severe?)
eczema
allergies

Follow-up visits

As medications and lifestyle is optimized, ask about the following:

Symptoms and activities

daytime symptoms	<4 days/week
nighttime symptoms	<1 day/week
physical activity	normal

medications

what patient is taking
frequency of rescue medication use
technique
adherence to plan

absenteeism

enviromental changes and triggers, stressors

complicating problems and alternative diagnoses

Physical Exam

Physical exam can be normal may reveal:

increased AP diameter
decreased air entry
wheeze
prolonged expiration

ENT: rhinitis, inflammed mucosa, horizontal crease on nasal bridge, polyps

excema

In acute asthma attacks, or status asthmaticus, patients may display:

increased respiratory rate
decreased oxygen saturation
wheeze, initially on expiration and then on inspiration as well
difficulty talking
accessory muscle use
pulsus paradoxus
orthopnea and tripoding
mental status changes

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Investigations

lab investigations
diagnostic imaging

Lab Investigations

Diagnostic Imaging

Chest X-ray may reveal generalized hyperinflation

Pulmonary Function Testing

Pulmonary function testing, (most commonly spirometry as a component of PFTs) is very valuable in diagnosing asthma. Asthma and COPD both have an obstructive pattern on spirometry,

FEV₁ and FEV₁/FVC are the most important indicators.

FEV₁ less than 80% of predicted is used to diagnose lung disease some some type.

FEV₁/FVC less than 70% suggests obstructive disease, such as asthma or COPD.

Reversibility of flow limitation with bronchodilators should result in a improvement in a change in FEV₁ of over 12%, or 9-12% for children and infants. The FEF_25-75 is also important.

A bronchoprovocation challenge can be done with cold air, methacholine, or histamine to demonstrate airway hyperresonsiveness. Everyone will respond to these agents, but people with asthma will develop airflow limitation at a lower challenge dose.

Variable airflow limitation over time is also usually seen.

Lung volume may show hyperinflation during active disease, but DLCo is typically normal.

Peak Flow Meters

Peak flow meters are hugely variable and dependent on effort. However, for engaged, responsible patients, they may be helpful for home monitoring of disease severity.

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Differential Diagnosis

Asthma cannot be diagnosed at first presentation. Instead, it is called reactive airway disease until a pattern is established.

Other diseases that could be confused for asthma include:

bronchiolitis
pneumonia
reflux
croup, epiglottitis (more stridor)
foreign body
cystic fibrosis
vascular ring
pertussis
tuberculosis
Churg-Strauss vasculitis
allergic pulmonary aspergillosis
immunodeficiencies
bronchiectasis

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Asthma Control

Control of inflammation and bronchodilation are both crucial to controlling asthma.

targets for
control
patient
education
medical
management
children
acute
attacks
reasons for
poor control

Targets for Control

Canada's guidelines are a bit more liberal than world standards.

Good control is:

symptoms less than 4 times weekly
not waking up at night
normal activity levels
maintain PFTs as close to normal as possible
prevent exacerbations
avoiding adverse effects of asthma meds
decrease asthma mortality

Most patients and physicians think asthma is under control, but according to criteria, over 50% of patients are not (ref).

Patient Education

A lot of people think they are fine when they are not. Describe risks, including death, to patients.

Environmental control, education, and written action plan.

Breathing exercises can improve quality of life and decrease depression and anxiety scores, though don't necessarily improve lung function in adults (Thomas et al, 2009).

Use a diary.

Most people have concerns of inhaled corticosteroids (ICS)

1 in 3 people have no intention of filling their maintenance ICS (Asthma Society of Canada, state of asthma nation, Nov 2006)
education is extremely important.

Reasons for not taking medications

people feel well and don't want to take their meds
finances
corticosteroids don't result in feeling any better

They know reducing medications causes increases symptoms, but for various reasons (side effect, costs, etc) they do not use them.

Action plans

Medical Management

Canadian guidelines, 2010

mild intermittent	salbutamol, as needed
mild persistent	inhaled corticosteroids (fluticasone/budesonide, mometasone) + salbutamol PRN second line: monteleukast
moderate persistent	(fluticasone + salmeterol) + salbutamol PRN
severe persistent	(fluticasone + salmeterol) + oral prednisone + salbutamol PRN

Steroids should be used at the lowest dose as possible in children, given the adverse effects (esp growth delay).

Alternatives include ipratroprium, monoleukast, theophylline, and cromolyn sodium

Do not use LABA alone, as this increases mortality.

Ciclesonide (Alvesco)

given once a day
inert until it contacts respiratory epithelium esterases, so prevents oral thrush

Steroid-resistant asthma

Steroid-resistant asthma patients appear to produce higher levels of GRβ, a dominant-negative corticosteriod receptor, leading to a loss of effect with administered steriods.

Children

2/3 of children under 3 with recurrent cough and wheeze will NOT develop long-term asthma. Puffers have limited benefit here, with NNT seven. It is important to be frank about the limitations of treatment. Avoid high doses of steroids, as if it doesn't work at a low dose, it won't work on a high dose.

Moteleukast (Singulair) is labelled for ages 2+ in Canada and over 6 months in the US.

In children 6-11, increase ICS to a moderate dose

In children >12, add LABA

LABA
LTRA (monoleukast)

Carefully monitor height and weight.

Acute Attacks

During an acute attack, as always, focus initally on the ABC's. Assess vitals and use oxygen to maintain saturation above 92%. Provide fluids to maintain blood pressure.

Regular doses of salbutamol, either by MDI or nebulizer, may be given, according to the patient's age and size. Ipratroprium may also be used.

In terms of treating disease with increased severity, including status asthmaticus, consider: