Obstructive Pulmonary Diseases

Asthma
Asthma is a chronic inflammatory disorder of the
airways, in which many cells and cellular elements play
a role.
(associated with airway hyper-responsiveness ) leads to
recurrent episodes of wheezing, breathlessness, chest
tightness and coughing, particularly at night and in the
early morning.
These episodes are usually associated with widespread
but variable airflow obstruction within the lung that is
often reversible, either spontaneously or with treatment.
❖ Affect all age group
❖ The prevalence of asthma increased steadily over the latter part of
last century.
❖ The development and course of asthma and the response to
treatment are influenced by genetic determinants and environmental
factors.
❖ The potential role of indoor and outdoor allergens, microbial
exposure, diet, vitamins, breastfeeding, tobacco smoke, air pollution
and obesity have been explored but no clear consensus has emerged.
Pathophysiology
Airway hyper-reactivity (AHR) – the tendency for airways to
narrow excessively in response to triggers that have little or no
effect in normal individuals – is integral to the diagnosis of asthma
and appears to be related,
Other factors effect airway smooth muscle include the degree of
airway narrowing and neurogenic mechanisms.
The relationship between atopy (the propensity to produce IgE)
and asthma is well established and in many individuals there is a
clear relationship between sensitisation and allergen exposure, as
demonstrated by skin-prick reactivity or elevated serum-specific
IgE.
Common examples of allergens include :
house dust and mites,
pets such as cats and dogs,
pests such as cockroaches, and fungi.
Inhalation of an allergen into the airway is followed by
an early and late-phase bronchoconstrictor response
Allergic mechanisms are also implicated in some cases
of occupational asthma .
❖ In cases of aspirin-sensitive asthma,
❖ In exercise-induced asthma, hyperventilation results in water
loss from the pericellular lining fluid of the respiratory mucosa,
which, in turn, triggers mediator release. Heat loss from the
respiratory mucosa may also be important.
❖ In persistent asthma,
a chronic and complex inflammatory response ensues, characterised by
an influx of numerous inflammatory cells, the transformation and
participation of airway structural cells, and the secretion of an array of
cytokines, chemokines and growth factors.
❖ With increasing severity and chronicity of the disease, remodelling of
the airway may occur, leading to fibrosis of the airway wall, fixed
narrowing of the airway and a reduced response to bronchodilator
medication.
Clinical features
Typical symptoms include:
❑ recurrent episodes of wheezing,
❑ chest tightness, breathlessness and
❑ cough.
Patients with mild intermittent asthma are usually asymptomatic between
exacerbations.
Individuals with persistent asthma report ongoing breathlessness and
wheeze but these are variable, with symptoms fluctuating over the course
of one day, or from day to day or month to month.
Asthma characteristically displays a diurnal pattern, with symptoms and
lung function being worse in the early morning.
Cough may be the dominant symptom in some patients, and the lack of wheeze
or breathlessness may lead to a delay in reaching the diagnosis of so-called
‘cough-variant asthma’.

Some patients with asthma have a similar inflammatory response in the upper
airway. Careful enquiry should be made as to a history of sinusitis, sinus
headache, a blocked or runny nose and loss of sense of smell.

Particular enquiry should be made about potential allergens, such as exposure to

a pet cat, guinea pig, rabbit or horse, pest infestation, exposure to moulds
following water damage to a home or building, and any potential occupational
agents .
In some circumstances, the appearance of asthma is triggered by medications.
Beta-blockers, even when administered topically as eye drops, may induce
bronchospasm, as may aspirin and other non-steroidal anti-inflammatory drugs
(NSAIDs).

The classical aspirin-sensitive patient is female and presents in middle age with
asthma, rhinosinusitis and nasal polyps.

Aspirin-sensitive patients may also report symptoms following alcohol and

foods containing salicylates.

Other medications implicated include the oral contraceptive pill, cholinergic

agents and prostaglandin F 2α . Betel nuts contain arecoline, which is
structurally similar to methacholine and can aggravate asthma.

An important minority of patients develop a particularly severe form of asthma

and this appears to be more common in women. Allergic triggers are less
important and airway neutrophilia predominates.
Diagnosis
Spirometry by measuring the FEV1 ,FVC and reversibility
test
PEF( Peak Expiratory Flow) to find diurnal variation.
Bronchial challenge test
Exercise test in exercise induced bronchospasm
How to diagnosis Asthma
• Measurement of allergic status : presence of atopy demonstrated by

skin-prick tests or measurement of total and allergen-specific IgE,

Assessment of eosinophilic airway infl. > 2 important. Or exheald breath

Nitric oxide concentration

a peripheral blood eosinophilia.

Chest X-ray appearances are often normal but lobar collapse may be seen if
mucus occludes a large bronchus and, if accompanied by the presence of flitting
infiltrates, may suggest that asthma has been complicated by allergic
bronchopulmonary aspergillosis. A high-resolution CT scan (HRCT) may be
useful to detect bronchiectasis.
Management
• Asthma is a chronic condition but may be controlled with appropriate treatment
in the majority of patients. The goal of treatment should be to obtain and maintain
complete control but aims may be modified according to the circumstances and
the patient.

• A full explanation of the nature of the condition, the relationship between

symptoms and inflammation, the importance of key symptoms such as nocturnal
waking, the different types of medication and, if appropriate, the use of PEF to
guide management decisions should be given.
 Avoidance of aggravating factors

This is particularly important in the management of occupational asthma but

may also be relevant in atopic patients, when removing or reducing exposure to
relevant antigens, such as apet, may effect improvement. Many patients are
sensitized to several ubiquitous aeroallergens, making avoidance strategies
largely impractical.

Measures to reduce fungal exposure may be applicable in specific circumstances

and medications known to precipitate or aggravate asthma should be avoided.

Smoking cessation is particularly important, as smoking not only encourages

sensitisation but also induces a relative glucocorticoid resistance in the airway.
The stepwise approach to the
management of asthma
Step 1: Occasional use of inhaled short-acting β 2
-adrenoreceptor agonist bronchodilators

For patients with mild intermittent asthma (symptoms less than once a
week for 3 months and fewer than two nocturnal episodes per month), it
is usually sufficient to prescribe an inhaled short-acting β 2 -agonist,
such as salbutamol or terbutaline, to be used as required. However,
many patients (and their physicians) under-estimate the severity of
asthma. A history of a severe exacerbation should lead to a step-up in
treatment.
 Step 2: Introduction of regular preventer therapy

Regular anti-inflammatory therapy (preferably inhaled glucocorticoids (ICS),

such as beclometasone, budesonide BUD), fluticasone, mometasone or
ciclesonide) should be started in addition to inhaled β 2 -agonists taken on an
as-required basis for any patient who:

1. has experienced an exacerbation of asthma in the last 2 years

2. uses inhaled β 2 -agonists three times a week or more

3. reports symptoms three times a week or more

4. is awakened by asthma one night per week.

For adults, a reasonable starting dose is 400 μg beclometasone dipropionate

(BDP) or equivalent per day in adults, although higher doses may be required
in smokers. Alternative but much less effective preventive agents include
chromones, leukotriene receptor antagonists and theophyllines
 Step 3: Add-on therapy
If a patient remains poorly controlled despite regular use of an inhaled
glucocorticoid, a thorough review should be undertaken of adherence, inhaler
technique and ongoing exposure to modifiable aggravating factors. A further
increase in the dose of inhaled glucocorticoid may benefit some patients
but, in general, add-on therapy should be considered in adults taking 800
μg/day BDP (or equivalent).

The addition of a long-acting β 2 -agonist (LABA) to an inhaled glucocorticoid

provides more effective asthma control compared with increasing the dose of
inhaled glucocorticoid alone.

Fixed-combination inhalers of glucocorticoids and LABAs have been

developed; these are more convenient, increase adherence and prevent patients
using a LABA as monotherapy – the latter may be accompanied by an increased
risk of life-threatening attacks or asthma death.
The onset of action of formoterol is similar to that of
salbutamol such that, in carefully selected patients, a fixed
combination of budesonide and formoterol may be used as
both rescue and maintenance therapy.
Oral leukotriene receptor antagonists (e.g. montelukast 10 mg
daily) are generally less effective than LABAs as add-on
therapy but may facilitate a reduction in the dose of inhaled
glucocorticoid and control exacerbations.
Step 4: Poor control on moderate dose of inhaled
glucocorticoid and add-on therapy: addition of a
fourth drug

In adults, the dose of inhaled glucocorticoid may be increased to

2000 μg BDP/BUD (or equivalent) daily.

A nasal glucocorticoid preparation should be used in patients

with prominent upper airway symptoms.

Leukotriene receptor antagonists, long-acting antimuscarinic

agents, theophyllines or a slow-release β 2 -agonist may be
considered. If the trial of add-on therapy is ineffective, it should
be discontinued.
 Step 5: Continuous or frequent use of oral
glucocorticoids
At this stage, prednisolone therapy (usually administered as a single daily dose
in the morning) should be prescribed in the lowest amount necessary to control
symptoms. Patients who are on long-term glucocorticoid tablets (> 3 months) or
are receiving more than three or four courses per year will be at risk of systemic
side-effects. The risk of osteoporosis in this group can be reduced by giving
bisphosphonates.

In patients who have symptoms and asthma despite step 5, Omalizumab, a

monoclonal antibody directed against IgE, should be considered for those with a
prominent atopic phenotype,

Mepolizumab, a monoclonal antibody that blocks the binding of IL-5 to its

receptor on eosinophils, should be considered in those with
eosinophilic-mediated disease.
 Step-down therapy

Once asthma control is established, the dose of inhaled (or oral) glucocorticoid
should be titrated to the lowest dose at which effective control of asthma is
maintained. Decreasing the dose of glucocorticoid by around 25–50% every 3
months is a reasonable strategy for most patients.
Exacerbations of asthma
The course of asthma may be punctuated by exacerbations with:

increased symptoms,

deterioration in lung function

an increase in airway inflammation.

Exacerbations are most commonly precipitated by :

viral infections but

moulds (Alternaria and Cladosporium),

pollens (particularly following thunderstorms) and

air pollution are also implicated.

Most attacks are characterised by a gradual deterioration over several hours to days but
some appear to occur with little or no warning: so-called brittle asthma.

An important minority of patients appear to have a blunted perception of airway narrowing

and fail to appreciate the early signs of deterioration.
 Management of mild to moderate exacerbations

❖ Doubling the dose of inhaled glucocorticoids does not prevent an impending exacerbation.

❖ Short courses of ‘rescue’ glucocorticoids (prednisolone 30–60 mg daily) are therefore

often required to regain control. Tapering of the dose to withdraw treatment is not
necessary, unless glucocorticoid has been given for more than 3 weeks.

Indications for ‘rescue’ courses include:

❖ symptoms and PEF progressively worsening day by day, with a fall of PEF below 60% of the
patient’s personal best recording

❖ onset or worsening of sleep disturbance by asthma

❖ persistence of morning symptoms until midday

❖ progressively diminishing response to an inhaled bronchodilator

❖ symptoms that are sufficiently severe to require treatment with nebulised or injected
bronchodilators.
Management of acute severe asthma

Measurement of PEF is mandatory, unless the patient is too ill to

cooperate, and is most easily interpreted when expressed as a
percentage of the predicted normal or of the previous best value
obtained on optimal treatment .
Arterial blood gas (ABG) analysis is essential to determine the
PaCO 2 , a normal or elevated level being particularly dangerous.
A CXR is not immediately necessary, unless pneumothorax is
suspected.
 Treatment includes the following measures:

❖ Oxygen. High concentrations (humidified if possible) should be administered to

maintain the oxygen saturation above 92% in adults. Failure to achieve
appropriate oxygenation is an indication for assisted ventilation.

❖ High doses of inhaled bronchodilators. Short-acting β 2 -agonists are the

agent of choice. In hospital, they are most conveniently given via a nebuliser
driven by oxygen, but delivery of multiple doses of salbutamol via a
metered-dose inhaler through a spacer device provides equivalent
bronchodilatation and can be used in primary care.

❖ Ipratropium bromide provides further bronchodilator therapy and should be

added to salbutamol in acute severe or life-threatening attacks.
❖ Systemic glucocorticoids.They can usually be administered orally as prednisolone
but intravenous hydrocortisone may be used in patients who are vomiting or unable to
swallow.

❖ There is no evidence base for the use of intravenous fluids but many patients are
dehydrated due to high insensible water loss and will probably benefit. Potassium
supplements may be necessary, as repeated doses of salbutamol can lower serum
potassium.

❖ If patients fail to improve, a number of further options may be considered.

Intravenous magnesium may provide additional bronchodilatation in patients whose
presenting PEF is below 30% predicted.

❖ intravenous aminophylline but cardiac monitoring is recommended.

Follow up

❑ PEF should be recorded every 15–30 minutes and then every 4–6
hours.
❑ Pulse oximetry should ensure that SaO 2 remains above 92%, but
❑ Repeat arterial blood gases are necessary if the initial PaCO 2
measurements were normal or raised, the PaO 2 was below 8 kPa
(60 mmHg) or the patient deteriorates.
Prognosis

The outcome from acute severe asthma is generally good but a

considerable number of deaths occur in young people and many are
preventable.

Failure to recognise the severity of an attack, on the part of either the

assessing physician or the patient, contributes to delay in delivering
appropriate therapy and to under-treatment.
 Prior to Discharge
Patients should be stable on discharge medication (nebulised therapy should
have been discontinued for at least 24 hours)

The PEF should have reached 75% of predicted or personal best.

The acute attack should prompt a look for and avoidance of any trigger factors,
the delivery of asthma education and the provision of a written
self-management plan.

The patient should be offered an appointment with a GP or asthma nurse

within 2 working days of discharge, and follow-up at a specialist hospital
clinic within a month.