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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2935_Библиотеки_им_академика_М_И_Перельмана
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Respiratory Infection46
https://t.me/med1917
• Post–COVID-19 syndrome (“long Covid”)
– Definitions vary:
◯
WHO: “a condition that occurs in people with a history of
probable or confirmed SARS-CoV-2 infection, usually occurring
3 months from the onset of symptoms and lasting for at least 2
months, that cannot be explained by an alternative diagnosis”.
◯
NICE: “signs and symptoms that develop during or after an
infection consistent with COVID-19, continue for more than
12 weeks, and are not explained by an alternative diagnosis”.
9. PROGNOSIS
Risk of death in patients <65 years old and without comorbidities is low.
•
Mortality rates have fallen since the beginning of the pandemic.
•
• Factors include better hospital processes for managing COVID-19
positive patients, adherence to evidence-based guidelines, vaccination
uptake and emergence of less virulent strains of the virus.
e main cause of death from COVID-19 is ARDS.
•
• e overall mortality rate from Covid-related ARDS is 39% .
MICRO-references
COVID-19 rapid guideline: Managing COVID-19 – The National Institute for
Health and Care Excellence. Available at: www.nice.org.uk/guidance/ng191/
resources/covid19-rapid-guideline- managing-covid19-pdf-51035553326
Respiratory Medicine
3
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1. DEFINITION
Asthma is a chronic inflammatory disorder affecting large and small airways
•
associated with:
• Airway hyper-responsiveness
• Variable airflow obstruction.
2. EPIDEMIOLOGY
Asthma affects around 1 in 11 children and 1 in 12 adults in the UK.
•
Asthma prevalence is on the increase worldwide.
•
Traditionally the peak age of diagnosis is 5–15 years old, with a second peak
•
in the sixth decade of life; however, some adults may have persistent subclinical symptoms which manifest more prominently in middle-age.
3. AETIOLOGY AND RISK FACTORS
Atopy: a triad of asthma, eczema and food allergies can occur.
•
Genetic predisposition.
•
Exposure to smoking (including passive smoking).
•
Low income.
•
Occupation.
•
4. PATHOPHYSIOLOGY
Asthma
e clinical features in asthma are related to two main pathological
•
processes:
• Airway hyper-responsiveness and bronchospasm
• Chronic inflammation and remodelling.
Airway hyper-responsiveness and bronchospasm:
•
• It is suggested that IgE stimulation is a cause of mast cell degranulation.
• Mast cell degranulation appears to have a close relationship with bron-
chial smooth muscle as this event alters contractility.
• is relationship is complex and not consistent and is only one feature
of the pathway to explain airway hyper-responsiveness.
DOI: 10.1201/9781315113937-4
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Chronic inflammation and remodelling:
•
• Oedema.
• Cellular infiltration: eosinophils, mast cells, lymphocytes, neutrophils.
• Disruption of the epithelial lining.
• Increased smooth muscle.
• Fibrosis in the subepithelial layer.
• Mucous gland hypertrophy.
MICRO-print
Phenotyping
The population of patients with asthma has been subdivided based on:
Demographic status
•
Lung function
•
Atopic status
•
Airway inflammation profile.
•
This is relevant in the severe asthma population on deciding treatment
regimens when British Thoracic Society (BTS) 1–4 (see below) is not
effective.
Recognised phenotypes are:
Early onset and atopic.
•
Non-eosinophilic inflammation.
•
Late onset disease with eosinophilic inflammation but non-atopic
•
status.
5. CLINICAL FEATURES
e clinical features (see also Table 3.1) are used to classify patients as:
•
• High probability – diagnosis of asthma likely.
• Intermediate probability – diagnosis uncertain.
• Low probability – diagnosis other than asthma likely.
e probability of asthma informs subsequent management (see below).
•
Symptoms
•
• Cough
• Wheeze
• Shortness of breath
• Chest tightness.
Signs
•
• May be none.
• On auscultation: Expiratory wheeze, prolonged expiratory phase.
Respiratory Medicine
• Chest hyperinflation in long-term poorly controlled asthma.
• Silent chest – severe life-threatening asthma (see below).
Table 3.1 Clinical features that increase or decrease the probability of asthma.
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FACTORS THAT INCREASE THE FACTORS THAT DECREASE THE
PROBABILITY OF ASTHMA PROBABILITY OF ASTHMA
• >1 of wheeze, cough, difficulty • Prominent dizziness, light-headedness
breathing, chest tightness or peripheral tingling
• Especially if worse at night/early • Chronic productive cough in absence
morning; occur in response to of wheeze or breathlessness
exercise/other triggers; occur after • Repeatedly normal chest examination
taking aspirin or beta blockers when symptomatic
• Personal or family history of atopic • Voice disturbance
disorders • Symptoms with colds only
• Widespread wheeze on auscultation • Significant smoking history (>20
• Otherwise unexplained low FEV
or peak flow • Cardiac disease
• Otherwise unexplained • Normal peak flow/spirometry when
eosinophilia symptomatic
Important points for history taking
•
pack-years)
1
• Are the symptoms the same all the time, or do they vary throughout
the week/day?
• Is worsening of symptoms associated with any particular triggers (e.g.
pets, pollen, cold air, exercise, occupational exposure)?
• Are there any nocturnal symptoms?
• Is there a past medical history of eczema, hay fever or allergy?
• Is there a family history of asthma?
• Has the patient tried any bronchodilators and, if so, what effect did
these have?
• Is there a history of smoking?
• Are there any pets?
• Are symptoms better away from work i.e. is there occupational asthma?
(For more information on occupational asthma, see Chapter 15:
Occupational lung disease.)
49Asthma
Respiratory Medicine
MICRO-references
British Thoracic Society (BTS) Guideline for Asthma (updated 2019),
available at:
www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma/
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6. INVESTIGATIONS
In adults, lung function tests are performed as part of the routine clinical
•
assessment and patients are stratified as below (see Table 3.2).
Table 3.2 Management of asthma based on probability and spirometry findings.
HIGH PROBABILITY INTERMEDIATE LOW PROBABILITY
OF ASTHMA PROBABILITY OF ASTHMA OF ASTHMA
• Perform a trial of • Tests for airway obstruction • Refer as appropriate
asthma treatment e.g. spirometry, peak flow • Investigate/treat
• If responding, measurement, challenge other condition
continue treatment tests • Assess response and
• If not responding, • Other additional tests perform further
assess compliance include measurement of investigation/refer if
and inhaler blood eosinophils, total poor response
technique. Consider IgE, IgE to aeroallergens,
further investigation skin prick tests, exhaled
nitric oxide
Spirometry
•
• FEV
/FVC may show obstructive ratio (<0.7) but may be normal as
1
airflow obstruction is variable.
• Demonstrable reversibility: increase of > 200 mL (or 15% ) in FEV
after administration of inhaled b2-agonists.
Flow-Volume Loop
•
• is will demonstrate lower (smaller) airways obstruction:
– is is characterised by a decrease in flow at lower lung volumes.
Airway hyper-responsiveness testing:
•
• Methacholine, histamine and mannitol induce bronchospasm in nor-
neicid MeyrotarpiseR
•
mal individuals in sufficient amounts.
• Bronchial hyper-responsiveness is measured as PC
of the agent which provokes a 20% decrease in FEV1.
• PC
Peak expiratory flow rate (PEFR):
will be lower in patients with asthma compared to healthy
20
individuals.
: the minimum dose
20
• Useful in assessing variability and later response to treatment.
– > 20% diurnal variability on >3 days in the week is highly
suggestive.
• Patients can perform their own PEFR at home and record the results.
• Sensitivity is only 20% .
1
Establishing specific allergens:
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•
• Skin prick tests:
– A small amount of the test substance is introduced to the superficial
layers of the epidermis.
– A wheal >3 mm larger than the control suggests a positive result.
Blood tests:
•
• IgE: A higher total IgE level is associated with atopic disease.
– Specific IgE to allergens such as tree and grass pollens, house dust
mite and pets can be performed.
– is can aid management with allergen avoidance.
• Eosinophils: Increased eosinophils are seen in acute exacerbations and
poorly controlled disease.
– Blood eosinophils > 03./xc10
– Also, consider eosinophilic granulomatosis and polyangiitis (known
as Churg-Strauss disease).
Fractional exhaled nitric oxide (FeNO): Non-invasive method which may
•
act as possible surrogate marker for eosinophilic airway inflammation which
may influence corticosteroid use.
Induced sputum: Available in a limited number of centres in UK. Pres-
•
ence of sputum eosinophils (>3%) suggests risk of exacerbation and need for
increased corticosteroid treatment.
7. DIFFERENTIAL DIAGNOSIS
3
ells µL .
Asthma
51
In adults:
•
• Chronic obstructive pulmonary disease (COPD).
• Tumour or other cause of large airways obstruction.
• Pulmonary oedema (congestive heart failure – “cardiac asthma”).
• Churg-Strauss disease:
– Vasculitic process that can mimic severe asthma (see Chapter 11.
Interstitial Lung Disease and Vasculitis).
◯
Bronchiectasis
◯
Interstitial lung disease
◯
Post-nasal drip
◯
Vocal cord dysfunction
◯
Gastro-oesophageal reflux disease
◯
Carcinoid syndrome.
8. MANAGEMENT OF CHRONIC ASTHMA
Goals of treatment:
•
• e British oracic Society (BTS) states that the goal of treatment is
control of the disease, defined as:
– No daytime symptoms.
Respiratory Medicine
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– No night time awakening due to asthma symptoms.
– No need for rescue medication.
– No exacerbations.
– No limitations on activity.
– Normal lung function (FEV1 or PEFR >80% predicted/best).
MICRO-facts
The Royal College of Physicians 3 Questions Approach to monitoring
asthma:
In the last month/week, have you had difficulty sleeping because of
•
your asthma?
Have you had your usual asthma symptoms during the day?
•
Has your asthma interfered with your usual daily activities?
•
One positive=medium morbidity; two/three positive=high morbidity
– Minimal medication side effects.
• Different clinical questionnaires are available e.g. asthma control test,
RCP 3 Questions Approach to assess impact of disease and control (see
MICRO-Facts box).
Inhaled erapy: there are a lot of different inhalers with different medica-
•
tions, combinations of medications, and delivery systems. Input from a specialist asthma nurse can be critical in choosing the right device (metered dose
inhaler vs. dry powder) and checking for adequate inhaler technique. ey are
generally prescribed according to the BTS Stepwise approach (see Figure 3.2).
Figure 3.1 Flow volume loop and spirometry: on the left, the flow volume loop shows
a reduced lung capacity; on the right, the spirometry shows a reduced FEV
demonstrating a restrictive picture typical of asthma.
Respiratory Medicine
. This is
1
Asthma
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53
• Short-acting β
agonists (SABA): salbutamol, terbutaline.
2
– Take effect quickly (~15 minutes) and last 4–6 hours.
– Side effects may include tremor, palpitations and muscle cramps.
– Short-acting anticholinergic/antimuscarinic bronchodilators are
rarely used now as long-acting compounds are more effective
(see below).
• Long-acting β
agonists (LABA): salmeterol, formoterol.
2
– Similar side effect profile to SABA.
– Formoterol has more rapid onset than salmeterol.
– Increased risk of mortality with monotherapy use so expected to be
given in combination with an inhaled steroid (can be combined in a
single inhaler).
• Long-acting anticholinergic/anti-muscarinic (LAMA): tiotropium
bromide.
– Can be considered as add-on therapy in patients poorly controlled
on ICS/LABA.
– Commonly causes dry mouth.
– Caution in severe renal impairment.
• Inhaled corticosteroids (ICS): beclamethasone diproprionate (BDP),
budesonide, fluticasone, mometasone.
– e most effective preventative therapy.
– Reduces symptoms, exacerbations and improves lung function with
an impact on airway inflammation.
– Have a low threshold for starting in any symptomatic patient but
strongly consider in patients using SABA alone who:
◯
Are symptomatic >3x per week.
◯
Wake 1x overnight per week.
◯
Have suffered an exacerbation in the previous 2 years.
– Side effects include oropharyngeal candidiasis and dysphonia.
– In high-dose long-term use, may have impact on bone mineral
density.
– Potency of hydrofluoroalkane BDP is dependent upon inhaler brand
and so must be prescribed by inhaler brand not generic name e.g.
Clenil 400 mcg is equivalent to Qvar 200- 300mcg .
Systemic erapy:
•
• eophylline:
– Requires therapeutic drug monitoring.
– Clearance is increased by smoking, alcohol and enzyme-inducing
drugs and reduced by some antibiotics e.g. erythromycin.
– Side effects include nausea, vomiting and abdominal discomfort,
headache, malaise, tachycardia and fits.
Respiratory Medicine
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• Leukotriene-receptor antagonists (LTRA): montelukast, zafirlukast.
– Inhibit leukotriene receptors on smooth muscle preventing broncho-
constriction, oedema and mucus production.
– Used as an adjunct to inhaled therapy.
– Can improve exercise induced bronchoconstriction.
– May benefit those with NSAID/aspirin sensitivity.
• Oral Steroids:
– Short courses (e.g. 40 mg prednisolone for 5 days) can be given dur-
ing acute exacerbations.
– Patients may occasionally require long-term steroid therapy.
– Side effects include osteoporosis, immunosuppression, weight gain,
hyperglycaemia and adrenal suppression.
– Other immunosuppressants (cyclosporin, methotrexate) are rarely
used now.
• Anti IgE therapy (omalizumab)
– 2–4 weekly subcutaneous therapy in severe disease for patients with
elevated total IgE to and sensitivity to a perennial aeroallergen.
– Currently licensed by NICE for patients with 4 or more exacerba-
tions per year requiring oral corticosteroid therapy or continuous
corticosteroid use.
– Non-compliance with existing treatments must be addressed prior to
use.
– Has a steroid sparing effect and can improve QoL and symptom
score.
– Side effects: Local skin irritation, anaphylaxis and serum sickness.
• Anti-IL 5 therapy (mepolizumab, reslizumab, benralizumab)
– Either subcutaneous or intravenous monoclonal antibody therapy
to target IL-5 – a cytokine involved in eosinophil migration and
activation.
– Criteria for use varies for each individual drug but in general
licensed for patients with elevated blood eosinophil count who
have a high exacerbation frequency and/or maintenance steroid use
(dependent upon drug being used).
Respiratory Medicine
Stepwise management of asthma:
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Asthma
55
Figure 3.2 The stepwise control of asthma, adapted from BTS guidelines (see micro-
reference). Move up and down the steps according to response to achieve optimum
control. SABA – short acting beta antagonist; ICS – inhaled corticosteroid; LABA –
long acting beta antagonist; LTRA – leukotriene receptor antagonist; SR theophylline–
sustained release theophylline.
Asthma action plans
•
• ese form part of the self-management of asthma and should be given
to all patients.
• ey include clear written instructions on avoiding triggers, explaining
medications, recognising worsening asthma symptoms and what action
to take in this case.
• Advice should be clear, simple and tailored to the individual.
• Can reduce hospital admission frequency.
Respiratory Medicine
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