Pulmonology

ASTHMA

I. PATHOLOGY
A. Reversible airway bronchoconstriction, often due to allergic stimuli
B. Presents in childhood; often associated with allergic rhinitis, eczema,
and FHx of atopy
1. Adults – usually intrinsic aetiology vs. kids usually extrinsic = atopy
2. Most young asthmatics grow out of it in adolescences, or suffer
much less as adults (atopic march), although a few develop chronic BOYS tend to present < 2y, and
asthma later in life. GROW OUT.
a. Precipitants (non-specific) can include anything that irritates
airway e.g. cold air, exercise, emotions, allergens (house mite
dust, pollen, fur), infection, smoking (including passive),
pollution, NSAIDs (not just ASA!), beta blockers!
C. Risk factors: prematurity, low birth weight, and parental smoking, age,
gender, frequent/severe episodes of wheezing in childhood, atopy, FHx
atopy esp. maternal.
D. Pathogenesis = type I HS
1. Allergens induce Th2 phenotype in CD4+ T-cells of genetically
susceptible individuals
2. Th2 secrete IL-4 (mediates IgE class switch); IL-5 (attracts
eosinophils); and IL-10 (stimulates Th2, inhibit Th1)
3. Re-exposure to allergens leads to degranulation of mast cells (IgE-
mediated activation)
a. Release pre-formed histamine granules and generates
leukotrienes C4, D4, E4  bronchoconstriction, inflammation,
and oedema (early-phase reaction)
b. Inflammation, esp. major basic protein derived from eosinophils,
damages cells and perpetuates bronchoconstriction (late-phase)
E. Histological features
1. Obstructive pathology
a. Smooth muscle contraction and hypertrophy
b. Oedema and inflammatory exudate (eosinophils, lymphocytes,
plasma cells, mast cells, & vasodilation)
c. Excess mucus
d. Squamous metaplasia (less ciliary action)
e. Creola bodies (clumps of cells lining airway) & sloughing
epithelium
F. Clinical symptoms are episodic/intermittent and related to allergen
exposure
1. Dyspnoea + wheezing
a. Usually diurnal – worse at night + marked morning dipping;
normal other times
b. Quantify exercise tolerance
2. Productive (nocturnal) cough  sputum = classically spiral-shaped
mucus (Curschmann spirals) & eosinophils-derived crystals (Charcot-
Leyden crystals)
a. Disturbed sleep from nocturnal coughs = sign of severe dz
3. Atopic disease
a. Hay fever, foot allergies, eczema, FHx?
G. Clinical signs

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1. Tachypnoea, audible wheeze

2. Hyperinflated chest
3. Hyperressonant percussion Carpet, feather pillows, duvets,
4. Reduced air entry + polyphonic (continuous, high-pitched, musical) soft furnishing!
wheeze
H. Asthma may also arise from non-allergic causes (non-atopic) e.g.
asthma, viral, ASA (triad of nasal polyps + bronchospasms + asthma,
10% adults), and occupational (see OH).
1. Try to find it  home esp. bedroom
2. Job  better during weekends (or holidays); confirm by serial peak
flows.
I. Complications:
1. Aspergilloma (steroids use; also other infection)
2. Focal lung collapse (mucus plugging)
3. Overdistended lungs Signs of moderate asthma:
4. Bronchiectasis (obstruction + chronic infection  scar  dilate) PEF: > 50-75% best/predicted
5. Severe, unrelenting attack  status asthmaticus & death. SpO2 > 92%
Speech normal
a. Signs of severe asthma: can’t complete sentences, HR > 110, RR
RR < 25
> 25, PEF: < 50% predicted  send to A&E, consider admission HR <110
b. Signs of life-threatening asthma: silent chest, confusion/coma, Treat at home or at surgery
exhaustion  cyanosis (SpO2 < 92%) & respiratory acidosis (pH Assess response to Tx
< 7.35, PaCO2 = 4.6 – 6) from failed tachypnoea
“compensation”. PEF < 33% predicted  IMMEDIATE NEAR FATAL if PaCO2 is rising…
too exhausted
admission

II. DIAGNOSIS
A. Is clinical; 2016 BTS/SIGN guidelines – probability-based approach
1. Characteristic pattern of SiSx
2. Measurement of airflow obstruction (spirometry is preferred
because it allows clearer identification of this obstruction, and results
less dependent on effort)
3. Absence of alternative explanation
B. The key to this is careful history
1. If asthma is likely to be Dx, Hx should explore causes esp.
occupational
C. Factors that increase probability N.B. interval Sx may increase
1. >1 of the following Sx: probability BUT minority of
children w VIRAL-induced wheeze
a. Sx worse at night, and in early morning will also get interval Sx triggered
b. Sx in response to exercise, allergen exposure, cold air by other things.
c. Sx worsen after ASA/NSAIDs or BB
d. Frequent, recurrent, occur apart from colds/with emotion
(children).
OCCUPATIONAL HX! Rhinitis often
2. Hx atopy precedes respiratory Sx in
3. FHx asthma or atopy occupational asthma.
4. Widespread wheeze on auscultation
5. Otherwise unexplained low FEV1 or PEF (historical or serial) For Dx of occupational asthma,
see flow chart in public health
6. Otherwise unexplained peripheral blood eosinophilia notes.
7. Sx/lung function improve with treatment
D. Factors that decrease probability
1. Sx only w cold; no interval Sx
2. Chronic productive cough W/O wheeze or SOB
Persistent moist cough in children

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Pulmonology

3. Dizziness/peripheral tingling/ light headedness DDx:

4. Repeatedly normal O/E, PEFR, or spirometry even when Sx CF
Ciliary dyskinesia
5. Voice disturbance Bronchiectasis
6. Cardiac Hx Protracted bronchitis
7. Significant smoking Hx (>20 pack years) Immunodeficiency
8. NO response to trial of Tx (children)
9. Clinical Hx suggest different Dx (children  take a BIRTH and PERI-
NATAL Hx).

Children Adults
Cystic Fibrosis Malignancy
Congenital laryngeal or tracheal structural COPD
abnormality or congenital heart defects
Inhaled foreign body HF
Postnasal drip IHD
GORD esp. if vomiting or aspiration GORD
Bronchiectasis, or TB Rare causes: ILD, pulmonary Fb, recurrent
PE, TB

Table 1.  for asthma in children and adults

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 Pulmonology

III. ASTHMA-COPD OVERLAP SYNDROME Global initiative for asthma (GINA)

A. Characterised by persistent airflow limitation w several features and global initiative for COPD
(GOLD); NEJM 2015
associated with both conditions (prevalence of overlap in 1 study was
27%)
B. Associated w higher rates of exacerbation, hospitalisation, and
mortality. Faster decline in lung function and reduced QoL.
C. Identify patients w asthma or COPD on Hx & O/E + radiology
D. Assess features of each (investigations cannot reliably separate the 2,
as often have chronic airflow limitation w significant airways
reversibility)
1. 3+ features from one of asthma or COPD (syndromic Dx of airway dz)
makes that one the likely Dx (Table 2).
2. While similar features from both suggest ACOS
3. Patients will be on a spectrum: from pure asthma and pure COPD at
opposite ends.
E. Spirometry
1. Before & after trial of Tx
2. Normal FEV1/FVC incomptabile w ACOS, unless other evidence of
chronic airways limitation
3. Post-bronchodilator FEV1/FVC usually < 0.7
4. FEV1 > 80% predicted – compatible w mild ACO
5. FEV1 < 80% predicted – indicates severity in same manner as COPD
6. Post-bronchodilator increase in FEV1 of 12% and 400 ml from
baseline indicates marked variability  either asthma or ACOS
F. If we suspect ACOS – then Tx should be started as for ASTHMA

Asthma
Onset < 20 y
Variation in Sx over mins, hrs, or days
Sx worse during night or early morning
Sx triggered by exercise, dust, emotions,
allergens exposure
Airway limitation variability
PFTs normal between Sx
Previous Dx of asthma
FHx asthma or other allergic conditions
No worsening of Sx over time – varies
seasonally or from year-to-year
May improve spontaneously, or have
immediate response to bronchodilator or
steroids over weeks
CXR normal
COPD
Onset > 40 y
Persistent Sx despite Tx
Good and bad days, but always daily Sx
and exertional SOB
Chronic cough + sputum (Sx) precedes
onset of SOB, unrelated to triggers
Persistent airflow limitation, post-
bronchodilator FEV1/FVC < 0.7)
PFTs abnormal between Sx
Previous Dx of COPD, chronic bronchitis, or
emphysema
Heavy exposure to a risk factor in HX e.g.
cigarette smoke
Progressively worsens
Rapid acting bronchodilator e.g. SABA,
SAMA only provides limited relief
CXR shows severe hyperinflation

Table 1. Syndromic diagnosis of airway disease (asthma vs. COPD)

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 Pulmonology

IV. MANAGEMENT
A. Asthma ladder (updated 2016 BTS/SIGN)
1. Now start with ICS
2. Step up if >3X SABA required a week. Step down if lower.
B. Brief pharmacology
Beta2-agonists Increases cAMP = relax bronchial SM within minutes.
S/E: tachycardia, hypokalaemia, tremor, anxiety.
Blue inhaler SABA = salbutamol, terbutaline
(SABA) LABA = salmeterol, formoterol  reduces nocturnal Sx; can
Green inhaler be an alternative to increase ICS dose
(LABA)
Corticosteroids Reduces bronchial inflammation. Affects gene transcription Rx by brand name:
hence acts within days. Beclomethasone = Clenil
Brown inhalers Best route is INH (avoids systemic effect) e.g. Modulate; fluticasone = Flixotide,
beclomethasone budesonide = Pulmocort
S/E: oral candidiasis– rinse mouth after use of ICS.
Qvar (CFC containing) = 2X more
Increase rate of cataracts if lifetime dose > 2g potent than Clenil Modulate
bleclometasone.
PO steroids used acutely (high doses, short courses. E.g. Symbicort = budesonide +
prednisolone 40 mg/d PO for 1 week). Can be used longer if salmeterol
lower doses (5-10 mg/d) if INH cannot control. Carry a steroid card if significant
Aminophyllines Is metabolised to theophylline. They are the steroid absorption (doses > 250
phosphodiesterase inhibitors  increase cAMP  reduce mcg). Low doses beclomethasone,
bronchoconstriction. don’t really need.
PPx at night (PO) to prevent the morning “dipping”. May be a
useful adjunct* to other inhaled therapy. Try to avoid theophylline:
Stick with one brand (different bioavailability). narrow TI + S/E nasty e.g.
In acute severe asthma, it can be given as IVI. arrhythmias, seizures and
Anti- E.g. ipratropium (SAMA) & tiotropium (LAMA). May reduce electrolyte imbalances. Need ECG
monitoring, electrolytes, and
cholinergics bronchospasm synergistically with 2-agonists. However, not theophylline plasma levels if IVI in
recommended in current guidelines for chronic asthma. emergencies.
(yellow inhaler) More of a benefit to COPDers. Mild S/E: GI upset.
Cromoglicate PPx mild or exercise-induced asthma, esp. children. It is
always administered INH. It is a mast cell stabiliser,
preventing histamine release. S/E: may ppt. asthma.
Leukotriene E.g. montelukast, zafirlukast (PO).
receptor Blocks effects of Cys-LKT in airways by inhibiting CystLT1 R.
antagonists
Anti-IgE Mab Omalizumab used in highly selected patients w persistent
allergic asthma. It is given SC every 2-4 weeks (depends on
dose). Specialists only.

C. Effects of corticosteroids on growth

1. 2 long-term studies show no effect
2. BTS/SIGN suggest 400 mcg/day equivalent may be associated w S/Es
3. At 800 mcg and above  risk adrenal suppression.
4. Plot the height and weight of all children w asthma annually. If on
800 mcg or more  get a steroid card + under care of paeds.
5. Consider adrenal insufficiency if child on ICS presenting with shock
or reduced LOC.
6. Assess FEV1 or PEF and/or Sx
Evidence of steroids on growth:

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a. Before and after 400 mcg inhaled salbutamol with diagnostic NEJM 2000 (Agertoft & Pederson)
uncertainty and airflow obstruct present at time of assessment. – children on budesonide attained
normal height (predicted from
b. In other patients, or if there is incomplete response to INH parental height)
salbutamol, after either ICS (200 mcg BD beclomethasone NEJM 2000 CAMP research group
equivalent for 6-8 weeks) or PO steroids (30 mg OD for 2 weeks) Lag was greatest in first year of Tx
7. Adults = currently little evidence at <800 mcg day BDP – bone mineral but eventually after 4-6 years,
projected final height attained in >
density / adrenal function: unknown… lowest dose possible. 1000 children.
8. Note bone growth also affected by under-treated asthma.

D. LABA and asthma  always use w ICS Evidence LABA to be used with
1. SIGN 2016: LABA must only be used in those already on ICS. Use ICS:
MHRA 2007 – benefit outweigh
lowest dose as possible. Combination inhalers (SIT) recommended risk
to aid compliance. Cochrane 2010 review of 77 RCTs
2. Do not start in patients with acutely deteriorating asthma! (> 21000 patients) = show
reduced exacerbations +
improved PFTs if use a LABA with
E. Single Inhaler Therapy (SIT) = combination of ICS + LAMA ICS. No significant increased risk
1. The latest Cochrane review (2013) suggested SIT improved control in of death/adverse events in LABA
patients with milder asthma vs. increase in ICS with separate PRN treated group but absolute risk is
reliever therapy, but was no more effective than combined low.
ICS/LABA for Sx.
2. Exacerbations reduced compared to Tx w standard ICS/LABA.

F. Other steroid S/E

1. Longer than 3 months = long-term; or require frequent courses (3-4
X per year)  risk systemic S/E. Monitor:
a. BP
b. Urine, BM, cholesterol (DM & hyperlipidaemia)
c. Bone mineral density – when a significant reduction occurs, Tx
with long-acting bisphosphonate (as per British Osteoporosis
Guidelines); BMD should be monitored in children > 5 (American
Academy of Paediatrics)
d. Growth (height + weight centile) in children
e. Cataracts may be screened in children through community
optometric services.

G. For exercise-induced asthma in a person who is taking ICS, and

otherwise well-controlled:
1. Add LKT receptor antagonists or LABA or sodium
cromoglicate/nedocromil sodium, or theophyllines
2. SABA is DOC immediately prior to exercise (PPx)

H. Improving asthma management in adolescents (recommendations)

1. Self-management plan (youthhealthtalk.org + BTS guidelines =
components of such programme)
2. Adolescents w cardio-respiratory Sx  consider asthma
3. Address co-morbidities and modifiable RF
a. Co-morbidities  anxiety, depression, obesity, GORD, smoking

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Diagnostic criteria for moderate, severe and life-threatening asthma discussed on page 2.

V. ACUTE MANAGEMENT OF SEVERE ASTHMA

A. Refer to diagram in page 6 also.
B. SIGN 2014 guidelines:
Have they been admitted to ICU
before? Previous acute attacks?

DDx = acute infective

exacerbation of COPD, pulmonary
oedema, URT obstruction, PE,
anaphylaxis, PTX

Investigations = check PEF (may

be too sick), ABGs if SpO2 < 92%,
CXR if suspect PTX, infection, life-
threatening attack.

C. Keep repeating salbutamol if PEF < 75% in acute severe asthma. Keep
monitoring RR, HR, sats.
D. Before discharge – stabilisation of discharge med for 1 day, INH technique
checked, PFR > 75%, diurnal variability < 25%. Own PEF + action plan + GP
review in 1 week. Resp clinic appt in 4 weeks.
E. Aminophylline used much less frequently, according to current BTS
guidelines. It is a nasty drug with narrow TI and shit S/Es.
1. If you have to use it – make sure tailor IVI dose
2. Reduce if cardiac + liver failure or any drugs that increases half-life

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(CYP450 inhibitors) – ciprofloxacin, erythromycin, cimetidine, COCP.

3. Increase dose if CYP450 inducers – “CRAP GPS” e.g. carbamazepine,
rifampicin, alcohol (chronic), phenytoin, griseofulvin,
phenobarbitone, sulphonylureas.
F. Aim for concentrations of 10-20 g/mL to avoid toxicity (> 25 g/mL).
G. Measure K+ (hypokalaemia risk)
H. Don’t load it on patients who are already on PO preparations.

VI. NON-PHARMACOLOGICAL THERAPY

A. Primary vs. secondary PPx
B. Breastfeeding in children encouraged - ?protective against early asthma
C. Avoidance of tobacco smoke. Quit smoking.
D. Advise weight loss in obese
E. Immunotherapy if allergen can’t be avoided Early exposure to dust/allergens
F. Breathing exercise programmes may help QoL and Sx control cause SN = RF for asthma.
1. Papworth method – psychological + physical = drop shoulders, relax
abdomen, breathe calmly Teach use of PEF BD ma be useful.
2. Buteyko breathing technique and yoga also common Self-management of medications
3. All of these share the common elements of nasal breathing, in light of Sx. Written action plan
in emergencies.
relaxation techniques, and reduce hyperventilation  increase
diaphragmatic and resp muscle strength + stamina
4. Breathing device to produce resistance to inspiration at set
pressure  increases thoracic cage flexibility and improve posture
5. N.B. no change in lung functions but reduce Sx and bronchodilator
use + QoL scores improvement.
G. Air ionisers not recommended
H. Reduce exposure to house dust mite not recommended
I. Pet removal reported effects paradoxical
J. Possible adjunct for family therapy in difficult childhood asthma

VII. THE ASTHMA REVIEW

A. Assess
1. Control
a. Complete asthma control means
i. No daytime Sx
ii. No night-time awakening due to asthma BTS/SIGN 2014
iii. No need rescue meds
iv. No asthma attacks
v. No exacerbations
vi. No limitations on activity including exercise
vii. Normal PFTs
viii. Minimal side effects from meds
b. Can be simply assessed using a few questions
i. “Have you had difficulty sleeping due to your asthma?”
ii. “Have you had your usual asthma Sx during day?” Assessment form also includes
iii. “Has your asthma interfered w usual activities?” date. Applies to all patients w
asthma > 16 (easy but NOT well
c. Reasons for inadequate control
validated). Only used after Dx
i. Compliance established. Better alternatives
ii. Patient’s concerns (Re: S/Es) e.g. SIGN 2008 asthma control
iii. INH technique questionnaire.
iv. Trigger factors

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v. Consider other Dx.

2. Lung function (spirometry – gold standard, PEFR – easier)
PFTs can’t be used reliably to
3. Exacerbations, ICS use, time-off work or school guide treatment under 5!
4. Inhaler technique
a. For ALL inhalers - (1) breathe out first (creates more space in Before starting new drugs = check
airways for when you breathe in next w the puff = drug can compliance to existing drug, INH
technique, eliminate triggers
reach smaller airways); (2) hold breath after inhaling ~ 10 secs
(keeps air movement still = allow medications to get into lungs)
b. If have “press and breathe” MDI (metered dose inhalers) =
puffers  shake and mix; then after pressing canister fully =
breathe in at right time (ensure not too early = lungs full before Press & breathe MDI works better
w spacer
all meds release; or too late = ends up in the mouth instead).
Leave enough time between dose (shake then 30-60 s). Breathe normally MDI e.g.
c. Guide patients to Asthma UK website Autohalers (breath-actuated). Rx
d. Static can reduce dose delivery (in some devices), so wash in if trouble with normal MDI.
water before dosing & leave dry, do not rub. DPI (dry powdered INH) releases
e. If using spacer: pointless to squirt many puffs into device – best fine powder = need to breathe in
to repeat single doses, and ensure INH as soon as drug in spacer. very hard.
5. Concordance/compliance
6. Frequency of beta-agonists Rx
7. Possession and use of a personal action plan i.e. what to do when
exacerbation
a. It saves lives (national review of asthma deaths, 2014)
8. Flu jab
9. Children  assess exposure to smoke; assess GROWTH

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