Adult Asthma (Medicine)Mohd Hanafi Ramlee

History Asthma : derived from the Greek aazein, meaning "sharp

breath." The word first appears in Homer's Iliad. In 450 BC. Hippocrates: more likely to occur in tailors,

anglers, and metalworkers. Six centuries later, Galen: caused by partial or complete

bronchial obstruction. 1190 AD, Moses Maimonides: wrote a treatise on asthma,

describing its prevention, diagnosis, and treatment 17th century, Bernardino Ramazzini: connection between

asthma and organic dust. 1901: The use of bronchodilators started. 1960s: inflammatory component of asthma was

recognized and anti-inflammatory medications were added to the regimens.

What is known about asthma?

ASTHMAChronic inflammatory condition of the

airways characterized by;- airflow limitation (reversible with treatment)- airway hyper-responsiveness to a wide range stimuli- inflammation of the bronchi

In chronic asthma, inflammation maybe accompanied by irreversible airflow limitation

Symptoms are cough, wheeze, chest tightness, and shortness of breath which often worse at night

Simple DefinitionA reversible chronic inflammatory

airway disease which is characterized by bronchial hyper-responsiveness of the airways to various stimuli, leading to widespread bronchoconstriction, airflow limitation and inflammation of the bronchi causing symptoms of cough, wheeze, chest tightness and dyspnoea.

Epidemiology Common disease with

unacceptably high morbidity and mortality

Commonly underdiagnosed and undertreated

Only 36.1% of adult asthmatics ever had their peak flow measured

Higher prevalence in rural (4.5%) than in urban areas (4%),lower educational status(5.6%) and lower income

Majority of patients(87.3%) had mild asthma; 9.9% had moderate asthma and 2.7% had severe asthma

Among severe asthmatics, only 19.4% were on inhaled corticosteroids

87%

10%3%

Asthmatic patient

Mild Moderate Severe

Epidemiology

EPIDEMIOLOGY The prevalence of asthma has

increased 61% over the last two decades.

Asthma is the leading chronic illness among children.

Asthma results in 10 million lost school days and 3 million lost work days.

Deaths from asthma have increased by 31% since 1980.

Classification Extrinsic – implying a definite external cause

more frequently in atopic inviduals (atopic – individual which tends to develop

hypersensitivity by contact with allergens) often starts in childhood - accompanied by

eczema

Intrinsic/cryptogenic – no causative agent can be identified starts in middle age

Types of AsthmaAccording to the severity: helpful for treatment and management.

Very mildMild

ModerateModerately Severe

Severe

Types of AsthmaAccording to pathophysiology

Allergic asthma

Intrinsic (Non-Allergic)

Exercise-induced

Occupational (allergic)

Steroid-resistant

ABPA (allergic)

Pathogenesis Complex, not fully understood numbers of cells, mediators, nerves, and

vascular leakage -activated by expose to allergens or several mechanism

Inflammation Eosinophils, T-lymphocytes, macrophages and mast

cell Remodeling Deposition of repair collagens and matrix proteins-

damage Loss of ciliated columnar cells- metaplasia – increase

no of secreting goblet cells

Pathologic features of asthmai. Inflammatory cell infiltration of the airwaysii. Increased thickness of the bronchial

smooth muscleiii. Partial or full loss of the respiratory

epitheliumiv. Subepithelial fibrosisv. Hypertrophy and hyperplasia of the

submucosal glands and goblet cellsvi. Partial or full occlusion of the airway lumen

by mucous plugsvii. Enlarged mucous glands and blood vessels

Pathophysiology Smooth muscle contraction Thickening of airway –cellular infiltration and

inflammation Excessive secrection of mucus Genetic factorCytokine gene complex (chromosome 5)-IL-4

gene cluster control IL-3, IL-4 , IL-5 and IL-13Environment factorChildhood expose irritants or childhood infection

PathophysiologyExtrinsic asthma: Atopic/allergic,

occupational, allergic bronchopulmoary aspergillosis.

Atopic or allergic Dust, pollens, animal dander, food etc.

Family history of atopy. ↑ serum IgE. Skin test with Ag wheal, flare

( Classical IgE mediated response) Exposure of pre-sensitised mast cells

to the Ag stimulates chemical mediators from these cells. Type 1 hypersensitivity.

1.Early phase Inhaled Antigen

Sensitised mast cells on the mucosal surface mediator release.

Histamine bronchoconstriction, increased vascular permeability.

prostaglandin D 2 bronchoconstriction, vasodilatation.

Leucotriene C4,D4, E4 Increased vascular permeability, mucus secretion and bronchoconstriction.

Direct subepithelial parasympathetic stimulation bronchoconstriction.

2.Late phase starts 4 to 8 hours later Mast cell release additional cytokine Influx of leukocytes(neutrophil,eosinophil) Eosinophils are particularly important-

exert a variety of effect

Pathophysiology Atopic Asthma

TriggerEg.dust,pollen, animal dander

TH2 cell

IL5

IL4

Eosinophil

IgE B cell

Mast cell

IgE antibody

MediatorsEg.Histamine,

leukotrines

BronchospasmIncrease vascular permeability

Mucus production

Immediate phase(minutes)

Bronchial inflammation

Environment factor Genetic prediposition

Bronchial hyperreactivity + trigger factors

Cough, Wheeze, Breathlessness, Chest tightness

OedemaBronchoC

Mucus production

Airways narrowing

Aetiology and triggers Complex and multiple environmental and

genetic determinanta) Genetic factorsb) Allergen exposure house dust mite,

household pets, grass pollenc) Atmospheric polution sulphur dioxide,

ozone, ciggerate smoke, perfumed) Dietary deficiency of antioxidants vit E

and selenium may protect asthma in children(freshfruits and vegetables)

Aetiology and triggerse) Occupational sensitizers

isocyanates(from industrial coating, spray painting) colophony perfumes(electronic industries)

e) Drugs NSAIDS B-blocker(B1 adrenergic blocker drug such as atenolol

is avoided to treat HPT and angina in asthmatic pt f) Cold airg) Exercise exercise-induced wheeze is driven by

histamin and leukotrienes which are release from mast cells when epithelial lining fluid of the bronchi become hyperosmolar owing to drying and cooling during exercise

h) Emotion

History Presenting symptoms: Cough ± sputum

- time: become worse at night- duration: chronic / acute- associated with wheezing- fever? URTI

Wheeze- max during expiration and accompanied by prolonged expiration

Cough History1.Ask specifically about the symptoms: -Cough?how is the cough? more severe at night or on day? associated symptoms like dyspnea & wheezing? how long is the cough? Recurrent?Any previous similar episode? Aggravated factor?like cough become severe after exercise?or the cough is initiated after exercise?

Cough History2.If the cough is associated with dyspnea and

wheezingis it relieved by bronchodilator?

3.Ask for any precipatating factors -whether the symptoms(cough,dyspnea,wheezing) started after exposure to weather changes, dust, exercise, infection or drugs?

4.Is there any pets,carpet or feather pillow in home?(easily trapped dust and the dust or animal

fur will cause exacerbation of asthma)

Dyspnoea HistoryDyspnoea

- onset: after exercise? cold? dust? animal fur? emotion?- severity and pattern: varies from day to day or from hour to hour- no chest pain

HistoryClinical features Recurrent episodes of wheezing,chest

tightness,breathlessness and cough Precipitants- cold,allergen,pollutant,viral urti Exercise tolerance Disturbed sleep Other atopic disease Home-Pet?Carpet? Occupation

HistoryClinical features Display diurnal pattern,symptoms

and PEF worse in the morning Mild intermittent asthma-

asymptomatic between exacerbation

Persistent asthma-chronic wheeze and breathlessness

History5.Any history of atopy(eczema,hay fever) or

allergic rhinitis?

6.Any family history of asthma?Any childhood asthmatics?

7.Whether he is a smoker or any family members is a smoker?

8.What is his occupation? Exposure to chemicals?

HistoryPast medical history: Experienced asthma attack before Taking any medications: NSAIDs / β-blocker /

aspirin (non atopic asthma)

Family history: Has family history of asthma

HistorySocial history: Occupation: expose to fumes/organic/chemical

dust House: near to factory? Pets? Dust? Carpet?

Feather pillow? Smoking in any family members

known asthmatic When he was diagnosed with asthma? How the asthma was diagnosed? Who diagnosed it? Whether he is on prophylaxis?

What type of prophylaxis? How he get the drugs and how many

dosage of the drugs? Whether he know how to deliver the

drugs properly? How is his compliance to drugs?

Physical examination General inspection:

- tachypnoeic, sign of respiratory distress, effort of breathing, cyanosis (life-threatening)

Inspection:- fingers: tar staining- pulse rate: tachycardia and pulsus paradoxus, bradycardia (life-threatening)- used of accessory muscles or recession- wheezing

Chest Inspection:

- shape: hyperinflated in severe asthma- movement of chest/silent chest (life-threatening)- chest deformity:- recession:

Palpation:- chest expension may be reduce (hyperinflated)/ normal- apex beat: may be displaced-vocal fremitus: decrease

Percussion:- may be hyperresonance / normal

Auscultation:- breath sound: vesicular- ronchi in expiratory phase, may be both in severe asthma- prolonged expiratory phase-vocal resonance decrease / normal

Clinical featuresSign• Tachypnoea,audible wheeze,hyperinflated

chest,hyperresonant percussion note,diminished air entry,widespread polyphonic wheze

• Severe attack – inability to complete sentences, pulse >110bpm, RP>25/min, PEF 33-50%

• Life-threatening attack- silent chest,cyanosis,bradycardia,exhaustion, PEF < 33%,confusion

• Pulsus paradoxus (exaggeration of the normal variation in the pulse volume with respiration, becoming weaker with inspiration and stronger with expiration )

Correlation+ The symptoms of asthma consist of a triad of dyspnea,

cough, and wheezing.+ At the onset of an attack, patients experience a sense of

constriction in the chest, often with a nonproductive cough.

+ Respiration becomes audibly harsh; wheezing in both phases of respiration becomes prominent; expiration becomes prolonged; and patients frequently have tachypnea, tachycardia, and mild systolic hypertension.

+ The lungs rapidly become overinflated.+ If the attack is severe or prolonged, there may be a loss

of adventitial breath sounds, and wheezing becomes very high pitched.

+ The accessory muscles become visibly active, and a paradoxical pulse often develops.

Diagnosing asthma

Diagnosing asthma Reversible and variable airflow limitation-as

measured by a peak expiratory flow (PEF) meter in any of the following ways:

PEF increases more than 15% and 200mls 15 to 20 mins after inhaling a short acting beta2 agonist, or

PEF varies more than 20% from morning measurement upon arising to measurement 12 hours later in patients who are taking a bronchodilator, or

PEF decreases more than 15% after 6 mins of running or exercise

Differential diagnosis+ Upper airway

obstruction    – Tumor    – Epiglottitis    – Vocal cord dysfunction

   – Obstructive sleep apnea

+ Bronchomalacia + Endobronchial lesion + Foreign body + Congestive heart failure + Gastroesophageal

reflux

+ Sinusitis + Adverse drug reaction

   – Aspirin    – Beta-adrenergic

antagonist    – ACE inhibitors    – Inhaled pentamidine

+ Allergic bronchopulmonary aspergillosis

+ Hyperventilation with panic attacks

Non-specific investigation Non-specific:

- full blood count and differential count: increase number of eosinophils number- arterial blood gases- sputum test: number of eosinophils- chest X-ray: hyperinflated

Specific investigation Specific:

- respiratory function test:1. peak expiratory flow2. spirometry

- exercise tests -histamine/methacholine bronchial provocation test- trial of corticosteroids

Reversibility Test+ This test is done to see whether the

obstruction can be relieved by the use of a short-acting bronchodilator eg salbutamol

+ An improvement of 15% or more (as measured on the peak flow meter) is diagnostic of asthma.

+ However, in severe chronic disease or patient who has treated with long-acting bronchodilators, little reversibility will be demonstrated.

Reversibility testForced expiratory manoeuvres before 20 minutes after inhalation of a beta-2-adrenoceptor agonist. Note the increase in FEV1 from 1.0 to 2.5 litres.

Peak expiratory flow rate Simple and cheap Subject take full inspiration then blow

out forcefully into peak flow meter. Best used to monitor progression of the

asthma and its treatment. To access possible occupational asthma PEFR value varies with sex, age and

height.

Peak Expiratory Flow Rate (PEFR) The maximum rate of air breathed out as

hard as possible through a measuring device called a peak flow meter, (after a full breath taken in).

Reading is measured in litres/minute (l/min).

Take 3 readings and choose the best Reading < 80% - presense of obstruction,

but not diagnostic of asthma

Require to take a series of reading - on waking up

- prior taking bronchodilator- after taking bronchodilator (before sleep)

PEF measurements1. During periods of well-being: provides measurement

of the patients best PEF value which will provide the target for the doctor and the patient to aim for.Twice daily measurements before any inhaled bronchodilator tx will determine the diurnal variability of airway calibre.Good control of asthma means PEF variability is maintained at less than 10%.

2. During symptomatic episodes: During an attack of asthma PEF fairly accurately measures the degree of bronchospasm.A PEF of less than 50% of normal or best suggests a very severe attack and a PEF of less than 30% suggests a life-threatening attack

Response to treatment

Occupational asthma

Spirometry Test+ It is the single best diagnostic test for patients

with airflow limitation. + A Spirometry Test

+ - measures the volume of air blown out against time + - gives more specific information about lung function.

+ A value is calculated for the amount of air blown out in one second - “Forced Expiratory Volume” or FEV1).

+ This is divided by the total amount of air blown out until all air is expired - Forced Vital Capacity or FVC).

+ FEV1/FVC expressed as a percentage value

+ Reading is affected by age, gender and height+ Male Spirometry reading range

Mild reduction: 2.5 litres or more Moderate reduction :1.5 to 2.49 litres Severe reduction :Less than 1.5 litre  

+ Female Spirometry reading rangeMild reduction :2.0 litres or more Moderate reduction: 1.0 to 1.99 litres Severe reduction: Less than 1.0 litre

+ In asthma, the readings will be reduced, returning to normal between episodes

TLC

VC

RV

IC

FRC

IRV

ERV

RV

TV

TLC : total lung capacity VC : vital capacityRV : reserve volumeIC : inspirational capacityFRC : functional residual capacityIRV : inspirational reserve volumeTV : tidal volumeERV : expiratory reserve volume

Normal:75-80% Obstructive airway disease:

reduced ratio Restrictive lung disease: ratio

normal or increase (enhanced elastic recoil).

Exercise Test+ Done especially in children+ Peak flow reading measured before hand+ Ask patient to run for 6 min, to increase HR

> 160 beats/min+ Cannot run – use cold air challenge,

isocapnoiec (CO2) hyperventilation, aerosol challenge with hypertonic solution

+ After exercise – take readings at intervals of 5, 10 and 15 minutes.

+ Diagnosed asthma - fall in peak flow of 15% or more, after exercise.

Exercise test

histamine/methacholine bronchial provocation test

Chest X-rayShowed lung hyperinflation.Not diagnostic of asthmaUseful to rule out other causes eg. Pneumothorax-----------------------------------------------Hyperinflation and increased bronchovascular markings

Allergies & AtophyAllergen Provocation Test

In suspected occupational asthma and food-allergy related asthma

Skin-Prick Test To identify allergens A drop of allergen is

placed on skin , site is marked and pricked with needle, measured any weals

Approach to management

Advise

Monitor

Treatment

Admit

Assessment

Management

Severity assessment for acute setting of AEBA

Mild Moderate Severe

Breathless Walking Talking At rest

Can lie down Prefer sitting Hunched forward

Talk in Sentences Phrases Words

Alertness May be Usually agitated Agitated

Central cyanosis Absent Absent Present

Use of accessory muscle

Absent Moderate Marked

Sternal retraction

Absent Moderate Marked

Wheeze on auscultation

Moderate, often end expiratory

Loud Loud Silent Chest

Pulsus paradoxus Not palpable May be palpable Often palpable

Initial PEF More than 80% 60 – 80% Less than 60%

Oximetry on presentation

More than 95% 91 – 95% Less than 90%

Severity of AEBA 1

Severity of AEBA 2

Severity of AEBA 3

Management of Chronic Asthma Aims of management

• to recognize asthma• to abolish symptoms • to restore normal or best possible long

term airway function • to reduce morbidity and prevent

mortality

Approach of chronic asthma Education of patient and family Avoidance of precipitating factors Use of the lowest effective dose of

convenient medications minimizing short and long term side effects.

Assessment of severity and response to treatment.

1) Education of patient and family

i. Nature of asthmaii. Preventive

measures/avoidance of triggers      

iii. Drugs used and their side-effects       

iv. Proper use of inhaled drugs       

v. Proper use of peak flow meter       

vii. Knowledge of the difference between relieving and preventive medications  

vii. Recognition of features of worsening asthma increase in bronchodilator

requirement development of nocturnal

symptoms reducing peak flow rates).

viii. Self management plan for selected, motivated patients or parents.

ix. The danger of non prescribed self medication including certain traditional medicines.

2) Avoidance of precipitating factors

The following factors may precipitate asthmatic attacks:

• Beta blockers contraindicated in all asthmatics

• Aspirin and nonsteroidal anti-inflammatory drugs if known to precipitate asthma, these drugs should be avoided.

• Allergens e.g. house dust mites, domestic pets, pollen should be avoided whenever possible.

• Occupation should be considered as a possible precipitating factor.    

• Smoking active or passive.

• Day to day triggers such as exercise and cold air. It is preferable to adjust treatment if avoidance imposes inappropriate restrictions on lifestyle.

• Atmospheric pollution.

• Food if known to trigger asthma, should be avoided.

3) Medication2 major groups of drugs:

Bronchodilator drugs

•to relieve bronchospasm and improve symptoms.

Anti inflammatory drugs

•to treat the airway inflammation and bronchial hyperresponsiveness, the underlying cause of asthma, i.e. to prevent attacks.

Drug Delivery The inhaled route is preferred for beta2-agonists

and steroids as it produces the same benefit with fewer side effects

Inhaled medications exert their effects at lower doses

pMDI is suitable for most patients as long as the inhalation technique is correct

Alternative methods include spacer devices,dry powder inhalers and breath-actuated pMDI

Nebulised route is preferred in the management of acute attacks

3 main groups of bronchodilators [β2 agonists]

Inhaled β2agonist

• Salbutamol (Ventolin, Respolin)

• terbutaline (Bricanyl)

• fenoterol (Berotec)

• salmeterol (Serevent) - long acting

Oral long acting β2 agonist:

• salbutamol (Volmax)

• terbutaline (Bricanyl durules)

• bambuterol (Bambec)

Oral short acting β2 agonist:

• salbutamol • terbutaline etc.

2. Anti-Inflammatory Drug

• Corticosteroids Examples: Beclomethasone dipropionate (Becotide, Becloforte, Beclomet, Aldecin, Respocort) Budesonide (Pulmicort)

• Sodium cromoglycate (Intal)

• Other treatmentsAnti-histamines including ketotifen

Anticholinergics Examples: Ipratropium bromide (Atrovent)

Methylxanthines Examples: Nuelin SR,

Theodur, Euphylline

Approach To Drug Therapy - "Stepwise Approach" [step 1]Start at the step most appropriate to severity, moving up if needed or down if control is good for > 3 months. Rescued courses of prednisolone may be needed

STEP 1MILD EPISODIC ASTHMA• Infrequent symptoms • No nocturnal symptoms • PEF 80-100% predicted

Treatment:  inhaled beta2 agonist "as needed" for symptom relief.

If needed more than once a day, advance to Step 2

Approach To Drug Therapy - "Stepwise Approach" [step 2]STEP 2

MODERATE ASTHMA• Frequent symptoms • Nocturnal symptoms present • PEF 60-80% predicted

Treatment  • inhaled steroids, e.g. beclomethasone or

budesonide 200-800 mcg/day • inhaled sodium cromoglycate plus  • inhaled beta2 agonist "as needed"

Approach To Drug Therapy - "Stepwise Approach" [step 3]STEP 3SEVERE CHRONIC ASTHMA• Persistent symptoms • Frequent nocturnal symptoms • PEF 60% predicted or less Treatment:  • inhaled beclomethasone or budesonide 800-2000 mcg/day plus • inhaled beta2 agonist as needed plus, if necessary • oral beta2 agonist preferably long acting, or • inhaled long acting beta2 agonist, or • inhaled ipratropium bromide 40 mcg 3-4 times a day, or • oral theophylline (sustained release), or • nebulised beta2 agonist, 2-4 times a day

Approach To Drug Therapy - "Stepwise Approach" [step 4]STEP 4VERY SEVERE ASTHMA• Persistent symptoms not controlled by step 3 medications

Treatment:  • as in step 3, plus oral steroids (the lowest dose possible) STEP DOWN • Patients should be reviewed regularly. • When the patient’s condition has been stable for 3-6

months, drug therapy may be stepped down gradually. • The monitoring of symptoms and peak flow rate should be

continued during drug reduction.  

Management of acute severe asthma• RR >50/min• PEFR <50%

• Pulse >140 beats/min• breathlessness

• 10 puffs Bronchodilator and

Metered Dose Inhaler

• High flow 02, bronchoD

• MDI, nebulizer(1-2h)

• Oral prednisolone (3-5d)

• Monitore PEFR/O2

• B2 agonist / 02 if required

• PEFR <33%• Tiredness• Cyanosis• Decrease

respiratory effort• Silent chest

• iv aminophylline• Iv hydrocortisone

• Salbutamol• Ipratropium bromide• Adequate hydration

• antibiotic

• ICU• Artificial ventilation• Wean iv

• Β2 Agonist• Oxygen if required• Oral prednisolone

• Monitor PEFR• Patient’s education

• Review maintenance medication

• Review inhaler technique

• Follow up• PEFR monitor

DISCHARGE PLAN

response

Non- response

Give treatment

improve

Not improve

Management Of Acute Asthma Aims Of Management

i. To prevent death

ii. To relieve respiratory distress        

iii. To restore the patient’s lung function to the best possible level as soon as possible.

iv. To prevent early relapse

1. Assess severe attackSevere attack:

a) Unable to complete sentencesb) RR>25/minc) PR>110 bpmd) PEF< 50% of predicted or best

Life-threatening attack:a) PEF<33% of predicted or bestb) Silent chest, cyanosis, feeble respiratory effortc) Bradycardia/ hypotensiond) Exhaustion, confusion, or comae) ABG : normal/high PaCO2>5kPa (36mmHg) PaO2< 8kPa (60mmHg) low pH, e.g. <7.35

2. Start treatment immediately• Sit patient up & give

high dose O2 in 100% via non-rebreathing bag

• Salbutamol 5mg (or terbutaline 10mg) + ipratropium bromide 0.5 mg nebulized with O2

• Hydrocortisone 100mg IV/prednisolone 30 mg PO (both if very ill)

• CXR to exclude pneumothorax

If life threatening features (above) present:

• Inform ITU, and seniors

• Add MgSO4 1.2-2g IV over 20 min

• Give Salbutamol nebulizers every 15 min, or 10mg continuously per hour

Further managementIf improving• 40-60% O2• Prednisolone 30-60mg/24h PO• Nebulized salbutamol every 4 h• Monitor peak flow and O2 saturations

If not improving after 15-30min• Continue 100% O2 and steroids• Hydrocortisone 100mg IV or prednisolone 30mg PO if not

already given• Give Salbutamol nebulizers every 15 min, or 10 mg

continuously per hour• Continue ipratropium 0.5 mg every 4-6h

Post-attempt….If patient still not

improving

• Discuss with seniors and ITU.

• Repeat salbutamol nebulizers every 15 mins

• MgSO4 1.2-2g IV over 20 min, unless already given.

• Consider aminophylline, if not already on a theophylline. Alternatively, give salbutamol IVI.

Monitoring the effects of treatment

• Repeat PEF 15-30min after initiating treatment

• Pulse oximeter monitoring: maintain SaO2 >92 %.

• Check blood gases within 2h if:initial PaO2 was normal/ raised or initial PaO2 <8 kPa (60mmHg) or patient deteriorating

• Record PEF pre- and post- β-agonist in hospital at least 4 times.

Once patient improving…Once patient is improving

• Wean down and stop aminophylline over 12-24 h.• Reduced nebulized salbutamol and switch to inhaled β-

agonist.• Initiate inhaled steroids and stop oral steroids if possible• Continue to monitor PEF. Look for deterioration on

reduced treatment and beware early morning dips in PEF• Look for the cause of the acute exacerbation and

admission

Component 1: Patient-Doctor relationship

Component 2: Identify and Reduce Exposure to Risk Factors

Follow-Up and MonitoringInclude review of symptoms and

measurement of lung functiono PEF monitoring at every visit along with

review of symptoms helps in evaluating the patient’s response to therapy and adjusting tx.PEF consistently >80% of the patient’s personal best suggests good control.

o Regular visits (at 1 to 6 month interval as appropriate) is essential even after control of asthma is established

Asthma Management Plan When PEF >80%: continue current dose of

inhaled corticosteroids When PEF 60-80%:double the dose of inhaled

corticosteroids When PEF 40- 60%:start rescue course

prednisolone When PEF persists below 60% despite rescue

course prednisolone with worsening symptoms,advised to come to EMERGENCY DEPT immediately

Management of asthma in pregnancy In general during pregnancy,asthma

becomes worse in a third of women,is stable in another third and improves in the remaining third.

Women should be reassured that their asthma medication carries less risk to the foetus than a severe asthma attack

Inadequately treated asthma can cause maternal and foetal hypoxaemia,which leads to complications during pregnancy and poorer birth outcomes

Management: Pregnancy in asthmatics Treatment should be aggressive,with the aim

of eliminating symptoms and restoring and maintaining normal lung function

Beta2 agonists: No evidence of a teratogenic risk with the commonly used inhaled beta2 agonists

Ipratropium bromide: appears to be safe for use during pregnancy

Salmeterol/formoterol: not been tested extensively in pregnant women

Management: Pregnancy in asthmatics

Theophyllines: may aggravate the nausea and GERD and can caause transient neonatal tachycardia and irritabilityTeratogenicity has been shown in animals.

Sodium cromoglycate: no adverse foetal effects Inhaled corticosteroids: mainstay of tx in

persistent asthma,good safety profile in pregnancy Oral corticosteroids: necessary for severe

asthma in pregnancy but usually only for short periods.Increased risk of cleft palate in animals given huge doses of oral steroids

Anti-leukotrienes: no data available

Labour and Breastfeeding Women with very severe asthma may be

advised to have an elective caesarean section at a time when their asthma control is good

Breastfeeding should be continued in women with asthma

In general,asthma medications are safe during pregnancy and lactation and the benefits outweigh any potential risks to the foetus and baby

Allergic Rhinitis and Asthma 80% of patients with asthma have

allergic rhinitis When allergic rhinitis is undetected or

untreated,patients have frequent exacerbations not responding to conventional treatment

Nasal inhalation of corticosteroids are mainstay of treatment with or without oral antihistamine

Status AsthmaticusAcute exacerbation of asthma that does not

respond to standard treatment of bronchodilators and corticosteroids.

Symptoms include chest tightness, rapidly progressive dyspnoea, dry cough and

wheezing

The lung failure means that oxygen can no longer be provided, carbon dioxide can no

longer eliminated.Hence, leading to acidosis.

It is not just asthmaCase Presentation / UMMC

MIBMH 10.5 years old boy, known case of mild

intermittent asthma presented to HSB with: Fever, cough and runny nose ----- 1 wk. Hemoptysis and loss of appetite ---- 5d No night sweating . Seen by GP and managed with oral antibiotic

and symptomatic treatment but the patient did not improve.

Review of symptoms The patient is unable to lie flat for the

past 2 weeks due to feeling of breathlessness.

In HSB respiratory distress upon admission CXR:

mediastinal mass on right perihilar region multiple cannon ball lesions in both lung fields,

so CT thorax, abdomen and pelvis done

Huge anterior mediastinal mass encasing great vessels with lung metastasis and lymphadenopathy.

Referred to UMMC for possibility of malignancy.

Past history Asthma

since age of 7 years not on regular follow-up or

treatment/prophylaxis mild infrequent diurnal symptoms no interference with general activity or school

attendance. acute exacerbation: twice a year and

precipitated mainly by coldness. No hospital admission

Perinatal history: uneventful. Developmental history: attends school,

average level, very shy. Immunization: full schedule. Allergy: allergic to dust. Family and social history: No ill family member. No H/O contact with T.B

O/E Looks lethargic, dyspneic RR 32/min with

recessions, HR 120/min, SpO2 96% on face mask O2 5l/min, temp 36.4C

No lymphadenopathy. Lungs: -reduced breath sounds on right

medial and lower zones with crepitations on the right side

CVS: S1 + S2 , no murmur. Abdomen: soft, liver 2cm firm.

Genitalia: pubic hair stage 3, penile length 7.5cm, testes 2 ml each.

Breast tissue: gynaecomastia.

Growth parameters

Height: 166 cm Upper/lower segment ratio = 1

investigations FBC: Hb 11.9gm/dl wbc 12,600/ul plt

397,000/ul ANC 9,500/ul. BUSE: Na 131mmol/l K 3.9mmol/l Cl

95mmol/l urea 2.4mmol/l creat 77umol/l LFT: alb 29gm/l t-bili 4umol/l ALP 146u/l

ALT 41u/l AST 58u/l Ca 2.37mmol/l PO4 1.23mmol/l Mg

0.83mmol/l PBF: normal findings.

ESR: 110mm/hr CRP: 14.8mg/dl LDH: 511U/L

Radiological investigations

BhCG: <2 mu/ml (L) (0-10) AFP: 397040.9 (H) (0-6.7)

LH 11 mu/ml (H) (<0.1-6) FSH 33 mu/ml(H) ( 1.2-2.5) Estradiol <37 pmol/l (0-198) Testosterone 2.3 nmol/l (L) (8.4-28.7) DHEAS 0.5 umol/l (L) (2.2-15.2)

Karyotyping: 47 XXY, how many cells? Any evidence of mosaic Klinefelter? (waiting formal report).

diagnosis Mediastinal germ cell tumor with

bilateral lung metastasis and pseudoprecocious puberty.

Klinefelter syndrome.

Management and progress Respiratory support, required BiPAP . Required neb Salbutamol 4 hourly. Had spikes of fever, covered with

Erythromycin and Ceftriaxone. After 4 days in PICU transferred to P6. Started chemotherapy(UKCCSG). Had NNF covered with piptazocin then

imipenem and later on Ampho-B.

Became neutropenic. All blood and respiratory cultures have

no growth.

Discussion

Klinefelter syndrome In 1942 Klinefelter et al published a paper on

9 men with large breasts, minimal sexual and body hair, small testes and inability to produce sperms.

It is the most common syndrome assoc with male hypogonadism and infertility.

Classically 47XXY, but many variants like 48 XXXY, 48XXYY,49XXXXY,49XXXYY,50XXXXYY.

It is due to meiotic non-disjunction. mosaic patients may be fertile .

Features Hypogonadism (small testes and azoospermia-

hyalinzation and fibrosis of seminiferous tubules). Gynaecomestia in late puberty (30-50%) due to

increase estradiol/testosterone ratio. Psychosocial problems. Elevated urinary gonadotrophins. Mental retardation is affected by number of X

chromosomes (decreased IQ 15 points for each X chromosome) [most males with 47XXY have normal intellegence, 70% have minor developmental and learning disability]

Other features: Pes cavus, genu valgus, fifth finger

clinodactily. Taurodontism (prominent molar teeth):

40% in Klinefelter, 1% in general population.

Radio-ulnar synostosis---- 49XXXXY.

http://images.google.com/imgres?imgurl=http://www.mun.ca/biology/scarr/Klinefelter_Syndrome_XXYY.jpg&imgrefurl=https://eobiology.wikispaces.com/Klinefelter+Syndrome?f=print&usg=__SYSK-byG42Y-6vtHd9VG6gA8ri8=&h=282&w=197&sz=15&hl=en&start=3&um=1&itbs=1&tbnid=Zi9cfl-i8GqUmM:&tbnh=114&tbnw=80&prev=/images?q=klinefelter&um=1&hl=en&sa=N&rlz=1T4SKPB_enMY310MY312&tbs=isch:1

Increased risk of: DM. CVS: varicose veins, venous ulcer, DVT ,

pulm embolism, mitral valve prolapse. Cancer: breast, leukemia, mediastinal

germ cell tumors. Osteoporosis. Autoimmune disease (SLE, RA, Sjogren

with increased mortality).

Mortality 40% of conceptions with Klinefelter

survive fetal period. Mortality is not significantly higher in

healthy individuals.

Prevalence: in USA 1:500-1000 Race: no race difference. Age: it goes undetected in most affected

males until adulthood. the common indication for karyotyping is hypogonadism and infertility.

investigations Mid-puberty: increase FSH and LH, decrease

testosterone. Increase estradiol/testosterone ratio-----

gynaecomastia 80%. Cortisol should be checked (47% have low

cortisol). Decrease osteocalcin---- bone resorption. Coagulation profile because of increased risk of

DVT and pulm embolism. Karyotyping:47 XXY 80-90 % - 10% mosaic.

Germ cell tumors Classification: -suppressed differentiation: seminoma, dys-germinoma. -differentiation:Initial embryonal carcinomaEmbryonic mature and immature teratomaExtra-embryonic(choriocarcinoma-yolk sac

tumor{endodrermal sinus tumor}) -mixed histology: mixed GCT.

Primary mediastinal germ cell tumors Comprise only 1-3% of germ cell tumors. Overall teratoma is the most common variant,

seminoma is the most common malignant variant.

Malignant variants are uncommon and more in males.

Benign variants are equally disributed among males and females.

Testicular examination, U/S and CT are mandatory to rule out testicular primary cancer.

Serum markers Alpha-fetoprotein: indicates malignant

non-seminomatous type. BhCG: suggests trophoblastic

component.

Malignant non-seminomatous and mixed GCTs carry worse prognosis than other GCTs.

Association of M- GCTs with Klinefelter syndrome Klinefelter syndrome is present in 20%

of patients with M-GCT. The incidence of M-GCT is 50 fold

increased in patients with Klinefelter syndrome.

M-GCT mask the usual clinical signs of Klinefelter syndrome by inducing puberty by BhCG.

Comparison of GCT between KS and general population Klinefelter syndrome: All contain non-seminominatous

elements

Present at younger age (mean 17 years)

Precocious puberty is seen more often.

Almost exclusively extragonadal.

General population: Pure seminoma is the most

common malignant variant.

Older age at presentation (mean 29 years)

Precocious puberty is less often.

Only 2-5% extragonadal.

references http://emedicine.medscape.com/ Ann Thorac Surg 1998;66:547-548

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