Difficult Asthma by Dr. S.K Jindal | Jindal Clest Clinic

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DIFFICULT ASTHMA

• Dr. S. K. Jindal
• www.jindalchest.com

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Difficult Asthma

• Difficult for the patient
• Difficult for the physician
• Difficult for the family
• Difficult for the society

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Clinical Spectrum of Asthma
Mild Intermittent
Severe Persistent
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Confusing Terminology

• Severe asthma
• Difficult asthma
• Difficult to control asthma
• Steroid dependent /or resistant asthma
• Irreversible asthma
• Brittle asthma
• Refractory asthma (ATS)

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Difficult Asthma

• Asthma which is difficult to control with maximum
  treatment recommended as appropriate for that
  stage
• Persistence of symptoms, frequent exacerbations
  or airway obstruction despite high (or optimum)
  medication

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Case Report (Brittle Asthma)

• 42 F, Asthmatic
• Daily drug intake (SVC catheter)
• Theophylline 200 mg X 5 times
• Prednisolone 50 mg bd
• Terbutaline 0.25 mg tds (S/C)
• Inhalations Terbutaline 2 puffs X 6
• Ipratropium 2 puffs X 6
• Budesonide 1200 ug
• Frequent hospitalization
• Added continuous IV infusion of theophylline
  with CADD I- pump
• Speelberg et al, ERJ, 1988

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• K 60 F, Housewife
• Asthma gt 30 yrs
• Obesity, diabetes, hypertension, IHD, GER,
  cholelithiasis, OA, UV prolapse, panic-anxiety
  syndrome
• Asthma tmt Fluticasone 100 mg
• Salmetrol 100 mg
• Ipratropium 2 puff QDS
• Theophylline 300 mg BD
• Montelukast 10 mg OD
• Frequent oral / parenteral CS, antibiotics,
  mucolytics (etc.)

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• AS 48 M, Teacher NFA
• Known asthma gt 15 yrs
• Oral diclofenac for pain
• Severe attack after 3 hours
• During transportation fell, gasping, hypotension
• Intubated Ambu bag vent.
• Mech vent (CMV 12) VT 400 ml, FiO2 1 0.6
• Weaning (T piece) after 4 hrs.

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What is Difficult Asthma?

• Difficult to diagnose
• The basic disease (wrong diagnosis)
• B. Difficult to manage
• The disease associations
• The trigger control
• Acute exacerbation
• Fatality prone asthma
• Status asthmatics
• Steroid resistant

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Difficult Asthma

• Epidemiology
• Rare, lt 5
• Although rare, but account for majority of the
  asthma induced burden through
• Frequent hospitalization
• ER visits
• Absence from work or school
• Use of medications
• Higher prevalence among young females (15-30
  years)

AJRCCM 2000 162 2341
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Brittle Asthma

• Turner-Warwick (1977) Chaotic patterns on the
  daily PEF monitoring
• BTS asthma guidelines Sudden life threatening
  attacks usually without pre-morbidity

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Definitions

• Type I Brittle Asthma
• 40 diurnal variation in PEF
• Maintained over gt50 of a time period of at least
  150 days
• Despite maximal medical treatment including
  inhaled cortico-steroids (iCS) of 1500 mg BDP or
  equivalent.
• Type II Brittle Asthma
• Sudden acute attacks occurring in lt 3 hrs on a
  background of apparently well controlled asthma

Thorax 1998 53 315-321
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Refractory Asthma (ATS)

• Major Characteristics
• Control requiring use of
• 1. continuous or near continuous (gt50 of year )
  oral steroids
• 2. high dose iCS ( gt 1260 BDP, etc)
• Minor Characteristics
• 1. Use of daily controller medications in
  addition to iCS
• 2. Short acting ß-agonist use on a daily basis
• 3. Persistent airway obstruction
• 4. One or more ER visits per year
• 5. Three or more oral steroid bursts per year
• 6. Prompt deterioration on reducing oral steroids
• 7. Near fatal asthma event in past

AJRCCM 2000 162 2341
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Steroid Resistant Asthma

• Persistent respiratory symptoms
• Nocturnal exacerbations
• Chronic airflow limitation
• (FEV1 lt 70 of predicted)
• No response to short course (7-14 days) of high
  dose (gt 40 mg/day) oral glucocorticoids

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SRA Characteristics

• Longer duration Family history
• Blunted eosinophilic response to single dose of
  cortisol 21 succinate
• Increased cortisol clearance
• Distinct spirometric patterns
• a. Chaotic wide fluctuations with no baseline
  improvement
• b. Nonchaotic Little diurnal variability but
  adequate bronchodil response

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Causes of Failure to Respond in Refractory
Asthma

• Down regulation of beta receptors
• Fibrosis or other structural alterations that
  limit dynamic responses
• Unknown factors of AO - non-responsive to BD or
  CS
• 4. Altogether, a different disease

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Difficult Asthma Physicians assessment

• Is the diagnosis correct?
• Does any other disease, drug or trigger
  complicate the problem?
• Is the anti asthma treatment adequate and
  appropriate?
• What about patient compliance and inhaler
  technique?
• Environmental control measures?
• Any pharmacokinetic abnormality of the pt?
• Are the drugs being used reliable,..?

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Wrong Diagnosis

• Chronic Obstructive Pulmonary Disease
• Cardiac asthma
• Upper airway obstruction
• Vocal cord dysfunction
• Sleep apnoea
• Local obstruction by tumours/foreign body
• Hypersensitivity pneumonias
• Infections/Bronchiectasis
• Pulmonary embolism

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Case summary 40 M, shop owner Presenting
complaints Recurrent episodes of apnea 10
months Background Frequent cough Occasional
Breathlessness for 10 years No definite h/o
wheeze h/o loud snoring, no day time somnolence
No h/o seizures, abnormal behavior No h/o
stridor (but documented in PGI)
J Assoc Physicians India 2001 49488-90
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• Current Illness Nov 1999 First episode at
  night
• Uneasiness and difficulty in breathing
• Impaired consciousness
• Blue
• Admitted to ER, intubated,
• Recovered with in a day
• Subsequently Five admissions to DMC
• 10 episodes requiring ETT and short term
  mechanical ventilation (few hours to 1 day)
• Normal in between the episodes

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• No response to anti asthma measures
• Very quick reversal on intubation
• Normal lung functions in between
• Documented stridor

VOCAL CORD DYSDFUNCTION
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Disease Association

• Rhino-sinusitis / Polyps
• G.E. Reflux
• Obstructive sleep apnoea
• COPD
• Allergic broncho pulmonary aspergillosis
• Other infections
• Churg-Strauss syndrome / vasculitides
• Psychological problems

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• SS 31M Farmer
• H/o breathlessness, wheezing (episodic)
• mucoid/mucopurulent sputum gt 10 yrs
• Acute severe attacks
• Poor response to asthma tmt.
• H/o ATT in the past (twice)
• Exam Extensive rhonchi crackles
• Haemogram TLC 12000/cum. E 8

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Allergic Broncho Pulmonary Aspergillosis

• Skin test Immediate delayed ve
• Sputum for aspergillus ve
• Serology ve
• Treated with oral CS
• Antifungal tmt ?
• Maintenance tmt ?

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Asthma - triggers

• Home environment
• Aero allergens
• House dust (mites/others)
• Tobacco smoke (ETS)
• Solid fuel smoke
• Infections
• Outdoor exposures SO2, Ozone
• Occupational exposures
• Psychological stresses
• Drugs aspirin, betablockers, ACE inhibitors

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Aggravating Factors (GER)

• Old age
• Autonomic dysfunction lowering of LESP
• Increased pressure gradient between esophagus and
  stomach
• Medication Nicotine, Caffiene, calcium channel
  blockers, atropine, theophylline, nitroglycerine
  etc.

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ETS Exposure in Asthma

• No Yes
• ED visits 0.6 0.82
• Hospitalisation 0.33 0.34
• Ac. episodes 0.6 1.32
• Parenteral BD 6.0 8.6
• Work absence (wks) 3.0 3.6
• Steroid use (wks) 8.6 11.3
• BD use (wks) 36.3 38.3
• p lt 0.01

(Jindal et al, Chest 1994)
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ETS Exposure (Children)

• Parental smoking at home
• Asthmatics 41 OR 1.78
• Non asthmatics 28 95 CI 1.33-2.31
• Respiratory symptoms
• ETS exposed OR 1.6 -2.25
• Not exposed
• Asthma (questionnaire diag.)
• ETS exposed OR 1.78
• Not exposed 95 CI 1.34-2.36

(Gupta et al, J Asthma 2001)
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Case of brittle asthma

• 40 M, Bank official
• Br. Asthma gt 23 yrs
• BDP 800 mcg/dg
• Salbutamol 800 mcg/d
• Theophylline 600 mg/d
• Prednisolone 15-20 mg/d
• Hypertension in 1976 (Nifedipine)
• Pulm TB in 1994. Given ATT
• Worsening of asthma acute episodes
• Prednisolone increased 40 mg/d
• Hospitalization repeated
  
• 
  
  Gupta et al, IJCDAS 1995

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Worsening of Asthma Control in TB

• Rifampicin induces hepatic enzyme systems
• Increase in steroid clearance (45)
• Decrease in steroid bioavailability to tissues
  (upto 60)
• (Rifampicin requires to be omitted)
• Powell-Jackson et al 1983
• Acocella 1978 Udwadia et al 1993

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Management Recommendations

• Confirm the diagnosis
• Evaluate and treat confounding or exacerbating
  factors
• 3. Optimize the standard asthma pharmacotherapy

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• Maintenance treatment
• Labile/Brittle asthma
• Steroid dependent
• Other comorbidities
• Specific situations
• Pregnancy
• Surgery
• Concurrent diseases and drugs
• Occupational asthma

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Managing Aggravating Factors

• Tmt of sinusitis and polyps
• Managing GE reflux
• Weight reduction
• Sleep disorder evaluation
• Tmt of psychological stress
• Management of VCD if any
• Reducing allergen load, dust, smoke/ETS, pets
  (etc.)

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Pharmacotherapy

• High dose/high potency ICS
• Oral CS at the lowest possible dose
• Additional 1 to 3 controllers
• PEF monitoring (daily)
• Asthma action plan rescue steps
• Frequent clinic visits/advice

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Management of Type I Brittle Asthma

• Usual guidelines do not apply
• Test of patience
• Compliance doctor-patient rapport is crucial
• Realistic goals of treatment should be aimed at
• Even small benefits can be important if perceived
  correctly

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Type I Brittle Asthma

• Continuous Subcutaneous Infusion of Terbutaline
  (CSIT)
• Described in 1984
• 3-12 mg/day by infusion pump
• 50 show marked improvement
• ? Mechanism of action
• Problems

1. BMJ 1984 288 1715-16, 2. Br J Dis Chest
1988 82360-5
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Continuous Subcutaneous Infusion of Terbutaline
(CSIT)
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Type I Brittle Asthma

• Other treatment modalities
• Immuno-modulators
• LABA
• LTA
• Psychotherapy

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Management of Type II Brittle Asthma

• Medic-Alert card
• Self administered epinephrine epi-pen
• Regular controller medications
• Avoid triggers if known!

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Difficult and Brittle Asthma SUMMARY

• Few of the asthmatics are difficult to manage
• Careful exclusion of asthma mimics and control of
  exacerbating factors is sufficient in most of
  them
• Very few are truly brittle asthma which is
  perhaps a separate phenotype
• Objective monitoring is very important in this
  subset of patients
• Drastic treatment steps may be required
• Treatment approach should be holistic

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