ASMA DIFICIL ERJ

8/2/2019 ASMA DIFICIL ERJ

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EL DISCURSO MAS CORTO por Bryan Dyson, ex Presidente deCoca ColaQue cosa extraa es el hombre,nacer no pide,vivir no sabe,y morir no quiere

"Imagina la vida como un juego en el que ests malabareando cinco pelotas en el aire. Estas son: -

Tu Trabajo,- Tu Familia,- Tu Salud,- Tus Amigos y - Tu Vida Espiritual, Y t las mantienes todas stas enel aire.

Pronto te dars cuenta que el Trabajo es como una pelota de goma. Si la dejas caer, rebotar yregresar. Pero las otras cuatro pelotas: Familia, Salud, Amigos y Espritu son frgiles, como de cristal. Sidejas caer una de estas, irrevocablemente saldr astillada, marcada, mellada, daada e incluso rota.Nunca volver a ser lo mismo. Debes entender esto: apreciar y esforzarte por conseguir y cuidar lo msvalioso.

Trabaja Eficientemente en el horario regular de oficina y deja el trabajo a tiempo.

Dale el tiempo requerido a tu familia y a tus amigos.Haz ejercicio, come y descansa adecuadamente.Y sobre todo.....crece en vida interior, en lo espiritual, que es lo ms trascendental, porque es eterno.


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We would like to remind you that thismaterial is the property of the author. It is

provided to you by the ERS for yourpersonal use only, as submitted by the

author.

2008 by the author


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Why isnt his Asthma

getting better, Doctor?

Andrew Bush

Andrew Bush, Cara Bossley, Pippa HallRoyal Brompton Hospital,

London UK


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Most screened were not taking their medication or did not have asthma!

JACI 2008; 122: 1138-44

Does azithromycin work in severeasthma?


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Stepwise Approach to Asthma

Is the diagnosis correct?

Is the drug delivery device appropriate?

If the child is still not right:

Is it Difficult to Treat or Severe, therapyResistant


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Case Study 1

Dr Cara Bossley

Paediatric Respiratory SpRRoyal Brompton Hospital


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MC 14 year old boy

Brittle asthma and allergic rhinitis

Asthma since 1 year, worse over past 3 years

Productive cough

Flixotide (500mcg/day), salmeterol (100mcg/day), theophylline

(250mg/day)

FEV1 57%, no reversibility

No improvement with high dose oral steroids


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What would you do next?

1. Increase the dose of inhaled corticosteroid

2. Start anti-IgE therapy

3. A series of investigations to check thediagnosis is correct

4. Refer to ENT surgeons for advice

5. None of the above


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What would you do next?1. Increase the dose of inhaled corticosteroid

2. Start anti-IgE therapy

3. A series of investigations to check the diagnosis is

correct

4. Refer to ENT surgeons for advice


The productive cough, poor response to steroids andabsence of bronchodilator reversibility arepointers that the diagnosis could be incorrect


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What would you do now?

1. Give a course of oral prednisolone

2. Give a course of oral augmentin

3. Give a course of intravenous cefuroximeand gentamicin

4. Give a course of oral rifampicin

5. Commence omeprazole and domperidone


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1. Give a course of oral prednisolone

2. Give a course of oral augmentin

3. Give a course of IV cefuroxime and gentamicin

4. Give a course of oral rifampicin

5. Commence omeprazole and domperidone

Due to the poor lung function and severity ofinflammation and infection seen on bronchoscopya 2 week course of IV antibiotics was given


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What further investigationsshould be done?

1. Exercise tolerance test

2. Psychological testing

3. Milk scan

4. Nasal nitric oxide testing

5. Blood sugar testing


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What further investigationsshould we do?

1. Exercise tolerance test

2. Psychological testing

3. Milk scan

4. Nasal nitric oxide testing

5. Blood sugar testing

Nasal nitric oxide testing can be performed asa screening test for primary ciliarydyskinesia which can be a cause of chronicproductive cough and rhinitis


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Diagnosis: PRIMARY CILIARYDYSKINESIA

Nasal NO

30ppb (normal >200ppb)

Ciliary studies


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Normal cilia PCD: Absent outer dynein arms


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Progress

Did very well after intravenous antibiotics

Regular physiotherapy

Stopped theophylline

Halved flixotide dose (500 to 250mcg/d)

Spirometry improved; FEV1 57% rising to 94%

Symptomatically much better


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Summary

Ongoing poorly controlled symptoms despite highdose inhaled corticosteroids and add-on therapy

Chronic productive cough

Non-atopic

Low lung function, with no evidence of bronchodilator

reversibility or steroid responsiveness

Other diagnoses must be considered

Difficult asthma alternative


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Difficult asthma alternativediagnoses; our experience

(n=102) One vascular ring

Two had bronchiectasis

idiopathic primary ciliary dyskinesia

One Jobs syndrome

One severe sinus diseasecorrected by sinus surgery

bronchiectasis

Vascular ring


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Co-morbidities Immune abnormality

10/74 (14%) 5/12 non-atopic patients vs

5/62 atopic children (p=0.04)

41/55 (75%) gastro-oesphagealreflux disease

4/99 (4%) airway malacia

5/99 (5%) enlarged adenoids

1/99 (1%) narrow right mainbronchus Tracheomalacia

Enlarged adenoids


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Alternative / Additional diagnoses

Royal London Hospital

57 difficult asthma children, 9 alternative diagnosis

3/57 (5.2%) bronchiolitis obliterans

2/57 (3.5%) functional dyspnoea

1 hyperventilation

1 vocal cord dysfunction

1/57 (1.8%) interstitial pneumonitis

2/57 (3.5%) over reporting of symptoms

Pediatr Pulmonol, 2001:31:114-120


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Definitions-1

Problematic Severe Asthma = A new concept in the literature Presentation label

Symptoms >3 times per week despite high dose ICS(>800 mcg BDP equivalent), LABAs, LTRAs &Theophyllines (?)

Multiple severe exacerbations or a single PICUadmissionBrittle (chronically chaotic peak flow Type 1,

catastrophic exacerbations out of the blue Type 2)Daily or alternate day prednisolonePersistent airflow limitation

Comprises two (four) categories: Difficult asthma Severe, therapy resistant asthma (Not asthma at all wrong diagnosis) (Asthma plus co-morbidities)


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Definitions-2

Difficult to treat asthma = becomes easier when the basics are got right

(adherence, environment, etc.)

NOT candidates for novel therapies

Severe, therapy resistant asthma = treatment still extremely difficult despitegetting

the basics right

Would be potentially suitable for cytokine specifictherapies


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The Protocol

Visit two: FOB

Assess symptoms,

use of rescue medication

Spirometry & reversibilityInduced sputum, eNO

FOB, BAL, biopsy

Visit three: Decision time

Assess symptoms, diary card,use of rescue medication

Spirometry & reversibility

Induced sputum, eNO

Develop treatment plan

IntramuscularTriamcinolone

4 weeks

Visit one: MDT Assessment

Drug delivery device

Assess symptoms, use of

rescue medicationSpirometry & reversibilityInduced sputum, eNO

Home visit: environment

School visit: bullying?

Assess compliance

Psychological assessment

1-2 months


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What does a home visitachieve?

Psycho-social issues re-addressed Anecdotally, more likely to open up

74% referrals were after home discussions

Adherence

Smoking

Allergens


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Case Study 2

Pippa Hall

Childrens Respiratory NurseRoyal Brompton Hospital


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Child B - History

16 year old female

Referred from local Paediatrician

Ongoing persistent symptoms despitebeyond guideline treatment

Psychological issues

9 hospital admissions in past 12 months including an admission to PICU


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Treatment at Referral

Regular Medication

Symbicort 400/12mcg (x3 puffs) BD

Montelukast 10mg OD

Uniphylline 400mg BD

Omalizumab 300mg 2 weekly Triamcinolone 80mg (i/m) monthly

Rescue Medication

11 courses of high dose oral steroids in last year

Short acting beta agonist (SABA) use >3 times daily


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Investigation Results

FEV1: 73% predicted

BDR: 26%

FeNO50: 16ppb

Asthma Control Test (ACT): 15/25

Skin Prick Tests: all negative

Total IgE: 454


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1. Prescribe alternate day prednisolone

2. Prescribe daily prednisolone3. Prescribe oral methotrexate

4. Trial of subcutaneous terbutaline



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1. Prescribe alternate day prednisolone

2. Prescribe daily prednisolone3. Prescribe oral methotrexate

4. Trial of subcutaneous terbutaline



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How did we assess adherence?

1. Asked the child how often they took themedication

2. Asked the parents how often they gave

the medication3. Checked GP and hospital prescriptions

4. Checked in the home for availability of

in-date medications5. Shouted at everyone until a confession

was made


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How did we assess adherence?

1. Asked the child how often they took themedication

2. Asked the parents how often they gave themedication

3. Checked GP and hospitalprescriptions

4. Checked in the home foravailability of in date medications5. Shouted at everyone until a confession was

made


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How much in fact had beencollected?

1. 75 100%

2. 50 75%3. 25 50%

4.


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How much in fact had beencollected?

1. 75 100%

2. 50 75%3. 25 50%

4.


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Interventions

Patient education Importance of regular inhaled medication

discussed

Parental supervision of medication Parental involvement encouraged

Simplification of medication regime Montelukast stopped


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Investigations Continued

Adherence Poor understanding of Turbohaler use

GP prescription uptake


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Outcome After 6 months

SABA use:


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Conclusion

Poor adherence to treatment was the maincontributor to ongoing poorly controlled

symptoms

In our cohort of difficult asthmatics1: Prescription uptake was


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Did they take medications?

55 (77%) had a complete setof in-date, accessiblemedication

44 (62%) had a goodtechnique

34 (48%) medication issuescontributed to poor control

0

510

15

20

2530

35

40

45

Nos.

%

80

Prescription Records


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The Buck Stops Where?

Pediatrics 2008; 122: e1186-92


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Case Study 3

Pippa Hall

Childrens Respiratory Nurse Specialist

Royal Brompton Hospital


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H h ld h hild b d


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How should the child be assessedfor sensitivity to allergens?

1. Skin prick testing

2. Histamine challenge

3. Total serum IgE

4. Specific IgE in serum

5. Inhalant allergy challenge

H h ld h hild b d


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How should the child be assessedfor sensitivity to allergens?

1. Skin prick testing

2. Histamine challenge3. Total serum IgE

4. Specific IgE in serum

5. Inhalant allergy challenge


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Investigation Results

FEV1: 61% predicted

BDR: 48%

FeNO50: 120ppb

Asthma Control Test (ACT): 7/25

Skin Prick Tests: +ve grass, cat, dog


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Home Visit

Adherence

Chaotic medication regimen noted in thehome

Smoke Exposure

Step father smokes outside (no evidenceof smoke inside)

Allergen Exposure

4 cats at home


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Changes Following Home Visit

Medication

Simplified medication regimen SMART

Smoke Exposure

Step father to attempt to give up smoking

Allergen Exposure

Cats removed from the home

Wh t h d t th hild


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What happened to the childs

asthma after removal of the cats?

1. Became completely symptom free

2. Dramatically improved control

3. Stayed the same

4. Got worse

5. The child became psychoticallydepressed at the loss of a pet

Wh t h d t th hild


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What happened to the childs

asthma after removal of the cats?

1. Became completely symptom free

2. Dramatically improved control3. Stayed the same

4. Got worse

5. The child became psychoticallydepressed at the loss of a pet


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6 months After Home Visit

SABA use: < once daily

FEV1: 85% predicted

BDR: 15%

FeNO50: 68ppb

ACT: 16/25

No hospital admissions or courses of high dose

oral corticosteroids


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Conclusions

Removing allergens in the home andsimplifying medication regimen improved

patient outcomes


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Allergen avoidance?

HDM n=31 sensitised

Avoidance:

5 (16%) reasonable

15 (48%) some 11 (36%) none

Pets n=30 owners, 17 sensitised Avoidance: n=2


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Subclinical Allergen

Exposure

Low dose allergenchallenge (no decline inFEV1)

Worsening AHR,sputum eosinophiliawith no acutedeterioration

ERJ 1998; 11: 821-7
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Dose-response curves for inhibition of PHA stimulation.

White = no IL-2 or 4; Black = IL-2 & IL-4

IL-2 & IL-4 decrease sensitivity to the anti-proliferative effects of

dexamethasone

Persistent Asthmatics
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Lancet, April 2008

A: Because the wrong question has been askedin the wrong population!
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Cochrane review: Problems

Combined adult and children

Intervention duration 3 weeks - 2 years

Wide variety of types and scope of interventions Mattress-only studies included

Minority showed intervention successful Most did not reduce HDM burden

Unsuitable candidates Not all had clinical allergy

Demanding intervention did they have a problem?

Should have adjusted for season/ virus infections in small trials

How many really severe asthmatics?
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Viruses, Asthma, Allergens

84 children, 3-17yr

Acute exacerbation ofasthma vs. stable asthma vs.controls

SPT, RASTs, home allergenlevels

Viral PCR on nasal lavage

Thorax 2006; 61: 376-82 02

4

6

8

1012

14

16

18

20

OR(mv)

+ - + + + Sensitized- - + - + Exposed- + - + + Virus

P


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Summary and Conclusions

Do not forget the obvious Wrong diagnosis Not taking treatment Cannot use device

Ask the key question: What makes this asthmadifficult?

Consider environmental causes of steroid resistance

Only then think of escalating therapy
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