ASTHMA- DO YOU NEED AN UPDATE? Dr. Hitasha Rupani Consultant Respiratory Physician April 2017

Transcription

1 ASTHMA- DO YOU NEED AN UPDATE? Dr. Hitasha Rupani Consultant Respiratory Physician April 2017

2

3 Case 1 Clair is a 32 year old police woman who has a history of childhood onset asthma Recent frequent exacerbations leading to considerable time off work Concerned as may hinder her application for detective job Very helpful GP has already started: Symbicort 100/6 two puffs twice a day and Montelukast

4 Is it asthma? Over diagnosis is common: 25-35% No single diagnostic test Wheeze Symptoms Airway inflammation Variable airflow obstruction

5 Is it asthma? 1. Tests that demonstrate variable airflow obstruction Spirometry FEV1/FVC <0.70 Reversibility: Improvement in FEV1 of 12% and 200ml PEF monitoring: Diurnal variability

6 Airway hyperresponsiveness: Methacholine or histamine 20% decline in FEV1

7 Is it asthma? 2. Evidence of inflammation: FeNo (Fractional Exhaled Nitric Oxide) Positive test suggest (eosinophilic) airway inflammation >40 ppb Predicts steroid responsiveness Can also use to guide treatment But: 1 in 5 people with a positive FeNO will not have asthma and 1 in 5 with a negative FeNO will have asthma

8

9 Look for eosinophils 1. Sputum 2. Blood 3. Bronchoalveolar lavage 4. Bronchial biopsies Green et al Lancet 2002 Westerhof et al ERJ 2015

10 Going back to Case 1 Spirometry: FeNO 160 ppb ACQ 2.8

11

12 1. Evaluate Inhaler Technique: can be suboptimal in up to 80%

13 2. Assess adherence 30 n = 182 Regional Difficult Asthma Clinic % 25 54% % 19% 26% 30% 321% % 14% 10-29% 26-50% 51-75% % >100 % of inhalers filled over 6 month period

14 50% ICS/LABA (n=63) 50% ICS/LABA (n=119) Admissions in previous 12 months 25% =3 10%= Owns a compressor for nebulised drugs 31 (49%) 35 (29%) 0.01 Total short-acting β2-agonist nebules prescribed in preceding 6 months P value FEV1, % predicted ns Rescue oral steroid courses in preceding 12 months ns AQLQ total score How to identify patients with low adherence Do you find it easier to remember your medication in the morning or the evening? Would you say you are taking it 3 days a week, or less, or more?

15 Serum prednisolone(nmol/l) Serum cortisol (nmol/l) Prednisolone assay Only 36% of patients adherent h Timepoint 3h 0 0h 3h Timepoint

16 Case 1- Management 3) Increase dose of ICS a) Increase to Fostair 200/6 b) Add in Ciclesonide Lung deposition of inhaled corticosteroids Seretide DPI 12% Seretide MDI 12-20% Budesonide MDI 12-18% Symbicort 15-28% Clenil 4-7% QVAR 53-60% Ciclesonide 52%

17 Case 2 Emily is a 29-year old magazine editor who is 28-weeks pregnant and has lifelong asthma. Asthma problematic for the past 2 years despite taking Seretide puffs twice daily and Montelukast once a day. Has had daily symptoms and uses her salbutamol inhaler several times a day and has require 2 courses of oral corticosteorids in the last 6 months. She had another exacerbation last week and has been referred by her GP for an urgent review.

18 Is it really asthma? Spirometry FEV1/FVC remain unchanged in pregnancy FeNO: assesses airway inflammation Guide treatment with inhaled steroids Studies suggest fewer exacerbations Babies: lower incidence of bronchiolitis Methacholine challenge testing generally not recommended Would you do a CXR?

19 A dummies guide understanding radiation to the foetus Threshold for dangerous radiation 0.1 Gy = 100 Foetal absorbed CXR is 0.1 pence Background radiation to foetus over 9 months is 5 CTPA pence V/Q cents Difficult to reliably measure these doses and effects in utero

20 When women with asthma become pregnant: 1/3 improve 1/3 worsen 1/3 remain unchanged Similar in successive pregnancies Asthma symptoms typically peak in the late second or early third trimester (24-36 weeks) Symptoms typically Decrease in last 4 weeks Uncontrolled asthma is associated with maternal and foetal complications: hyperemesis, pre-eclampsia and foetal grown retardation

21 Management of asthma in pregnancy All drugs are SAFE 1. β2 agonists (short and long-acting): Not associated with major congenital malformations or adverse perinatal outcome 3. Theophyllines: both oral and IV theophyllines are safe Check levels and aim for a lower therapeutic range 4. Montelukast: does not cause congenital malformations or pre-term delivery; BTS guidelines: if required to achieve adequate control, should not be withheld 5. Prednisolone is oral corticosteroid of choice: extensively metabolised by placenta, only 10% reaches baby Often withheld during an acute attack Not teratogenic (concern regarding cleft palate)

22 Case 3: Sophie, 42 year old mum Tightness in throat I feel like I m being strangled Cough ++++ Lump in throat Stridor 6 x salbutamol nebulisers Magnesium, aminophylline Previous ITU admission

23

24 Normally, when you inhale the vocal cords abduct allowing air to flow into your trachea and reach your lungs With VCD the vocal cords adduct when you inhale. This leaves only a small opening for air to flow into your trachea

25 Laryngeal dysfunction: Co-existent asthma in >50% Prominent feature in most (>90%) patients with brittle asthma Frequent use of emergency services VCD (n=42) VCD + Asthma (n=53) Duration of symptoms (years) Asthma (n=42) Prednisolone dose 30 mg 20 mg 25 mg Duration of prednisolone (years) ED visits (1 year) Hospital admissions Number of patients intubated

26 Clinical features Inducible laryngeal obstruction Asthma/ lower airway dysfunction Onset Rapid- within seconds Can be rapid, but typically gradual Duration/ pattern Regress rapidly Prolonged Inhaled drug therapy for attacks Breathing characteristics Largely ineffective Monophonic stridor, prolonged inspiratory phase Β2-agonist usually effective Polyphonic expiratory wheeze, prolonged expiratory phase Localisation of symptoms Upper airways, neck Lower airways, chest Symptoms Precipitating factors Breathlessness, cough, throat/chest tightness, voice disturbance Exercise, emotional stress, cold air, strong odours Breathlessness, wheeze, cough, chest tightness Exercise, infections, cold air, allergens, stress

27 Precipitant E.g. aspiration event, upper respiratory tract infection Aggravating comorbidity E.g. asthma, reflux, chronic rhinosinusitis Laryngeal sensitisation Triggers Exaggerated response Inducible laryngeal obstruction

28 Management 1. Speech and language therapy Mainstay of treatment Education, reassurance, strategies to relax laryngeal muscles and gain more control Physiotherapy and clinical psychology Use nasendoscopy as biofeedback during therapy 60-70% significant clinical improvement

29 SLT Secret yawn Sniff and blow Pursed lip blowing Controlled panting Five patients Pre-respiratory SLT Post-respiratory SLT % Reduction Number of ED visits % Length of hospital overnight stay days %

30 2. Pharmacotherapy Inhaled ipratropium bromide in exercise induced laryngeal obstruction Heliox (79% Helium and 21% oxygen): lowers inspiratory airflow resistance Acute setting: short acting benzodiazepine e.g. Midazolam 5 patients with confirmed VCD: All also had asthma (BTS step 5) Mean 11 (8-13) admissions in 6 months Reduction by 81%- 2 admissions 160 set-up and 8.50/month

31 Case 4 James is 21 and at university Presents to ED, SOB, wheeze, cough On prn Ventolin ( Step 1): used it so much in the last few days that he has run out Cold a few days ago, but still able to play football and go out with friends

32 Management- Start Inhaled Steroid

33 Asthma symptoms more than twice a month Waking due to asthma more than once a month Asthma symptoms most days Low dose ICS Low dose ICS Medium/high dose ICS or ISC/LABA GPs to give ipratropium nebs along with salbutamol Controlled oxygen therapy (NOT high-flow), target saturations 93-95% Start ICS after ED admission

34

35 Case 5 Gavin is a 47 year old self-employed builder He has adult onset asthma Currently is on: Fostair 200/6 Montelukast Prednisolone 12.5 mg daily Avamys nasal spray Omeprazole twice daily 2 hospital admissions and 5 courses of steroids in the last 12 months Highly dust sensitive, IgE 496, eosinophils 1.2 x 10 9

36 Omalizumab: anti- IgE therapy- allergic asthma Severe exacerbation rate 50.0% p= Large imbalances in asthma 0.5 exacerbation rate during both the year prior to start of study drug 0.43 and the run-in Previous exacerbations are the 0.24 single most important predictive 0.2 factor of future events 0.1 Total emergency visit rate 43.9% p= Omalizumab (n=209) Placebo (n=210) 0 Omalizumab (n=209) Placebo (n=210) Humbert M. et al. Allergy 2005.

37 Traditional clinical studies (crct) Real life

38 Omalizumab: also works in real world setting - 65,0 %* - 57,2 %* previous 12 months PP Omalizumab PP 0 non severe Severe total Brusselle G et al, Respiratory Medicine 2009.

39 Anti-IL5: Mepolizumab Frequent exacerbators: >4 in 12 months Eosinophil > 0.4 Only just NICE approved Pavord et al., Lancet 2012

40 Severe (Difficult) Asthma: Burden 5.4m people in the UK have asthma, of which: 4.3 million adults, 1.1m children 2.6 million severe symptoms 500,000 have very severe symptoms 1:20 of all asthmatics will have severe asthma 1,302 asthma deaths in the UK in 2015: 1 person every 7 hours die from asthma Every 10 seconds someone is having a potentially life-threatening asthma attack in the UK. and death rates have hit an all-time high (up 17% 2014 to 2015)

41 Prevalence vs. Costs 2% 8% 20% 30% 40% Very severe Severe Moderate Mild Very mild 24% 30% 33% 10% 3% Proportion of patients Proportion of total cost Boston Consulting Group 2005

42 Severe Asthma Centres in England Newcastle x1 North West x1: Manchester Liverpool Yorkshire x1: Leeds Sheffield Birmingham x1 E Midlands x1 Leicester Nottingham Cambridge x 1 Wessex x1: Southampton Portsmouth London x3: Royal Brompton Kings Health (Guys) Barts Oxford x1

43 Specialist difficult asthma clinic- what happens? Detailed systemic evaluation with a multi-disciplinary team 5 major questions: 1. Does the patient have asthma? 2. Is it all asthma? (characterise the clinical problem- phenotyping) 3. Are they taking their treatment? 4. Are there any treatable co-morbidities? 5. Are there any modifiable aggravating factors? Stable disease- standard doses medication Therapy resistant/ refractory asthma

44 Treatment Based Approach for Patients with Severe Asthma General Physicians Specialist MDT Assessment and Follow Up RECOGNITION: Persisting symptoms Poor lung function Regular use of healthcare resources Primary Care visits Admissions ED Visits Frequent OCS Diagnosis Assess, Treat, Review Uncontrolled or Severe? ORGANISATION OF CARE: Access to Specialist Care Guideline Treatment Education of HCPs Refer to a Specialist Clinic Phenotype, Endotype, Inflammation Eosinophilic Inflammation High Intensity Airway Inflammation Airflow Limitation Thickened Airways NON Eosinophilic Inflammation Neutrophilic Allergic Non Allergic Anti IgE TLA Anti Fungal MoAbs Anti IL-4 Anti IL-5 Anti IL-11 Anti IL-13 Thermoplasty Macrolides PDE4 Anti IL-17

45 THANK YOU