Asthma

고려대학교 안암병원 이은주 2016.6.7

Definition-1 Heterogeneous dz, characterized by chronic airway

inflammation

Dx : characteristic Sx (wheeze, shortness of breath, chest tightness, cough worse at night or in the early morning triggered by infection, exercise, allergen, weather…) + variable airflow limitation (bronchodilator reversibility test, hyperresponsiveness

test..)

Definition-2 Asthma phenotypes Allergic asthma: childhood, PHx/FHx(+) of allergic dz, eosinophilic inflammation in sputum, well response to ICH Non-allergic asthma: adult, less well to ICS Late-onset asthm: women, adult, often require higher doses of ICS relatively refractory steroid Asthma with fixed airflow limitation: long-standing, d/t remodeling Asthma with obesity: prominent Sx, little eosinophilic inflammtaion

Diagnosis-1 Confirmed variable expiratory airflow limitation*Documented excessive variability in lung function AND airflow limitation(* 아래의 test 중 하나 이상에서 증명 )

The greater the variations, the more confident the DxAt least once, when FEV1 is low, confirm that FEV1/FVC is reduced (normally >0.75-0.8)

BDR(+) Increase in FEV1 >12% & 200ml (after 200-400mcg albuterol)

Excessive variability in twice-daily PEF over 2 weeks

Average daily diurnal PEF variabilitity >10%

Significant increase in lung function after 4 weeks of anti-inflammatory Tx

Increase in FEV1 >12% & 200ml from 4 weeks of Tx (PEF > 20%)

Exercise challenge test(+) Fall in FEV1 >10% & 200ml from baselineBronchial challenge test(+) Fall in FEV1 >20% (metacholine or histamine)

Fall in FEV1 >15% (hyperventilation, hypertonic saline, or mannitol)

Excessive variation in lung function between visits(less reliable)

Variation in FEV1 >12% & 200ml between visits

Diagnosis – 2 Reversibility : improvement of FEV1(or PEF) after

bronchodilator or controller (ICS..) ≥ 12% & 200mL Variability : Sx / lung function 의 improvement /

deterioration 예 > diurnal variability

Diagnosis -3 Peak expiratory flow (PEF) diurnal PEF variability = (1-2 주간의 평균 )

≥ 10% 시 Dx 에 도움

( 밤 PEF)- ( 아침 PEF){( 밤 PEF)+ ( 아침 PEF)} /2

Diagnosis -4 Airway responsiveness methacholine, histamine, mannitol, exercise challenge PC(or PD) 20%

(+): asthma, allergic rhinitis, cystic fibrosis, COPD

Diagnosis -5 Allergic status : strong association between asthma & allergic dz skin test, specific IgE in serum (not total)

skin-prick test : 팽진≥ 3mm & 발적 ≥ 10mm

Differential Diagnosis Vocal cord dysfunction Hyperventilation, dysfunctional breathing COPD Bronchiectasis Cardiac failure Medication related cough Parenchymal lung dz, pulmonary embolism..

ClassificationCharacteristic Controlled

(All of the following)Partly controlled

(Any present in any week)

Uncontrolled

Daytime symptoms None (2 or less / week)

More than twice / week

3 or more features of partly controlled asthma present in any week

Limitations of activities None Any

Nocturnal symptoms / awakening None Any

Need for reliever / rescue treatment

None (2 or less / week)

More than twice / week

Lung function (PEF or FEV1) Normal

< 80% predicted or personal best (if

known)

Assessment-1(Sx control)

Asthma Control Test(ACT)

Assessment-2(Future risk)Risk factors for poor asthma outcomes Potentially modifiable independent risk factors for flare-ups (exacerbations) uncontrolled asthma Sx High SABA use ( increased mortality if > 1x 200-dose canister/month) Inadequate ICS: not prescribed ICS : poor adherence : incorrect inhaler technique Low FEV1 (<60%) Major psychological or socioeconomic problems Exposures: smoking, allergen Comorbidities : obesity, rhinosinusitis, confirmed food allergy Sputum / blood eosinophilia Pregnancy Other major independent risk factors for flare-ups (exacerbations) Ever intubated or in intensive care unit for asthma ≥ 1 severe exacerbation in last 12 months Risk factors for developing fixed airflow limitation Lack of ICS Tx Exposures: smoke; noxious chemicals; occupational exposures Low initial FEV1 ; chronic mucus hypersecretion; sputum or blood eosinophilia

Risk factors for medication side-effects Systemic : frequent OCS; long-term, high dose/potent ICS; also taking P450 inhibitors Local: high-dose / potent ICS; poor inhaler technique

Medication - Controller MedicationsController Medications

Inhaled / systemic glucocorticosteroids (ICS) Leukotriene modifiers Long-acting inhaled / oral β2-agonists (LABA) Theophylline ( sustained-release) Anti-IgE

Medication - Reliever MedicationsReliever Medications

Rapid-acting inhaled β2-agonists Inhaled anticholinergics Systemic glucocorticosteroids Theophylline (short-acting) Short-acting oral β2-agonists

Control-based asthma Mx

SxExacerbationsSide-effectsPt satisfactionLung function

DxSx control & risk factors(including lung function)Inhaler technique & adherencePt preference

Asthma medicationsNon-pharmacological strategiesTx modifiable risk factors

Stepwise approach-1Step 1 Step 2 Step 3 Step 4 Step 5

Preferred controller choice

Low dose ICS

Lose doseICS/LABA

Med/highICS/LABA

Refer for add-on Txe.g. tiotropium, omalizumab,mepolizumab

Other controller options

Consider low dose ICS

LTRALow dose theophylline

Med/high dose ICS

Low dose ICS+LTRA(or + theoph)

Add tiotropiumHigh dose ICS+LTRA(or + theoph)

Add low dose OCS

Reliever As-needed SABA As-needed SABA or low dose ICS/formoterol

Stepwise approach-2 3 개월 이상 Sx, PFT 가 안정적이면 stepdown 고려 - ICS dose 를 25-50% 정도를 3 개월 이상 간격으로 줄임

만약 6-12 개월간 증상이 없고 , risk factor 가 없다면 controller 를 중단 고려 . 하지만 ICS 의 complete cessation 은 exacerbation 이 증가한다는 보고가 많아 권하지 않음 .

Manage asthma exacerbations

Repetitive administration of rapid-acting inhaled bronchodilators

Early introduction of systemic glucocorticosteroid

Oxygen supplement

Manage asthma exacerbations-1

Manage asthma exacerbations-2

Manage asthma exacerbations-4

Oxygen : target 93-95% SABA : 4-10 puffs q 20min for 1 hr 4-10 puffs q 3-4 hrs ~ 6-10 puffs q 1-2hrs (primary care) nebulizer 일때는 초기엔 continuous 이후엔 prn 으로 (adm 시 ) Epinephrine: only anaphylaxis, angioedema Systemic steroid : prednisolone 1mg/kg(max 50mg) for 5-7 days 1 시간 이내로 투여 효과 보는데 4 시간은 걸려 oral = IV Ipratropium bromide (atrovent): addictive bronchodilation 항생제는 routine 으로 주지 말 것 !!

Manage asthma exacerbations

Magnesium : MgSO4 2g/IV (20 분간 ) single dose FEV1 25-30% at presentation pt who fail to response to initial Tx 재원 기간 줄임

Leukotriene modifiers : little data to suggest a role in acute

asthma

Sedative : avoided during exacerbation

Drug side effects β2-agonists : muscle tremor, palpitation, K 저하

Anticholinergics: dry mouth, urinary retension, glaucoma

Theophylline : N/V, headache, diuresis, palpitation, arrhythmia, seizures, death… Steroid: hoarseness, oral candidiasis, truncal obesity, bruising, osteoporosis, DM, HTN, gastric ulcer, proximal myopathy, depression, cataracts

Special consideration - Pregnancy Severity : 1/3 은 호전 , 1/3 은 악화 , 1/3 은 unchanged AE 가 중기에 흔함 . 분만 도중 AE 가 흔하지는 않지만 , hyperventilation 에 의해

bronchoconstriction 발생 가능 SABA 로 조절 가능 BA 를 많이 사용시 baby 에서 HypoG 가능 (24 시간 monitoring 요망 )

Tx: theophylline, ICS, BA, leukotriene modifier(montelukast)

Exacerbation : to avoid fetal hypoxia rapid-acting BA, O2, systemic steroid

Medications

Ventolin / Atrovent (MDI)

Foster (MDI)Seretide (Diskus, MDI) Symbicort (Turbuhaler)

Oral steroid/ theophylline

Oral long acting β2-

agonist

Leukotriene modifiers

기 타

27Ref) 세레타이드 에보할러 , 벤토린 에보할러 제품 설명서

Spacer

29※ 사용법은 보조흡입기의 종류에 따라 다를 수 있으며 , 정확한 사항은 보조흡입기 사용법을 참고해주십시오 .

환자 자신의 들여 마시는 힘에 의해 약물이 비산되어 흡입 흡입기를 입에 물고 숨을 내쉬지 않도록 교육 빠르고 세게 흡입

터부헬러 (Turbuhaler)디스커스 (DisKus)

DPI : Dry Powder Inhaler

31

숨을 끝까지 내쉰다 . 한번에 강하고 깊게 들이 마신다 .

5~10 초간 숨을 참은 후 코로 숨을 천천히 내쉰다 .

손잡이를 돌려 한번에 닫는다 .

물로 입안을 깨끗이 헹군다 .

Ref) 세레타이드 디스커스 제품 설명서

Cases

Case 1 M/ 38 CC: dyspnea, wheezing (onset: 3 일전 ) PI : 약 10 일 전부터 cough, rhinorrhea 있어 오다가 내원 3 일 전부터 dyspnea, wheezing 발생하여 내원

Never smoker

PHx : DM/HTN/TBc/Hepatitis(-/-/-/-) Allergic rhinitis(+)

PEx; whole lung wheezing(+)

Case 2 M/ 51 CC: cough (onset: 3 달 전부터 ) PI : 특이 병력 없는 never smoker 남자로 3 개월 전부터 dry cough 지속되어 내원

PHx : DM/HTN/TBc/Hepatitis(-/-/-/-)

PEx: SBS without c/w

CXR 및 PNS

Esophageal 24hr pH monitoring

PFT 및 Provocation test