Diagnosis and Differen-al Diagnosis of Asthma
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1 Diagnosis and Differen-al Diagnosis of Asthma Jay Peters MD Professor and Chief Pulmonary/Cri7cal Care Medicine University of Texas Health Science Center San Antonio Disclosures: None
2 Disclosures Nothing to disclose
3 Objec-ve Delineate the steps to accurately iden-fy pa-ents with refractory asthma and to rule out other condi-ons and comorbidi-es that may mimic the disease
4 Difficult to Control Asthma: Case Study 29 yo physician referred by Pulmonologist Recurrent wheezing/sob/chest 7ghtness las7ng up to 2 hrs Symptoms worse x 8 months PMHx Age 8-10: nocturnal awakening with dyspnea Age 19: episodic bronchi7s/wheeze the wk before menses Severe exacerba7on: 1 month ago (ER x 24 hours) ROS Triggers: cold air, perfume, dust, ETS Unable to walk up 1 flight of stairs
5 Case Study Social: life7me non- smoker Allergies: Sulfa, ASA, Ibuprofen Meds: BCP, LABA/high dose ICS combina7on, LTRA, Albuterol nebs prn PE: 138/78 RR 14 WNL including normal lung exam Prior w/u Echo nl LV fxn with PASP 16 (normal); stress test- nega7ve PFTs: WNL FEV13.04 L (98%), FEV1/FVC (91%),FEF25-75 (134%); DLCO (102%) Labs: normal CBC, BNP, D- dimer, total eosinophil count, Ig- E CXR and HRCT both WNL
6 Diagnosis of Refractory Asthma
7 Pathobiology of Asthma: Why Different Pa7ents Need Different Therapies - Pelaia G, et al. Nature Reviews. Drug Discovery 2012; 11: Neutrophilic Asthma Severe asthma Occupational asthma Obesity Hyper acute asthma
8 Phenotypes in Asthma Wenzel SE. Nat Med May 4;18(5):
9 - Does our pa7ent have refractory asthma? - What is the differen7al diagnosis to consider in pa7ents with refractory asthma? - What happened to our pa7ent?
10 Defini7on of Asthma: Making Sure the Pa7ent Really Is Asthma7c Symptoms: Cough, dyspnea, and/or wheeze Reversible airflow obstruc7on By spirometry (obstruc7on with 12%/200cc increase in FEV1 post- BD) Methacholine/mannitol challenge test Ruling out other disorders that mimic asthma
11 Defini7on of Refractory Asthma Diagnosis of asthma confirmed & comorbidi7es treated Requiring high dose ICS and second controller (LABA) To prevent asthma from being uncontrolled Remains uncontrolled Uncontrolled asthma is defined by: Poor Sx control: ACQ consistently > 1.5; ACT < 20 Two or more burst of oral steroids/yr At least one hospitaliza7on/yr Persistent airflow limita7on (FEV1 < 80%; FEV1/FVC < LLN) Eur Respir J 2014; 43:
12 Defini7on of High Dose Inhaled Cor7costeroids Ciclesonide Beclomethasone Flu7casone propionate Mometasone Budesonide > 320 mcg/day HFA or DPI > 640 mcg/day HFA > 880 HFA; 1000 mcg/day DPI > 1000mcg/day HFA or DPI > 1600 mcg/day HFA or DPI
13 Differen7al Diagnosis of Refractory Asthma
14 Differen7al Diagnosis in Asthma Vocal Cord Dysfunc7on (ILO) Bronchiectasis (ABPA/Cys7c Fibrosis) Hypersensi7vity pneumoni7s/sarcoidosis Churg- Strauss Syndrome COPD/ Overlap Syndrome Obstruc7ve Bronchioli7s Pulmonary emboli Conges7ve Heart Failure (Cardiac asthma) Tracheal stenosis/airway tumors
15 Features of VCD Common Triggers Exercise 25-30% Irritants 20% - GERD - Rhinosinusis7s - Dust, fumes, vapors Psychogenic 20% Depression Sexual abuse Neurogenic 5% (ALS, MG)
16 Vocal Cord/Laryngeal Dysfunc7on Vocal Cord dysfunc7on Adduc7on of anterior 2/3 of vocal cords Usually inspiratory (60-70%) Expiratory (20-30%) Bilateral (5%) Co- existent asthma: 32% Not present during sleep FEV1 out of propor7on to airway resistance Rx: Speech pathology, Biofeedback
17 Ques-on: 45 y.o. male with hx of stable asthma for 5 years. Recent asthma exacerba-ons 2-3 -mes/month. New hobby- woodworking. A possible cause of his exacerba-ons is: A. B. C. D. E. Acute hypersensi-vity pneumoni-s Sub- acute hypersensi-vity pneumoni-s Chronic hypersensi-vity pneumoni-s Acute Bacillus sub-lis infec-on Chronic Bacillus sub-lis infec-on
18 Hypersensi-vity Pneumoni-s Granulomatous inflamma7on secondary to organic par7cles or fumes Over 200 an7gens have been iden7fied Not an atopic disorder (no increase in IgE or Eosinophils) 95 % of HP cases occur in nonsmokers Curr Opin Pulm Med 2004; 10:
19 Hypersensi-vity pneumoni-s Acute HP Flu- like sx 4-8 hours aoer exposure Peak hours: fever; elevated WBC; mixed obstruc7on/restric7on CXR: GGO or patchy infiltrates Subacute HP Dyspnea, fa7gue, cough Mimics asthma or acute bronchi7s Chronic HP (5%: may progress to IPF) Treatment: Avoidance of an7gen exposure and cor7costeroids HSP: 20% Nl CXR Chronic HP: classic CT AJR 1992;159:
20 Allergic Bronchopulmonary Aspergillosis ABPA Allergic immune response to Aspergillus Frequency: 2% asthma; 2-15% CF Clinical features Finger-in-glove sign Cough, wheeze, +/- sputum Hallmark: serum IgE > 1000 IU/ml Radiographic features Flee7ng infiltrates or nodules Mucus plugging +/- atelectasis Central bronchiectasis Hyper attenuation in mucus
21 Allergic Bronchopulmonary Aspergillosis Consider in refractory asthma Diagnos-c criteria Asthma with IgE >1000 IU/ml Immediate skin test posi-ve IgE or IgG to Aspergillus pos-ve Central bronchiectasis Therapy for ABPA Prednisone.5 mg/kg x 2 wks Convert to.5 mg/kg QOD x 8 wks Taper 5-10 mg every 2 weeks Monitor IgE q2 months x 1yr Two fold rise suggest relapse Chest 2009;135:
22 Eosinophilic granulomatosis with polyangii7s: (Churg- Strauss/EGPA) Clinical features - Asthma (adult onset/poorly controlled) - Eosinophilia (> 1,500/L or 10%) - Necro-zing vasculi-s EGPA Subtypes ANCA (MPO) posi-ve Kidney: necro-zing GN ANCA nega-ve (asthma phenotype) More cardiac involvement EGPA/CSS CXR: nl 35% CT: GGO +/nodules Pathologic features: Extravasc granulomas Necro7zing vasculi7s Tissue eosinophilia CT: EGPA
23 Eosinophilic granulomatosis with polyangii7s Pulmonary involvement with EGPA Worsening or refractory asthma Severe sinusi-s +/- polyposis (Note: HRCT: GGO 86%in EGPA vs. 4% in asthma) Other organs frequently involved: nerve; abdomen, kidney, cardiac (eosinophilic infiltra-on or vasculi-s) Treatment Prednisolone 1 mg/kg/day Cytoxan.6 gm/m2 monthly (Hemorrhagic cys--s: Cellcept) Salvage therapy: retuximab or mepolizumab
24 What happened to our pa7ent? Normal Inspira-on Pre-exercise Vocal Cord Dysfunc-on Fiberoptic laryngoscopy Gold Standard Case study: Exercised up/down steps then carried her into PFT lab (flow-volume loop) Exercise prior to bronshoscopy: - Contraction of vocal cords inspiration/expiration - Biopsy: thickening of basement membrane - BAL: 4% eosinophils Post-exercise
25 CASE STUDY: Follow- up Pa7ent seen by ENT (Speech Therapist) Trained in control of breathing/airway relaxa7on Did well for 18 months; became pregnant Asthma worsened last trimester/post- partum Rx with high dose ICS, LABA, LTRA Visi7ng ER every 1-2 months Re- evaluated pa7ent in clinic (3 months post- partum) Sent sputum eosinophils, IgE Sent repeat RAST/Immunocap for aeroallergens
26 Ques-ons to be considered: What would you do with this pa-ent at this point? What pharmacologic therapies could be added to improve her asthma control? If her asthma remains poorly controlled, is she a candidate for bronchial thermoplasty? What future therapies are likely to be available to control refractory asthma?
27 Ques-on: 45 y.o. male with hx of stable asthma for 5 years. Recent asthma exacerba-ons 2-3 -mes/month. New hobby- woodworking. A possible cause of his exacerba-ons is: A. B. C. D. E. Acute hypersensi-vity pneumoni-s Sub- acute hypersensi-vity pneumoni-s Chronic hypersensi-vity pneumoni-s Acute Bacillus sub-lis infec-on Chronic Bacillus sub-lis infec-on
28 Questions?
29 Dr. Willaim Calhoun Current pharmacological therapies Future pharmacological therapies
30 Dr. Diego Maselli Non- pharmacological management of Refractory Asthma Trea7ng comorbidi7es Bronchial Thermoplasty
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