Chronic Obstructive Pulmonary Disease

Transcription

1 Chronic Obstructive Pulmonary Disease Practical Approaches to Diagnosis and Management MAY 14, :15 AM 12:30 PM Chicago, Illinois Sponsed by pmicme Educational Partner

2 Session 3: Chronic Obstructive Pulmonary Disease: Practical Approaches to Diagnosis and Management Learning Objectives 1. Evaluate the role of spirometry in chronic obstructive pulmonary disease (COPD) diagnosis and moniting. 2. Review recommended pharmacologic interventions to reduce COPD symptoms and decrease exacerbations. 3. Select appropriate patient counseling strategies Faculty Barbara P. Yawn, MD, MSc, FAAPP Direct of Research Olmsted Medical Center Adjunct Profess Department of Family and Community Health University of Minnesota Rochester, Minnesota Dr Barbara Yawn is a family physician with many years of both practice and research experience. She has published me than 350 articles in peer reviewed journals, including many regarding obstructive lung disease such as asthma and chronic obstructive pulmonary disease (COPD). She served on the National Heart, Lung, and Blood Institute national asthma guidelines committee in 2007 and on the Wld Health Organization s COPD and asthma guidelines committees. Much of Dr Yawn s respiraty related research is designed to develop tools and methods to translate guidelines into everyday practice to improve patient outcomes. Her research is funded by the National Institutes of Health, the Agency f Healthcare Research and Quality, and the Centers f Disease Control and Prevention. She has been a frequent speaker f Pri-Med and has also given many presentations on COPD in the United States and internationally. Her role as a primary care educat includes not only podium talks, but webinars, interactive virtual presentations, and group menting. Dr Yawn hopes to make COPD a comftable and productive part of every primary care physician s practice while also facilitating other clinicians imptant roles in chronic disease management. David M. Mannino, MD Profess and Chair Department of Preventive Medicine and Environmental Health Direct of Graduate Studies, Master of Science in Clinical Research Design Direct, Pulmonary Epidemiology Research Labaty Direct, Southeast Center f Agricultural Health and Injury Prevention University of Kentucky College of Public Health Lexington, Kentucky Dr David Mannino is profess and chair, department of preventive medicine and environmental health, at the University of Kentucky College of Public Health, Lexington, Kentucky. His research interests there include the epidemiology of asthma and chronic obstructive pulmonary disease (COPD) and the effects of air pollution exposure on respiraty function and lung diseases. Dr Mannino received his medical degree from Jefferson Medical College, Philadelphia, Pennsylvania, and served both his internship and residency at Lankenau Hospital, Philadelphia. He went on to complete a fellowship in pulmonary medicine at West Virginia University School of Medicine/National Institute f Occupational Safety and Health, Mgantown, West Virginia. Session 3

3 Early career appointments included medical staff officer at a federal crectional institution in Kentucky and section chief, analytic epidemiology section, at the National Center f Environmental Health, Centers f Disease Control and Prevention, Atlanta, Gegia. Dr Mannino has served as cocodinat of the respiraty section of Global Burden of Disease, among several other international and national consultative positions. He is the recipient of the COPD Foundation award f development of the COPD Pocket Consultant Guide and the Soffer Research Award from the American College of Chest Physicians (f best scientific abstract at a scientific meeting). Dr Mannino has authed me than 200 articles f peer reviewed journals, in addition to book chapters, editials, and book reviews. He has spoken nationally and internationally, as well as having held the position of principal investigat on a number of COPD related studies. Faculty Financial Disclosure Statements The presenting faculty repted the following: Dr Barbara Yawn receives research funding from Boehringer Ingelheim. Dr David Mannino receives advis honaria from Amgen, Astra-Zeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis. Education Partner Financial Disclosure The content collabats at Miller Medical Communications, LLC, rept the following: Lyerka D. Miller, PhD, has no financial relationships to disclose. Suggested Reading List Centers f Disease Control and Prevention (CDC). Chronic obstructive pulmonary disease among adults--united States, MMWR Mb Mtal Wkly Rep. 2012;61(46); Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how imptant is it? Thax. 2009;64(8): Schnell K, Weiss CO, Lee T, et al. The prevalence of clinically-relevant combid conditions in patients with physician-diagnosed COPD: a cross-sectional study using data from NHANES BMC Pulm Med. 2012;12:26. Mannino DM, Thn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J. 2008;32(4): Barnes PJ, Celli BR. Systemic manifestations and combidities of COPD. Eur Respir J. 2009;33(5): Mackay AJ, Hurst JR. COPD exacerbations: causes, prevention, and treatment. Med Clin Nth Am. 2012;96(4): Hurst JR, Vestbo J, Anzueto A, et al; f the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigats. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363(12): Vestbo J, Hurd SS, Agustí AG, et al. Global strategy f the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4): Maas AK, Mannino DM. Update on the management of chronic obstructive pulmonary disease. F1000 Med Rep. 2010;2. Tashkin DP, Ferguson GT. Combination bronchodilat therapy in the management of chronic obstructive pulmonary disease. Respir Res. 2013;14:49. Session 3

4 Belletti D, Liu J, Zacker C, Wogen J. Results of the CAPPS: COPD--assessment of practice in primary care study. Curr Med Res Opin. 2013;29(8): Perez X, Wisnivesky JP, Lurslurchachai L, Kleinman LC, Kronish IM. Barriers to adherence to COPD guidelines among primary care providers. Respir Med. 2012;106(3): Joo MJ, Au DH, Fitzgibbon ML, McKell J, Lee TA. Determinants of spirometry use and accuracy of COPD diagnosis in primary care. J Gen Intern Med. 2011;26(11): Joo MJ, Sharp LK, Au DH, Lee TA, Fitzgibbon ML. Use of spirometry in the diagnosis of COPD: a qualitative study in primary care. COPD. 2013;10(4): Salinas GD, Williamson JC, Kalhan R, et al. Barriers to adherence to chronic obstructive pulmonary disease guidelines by primary care physicians. Int J Chron Obstruct Plumon Dis. 2011;6: Session 3

5 SESSION 3 11:15am 12:30pm Chronic Obstructive Pulmonary Disease - Practical Approaches to Diagnosis and Management SPEAKERS Barbara P. Yawn, MD, MSc, FAAPP David M. Mannino, MD Presenter Disclosure Infmation The following relationships exist related to this presentation: Dr Yawn receives research funding from Boehringer Ingelheim. Dr Mannino receives advis honaria from Amgen, Astra-Zeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis. Off-Label/Investigational Discussion In accdance with pmicme policy, faculty have been asked to disclose discussion of unlabeled unapproved use(s) of drugs devices during the course of their presentations. Faculty Learning Objectives David M. Mannino, MD Profess and Chair Department of Preventive Medicine and Environmental Health Direct of Graduate Studies, Master of Science in Clinical Research Design Direct, Pulmonary Epidemiology Research Labaty Direct, Southeast Center f Agricultural Health and Injury Prevention University of Kentucky College of Public Health Lexington, Kentucky Barbara P. Yawn, MD, MSc, FAAFP Direct of Research Olmsted Medical Center Adjunct Profess Department of Family and Community Health University of Minnesota Rochester, Minnesota 3 Upon completion of this activity, participants should be better able to: Evaluate the role of spirometry in COPD diagnosis and moniting Review recommended pharmacologic interventions to reduce COPD symptoms and decrease exacerbations 4 Friday Afternoon 4:45 PM Visit Nancy 56 yo with cc of bronchitis Wants antibiotics befe the weekend Coughing me f 2 weeks, productive yellow?fever, some breathlessness up stairs Does not want to go to the ED again Does not want chest x ray The last kind she received wked 9 What should we do? Take me histy Smoker 35 pack years Third episode of bronchitis in past 2 years Colds last f weeks Always wse than others Decrease in activities due to trouble breathing with walking. Now SOB with 6 stairs Has smoker s cough f past 3 years Mother developed asthma at age 60 and died of CHF at age 68 Think chronic lung disease! 11 1

6 Definition of COPD Chronic Obstructive Pulmonary Disease Common, preventable and treatable disease Characterized by: persistent airflow limitation progressive and associated with an enhanced chronic inflammaty response in the airways and the lung to noxious particles gases Exacerbations and combidities contribute to the overall burden of disease in individual patients Mechanisms Underlying Airflow Limitation in COPD Small Airways Disease Airway inflammation Airway fibrosis, luminal plugs Increased airway resistance Parenchymal Destruction Loss of alveolar attachments Decrease of elastic recoil AIRFLOW LIMITATION Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4): Why Is COPD Underdiagnosed? Clinicians Tell All Patient has multiple chronic conditions Patient fails to rept/recognize dyspnea Inadequate knowledge and training Patient lacks specific symptoms Lacks access to spirometry Lack of effective treatment Survey of 278 Clinicians MDs NPs/PAs Key Barriers to COPD Diagnosis Failure of patients to notice and rept symptoms Early symptoms often do not interfere with completing activities of daily living Symptom severity increases very slowly Failure of health professionals to inquire about respiraty issues Tools to help the COPD Population Screener Be specific Misdiagnosis of COPD as asthma bronchitis Perceived Barrier (%) Underuse of spirometry Yawn BP, Wollan PC. Int J Chron Obstruct Pulmon Dis. 2008;3(2): Yawn BP, Wollan PC. Int J Chron Obstruct Pulmon Dis. 2008;3(2): The COPD Population Screener (COPD PS) 1. During the past 4 weeks, how much of the time did you feel sht of breath? None of A little of Some of Most of All of the time the time the time the time the time Asthma vs COPD Feature COPD Asthma 2. Do you ever cough up any stuff, such as mucus phlegm? Only with No, never occasional Yes, a few Yes, most Yes, colds chest days days infections every day a month a week Please select the answer that best describes you in the past 12 months: I do less than I used to because of my breathing problems. Strongly Disagree Unsure Agree Strongly disagree agree Have you smoked at least 100 cigarettes in your ENTIRE LIFE? No Yes Don t know 5. How old are you? Age 35 to 49 Age 50 to 59 Age 60 to 69 Age Martinez FJ et al; COPD-PS Clinician Wking Group. COPD. 2008;5(2): Onset Often in midlife Often in childhood Family Histy Variable Often Medical Social Histy Patients rept symptoms as Airflow Obstruction Smoking (often 20 pack years) Most notable during exercise Mostly bad days May be some reversibility with bronchodilation Atopy (ie, allergy and/ eczema) Most notable at night early mning Mostly good days Largely reversible with bronchodilation Briggs DD Jr, et al. J Respir Dis. 2000;21(9A):S1-S21. Doherty DE. Am J Med. 2004;117(suppl 12A):11S-23S. 18 2

7 Key Indicats of COPD Symptoms Chronic cough Chronic sputum production Dyspnea: Progressive, persistent Wse with exercise and respiraty infections Risk Facts Host facts Genetics (eg, alpha 1 antitrypsin deficiency), hyperresponsiveness, lung growth Exposures Tobacco, smoke from cooking fires, occupational dust, flour, chemicals 19 Hypothetical Male Patient With COPD Symptoms 42% diagnosed as COPD by physicians 42% COPD Mis Diagnosis Miravitlles M et al. Arch Bronconeumol. 2006;42(1):3-8. COPD symptoms in women were most commonly misdiagnosed as asthma Hypothetical Female Patient With COPD Symptoms 32% diagnosed as COPD by physicians 32% 20 Nancy needs spirometry! Spirometry: Obstructive Disease Needs pre and post bronchodilat to see about reversibility and if she meets obstruction definition Needs FEV1 and FVC to determine severity and how to begin maintenance therapy Volume, liters FEV 1 = 1.8 L FVC = 3.2 L FEV 1 /FVC = 0.56 Nmal FEV 1 = 4 L FVC = 5 L FEV 1 /FVC = 0.8 Obstructive FVC=fced vital capacity FEV1=fced expiraty volume in 1 second Time, seconds Algithm f Interpreting Spirometry Results Yes Obstructive defect Yes Is FVC low? Mixed obstructive/ restrictive defect hyperinflation Further testing No Acceptable Spirogram Near total reversal with use of beta agonist? Yes Asthma Is FEV 1 /FVC ratio low? Pure obstruction No COPD Yes Restrictive defect Further testing No Is FVC low? No Nmal Nancy s Numbers You do spirometry on Nancy and get the following results: Good quality tracing rated B Pre bronchodilat Post bronchodilat FEV L 65% pred FEV1 2.7 L 68% pred FVC 4.0 L FVC 4.1 L FEV 1 /FVC 0.55 FEV1/FVC 0.66 Petty TL. Spirometry made simple. National Lung Health Education Program. 1999;8:37,38,41. Published January Accessed January 5,

8 Avoid Interpretation Pitfalls COPD Management Suspect COPD Common Interpretation Errs Among Family Physicians (N=12 practices) new to spirometry use Select Rx based on: Symptoms FEV1 Spirometry Interpreting a nmal result as an obstructive pattern Exacerbations Interpreting a po efft as a restrictive pattern Modifications Inadequate response Adequate response Diagnosing COPD in the absence of an FEV 1 /FVC ratio <70% Yawn BP et al. Chest. 2007;132(4): Why inadequate? Adherence Triggers Combidities Psycho social Inhaler technique Exacerbations Disease progression 28 COPD Accding to GOLD 2014 Determine: Current level of patient s symptoms Severity of the spirometric abnmality Frequency of exacerbations Presence of combidities Assess symptoms Assessment of COPD Dyspnea: Progressive, persistent, and characteristically wse with exercise Chronic cough: May be intermittent and may be unproductive Chronic sputum production: COPD patients commonly cough up sputum Use mmrc, CAT, CCQ to assess the patient s level of symptom burden. mmrc=modified Medical Research Council. Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4): Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4): Modified MRC (mmrc) Questionnaire Assessment of COPD Assess symptoms Assess airflow limitation using spirometry GOLD 1: Mild GOLD 2: Moderate GOLD 3: Severe GOLD 4: Very severe FEV 1 80% predicted FEV 1 50% to 79% predicted FEV 1 30% to 49% predicted FEV 1 <30% predicted

9 Assessment of COPD Nancy, cont d Assess symptoms Assess degree of airflow limitation using spirometry Assess risk of exacerbations Use Assess histy combidities of exacerbations and spirometry. 2 exacerbations me within the last year FEV 1 <50 % of predicted value indicats of high risk. mmrc is 2 Exacerbations???? Probably 2 per year FEV1 68% of predicted On no therapy until you treated bronchitis and began SABA Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4): SABA=sht acting beta 2 agonist 34 Combined Assessment of COPD (C) (A) mmrc 0 1 CAT <10 (D) (B) mmrc 2 CAT 10 Symptoms (mmrc CAT sce) Assess symptoms first Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4): If mmrc 0 1 CAT <10: Less Symptoms (A C) If mmrc 2 CAT 10: Me Symptoms (B D) 35 Risk (GOLD Classification of Airflow Limitation) Combined Assessment of COPD Assess risk of exacerbations next (C) (A) mmrc 0 1 CAT <10 (D) (B) mmrc 2 CAT 10 Symptoms (mmrc CAT sce) 2 1 leading to hospital admission 1 0 Risk (Exacerbation histy) If GOLD 1 2 and only 0 1 exacerbations per year: Low Risk (A B) If GOLD 3 4 two me exacerbations per year 1leading to hospital admission: High Risk (C D) 36 Increasing Risk Pharmacological Therapy of Stable COPD: GOLD 2011 GOLD spirometric classification When assessing risk, choose the highest risk accding to GOLD grade exacerbation histy C A mmrc 0-1 CAT <10 D B mmrc 2 CAT 10 Increasing Symptoms 0 1 >2 1 hosp Exacerbation histy Increasing Risk Patient is now in 1 of 4 categies: A: Less symptoms, lower risk B: Me symtoms, lower risk C: Less symptoms, higher risk D: Me Symtoms, higher risk 37 Additional Investigations Chest X ray: Seldom diagnostic, but valuable to exclude alternative diagnoses (CHF, lung cancer) and establish presence of significant combidities Alpha 1 Antitrypsin Deficiency Screening: In COPD patients of Caucasian descent <45 yrs old, with strong family histy of COPD Lung Volumes and Diffusing Capacity: Help to characterize severity, but not essential to patient management Oximetry and Arterial Blood Gases: Pulse oximetry can be used to evaluate a patient s oxygen saturation and need f supplemental oxygen therapy Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4):

10 Manage Stable COPD: Goals of Therapy Therapeutic Options: Key Points Assess and relieve symptoms Individual tools f assessment Improve exercise tolerance Pulmonary rehab Improve health status Prevent disease progression Exposure to smoking, occupational Prevent and treat exacerbations Pharmacotherapy, exposures Reduce mtality Reduce Symptoms Reduce Risk Smoking cessation has the greatest capacity to influence the natural histy of COPD Pharmacotherapy and immunizations improve the lives of people with COPD Regular physical activity and should repeatedly be encouraged to remain active Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4): Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4): Existing Pharmacologic Treatment Options Sht Acting Agents SABA Albuterol Levalbuterol Pirbuterol SAMA Ipratropium Bronchodilats Long Acting Agents LABA Salmeterol Fmoterol Arfmoterol LAMA Tiotropium Aclidinium LABA/LAMA Vilanterol/ Umeclidinium Theophylline Anti inflammaty ICS ICS/LABA Salmeterol + Fluticasone Fmoterol + Budesonide Vilanterol + Fluticasone ICS=inhaled cticosteroid; LABA=long acting beta 2 agonist; LAMA=long acting muscarinic antagonist (anticholinergic); SAMA=shtacting muscarinic antagonist (anticholinergic). Nonpharmacologic Management: GOLD Overview A B C D Active reduction of risk facts Administer vaccinations Increase physical activity Add pulmonary rehabilitation Consider evaluation f need f supplemental oxygen Consider surgical eval PDE4 Inhibits Roflumilast Antibiotics????? Statins????? Adapted by Adams SG; from the Global Strategy f Diagnosis, Management, and Prevention of COPD 2013, Global Initiative f Chronic Obstructive Lung Disease (GOLD), 43 Recommended Pharmacotherapy A B C D Sht-acting bronchodilat (prn) SABA (prn) Albuterol Levalbuterol Pirbuterol OR SAMA (prn) Ipratropium Severe symptoms Exacerbations( 2/yr) Recommended Pharmacotherapy A B C D Severe symptoms Sht-acting bronchodilat (prn) LABA (scheduled) SABA SAMA (prn) Arfmoterol Indacaterol Salmeterol OR LAMA (scheduled) Tiotropium Aclidinium Exacerbations( 2/yr) Adapted by Adams SG: from the Global Strategy f Diagnosis, Management, and Prevention of COPD 2013, Global Initiative f Chronic Obstructive Lung Disease (GOLD), 44 Adapted by Adams SG: from the Global Strategy f Diagnosis, Management, and Prevention of COPD 2013, Global Initiative f Chronic Obstructive Lung Disease (GOLD),

11 Recommended Pharmacotherapy A B C D Sht-acting bronchodilat (prn) Severe symptoms Exacerbations( 2/yr) Recommended Pharmacotherapy A B C D Sht-acting bronchodilat (prn) Severe symptoms Exacerbations( 2/yr) SABA SAMA (prn) LABA LAMA (scheduled) ICS/LABA Budesonide/Fmoterol Fluticasone/Salmeterol Fluticasone/Vilanterol SABA SAMA (prn) LABA LAMA (scheduled) ICS/LABA LAMA (scheduled) ICS/LABA Budesonide/Fmoterol Fluticasone/Salmeterol Fluticasone/Vilanterol OR &/OR LAMA Tiotropium Aclidinium LAMA Tiotropium Aclidinium Adapted by Adams SG: from the Global Strategy f Diagnosis, Management, and Prevention of COPD 2013, Global Initiative f Chronic Obstructive Lung Disease (GOLD), 46 Adapted by Adams SG: from the Global Strategy f Diagnosis, Management, and Prevention of COPD 2013, Global Initiative f Chronic Obstructive Lung Disease (GOLD), 47 First choice: SABA SAMA (prn) Pharmacotherapy (Summary) A B C D Sht-acting bronchodilat (prn) Severe symptoms First choice: LABA LAMA Exacerbations( 2/yr) First choice: ICS/LABA LAMA First Choice: ICS/LABA &/ LAMA ß 2 Agonists Tachycardia Palpitations Adverse Effects of Therapy Anticholinergics Dry mouth Urinary retention Inhaled Glucocticoids Dysphonia Thrush PDE-4 inhibit (Roflumilast) Diarrhea Weight decrease Alternative choice: LABA LAMA SABA + SAMA (scheduled) Alternative choice: LABA + LAMA Alternative choice: LABA + LAMA LABA + PDE-4 inhibit LAMA + PDE-4 inhibit Alternative choice: ICS/LABA + LAMA ICS/LABA + PDE-4 inh LABA + LAMA LAMA + PDE-4 inh PVC* Trems Hypokalemia Glaucoma Systemic effects: bruising, bone density, cataract Pneumonia Local irritation Headache Insomnia Depression/Suicidal ideations Consider Theophylline Consider Theophylline Consider Theophylline Consider Theophylline *PVC=premature ventricular contraction Adapted by Adams SG: from the Global Strategy f Diagnosis, Management, and Prevention of COPD 2013, Global Initiative f Chronic Obstructive Lung Disease (GOLD), 52 Tashkin DP et al. Respir Res. 2010;11:149 Rennard SI. Lancet ;364(9436): Saag et al. UpToDate Daliresp [package insert] Therapeutic Options: Other Pharmacologic Treatments Manage Stable COPD: Nonpharmacologic Treatments Influenza vaccines can reduce serious illness. Pneumococcal polysaccharide vaccine is recommended f COPD patients 65 years and older and f COPD patients younger than age 65 with an FEV 1 <40% predicted. The use of antibiotics, other than f treating infectious exacerbations of COPD and other bacterial infections, is currently not indicated. Patient Essential Recommended A B, C, D Smoking cessation (can include pharmacologic treatment) Smoking cessation (can include pharmacologic treatment) Pulmonary rehabilitation Physical activity Physical activity Depending on Local Guidelines Flu vaccination Pneumococcal vaccination Flu vaccination Pneumococcal vaccination Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4): Wongsurakiat P et al. Chest. 2004;125(6): Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4):

12 Activity in People With COPD Therapeutic Options: Rehabilitation minutes Healthy GOLD I & II GOLD III GOLD IV FEV 1 65% FEV 1 38% FEV 1 25% Walking COPD patients are very inactive This inactivity is present in all GOLD stages All COPD patients benefit from exercise training programs with improvements in exercise tolerance and symptoms of dyspnea and fatigue Although an effective pulmonary rehabilitation program is 6 weeks, the longer the program continues, the me effective the results If exercise training is maintained at home, the patient's health status remains above pre rehabilitation levels Nutrition counseling and education Pitta F et al. Am J Respir Crit Care Med. 2005;171(9): Vestbo J et al. Am J Respir Crit Care Med. 2013;187(4): Address Combidities of COPD Must Haves f COPD Lung Cancer Pulmonary Hypertension Anemia Diabetes Metabolic Syndrome Cachexia Anxiety, Depression Cardiovascular Disease Peripheral Muscle Wasting & Dysfunction Osteoposis Peptic Ulcers GI Complications Spirometry Smoking cessation Pulmonary rehabilitation Pharmacotherapy Assessment and therapy of combidities Good across group communications Team approach Kao C, Hanania, NA. Atlas of COPD COPD Management Suspect COPD Spirometry Select Rx based on: Symptoms FEV1 Exacerbations Questions? Modifications Why inadequate? Inadequate response Adherence Triggers Combidities Psycho social Inhaler technique Exacerbations Disease progression Adequate response 70 8