Bronchial Asthma PDF

Bronchial Asthma Dr Ramez M Othman MBBS, ABI, SBF, ERSD Pulmonary Consultant Asthma - definition The term ‘asthma’ originates from the Greek word ‘aazein’ that means ‘short-drawn breath’ or ‘panting’ Usually chronic Symp...

Bronchial Asthma Dr Ramez M Othman MBBS, ABI, SBF, ERSD Pulmonary Consultant Asthma - definition The term ‘asthma’ originates from the Greek word ‘aazein’ that means ‘short-drawn breath’ or ‘panting’ Usually chronic Symptoms that Variable Heterogeneous expiratory disease airway vary in intensity inflammation and over time airflow limitation GINA report 2020. ginaasthma.org Gene/Environment interactions as e a 00 0 Szefler & Dakhama. Curr Opin Immunol 2011 Objectives  Definition, Epidemiology and risk factors  Immunology and pathophysiology of asthma  Concept of endotyping and phenotyping  Objective and accurate evaluation of asthma  Guidelines-based stepped treatment of mild, moderate and severe asthma  Occupational asthma  Airwayhyperresponsiveness Asthma pathophysiology FEE b iii us Airway Hyperresponsiveness12 41125 1L 13 Airway Remodeling Mucus hypersecretion 12 13 Smooth muscle hypertrophy TGF B he Potteries  T2 High T2 Low Allergic, atopic Neptune Allersic Non-atopic Non-eosinophilic Eosinophilic Steroid responsive Poorly steroid responsive Type-2 immune responses in asthma eosinophils DE tie T gers8 I É Ég f fÉÉiÉiÉ I eosinophilia rapidresponsetotreatment corticosteroids Type-2 immune responses in asthma Type-2 immune responses in asthma Type-2 immune responses in asthma 1- Allergens enter the respiratory system. pollutants and microbes stimulate airway epithelial cell. stimulat 2- Airway epithelial cell: release in ammatory mediators such as 4. Resulting symptoms: IL-33,IL-25 and TCLP which activate immune Airway narrowing. brelene cells. increased mucus production by goblet cells. chronic airway in ammation 3- activate immune cell: Th2 cells - secrete IL-4 and IL-13, which: IEEE g 1.activates B cells to produce IgE antibodies. 2.stimulate mast cells and basophils, causing the release of in ammatory substances like histamine. ILC2 cells: 1.Produce IL-5, promoting the recruitment and activation of eosinophils. 2.produce IL-13, leading to smooth muscle contraction in the Airways. Eosinophilic inflammation may be allergic or non-allergic Cytokines in Type 2 Asthma  Epithelial cytokines (alarmins) – TSLP, IL-33, IL-25 11 4,11 13 1L 5  IL-4, IL-5, IL-13 are produced by helper T cells, basophils, mast cells & eosinophils  IL-5 → differentiation and maturation of eosinophils  IL-13 → recruitment of eosinophils into the airway, mucus hypersecretion, airway hyperresponsiveness  IL-4 → IgE production by B-cells (class switching)  IgE → activates mast cells & basophils to produce leukotrienes that recruit and activate eosinophils Objectives  Definition, Epidemiology and risk factors  Immunology and pathophysiology of asthma  Concept of endotyping and phenotyping  Objective and accurate evaluation of asthma  Guidelines-based stepped treatment of mild, moderate and severe asthma  Occupational asthma Phenotypes & Endotypes in Asthma o Wenzel Nature Medicine 2012 Holgate Nat. Rev. Dis. Primers 2015 Exercise Induced Bronchoconstriction (EIB)  Triggered by inhalation of large volumes of relatively cool dry air during vigorous exercise  Symptoms occur after the end of exercise or during prolonged exercise  Initial bronchodilation followed by bronchoconstriction that peaks 10-15 minutes after exercise  Diagnosis by exercise challenge test (15% decrease in FEV1 suggests EIA)  Treatment  Pre-treatment with short-acting bronchodilators (alone or combination)  Chromoglycates, ICS + LABA, leukotriene modifiers response Ic c Site.rs Eiqmmationbreaieittigato bronchoconstriction Smoking & Asthma  Type-2 low; Neutrophilic ieeEEEEtiEeEEea mil  Steroid resistant smokinesinducers  Mechanisms – oxidative stress leading to neutrophil and macrophage activation thiscontributeto and Airwayinflammation damage  Smoking also increases risk of sensitization to allergens  Asthma-COPD overlap (ACO) condition weather.atientnavessmptonedastnmanc.pe Patients with ACO may experience more  Persistent airflow limitation in patients >40 years of age severe symptoms and have a greater decline in lung function due to the combined e ects  At least 10 pack-years smoking of asthma and COPD. Treating ACO requires careful management of both asthma and  Onset of asthma 200 ml AND 12% Look for between-visit FEV1 variability - FEV1 change >200 ml AND 12% Diurnal PEFR variability, >10% in adults, performed twice daily over 2 weeks Bronchoprovocation testing Exercise challenge – fall in FEV1 >10% and 200 ml from baseline Methacholine or histamine challenge – fall in FEV1 >20% so Mannitol or Eucapnic hyperventilation – fall in FEV1 >15% PEFR= Peak Expiratory Flow Rate Methacholine Challenge Test are constrictor broncho Procedures and devices for nebulizing methacholine are not standardized If a nebulizer has well-defined and reproducible output characteristics, then the inhaled dose can be estimated PD20 compares better than PC20 between devices PD20 PC20 Severity (micrograms) (mg/mL) Normal >400 >16 not Borderline 100-400 4-16 Mild 25-100 1-4 Moderate 6-25 0.25-1 Marked 2/yr Frequency & Severity NHLBI. NAEPP EPR 3: Guidelines for the Diagnosis and Management of Asthma (NIH Publication No. 07-4051) (US Department of Health and Human Services, Bethesda, 2007) Asthma management Assess – Adjust – Review response 2020 GINA report, global strategy for asthma management and prevention a e O Severe Asthma - Definition corticosteroid Asthma that requires treatment at GINA steps 4–5 or systemic CS for of e >50% of the previous year to prevent it from becoming ‘‘uncontrolled’’ or remains ‘‘uncontrolled‘‘ despite this therapy Or Controlled asthma that worsens on tapering of these high doses of ICS or systemic CS (or additional biologics) Chung et al. Eur Respir J 2014; 43: 343–373 Association, prevalence and treatment outcomes of comorbidities in difficult asthma Does treatment Comorbidity Associated with asthma? Prevalence in asthma improve asthma? Sino-nasal disease AR Yes 80% # Yes Sino-nasal disease CRS Yes 70-74% * Yes GERD Yes 59% # Inconsistent OSA Yes 75-95% * Yes VCD Yes 75% * Inconsistent DB Yes 29% # Yes Anx/Dep Yes 49% * Yes * Difficult asthma # All asthma A dapted from Radhakrishna N. Journal of A sthma. 2016 GERD & Asthma  Prevalence 32-84% by esophageal pH-monitoring studies; about half are asymptomatic  Carefully review symptoms: Heartburn, Regurgitation, Water brash, Dysphagia, Sore throat, Choking, Hoarseness, Dental erosions, Chest pain, Cervical pain, Worsened asthma symptoms with Eating, Alcohol, Supine position, Theophylline  Proposed mechanisms – ‘Reflux’ vs ‘Reflex’  Likely a bi-directional relationship  Studies demonstrate some benefit in symptomatic GERD and uncontrolled asthma  Improvement in peak flow, quality of life, exacerbations AJRCCM2006 May 15;173(10):1091-7 AJRCCM 2010 May 15;181(10):1042-8. Chest 2005 Sep;128(3):1128-35 N Engl J Med 2009; 360:1487-1499 CRS & Asthma  Symptomatic inflammation of the paranasal sinuses and the nasal cavity   F Chronic Rhino-Sinusitis = lasting > 12 weeks With or without nasal polyps (CRSwNP or CRSsNP)   The unified airway model 9 Links the upper and lower airway as a single functional group  Shared systemic inflammatory pathways  Prevalence of CRS  10-12% general population  23.4-74% in all asthma  84% in severe asthma  Associated with decreased lung function, QOL, severe exacerbations Ear Nose Throat J 2007; 86: 409. J Allergy Clin Immunol 2001;107:73. J Allergy Clin Immunol 2002;109:621. Otolaryngol Head Neck Surg. 2007;136:S75-S106. Otolaryngol Clin N Am. 2008;48:297-309. 2015 NHIS data. Obesity & Asthma Inflammation  Obesity is associated with Mechanical factors Increased peripheral airway High fat/low fiber diet   0 Worse asthma control Higher health care utilization closure Increased impedance Mass loading Adipose tissue & adipokines Innate & adaptive immune function Decreased ERV Gut microbiome  Poor response to standard controller therapy  Weight loss – dietary or surgical – is effective Comorbidities  Recent studies support a role for exercise Anxiety/Depression GERD OSA  I Diet quality – high protein/low glycemic index, plant-based, Mediterranean Dixon AE. AJRCCM 2016 Occupational Asthma (OA)  Asthma due to causes and conditions attributable to a particular occupational environment and not to stimuli encountered outside the workplace  Two types of OA: Immunological (sensitizing) or non-immunological  Needs to be distinguished from workplace exacerbated asthma  When to suspect OA?  Any new adult onset asthma  Worsening asthma control in a previously well-controlled asthmatic  Symptoms worse at work; improve over weekend and holidays  Latency period for onset of symptoms is highly variable Occupational Asthma (OA) - Etiologies High Molecular Weight Low Molecular Weight Flour: Bakers, pastry, cook Di-isocyanates: Auto-body shops, insulation, electronics Animals: Handlers, pet shop Woods (red cedar, exotic): Carpentry, sawmills, Crab: crab processing doors/windows Psyllium: Nurses, pharma Meth/cyanoacrylates: dental hygienist, orthesist, glues 8 Latex: Healthcare workers Antibiotics, enzymes: Nurses, pharma Phtalic anhydrides: plastic indurty, glues, epoxy Colophony: Electric soldering THANK YOU