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•Chronic Obstructive Pulmonary Disease • It is a progressive disease, • Characterized by air flow limitations (irreversible), • It adds to the heart work. 1. Chronic bronchitis with an obstructive ventilatory pattern that is defined by the existence of chronic bronchitis with permanent obstruction of airways (FEV1/FVC<70%) 2. Chronic respiratory failure, which is defined by the existence of chronic obstructive bronchitis with hypoxaemia. 3. Emphysema with or without α1-anti-trypsin deficiency Chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of productive chronic cough have been excluded. Permanent enlargement of airspaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis. EPIDEMIOLOGY was the 6th cause of death in USA in 1990 2000: 120,000 died from COPD 2002: 12.1 million were reported having COPD 2020: is expected to be the 3rd cause of death However, the exact prevalence of COPD is under-estimated, due to it is an underdiagnosed (and undertreated) disease, because most patients do not present for medical care until the disease is in a late stage. It ETIOLOGY Cigarette smoking (the leading cause, 80-90%) Occupational exposure to dusts & chemicals (fumes, vapors, irritants….) Environmental air pollution (exact role ?) Genetic factors, viz., of α1 antitrypsin (AAT) Asthma & hyper-responsiveness are risk factors, but how they COPD is ? Recurrent infections &/or exposure to tobacco smoke during childhood → ↑ risk to COPD Intravenous drug use of methadone or methylphenidate pulmonary vascular damage that results from the insoluble filler (e.g, cornstarch, cotton fibers, cellulose, talc) contained in them Chronic inflammation dt repeated exposure to noxious particles & gases • Proteinases ≠ Antiproteinases Pathologic changes in Central airways Peripheral airways Lung Parenchyma • Oxidative stress (OS, tobacco + inflammation) Pulmonary vasculature 1- Chronic inflammation is mediated primarily by the activation of inflammatory cells, e.g. neutrophils, macrophages, CD8+T-lymphocytes and eosinophils (during exacerbation) inflammatory mediators (LTB4, IL-8, TNF-α). 2- Proteinases ≠ Anti-proteinases → unopposed proteinase activity (elastase, proteinase-3, etc…….) 3- OS ROS & RNS →damage of cell macromolecules & cell dysfunction promotes inflammation & prot./anti-prot. imbalance oxidants constrict airway smooth muscle→ narrowing airways Central Airways (trachea, bronchi, bronchioles >2mm diameter) [mainly hypersecretory phase] hyperplasia & hypertrophy of mucus secretory glands & goblet cells ↑ mucus secretion ciliary dysfunction chronic cough & sputum production + susceptibility to respiratory infections (viral followed by Peripheral Airways obstruction (bronchioles<2mm diameter)bacterial, Steptococcus pneumoniae and Obstruction phase Haemophilus influenzae). 1- Inflammatory exudates & mucus hypersecretion → cell remodeling + thickening the airway walls + narrowing of the airways. 2- Advanced chronic bronchitis: squamous metaplasia and fibrosis → ↑fixed limitation of airflow. 3- Loss of alveolar wall & elasticity → closure of small airways during expiration & fixed obstruction. Hyperplesia: ↑ in the number of normal cells in a tissue or organ Hypertrophy: ↑ in the size of cells → overgrowth of an organ or part of it. Worsened airflow obstruction → slow emptying of the lung → lung hyperinflation (1st upon exercise, then even at rest ) Airflow obstruction + damaged alveoli & bronchioles + pulmonary vascular abnormality (inadequate ventilation/ perfusion V/Q) → hypoxemia/hypercapnia. Severe hypoxemia → pulmonary artery V.C. → pulmonary H.T. → right-sided HF (cor pulmonale) Cor pulmonale → venous stasis, thrombosis → pulmonary embolism Fibroblast proliferation ↑ Proteases Chronic lung inflammation Airway mucus cells metaplasia/ hyperplasia ↓Immune response to infection Hypoxemic V.C & vascular remodeling Small airway fibrosis Destructed parenchyma Airway obstruction, hyperinflation, hypercapnia, hypoxemia, chronic dyspnea ↑Mucus secretion & viscosity Bacterial colonization Pulmonary hypertension Mucus plug Chronic cough & pneumonia Corpulmonale Hypoxic pulmonary vasoconstriction a si hcihw ni nonemonehp lacigoloisyhp ,lacixodarap fo ecneserp eht ni tcirtsnoc seiretra yranomlup ainpacrepyh tuohtiw )slevel negyxo wol( aixopyh ot wolf doolb gnitcerider ,)slevel edixoid nobrac hgih( .tnetnoc negyxo rehgih a htiw iloevla The process might at first seem illogical, as low ot dael yllaciteroeht dluohs slevel negyxoincreased suoesag desaercni eviecer ot sgnul eht ot wolf doolb taht tcaf eht yb denialpxe si ti ,revewoH .egnahcxe ot wolfdoolb fo noitubirtsider ot sdael noitcirtsnoc sesaercni hcihw ,gnul eht fo saera detalitnev-retteb .egnahcxe suoesag ni devlovni aera latot eht Types of respiratory failure 1- Type one respiratory failure: • caused by a ventilation-perfusion mismatch • This processes impairs oxygen transfer in the lung & causes hypoxaemia (acute or hypoxaemic respiratory failure) → hypoxaemia. • Treatment: correction of hypoxaemia with a high conc. of O2 to establish a PaO2 > 60 mmHg to ensure O2 saturation is maintained above 92 %, as tissue hypoxia will not occur at this level. 2- Type two respiratory failure: • caused by alveolar hypoventilation, e.g. patient with an exacerbation of COPD may not be able to ventilate alveoli sufficiently to remove CO2 leading to retention of CO2, with hypercapnia and hypoxaemia (chronic, ventilatory or hypercapnic respiratory failure). - Treatment is a high conc. of O2 despite a high CO2 level. - The aim is to achieve acceptable PaO2 without a fall in pH below 7.35. A pH below 7.26 is predictive of a poor outcome, so monitoring O2 saturation alone is not advisable & blood gas analysis is recommended to detect rise in PaCO2. Normal Arterial Values Range: • pH 7.35-7.45, • pCO2 35-45, • pO2 80-100, • O2 Sat. 95-100% , • HCO3 22-26 Abnormal values: • pH 7.30 (acidotic), • pCO2 58 (acidotic), • pO2 50 (low) • O2 Sat. 80% (low) -In case of respiratory failure we can use resp. stimulants as I.V. infusion of Doxapram (1-4 mg/min). S.E. narrow therap. index, HT, tachycardia, convulsion 1. A diagnosis of COPD should be considered in patients over the age of 35 who have a risk factor (generally smoking) 2. and who present with exertional breathlessness, chronic cough, regular sputum production, frequent winter ‘bronchitis’ or wheeze. 3. The presence of airflow obstruction should be confirmed by performing spirometry. •A suspected diagnosis of COPD should be based on the patient’s symptoms and/or history of exposure to risk factors. - History: •Do you smoke? •Have you had chronic exposure to dust or air pollutants? •Do other members of your family have lung disease? •Are you short of breath? •Do you get short of breath with exercise? •Do you have chronic cough and/or wheezing? •Do you cough up excess mucus? - COPD is asymptomatic at first, then symptoms develop when FEV1/FVC post-bronchodilator<70%. This’ll confirm airflow limitation that is not fully reversible. -SYMPTOMS & SIGNS: -Symptoms: •Initial: 1- chronic cough > 3 months in 2 successive years 2- chronic sputum production 3- dyspnea on exertion • As COPD progresses: 1- dyspnea at rest develops - decreased ability to perform daily activities N.B. Breathlessness is one of the 1ry symptoms of COPD. Graded by “The Medical Research Council (MRC) dyspnoea scale. -Signs: • Observation of the patient: 1- pat. starts to respire in a see-saw movement + use of accessory muscles 2- pursed-lips breathing 3- hyperinflation of the chest with increased anterior-posterior diameter (barrel chest). - On auscultation of the lungs: 1- wheezing, 2- a prolonged expiratory phase 3- rhonchi (breathing sound as snoring, due to obstructed airways with mucus & swollen mucus membrane). • In advanced COPD: 1- cyanosis & tachycardia (signs of hypoxemia) • Cor-pulmonale signs: 1- jugular venous distention (JVD), 2- lower extremity edema 3- hepatomegaly • Infection signs: yellowish or greenish sputum, which involves bacteria, macrophages & epithelial cells with no fever. GOLD Spirometric Criteria for COPD Severity I. Mild COPD FEV1/FVC < 0.7 * FEV1 > or = 80% predicted At this stage, the patient is probably unaware that lung function is starting to decline II. Moderate COPD FEV1/FVC < 0.7 * FEV1 50% to 79% predicted Symptoms during this stage progress, with shortness of breath (SOB) developing upon exertion. III. Severe COPD FEV1/FVC < 0.7 * FEV1 30% to 49% predicted SOB becomes worse at this stage & COPD exacerbations are common. IV. Very Severe FEV1/FVC < 0.7 * FEV1 < 30% predicted OR COPD FEV1 < 50% predicted with chronic respiratory failure Quality of life at this stage is gravely impaired. COPD exacerbations can be life threatening. GOLD: Global Initiative for Obstructive Lung Disease GOLD I: Mild COPD • There may be mild airflow limitation, but one may be unaware that lung function has started to decline. • FEV1≥ 80% of the predicted normal values with an FEV1/FVC <70%. One may not yet have any COPD symptoms, or may have symptoms of chronic cough and excessive mucus. • People at this stage are not likely to associate symptoms with the disease process and therefore, rarely seek treatment. GOLD II, Moderate COPD • Airflow limitation worsens and one may start to notice symptoms, particularly shortness of breath (SOB) upon exertion along with cough and sputum production. • FEV1 will be anywhere between 50% - 79% of the predicted normal values and FEV1/FVC <70%. • During this stage most people seek medical treatment. GOLD III, Severe COPD • Limitation of airflow significantly worsens, shortness of breath becomes more evident and COPD exacerbation is common. • FEV1 will be between 30% - 49% predicted and • FEV1/FVC <70 %. • This stage, is accompanied by ↓ in activity tolerance & ↑in fatigue-ability. GOLD IV, Very Severe COPD • Quality of life is greatly impaired & COPD exacerbations are life threatening. • Airflow limitation is severe (FEV1 <30% predicted, FEV1/FVC <70 %). • Chronic respiratory failure is often present at this stage, and may lead to complications with heart, such as cor pulmonale and/or eventually, death. GROUP SYMPTOMS L O W R I S K H I G H R I S K A Mild or infrequent B Moderate to severe C Mild or infrequent D Moderate to severe RISK FEV1 ≥ 80% predicted & 0-1 exacerbations within the past year, mMRC dyspnea score: 0-1 FEV1 ≥ 50% predicted & 0-1 exacerbations within the past year, MRC ≥ 2 FEV1 < 50% predicted & ≥ 2 exacerbations within the past year or ≥ 1 + hospitalization, MRC: ≥ 2 FEV1 < 30% predicted & ≥ 2 exacerbations within the past year or ≥ 1 + hospitalization, mMRC ≥ 2 From: The MRC breathlessness scaleFrom: The MRC breathlessness scale CAT: COPD assessment test mMRC: modified Medical Research Council dyspnea scores ody mass index, bstruction, yspnea, xercise POINTS BMI FEV1 Medical research council dyspnea score Distance walked in 6 min. (m) 0 1 2 3 > 21 ≥ 65 0-1 ≥ 21 50 - 64 2 36-49 3 ≥ 35 4 ≥ 350 250-349 150-249 ≥ 149 •Laboratory tests: 1- Hematocrit (polycythemia: no. of RBCs may be >55%). 2- Arterial blood gases (ABGs) [sp. in patients with an FEV1 less than 40% predicted [severe] or respiratory failure (hypoxemia with or without hypercapnia) or S&S of cor pulmonale. 3- α1-antitrypsin level [sp. pat.<45 years, with COPD S&S, & family history of emphysema]. 4- sputum bacterial analysis in case of pat. with infection signs. Besides the spirometry test [FEV1, FEV1/FVC] Typically begins in childhood No direct relationship Episode attacks with exposure to allergen, irritant or exercise Typically a dry cough at night Proximal airways IL-4+ IL-5+IL-13 CD4+ T cells + EOSINOPHILS + mast cells + plasma cells Age? Typically > 40 years age Smoking? Mainly smokers & ex-smokers Dyspnea? Progressive shortness of breath, usually with exertion Cough? Productive cough, typically in the morning Site of inflammation Key mediators Primary involved cells Distal Airways + parenchyma IL-18+TNF-α CD8+T cells, NEUTROPHILS+ macrophages I- Smoking Cessation 1-slow the rate of decline in pulmonary function 2- Reduce cough & sputum, 3- decrease airway reactivity Patients should be treated with a combination of counseling on behavioral and cognitive strategies and pharmacotherapy ( mainly nicotine replacement therapy). II- Pulmonary Rehabilitation •It should cover a range of non-pulmonary problems including: 1- exercise de-conditioning, 2- relative social isolation, 3- altered mood states (especially depression), 4- muscle wasting, and 5- weight loss. III- Long-term O2 therapy 1- In patients with chronic respiratory failure: give O2 therapy > 15 hrs/day to reduce mortality & improve life quality. 2- Very severe COPD with: a. resting PaO2 at or below 55 mm Hg b. PaO2 between 55 and 60 mm Hg & evidence of pulmonary hypertension, peripheral edema (suggesting CHF), or polycythemia. • Use the dual-prong nasal cannula to deliver continuous O2flow to O2 baseline saturation to at least 90% to oxygenate vital organs. The flow rate(L/minute), must be during exercise, sleep & air travel (2L/min). Oxygen therapy should be continued indefinitely. IV- Surgery Bullectomy, & lung transplantation (v. severe COPD) improved spirometry, lung volumes, exercise capacity, dyspnea, healthrelated quality of life, and possibly survival. A- β2-Agonists: • cause airway smooth muscle relaxation( adenyl cyclase cAMP) •Short acting [SABA]: - albuterol, salbutamol; levalbuterol, pirbuterol, & terbutaline. - “rescue” therapy for acute symptom relief (Releivers) • Long-acting [LABA]: (Controllers) -salmeterol & formoterol, last at least 12 hours, allowing for twice-daily dosing, better in maintenance schedule N.B. - salmeterol (partial agonist, slower onset of action than short-acting β2-agonists). - formoterol (pure full agonist, onset of action = albuterol) Adverse effects: palpitations, tachycardia, tremor & sleep disturbance B- Anticholinergics: (Controllers) • act by competitively blocking M3 receptors in bronchial SM.M [bronchodilation] & mucus secretory cells [dec. mucus] Ipratropium (half-life =2 hours, so dosing every 6 - 8 hrs). Tiotropium LAMA (long acting muscarinic antagonist) - once daily bec. it dissociates slowly from receptors, with half-life > 36 hrs) - improves lung function > ipratropium & salmeterol, but expensive). - tiotropium as maintenance + albuterol as rescue therapy. C- Theophyllines: (Controllers) • they ↓ phosphodiesterase (PDE) → ↑ cAMP • have a modest bronchodilator effect in patients with COPD. • limited use (narrow therapeutic index, multiple drug interactions [cimetidine, phenytoin alter metabolism], & adverse effects). • Caution in: CV complicated patients & hepatic impairment. •Theophylline should be reserved for patients who remained symptomatic despite appropriate use of inhaled bronchodilators. •Common adverse effects: heartburn, restlessness, insomnia, irritability, tachycardia, tremor & dose-related nausea, vomiting, seizures, & arrhythmias. • Adjust dose in COPD pat. bec. chemicals in tobacco smoke may induce cyt. P-450 that metabolizes theophylline. D- Combinations: • COPD pat. may need combination of 2 or 3 bronchodilators. • albuterol + ipratropium, • OR LABA + theophylline, •OR LABA + tiotropium •OR LABA + ipratropium OR the 3 bronchodilators II- Corticosteroids: (Preventers) • Used in symptomatic patients with severe COPD (FEV1 ≤ 50%) + frequent exacerbations [2 or more], requiring treatment with antibiotics or oral corticosteroids in a 12-months period. • Corticosteroid is used to ↓ no. of exacerbations/year. • However, corticosteroids do not slow the long-term decline in pulmonary function. • Combination inhaler device is recommended when using LABD + inhaled corticosteroid [e.g., Advair/ seretide (fluticasone/salmeterol), ]. • Assess after 6-8 weeks, if FEV1 is not improved (>15 %), stop corticosteroids, BUT reinstitute in pat. who develop deterioration in lung function, increase in dyspnea & mild exacerbations. • Long-term use of oral corticosteroids should be avoided dt unfavorable risk/benefit ratio. • Common adverse effects: 1- oropharyngeal candidiasis & hoarse voice 2- bruising & decreased bone density 3- myopathy in long-term use. • + theophylline: improved response to corticosteroids in COPD!!!! III- Immunization: • annual influenza vaccination (early October through mid-November) reduces serious illness and death by 50%. • All patients with COPD should also receive a one-time vaccination with the pneumococcal polysaccharide vaccine, even though sufficient data supporting its use in COPD patients are lacking. IV- Alpha1-Antitrypsin Augmentation Therapy: • I.V. augmentation therapy for AAT deficient patients & moderate airflow obstruction (FEV1 35% - 60% predicted). • carried out by weekly transfusions of pooled human AAT to maintain adequate plasma levels of the enzyme. • not recommended for individuals with AAT deficiency who do not demonstrate lung disease. V- Other Pharmacologic Therapies: A- Selective phosphodiesterase (PDE)4 inhibitor: • Roflumilast (Daxas, Daliresp) • is a drug that acts as a selective, long-acting PDE-4 inhibitor. • It has anti-inflammatory effects and is used as an orally administered drug for the treatment of inflammatory conditions of the lungs such as COPD. • In June 2010, Daxas was approved in the EU for severe COPD associated with chronic bronchitis. • In March 2011, Daliresp gained FDA approval in the US for reducing COPD exacerbations. B- Leukotriene modifiers (e.g., zafirlukast and montelukast): • not adequately evaluated in COPD patients & not routinely recommended, • however, small, short-term studies showed better pulmonary function, dyspnea, & life quality when LT modifiers were added. C- Mast cell stabilizer (e.g. Nedocromil), • not adequately tested in COPD patients & • is not included in the GOLD (Global Initiative for Chronic Obstructive Lung Disease) recommendations. D- N-acetylcysteine: • has antioxidant & mucolytic activity, can be suitable for COPD pat. , • However, clinical trials have produced conflicting results, so not routinely recommended. • One of the largest trials found N-acetylcysteine to be ineffective at reducing the decline in lung function & preventing exacerbations. E- Prophylactic antibiotics: • no effect, so used only to treat infectious exacerbations. • Anti-tussives: contraindicated bec. cough has protective role. COPD Treatment: GOLD 2017 Guidelines Long-acting bronchodilators: Almost all patients with COPD who experience more than occasional dyspnea should be prescribed long acting bronchodilator therapy. This could be a long-acting beta agonist (LABA), a long acting muscarinic antagonist (LAMA), or both. Patients with persistent COPD symptoms while taking one long-acting bronchodilator should be prescribed two (or a combination agent containing two long acting bronchodilators). Inhaled corticosteroids: are not recommended as monotherapy in COPD. Combination agents containing inhaled corticosteroids along with LABA are considered appropriate step-up therapy for patients experiencing COPD exacerbations while taking long-acting bronchodilators. Oral PDE4 inhibitors are considered an add-on therapy only for patients with COPD with chronic bronchitis and severe airflow restriction who experience COPD exacerbations despite use of a combination bronchodilator with inhaled corticosteroid. Treatment Algorithm for Stable COPD GOLD Stage Recommended Therapy Avoidance of risk factor(s), especially smoking cessation; influenza vaccination ADD I: Mild Inhaled short-acting bronchodilator when needed (e.g., ipratropium, albuterol, or combination inhaler) ADD II: Moderate Pulmonary rehabilitation , Inhaled LABD on a scheduled basis (e.g. tiotropium, salmeterol, or formuterol) Inadequate response to Use alternative class or combine classes of LABD? YES inhaled LABD 0: At Risk Inadequate response to LABD? YES ADD Inhaled corticosteroids if repeated exacerbations Add/substitute oral theophylline III: Severe IV: v. Severe ADD Long-term O2 if chronic respiratory failure; Consider surgical treatment The 2017 GOLD guidelines COPD GOLD Grade A: Any bronchodilator (short or long acting), titrating or switching to another as appropriate. COPD GOLD Grade B: A long acting bronchodilator (LAMA or LABA), and both if symptoms persist on one drug. COPD GOLD Grade C: A long acting muscarinic antagonist (LAMA), switching to LAMA+LABA or to LABA+ICS if further exacerbations occur. COPD GOLD Grade D: More complicated, requires individual management, often multiple drugs, consideration of roflumilast and azithromycin in selected patients. COPD exacerbations are defined as an acute worsening of respiratory symptoms that result in additional therapy. • The most common causes of an exacerbation are respiratory infection & air pollution, but the cause cannot be identified in about 1/3 of severe exacerbations. Mild exacerbations: • increase bronchodilator therapy with or without oral corticosteroids • antibiotics indicated only if clinical signs of airway infection (e.g., inc. volume & change in color of sputum and/or fever). Moderate – Severe exacerbations: 1- controlled oxygen therapy, 2- bronchodilators, 3- oral or I.V. corticosteroids, 4- antibiotics if indicated, and 5- consideration of mechanical ventilation (noninvasive or invasive). A- Bronchodilators: 1- Albuterol (acute exacerbations because of its rapid onset of action). 2- Ipratropium can be added to allow for lower doses of albuterol. Deliver through nebulizer (in patients with severe dyspnea and/or cough that would limit delivery of medication through an MDI with spacer. 3- Theophylline can be considered. B- Oral Corticosteroids : •Oral prednisone 30 to 40 mg/day for 10 to 14 days. •If inhaled corticosteroids are part of the patient’s usual treatment regimen, they should be continued during systemic therapy. •Systemic corticosteroids shorten the recovery time, quickly restore lung function, and may reduce the risk of early relapse. • Oral cort. should be tappered, then move to inhalers (beclomethasone 200-500 µg/ twice daily). C- Antibiotics: Antibiotics should be used in patients with COPD exacerbations who have either of the following characteristics: (1) at least 2 of 3 cardinal symptoms: - increased dyspnea, - Sputum volume, or - sputum purulence (sputum containing a lot of pus); or (2) a severe exacerbation requiring mechanical ventilation. Common m.o.: -Streptococcus pneumoniae, - Haemophilus influenzae, & - Moraxella catarrhalis. •In patients with more severe COPD: other bacteria, such as 1- enteric gram -ve bacilli (Escherichia coli, Klebsiella pneumoniae, & Enterobacter cloacae) and 2- Pseudomonas aeruginosa can be detected. Antibiotic treatment for most patients require 3 to 10 days, until the patient has been afebrile for 3 consecutive days. •Exacerbations due to uncommon bacteria require 21 to 42 days. • If no response in 48 to 72 hrs, adjust antimicrobial therapy considering sputum Gram’s stain & culture if not already obtained. D- Oxygen: • The goal is to maintain PaO2 > 60 mm Hg or SaO2 > 90% (to prevent tissue hypoxia & preserve cellular oxygenation). T21 RF •Increasing the PaO2 much further adds little benefit & may increase the risk of CO2 retention, which may lead to respiratory acidosis. In advanced COPD, (patients with chronic hypercapnia, T2 RF) caution should be used since overly aggressive administration of oxygen may result in respiratory depression & respiratory failure. In these patients, mild hypoxemia, rather than carbon dioxide accumulation, triggers their drive to breathe. • An arterial blood gas should be obtained after 1 to 2 hours to assess for hypercapnia. Oxygen Not Recommended Patients in GOLD 2017 for Most COPD • The 2017 GOLD guidelines generally advise against ecitcarp enituor eht of prescribing supplemental oxygen to stable COPD patients without severe resting hypoxemia . • In randomized trial in 700 >stable COPD patients with moderate hypoxemia, supplemental oxygen did not improve clinical outcomes or quality of life during the followup period . • COPD patients with severe resting hypoxemia 88% ≤ noitarutas negyxo(and certain other patients with COPD) should all receive supplemental oxygen to be worn continuously. E- Assisted Ventilation • Mechanical ventilation can be administered as follows: (1) Invasive (through endotracheal tube); (2) (NPPV) non-invasive positive pressure ventilation, using +ve pressure devices, which is preferred whenever possible as it -improves S&S, -decreases hospital stay, and -reduces mortality. • Appropriate patients to consider for NPPV include those with: (1) moderate to severe dyspnea with use of accessory muscles and paradoxical abdominal motion; (2) moderate to severe acidosis (pH between 7.25 and 7.35) & hypercapnia (PaCO2 between 45 and 60 mmHg). (3) respiratory rate between 25 and 35 breaths/min. • Invasive mechanical ventilation should be used in patients with more severe symptoms & in those failing NPPV. Non-Invasive positive pressure O2 Invasive mechanical ventilation • Recommended Antibiotic Patient: Characteristics Uncomplicated exacerbation 1- Not requiring hospitalization Therapy in Acute Exacerbations of COPD Likely Pathogens Recommended Antibiotics •Strepto pneumoniae, ORAL: • Macrolide (azithromycin, clarithromycin) • Ketolide (telithromycin) •Haemophilus influenzae, 2- < 3 exacerbations/ year •Moraxella catarrhalis 3- No comorbid illness • 2nd or 3rd generation cephalosporin (cefuroxime, cefpodoxime, cefdinir,cefprozil) 4- FEV1 > 50% predicted 5- No recent antibiotic therapy • Doxycycline • β-Lactam/β-lactamase inhibitor (amoxicillinclavulanate Above organisms plus: Complicated • drug-resistant pneumococci, exacerbation • β-lactamase producing H. 1- FEV 1 < 50% predicted influenzae & M. catarrhalis, 2- Comorbid cardiac Escherichia coli, Proteus spp., disease Enterobacter spp., Klebsiella 3- >3 exacerbations/ pneumoniae year 4- Antibiotic in previous 3 months ORAL: • amoxicillin-clavulanate • Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, gemifloxacin, moxifloxacin) INTRAVENOUS: • ampicillin-sulbactam • 2nd or 3rd generation cephalosporin (cefuroxime, ceftriaxone) •Fluoroquinolone(levofloxacin, moxifloxacin) Complicated exacerbation with risk factors for P. aeruginosa 1- Recent hospitalization 2- > 4 courses of antibiotics in the last year 3- Very severe COPD 4- Previous isolation of P. aeruginosa Antipseudomonal fluoroquinolone (ciprofloxacin, highdose levofloxacin) C- Above organisms plus P. aeruginosa ORAL: Antipseudomonal fluoroquinolone (ciprofloxacin, high-dose levofloxacin) INTRAVENOUS: a- Antipseudomonal β-lactamase resistant penicillin (piperacillintazobactam) b- 3rd or 4th generation cephalosporin with antipseudomonal activity (ceftazidime, cefepime) -Videos links: https://www.youtube.com/watch?v=fmLZrZv10NM https://www.youtube.com/watch?v=tusMPvA4wU&list=PLYojB5NEEakWxqnCBgl5_5rGXEP7VYGVT&index=2