Session 8 Flashcards
What is COPD?
• A disease characterised by – Persistent respiratory symptoms – Airflow limitation
• Due to airways and/or alveolar abnormalities
• Caused by significant exposure to noxious particles or gases
COPD is an “Umbrella Term”
• Not one disease but a syndrome
• Number of distinct pathologies – Usually co-exist
• Treatments are similar in most aspects
Aetiology of COPD
Smoking Biomass exposure Genetic (alpha one anti trypsin) Air pollution Illicit drug use
Epidemiology of COPD
Panopto
Pathophysiology of Disease
Small Airways Disease • Airway inflammation • Airway fibrosis, luminal plugs • Increased airway resistance
Parenchymal Destruction • Loss of alveolar attachments • Decrease of elastic recoil
both lead to airflow limitation
Chronic bronchitis
Emphysema
How is COPD diagnosed?
Look at symptoms
spirometry - required to establish diagnosis
Look at risk factors: Host factors, tobacco, occupation, indoor/outdoor pollution
Symptoms of COPD
slide 16 lec 1
Measuring dyspnoea
slide 17
Signs of COPD
- Often few or none especially at rest – Clinical observation and on exertion – Purse lip breathing – Hyperinflation or a barrel-shaped chest – Prolonged expiratory phase
- On examination – Maybe wheeze on auscultation – In advanced cases • Cyanosis (rarely) • Cor pulmonale (right sided heart failure)
How is spirometry used to diagnose COPD?
Confirm Airflow Obstruction
use panopto
Other investigations to look at COPD?
- Chest X-Ray not diagnostic – May suggest hyperinflation – Mandatory to exclude other diagnoses (e.g. cancer)
- High-resolution computed tomography (HRCT) – Detailed assessment of the degree of emphysema. – If suspicion of bronchiectasis – Not required for routine assessment of COPD.
- Full pulmonary function tests – Static lung volumes can assess for hyperinflation – Gas transfer to look at alveolar destruction
- If suspicion of respiratory failure (e.g. SpO2 <92%) – Arterial Blood Gas
- Alpha-1-antitrypsin blood test for younger patients or atypical lower lobe emphysema
Exacerbations of COPD
– At least one symptom of at least one major symptom (increased dyspnoea, sputum volume and sputum purulence) and one minor symptom (upper respiratory exacerbation in previous five days, wheezing, cough, fever or 20% increase in respiratory rate or heart rate)
– COPD exacerbations are defined as an acute worsening of respiratory symptoms that result in additional therapy
– A sustained worsening of the patient’s condition, from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitate a change in regular medication in a patient with underlying COPD
– An acute event characterised by a worsening of the patients’ respiratory symptoms that is beyond normal day-to-day variations, and leads to a change in medication
Epidemiology of Exacerbations of COPD
- Hospitalisation – 115,000 admissions/year in England – 16,000 deaths within 90 days of admission – Second most common cause of admission – Highest cause of readmission
- HQIP/RCP National COPD audit: 2014 – 11.9% mortality at 90 days (4.3% inpatient) – 43% readmitted at 90 days
Who’s at risk of a COPD Exacerbation?
- Previous exacerbations – Always strongest risk factor – “Frequent exacerbator” phenotype
- Disease severity – Airflow obstruction – MRC dyspnoea score
- Gastro-oesophageal reflux
- Pulmonary hypertension
- Respiratory Failure
Aetiology of Exacerbations
Common Bacteria Haemophilus influenzae (11%) Streptococcus pneumoniae (10%) Moraxella catarrhalis (10%) Haemophilus parainfluenzae (10%) Pseudomonas aeruginosa (4%) (20-30% patient chronically colonised)
Common Viral pathogens Rhinoviruses (23%) Coronavirus RSV (6%-11%) Influenza (5-28%) Parainfluenza Adenovirus
Atypical organisms Myoplasma pneumoniae (14%) Chlamydia spp (8.9%)
Environmental Factors Pollution (PM10 and PM2.5) (9%)
Eosinophilic Eosinophils (>0.30)
Is an Exacerbation a Type?
panopto slide 28
Treatment of COPD
Goals for Treatment
• Improve Symptoms – Relieve dyspnoea – Improve exercise tolerance – Improve health related quality of life
• Reduce Risk – Slow disease progression – Prevent and treat exacerbations – Reduce mortality
*Improves both symptoms and risk
Improves Symptoms
• Pulmonary Rehabilitation* • Bronchodilators (long-acting and short acting)* – Beta 2 agonists (LABA or SABA) – Anti-muscarinics (LAMA or SAMA) – Methylxanthines • Mucolytics* • Refractory dyspnoea management – Low dose opiates – Airflow therapy (fan) – Cognitive behaviour therapy/psychological input • Lung volume reduction surgery* • Lung transplant* • Palliative Care
Improves risk
• Smoking cessation* • Oxygen therapy – Long term oxygen therapy (LTOT) – Ambulatory oxygen therapy (ABOT)* • Anti-inflammatories* – Inhaled corticosteroids (ICS) – Long-term macrolides – Phosphodiesterase type 4 inhibitor (PDE inhibitor) • Non-invasive ventilation • Future/research in next 5 years – Monoclonal antibodies targeting inflammatory pathways • e.g. IL-5, IL-33, TSLP
COPD value pyramid
slid 32
Doing what, slows the rate of Lung Function Decline in patients with COPD?
What are the benefits of doing this and how might a patient do it?
Quitting smoking
Smoking cessation
• Reduces mortality (very little else does) • Improves symptoms • Slows down loss of lung function • Reduces exacerbations • The drugs work better
• It’s never too late to stop smoking – Nicotine replacement therapy – Champix – Behavioural support – (Vaping)
What is Pulmonary Rehabilitation?
“Pulmonary rehabilitation can be defined as an interdisciplinary programme of care for patients with chronic respiratory impairment that is individually tailored and designed to optimise each patient’s physical and social performance and autonomy. Programmes comprise individualised exercise programmes and education.”
• Exercise – 6-8 week course – Hospital or community basis – 2 supervised sessions/week – 1 unsupervised/week • Education programme • Referral or ongoing plan onto maintenance therapy
How do bronchodilators work?
slide 38
• Relax airways smooth muscle • Increase airway calibre
• Reduce breathlessness • Reduce exacerbations – Likely due to less perceived breathlessness
• Long acting bronchodilators (i.e. LABA/LAMA) – Used routinely as maintenance therapy either OD or BD
What are the Effects of ICS on airway inflammation
ICS reduced neutrophil and lymphocyte counts, increased macrophage counts, but had no significant effects on eosinophil counts in bronchoalveolar lavage studies
ICS reduced CD8+ and CD4+ lymphocyte counts, but had no significant effects on neutrophil, eosinophil and CD68 macrophage counts in bronchial biopsies
How are inhaled corticosteroids used to treat COPD?
- Reduce exacerbation frequency – 25% reduction with ICS (ISOLDE study) (Burge BMJ 2000) – 25% reduction with ICS/LABA (TORCH study) (Calverley NEJM 2007) – NNT=4
- Is this biomarker led? – Pascoe et al Lancet Resp Med 2014
How is Oxygen Therapy
used to treat COPD?
• Long term oxygen therapy (LTOT) – Extended periods of hypoxaemia cause end-organ damage to heart and kidneys – If PO2 <7.3KPa at rest (or PO2 <8.0KPa if cor pulmonale) – Minimum 16 hours/day – Improves survival – Non-smokers and not retain high levels of CO2 – Safety – Home Fire Risk Assessment • Ambulatory oxygen (ABOT) – If patients desaturate when walking (>4%) – Use during exertion and be willing to use – Need to walk further on oxygen – No prognostic benefit
Treatment of Severe Exacerbations Requiring Hospitalisation
• Hospitalisation – 12% mortality at 3 months – 43% readmitted at 3 months • Bronchodilation – May use nebulised therapy (SABA & SAMA) • Oral corticosteroids – Give oral prednisolone for 5 days – In future may be based on blood eosinophil count • Controlled oxygen if at risk of type 2 respiratory failure – SpO2 88-92% – Arterial blood gas • Antibiotics if indicated – If CRP is raised or white cell count raised – If symptoms suggested • Wider therapy – Inhaler technique and optimisation – Post-exacerbation pulmonary rehabilitation – Smoking cessation – Action plan for future
Acute Non-Invasive Ventilation
• PaCO2 is inversely proportional to ventilation – Minute Ventilation=Tidal volume*Respiratory rate – Tidal Volume is amount of air inspired in 1 breath
• Tidal volume α inspiratory pressure (IPAP) – i.e. Increase IPAP → increase Tidal Volume
side 44
Aims of Non-Invasive Ventilation
Support ventilation and improve ventilatory function
• Reduce PaCO2 (& raise PaO2) • Improve symptoms • Increase life expectancy • Reduce hospitalisation
Microbiota of the Respiratory Tract
Lungs are not sterile Normal alveolar microbiota Aspiration Blood stream spread Direct spread
Common Viridans streptococci, Neisseria spp, Anaerobes Candida sp
Less common Streptococcus pneumoniae Streptococcus pyogenes Haemophillus influenzae
Other Pseudomonas, Escherichia coli
Defences of the Respiratory tract
- Muco-ciliaryclearance mechanisms nasal hairs, ciliated columnar epithelium of the respiratory tract
- Cough & the sneezing reflex
- Respiratory mucosal immune system Lymphoid follicles of the pharynx and tonsils, alveolar macrophages, secretary IgA and IgG
- Alveolar microbiota
Course of a ‘typical’ infection
Lungs 1. alveolar macrophage fails to stop pathogen 2. cytokines to recruit more macrophages 3. inflammation = increased permeability 4. more WBCs/proteins (neutrophils/lymphocytes/antibodies to aid macrophages)
• Outside the lungs 1. inflammatory mediators (cytokines/chemokines) into systemic circulation 2. this itself is physiological -activates bone marrow /more cardiac output/raised body temp 3. dysregulation -signs of tissue injury/organ injury
What causes damage to the tissue or organ in disease?
The tissue / organ injury is a result of dysregulation
Causes of dysregulation
• The pathogen • Host factors • Drugs
Pathogen factors (virulence) that cause dysregulation
Chlamydia pneumoniae -ciliostatic factor Mycoplasma pneumoniae -shear off cilia Influenza virus - reduces mucus velocity (up to 12wk post infection) Strep pneumoniae /Neisseria meningitides -split immunoglobin (IgA) Pneumococcus - capsule inhibits phagocytosis (pneumolysin) Mycobacterium / Nocardia/ Leigonella -resistant to phagocytosis (intracellular survival)
Host factors that contribute to dysregulation?
Age > 65 Lifestyle —smoking (abnormal ciliary function) / alcohol/drugs Chronic lung diseases (bronchiectasis, cystic fibrosis) Aspiration —change in level of consciousness/ dysphagia/wearing dentures while sleeping (i.e. poor swallow (CVA, muscle weakness, alcohol) Immunocompromised –i.e. DM/HIV Metabolic –malnutrition/hypoxaemia/acidosis/ uraemia Co-infection with viruses (abnormal ciliary function)
How can drugs contribute to dysregulation
Antacids (PPI /H2 antagonist) PPI – increases risks for pneumonia H2 antagonist -myelosuppression (rare, long term) Antipsychotics -unclear association 258 cases + 1686 control + 65 years/older + 1996 to 2006 almost 60% increase in risk among older persons atypical antipsychotic associated fatal pneumonia (OR, 5.97 [CI, 1.49 to 23.98]) ACE inhibitors -associated reduced risk but only seen in observational studies with reporting bias Glucocorticoids -use of inhaled corticosteroids
Upper Respiratory Tract Infections
- Most commonly caused by viruses Rhinovirus, coronavirus, influenza, /parainfluenza Respiratory syncytial virus (RSV) • Bacterial super-infection common with sinusitis and otitis media –can lead to mastoiditis, meningitis, brain abscess
- Rhinitis (common cold) • Pharyngitis • Epiglottis • Laryngitis • tracheitis • Sinusitis • Otitis media
Lower respiratory tract infections
Pneumonia bronchiectasis empyema lung abscess Bronchitis Bronchiolitis
Acute Bronchitis
• Inflammation of medium sized airways. • Mainly in smokers • Cough, fever, increased sputum production, increased shortness of breath. • CXR: normal • Organisms: – viruses – S. pneumoniae – H. influenzae – M. catarrhalis • Bronchodilation; Physiotherapy; +/-Antibiotics
Chronic bronchitis
NOT primarily infective. Exacerbations have been associated with many organisms, but the role of infection remains controversial
LRTI - Definitions (Inflammation of the lung alveoli)
- Community acquired pneumonia (CAP)-outside healthcare setting
- Hospital acquired pneumonia (HAP) - 48 hours post admission
- Ventilated acquired pneumonia (VAP) - 48 hours post intubation
Acute inflammatory response Exudation of fibrinrich Fluid Neutrophil infiltration Macrophage infiltration
lobar pneumonia and bronchopneumonia
Microbiology - Community acquired pneumonia
• No microbiological ID made in most cases.
• True prevalence difficult to establish due to use of indirect methods / mixed infections
• Typical and Atypical organisms
Typical Organisms (85%) • Strep. pneumoniae (commonest) • Haemophillus influenzae(underlying chronic lung disease –COPD) • Moraxella catarrahalis • Staph aureus & MRSA • Klebsiellapneumonia • Group A Streptococcus pyogenes • Anaerobes • Viruses (RSV/Rhinovirus/Influenza/Parainfluenza)
Atypical Organisms (15%) • Mycoplasma -commonest (epidemics 4-6 yrs) • Legionella – contaminated water sources (aerosols / travel associated) • Coxiellaburnetii(Q fever)-worldwide, farm animals, (hepatitis) • Chlamydophilapneumoniae • Chlamydophilapsittaci(Psittacosis)-exposure to birds (splenomegaly, rash, haemolytic anaemia)
Diagnosing community acquired pneumonia
Clinical syndrome + imaging finding - Clinical cough (with/ without sputum) /dyspnoea/pleurisy fever/tachycardia/ organ dysfunction (e.g. hypotension /mental status change) crackles / bronchial breathing - Imaging consolidations/infiltrates/cavitations - When to admit? -use CURB-65
• CURB-65 score – Confusion – Urea >7 mmol/l – Respiratory Rate >30 – Blood Pressure <90 systolic <60 diastolic – >65 years • Score 2 = ?admit • Score 2-5 = manage as severe
Investigations
• Full Blood Count, • Urea & Electrolytes • C Reactive Protein • Arterial Blood Gases • Chest X Ray
Microbiological –samples/ investigations
• Sputum / Induced sputum • Blood culture • BronchoAlveolar Lavage fluid (BAL) • Nose & Throat swabs or NPAs (viruses) • Urine (antigen test for legionella / pneumococcus) • Serum (antibody test) acute & convalescent sera (usually collected at presentation and 10-14 days later)
Approach to managing a patient with LRTI
- mild CAP: treatempirically
- moderate CAP: blood cultures/sputum culture/urinary streptococcal antigen, legionella (+PCR)/viral screen
- severe CAP: moderate + bronchoscopic specimens
Differential diagnoses for CAP
Heart failure+ pulmonary oedema Pulmonary embolism Atelectasis Aspiration/ chemical pneumonitis Drug reactions Lung cancer Vasculitis Acute exacerbation of bronchiectasis Interstial LungDisease
Treatment of CAP
Principles of antibiotic treatment Empirical regimes can differ hospital /allergy status/ comorbidities General approach 5-7 days for mild CAP 7 - 10 days for severe CAP
UHL - Antibiotic treatment • Mild-moderate: – Amoxicillin – Or doxycycline or erythromycin / clarithromycin • Moderate-severe: – Needing hospital admission: Co-amoxiclavANDclarithromycin / doxycycline
Complications of community acquired pneumonia
- Initial infection progression – empyema/lung abscess/bacteraemia
- Non resolving CAP – delayed clinical response/closed space infections/ bronchial obstruction (e.g. tumour)/subacute, chronic CAP (TB/fungal)/incorrect initial diagnosis
Aetiology and management of hospital acquired pneumonia
• Staphylococcus aureus • MRSA • Enterobacteriaciae (E coli and Klebsiella spp) • Pseudomonasspp • Acinetobacter baumanii • Fungi (Candida sp.) • Other
Management - Cover Staph aureus + gram negative enteric bacilli (e.g. Klebsiella) + typical/atypical pathogens Co-amoxiclav - Pseudomonas risk -antipseudomonal beta lactam (piperacillin / tazobactam/ ceftazidime/meropenem) oranti-pseudomonalfluoroquinolone (ciprofloxacin) - MRSA risk –Vancomycin/Linezolid
- First line: Co-amoxiclav
- Second line/ITU: Piperacillin / tazobactamOr Meropenem
Aspiration Pneumonia
• Aspiration of exogenous material or endogenous secretions into the respiratory tract • Common in patients with neurological dysphagia (strokes), epilepsy, alcoholics, drowning • At risk groups -nursing home residents and drug overdose • Mixed infection -viridans streptococci & anaerobes • Mild infection –? treatment • Moderate to severe -Co-amoxiclav
Immunosuppression & LRTI
• HIV: Pneumocystis jirovecci, TB, atypical mycobacteria • Neutropenia: fungi e.g. Aspergillus spp • Bone marrow transplant: Cytomegalovirus • Splenectomy: encapsulated organisms – e.g. S. pneumoniae, H. influenzae, malaria
Prevention of pneumonia
• Immunization Flu vaccine –given annually to high risk patients Pneumococcal vaccine –every five years 23 polyvalent polysaccharide vaccine dose 13 valent conjugate vaccine Given to patients with co-morbities-increase risk of invasive pneumococcal disease • Chemoprophylaxis Oral penicillin / erythromycin to patients with higher risk of lower respiratory tract infections (i.e. asplenia, dysfunctional spleen, immunodeficiency) • Smoking advice
