T2 L11: Obstructive Lung Diseases

• asthma defn.

  heterogeneous disease characterised by chronic airways inflammation

  includes recurrent attacks of breathlessness and wheezing, which vary in severity and frequency from person to person
• 3 people die from an asthma attack in the UK every day

  most commonly present in childhood / middle age

  mild asthma - 50% of children will be symptom-free by the age of 21

  persistent asthma - 70% of children will continue to have symptoms in adult life

  adult-onset asthma is more likely to be persistent
• what causes the airflow obstruction?

  bronchoconstriction

  bronchial secretions and plugs of mucus

  oedema of the bronchial wall
• asthma in young people is usually linked to atopy
• what is atopy?

  tendency to form IgE antibodies to allergens

  often associated hay fever/eczema in the personal/family history
• the inflammatory cascade in allergic asthma

  inflammation cascade → chemokines recruit mast cells → positive feedback loop

  ICS - inhaled corticosteroid

  
• asthma symptoms

  cough, wheeze, breathlessness, chest tightness

  occurs in episodes

  diurnal variability
• triggering factors

  inflammation

  constriction

  others (i.e. medication, tobacco)
• medications as triggers

  aspirin

  ibuprofen

  beta blockers
• asthma investigations - GP

  Peak flow monitoring - twice day for 2 weeks

    Spirometry may show airflow obstruction
• asthma investigations: hospital

  Chest X-ray often normal, but may show hyperinflation

    Increased eosinophil count in the blood

    Fraction exhaled nitric oxide (FeNO)

  Skin prick or blood tests may confirm allergies
• if airflow obstruction

  FEV1/FVC ratio <70
• peak expiratory flow rate (PEFR) monitoring shows 20% diurnal variation
• FeNO - Fraction of exhaled nitric oxide

  measure of airways eosinophilic inflammation

  only on patients not on treatment

  used to monitor treatment/ look at compliance

  +ve test = asthma diagnosis
• long term asthma management - non-pharmacological

  smoking cessation

  weight reduction

  avoid pollution
• long term pharmacological management

  inhaled corticosteroids (ICS)

  eg. beclometasone

  inhaled long-acting beta 2 antagonists (LABA)

  eg. formoterol (in combination with ICS - never single treament)
• pharmacological management: oral treatment

  oral leukotriene antagonist - montelukast

  oral theophyllines
• In patients with chronically poorly controlled asthma: low dose long-term oral steroids (prednisolone). Hospital directed treatment
• what is used for immediate relief of symptoms?

  short-acting beta antagonists (SABA)

  salbutamol
• maintenance and reliever therapy (MART)

  •certain specific ICS/LABA combinations can be used as relievers as well as preventers

  •So patients can take additional doses for short period to rapidly treat any worsening asthma symptoms
• what are the two different inhaler devices?

  dry power inhalers (DPIs)

  pressurised metered dose inhalers (pMDIs)
• DPIs - mechanism

  activated by inspiration

  powdered drug is dispersed into particles
• pMDIs - mechanism

  drug dissolved in propellant hydrofluorocarbons under pressurised valve system releases a metered dose
• what to consider when deciding which inhaler to prescribe

  where they are in treatment

  what device they can use

  side effects - oral candidiasis, tremor, tachycardia

  cost
• very specialised treatments for small numbers of patients with difficult asthma

  monoclonal antibody

  -anti-IgE injections (omalizumab)

  -anti-IL-5 treatment (mepolizumab)

  bronchial thermoplasty
• personal asthma action plan (PAAP)

  •List daily medication to take + why

  •List which asthma triggers to avoid

  •List what to look for signs of deterioration of asthma/ values for PEFR

  •List names and doses of medication

  •List indicators of how + when to seek medical attention
• purpose of a PAAP

  improved asthma control

  reduces emergency contacts with GP

  reduces hospital admissions
• features of acute severe asthma

  –Peak expiratory flow rate (PEFR) 33-50% of best

  –Can’t complete sentences in one breath

  –Respirations ≥25 breaths/min

  –Pulse ≥110 beats/min
• life-threatening features

  – PEFR <33% of best or predicted

  – SpO2 <92%ƒ

  – Silent chest, cyanosis, or feeble respiratory effort

  – Arrhythmia/hypotension

  – Exhaustion, altered consciousness
• management of acute severe asthma

  oxygen

  corticosteroids

  nebulised bronchodilators
• what to do if poor response in management of acute severe asthma

  intravenous MgSO4/ aminophylline

  intubation and ventilation
• when to discharge from hospital

  •PEFR >75% of best or predicted and PEFR diurnal variability<25%
• What are the characteristics of COPD?

  heterogeneous lung condition

  Characterised by respiratory symptoms (dyspnoea, cough, sputum production and / or exacerbation)

  Due to abnormalities in the airways (bronchitis, bronchiolitis) or alveoli (emphysema)

  results in persistent, progressive airflow obstruction
• What is the burden of COPD?

  leading cause of morbidity and mortality worldwide with economic and social burden

  prevalence, morbidity and mortality vary across countries

  Prevalence often directly related to the prevalence of tobacco smoking
• How is the prevalence of COPD?

  Higher in smokers and ex-smokers

  Men > Women

  Higher in ≥ 40 years of age

  UK: second most common lung condition; 2% of whole population

  prevalence increasing
• How are the morbidity and mortality of COPD?

  Morbidity:

  • increases with age; comorbid conditions increase (e.g. CVD)
  • COPD 7th leading cause of poor health worldwide

  Mortality:

  • WHO – 3rd leading cause of death worldwide
  • ~90% deaths are in those under the age of 70 years olf and occur in low- and middle-income countries
• What is the pathogenesis of COPD?

  End-result of complex, cumulative and dynamic gene-environment interactions over the life time
• What are the environmental risk factors for COPD?

  Cigarette smoking

  Biomass exposure

  Occupational exposure

  Air pollution
• What are the genetic factors underlying COPD?

  significant familial risk of airflow obstruction

  in people who smoke and are siblings of people with COPD

  best documented genetic factors:

  • SERPINA1 gene → hereditary alpha-1 antitrypsin deficiency (AATD)
• What are the changes happening in COPD?

  Inflammatory changes:

  • increased number of macrophages in peripheral airways, lung parenchyma and pulmonary vessels
  • oxidative stress

  Structural changes:

  • imbalance between proteases derived from inflammatory & epithelial cells that break down connective tissue components
  • can result in emphysema