CLI Week 5

Question 1

Asthma

Answer 1

• Atopic asthma is caused by a TH2 and IgE response to environmental allergens in genetically predisposed individuals à airway inflammation à release of mediators + remodelling of airway à airway dysfunction
• As the disease becomes more severe there is increased secretion of growth factors à mucous gland hypertrophy, smooth muscle proliferation, angiogenesis, fibrosis and nerve proliferation.
• Hypersensitivity with immediate and late-phase reaction
• Non-atopic asthma has the same pathogenesis but without the TH2 + B cell involvement
• As the disease becomes more severe and chronic and loses its sensitivity to corticosteroids, there is greater evidence of a Th1 response with release of mediators such as TNF-α and associated tissue damage, mucous metaplasia and aberrant epithelial and mesenchymal repair.

Acute Phase:

• Allergen (re-exposure) transported by dendritic cell through mucosal lining à presented to TH2 cell which secretes IL-4, IL-5 à Stimulates B cells to produce IgE à IgE binds to Fc receptor on mast cells à release of granule contents + production of cytokines (IL-5 – recruits eosinophils) and other mediators
• When eosinophils that are recruited are activated they also release granules and mediators exacerbating the reaction
• Leads to bronchoconstriction, increased mucous production, variable degrees of vasodilation + increased vascular permeability
  
  • Bronchoconstriction is triggered by direct stimulation of sub epithelial vagal receptors through central and local reflexes triggered by mediators produced by mast cells and other cells in the reaction.
    
    • Antigen directly stimulates vagal afferent nerve (central)
    • Mast cell mediators stimulate vagal efferent nerve (local)

Late phase:

• Dominated by recruitment of leukocytes, notably eosinophils, neutrophils, and more T cells à release additional mediators
  
  • Several factors released from eosinophils also cause damage to epithelium
• TH2 predominant type of T cell but TH17 also contributes and they recruit neutrophils

Inflammatory mediators and cytokines:

• IL-3 – Activation of mast cells, eosinophils
• IL-4 – Stimulates production of IgE
• IL-5 – Activates locally recruited eosinophils
• IL-9 – Activation of mast cells
• IL-13 – Stimulates mucous secretion from bronchial submucosal glands and also promotes IgE production by B cells
• Leukotrienes C4, D4 and E4 – Prolonged bronchoconstriction + increased vascular permeability + increased mucous secretion
• Acetylcholine – Released from intrapulmonary parasympathetic nerves à airway smooth muscle constriction via stimulation of muscarinic receptors
• Histamine – Bronchoconstriction
• Prostaglandin D2 – Bronchoconstriction + vasodilation
• Platelet activating factor – Aggregation of platelets and release of serotonin from their granules

Question 2

Idiopathic pulmonary fibrosis

Answer 2

1. Pulmonary disorder of unknown aetiology
2. Characteristics = patchy, progressive bilateral interstitial fibrosis
   
   • Can result in severe hypoxaemia and cyanosis in severe cases
   • More common in males over 60yo (according to Robbins)
3. Pathologic changes are known as usual interstitial pneumonia – seen in many diseases such as asbestosis etc. therefore IPF is when there is no known cause
4. Pathogenesis:
   
   • Repeated cycles of epithelial activation/injury by some unidentified agent
   • Inflammation and induction of T_H2 type T cell response w/ eosinophils, mast cells, Il-4 and IL-13 in lesions
   • Abnormal epithelial repair at site of damage and inflammation Ú fibroblastic proliferation
   • TGF-beta1 might be causing abnormal repair – release from injured type I pneumocytes
     
     • Transformation of fibroblasts into myofibroblasts
     • Therefore excessive deposition of collagen and ECM
5. Histological hallmark = patchy interstitial fibrosis worsening with time
6. Dense fibrosis causes collapse of alveolar walls and formation of cystic spaces lined with hyperplastic type II pneumocytes resulting in honeycomb fibrosis
7. Clinical features:
   
   • Gradual onset of non-productive cough and progressive dyspnoea
   • Velcro-like crackles during inspiration
   • Late stages: cyanosis, cor pulmonale, peripheral oedema

Question 3

Pneumoconiosis

Answer 3

Pneumoconiosis = non-neoplastic lung reaction to inhalation of organic and inorganic particulates (may also include chemical fume and vapour-induced)

1. Usually mineral dust – coal dust, silica and asbestos
2. Usually by particles 1-5μm in diameter because lodged at bifurcation of distal airways
3. Pulmonary alveolar macrophages play central role in pathogenesis of lung injury by promoting inflammation and producing reactive oxygen species and fibrogenic cytokines

Question 4

Coal Worker’s Pneumoconiosis

Answer 4

CWP stages

1. Asymptomatic anthracosis (pigment without perceptible cellular reaction)
   
   • Carbon pigment accumulated in CT, lymphatics or in lymph nodes
2. Simple CWP (accumulation of macrophages with little to no dysfunction)
   
   • Characterised by coal macules and nodules scattered throughout the lungs
   • Coal macules = dust-laden macrophages
   • Coal nodule = coal macules + small amounts of collagen fibres arrayed in delicate network
3. Complicated CWP/PMF (extensive fibrosis and lung function compromised)
   
   • Background of simple CWP by coalescence of coal nodules and generally requires many years to develop
   • Characterised by: multiple, intensely blackened scars larger than 2cm that consist of dense collagen and pigment

Note: less than 10% of simple CWP progress to PMF

CWP Clinical Features

• In PMF – increasing pulmonary dysfunction, cor pulmonale

Question 5

Silicosis

Answer 5

• Silicosis = inhalation of crystalline silica which interact with epithelial cells and macrophages, causing activation and release of mediators incl. IL-1, TNF, fibronectin, fibrogenic cytokines etc.
• Most prevalent chronic occupational disease in the world
• Characterised by silicotic nodules (concentrically-arranged hyalinised collagen fibres) with a silica particle in the centre of the nodules
  
  • These nodules coalesce into collagenous scars which progress to PMF
• Clinical features:
  
  • Pulmonary function either normal or only moderately affected
  • Most don’t have SOB until later, after PMF is present

Question 6

Asbestosis

Answer 6

1. Asbestos = crystalline hydrated silicates
2. Causes fibrosis by process involving interaction of particulates with lung macrophages
3. Asbestos is also a tumour initiator and promotor – oncogenic on the mesothelium mediated by reactive free radicals generated by asbestos fibres themselves
4. Can’t distinguish asbestosis from UIP morphologically except for presence of asbestos bodies = asbestos fibres coated with iron-containing proteinaceous material which are formed when macrophages attempt to phagocytose asbestos fibres
   
   • Iron from phagocyte ferritin
5. Pleural plaques are most common manifestation of asbestos exposure (plaques of dense collagen containing calcium)
6. Clinical features:
   
   • Same as other chronic interstitial lung diseases

Question 7

Airway obstruction

Answer 7

Can be incomplete or complete

• Complete obstruction of the upper airway occurs when there is inability to talk, cough or breath. Apnea and cyanosis are present and paradoxical respirations may be noted.
• Incomplete obstruction occurs when there is partial upper airway obstruction and ability to breath is maintained. Inspiratory stridor and increased work of breathing are the hallmarks.

Upper airway obstruction can be due to the following factors:

• luminal (e.g. foreign body)
• intramural (e.g. tumour, neuromuscular diseases)
• extramural (e.g. thyroid mass)

Question 8

Acute bronchitis

Answer 8

It is usually viral but can be complicated with bacterial infection, particularly in smokers and in patients with chronic airflow limitation. Symptoms include cough, retrosternal discomfort, chest tightness, and wheezing. This usually resolves spontaneously over 4-8 days.

Question 9

Acute laryngotracheobronchitis or croup

Answer 9

Usually a result of infection with one fo the parainfluenzae viruses or measles virus. Symptoms are most severe in children under 3 years of age. Inflammatory oedema involving the larynx causes a hoarse voice, barking cough (croup) and stridor. Tracheitis produces a burning retrosternal pain. Treatment is oxygen and inhaled steam, tracheostomy is needed in severe cases

Question 10

Epiglottitis

Answer 10

Epiglottitis is an acute inflammation in the supraglottic region of the oropharynx with inflammation of the epiglottis, vallecula, arytenoids, and aryepiglottic folds. In adults, the most common organisms that cause acute epiglottitis are Haemophilus influenzae (25%), followed by H parainfluenzae, Streptococcus pneumoniae, and group A streptococci.

In spite of acute epiglottitis generally having a good prognosis, the risk of death for persons is high due to sudden airway obstruction and difficulty intubating patients with extensive swelling of supraglottic structures.

Question 11

Cystic fibrosis

Answer 11

An autosomal recessive condition occurring in 1:2000 live births. It is caused by mutations in a single gene on the long arm of chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR). Mutations in the CFTR gene result in the production of a defective transmembrane protein which is involved in chloride transportation across epithelial cell membranes in the pancreas, respiratory, GI and reproductive tracts. The decreased chloride transport is accompanied by decreased transport of sodium and water, resulting in dehydrated viscous secretions that are associated with luminal obstruction and destruction and scarring of exocrine glands.

Neonates may present with meconium ileus or, rarely, with other features such as anasarca. Patients younger than 1 year may present with wheezing, coughing, and/or recurring respiratory infections and pneumonia. GI tract presentation in early infancy may be in the form of steatorrhea, failure to thrive, or both.

Patients diagnosed later in childhood or in adulthood are more likely to have pancreatic sufficiency and often present with chronic cough and sputum production. Approximately 10% of patients with cystic fibrosis remain pancreatic sufficient; these patients tend to have a milder course.

Question 12

Acute Respiratory Distress Syndrome

Answer 12

Acute Respiratory Distress Syndrome

• ARDS is a clinical syndrome of progressive respiratory insufficiency caused by diffuse alveolar damage in the setting of sepsis, severe trauma or diffuse pulmonary infection
• Damage to the endothelial and alveolar epithelial cells with inflammation, are the key initiating events and the basis of lung damage
• The characteristic histologic picture is that of hyaline membranes lining alveolar walls. Edema, scattered neutrophils and macrophages and epithelial necrosis are also present.

Question 13

Acute lung injury

Answer 13

Also called non-cardiogenic pulmonary oedema and is characterized by the abrupt onset of significant hypoxemia and bilateral pulmonary infiltrates in the absence of cardiac failure. ARDS is a manifestation of severe ALI.

Question 14

Severe Acute respiratory syndrome (SARS)

Answer 14

A viral respiratory disease of zoonotic origin caused by the SARS coronavirus (SARS-CoV).- first appeared in November 2002 in china and subsequently spread to hong kong, taiwan, Singapore, Vietnam and Toronto where large outbreaks occurred. The main way that SARS seems to spread is by close person-to-person contact. The virus that causes SARS is thought to be transmitted most readily by respiratory droplets (droplet spread) produced when an infected person coughs or sneezes.

In general, SARS begins with a high fever (temperature greater than 100.4°F [>38.0°C]). Other symptoms may include headache, an overall feeling of discomfort, and body aches. Some people also have mild respiratory symptoms at the outset. About 10 percent to 20 percent of patients have diarrhea. After 2 to 7 days, SARS patients may develop a dry cough. Most patients develop pneumonia.

Question 15

Idiopathic pulmonary fibrosis

Answer 15

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, primarily occurring in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP)

Idiopathic pulmonary fibrosis portends a poor prognosis, and, to date, no proven effective therapies are available for the treatment of idiopathic pulmonary fibrosis beyond lung transplantation.

Pathophysiology:

it is currently believed that idiopathic pulmonary fibrosis (IPF) is an epithelial-fibroblastic disease, in which unknown endogenous or environmental stimuli disrupt the homeostasis of alveolar epithelial cells, resulting in diffuse epithelial cell activation and aberrant epithelial cell repair.

In the current hypothesis regarding the pathogenesis of idiopathic pulmonary fibrosis, exposure to an inciting agent (eg, smoke, environmental pollutants, environmental dust, viral infections, gastroesophageal reflux disease, chronic aspiration) in a susceptible host may lead to the initial alveolar epithelial damage. Reestablishing an intact epithelium following injury is a key component of normal wound healing. In idiopathic pulmonary fibrosis, it is believed that after injury, aberrant activation of alveolar epithelial cells provokes the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic/myofibroblastic foci, leading to the exaggerated accumulation of extracellular matrix with the irreversible destruction of the lung parenchyma.

Question 16

Sarcoidosis

Answer 16

Sarcoidosis

A multisystem granulomatous disorder of unknown aetiology that commonly affects young adults and usually presents with bilateral hilar lymphadenopathy (BHL), pulmonary infiltration and skin or eye lesions. The diagnostic histopathological feature is the presence of non-caseating granulomas in various tissues. Immunological abnormalities include high levels of CD4+ T cells in the lung that secrete Th1 dependent cytokines such as IFN-gamma and IL-2 locally.

Clinical manifestations include lymph node enlargement, eye involvement, skin lesions (erythema nodosum, painless subcut nodules), and visceral (liver, marrow) involvement. Lung involvement occurs in 90% of cases with formation of granulomas and interstitial fibrosis.

Question 17

Anatomy of Airways:

Answer 17

Upper Airway – nose to trachea

Trachea:

• Starts at C6 ends at T4 when the Primary Bronchi start
• Has C shaped cartilage rings – no cartilage posteriorly
• 1.8cm diameter, 12-14cm long
• Respiratory Mucosa: pseudostratified ciliated columnar epithelia with goblet cells
  
  • In smokers transforms to stratified squamous to protect from toxins – but lose cilia ability

Primary Bronchi:

• Left is more horizontal than right – hence right gets blocked more when ya inhale the peanut
• Bifurcation is called carina
• Secondary Bronchi – one for each lung lobe, 3 on right, 2 on left, then Tertiary Bronchi then Bronchioles

Lower Airway – bronchi to alveoli

Conduction Zone:

• Filters, warms, moistens air – nose, nasal cavity
• Bronchi have cartilage plates for support
• Bronchioles – no cartilage – so this is where collapse can happen in emphysema
  
  • Less than 1mm diametre

Respiratory Zone:

• Gas exchange – alveoli
• Pulmonary Acinus:
  
  • Respiratory Bronchioles
  • Alveolar Ducts
  • Alveolar Sacs

Alveoli:

• Made of Pneumocytes
  
  • Type 1: simple squamous epithelium – the lining
  • Type 2: cuboidal – secrete surfactant – fewer than Type 1
  • Also have Alveolar Macrophages to munch the bad things – both fixed and free macrophages

Question 18

Control of Breathing:

Answer 18

• Central Controller – Pons, Medulla
• Sensor – chemoreceptors in brain, aorta, carotid bodies
  
  • Mechanoreceptors in lung
• Effectors: Respiratory muscles – diaphragm, intercostals, abdominal muscles

Medulla:

• Dorsal Respiratory Group – Inspiration
  
  • Input from CN 9 and 10
  • Receives information from peripheral chemoreceptors, baroreceptors and pulmonary stretch receptors
    
    • Pulmonary stretch receptors feed back via the Vagus Nerve
  • Sends information back to Phrenic and Intercostal Nerves – activates diaphragm and intercostals
• Ventral Respiratory Group – active inspiration and expiration
  
  • Mostly inactive in normal quiet breathing
  • Contribute extra respiratory drive during increased demand

Pons:

• Pontine Respiratory Group – contains the pneumotaxic (limits inspiration) and apneustic (prolongs inspiration)centres

Question 19

Chemical Control: Important bit

Answer 19

• Arterial CO2 – acts indirectly on medulla respiratory centres
• Arterial H+ - acts on peripheral chemoreceptors and indirectly (via CO2 changes) on the medulla respiratory centres
• Arterial O2 – acts on peripheral chemoreceptors in carotid and aortic bodies
• IMPORTANT: increased PaCO2 has a potent acute effect on respiratory drive but only a weak chronic effect after a few days
  
  • SO PATIENTS WITH COPD RELYING ON THEIR HYPOXIC DRIVE TA-DA!

Peripheral Chemoreceptors:

• Carotid bodies and Aortic arch – most sensitive to changes in PaO2
• Carotid input to medulla via Glossopharyngeal nerve
• Aortic input to medulla via Vagus nerve

Question 20

Hypoxia, Respiratory Drive in health and Disease.

Answer 20

• Respiratory drive refers to the process by which detected changes in the body’s pH and PCO2 levels are responded to by the central nervous system’s corrective stimulation of the rhythm, effort and rate of breathing. The control and response of the respiratory system takes place within the medulla of the brain stem. The spinal cord serves as the conduit through which the appropriate neural signals are converyed to the muscles of respiration.
• It is affected by the levels of CO2 in the blood. Level changes are detected by central chemoreceptors in the medulla and by peripheral chemoreceptors in the carotid artery and aorta. The feedback loop and resulting neural signals cause breathing patterns to change accordingly and the body is able to maintain the correct acid-to-base and O2 to CO2 ratios.
• Hypoxic drive is when the body uses oxygen chemoreceptors instead of carbon dioxide receptors to regulate the respiratory cycle.
• In the case such as COPD ® when there are chronically high levels of CO2 in the blood, the body will begin to rely on the O2 receptors and less on the CO2 receptors. So if there is an increase in oxygen levels the body will decrease the rate of respiration.

Question 21

Pathophysiology of Shortness of Breath in Asthma and COPD.

Answer 21

• Damage to the air sacs in the lungs causes them to become large which leads to breathing difficulties as well as inflammation and irritation in the lining of the lungs.
• Not as much oxygen exchange across the damaged alveoli.

Question 22

Pulmonary Function tests.

Answer 22

• Spirometry measures airflow. By measuring how much you exhale, and how quickly you exhale, spirometry can evaluate a broad range of lung diseases. In a spirometry tst, while you are sitting, you breathe into a mouthpiece that is connected to an instrument called a spirometer. This records the amount and the rate of air that you breathe in and out over a period fo time.
• In COPD, emphysema, asthma, chronic bronchitis and infections ® the lungs contain too much air and take longer to empy ® obstructive lung disorders
• To interpret a PFT ®
• Determine if the FEV1/FVC is low ® if low ® obstructive, if normal ® restrictive
• Determine if the FVC is low
• Confirm the restrictive pattern
• Grade the severity fo the abnormality
• Determine reversibility of the abnormality

Question 23

Clinical assessment and definition/diagnosis of Asthma:

Answer 23

• Paroxysmal recurrent attacks of wheezing (or in childhood of cough) due to airways narrowing, which changes in severity over short periods of time
  
  • Airflow limitation
  • Airway hyperresponsiveness
  • Bronchial inflammation
• The principal symptoms of asthma are wheezing attacks and episodic shortness of breath. Symptoms are usually worst during the night, especially in uncontrolled disease. Cough is a frequent symptom that sometimes predominates, especially in children in whom nocturnal cough can be a presenting feature. Attacks vary greatly in frequency and duration. Some patients only have one or two attacks a year that last for a few hours, while others have attacks lasting for weeks. Some patients have chronic persistent symptoms, on top of which there are fluctuations.
• In chronic asthma, inflammation may be accompanied by irreversible airflow limitation as a result of airway wall remodelling that may involve large and small airways and mucus impaction. 

• Extrinsic asthma occurs most frequently in atopic individuals: i.e. those with positive skin-prick reactions to common inhalant allergens such as dust mite, animal danders, pollens and fungi; 90% of children and 70% of adults with persistent asthma have positive skin- prick tests to inhalant allergens. Childhood asthma is often accompanied by eczema. Sensitization to chemicals or biological products in the workplace is a frequently overlooked cause of late-onset asthma in adults.
• Intrinsic asthma often starts in middle age. Nevertheless, many patients with adult-onset asthma show positive allergen skin tests and on close questioning some of these will give a history of childhood respiratory symptoms suggesting they have extrinsic asthma.
• Non-atopic individuals may develop asthma in middle age from extrinsic causes such as sensitization to occupational agents such as toluene diisocyanate, intolerance to non- steroidal anti-inflammatory drugs such as aspirin or because they were given β-adrenoceptor-blocking agents for concur- rent hypertension or angina that block the protective effect of endogenous adrenergic agonists. Extrinsic causes must be considered in all cases of asthma and, where possible, avoided.

Question 24

Triggers of asthma- Atopy:

Answer 24

• Occupational sensitisers (increased in smokers)
  
  • Low molecular weight compounds, e.g. reactive chemicals such as isocyanates and acid anhydrides that bond chemically to epithelial cells to activate them as well as provide haptens recognized by T cells.
  • High molecular weight compounds, e.g. flour, organic dusts and other large protein molecules involving specific IgE antibodies 

• Non-specific factors
  
  • Cold air and exercise
    
    • Exercise-induced wheeze is driven by release of histamine, prostaglandins (PGs) and leukotrienes (LTs) from mast cells as well as stimulation of neural reflexes when the epithelial lining fluid of the bronchi becomes hyperosmolar owing to drying and cooling during exercise.
  • Atmospheric pollution, irritant dusts, vapour and fumes
  • Diet
    
    • Intake of fresh fruit and vegetables shown to be protective (possibly due to antioxidants in them)
  • Emotion
    
    • May influence acutely and chronically
    • Understandably anxious patients at risks of life-threatening attacks
  • Drugs
    
    • NSAIDs (other than COX-2 alone)
      
      • NSAIDs inhibit arachidonic acid metabolism via the cyclooxygenase (COX) pathway, pre- venting the synthesis of certain prostaglandins. In aspirin- intolerant asthma there is reduced production of PGE2 which, in a sub-proportion of genetically susceptible subjects, induces the overproduction of cysteinyl leukotrienes by eosinophils, mast cells and macrophages.
    • Beta-blockers
      
      • There is no direct sympathetic innervation of the smooth muscle of the bronchi, and antagonism of parasympathetically induced bronchoconstriction is critically dependent
upon circulating epinephrine (adrenaline) acting through β2-receptors on the surface of smooth muscle cells. Inhibition
of this effect by β-adrenoceptor-blocking drugs such as propranolol leads to bronchoconstriction and airflow limitation,
but only in asthmatic subjects. Selective β1-adrenergic-blocking drugs such as atenolol may still induce attacks of
asthma; ideally alternative drugs should be used to treat hypertension or angina in asthmatic patients.
  • Allergen – as seen in major pathology issues

Question 25

Recognition of severe asthma – 1 death a week in Australia:

Answer 25

* The term acute severe asthma is used to mean an exacerbation of asthma that has not been controlled by the use of standard medication. * Patients with *acute severe asthma* typically have: * The inability to complete a sentence in one breath 
 * A respiratory rate of ≥25 breaths/min 
 * Tachycardia ≥110 beats/min (pulsus paradoxus is not useful as it is only present in 45% of cases) 
 * PEFR \<50% of predicted normal or best. 
 * Features of life-threatening attacks are: 
 * A silent chest, cyanosis or feeble respiratory effort 
 * Exhaustion, confusion or coma 
 * Bradycardia or hypotension 
 * PEFR \<30% of predicted normal or best (approximately 
150 L/min in adults).
 * Arterial blood gases should always be measured in asthmatic patients requiring admission to hospital, with particular attention paid to the *P*aCO2. Pulse oximetry is ![]()useful in monitoring oxygen saturation during the admission and can reduce the need for repeated arterial puncture. Features suggesting very severe life-threatening attacks are: * A high *P*aCO2 \>6 kPa * Severe hypoxaemia \<8 kPa despite oxygen treatment * Low and falling arterial pH

Question 26

Taking a ‘cough history’:

Answer 26

* How long have you had the cough? * Do you cough up anything? What? How much? * Have you had sinus problems? * Is the sputum clear or discoloured? Is there any blood in the sputum? * Have you had high temperatures? * Does coughing occur particularly at night (acid reflux)? * Have you become short of breath? * Have you had lung problems in the past? * Have you been a smoker? Do you still smoke? * Have you noticed wheezing? (Asthma, COPD)? * Do you take any tablets? (e.g. ACE inhibitors)

Question 27

Cough history- Acute and Chronic:

Answer 27

* **Acute** * URTI * Common cold, sinusitis * LRTI * Pneumonia, bronchitis, exacerbation of COPD * Irritation – inhalation of bronchial irritant (e.g. smoke or fumes) * **Chronic** * COPD – smoking history * Asthma – wheeze, relief with bronchodilators * GORD – worse lying down, burning central chest pain * Upper airway cough syndrome – history of rhinitis, postnasal drip, sinus headache and congestion * Bronchiectasis – chronic, very productive * ACE inhibitor medication – drug history * Carcinoma of the lung – smoking, haemoptysis * Cardiac failure – dyspnoea, PND * Psychogenic – Variable, prolonged symptoms, usually mild

Question 28

Investigations of Chronic Cough:

Answer 28

**Chest radiograph:** Patients referred to specialist cough clinics most commonly have a normal chest radiograph. However, review of a recent film is mandatory as any significant abnormality will alter the diagnostic algorithm and avoid unnecessary investigation. **Spirometric and peak expiratory flow measurements:** Baseline spirometric results are likely to be normal in patients referred for specialist opinion. Spirometry is available in most hospitals and in an increasing number of primary care clinics. When available, it should be performed with reversibility testing in all patients with chronic cough. Peak expiratory flow (PEF) measurement in patients with persistent cough presenting in primary care has focused on the diagnosis of airflow obstruction. For this purpose, it may have some merit, but the use of PEF measurements to assess bronchodilator response appears to have limitations compared with conventional measurements of forced expiratory volume in 1 second (FEV₁). The value of serial PEF measurements for determining diurnal variability has not been properly assessed and is infrequently requested by specialist cough clinics. **Bronchoprovocation testing:** Bronchial challenge testing can provide very useful clinical information about patients with chronic cough. Virtually every diagnostic protocol for cough uses direct challenge methods (usually histamine or methacholine) and this review will be restricted to these. Bronchial hyperreactivity in a patient with cough and normal spirometric measurements raises the possibility of cough variant asthma. However, a definitive diagnosis cannot be made until the cough responds to specific asthma treatment. Airway hyperreactivity may develop during an acute viral respiratory illness and may persist for some months afterwards. Cough may persist for many weeks following an upper respiratory tract infection and a positive challenge test in this circumstance may be diagnostically misleading. Airway hyperreactivity to methacholine has also been found in patients with reflux oesophagitis but no respiratory complaints. * A negative bronchial challenge effectively excludes asthma as the diagnosis but does not eliminate a cough that may respond to steroid treatment. Particular interest has focused on patients with chronic cough and an eosinophilic bronchitis but with none of the airway dysfunction typically associated with asthma. A negative bronchial challenge may therefore prompt the clinician to assess the airway (most commonly using induced sputum) for evidence of an eosinophilia. **Upper airway provocation studies:** Extrathoracic airway dysfunction may account for asthma-like symptoms in particular cough. Extrathoracic airway responsiveness can be assessed by recording the maximal inspiratory flow-volume curve during conventional bronchial challenge testing. Extrathoracic airway hyperresponsiveness in the absence of bronchial hyperresponsiveness may be an indicator of upper airway disease as a cause for cough. Using flow-volume loops, variable extrathoracic upper airway obstruction has been observed in a series of patients with cough due to postnasal drip syndrome which improved with treatment. Precise interpretation of extrathoracic reactivity is difficult and the test is likely to remain primarily a research tool. **Sinus imaging:** Plain sinus radiographs therefore are of little value in the evaluation of chronic cough, and sinus CT scanning should be reserved for refractory cases which may require surgical intervention. **Gastrointestinal investigations:** Although not always available, 24-hour oesophageal pH monitoring is currently the best single test to help characterise any link between gastro-oesophageal reflux and cough. Dual probe pH studies are now commonly used and have extended our knowledge of the site and extent of reflux disease. However, 24 hour oesophageal pH monitoring is not without limitations and no consensus exists as to how best to define the temporal association between a cough and a reflux episode or to identify individuals most likely to benefit from antireflux therapy. There needs to be some caution in the interpretation of a negative pH profile. **Induced sputum:** A number of groups have recently adapted the conventional diagnostic strategies for chronic cough to include induced sputum. The key aspect has been the demonstration of an airway eosinophilia in patients without functional abnormalities, in particular bronchial hyperreactivity associated with asthma. Ideally, induced sputum should be requested after exclusion of the other common causes and after demonstration of normal airway hyperresponsiveness (provocative concentration of methacholine or histamine producing a 20% decrease in FEV₁ (PC₂₀) \>16 mg/ml). **Exhaled breath:** Exhaled nitric oxide (NO) levels appear to be lower in non-asthmatic coughers, allowing some differentiation from asthmatic cough. Exhaled NO may represent a simpler alternative to induced sputum tests, but currently it has no clear diagnostic role in the management of chronic cough. The measurement of many different inflammatory molecules in breath condensate, although currently a research procedure, may have a place in the diagnosis of chronic cough in the future. **Inhalation cough challenge:** Patients with persistent cough have a hypersensitive cough reflex to a range of tussive agents which diminishes with successful treatment.[¹⁰](http://thorax.bmj.com/content/59/4/342.full#ref-10) Citric acid and capsaicin are the two most widely used in cough challenge testing, although others include tartaric acid and ultrasonically nebulised distilled water.[^39,](http://thorax.bmj.com/content/59/4/342.full#ref-39)[⁴⁰](http://thorax.bmj.com/content/59/4/342.full#ref-40) The methodology involved is similar to bronchial provocation testing but, in contrast to these inhalation tests, no agreed universal standards for cough challenge testing exist.[⁴¹](http://thorax.bmj.com/content/59/4/342.full#ref-41) The particular value of cough reflex testing is in assessing the efficacy of antitussive therapy. There are no discriminating features on cough challenge testing which are likely to be of diagnostic value, and hence its place outside a research capacity is likely to remain limited. **Cough recording** Interest in cough monitoring has concentrated mainly on developing an objective means of measuring cough frequency and assessing severity. Differences in the characteristics of the cough sound and flow pattern between asthma, bronchitis, and interstitial fibrosis have been reported. Analysis of overnight cough recording determined differences in character and intensity of cough sounds between patients with cystic fibrosis and cryptogenic fibrosing alveolitis. These observations open the possibility of using cough monitoring as a diagnostic tool. **Psychological assessment** Psychogenic cough can be included in the range of recognised functional respiratory disorders. In children a characteristic “honking” or barking sound is described and is often attributed to a “habit cough”. However, a more complex “cough tic” disorder may underlie the problem. Psychogenic cough in an adult patient should only be considered following thorough exclusion of a physical cause. The value of a prompt and accurate diagnosis is manifest in the successful outcomes reported after psychotherapy. As cough is known to have an adverse impact on the quality of an individual’s life (in particular psychosocial aspects), cough specific quality of life questionnaires have been developed. Although not diagnostic, such instruments provide a measurement of the size and nature of this effect.

Question 29

Diagnosis of Epiglottitis and Croup:

Answer 29

* Examination * Throat Swab * CXR * Epiglottitis and croup are often confused because they share symptoms and signs including stridor. However, differentiation in early illness is possible by additional observation of coughing and absence of drooling in croup and by the additional observation of drooling with absence of coughing in epiglottitis. **Asthma:** 1^st line treatment of acute asthma. Tachycardia, increase RR and inability to form full sentences is indicative of sever attack. When PEFR \<150 L/min need to admit to hospital. Nebulise 5mg salbutamol. Hydrocortisone sodium succinate 200mg i.v. Oral prednisolone 200mg. O2 40-60%.

Question 30

X-ray:

Answer 30

**_Document_**: supine film is more plethoric due to distension of vessels due to gravity. On full inspiration diaphragm should sit at 11^th rib posteriorly. Dextrocardia. **_Chest:_ Lung:** upper zone 2 costal cartilage, middle zone 2^nd-4^th and lower zone 4^th -6^th. Apices of the lung is less perfusion but with LVF there will be increase opacity due to congestion. The right upper lobe has 3 segments, middle has 2 and 4 at lower lobe. The left upper has 4 and 4 lower. **Airway:** Trachea is normally deviated to the left due to the aortic knuckle. The aortic becomes wider and unfold with age. **Mediastinum:** hilum composed of pulmonary arteries and veins, lymphoma or pulmonary hypertension will cause enlargement of hilum. Heart. **Diaphragm:** peritoneal gas. **And Pleura.** **_Bone and soft tissue:_** breast shadow, soft tissue gas after thoracotomy, calcified glands in the neck and erosion/arthritis. **_Apices and review:_** Apices for TB and Pancoast’s tumors. Retrocardiac region for collapse left lower lob, appear as triangle. Lateral film: 4to4 rule for oblique fissure – 4cm behind anterior costal margin to hilum of T4 vertebral. Pulmonary venous congestion occur when venous pressure reach 15mmHg. Occur in LV failure cause redirection of blood to upper zone so blood vessels above the hila is larger. Interstitial pulmonary oedema when capillaries pressure exceed 25mmHg. Kerley B lines caused by odematous interlobular septae. Alveolar odema is seen when pressure reaches 30mmHg, giving bat’s wing appearance. Bulging of any cardiac boarder suggest ventricular aneurysm post MI. Pulmonary plethora indicate left to right shunt, there is mark dilatation of the pulmonary artery at the left hilum. Hydropneumothorax – air and fluid in pleura so no meniscus sign.

Question 31

Pneumothorax

Answer 31

Risk: associated with asthma, emphysema and TB. Spontaneous Idopathic pneumothorax occur in young. Sign – reduce lung expansion. SOB. Hyperresonance. Reduce breath sound. Subcutaneous emphysema. Primary: spontaneous rupture of subpleural bullae usually at the apice. Occur commonly tall young male, postulate there is underlying CT defects in the alveolar. Secondary: trauma, emphysema bullae, iatrogenic (caused by med intervention). Treatment – the air is absorbed at a rate of 1.25% of the radiographic volume of the hemithorax per day. \<20% radiographic volume – re-access in two weeks avoid strenuous exercise. Medium 20-50% and large \>50% aspirate air. If recurrence intercostal drainage tube in place for 2-3 days. If pneumothorax remain and tube bubbling, Video Assisted Thoracoscopic (VATS). Recurrence more than twice -\> VATS

Question 32

imaging

Answer 32

Pneumococcal pneumonia Consolidation with air bronchogram & arrows show bulging of oblique fissure (arrows). TB pneumonia Arrows show paratracheal lymphadenopathy. Arrowhead show enlarged nodules at parenchyma indicative of miliary TB Lung abscess A large circumscribed lesion with a well defined wall and air-fluid level is consistent. Radiology Right heart boarder – right middle lobe. Fat less dense than muscle/ soft tissue. Right parasternal margin. Mass (tumor, abscess, fungus), nodule (\<1cm tb, granuloma, pneumoconiosis, allergic alveolitis, metastasis), consolidation, atelectasis – pneumonia (air bronchogram - consolidation, lung expansion occur) or collapse (plate atelectasis – lobule collapse) due to mass obstruction (white no air, lose volume diaphragm move, hilum and mediastinum shift), interstitial lung marking – odema kurlley b line, fibrosis, inflammatory – viral (check old x-ray acute or chronic). Non small cell - SCC – cavitate, hilum and bronchus where most expose to smoke and squamous cells are. Smoker.Adeno – fill aveloar because they secrete mucus, start off small consolidation. Starts off in the periphery and apice. Small cell – neuroendocrine. Hilum and medisternum tropisium. Metastatic – cannon ball round. Sihouette sign blurring of margins. Reticulonodular – white lines kurlley b line interstitial.

Question 33

Role of asthma plans

Answer 33

Written asthma action plans are one of the most effective asthma interventions available. An asthma action plan helps the person with asthma and/or their carer recognise worsening asthma and gives clear instructions on what to do in response. Every adult and child with asthma should have their own written asthma action plan that provides clear instructions on how to adjust medication in response to asthma symptoms, and when and how to get medical care, including during an emergency. Written asthma action plans should be individualised for the patient (e.g. clearly naming the medicines the person uses, using words they will understand, identifying individual signs of flare-ups). They should be reviewed regularly.

Question 34

Maintenance therapy in asthma

Answer 34

* Relievers (prescribe a reliever and train the patient to use it correctly): * Advise all patients with asthma to carry a reliever containing a rapid-onset inhaled beta₂ agonist at all times and use it when they experience difficulty breathing * Preventers (consider regular preventer treatment with inhaled corticosteroids or other preventer): * Explain to the patient that preventers should be taken every day and continued long term to reduce the risk of flare-ups * For adults prescribed low-dose ICS for an indefinite period, explain that: * The main purpose of long-term low-dose ICS-based preventer is to reduce the risk of flare-ups, even if day-to-day symptoms are infrequent * Even if the person has not experienced asthma symptoms for some time, they should not stop taking their preventer without discussing first

Question 35

Role of short-acting and long-acting beta agonists

Answer 35

* Beta₂-agonists (bronchodilators) are a group of drugs prescribed to treat asthma * Short-acting beta-agonists (SABAs) are used for quick relief of asthma symptoms, such as wheezing, ‘feeling tight’ when breathing, coughing and shortness of breath. SABAs act within minutes to temporarily relieve these symptoms by reversing the muscular bronchospasm in the airways; they are very effective in opening the airways * Examples – salbutamol and terbutaline * Long-acting beta agonists cause relax the muscle bands that surround the airways (bronchodilation) and allow you to breathe in and out more easily. These medicines can improve asthma control only when used in combination with an inhaled corticosteroid medicine. They are used every day, even when there are no asthma symptoms. LABAs are not rescue medicines and do not relieve sudden asthma symptoms. They are often used in people who have asthma symptoms at night or used to prevent exercise-induced asthma symptoms * Examples – salmeterol, formoterol

Question 36

Role of corticosteroids

Answer 36

Inhaled corticosteroids are the most effective preventer medicines for adults. ICS are effective in reducing asthma symptoms, improving quality of life, improving lung function, decreasing airway hyper-responsiveness, controlling airway inflammation, reducing the frequency and severity of asthma flare-ups and reducing the risk of death due to asthma

Question 37

Atopy- hay fever /eczema management.

Answer 37

The most important point of management for both of these conditions is to try and avoid the precipitating allergen. Allergen testing by skin prick or IgE blood test is recommended for those with persistent allergic rhinitis- the evidence is less substantial for eczema. _Drug treatment for allergic rhinitis:_ (as per eTG) ![]() ![]()

Question 38

Management of atopic eczema:

Answer 38

* Modification of lifestyle to avoid exacerbating factors * Avoid wool and synthetics * Avoid soaps and shampoos etc. use soap substitutes * Avoid HOT baths * Cold windy weather exacerbates it * Use moisturisers and bath additives * Investigation and treatment of infection * MCS if there is a flare up * Treatment appropriate antibiotics e.g. cephalexin against staph infection * Use of topical anti-inflammatory agents * Use of wet dressings

Question 39

Oxygen therapy in Respiratory Disease.

Answer 39

Oxygen is the most commonly used drug in acute clinical settings. Normal atmospheric oxygen is 21% - another way of expressing this is talking about the amount of ‘inspired oxygen’. This is often written as FiO2. This means room air has an FiO2 of 0.21. It is essential for cell function and without oxygen some cells (such as the brain) may become damaged or dysfunctional very quickly (minutes). Therefore neurological dysfunction is an early sign of hypoxia. The following values hold for otherwise healthy individuals (with illness symptoms may appear earlier) PaO2 of 90 mmHg - normal person with no symptoms PaO2 of 55 mmHg - short term memory loss, euphoria, impaired judgement PaO2 of 30 -55 mmHg - progressive loss of cognitive and motor function PaO2 \< 30 mmHg - loss of consciousness Oxygen is indicated in the treatment of most respiratory diseases, asthma, COPD, restrictive lung conditions, fibrotic lung conditions, pneumonia etc. By increasing the FiO2 we increase the amount of oxygen getting down to the alveoli without having to increase the patients tidal volume or respiratory rate (which are usually limited in these diseases). * Remember: before using oxygen we MUST SECURE THE AIRWAY- if we have a blocked trachea, oxygen is not going to do the patient any good. Oxygen of limited effectiveness in conditions where the alveoli themselves are destroyed (such as ARDS). * When we have a patient who comes in with COPD- we must use a venturi mask to control the oxygen flow and ensure their O2 sats do not rise above 95%. This is because patients with COPD have chronic CO2 retention and thus rely on their HYPOXIC DRIVE.

Question 40

Vaccination (Fluvax?)

Answer 40

* The administration of influenza vaccine to persons at risk of complications of infection is the single most important measure in preventing or attenuating influenza infection and preventing mortality * After vaccination, most adults develop antibody levels that are likely to protect them against the strains of virus represented in the vaccine * There is also likely to be protection against many related influenza variants ![]() **Influenza vaccine:** * Trivalent and quadrivalent flu vaccines: 2xFlu A (H3N2 & H1N1) plus 1 or 2 Flu B strains * Subunit vaccines prepared from purified inactive influenza virus (it is an egg vaccine) Efficacy is 70-90% depending on the age and immunocompetence

Question 41

Health promotion- asthma. concept of primary, secondary, tertiary and quarternary prevention

Answer 41

and quarternary prevention Primary prevention * Eat from 5 food groups, limiting intake of fatty, processed foods à increases asthma risk in children * Aim for healthy weight as obese people have higher rates of asthma due to mechanical, inflammatory and genetic/developmental factors * Promote breastfeeding as it is preventative against early childhood wheezing and development of asthma Secondary prevention * Continue to avoid tobacco smoke/ airway pollutants * Encourage environmental control for patients sensitised to house dust mites * Screen for asthma using spirometry à look for improvement in FEV1/FVC following bronchodilator therapy * Screen those at high risk- family history, existing atopic tendencies to promote early detection and appropriate management Tertiary prevention * Eliminate/reduce exposure to sensitised allergens * High fat and low fibre diets associated with increased airway inflammation and lower lung function in people with asthma. High fat meals reduce efficacy of bronchodilator response * Maintain physical activity as it improves cardiopulmonary fitness (exercise induced bronchoconstriction can be managed effectively). Recommend structured exercise and training as part of comprehensive asthma management * Weightloss improve asthma- improved airway hyperresponsiveness, lung function, asthma symptoms and control, and medication needs * Vaccinate against influenza and pneumococcal – to prevent acute exacerbations of asthma * Screen patients with asthma for depression and anxiety- as these conditions can also contribute to asthma Quaternary prevention (prevent overdiagnosis and overtreatment) * Focus on maintaining quality of life with asthma * Minimise side effects or drug-drug interactions from treatment * Avoid unnecessary or excessive intervention of the health system by still promoting lifestyle modifications in conjunction with Ventolin/corticosteroids [https://www.nationalasthma.org.au/living-with-asthma/resources/health-professionals/information-paper/asthma-healthy-living](https://www.nationalasthma.org.au/living-with-asthma/resources/health-professionals/information-paper/asthma-healthy-living)

Question 42

management of asthma in remote rural australia

Answer 42

![]() **Management process:** * Confirm diagnosis * Assess asthma control (table above) * Choose initial treatment in collaboration with patient to ascertain their preference * Provide information, skills and tools for self management * Correct inhaler technique * A written asthma action plan * Information about avoiding triggers where appropriate * Manage flare ups * Manage comorbid conditions affecting asthma or contribute to respiratory conditions * Provide advice about smoking, healthy eating, physical activity, healthy weight and immunisation **Working with indigenous populations** * Utilise interpreter where appropriate * Involve aboriginal and Torres Straight Islander health workers/practitioners * Be trained in how to provide culturally appropriate secure care * Ask if they smoke/ are exposed to another person’s smoke * Take comprehensive respiratory health history * Routinely ask about coughing (frequency and type), observe for cough even if patient does not mention it * When cough is present (especially wet or productive), consider possibility of other lung diseases (bronchiectasis, chronic suppuratives lung disease and COPD) * Offer referral to specialist in children with symptoms and signs suggestive of chronic suppuratives lung disease (if possible) * Consider existing comorbidities: diabetes, cardiovascular and kidney disease, and ear problems **Incidence/prevalence of Asthma and smoking in Indigenous populations** * Asthma prevalence: Higher among ATSI than non ATSI Australians * 2004-2005: overall prevalence 16.5% compared to 10.2% non ATSI * Fewer ATSI people living in remote areas report having asthma compared to those living in non-remote areas * Rate of hospitalisation for asthma is twice as high in ATSI population * Smoking rates: 45% ATSI \>15yrs old smoke daily (more than twice the rate of non ATSI) * 50% ATSI mothers smoked during pregnancy (3.7 times the rate among non ATSI) * 65% ATSI children live in households with someone who smokes daily (twice the rate of non indigenous children) * Note: smoking hinders asthma medication efficacy and makes asthma harder to control since inducing airway inflammation and irritation **Language and cultural awareness in long term management and prevention of smoking related diseases** * See above- ‘working with indigenous populations’ [http://www.asthmahandbook.org.au/populations/atsi-peoples/diagnosis](http://www.asthmahandbook.org.au/populations/atsi-peoples/diagnosis)

Question 43

incidence of Asthma in australia

Answer 43

1/9 Australians have asthma à around 2.5 million * More common in males 0-14yrs * More common in females \>15yrs * More common in socioeconomically disadvantaged areas * Prevalence is significantly higher in people living in inner regional areas compared to those in major cities, outer regional or remote areas $655 million spend on asthma in 2008-2009 [https://www.asthmaaustralia.org.au/national/about-asthma/what-is-asthma/statistics](https://www.asthmaaustralia.org.au/national/about-asthma/what-is-asthma/statistics)

Question 44

Concept of Chronic Disease and Self Management.

Answer 44

Concept of Chronic Disease and Self Management. * Self management = active participation by people in their own health care à allows people with chronic illnesses to develop the skills to manage their risk factors, monitor their diseases, make effective use of services and medications and cope with the impact of the disease on their lives * Example: asthma – patient needs to know/manage/avoid triggers, use preventer and reliever as required/prescribed, inhaler technique, written asthma action plan, PEFR devices to monitor asthma control, when to use emergency department, the importance of regular medical review * Incidence of allergies and atopy –environment, genetic factors. ![]() * 20% of the Australian population have an allergic disease (increasing) * 3 atopic diseases: allergic rhinitis, eczema, asthma 1. asthma: 11% of Australian population 2. eczema: 3. allergic rhinitis: 20% of individuals in western populations * The risk of developing atopy increases by a factor of two with each first-degree family member already suffering from atopy * 20% of all children develop atopic dermatitis in sometime in their lives, a child with mod-severe dermatitis has a 50% chance of developing asthma and a 75% chance of developing allergic rhinitis * 75% children with asthma have a history of atopy: 50% of adults with asthma have a history of atopy * Study carried out on monozygous and dizygous twins – all with a history of atopy àindicated that for the large part genetic makeup does influence inheritance of atopy however there is still some observed variability – ie. Not 100% genetic à it is believed that only 30% of the observed variability can be explained by environmental factors, and that the remaining 70% must be due to such a “third factor”, currently attributed to epigenetics

Question 45

COPD life expectancy.

Answer 45

* Not easy to gauge – no evidence with exact values (depends on staging, age, comorbidities, smoking status) * Different staging of COPD – higher the stage the shorter the life expectancy *GOLD staging* ![]() *GOLD classification for COPD* ![]() * The GOLD classification uses risk factors (GOLD 1 to 4 and number of exacerbations) and symptom severity (mMRC or CAT scale). In case both risk factors would fall in a different category, the highest risk factor is used (eg: GOLD 1 (GOLD A or B) with 2 COPD exacerbations last year (GOLD C or D) would be GOLD C or GOLD D). * GOLD A and B are low risk, GOLD C and D are high risk patients. * GOLD A and C have few symptoms, GOLD B and D have more symptoms * BODE index can be used to measure life expectancy * B: body mass index * O: obstruction of airflow (FEV1) * D: dyspnea (note: grade 0-4 of dyspnea) * E: exercise capacity (distance walked in 6 minutes) ![]() * *Fletcher-Peto graph* below clearly shows that smoking cessation can extend life expectancy and improve QOL even in late stage COPD ![]()