The ‘thumb’ sign	Oedema of the normally leaf-like epiglottis resulting in a round shadow resembling an adult thumb. The width of the epiglottis should be less than one-third the anteroposterior width of C4.
The vallecula sign	Progressive epiglottic oedema resulting in narrowing of the vallecula. This normally well-defined air pocket between the base of the tongue and the epiglottis may be partially or completely obliterated.
Swelling of the aryepiglottic folds
Swelling of the arytenoids
Prevertebral soft tissue swelling	The width of the prevertebral soft tissue should be less than half the anteroposterior width of C4.
Hypopharyngeal airway widening	The ratio of the width of the hypopharyngeal airway to the anteroposterior width of C4 should be less than 1.5.

Computed tomography

In the patient with a mechanical obstruction a computed tomography (CT) scan of the neck and upper thorax may be helpful in diagnosing the cause of the obstruction as well as the extent of any local involvement. It may aid in planning further management, especially if surgical intervention is indicated, for example for a retrothyroid goitre or a head and neck neoplasm.

Management

Management initially consists of securing the airway. This is discussed in more detail elsewhere in this book, but simple interventions include chin lift or jaw thrust and an oropharyngeal airway, or more sophisticated items such as the laryngeal mask, endotracheal tube or surgical airway. A surgical airway is rarely necessary in the ED, although it is important that equipment is always available and that the techniques have been practised. These include needle insufflation and cricothyrostomy. A number of commercial kits, such as the ‘Mini-trach II’ and the Melker Emergency Cricothyroidotomy Catheter Set, are available. Further management will depend on the underlying cause.

Trauma

Trauma to the upper airway may involve obstruction by a foreign body, blunt or penetrating trauma or thermal injury.

Foreign body airway obstruction

Foreign body aspiration is often associated with an altered conscious state, including alcohol or drug intoxication as well as cerebrovascular accident (CVA) or dementia. Elderly patients with dentures are at increased risk. Laryngeal foreign bodies are almost always symptomatic and are more likely to cause complete obstruction than foreign bodies below the epiglottis. If the obstruction is incomplete and adequate air exchange continues, care should be taken not to convert partial obstruction into a complete block by overzealous interference. Foreign bodies in the oesophagus are an uncommon cause of airway obstruction, but if lodged in the area of the cricoid cartilage or the tracheal bifurcation, can compress the airway, causing partial airway obstruction. Oesophageal foreign bodies may also become dislodged into the upper airway.

Management

The Heimlich manoeuvre or abdominal thrust is one recommended technique for dislodgement of a foreign body. The rescuer stands behind the patient, placing clenched fists over the patient’s upper abdomen well clear of the xiphisternum. A short, sharp upward thrust is made to force the diaphragm up and expel the foreign body. There is a risk of injury to internal organs and so this should only be done by rescuers who have been trained in the technique. Chest thrusts may be more effective in obese patients if the rescuer is unable to encircle the patient’s abdomen.

Chest thrusts are a similar technique that may be used in children or pregnant women, and back blows can be used in small children. Patients who are asymptomatic after uncomplicated removal of a foreign body should be observed for a time in the ED, and if they remain well may be discharged home.

In the unconscious patient direct laryngoscopy may be performed, with removal of the foreign body under direct vision with Magill forceps or suction.

Blunt trauma

Laryngotracheal trauma is rare, comprising 0.3% of all traumas presenting to an ED. The upper airway is relatively protected against trauma as the larynx is mobile and the trachea compressible, and because the head and mandible act as shields. Blunt trauma may be difficult to diagnose, as external examination may be normal and there may be distracting head or chest injuries.

Penetrating trauma

Mechanism

Penetrating injuries may be secondary to assault or to sporting or industrial accidents. A focused history is mandatory.

Clinical

Penetration of the airway should be suspected if there is difficulty breathing, a change in voice, pain on speaking, subcutaneous emphysema or bubbling from the wound. This is often associated with great vessel or pulmonary injuries, and the patient may require an emergency airway procedure. Uncontrolled haemorrhage is a potentially life-threatening condition. Other causes include head and neck malignancies eroding vascular structures, or following radiotherapy. Uncontrolled haemorrhage may lead to exsanguination as well as compromising the airway, and requires prompt surgical intervention.

Management of blunt and penetrating trauma

Airway management with protection of the cervical spine is essential. Fibreoptic bronchoscopic intubation is preferable to minimize complications such as laryngeal disruption, laryngotracheal separation or the creation of a false tracheal lumen. Cricothyrostomy is relatively contraindicated because of the altered anatomy. Emergency tracheostomy may even be required, ideally performed in the operating theatre. Early ENT involvement is important, and indications for surgical exploration include airway obstruction requiring tracheostomy, uncontrolled subcutaneous emphysema, extensive mucosal lacerations with exposed cartilage as identified on bronchoscopic or laryngoscopic examination, vocal cord paralysis, and grossly deformed, multiple or displaced fractures of the larynx, thyroid cartilage or cricoid cartilage.

Thermal injury

Pathology

Burns may affect the airway because of facial and perioral swelling, laryngeal oedema or constricting circumferential neck burns. Smoke inhalation occurs in about 25% of burn victims and may cause bronchospasm, retrosternal pain and impaired gas exchange.

Clinical

External examination may show evidence of burns. Carbonaceous material in the mouth, nares or pharynx suggests the possibility of upper airway thermal injury. If the patient presents with stridor or hoarseness, early intubation is essential because of the danger of increasing airway oedema. Smoke inhalation may be associated with carbon-monoxide poisoning, and in the setting of domestic or industrial fires cyanide poisoning should also be considered.

Investigations

Endoscopy

Endoscopy includes both laryngoscopy and bronchoscopy, performed in the operating theatre, as urgent surgical intervention may be required. Fuhrman et al. (see Further reading) suggest a classification system for the severity of blunt upper airway injury based on endoscopic and radiological findings (Table 6.1.3).

Table 6.1.3 Grading of blunt laryngeal injury

Grade	Endoscopic and radiological findings
I	Minor laryngeal haematoma without detectable fracture
II	Oedema, haematoma or minor mucosal disruption without exposed cartilage, or non-displaced fractures on CT
III	Massive oedema, tears, exposed cartilage, immobile cords

Imaging

Plain X-ray

X-rays should only be considered if the patient is stable, with adequate ventilation. Lateral soft tissue X-rays of the neck may provide information about airway patency, subcutaneous or soft tissue emphysema, and fractures of the hyoid and larynx. Elevation of the hyoid bone indicates cricotracheal separation. Plain X-rays may also confirm the presence of a foreign body. Cervical spine X-rays should be considered because of the association between upper airway injuries and cervical spine injuries. Chest X-rays may show signs of trauma and subcutaneous or mediastinal emphysema.

CT

CT scans of the neck are useful in assessing the extent of injuries to the larynx, oesophagus, cervical spine and adjacent structures, but should only be considered in the stable patient.

Infections

Infections may involve the upper respiratory tract directly or affect adjacent structures. They range from the common and trivial to the rare and potentially life-threatening. Croup and epiglottitis usually occur in children, but may be seen in adults. Acute respiratory infections are the most frequent reason for seeking medical attention in the USA, and are associated with up to 75% of total antibiotic prescriptions there each year. Unnecessary antibiotic use can cause a number of adverse effects, including allergic reactions, GI upset, yeast infections, drug interactions, an increased risk of subsequent infection with drug resistant Streptococcus pneumoniae and added costs of over-treating.

Non-specific upper airway infections

Upper airway infections are generally diagnosed clinically. Symptom complexes where the predominant complaint is of sore throat are labelled pharyngitis or tonsillitis, and where the predominant symptom is cough, bronchitis. Acute respiratory symptoms in the absence of a predominant sign are typically diagnosed as ‘upper respiratory tract infections’ (URTI). Each of these syndromes may be caused by a multitude of different viruses, and only occasionally by bacteria. Most cases resolve spontaneously within 1–2 weeks. Bacterial rhinosinusitis complicates about 2% of cases and should be suspected when symptoms have lasted at least 7 days and include purulent nasal discharge and other localizing features. Those at high risk for developing bacterial rhinosinusitis or bacterial pneumonia include infants, the elderly and the chronically ill. The antibiotic prescription rate for uncomplicated URTIs in the USA has been previously shown to be 52%, despite the fact that these infections are typically viral in origin and that antibiotic treatment does not enhance illness resolution nor alter the rates of these complications. Treatment should be symptomatic only.

Pharyngitis/tonsillitis

Sore throat is one of the top 10 presenting complaints to EDs in the USA. The differential diagnosis is large and includes a number of important conditions (Table 6.1.4). Pharyngitis has a wide range of causative bacterial and viral agents, most of which produce a self-limited infection with no significant sequelae. The major role for antibiotics in treating pharyngitis is for suspected group A β-haemolytic streptococcal infection (GABHS) or Streptococcus pyogenes. Timely use of appropriate antibiotics reduces the duration of symptoms by an average of 8 hours but increases the rate of adverse effects. Antibiotic use also reduces the incidence of suppurative complications such as otitis media, quinsy and retropharyngeal abscess. If given in the first 9 days they prevent the development of acute rheumatic fever. Antibiotics have not been shown to reduce the incidence of post-streptococcal glomerulonephritis, which is related to the subtype of streptococcus. Antibiotic therapy is also recommended for patients from the following groups: patients with scarlet fever, with known rheumatic heart disease, or from populations with high incidence of acute rheumatic fever, including some Aboriginal populations in Central and Northern Australia.

Table 6.1.4 Differential diagnosis of sore throat in the adult

Infective pharyngitis

Bacterial: Group A β-haemolytic streptococcus most common pathogen.

Diphtheria should be considered in patients with membranous pharyngitis

Viral: including EBV and HSV

Traumatic pharyngitis (exposure to irritant gases) Non-specific upper respiratory tract infection Quinsy (peritonsillar abscess) Epiglottitis Ludwig’s angina Parapharyngeal and retropharyngeal abscesses Gastro-oesophageal reflux Oropharyngeal or laryngeal tumour

Up to 50% of pharyngitis in children is caused by GABHS, but only between 5% and 15% of adult cases. The most reliable clinical predictors for GABHS are Centor’s criteria. These include tonsillar exudates, tender anterior cervical lymphadenopathy or lymphadenitis, absence of cough and a history of fever. The presence of three or more criteria has a positive predictive value of 40–60%, whereas the absence of three or more has a negative predictive value of approximately 80%.

Rapid antigen tests are available which have sensitivities ranging between 65% and 97% but are not widely used. They may have a future role in deciding the need for antibiotics. Throat cultures take 2–3 days and may give false positive results from asymptomatic carriers with concurrent non-GABHS pharyngitis. The Infectious Diseases Society of America recommends cultures for children and adolescents with appropriate clinical criteria but negative rapid antigen testing. In adults, because of the lower incidence of streptococcal infection and lower risk of rheumatic fever, a negative rapid antigen test is considered sufficient. Despite the availability of a number of guidelines, there are still wide variations in the management of pharyngitis. Serological testing is not useful in the acute treatment of pharyngitis but is useful in the diagnosis of rheumatic fever.

Neisseria gonorrhoeae is an uncommon cause of pharyngitis and may be asymptomatic. It is seen in persons who practise receptive oral sex. It is important to correctly diagnose N. gonorrhoeae pharyngitis, both for appropriate treatment and because of the need to trace and treat contacts. Ceftriaxone 125 mg i.m. as a single dose is the recommended treatment for uncomplicated pharyngeal gonorrhoea, and consideration should be given to concomitant treatment for chlamydia if this has not been ruled out. HIV is an unusual cause of pharyngitis but should be considered in high-risk populations. The acute retroviral syndrome may present with an Epstein–Barr virus (EBV) mononucleosis-like syndrome.

Most patients with pharyngitis are managed as outpatients. Airway compromise is rare, as the nasal passages provide an adequate airway. Some patients who are toxic or dehydrated may need admission for i.v. hydration and antibiotics. High-dose penicillin remains the drug of choice for streptococcal pharyngitis. The role of oral, i.m. or i.v. steroids remains controversial, but they may be useful in relieving airway obstruction and reducing the duration of symptoms.

Quinsy/peritonsillar abscess

Peritonsillar infections occur between the palatine tonsil and its capsule. Peritonsillar cellulitis may form pus and progress to abscess formation. Cellulitis responds to antibiotics alone, but differentiating between the two and identifying those that require drainage may be difficult clinically. Peritonsillar abscesses occur most commonly in males between 20 and 40 years of age. Symptoms include a progressively worsening sore throat, fever and dysphagia. On examination the patient may have a muffled ‘hot potato’ voice, trismus, drooling, a swollen red tonsil with or without purulent exudate, and contralateral deviation of the uvula. Complications include airway obstruction and lateral extension into the parapharyngeal space. GABHS is the most common organism associated with quinsy, but others include Staphylococcus aureus, Haemophilus influenzae and anaerobic species such as fusobacterium, peptostreptococcus and bacteroides. Treatment generally requires admission for i.v. penicillin and metronidazole. Clindamycin may be used as an alternative. Needle aspiration in experienced hands can be useful, but has a 12% false negative rate and carries the risk of damaging the carotid artery. Formal surgical drainage may be necessary.

Ludwig’s angina

Peripharyngeal space infections have become rare in the post antibiotic era but, of these, Ludwig’s angina or cellulitis of the submandibular space remains the most common. It was first described by Wilhelm Fredrick von Ludwig in 1836, and at that time was usually fatal because of rapid compromise to the airway. With prompt treatment, including i.v. antibiotics, the mortality rate has declined to less than 5%. Clinical features include toothache, halitosis, neck pain, swelling, fever, dysphagia and trismus. Ludwig’s angina is classically bilateral. Infection may spread rapidly into adjacent spaces, including the pharyngomaxillary and retropharyngeal areas and the mediastinum. Ludwig’s angina is related to dental caries involving the mandibular molars, or it may be associated with peritonsillar abscess, trauma to the floor of the mouth or mandible, and recent dental work. Cultures are usually polymicrobial and include viridans streptococci (40.9%), Staph. aureus (27.3%), Staph. epidermidis (22.7%) and anaerobes (40%) such as bacteroides species. Treatment necessitates admission and careful airway management. This may include endotracheal intubation, as abrupt obstruction can occur. Surgical drainage is indicated if the infection is suppurative or fluctuant. The i.v. antibiotics of choice are high-dose penicillin plus metronidazole or clindamycin.

Other abscesses

Parapharyngeal abscesses involve the lateral or pharyngomaxillary space. Presentation and treatment are similar to those of Ludwig’s angina, from which they may develop. As well as the complications of Ludwig’s angina, including airway obstruction and spread to contiguous areas, there is the added risk of internal jugular vein thrombosis and erosion of the carotid artery, which has a mortality of 20–40%.

Retropharyngeal abscesses are more common in children under 5 years of age. In adults they often result from foreign bodies or trauma. Presenting symptoms and signs include fever, odynophagia, neck swelling, drooling, torticollis, cervical lymphadenopathy, dyspnoea and stridor. Lateral neck X-rays show widening of the prevertebral soft tissues and sometimes a fluid level. CT of the neck may help in determining the extent and in differentiating an abscess from cellulitis. MRI, if available, is more sensitive than CT in assessing soft tissue infections of the head and neck, but demonstrates cortical bone poorly. Treatment requires admission, airway management and i.v. antibiotics, and may include surgical drainage.

Epiglottitis

Epiglottitis is becoming an adult disease, although in adults there is significantly less risk to the airway than in children. The incidence of adult epiglottitis has remained relatively stable at 1–4 cases per 100 000 per year, with a mortality of 7%, but this may change over the next 10–20 years as vaccinated children grow into adolescents and adults. Acute adult epiglottitis is often referred to as supraglottitis because the inflammation is not confined to the epiglottis, but also affects other structures such as the pharynx, uvula, base of tongue, aryepiglottic folds and false vocal cords. H. influenzae has been isolated in 12–17% of cases, and the high rate of negative blood cultures may reflect viral infections or prior treatment with antibiotics in cases that present late. Strep. pneumoniae, H. parainfluenzae and herpes simplex have also been isolated. Epiglottitis may also occur following mechanical injury such as the ingestion of caustic material, smoke inhalation, and following illicit drug use (smoking heroin).

Sore throat and odynophagia are the most common presenting symptoms. Drooling and stridor are infrequent. Factors shown to be associated with an increased risk of airway obstruction include stridor, dyspnoea, sitting upright, and short duration of symptoms. A number of X-ray changes have been described in epiglottitis, which are listed in Table 6.1.2. Management requires admission and i.v. ceftriaxone or cefotaxime. The role of steroids and nebulized or parenteral epinephrine (adrenaline) is controversial. Chloramphenicol may be used in patients with cephalosporin sensitivity. Most adults can be treated conservatively without the need for an artificial airway.

Controversies

• The role of steroids in acute pharyngitis/tonsillitis and quinsy.

• Reaching a uniform approach to the use of antibiotics in adult pharyngitis.

• The role of intubation, steroids and nebulized or parenteral epinephrine (adrenaline) in adult epiglottitis.

Introduction

The prevalence of asthma varies significantly between regions across the world. In Australasia, New Zealand and the UK it is thought to affect about 20% of children and 10% of adults. Sufferers tend to present to emergency departments (ED) when their usual treatment plan fails to control symptoms adequately. The respiratory compromise caused can range from mild to severe and life-threatening. For these patients the main role of the emergency physician is therapeutic. Other reasons for patients with asthma to attend EDs include having run out of medication, having symptoms after a period of being symptom and medication free, and a desire for a ‘second opinion’ about the management of their asthma. For this smaller group the primary role is one of educating about the disease, of planning an approach to the current level of asthma symptoms, and of referral to appropriate health professionals, e.g. respiratory physicians or general practitioners.

Epidemiology

Asthma is a major health problem in many countries, resulting in significant morbidity and mortality. The cost in terms of long-term medications and lost school and work days is difficult to quantify, but would run to millions of US dollars annually. Australasia, the UK and North America have a greater prevalence of asthma than the Middle East and some Asian countries. There is also considerable geographical variation in severity, with Australasia reporting the highest proportion of severe disease. The reason for this geographical variation is unclear, but may relate in part to ethnicity, rural versus metropolitan environment, and air pollution. A number of epidemiological studies suggest that the prevalence and severity of asthma is slowly increasing worldwide.

Pathophysiology

Asthma is characterized by hyperreactive airways and inflammation leading to episodic, reversible bronchoconstriction in response to a variety of stimuli. Traditionally, it has been divided into extrinsic (allergic) and intrinsic (idiosyncratic) types.

Extrinsic asthma is initiated by a type I hypersensitivity reaction induced by an extrinsic allergen. IgE-mediated activation of mucosal mast cells results in the release of primary mediators (histamine and eosinophilic and neutrophilic chemotactic factors) and secondary mediators including leukotrienes, prostaglandin D₂, platelet-activating factor and cytokines. These result in bronchoconstriction via direct and cholinergic reflex actions, increased vascular permeability and increased mucous secretions.

In contrast, intrinsic asthma is initiated by diverse non-immune mechanisms, including respiratory infections (in particular viruses), drugs such as aspirin and β-blockers, pollutants and occupational exposure, emotion and exercise.

The morphological changes in asthma are over-inflation of the lungs, bronchoconstriction, and the presence of thick mucous plugs in the airways. Histologically there is thickening of the basement membrane of the bronchial epithelium, oedema and an inflammatory infiltrate in the bronchial walls, increased numbers of submucosal glands and hypertrophy of bronchial wall muscle.

Pathophysiologically the effects of acute asthma are:

• Increased physiological dead space.

• Respiratory muscle fatigue.

• Intrinsic positive end-expiratory pressure secondary to hyperventilation with air trapping.

There is increasing evidence that there are different phenotypes of both acute and chronic asthma. For acute asthma, a rapid onset may be closer to anaphylaxis in pathology, with minimal inflammation, and may respond more quickly to treatment.

Clinical assessment

History

Asthma is characterized by episodic shortness of breath, often accompanied by wheeze, chest tightness and cough. Symptoms may be worse at night, which is thought to be due to variations in bronchomotor tone and bronchial reactivity. Attacks may progress slowly over days or rapidly over minutes.

Features in the history indicating a significant risk of life-threatening asthma include a previous life-threatening attack, previous intensive care admission with ventilation, requiring three or more classes of asthma medication, heavy use of β-agonist therapy, repeated ED attendances, and having required a course of oral corticosteroids within the previous 6 months. It has been identified that behavioural and psychosocial features increase the risk of life-threatening episodes of asthma. These include non-compliance with medications, monitoring or follow-up, self-discharge from hospital, psychiatric illness, denial, drug or alcohol abuse, obesity, learning difficulties, employment or income problems, domestic, marital or legal stressors and major tranquillizer use. These should be sought in order to more accurately assess risk and plan management.

Examination

Physical findings vary with the severity of the attack and may range from mild wheeze and dyspnoea to respiratory failure. Findings indicative of more severe disease include an inability to speak normally, use of the accessory muscles of respiration, a quiet or silent chest on auscultation, restlessness or altered level of consciousness, and cyanosis. Clinical features are a good guide to the severity of attacks. Features of the major severity categories are summarized in Table 6.2.1. Pulsus paradoxus has been abandoned as an indicator of severity.

Table 6.2.1 Categorization of asthma severity based on clinical features. (Modified from Guidelines for Emergency Management of Adult Asthma, Canadian Association of Emergency Physicians, British Guideline on the Management of Asthma (SIGN) and Asthma Management handbook (NAC).)

Severity category	Features	Respiratory function
Near death	Exhaustion Confusion, coma Cyanosis Sweating Silent chest Inability to speak Reduced respiratory effort Dysrhythmia, bradycardia Hypotension

FEV₁/PEFR inappropriate SpO₂ <90% despite supplemental oxygen Severe

Laboured respiration

Sweating, restless

Tachycardia, heart rate >120

Tachypnoea, respiratory rate >25/min

Difficulty speaking: words or short phrases only

FEV₁/PEFR unable or <40% predicted

SpO₂ <90% on air

PEFR <200 L/min

Moderate

Dyspnoeic at rest

Able to speak in short sentences

Chest tightness

Wheeze

Partial or short-term relief with usual therapy

Nocturnal symptoms

FEV₁/PEFR 40–60% predicted PEFR 200–300 L/min Mild

Exertional symptoms

Able to speak normally

Good response to usual therapy

FEV₁/PEFR >60% predicted

Investigation

For mild and moderate asthma investigations should be limited to pulmonary function tests (PEFR or FEV₁) and pulse oximetry. A chest X-ray is only indicated if examination of the chest suggests pneumothorax or pneumonia. Arterial blood gases are not useful in this group of patients.

For severe asthma a chest X-ray is necessary, as localizing signs in the chest may be hard to detect. Arterial blood gas analysis is useful if the oxygen saturation is less than 92% on room air at presentation, if improvement is not occurring as expected, and if the patient appears to be tiring. For those with severe asthma, blood gases may show respiratory alkalosis and mild-to-moderate hypoxia (reflecting an increase in respiratory rate in an attempt to maintain oxygenation) or hypoxia and respiratory acidosis as the PaCO₂ rises with fatigue and air trapping. Blood gases may also be helpful if intubation is being considered. Otherwise, their impact taken early in management is minimal. They should never be considered ‘routine’.

Full blood examination is usually not useful, as a mild to moderate leukocytosis may be present in the absence of infection. Electrolyte measurements may show a mild hypokalaemia, particularly if frequent doses of β-agonists have been taken.

Management

The emergency management of acute asthma varies according to severity, as defined by the clinical parameters above. The principles are to ensure adequate oxygenation, reverse bronchospasm and minimize the inflammatory response.

Mild asthma

Mild attacks are managed using inhaled β-adrenergic agonists such as salbutamol by metered dose inhaler (MDI) or spacer, the commencement of inhaled corticosteroids if the patient is not already taking them, and education about the disease and the proposed management and follow-up plan.

Moderate asthma

Patients with moderate attacks may require oxygen therapy titrated to achieve oxygen saturation in excess of 92%. The mainstays of therapy are inhaled β-adrenergic agents (by MDI with a spacer or nebulizer) and systemic corticosteroids. The dosage of salbutamol is 5–10 mg by nebulizer or eight puffs by MDI and spacer, every 15 minutes for three doses. Corticosteroids are equally effective given by the oral or intravenous routes. The usual dose is 50 mg prednisolone orally or 250 mg hydrocortisone intravenously. Reassessment, including repeat pulmonary function tests, should occur at least 1 hour after the last dose of β-agonist, with a view to the need for further therapy and decision on hospital admission. For patients who are discharged, oral corticosteroids at a dose of 0.5–1 mg/kg/day, in addition to inhaled steroids at standard doses, should be continued for at least 5 days or until recovery.

Severe asthma

Severe attacks require supplemental oxygen to achieve oxygen saturation in excess of 92%. Because of high respiratory rates it is important to ensure adequate gas flow by the use of either a reservoir-type mask or a Venturi system. High oxygen concentrations may be necessary. Patients should have continuous cardiac and oximetric monitoring, and should receive continuous β-agonist by nebulizer at the doses described above, plus oral or intravenous corticosteroids. The addition of nebulized ipratropium (500 μg 2-hourly) is recommended. If patients fail to respond, an intravenous β-agonist (e.g. salbutamol as a bolus of 250 μg followed by an infusion at 5–10 μg/kg/hour) and/or ventilation should be considered. Intravenous magnesium (1.2–2 g) may be beneficial (see below). Although pooled studies and meta-analyses fail to show benefit in adults, there is anecdotal evidence that selected, rare patients who fail to respond to the above treatment may benefit from i.v. aminophylline (5 mg/kg loading dose over 20 minutes, followed by 0.3–0.6 mg/kg/h). It should not be used without specialist input, and should be used with particular care in patients already taking oral xanthines at admission.

If ventilatory support is required for patients with an acceptable conscious state and airway protective mechanisms, non-invasive ventilation may be suitable. Continuous intensive monitoring is mandatory. If the patient is unsuitable or does not improve with non-invasive ventilation, endotracheal intubation and ventilation will be needed. Ketamine, which has been shown to be an effective bronchodilator, is the induction agent of choice. Care must be taken with ventilation, as severe air trapping results in markedly raised intrathoracic pressure with cardiovascular compromise. A slow ventilation rate of 6–8 breaths/min with prolonged expiratory periods is recommended.

A number of other therapeutic modalities are outlined below.

Epinephrine (adrenaline)

Small studies have suggested that epinephrine administered by nebulizer and subcutaneously has a similar effect to nebulized salbutamol. These studies are limited by small sample size and the inclusion of patients with mild and moderate asthma.

Epinephrine may have advantages over salbutamol as a parenteral agent. This is based on the theoretical reduction of bronchial mucosal oedema by α-adrenergic mechanisms and inhibition of cholinergic neurotransmission. Anecdotes and small case series indicate that epinephrine is safe and effective, but no studies comparing epinephrine to more selective agents have been published.

Bicarbonate

The postulated mechanism of action of bicarbonate in severe asthma is the facilitation of adrenergic effects and the countering of acidosis, thereby improving respiratory muscle function. To date only small case series support this view, and the quality of evidence is poor. There are also concerns that its administration to patients with pure respiratory acidosis may have deleterious effects.

Non-invasive ventilation (NIV: CPAP and BIPAP)

In acute asthma, NIV has been shown to reduce airways resistance, bronchodilate, counter atelectasis, reduce the work of respiration, and reduce the cardiovascular impact of changes in intrapleural and intrathoracic pressures caused by asthma. It does not, when used alone, improve gas exchange. An unrandomized study of CPAP in combination with pressure support ventilation in patients with severe asthma found rapid correction of pH and improvement in ventilation at lower pressures than were necessary with mechanical ventilation. Other small studies also suggest that NIV may reduce the need for intubation in selected patients and result in faster improvement. NIV also appears to be associated with a lower risk of adverse events than endotracheal intubation. There are currently no guidelines governing the use of NIV in asthma; however, in suitable patients, a trial of NIV under closely supervised conditions would seem reasonable.

Heliox

Heliox is a blend of 70% helium and 30% oxygen. It may have advantages in asthma because of its better gas flow dynamics. Small studies have had conflicting results. A recent Cochrane Review concluded that the existing evidence did not support the use of heliox in patients with acute severe asthma in the ED.

Ipratropium bromide

β-Agonists have been shown to be more effective bronchodilators than ipratropium bromide when these agents are used alone, but evidence about the impact of combined therapy is contradictory. A meta-analysis concluded that combination therapy resulted in a statistically significant additional improvement in FEV₁, but doubted the clinical significance of this difference. Prospective trials have conflicting results, but there is little if any benefit from the addition of ipratropium to nebulized salbutamol in mild or moderate asthma. Subgroup analysis suggests that there may be benefit from combination nebulized therapy in severe asthma (PEFR <200 L/min). Ipratropium may also have a place in patients who fail to respond adequately to standard initial therapy, particularly those taking long-acting β-agonists, in whom a degree of tolerance to bronchodilation with short-acting β-agonists can occur.

Ketamine

A potential benefit from cautious subinduction doses of ketamine in severe asthma has been suggested. The postulated mechanisms of action of ketamine in asthma are sympathomimetic effects, direct relaxant effects on bronchial smooth muscle, antagonism of histamine and acetylcholine, and a membrane-stabilizing effect. There is only one randomized trial investigating the role of ketamine in acute asthma. It showed that in doses with an acceptable incidence of dysphoria, ketamine did not confer benefit. For intubated patients, there is some preliminary evidence that ketamine infusion (bolus 1 mg/kg, followed by 1 mg/kg/h) may improve blood gas parameters. No outcome benefit has yet been demonstrated.

Magnesium

The postulated mechanisms of action of magnesium in acute asthma are a bronchodilator effect by impeding the uptake of calcium ions into smooth muscle cells, and an anti-inflammatory effect by attenuation of the neutrophil respiratory burst associated with asthma. Magnesium can be administered i.v. or by nebulizer.

With respect to i.v. magnesium, a Cochrane Review suggests that there is no benefit from its use (in addition to standard therapy) in mild or moderate asthma, but that for severe asthma (FEV₁ < 25% predicted) the addition of magnesium resulted in highly significant increases in FEV₁ and reduced admission rates. No serious adverse reactions were noted in any of the studies.

Regarding nebulized magnesium, doses used have varied from 125 mg as a single dose to 384 mg every 20 minutes for three doses. A Cochrane Review failed to find evidence of benefit over inhaled β-agonists in mild to moderate asthma, but concluded that nebulized inhaled magnesium, in addition to β-agonists, appears to have benefits with respect to improved pulmonary function in patients with severe asthma.

Racemic salbutamol

The salbutamol in common use comprises a racemic mixture of (R) and (S) isomers. The (R) isomer is responsible for the therapeutic effects. The (S) isomer has been shown to oppose the bronchodilatory effects of the (R) isomer and to be proinflammatory. It is also metabolized more slowly than the (R) isomer. The single isomer salbutamol preparation ((R) isomer, levalbuterol) has been postulated to be more potent with fewer side effects, but is much more expensive. A recent review concluded that current clinical trials do not provide evidence of a substantial advantage of levalbuterol over racemic albuterol, although the data are insufficient to determine whether subsets of the patient population might benefit from single isomer therapy.

Leukotriene inhibitors

Leukotriene receptor antagonists (e.g. montelukast) were developed in response to the finding that leukotrienes exhibit biological activity that mimics some of the clinical features of asthma and are found in increased amounts in patients with asthma, especially during exacerbations. They may have a role in the management of chronic asthma. There have been no ED-based studies of acute asthma investigating the potential role of these agents.

Disposition

Patients with severe or life-threatening asthma require admission to an intensive care or respiratory high-dependency unit. Patients with mild disease can usually be discharged after treatment and the formulation of a treatment plan. Those for whom admission or discharge may be in question are the moderate group. Bedside pulmonary function tests can be useful to guide these decisions. Hospital admission is mandated if pre-treatment PEFR or FEV₁ is <25% of predicted, or post-treatment <40% of predicted.

For those with post-treatment pulmonary function tests in the 40–60% of predicted range, discharge may be possible if improvement is maintained over a number of hours. In addition, other factors should be considered in estimating the safety of discharge. These include history of a previous near-death episode, recent ED visits, frequent admissions to hospital, current or recent steroid use, sudden attacks, poor understanding or compliance, poor home circumstances, and limited access to transport back to hospital in case of deterioration.

All discharged patients should have an asthma action plan to cover the following 24–48 hours, with particular emphasis on what to do if their condition worsens. They should also have a scheduled review, either in the hospital or with a general practitioner within that time. A short course of oral steroids (e.g. 50 mg/day for 5–7 days) is usual.

Controversies

• The relative efficacy and safety of intravenous epinephrine compared to intravenous salbutamol.

• The role of intravenous and nebulized magnesium in severe asthma.

• The role of non-invasive continuous positive airway pressure as an alternative to intubation and mechanical ventilation.

Introduction

Community-acquired pneumonia (CAP) represents a spectrum of disease from mild and self-limiting to severe and life-threatening. The great majority of cases are treated in the community with oral antibiotics, many without radiological confirmation. In the emergency department (ED) CAP is generally not a great diagnostic challenge, but rather represents a challenge of separating the serious cases that require inpatient treatment and supportive care from the mild cases that can be managed with minimal expense to the community and minimal inconvenience to the patient at home. Infrequently CAP presents with the need for urgent, life-saving interventions and critical care.

A great deal of work in recent years has focused on risk stratification of CAP cases and a number of scoring systems have been developed in an attempt to reduce unnecessary admissions and to identify severe cases for early critical care.

A recent change in CAP investigation is the addition of urinary antigen tests (UAT) to the standard work-up of X-ray, blood and sputum microbiology, serology and general tests. The role of routine blood cultures has also increasingly been questioned in the literature. A rational approach to the use of pathology testing is required to avoid excess healthcare costs and to prevent inappropriate decisions based on spurious or misleading results.

Antibiotic management of CAP has changed little for some decades, but the recent development of new ‘respiratory’ fluoroquinolones such as moxifloxacin and levofloxacin, and the emergence of drug-resistant Streptococcus pneumoniae (DRSP) and community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) present new challenges in management.

Recent years have seen the publication of comprehensive evidence-based guidelines from the British Thoracic Society (BTS) and the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS), as well as similar documents from Japan, Sweden, Canada and other countries. The Australian Therapeutic Guidelines continues to provide up-to-date antibiotic guidelines for the Australian setting. There is mounting evidence that the use of a structured, guideline-based approach to CAP management improves mortality, and that such guidelines should be adapted to local conditions.

Pathogenesis and aetiology

Most cases of CAP result from the aspiration of flora from the upper respiratory tract. Certain organisms, such as Legionella spp. and Mycobacterium tuberculosis, may be aspirated directly in aerosolized droplets suspended in the atmosphere. Haematogenous spread to the lung also occurs, for example from right-sided endocarditis.

Large-volume aspiration of gastrointestinal and upper respiratory tract contents is normally prevented by a coordinated swallow and intact gag and cough reflexes; however, microaspiration occurs routinely in normal individuals during sleep. Any aspirated matter is generally quickly cleared by the mucociliary escalator and by periodic coughing.

Pathogens that lodge on the lower respiratory mucosa meet with a fine layer of mucus, rich in secreted IgA, that acts to prevent their adhesion and to activate other arms of the immune system, including macrophages, innate (natural killer) and specific (T and B cell) immune cells, the complement cascade, cytokines, neutrophil response and antibody production. These defences are still breached from time to time by the common organisms. Derangement of the defences allows ‘opportunistic’ organisms to cause infection, such as the Gram-negative rods, anaerobes, Staphylococcus spp. and fungi.

Estimates of the rates of occurrence of various organisms implicated in CAP are difficult for several reasons. Isolation of a causative organism occurs in only around 70% of cases in hospital-based studies, less so in community-based ones, and much less commonly in actual clinical practice (particularly in CAP treated in the community). The most common organism isolated in all settings and in all classes of CAP, Streptococcus pneumoniae, is one of the easiest to isolate, whereas Chlamydophila pneumoniae and psitacii (formerly Chlamydia pneumoniae and psitaccii) and the Legionella species present much greater difficulty, potentially skewing the data in favour of pneumococcus. There is a great deal of heterogeneity in the pneumonia studies with regard to underlying patient characteristics, setting, case definition, degree of diagnostic investigation and timing with relation to epidemics, which further complicates interpretation of the data.

Streptococcus pneumoniae

This encapsulated bacterium is isolated from around 30% of cases of CAP in the community, hospital wards and ICU (50–60% of cases where a cause is found) and more commonly when highly sensitive methods are used for its detection. It appears on Gram stain as a Gram-positive coccus in pairs or short chains. In about 25% of cases bacteraemia is identified, and in a few of these there are other foci of invasive disease (such as meningitis).

Traditionally this organism has been extremely sensitive to penicillin, but in recent years drug-resistant Strep. pneumoniae (DRSP) has emerged, with rates varying around the world. Sensitivity is generally described by the minimum concentration of antibiotic required to inhibit growth in vitro (MIC) with an MIC <0.1 mg/L representing a sensitive organism, MIC 0.1–1 mg/L representing intermediate sensitivity, and MIC ≥2 mg/L higher-level resistance. In Australia approximately 16% of isolates express intermediate sensitivity to penicillin, but only around 12% have high-level resistance, with considerable local variation. Invasive strains (isolated from blood or CSF) tend to be more susceptible: in Australia 5% are intermediate or highly resistant. Rates in the UK are lower, where less than 3% of pneumococcal bacteraemias are of intermediate or high penicillin resistance, whereas in Asia resistance is much more common, with 23% of isolates exhibiting intermediate sensitivity and 29% high-level resistance, again with marked local variation. Blood levels achieved by giving 1 g amoxicillin orally 8-hourly or 1.2 g benzyl penicillin i.v. 6-hourly, are sufficient to treat the sensitive and intermediate sensitivity strains. In fact, it is only strains with an MIC > 4 mg/L (<2% of Australian isolates, 3% in England and Wales and 6% in Canada) that present a significant likelihood of treatment failure at these doses.

Macrolide resistance ranges from 15% in the UK to 92% in Vietnam. Again, invasive strains are less commonly resistant than non-invasive ones.

Multiple drug resistance is a problem, with around 17% of Australian isolates demonstrating diminished sensitivity to two or more classes of antibiotic. Whereas respiratory fluoroquinolone resistance remains rare in Australia and the UK, in countries where levofloxacin or moxifloxacin have been more extensively used resistance is already becoming a problem.

Outbreaks occur in crowded institutions, but these make up a small percentage of cases.

Mycoplasma pneumoniae

These single-celled organisms are not strictly bacteria. They lack a cell wall and so are innately insensitive to β-lactams, but are treated by macrolides, tetracyclines and fluoroquinolones. They are fastidious in vitro, and so diagnosis is generally by serological or complement fixation testing. Pneumonia due to Mycoplasma is most common in 5–20-year-olds and is rare in the elderly and in the tropical north of Australia. A 4-yearly cycle of winter epidemics (with the number of reports varying by a factor of 6–7) is well demonstrated in the UK, and surveillance data from Australia suggests that the same phenomenon occurs. Mycoplasma accounts for perhaps 10–15% of cases of CAP. The disease is usually mild and probably self-limiting in adults, although patients with sickle cell disease or cold agglutinin disease are at risk of severe complications.

Legionella species

These organisms are aerobic Gram-negative bacilli which are fastidious in culture. They occur in sources of lukewarm water, probably hosted by fresh water amoebae, and are killed by temperatures above 60°C. Legionella pneumophila serogroup 1, L. pneumophila indeterminant serogroup and L. longbeachiae account for approximately equal shares of legionellosis in Australia. The genus causes a small percentage of cases of mild and moderate CAP (<5%) but is over-represented among severe cases, causing 17.8% of cases in UK intensive care units. Outbreaks occur due to contaminated water in air conditioning cooling towers and water supplies, and are a significant public health issue. The disease tends to be severe and is often a multisystem illness. Patients on long-term oral steroids are more susceptible, but it is less common among the elderly.

Staphylococcus aureus

Staph. aureus appears on microscopy as clusters of Gram-positive cocci. It is a commensal on the skin and in the oro- and nasopharynx, and may reach the lung by aspiration or by haematogenous spread. It is over-represented in severe disease, accounting for 25% of ICU pneumonia in the UK, and is associated with a high mortality. It is almost universally resistant to penicillin, but most cases are sensitive to flucloxacillin and dicloxacillin. Community-acquired methicillin-resistant strains (CA-MRSA) are an emerging problem. Staphylococcal pneumonia classically occurs following influenza and complicates two-thirds of cases of influenza pneumonia in the ICU.

Mycobacterium tuberculosis

A comprehensive review of TB pathogenesis and treatment is beyond the scope of this chapter. This slow-growing obligate aerobe is able to survive intracellularly in macrophages. The classic pattern of disease is for inhalation of the bacillus to lead to a chronic inflammatory reaction, usually in the right lower lobe, producing a walled-off granuloma that contains surviving organisms and giant macrophages, which gradually becomes calcified. At some time in the future, often in the context of immunocompromise due to steroids, malignancy, HIV, malnutrition or old age, the disease reactivates and lobar pneumonia develops (typically in the right upper lobe). The disease is usually subacute in onset and relentless without treatment. The patient often suffers chronic cough, weight loss, fevers and fatigue. That said, TB presents in many and varied ways, and a high index of suspicion should be maintained. The patient with pulmonary TB and a productive cough presents a significant infection control and public health risk and respiratory isolation must be initiated while the diagnosis is confirmed.

Other important organisms

Non-typable Haemophilus influenzae is a rare cause of mild CAP and is uncommon in young patients. Although it is associated with exacerbations of chronic obstructive pulmonary disease (COPD), it is no more common as a cause of CAP in these patients than in the general population. It does, however, become more common with increasing severity of pneumonia and increasing age. Less than 25% of isolates are β-lactamase producing; others are susceptible to aminopenicillins (and somewhat less so to benzylpenicillin). Moraxella catarrhalis has similar antibiotic susceptibilities and is less common than Haemophilus. Second-generation cephalosporins, tetracyclines or the combination of amoxicillin and clavulanate is adequate if amoxicillin alone fails.

Chlamydophila (formerly Chlamydia) pneumoniae causes a mild illness and there is some doubt about its role as a pathogen at all. It is sensitive to macrolides and tetracyclines.

Burkholderia pseudomallei occurs in the soil in the tropical north of Australia and in South East Asia. Infection with it (melioidosis) typically causes a severe pneumonia (although any organ may be affected) and 50% of cases are bacteraemic. Bacteraemic melioidosis has been reported to have 50% mortality. It is a problem mainly during the wet season and risk factors include diabetes mellitus, renal failure, chronic lung disease, alcoholism, long-term steroid use and excess kava intake. It is somewhat sensitive to third-generation cephalosporins, although better treated with ceftazidime or carbapenems. It is intrinsically resistant to aminoglycosides. The Gram-negative rod Acinetobacter baumanii occurs in a similar area, time of year and group of people, and also causes severe pneumonia. It is generally treated with aminoglycosides. Expert consultation should be sought.

Influenza A and B are common causes of pneumonia in adults. Disease may be mild, moderate or severe. Coinfection with Staph. aureus is a well-described complication. Clinical and radiological differentiation from bacterial pneumonia is unreliable, and diagnosis is usually made with viral studies on nasopharyngeal or bronchial aspirates or on serological testing after convalescence.

Anaerobic organisms are generally aspirated in patients with poor dentition. Edentulous patients are thus protected, and these organisms are actually rare in aspiration pneumonia among nursing home patients.

The Gram-negative rods are a varied group of opportunistic agents which all carry a high risk of severe pneumonia and mortality. They are more common in nosocomial pneumonia than in CAP. They include Pseudomonas aeruginosa, Serratia spp., and Klebsiella pneumoniae. Emergence of antibiotic resistance during treatment is a particular problem with Pseudomonas, and antibiotics from two classes should be used concurrently if infection is proven or highly likely.

Epidemiology

Rates of pneumonia are difficult to estimate because of issues of case definition and the fact that the majority of cases occur unstudied in the community. However, data from around the world suggest that the incidence is around 5–11/1000/year in 16–59-year-olds in the community, and over 30/1000/year in those over 75. The incidence of CAP requiring hospitalization in the UK is less than 5/1000/year and comprises probably less than 50% of CAP cases. On the other hand, CAP accounts for 8–10% of medical admissions to intensive care units.

Rates of admission to ICU vary enormously around the world and probably represent resource availability and usage more than differences in disease severity. New Zealand studies report 1–3% of cases needing ICU, whereas in the UK it is around 5%. Much higher percentages are reported from the United States.

The mortality rate of CAP treated in the community is thought to be very low, probably <1%. Mortality among hospitalized patients varies depending on health service, but is around 5–10%. Mortality among patients admitted to ICU with CAP is much higher, but the statistics are much more varied, again depending on ICU admission criteria. In the UK, where almost all ICU patients require mechanical ventilation, mortality is 50%, but in Spain and France it is around 35%. Mortality obviously varies with severity of disease (see the section below on severity assessment) and also with organism. Staph. aureus, Gram-negative bacilli (especially Pseudomonas), Burkholderia pseudomallei and Legionella spp. all carry a higher than baseline mortality, whereas Mycoplasma and Chlamydophila spp. have lower mortality.

Influenza and pneumonia (ICD codes J10–J18) account for 2.3% of all deaths in Australia and are a contributing cause in 13.3%.

Associations between particular risk factors and particular organisms in CAP patients are weak, and it is important to remember that routine questioning about risk factors is likely to be misleading. For example, despite the well-known association between Chlamydophila psittaci and sick parrots, 80% of patients with psittacosis have no history of bird contact. Stronger associations are those between Staph. aureus and influenza, between Staph. aureus and intravenous drug use (IVDU), and between Legionella and travel. Workers in the animal handling and slaughtering industries are at risk of infection with Coxiella burnetii (Q fever). Awareness of any local epidemics is important (particularly outbreaks of Mycoplasma or legionellosis).

Prevention

Prevention of pneumonia in the developed world centres on vaccination for influenza and pneumococcus. In developing regions, the provision of adequate nutrition and housing is more important. Legionellosis is avoided by appropriate design and maintenance of air-conditioning and water supply systems in large buildings. It is worth noting that aspiration pneumonia is not prevented by the use of nasogastric or PEG feeding tubes.

Clinical features

Pneumonia should be suspected in patients with:

• Fever

• New cough

• Rigors

• Change in sputum colour

• Pleuritic chest pain

• Dyspnoea.

Many patients with these features, however, will not have pneumonia, and certain groups of patients (particularly the elderly) may have pneumonia with few or none of these features.

A normal chest examination makes pneumonia less likely but does not rule it out. The classically described progression of chest examination findings is from crackles and reduced air entry in the first days, to a dull percussion note and bronchial breathing which persists until resolution begins at around day 7–10, when crackles return. Fever is said to be persistent until a ‘crisis’, followed by resolution. Of course the actual clinical reality may bear little resemblance to this. The presence of classic findings in the chest may precede radiological abnormality by several hours, particularly in pneumococcal pneumonia.

Much has been made of the role of the clinical syndrome as a predictor of aetiology, but the evidence shows it to be unreliable. Previously ‘typical’ and ‘atypical’ pneumonia were differentiated clinically, but there is now a general consensus that these terms should be abandoned as they are misleading. The term ‘atypical organism’, however, has persisted as an umbrella term for the Chlamydophila spp., the Legionella spp. and Mycoplasma. With these caveats in mind, there are certain associations that should be considered (Table 6.3.1).

Table 6.3.1 Clinical features associated with specific organisms

Streptococcus pneumoniae

Bacteraemic pneumococcal pneumonia

Legionella spp

• Young and previously healthy patient

• Smoker

• Multisystem illness (LFT abnormality, elevated CK, GIT upset, neurological disturbance)

• More severe illness

Mycoplasma

• Young and previously healthy patient

• Antibiotic use prior to presenting to hospital

• Isolated respiratory illness

Streptococcus aureus

• IVDU

• Severe illness

• History of influenza

Gram-negative rods

• Alcoholic

• Nursing home resident

The term ‘community-acquired pneumonia’ is as opposed to hospital-acquired pneumonia, which is generally defined as pneumonia occurring in a patient who has been an inpatient in hospital in the last 10 or 14 days. Patients with AIDS, cystic fibrosis, current chemotherapy or active haematological malignancy presenting with pneumonia should be considered to be presenting with a complication of their underlying condition rather than with CAP. The question of how to classify patients with pneumonia presenting from nursing homes remains unresolved. Nursing home patients have tended to be overlooked by authors of guidelines on CAP management, and the issue is clouded by ethical questions around care of the debilitated elderly. Nursing home status carries an increased mortality risk and an increased risk of both aspiration pneumonitis and infection with Staph. aureus and aerobic Gram-negative bacilli.

Differential diagnosis

The clinical syndrome of pneumonia is non-specific and the differential diagnosis is broad. CXR findings of a lobar infiltrate, however, narrow the possibilities significantly. Underlying malignancy should always be considered, especially in older smokers. Pulmonary embolus (PE) is less likely in the presence of a lobar infiltrate, but this should be differentiated from the wedge-shaped opacification of a pulmonary infarction due to PE. Bi-basal pneumonia can be very difficult to distinguish from left ventricular failure, especially in the elderly patient in whom clinical signs and white cell count can be unreliable. CXR changes may be pre-existing, such as in localized fibrosis due to radiotherapy, or when there has been a recent pneumonia with opacification yet to resolve. Aspiration pneumonitis should be differentiated from pneumonia as antibiotic therapy is less likely to be of benefit. The main indicators are on history (neurological deficit, loss of consciousness, choking while eating or vomiting in the patient with diminished airway reflexes) although most episodes go unwitnessed.

Complications

Pleural effusion is a fairly common occurrence in hospitalized patients with CAP, occurring in 36–57% of admitted patients. Effusion detectable on CXR is an indicator of severity, especially if bilateral. Persistent fever raises the likelihood of an effusion. The majority of effusions resolve with antibiotic treatment, but empyema requires drainage. As effusion and empyema are radiologically indistinguishable, any significant effusion should be aspirated. Cloudy fluid, pus cells or organisms on Gram stain, or a pH of <7.2 indicate empyema and the need for drainage. Aspiration will also provide a specimen for aetiological diagnosis, although the yield is not high.

Lung abscess is a rare complication, most common in the alcoholic, debilitated or aspiration pneumonia patient. Some will respond to antibiotics, but drainage is often required. Staph. aureus, anaerobes and Gram-negatives are more likely culprits and polymicrobial infection is common. Tuberculosis should be considered in any patient with a cavitating lesion.

Severe sepsis syndromes are a relatively common occurrence in CAP. Approximately 40% of hospitalized patients develop non-pulmonary organ dysfunction, with 28% having evidence of it at presentation. Septic shock develops in 4–5% of cases and is manifest at presentation in just under half of these. The presence or absence of systemic inflammatory response syndrome (SIRS) criteria has little or no predictive value for death, severe sepsis or septic shock in CAP; however, the Pneumonia Severity Index (see below) does correlate with the likelihood of severe sepsis.

Respiratory failure is the most common reason for ICU admission in CAP. In patients with moderate to severe disease a widened A-a gradient can be detected, with PCO₂ being depressed as the patient increases minute volume to compensate for failure of gas exchange. As severity increases the PCO₂ will return to normal as the patient tires, and PO₂ will fall. Type II respiratory failure generally occurs late.

Renal failure may occur in any case of severe CAP but is particularly associated with legionellosis. Multiorgan failure may occur as a result of severe sepsis.

Investigation

Imaging

Chest X-ray

The presence of a new infiltrate on CXR remains central to the diagnosis of pneumonia. Diagnosis without CXR is shown to be unreliable, although a normal chest examination makes the diagnosis unlikely.

CXR has proved to be an unreliable indicator of aetiology, but some clues may be found. Mycoplasma is less likely in the presence of homogeneous shadowing, but is suggested by lymphadenopathy. Multilobar infiltrates and pleural effusions make bacteraemic streptococcal pneumonia more likely, whereas a multilobar infiltrate with pneumatocoeles, cavitation and pneumothorax is suggestive of Staph. aureus. Klebsiella tends towards the right upper lobe, but the described association between this agent and a bulging horizontal fissure is unsupported by evidence.

Tuberculosis should always be considered in cases of an upper lobe infiltrate, especially in the presence of a Ghon focus or calcified nodule, usually found in the right lower lobe.

Clues to severity may be found on the CXR (see below).

The role of the repeat X-ray is unclear. The rate of improvement is quite variable. It is slower with increasing age, presence of comorbidity, multilobar infiltrates and streptococci (especially bacteraemic) or Legionella as pathogens. Legionella, in fact, is characterized by worsening radiological appearance after admission. The role of a convalescent film is likewise unclear. Rates of underlying lung cancer vary in studies of patients with pneumonia, and most cases are diagnosed on the acute film. Smokers over 50 are particularly at risk, and routine convalescent imaging should be considered in this group.

CT

CT currently has a limited role in diagnosis of pneumonia because of the cost, radiation dose and lack of a clear benefit over plain CXR. In some cases a diagnosis may be made on CT when another diagnosis is being excluded (e.g. CTPA for exclusion of pulmonary embolus).

General pathology

The roles of non-microbiological pathological testing in CAP are to help confirm the diagnosis, to assess severity, to identify complications and to screen for underlying or comorbid conditions. With this in mind, the majority of previously well young people with non-severe pneumonia are unlikely to benefit from routine tests.

Full blood count

The full blood count is routine in patients requiring hospitalization with pneumonia. Anaemia, thrombocytopenia, severe leukocytosis and leukopenia are all markers of severity (see below). Polycythaemia may indicate dehydration or underlying chronic hypoxia. A white cell count >15 000 cells/mm³ is suggestive of a bacterial cause (especially Strep. pneumoniae) but is insensitive and non-specific.

Urea and electrolytes

Urea, electrolytes and creatinine are also routinely measured in the hospitalized patient. Hyponatraemia (Na <130 mmol/L) and elevated urea (≥11 mmol/L) are proven markers of severe pneumonia. Acute renal impairment is a relatively common complication of severe pneumonia, whereas chronic renal failure is a risk factor for severe disease.

Liver function tests

Liver function tests frequently demonstrate some abnormality, although this may not change management. Chronic liver disease is a risk factor for severe pneumonia.

Blood gas testing

Measurement of arterial blood gases has been common practice in patients hospitalized with pneumonia. Recent evidence demonstrates that a venous blood gas is acceptable for assessment of acid–base status and may be a valid screening tool for hypercapnoea. Transcutaneous oxygen saturation measurement (SpO₂) is likewise an acceptable screening tool for hypoxia, although it becomes inaccurate when SpO₂ is <90%.

Inflammatory markers

Measurement of CRP remains contentious. The recent British Thoracic Society guidelines update concluded that ‘there is no clear consensus in the literature about value of CRP in differentiating between infective causes. There is no value of CRP in severity assessment’. At best, CRP may have a role in differentiation between exacerbation of COPD and pneumonia or non-infective causes and pneumonia in uncertain cases.

Both serum procalcitonin and D-dimer have been found to correlate with severity of pneumonia, but their discriminatory value and role, if any, remain undefined.

Testing for aetiology/microbiology

As discussed above, achieving an aetiological diagnosis in CAP is difficult, even in the research setting in tertiary referral centres. The advantages of doing so include the opportunity to tailor therapy, to detect outbreaks such as Legionnaire’s disease, influenza or Mycoplasma, and to identify resistant organisms. An emerging concern in recent years is that of bioterrorism, which may be identified early due to reporting of aetiological diagnoses. A further consideration is the paucity of published data on the aetiology of pneumonia, particularly from Australia and New Zealand. Current knowledge depends heavily upon laboratory reports to surveillance authorities and ‘accumulated knowledge’ rather than scientific studies.

Disadvantages of an aggressive diagnostic approach are the cost compared to the low yield, the risk of inappropriate changes to therapy based on false positive results from contaminants, the long lag time to obtain a result (particularly from culture and paired serology), the potential to delay treatment while specimens are obtained, and the exposure of the patient to added unpleasant and invasive procedures (such as multiple venepunctures for blood culture). Moreover, it is uncommon for therapy to be streamlined despite a microbiological diagnosis, and the only randomized controlled trial comparing empiric to directed therapy found no benefit to a pathogen-directed approach, although there was a small mortality benefit found in the ICU subgroup.

Sputum

Sputum can be collected for microscopy and for culture. The two should be considered separately as they are very different tests and are likely to be valuable in different settings. The value of sputum collection has been debated, however. Unfortunately, many patients are unable to produce sputum, and waiting for them to do so may cause significant delays to antibiotic treatment.

Microscopy (generally with Gram stain, although Zeil–Neilsen stain for acid-fast bacilli should be requested if tuberculosis is suspected) can potentially provide useful guidance for empiric prescribing as well as an indication of whether the specimen is of sufficient quality for culture to be useful.

If a good specimen can be obtained, transport is prompt, the laboratory staff are experienced in its examination and antibiotics are yet to be given, then a negative Gram stain is strong evidence against Staphylococcus, Pseudomonas and Gram-negative rods. A sputum Gram stain showing Gram-positive cocci in clusters is an indication to include anti-staphylococcal treatment. Gram-positive diplococci or cocci in short chains are suggestive of Strep. pneumoniae infection, but this is less reliable.

Sputum culture has a higher sensitivity than Gram stain and provides more definite identification, typing and sensitivity data; however, results are not available when treatment is started and colonization may be hard to distinguish from infection, particularly if the Gram stain was negative or not performed. Special culture is indicated if Legionella or M. tuberculosis is to be identified.

The sensitivity of both microscopy and culture declines if antibiotic therapy has already started, and even under ideal conditions neither is highly sensitive or specific. Likewise, tuberculosis requires both special stains and culture media as well as prolonged culture time. The provision of good clinical details to the laboratory, including suspected organism, timing of specimen and use of antibiotics, is essential.

Blood culture

Blood cultures have traditionally been recommended for all patients admitted to hospital with suspected pneumonia. More recently the performance of blood cultures in admitted pneumonia patients has been linked to hospital accreditation in the USA. The most common non-contaminant organism isolated is Pneumococcus, which is generally covered by empiric treatment and yields are generally low (around 7% overall and 25% at most in pneumococcal pneumonia). Contaminants are found with similar frequency. That said, a positive result (other than coagulase-negative Staphylococcus) is highly specific for a microbiological aetiology.

A rational approach is to limit blood culture use to cases where yield is higher, the likelihood of a resistant or non-pneumococcal organism is higher, the consequences of inappropriate prescription are greatest, or where there is concern about a significant outbreak or epidemic.

Independent predictors of a positive blood culture in CAP include coexistent liver disease, systolic blood pressure <90 mmHg, temperature <35°C or ≥40°C, pulse ≥125/min, urea ≥11 mmol/L, Na <130 mmol/L, WBC <5000 cells/mm³ or >20 000 cells/mm³, and lack of prior antibiotic therapy. A prediction rule has been developed based on these variables, with the presence of two or more predictors associated with a 16% rate of positive blood culture. These indicators are also markers of severity, and it is patients with severe pneumonia who are most at risk of an adverse outcome if initial antibiotics are not sufficient. A positive pneumococcal urinary antigen test is associated with a higher yield from blood culture and may be an indication for performing blood culture to monitor community resistance rates.

Current British Thoracic Society guidelines indicate that blood cultures have little role in non-severe pneumonia, and the IDSA/ATS guidelines recommend blood cultures for ICU patients and those with cavitation, leukopenia, alcoholism, chronic liver disease, asplenia, a positive pneumococcal UAT or a pleural effusion.

Urinary antigen testing

A relatively new addition in the field of diagnostic testing for CAP is the urinary antigen test (UAT). The two commonly available are the Legionella and pneumococcal antigen tests. Both are fast and simple to perform, and minimally affected by the use of antibiotics. The pneumococcal UAT is 50–80% sensitive and >90% specific. False positives occur in children with chronic respiratory illness and colonization with pneumococcus, and in adults who have had CAP in the last 3 months. The Legionella UAT is probably highly sensitive and specific for L. pneumophila serogroup 1, is positive from day 1, and remains so for up to 3 weeks.

The precise role of these tests remains uncertain, however. CAP is assumed to be pneumococcal by default, and so a positive test provides little helpful information, whereas a negative test is of little predictive value. As discussed above, the UAT might be used as a triage tool to identify patients who will have a higher yield from blood cultures. The Legionella UAT identifies only Legionella pneumophila serogroup 1, which accounts for less than half of cases in Australia. It is currently unclear whether a positive Legionella UAT justifies streamlining to macrolide monotherapy in sick inpatients, or whether it mandates upgrading from oral to i.v. macrolides. A positive Legionella UAT is associated with ICU admission, perhaps because the higher antigen load in positive cases represents a greater infective burden. A negative Legionella UAT, however, does not rule out legionellosis, as other species and serogroups are not detected.

Other tests

Serology has little to offer the emergency management of CAP but has a public health role if an outbreak of viral or ‘atypical’ pneumonia is suspected. If symptoms have been ongoing for more than 7 days then a high titre of Mycoplasma or Legionella IgM is diagnostic, but otherwise paired serology weeks apart is required, with the diagnosis coming only after treatment is completed.

Influenza rapid point-of-care testing has a low sensitivity (50–70%) and cross-reacts with adenovirus. A positive test may be an indication for treatment with antivirals, where available, and may be useful in outbreak detection, although it is unlikely to be superior to physician judgement in this role. Influenza direct fluorescent antibody testing is more reliable but takes 2 hours and requires special laboratory skills. It is used for identification of specific strains of influenza (e.g. H5N1).

Severity assessment

A key clinical problem in patients with suspected CAP is assessment of severity. The great majority of CAP cases are mild and self-limiting, although antibiotic treatment shortens the illness. However, a significant minority of cases cause an acutely debilitating illness, and a small minority are life-threatening. Attempts at formalizing the process of severity assessment have focused on two aims: identifying those who can safely be managed at home, thereby reducing unnecessary admissions and unplanned readmissions; and identifying those who are likely to need ICU care, with the aim of reducing mortality and complications from delayed recognition of severe disease while avoiding overuse of ICU. Those seeking the former goal have met with a great deal of success, but the latter has remained elusive. A number of scoring systems have been developed and validated, including the Pneumonia Severity Index (PSI), the British Thoracic Society’s BTS, modified BTS, CRB, CURB and CURB-65 scores, the American Thoracic Society’s ATS, modified ATS (m-ATS) and revised ATS (r-ATS) scores, and the Spanish SEPAR score.

Proven markers of severity

The following have all been defined as markers of severity in various studies:

• Demographic factors

Increasing age

Residence in a nursing home or being bedridden

Male gender

Comorbidity

Congestive cardiac failure, diabetes mellitus, coronary artery disease, chronic lung disease, liver disease, cerebrovascular disease, chronic renal failure and neoplastic disease

• Examination findings

Respiratory rate >30/min or <6/min

Confusion (AMTS <8 or new disorientation to time, place or person)

Systolic BP < 90 mmHg, diastolic BP< 60 mmHg or septic shock requiring aggressive fluid resuscitation or vasopressors

Temperature <35°C or ≥40°C

Heart rate ≥125/min

• Haematological

Haematocrit <30%

White cell count <4000 cells/mm³ or > 20 000 cells/mm³

Platelets <100 000 cells/mm³

• Biochemical

Urea elevated (cut-offs vary)

Sodium <130 mmol/L

Glucose >14 mmol/L

Arterial pH <7.35

Hypoxia (PaO₂ <60 mmHg, SpO₂ <92%, PaO₂:FiO₂ <250 mmHg)

• Radiological features

Bilateral or multilobar involvement

Effusions, especial bilateral

Worsening radiological changes after admission in the ICU patient

• Microbiological

Positive blood culture (not available at time of initial assessment)

Strep. pneumoniae, Gram-negative bacilli, Staph. aureus, and Ps. Aeruginosa.

The Pulmonary Severity Index (PSI)

The PSI was derived by retrospective chart review and validated both retrospectively and prospectively in separate groups of patients in the late 1980s and early 1990s. In all, over 54 000 patients and 275 hospitals from across the USA and Canada were involved in the study. The rule is a two-step process, with low-risk patients being identified on clinical grounds alone in the first step and then all other patients being further differentiated on the basis of age and 19 dichotomized and weighted clinical and investigation features into four further groups (Tables 6.3.2 and 6.3.3).

Table 6.3.2 Calculating the PSI

Step 1
The patient is Class I and needs no further investigation if they are ≤50 years old and have none of the following:
History
• Neoplastic disease • Liver disease • Renal disease • Congestive cardiac failure • Cerebrovascular disease

Examination

• Acutely altered mental state

• Respiratory rate ≥30/min

• Systolic BP <90mmHg

• Temperature <35°C or ≥40°C

• Pulse rate ≥125/min

Step 2 If the above is not satisfied then the PSI score need to be calculated as follows:

Factor	Score
Demographic
• Age • Sex • Nursing home (not hostel) resident	• Age in years • 10 if female • +10
Coexisting illness
• Neoplastic disease • Liver disease • Congestive cardiac failure • Cerebrovascular disease • Chronic renal disease	• +30 • +20 • +10 • +10 • +10
Signs on examination
• Acutely altered mental state • Respiratory rate ≥30/min • Systolic blood pressure <90mmHg • Temperature <35°C or ≥40°C • Pulse rate ≥125/min	• +20 • +20 • +20 • +15 • +10
Investigations
• Arterial pH <7.35 • Serum urea ≥11mmol/L • Serum sodium <130 mmol/L • Serum glucose ≥14mmol/L • Haematocrit <30% • PaO₂ <60mmHg or SpO₂<90% • Pleural effusion on CXR	• +30 • +20 • +20 • +10 • +10 • +10 • +10

(After Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. New England Journal of Medicine 1997; 336: 243–250.)

Table 6.3.3 Mortality and PSI class

Score	Class	30-Day mortality (%)
N/A	I	0.1
1–70	II	0.6
71–90	III	0.9
91–130	IV	9.3
>130	V	27

Despite its rigorous derivation and validation, criticisms have been levelled at the PSI. A major issue is its complexity. The large number of variables and their differing weights are difficult to remember and the score is complex to calculate. Also, the PSI is heavily weighted towards elderly patients. A young patient, compensating well early in an illness, might be significantly hypoxic and still be stratified into the lowest risk group. Social factors and the presence of unusual comorbidities are not accounted for, nor is the presence of bilateral or multilobar infiltrates on CXR. Moreover, the PSI has subsequently been used to stratify patients not only for discharge and admission but also for ICU care and for antibiotic regimen, purposes for which it was not originally intended.

In its favour, the variables used by the PSI are all available at the end of a typical work-up, particularly as there are data supporting the substitution of venous pH for arterial pH. PSI calculators are now readily available which makes calculation much easier.

Clinical judgement is recommended when using the PSI. The tool has been well validated for identifying patients who may be safely treated at home, but young patients, particularly if hypoxic (SpO₂ <94% on air), should be assessed with caution. A patient who is vomiting, homeless or unreliable should not be discharged on oral antibiotics from the ED, and some underlying conditions may warrant admission for relatively mild pneumonia, such as advanced neuromuscular disease and general frailty.

Patients likely to require ICU care are particularly poorly identified by the PSI and all other scoring systems. It is important to apply clinical judgement together with the PSI score and consider other markers of severity and the general clinical picture when deciding whether ICU might be needed in the patient with CAP.

Finally, the PSI was derived and validated in adult patients with no recent hospitalization who did not have HIV. Its use in immunocompromised patients has been investigated in one study and was found to perform well in patients with HIV, solid organ transplant or treatment with immunosuppressive drugs, and poorly in patients with haematological malignancy, on chemotherapy or after chest radiotherapy or bone marrow transplantation.

The CURB-65 score

The British Thoracic Society (BTS) currently recommends use of this score for stratification of CAP patients. The system stratifies patients on the basis of a scale of 0–6, with one point scored for each of:

• Confusion of new onset (AMTS <8 or new disorientation to time, place or person)

• Urea >7 mmol/L

• Respiratory rate ≥30/min

• Blood pressure <90 mmHg (systolic) or ≤ 60mmHg (diastolic), and

• Age ≥65 years.

Scores are correlated with risk of death and site of care is suggested (Table 6.3.4).

Table 6.3.4 Mortality and the CURB-65 score

Score	Risk of death or ICU admission (%)	Comments
0	0.7	Low risk. Non-severe pneumonia. May be suitable for treatment at home
1	3.2
2	13	Increased risk of death. Consider for short inpatient or hospital-supervised outpatient treatment
3	17	High risk of death. Treat as inpatients with severe pneumonia. Consider use of ICU
4	41.5
5	57