Suppurative lung disease - Essential respiratory medicine

Essential respiratory medicine. Shanthi Paramothayan

Chapter 12. Suppurative lung disease

Learning objectives

■ To understand the aetiology and predisposing factors for suppurative lung diseases

■ To understand the structure and function of cilia and the consequences of abnormally functioning cilia

■ To recognise the aetiology, diagnosis, and management of bronchiectasis

■ To understand the inheritance, diagnosis, and management of cystic fibrosis

■ To understand the inheritance, diagnosis, and management of primary ciliary dyskinesia

■ To understand the aetiology, diagnosis, and management of lung abscess

Abbreviations

A1AT alpha 1 antitrypsin

ABC ATP binding cassette

ABPA allergic bronchopulmonary aspergillosis

ATP adenosine triphosphate

BiPAP bi-level positive airway pressure

cAMP cyclic adenosine monophosphate

CAP community acquired pneumonia

CF cystic fibrosis

CFTR cystic fibrosis transmembrane conductance regulator

COPD chronic obstructive pulmonary disease

CRP C-reactive protein

CT computed tomography

CVID common variable immunodeficiency

CXCR1 chemokine receptor

CXR chest X-ray

DNA deoxyribonucleic acid

FEV₁ forced expiratory volume in one second

FVC forced vital capacity

HIV human immunodeficiency virus

HRCT high-resolution computed tomography

LTOT long term oxygen therapy

MAC Mycobacterium avium complex

MCE mucociliary escalator

MDCT multi detector computed tomography

NMCC nasal mucociliary clearance test

NO nitric oxide

NTM non-tuberculous mycobacteria

PCD primary ciliary dyskinesia

SGRQ St. George’s Respiratory Questionnaire

SLE systemic lupus erythematosus

UK United Kingdom

Introduction

Suppurative lung diseases are a group of disorders which result in chronic lung infection, with pus in the lungs. Individuals with suppurative lung diseases present with chronic purulent sputum and recurrent respiratory tract infections. The aetiology of these conditions is variable. Bronchiectasis is a relatively common condition whereas primary ciliary dyskinesia (PCD) is rare. Cystic fibrosis is a relatively common inherited condition which results in severe bronchiectasis. Empyema is pus in the pleural cavity. This is discussed in Chapter 10. Box 12.1 lists some suppurative lung diseases.

Box 12.1 Suppurative lung diseases.

• Bronchiectasis

• Cystic fibrosis

• Primary ciliary dyskinesia

• Lung abscess

• Empyema

_____

Bronchiectasis

Bronchiectasis is a chronic lung disease which occurs after destruction and dilatation of bronchi due to a cycle of recurrent infection and inflammation (Figure 12.1).

The healthy bronchial epithelium is lined with fine, hair-like structures called cilia. The cilium has a structure identical to that of a flagellum and is composed of nine pairs of microtubular doublets, each with an A and B sub-unit attached as a semi-circle. A central sheath contains a pair of microtubules which attach to the outer doublet by radial spokes with the outer doublets interconnected by nexin links. The A subunit is attached to two dynein arms (inner and outer) that contain adenosine triphosphate (ATP) which are responsible for ciliary motion. The central sheath, radial spokes, and nexin links maintain the structural integrity of the cilium. The cilium is anchored at its base by cytoplasmic microtubules and a basal body comprised of a basal foot and rootlet. The orientation of the basal foot indicates the direction of effective cilial stroke (Figure 12.2).

Cilia line the entire respiratory system: the nasal mucosa, paranasal sinuses, middle ear, the Eustachian tube, pharynx, trachea, and bronchi down to the respiratory bronchioles. Each ciliated cell has 200 cilia, 5—6 µm long. Cilia line the Fallopian tubes and important in the movement of the fertilised ovum. The structure of the spermatozoan tail is identical to that of the cilium.

Ciliary motion is responsible for the rotation of organs in embryogenesis so that the organs end up in their usual positions, with the heart on the left side of the thoracic cavity and the liver on the right side of the abdomen.

Healthy lungs have fully functioning cilia that beat synchronously in a two-part ciliary beat cycle: the power stroke and then the recovery stroke. This ciliary action propels the overlying mucus up the bronchial tree, up the trachea until it reaches the pharynx and is swallowed. The amount of mucus produced by normal lungs is relatively small. This constant movement and clearance of mucus forms the mucociliary escalator (MCE), which is an essential part of the lungs’ clearance and defence mechanisms. Bacteria, viruses, pollen, dust, and other particulate matter become trapped in the mucus layer and are cleared. The lungs’ defence mechanism is discussed more fully in Chapter 2.

Figure 12.1 Progression of bronchiectasis with cycle of infection and inflammation.

Figure 12.2 Electron microscopy image of cilium (diagram).

Pathogenesis of bronchiectasis

Ciliary function is impaired by cigarette smoke, bacterial toxins, and viral antigens that cause the shedding of ciliated respiratory cells and disruption to the MCE. Damage to the epithelial cells can take several weeks to repair, even after the common cold. Impaired ciliary function results in a build-up of mucus within the dilated bronchi. Bacteria and viruses get trapped in the mucus, multiply rapidly and colonise the lung, causing persistent infection and chronic mucus production. Bacteria prevent the healing of the damaged respiratory epithelium by binding to, and disrupting, the functioning of certain epithelial receptors: fibronectin, which is important in cell migration, and integrin, which is necessary for the adhesion of cells.

Bronchiectasis results in inflammation of the airways and airflow obstruction. Bacterial infection results in the outpouring of inflammatory cytokines, including interleukin 8 and interleukin 6, which recruit neutrophils through interaction with the chemokine receptor CXCR1. Proteases from bacterial pathogens, for example, Pseudomonas aeruginosa, cleave and disable CXCR1, resulting in a reduction in neutrophil recruitment, ineffective neutrophil function, and failure of bacterial killing. Neutrophils release proteases and reactive oxygen intermediates, such as hydrogen peroxide, as well as several inflammatory cytokines. High levels of human neutrophil peptides, called alpha defensins, are found in the sputum of patients with bronchiectasis. These impair neutrophil phagocytosis and reduce antimicrobial activity. Anti-proteases, such as alpha -1 antitrypsin, restore CXCR1 and enhance bacterial killing. Increased neutrophil elastase activity results in mucus which is more viscous and harder to clear. Collagen deposition in the bronchial wall causes permanent distortion and dilatation of major bronchi.

Aetiology of bronchiectasis

Bronchiectasis that results from infection and inflammation is referred to as non-cystic fibrosis bronchiectasis, thus differentiating it from the severe bronchiectasis that occurs in cystic fibrosis. The prevalence of bronchiectasis is unknown as it can arise from several different causes. The prevalence of bronchiectasis has declined in the developed world but is a common cause of morbidity and mortality in developing countries. Bronchiectasis is commoner in females compared to males, perhaps because of the higher prevalence of rheumatoid arthritis and related conditions in the female population. Bronchiectasis can occur after damage to the bronchial mucosa, due to immunodeficiency states which predispose to recurrent infections, abnormal ciliary function or abnormal viscosity of the respiratory secretions. Table 12.1 lists these conditions.

Bronchiectasis may be localised to a small area of the lung or be more diffuse due to generalised infection and inflammation. Localised bronchiectasis can occur after inhalation of a foreign body, such as a peanut, which traps purulent material within that segment, causing bronchial wall damage. An enlarged lymph node can compress a bronchus, resulting in bronchiectasis more distally.

Several international studies which looked at how often a specific aetiology for the bronchiectasis could be identified found a specific cause in 60—93% of patients after comprehensive tests. Severe and recurrent respiratory tract infections are the commonest cause of ciliary and bronchial wall damage, accounting for 20% of bronchiectasis. Bronchiectasis secondary to childhood infections, particularly measles and pertussis (whooping cough), was common prior to immunisation in the UK and still is a common cause of bronchiectasis in developing countries. In adults, bronchiectasis can develop after community acquired pneumonia, especially after infections with Staphylococcus aureus and Klebsiella pneumonia, although severe bronchiectasis is much less common now with prompt antibiotic treatment. Tuberculosis is still a common cause of bronchiectasis, especially in developing countries.

A heterozygous mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene may contribute to the development of diffuse bronchiectasis through dysfunction of the airway sodium and chloride channels.

Vitamin D deficiency may predispose to increased colonisation with bacteria, including Pseudomonas, and increase the frequency of exacerbations. Increased markers of neutrophilic inflammation were found in the sputum of those with bronchiectasis and vitamin D deficiency.

Recurrent aspiration pneumonia is a common cause of bronchiectasis in the elderly. The risk of aspiration pneumonia is increased in patients with reduced consciousness, for example, after a stroke, after a seizure, or when intoxicated with alcohol or other drugs. Neurological and neuromuscular conditions, such as Parkinson’s disease, multiple sclerosis, and motor neurone disease, result in impaired swallowing and aspiration, as do oesophageal diseases, such as reflux and achalasia.

Foreign body aspiration is more likely to occur in small children and the elderly. Common items aspirated include small toys, nut and seeds in children, and bones and a bolus of food in the elderly. There is usually a history of choking and coughing preceding the development of chronic symptoms, often weeks earlier. The foreign body is more likely to enter the right lung and lodge in the middle lobe. Clinical examination may reveal a monophonic wheeze. The CXR and CT thorax will be abnormal, showing signs of collapse or atelectasis. Flexible bronchoscopy may be required to remove the foreign body. In some cases, if the foreign body is lodged very far down the bronchial tree, rigid bronchoscopy under general anaesthetic, or surgery may be indicated. Post-obstructive pneumonia can progress to bronchiectasis or to a lung abscess.

Table 12.1 Aetiology of bronchiectasis.

Underlying cause	Diagnosis	Management
Infection	Childhood infections (pertussis, measles)	Childhood vaccination
Infection	Recurrent respiratory infections	Treatment of underlying cause Prompt antibiotics, mucolytics, bronchodilators and chest physiotherapy Prophylactic antibiotics
Infection	ABPA	Corticosteroids and antifungals
Allergic reaction	Mycobacterium tuberculosis	BCG vaccination in high risk groups Anti-tuberculous treatment
Infection	Non-tuberculous mycobacterial infection (NTM)	Anti-tuberculous treatment for 24 months
Infection	Aspiration pneumonia	Prevention by identifying groups at risk Prompt antibiotic treatment and chest physiotherapy
Bronchial obstruction	Foreign body inhalation Carcinoid tumour Enlarged lymph node	Bronchoscopy Surgical resection
Systemic disease	Rheumatoid arthritis Sjogren’s disease Crohn’s disease HIV	Treatment of underlying condition (immunosuppression) Anti-retroviral treatment
Abnormal cartilage	Tracheobronchomalacia Bronchomalacia Tracheobronchomegaly	Tracheal or bronchial stent Tracheobronchoplasty
Abnormal immune system	Congenital hypogammaglobulinaemia Combined variable immune deficiency (CVID) Selective immunoglobulin deficiencies Lymphoma Myeloma Post-transplant	Intravenous immunoglobulins Prophylactic antibiotics Prompt treatment of infections
Ciliary dysfunction	Primary Ciliary Dyskinesia Young syndrome	Treatment of bronchiectasis
Abnormal respiratory secretions	Cystic fibrosis	Treatment of severe bronchiectasis Lung transplantation

While non-tuberculous mycobacteria (NTM) infection can result in bronchiectasis with the characteristic tree in bud appearance, bronchiectasis from a different aetiology can predispose to NTM infection, particularly with Mycobacterium avium complex (MAC). These patients are more likely to develop ABPA and aspergilloma.

Tracheobronchomalacia (Williams-Campbell syndrome) and tracheobronchomegaly (Mounier- Kuhn syndrome) are diffuse or segmental weaknesses of the trachea or main stem bronchi due to anatomic defects of the airways arising from a deficiency of cartilage in the fourth to sixth order bronchi. Deficient cartilage support results in airway collapse during forced exhalation. This results in inefficient clearance of respiratory secretions and predisposes to the development of bronchiectasis. The CXR will show dilated trachea and bronchi. The diameter of the trachea (measured 2 cm above the main carina) will be greater than 3 cm, the right main bronchus greater than 2.5 cm and the left main bronchus greater than 2 cm. CT thorax with expiratory views will demonstrate airway collapse and narrowing. Placement of a tracheal stent will improve symptoms by reducing airway collapse. Tracheobronchoplasty could be considered in some patients.

Connective tissue disorders, particularly rheumatoid arthritis and Sjogren’s syndrome, predispose to the development of bronchiectasis, although the exact mechanism is unknown. Symptoms of bronchiectasis occur years after the diagnosis of the underlying condition is made. In one study, the frequency of an abnormal CFTR allele was increased in patients with bronchiectasis and rheumatoid arthritis relative to patients with rheumatoid arthritis but without bronchiectasis and normal controls. Bronchiectasis is a rare complication of other connective tissue disorders, especially systemic lupus erythematosus (SLE) and Marfan’s syndrome. Bronchiectasis is also associated with Crohn’s disease, ulcerative colitis, and yellow nail syndrome. It is assumed that optimal treatment of the underlying systemic disease will prevent the deterioration of bronchiectasis, although there are no studies supporting this assumption.

Alpha 1 antitrypsin (A1AT) deficiency is associated with bronchiectasis. A1AT deficiency is discussed in Chapter 6. Adult polycystic kidney disease (APKD), which is an autosomal dominant disease, occurs because of defective cilia and ciliary protein expression of polycystin-1 and polycystin-2, with the formation of renal cysts. Patients with APKD are more likely to develop bronchiectasis.

Congenital hypogammaglobulinaemia and selective immunoglobulin deficiencies present with recurrent upper and lower respiratory tract infections in childhood and, if undetected, will result in bronchiectasis. Hypogammaglobulinaemia may be associated with thymoma. Common variable immunodeficiency (CVID) results in small airway changes and bronchiectasis. It is not clear whether an isolated IgG subclass deficiency, for example, IgG₂ deficiency, can result in bronchiectasis as the levels of these vary greatly in normal adults. Investigation for bronchiectasis includes measurement of IgG, IgA, and IgM with serum electrophoresis and other specialist immunology assessments as indicated. Immunoglobulin deficiencies can be managed with intravenous or subcutaneous immunoglobulin replacement therapy, vaccination as well as prompt treatment of infections.

To evaluate the patient’s response to infection, baseline specific antibody levels to tetanus toxoid and the capsular polysaccharides of Streptococcus pneumonia and Haemophilus influenza type b should be measured. If baseline levels are low, the adequacy of the humoral response should be assessed by immunisation with the appropriate vaccines and remeasurement of antibody levels after four weeks.

Immunoglobulin deficiency can occur because of haematological malignancies, such as lymphoma and myeloma. Human immunodeficiency virus (HIV) also predisposes to recurrent bacterial infections and bronchiectasis.

Primary ciliary dyskinesia (PCD) is a rare, inherited abnormality of the cilium which will be discussed later in this chapter.

Abnormally viscid mucus, as occurs in cystic fibrosis (CF), is a cause of severe bronchiectasis and will be discussed later in this chapter.

Diagnosis of bronchiectasis

A careful history of presenting complaints, childhood infections, past medical history and family history should be taken. A meticulous clinical examination is essential. Box 12.2 lists the common symptoms and signs of bronchiectasis.

Box 12.2 Symptoms and signs of bronchiectasis.

• Cough (98%)

• Copious sputum production (78%)

• Wheezing (22%)

• Dyspnoea (62%)

• Rhinosinusitis (73%)

• Haemoptysis (27%)

• Fatigue (43%)

• Coarse crackles (75%)

• Digital clubbing (2%)

• Recurrent pleurisy (20%)

• Anosmia

____

Patients usually present with chronic, productive cough, recurrent chest infections, and minor haemoptysis. Information about hearing loss, sinusitis, gastrointestinal symptoms, and infertility should be ascertained. Only 2% of patients with bronchiectasis will have finger clubbing, although the majority will have coarse crackles on auscultation.

Table 12.2 lists the investigations that are routinely carried out to make a diagnosis of bronchiectasis and the investigations that should be done if PCD, immunodeficiency or CF is suspected.

The diagnosis of bronchiectasis is made on clinical history and radiological appearance. In early, mild, disease the CXR may appear normal. If the clinical presentation suggests bronchiectasis, then a high resolution computed tomography (HRCT) or multi-detector computed tomography (MDCT) scan of the thorax should be done which will be more sensitive at detecting changes. Expiratory scans best demonstrate air trapping and mosaic attenuation.

Box 12.3 lists the characteristic radiological finding in bronchiectasis, the abnormalities typically affecting the lower lobes (Figure 12.3, Figure 12.4, Figure 12.5). Airway dilatation results in the appearance of parallel lines, referred to as tram lines, and ring shadows when the airway is seen in cross-section. When the diameter of the airway is more than 1.5 times greater than the diameter of the adjacent blood vessel, this is termed cylindrical bronchiectasis. With severe bronchiectasis there is the formation of cysts, and this is termed cystic bronchiectasis.

Bronchiectasis predominantly affecting the upper lobes of the lungs suggests post-tuberculous bronchiectasis or CF, whereas a middle lobe distribution is consistent with PCD (Box 12.3). A tree in bud appearance is often seen with non-tuberculous mycobacterial infection. This is discussed in Chapter 8.

Nitric oxide (NO) levels can be measured quite simply by blowing into a NO monitor. Levels of NO are increased in patients with bronchiectasis because of airway inflammation, although raised exhaled NO is not diagnostic. Very low levels <77 nl min^-1 in a patient with bronchiectasis is consistent with PCD and should prompt the doctor to do ciliary studies.

Lung function tests will show obstruction, with a reduced forced expiratory volume in one second (FEV₁) and a reduced FEV₁/FVC ratio. The severity of clinical disease correlated well with HRCT changes and poor lung function in several studies. Individuals with severe bronchiectasis may develop type 1 respiratory failure, with hypoxia and normocapnia on arterial blood gas measurement.

The result of the shuttle walking test correlates well with the severity of bronchiectasis and may be of prognostic value. Shuttle walking test can be used to monitor the response to treatment and is used as an end-point in many trials. A validated respiratory questionnaire, for example, the St. George’s Respiratory Questionnaire (SGRQ), can be used to monitor the patient’s response to treatment. The details of these investigations are discussed in Chapter 4.

Differential diagnoses of bronchiectasis

The differential diagnosis of bronchiectasis includes other conditions which cause bronchial wall dilatation. Chronic obstructive pulmonary disease (COPD) can have a similar presentation to bronchiectasis, with chronic sputum production and frequent exacerbations but with a history of cigarette smoking. A quarter of patients with alpha 1 antitrypsin deficiency (A1AT) present with daily, chronic sputum production, and the majority have radiological evidence of bronchiectasis. It is therefore recommended that testing for A1AT deficiency is carried out in patients presenting with bronchiectasis with no obvious underlying cause.

Allergic bronchopulmonary aspergillosis (ABPA), which results in proximal bronchiectasis, with dilatation of central airways, develops in patients with asthma and is caused by an allergic reaction to the fungus Aspergillusfumigatus. COPD, A1AT deficiency, and ABPA are discussed in more detail in Chapter 6. Traction bronchiectasis describes stretching and distortion of bronchi due to pulmonary fibrosis, and is discussed in Chapter 7.

Table 12.2 Investigations for the diagnosis of bronchiectasis.

Diagnosis	Bloods	Radiology	Other
Diffuse bronchiectasis	Full blood count Differential cell count C-reactive protein Immunoglobulins G, M, A, and E Protein electrophoresis Antibody titres to pneumococcal vaccine Aspergillus precipitins (IgE and IgG antibodies) Total serum IgE IgG subclasses Rheumatoid factor Alpha-1 antitrypsin level	CXR: ring shadows, tram lines, mucus plugging HRCT: airway dilatation with bronchial wall thickening, mucus plugging, tree in bud and cysts CT sinus: opacification and mucosal oedema	Sputum for microscopy, culture, sensitivity, and differential cell count Lung function tests Nitric Oxide (NO) Bronchial lavage
Localised bronchiectasis		CXR CT thorax	Bronchoscopy
Immunodeficiency	Full blood count C-reactive protein Immunoglobulins Protein electrophoresis Immune function tests Specialist immune tests	CXR HRCT	Refer to Immunologist Refer to Haematologist
PCD	Full blood count C-reactive protein Immunoglobulins Protein electrophoresis Immune function test	CXR HRCT CT sinus	Nitric Oxide (NO) Ciliary studies: saccharin test, ultrastructure of cilia, microscopic photometry of ciliary function
CF	Full blood count C-reactive protein Immunoglobulins Protein electrophoresis Immune function tests Aspergillus precipitins	CXR HRCT	Sweat chloride test Sweat sodium test Nitric Oxide (NO) DNA analysis

Management of bronchiectasis

The management of bronchiectasis depends on the underlying cause. For example, bronchiectasis that occurs due to immunodeficiency will respond to intravenous or subcutaneous immunoglobulin therapy. However, there are several evidence-based treatments that improve symptoms, reduce the frequency of infections, thus preventing further bronchial wall damage. The management is summarised in Box 12.4.

The aim of the management of bronchiectasis is to improve the symptoms of breathlessness and productive cough, and to prevent recurrent chest infections. Long-acting bronchodilators, in combination with inhaled corticosteroids, should be prescribed to those with airway obstruction. Shortacting bronchodilators will improve the symptoms of breathlessness and wheeze. There is no evidence for the routine use of oral corticosteroids in the management of chronic bronchiectasis.

Box 12.3 Characteristic HRCT findings in bronchiectasis.

• Bronchial wall thickening

• Dilatation of bronchi

• Lack of airway tapering

• Tree in bud appearance

• Mucus plugging

• Post-operative air trapping

• Mosaic attenuation

• Cystic changes

____

Figure 12.3 CT showing dilated bronchi in bronchiectasis.

Figure 12.4 Coronal CT thorax showing bronchiectasis.

Figure 12.5 CT thorax showing cylindrical bronchiectasis.

Box 12.4 Management of bronchiectasis.

• Short-acting inhaled bronchodilators (β₂-agonists)

• Long-acting β₂-agonists

• Inhaled corticosteroids

• Long-acting anticholinergic medication

• Mucolytic drugs

• Sputum culture and sensitivity for exacerbations

• Prompt antibiotics, often longer course (rescue pack)

• Prophylactic antibiotics

• Chest physiotherapy

• Surgery for localised bronchiectasis

____

Annual influenza vaccination is recommended for all chronic respiratory diseases. Pneumococcal vaccination should be offered.

Pulmonary rehabilitation is effective in bronchiectasis, as it is in all chronic respiratory diseases, and will result in improvement in exercise tolerance and quality of life measures. Pulmonary rehabilitation has been shown to improve endurance capacity, breathlessness, the distance walked in the shuttle walk test, and the six-minute walk test.

However, a regular exercise regime is required to sustain any improvement.

Nutritional supplementation with a high protein diet may benefit those with bronchiectasis which is often associated with a poor appetite and weight loss. The recurrent infection and raised inflammation drive a catabolic process, therefore extra calories are required. Supplementation with hydroxyl-beta-methylbutyrate, which has antiinflammatory and anti-catabolic effects, may help.

If the bronchiectasis is confined to one lobe of the lung, wedge resection or lobectomy can be very effective and potentially curative. Recurrent, massive haemoptysis could be one indication for surgery. Single or double lung transplantation could be considered in those with severe diffuse bronchiectasis.

Infective exacerbations of bronchiectasis

An infective exacerbation should be suspected when the patient reports an increase in the volume of sputum, a change in the colour of sputum to yellow or green, sputum that is purulent, worsening breathlessness, chest pain, haemoptysis, and systemic symptoms, such as fever and decreased appetite.

Bacterial pathogens, including opportunistic organisms, are the main cause of exacerbations, although viruses, such as coronavirus, rhinovirus, and influenza can also cause infections. Bacteria often associated with exacerbations in bronchiectasis include Haemophilus influenza, Staphylococcus aureus, Moraxella catarrhalis, and the mucoid type of Pseudomonas aeruginosa. Many of these organisms will be resistant to the usual oral antibiotics; therefore, it is important to culture sputum to determine antibiotic sensitivities.

Infective exacerbations should be treated with prompt antibiotics for 10—14 days. The exact length of the treatment and the route of antibiotic therapy will depend on the clinical condition of the patient and the antibiotic sensitivities. Patients who become clinically unwell with hypotension, tachypnoea, and respiratory failure will need to be admitted for intravenous antibiotics, intravenous fluids, oxygen therapy, and chest physiotherapy to clear retained secretions, thus improving oxygenation. Blood cultures should be taken in patients who are febrile or show other signs of sepsis.

If information is available about the antibiotic sensitivities of the bacterial pathogen colonising the lungs of the patient, this should guide the choice of antibiotics given. If no sputum culture result is available, then a fluoroquinolone, amoxicillin, or a macrolide would be a suitable initial choice. The initial antibiotic therapy may need to be modified when sputum culture results become available. If there is a beta-lactamase-positive organism, then a second or third generation cephalosporin or macrolide should be used.

Pseudomonas aeruginosa colonises the lungs of patients with bronchiectasis and its presence in the sputum of a patient with bronchiectasis signifies a worse prognosis. Pseudomonas can overcome the lungs’ defence mechanisms by interacting with the CFTR, thus altering the milieu of the lungs. Patients colonised with Pseudomonas aeruginosa have decreased quality of life, severe bronchiectasis on HRCT, worse lung function tests, increased number of exacerbations and hospitalisations, and increased mortality compared to patients with bronchiectasis colonised with other organisms.

The usual choice of antibiotics for Pseudomonas is oral ciprofloxacin, 500 or 750 mg twice a day for 14 days. Resistance to ciprofloxacin can develop rapidly, so further sputum samples should be sent if there is no clinical improvement. Pseudomonas can be treated with nebulised colomycin.

The choice of intravenous antibiotic therapy will depend on the patient’s previous history of antibiotic resistance and the results of sputum culture and sensitivities. An anti-pseudomonal penicillin, such as ceftazidime, together with an aminoglycoside or fluoroquinolone, is the usual combination given. Aminoglycosides should not be given alone, and the level should be monitored carefully to avoid renal toxicity and ototoxicity.

If the sputum grows Aspergillus fumigatus, then a course of Itraconazole or Voriconazole should be given, with careful monitoring of liver function tests.

Other treatments during an exacerbation include nebulised bronchodilators, controlled oxygen therapy, regular chest physiotherapy, intravenous fluids, and systemic corticosteroids in some cases. Corticosteroids must be used with care as they are immunosuppressive drugs and therefore can worsen infection.

Prevention of exacerbations

There is evidence that meticulous attention to sputum clearance techniques will reduce the bacterial load in the lungs and reduce the frequency of exacerbations. Regular sputum clearance improves symptoms, improves lung function, and reduces infective exacerbations.

There are various mucolytic drugs that have been shown in in vitro studies to aid the clearance of mucus from the lungs, although trial evidence is limited. Carbocysteine, a commonly used mucolytic drug, reduces the viscosity of mucus and the number of exacerbations. In vitro studies have shown that nebulised hypertonic saline (6—7%) improves the flow of mucus, increases ciliary motility, and improves hydration of the secretions, thereby potentially improving expectoration. Although clinical trials have not shown a benefit, once-daily nebulised mannitol, which is a hyperosmolar agent, hydrates airway secretions and aids sputum clearance. Care must be taken not to use mannitol in patients with co-existing asthma as this can result in mast cell mediator release and bronchoconstriction. N-Acetylcysteine, a mucolytic agent that cleaves disulphide bonds in glycoproteins, has not demonstrated benefit in patients with CF and there are no studies using this in non- CF bronchiectasis. Aerosolised recombinant deoxyribonuclease (DNase), which breaks down DNA, improves lung function and decreases hospitalisation in patients with CF, and is not effective in non-CF bronchiectasis.

Chest physiotherapy, an essential part of the management of bronchiectasis, involves techniques of chest percussion, active cycle of breathing, and the use of various devices which break up the mucus into smaller particles, making it easier to expectorate. Standard physiotherapy applied by trained experts is time-consuming and not possible for patients who are at home. Devices which aid sputum clearance include positive expiratory pressure devices, high frequency chest wall oscillation devices, oral high frequency oscillation devices, intrapulmonary percussive ventilation, incentive spirometry, the flutter valve, the Acapella device, and the cornet. These devices are less timeconsuming, easier for the patient to use after training, and a good alternative to standard chest physiotherapy. These devices can be used by children, for example, those with cystic fibrosis, under the supervision of their parents. It is not within the scope of this book to discuss these devices in detail. The physiotherapist will recommend the most appropriate device for the individual.

There is trial evidence that patients who have more than two infective exacerbations every year benefit from low-dose prophylactic Azithromycin, 250 mg two or three times a week. Low-dose azithromycin appears to work by a mechanism other than the antimicrobial one, although the exact way it works is unclear. Three small randomised trials using prophylactic macrolide antibiotics, two of them using Azithromycin (EMBRACE and BAT) and one using erythromycin (BLESS) have shown a reduction in the number of exacerbations, reduction in the volume of sputum, improved symptoms using the SGRQ, and an improved dyspnoea index.

Side effects of macrolides include gastrointestinal discomfort, hepatotoxicity, ototoxicity, and bacterial resistance. Patients should be informed of the potential side effects and asked to report any adverse effects, such as change in hearing. It is recommended that liver function tests are monitored and the drug discontinued if there is any evidence of hepatotoxicity. Macrolide antibiotics are associated with a risk of prolongation of QT interval and torsades de pointes and should not be given to those with hypokalaemia, hypomagnesaemia, bradycardia, and heart failure. The length of treatment should be for 3—6 months with careful assessment of the patient at the end of this period. It is important to give a break after this period to reduce the risk of developing resistance to macrolide antibiotics.

If macrolide prophylaxis is contraindicated, amoxicillin 500 mg twice a day or doxycycline 100 mg twice a day should be considered.

The role of inhaled antibiotics in patients with non-CF bronchiectasis who are colonised with Pseudomonas aeruginosa is unclear. Inhaled tobramycin, ciprofloxacin and colistin have been shown to reduce the volume of sputum and reduce the bacterial load but are associated with bronchoconstriction. In patients with three or more exacerbations a year with Pseudomonas aeruginosa, a therapeutic trial of inhaled antibiotics could be considered. Spirometry 15 and 30 minutes after administration of the drug should be carried out and the drug stopped if there is evidence of significant bronchoconstriction with a reduction in FEV₁by more than 15% or >200 mL. Administering inhaled β₂-agonist prior to giving the inhaled antibiotic will reduce the risk of bronchoconstriction. There is less evidence for the use of inhaled Aztre- onam and inhaled gentamicin, so their use in this way is not recommended.

As gastro-oesophageal reflux may be a factor in the development of bronchiectasis, treatment with a proton pump inhibitor is recommended to reduce the risk of aspiration of gastric contents. In one small, single-centre, pilot study, atorvastatin 80 mg daily for six months resulted in improvement in cough compared to the placebo group but there were significant side effects. A larger, randomised, double-blind controlled study is required before the routine use of a statin is recommended in bronchiectasis.

It is essential to reiterate the importance of compliance with all these treatments to the patient. Annual influenza vaccination and regular pneumonia vaccination should be offered to the patient.

Cystic fibrosis

Cystic fibrosis (CF) is the commonest inherited genetic disorder in the United Kingdom’s Caucasian population, occurring at a frequency of 1 in 2500 live births. It is inherited as an autosomal recessive disorder, which means that the individual has inherited a defective gene from each parent. One in 25 of the Caucasian population is an asymptomatic carrier of the defective gene. There are approximately 9000 individuals with CF in the UK.

CF occurs due to a mutation in a gene on the long arm of chromosome 7 resulting in a defect in the cystic fibrosis transmembrane conductance regulator (CFTR), which is a protein comprising of 1480 amino acids. This CFTR protein is a member of the ATP Binding Cassette (ABC) family, and is an essential regulator of membrane physiology. CTFR sits in the membrane of epithelial cells and regulates the transport of chloride ions through activation of cyclic adenosine monophosphate (cAMP) and through calcium-activated chloride channels (Figure 12.6). CTFR also inhibits the transport of sodium through the sodium channels in the epithelial cell membrane and regulates the movement of bicarbonate anions.

Approximately 1800 different mutations of the gene have been identified which are classified into five groups based on their effect on CFTR function. The severity of the disease and the clinical presentation depend on the nature of the mutation. The most common mutation is a deletion of phenylalanine at position 508 of the protein, described as Delta F508, which is a Class 1 defect.

Figure 12.6 The structure of the cystic fibrosis transmembrane conductance regulator.

This results in the degradation of the CFTR protein in the endoplasmic reticulum of the cell so that no protein reaches the cell membrane.

Other mutations result in defective protein processing (Class 2), defective protein activation (Class 3), impaired chloride conductance (Class 4), and reduced amount of CFTR protein (Class 5). Defects belonging to Classes 4 and 5 will result in some active protein being produced so that the patient presents with less severe clinical disease than mutations in Classes 1, 2, and 3.

Epithelial cells line the bronchial mucosa, the gastrointestinal tract, the pancreas, the hepatobiliary system, the reproductive tract, and the sweat glands in the skin. Therefore, a defect in the CFTR gene will affect all these systems.

Abnormal CFTR protein results in decreased chloride reabsorption and increased sodium reabsorption, resulting in secretions that have a very high viscosity and reduced water content. This impedes mucociliary clearance in the bronchi so that respiratory secretions are stagnant. The high salt content of the secretions also disrupts the functioning of antimicrobial peptides which are part of the defence system of the respiratory tract. Therefore, the individual with CF is at a high risk of developing frequent respiratory infections, which will inevitably progress to severe bronchiectasis within a few years. Individuals with CF are particularly prone to developing infections with Gram-negative organisms, such as Pseudomonas aeruginosa and Burkholderia cepacia. There is a risk of this infection progressing to life-threatening necrotising pneumonia (Cepacia syndrome).

Defective CFTR also results in abnormal chloride transport in the pancreas leading to destruction of the pancreas, pancreatic exocrine insufficiency, reduction of lipase activity, and decreased absorption of fat in the small intestine, resulting in steatorrhoea. This, together with decreased water content in the intestines, results in thick faecal material which can cause intestinal obstruction, called the ‘meconium ileus equivalent’ in adults as it mimics meconium ileus in neonates. Lack of fat absorption will lead to nutritional deficiencies, especially of the fat-soluble vitamins, and failure to thrive. Over time, there is failure of endocrine pancreatic function, resulting in diabetes.

Clinical presentation of CF

The presentation of CF will depend on the severity of the genetic defect. The delta F508 mutation will present with symptoms and clinical signs in the neonate or young child. In 7% of cases, the mutation results in less severe disease so that the diagnosis may not be made until adolescence or even adulthood. Table 12.3 lists some of the features of CF in the different age groups.

Diagnosis of CF

A diagnosis of CF is made based on clinical features consistent with CF, an abnormal CXR, a positive sweat test, an abnormal potential difference across the nasal epithelium and DNA analysis. The commonest symptoms are sinusitis and bronchiectasis (Figure 12.7, Figure 12.8) which predominantly affects the upper lobes. Sputum samples usually grow Staphylococcus aureus in children and Pseudomonas aeruginosa in adolescents and adults. A sweat test involves instilling pilocarpine on the skin and stimulating the sweat glands by a small electric current which increases the production of sweat. A chloride content more than 60 mmol/L is abnormal, and two such readings confirms a diagnosis of CF. A chloride level of between 40 and 60 mmol/L may indicate one of the less severe forms of CF.

Genotyping can be done for the common mutations but would not be possible for all the known different types. Prenatal diagnosis can be offered when DNA analysis is conducted on a sample of the chorionic villus. Neonatal screening is done by measuring serum immunoreactive trypsin activity on a Guthrie card. This will be elevated in those with CF.

Management of CF

The care of patients with CF should be undertaken in a specialist centre with a multidisciplinary team of doctors, specialist nurses, physiotherapists, occupational therapists, dieticians, and psychologists. Patients with CF should be seen in the clinic at regular intervals and have assessments, which includes chest imaging, sputum culture, spirometry, oximetry, weight, height, body mass index measurement, and blood glucose. Compliance with the management plan can be ascertained and its importance reinforced.

The aim with CF is to reduce the number of respiratory exacerbations, thus preventing the progression of bronchiectasis, to give nutritional support, and give emotional and psychological support to the individual and their family.

Patients are taught techniques of sputum clearance which is the most important aspect of managing the bronchiectasis and will reduce the risk of infection. This includes chest percussion, postural drainage, active cycle of breathing technique, and the use of oscillating positive expiratory pressure devices (flutter valve or Acapella device). The use of mucolytic drugs will aid sputum clearance. Nebulised recombinant human DNase has been shown in clinical trials to reduce sputum viscosity, reduce exacerbations, and improve lung function. The DNase works by degrading the high concentrations of DNA in the sputum from dying cells. Nebulised bronchodilators and inhaled corticosteroids improve symptoms.

Infective exacerbations must be managed rapidly and effectively with intravenous antibiotics. Macrolide antibiotics, such as Azithromycin, can be effective in preventing exacerbations in the early stages of the disease in the same way as for those with non-CF bronchiectasis. Patients with frequent exacerbations may require permanent intravenous access so that antibiotics and fluids can be administered without delay and for long periods.

Individuals who have become colonised with the Gram-negative organisms (Pseudomonas aeruginosa and Burkholderia cepacia), are treated with long term nebulised colistin and nebulised tobramycin but will require intravenous antibiotics during exacerbations. They are usually treated with third generation cephalosporins, piperacillin, and aminoglycoside, but development of resistance is a major concern.

Table 12.3 Clinical presentation of cystic fibrosis.

Figure 12.7 CXR of patient with CF showing extensive bronchiectasis.

Figure 12.8 CT of patient with CF

As these severe infections can be transmitted from one patient to another, patients who are known to be colonised with a particular organism are segregated in different clinics and on different wards to prevent cross-transmission. Babies with CF should receive all their immunisation and all patients should have their annual influenza vaccination.

As the bronchiectasis gets progressively worse, there is a risk of recurrent pneumothoraces. Pleurodesis could be considered, although this may make lung transplantation difficult in the future. Massive haemoptysis due to hypertrophy of the bronchial arteries can be life-threatening and difficult to manage. Bronchial artery embolisation is the most effective treatment for this complication.

Patients who develop type 1 respiratory failure will require long term oxygen therapy (LTOT). Many patients develop type 2 respiratory failure requiring bi-level positive pressure ventilation (BiPAP).

Single lung, double lung or heart and lung transplantation is the only real hope for patients with respiratory failure and cor pulmonale secondary to CF. Patients should be referred for transplant assessment and, if suitable, put on to the transplant register.

Pancreatic insufficiency is treated with pancreatic supplements, for example, Creon, Pancrease or Nutrizym, which is taken with every meal. These supplements contain lipases which will help digest and absorb fat. Patients should receive advice and support from the dietician and take other dietary supplements, including vitamins A, D and E. Patients with severe malnutrition will require enteral feeding.

Patients may require specific treatment for intestinal obstruction with intravenous rehydration and intestinal lavage with Gastrograffin and N-acetylcysteine. Diabetes is managed with insulin and the complications of diabetes are actively treated.

CF is a serious and life-threatening condition and therefore a diagnosis in a baby or child can be extremely harrowing for the parents. Individuals and families will need a lot of emotional support from trained therapists. The Cystic Fibrosis Trust offers support and advice to these families.

All attempts should be made to ensure that children, adolescents, and adults live their lives as normal as possible, attend school, participate in physical activity, take up employment, and get married. It is not uncommon for women with CF to have a normal pregnancy, although there are associated risks, and they will need careful medical attention.

Despite all available treatments, most patients with the commonest forms of CF will deteriorate and die. Those approaching end of life should be referred to the palliative care team.

Prognosis of CF

Most individuals with CF die of progressive respiratory failure. The 2-year survival of those with severe airway obstruction is less than 50%. The prognosis has improved significantly in the past few decades, largely due to early diagnosis, prompt treatment of infections with antibiotics, chest physiotherapy, nutritional support, a multidisciplinary approach, and management in specialist centres with considerable expertise. The median survival in 2015 was approaching 40 years.

Future therapy for CF

A lot of research is being conducted into gene therapy, whereby a normal copy of the gene is placed into the lungs through liposomal or viral carriers. There is some optimism that this technique will significantly improve the prognosis of those with CF in the future.

Primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is also called the immotile cilia syndrome. PCD is an autosomal recessive disorder with a prevalence of 1 in 16 000 live births. The commonest genetic defect is a deficiency of the dynein arm which results in immotile cilia or cilia which move in an abnormal way. This condition will affect all the organs that rely on normal ciliary motion.

Failure of normal ciliary function results in recurrent otitis media leading to deafness, recurrent sinusitis, anosmia, and bronchiectasis. Most men with PCD will be infertile and women will be sub-fertile. As cilia are responsible for the rotation of the internal organs during embryogenesis, there is a random rotation of organs in PCD. So, 50% of those with PCD will have dextrocardia and situs inversus (Figure 12.9). The triad of bronchiectasis, dextrocardia, and sinusitis is called Kartagener’s syndrome.

There are at least eight categories of cilia in the human body. Defects in the ependymal cilia will result in hydrocephalus whereas defective cilia in the retinal photoreceptor cells will result in retinitis pigmentosa. Abnormal ciliary protein is also important in the development of APKD

Figure 12.9 CXR of patient with PCD showing dextrocardia.

Diagnosis of PCD

Patients with PCD are usually diagnosed in adolescence or early adulthood when they present with bronchiectasis, sinusitis, otitis media, and infertility. These patients should have the same investigations as for bronchiectasis, but should in addition have nasal mucociliary clearance test (NMCC), also called the saccharin test. A 0.5 mm particle of saccharin is placed on the lateral nasal wall, 1 cm behind the anterior end of the inferior turbinate. In a normal individual, the mucociliary mechanism will transport the saccharin to the nasopharynx and pharynx where it can be tasted within 30 min. In PCD there will be a considerable delay, or the saccharin may never reach the pharynx.

Using nasal or turbinate brush biopsies, the ultrastructure of the cilium can be looked at through electron microscopy, and phase contrast microscopy can be used to determine cilial beat frequency. Exhaled nitric oxide levels will be low (< 77 nL min^-1) in patients with PCD. CF is always in the differential diagnosis of this presentation and should be excluded.

Early diagnosis and prompt treatment of bronchiectasis will minimise symptoms and morbidity. Life expectancy is normal. Genetic counselling is available.

Young syndrome may be a variant of PCD or may have been caused by exposure to mercury in childhood. It results in bronchiectasis, sinusitis, and obstructive azoospermia, and is now rare.

Lung abscess

Lung abscess is a chronic lung condition due to a localised collection of pus within a cavity in the lung parenchyma. Patients will present with symptoms of productive cough, fever, malaise, cachexia, chest pain, haemoptysis, and weight loss. The patient will appear unwell and may be clubbed. If untreated, it can result in significant morbidity and mortality. Box 12.5 lists the aetiology of lung abscess.

The commonest cause of lung abscess is that secondary to community acquired pneumonia, which is discussed in Chapter 8. CAP due to Staphylococcus aureus and Klebsiella pneumonia especially predispose to the formation of a lung abscess. Aspiration of anaerobic organisms, which includes Fusobacteria and Prevotella, also predisposes to the formation of a lung abscess. Septic emboli can travel to the lungs from any source of bacteraemia. Individuals who use infected needles for intravenous drug use are at a high risk of developing abscesses.

Transdiaphragmatic spread of infection may occur from a subphrenic abscess, for example, after biliary surgery. Amoebic hepatic abscess also has the potential to spread to the lungs if untreated.

Box 12.5 Aetiology of lung abscess.

• Aspiration pneumonia

• Community acquired pneumonia (CAP)

• Intravenous drug use

• Secondary to bronchial obstruction

• Secondary to sepsis

• Dental infection

• Chronic sinus infection

• Subphrenic abscess

• Hepatic abscess

• Infected bulla

• Lung infarction

• Penetrating trauma to chest

• Bronchopulmonary sequestration

_____

Bronchial obstruction secondary to tumour or foreign body can result in chronic infection distal to the obstruction which causes lung infarction and cavitation, resulting in formation of a lung abscess. Pulmonary embolus can also result in lung infarction and the development of an abscess. Pulmonary embolus is discussed in Chapter 11.

Diagnosis of lung abscess is made based on the clinical presentation, a history suggestive of chronic sepsis, and a CXR showing a thick-walled cavity. Such a cavity can be seen more clearly on a CT scan (Figure 12.10, Figure 12.11, Figure 12.12).

Figure 12.10 CXR of right-sided lung abscess.

Figure 12.11 CT of right-sided lung abscess.

Figure 12.12 CT of left lung abscess.

Causative organisms in lung abscess

A variety of organisms result in the formation of a lung abscess; anaerobic organisms, Staphylococcus aureus, Klebsiella pneumonia and Gram-negative bacteria. Actinomyces and Nocardia are rarer causes of lung abscess.

Bronchopulmonary sequestration is a congenital anomaly when an area of the lung is not connected to the bronchial tree and has an anomalous blood supply, usually from the aorta. Infection of the sequestered area predisposes to abscess formation as there is inadequate drainage. Bronchial arteriography will identify the anomalous blood supply. Surgery will be required to remove the infected area of lung.

Box 12.6 Differential diagnosis of lung abscess.

• Cavitating lung cancer

• Pulmonary tuberculosis

• Pulmonary infarct

• Infected bullae

• Hiatus hernia

• Granulomatosis with polyangiitis (previously called Wegener’s Granulomatosis)

____

There are several conditions that can resemble a lung abscess, both clinically and radiologically. These are listed in Box 12.6.

Management of lung abscess

A prolonged course of appropriate antibiotics is indicated. A combination of high dose penicillin and metronidazole is usually recommended for at least six weeks, with careful monitoring of clinical and radiological improvement. The CRP level is often used as a marker of improvement. Percutaneous drainage of the abscess under radiological guidance should be undertaken whenever possible. Surgery to remove the abscess should also be considered.

Lung abscess has a significant morbidity and mortality, especially in the immunocompromised and malnourished individual. The abscess can rupture into the lungs causing severe infection.

■ Suppurative lung diseases are those with chronic purulent material in the lungs.

■ Suppurative lung diseases present with chronic sputum production, recurrent chest infections, and systemic symptoms of anorexia and weight loss.

■ Cilia are fine, hair-like structures that line the epithelial cells in the upper and lower respiratory tract, the tail of the spermatozoa, and Fallopian tubes and are responsible for the rotation of organs in embryogenesis.

■ A cilium, which resembles a flagellum, is comprised of nine pairs of microtubules arranged in a circle with a central pair of microtubules all linked together.

■ The commonest suppurative lung disease is bronchiectasis.

■ There are many different causes of bronchiectasis; careful history, clinical examination and investigations are required to make the diagnosis.

■ Recurrent respiratory infections, community acquired pneumonia, and aspiration pneumonia are common causes of bronchiectasis in the UK.

■ Mycobacterium tuberculosis is a common cause of bronchiectasis worldwide.

■ Typical HRCT appearance of bronchiectasis includes bronchial wall thickening, dilatation of bronchi, lack of airway tapering, and mucus plugging.

■ The management of bronchiectasis includes chest physiotherapy, bronchodila- tors, mucolytic agents, prompt treatment of infection after sputum microbiology, and prophylactic antibiotics.

■ Cystic fibrosis is a common autosomal recessive condition that affects 1:2500 live births in the UK.

■ CF is caused by a defect in the CFTR protein resulting in a high concentration of chloride in the secretions from epithelial cells.

■ Prenatal diagnosis of CF is possible, as is genetic counselling.

■ There are over 1800 genotypes of CF and the clinical presentation will depend on the actual defect.

■ The diagnosis of CF is made with an abnormal sweat test and DNA analysis.

■ The commonest genetic abnormality in CF, the F508 mutation, presents with recurrent respiratory infections leading to severe bronchiectasis in early adulthood, colonisation with mucoid Pseudomonas aeruginosa, and development of respiratory failure.

■ Patients with CF also develop pancreatic exocrine deficiency requiring pancreatic supplements, fat soluble vitamins, and nutritional supplements.

■ Patients with CF develop diabetes melli- tus requiring insulin therapy.

■ Patients with CF develop other complications, including liver cirrhosis, gallstones, intestinal obstruction, and infertility.

■ The management of CF is optimising the management of bronchiectasis with antibiotics, chest physiotherapy, mucolytic agents, including DNase, management of recurrent pneumothorax, management of haemoptysis, and lung transplantation.

■ PCD is a rare, autosomal recessive condition which occurs because of an abnormality in the dynein arm of the cilium.

■ PCD presents with bronchiectasis, sinusitis, otitis media, infertility, and in 50% dextrocardia and situs inversus.

■ The diagnosis of PCD is made when there is a very low exhaled NO, abnormal mucociliary clearance test, and abnormal ciliary structure and function.

■ PCD is managed by early diagnosis and management of bronchiectasis, sinusitis, and otitis media.

■ Lung abscess is an infected cavity within the lung parenchyma.

■ Lung abscess occurs as a complication of CAP, secondary to aspiration pneumonia, secondary to sepsis, and after dental infections.

■ A diagnosis of lung abscess is made on clinical presentation, and a CT thorax showing a fluid-filled cavity.

■ The management of lung abscess is with drainage, surgical resection, and prolonged course of antibiotics.

MULTIPLE CHOICE QUESTIONS

12.1 Which of the following is NOT a clinical feature of bronchiectasis?

A Clubbing

B Coarse crackles

C Chronic productive cough

D Haemoptysis

E Steatorrhoea

Answer: E

Bronchiectasis is due to the destruction and dilatation of the bronchi. Patients have retained secretions which get infected. Symptoms of bronchiectasis include chronic productive cough and haemoptysis. Clinical signs include clubbing in a small percentage and coarse crackles. Steatorrhoea is not seen with bronchiectasis but is a feature of cystic fibrosis due to pancreatic insufficiency, which results in an inability to absorb fat.

12.2 Which of the following statements about Primary Ciliary Dyskinesia is true?

A It is an autosomal dominant condition

B Individuals with PCD will require pancreatic supplements

C Life expectancy is reduced

D Individuals with PCD can present with deafness

E 100% of those affected will have dextrocardia

Answer: D

PCD is a rare, autosomal recessive condition which results in abnormal cilia which cannot beat synchronously. As a result, all the parts of the body which have ciliated epithelium are affected. PCD can result in repeated otitis media which can result in deafness. Cilia are also responsible for rotation of the organs during embryogenesis and therefore 50% of individuals with PCD will have dextrocardia and situs inversus. If detected early and the bronchiectasis treated adequately, individuals with PCD will have a normal life expectancy.

12.3 Which one of the following statements about cilia is NOT true?

A Cilia are responsible for the rotation of organs in embryogenesis

B A cilium is composed of five pairs of microtubules linked together C Ciliary motion is essential for the normal functioning of the mucociliary escalator

D Cilia are structured in the same way as flagella

E Defective ciliary protein expression results in adult polycystic kidney disease

Answer: B

A cilium is composed of nine pairs of microtubules (sub-units A and B) in a circle with a central pair of microtubules, all linked by dynein arms. A defect in these proteins will result in abnormal cilia. The structure of the cilium is identical to that of a flagellum. Abnormalities result in a non-functioning mucociliary escalator, random rotation of organs during embryogenesis, and adult polycystic kidney disease.

12.4 Which of the following statements about cystic fibrosis is true?

A It is inherited as an autosomal recessive condition

B Carriers of the condition have some clinical symptoms

C CF results in decreased chloride concentration in respiratory secretions

D Patients with CF have abnormal cilia

E Patients with CF are always infertile

Answer: A

CF is inherited as an autosomal recessive condition, so carriers have no symptoms. Abnormality of the CFTR protein results in an increased amount of chloride in the respiratory secretions. The cilia are normal in structure and function in CF. A significant number of male patients with CF are infertile, but not all, and only a small proportion of female patients are infertile.

12.5 Which of the following statements about the management of bronchiectasis is true?

A There is no evidence for the use of prophylactic antibiotics

B Chest physiotherapy is a key part of managing this condition

C Long term oral corticosteroids prevent recurrent infections

D Inhaled long-acting bronchodilators are contra-indicated E Surgery is never an option

Answer: B

The key in preventing recurrent infections is chest physiotherapy and sputum clearance. Inhaled bronchodilators and inhaled corticosteroids may by indicated in those with airway obstruction, co-existing asthma, and reversibility. Prophylactic macrolide antibiotics, given twice or three times a week, has been shown to reduce the number of exacerbations. Surgery in the form of wedge resection or lobectomy is a option in those with localised bronchiectasis.

12.6 Which one of the following investigations confirms the diagnosis of primary ciliary dyskinesia?

A High-resolution computed tomography.

B Nitric oxide breath test

C Nasal mucociliary clearance test

D Microscopy of ciliary structure and function

E Sweat test

Answer: D

HRCT will show features of bronchiectasis but will not determine the reason for the bronchiectasis. NO and the nasal mucociliary clearance test will be abnormal in PCD, but it is the ultrastructure of the cilium through an electron microscope and the movement of cilia with scanning electron microscopy that will diagnose that it is PCD.

12.7 Which of the following statements about CF is true?

A Staphylococcus aureus is the commonest pathogen to colonise the lungs of adults B Prenatal diagnosis of CF is still not possible

C Meconium ileus occurs in 90% of neonates with CF

D Individuals with CF thrive in hot weather

E 20% with CF develop nasal polyps

Answer: E

Staphylococcus aureus occurs in children with CF but in adolescent and adult CF patients, Pseudomonas aeruginosa is the commonest pathogen to colonise the lungs. DNA analysis of chorionic villus sample is possible to make a prenatal diagnosis. Meconium ileus occurs in 10% of neonates. CF results in a loss of salt in sweat with a risk of heat prostration and severe dehydration. Some 20% of those with CF develop nasal polyps and 20% develop sinusitis.

12.8 Which of the following statements about bronchiectasis is true?

A Rheumatoid arthritis predisposes to the development of bronchiectasis

B Haemophilus influenza is the commonest pathogen in sputum

C NO levels can be diagnostic

D The aetiology of bronchiectasis is rarely found

E Traction bronchiectasis suggests an infection with non-tuberculous mycobacteria

Answer: A

The aetiology of bronchiectasis can be determined in most patients if the appropriate investigations are carried out. Connective tissue disorders, including rheumatoid arthritis, predispose to the development of bronchiectasis. Common pathogens include Staphylococcus aureus and Klebsiella pneumonia. NO level is high in bronchiectasis but is not diagnostic. Traction bronchiectasis is a term used to describe the distortion of the bronchi in pulmonary fibrosis. Non-tuberculous mycobacterial infections cause a ‘tree-in-bud’ appearance.

12.9 Which of the following statements about lung abscess is true?

A Surgery is the only treatment

B It can be treated with a long course of oral antibiotics

C It presents most commonly in young children

D It is a collection of pus in the pleural cavity

E It can be associated with abnormal cilia

Answer: B

Lung abscess is commoner in the elderly. It is an infected cavity within the lung parenchyma. Pus in the pleural space is called an empyema. Although surgery should be considered, it is not the only option. If the patient is not fit for surgery, then drainage through a chest drain and a long course of oral antibiotics are indicated. A lung abscess is not caused by abnormal cilia.

12.10 Which one of the statements about lung abscess is NOT true?

A It can occur due to inhaled foreign body

B It can occur after aspiration pneumonia

C It is a common complication of community acquired pneumonia

D Diagnosis is made at bronchoscopy

E CT thorax is the diagnostic test of choice

Answer: D

Lung abscess can occur as a complication of CAP, aspiration pneumonia and inhaled foreign body. The diagnosis is made on the history, CXR and CT thorax. Bronchial washings taken at bronchoscopy may be helpful in identifying the organism but will not make the diagnosis of an abscess.