Respiratory

Respiratory Infections

Pneumonia

Introduction

  • Infection of the air spaces of the lung which then contain a purulent exudate
  • Infective agents involve bacterial, viruses and Chlamydia.
  • In all patients there is loss of local aeration of tissue with ventilation/perfusion mismatch and hypoxia
  • Pneumonias are often classified on their setting as this determines the likely organisms and therefore antibiotic therapy.

Types

  • Lobar pneumonia ? infection localised to one lung seen in those with preexisting good health. Classically Strep pneumoniae.
  • Bronchopneumonia where infection is patchy and often bilateral and seen in the elderly and those with coexisting disease.

Pathological stages of classical Pneumococcal disease (prior to antibiotic therapy)

  • Congestion and vascular engorgement and alveolar bacteria
  • Red hepatisation - alveolar spaces full of polymorphous and fibrin and red cells
  • Grey hepatisation - RBC breakdown, fibrin and suppurative inflammation
  • Resolution - exudate removed by macrophages

Different Pneumonias with a different mix of organisms

  • Hospital acquired/ Ventilator acquired ? Gram negatives coliform, MRSA, Streptococcus pneumoniae
  • Community acquired ? Strep pneumoniae, Mycoplasma, Viral, Chlamydia pneumonia, Chlamydia psitacci, Haemophilus influenza, Legionella pneumophila
  • Aspiration ? Anaerobes, Gram negatives
  • Immunosuppressed /HIV patient - Pneumocystis jirovecii

Community acquired Pneumonia

Organisms

  • Streptococcus pneumoniae
    • Cough, fever and rusty sputum and Cold sores due to HSV reactivation.
    • Lobar type distribution.
  • Viral
    • Influenza A and Influenza B, RSV, Rhinoviruses, Adenoviruses
    • Can become secondarily bacterial infected
  • Mycoplasma pneumonia
    • Seen in 3% seen in 3-4 yearly epidemics
    • Erythema nodosum, Erythema multiforme - target lesions, Headache, otalgia, bullous myringitis - painful vesicles seen on Tympanic membrane
    • Meningoencephalitis, cranial nerve, transverse myelitis Guillain-Barré Syndrome
    • Pericarditis and myocarditis, Hepatitis, Pancreatitis, Glomerulonephritis, Lymphadenopathy and splenomegaly
    • Cold agglutinins found in 50%.
  • Chlamydia pneumonia
    • Causes bilateral infiltrates and an atypical picture with cough, fever and a mild pneumonia
    • Check serology acute and convalescent IgM and IgG.
  • Chlamydia psittaci
    • Suspect if exposure to birds
  • Haemophilus influenzae
    • Seen in those with COPD. Often capsulated strains.
  • Legionella pneumophila
    • suspect in those with Recent travel, turkey, Spain
    • Organism grows in air conditioning and humidification systems, car windscreen washers. Hotels, conference centre, institutions. Features include renal failure and delirium.
    • Hyponatraemia, Check serology acute and convalescent IgM and IgG, Urine antigen tests for only one type.
  • Staphylococcal
    • post influenzal. Cavitates, lung abscesses.
  • Pneumocystis jirovecii
    • consider in those with HIV/AIDS

Clinical

  • Fever, sweats, rigors, Confusion, Delirium (elderly and Legionella), Breathlessness, Cyanosis, Tachycardia, Hypotension, Pleuritic type chest pain, Cough, Rusty sputum (Pneumococcus) yellow/green sputum, Haemoptysis, Flare up of herpes simplex (Pneumococcus)
  • Atypical - diarrhoea, myalgia, headache
  • Reduced air entry and expansions and dullness to percussion, Increased vocal resonance, Stony dull if effusion/empyema.

Investigations

  • The CXR changes may lag behind clinical symptoms both in the start of the illness and during recovery
  • A normal CXR early on should not exclude pneumonia.
CURB-65 score  to assesses severity
  • Confusion AMT <8 = 1 point
  • Urea > 7 mmol/l = 1 point
  • Respiratory rate > 30/min = 1 point
  • SBP < 90 and/or DBP < 60 mmHg = 1 point
  • Age > 65 = 1 point
Score 0 = low risk, Score 1-2 = moderate risk, Score 3+ High mortality

Points from CURB-65 : Those scoring
  • 0-1: Likely suitable for home treatment.
  • 2 - Consider hospital supervised treatment by either a short stay in-patient or supervised rapid medical follow up
  • 3 and over should be managed in hospital as severe pneumonia
  • Assess for ICU admission especially if CURB-65 score = 4 or Additional evidence of severity are a WCC > 20 or < 4 or multi lobe involvement on CXR or albumin < 35 g/L, positive blood culture, stroke, COPD, cardiac disease, diabetes

Investigations

  • FBC to look for elevated white cells
  • U&E - Hyponatraemia with legionella
  • Severe pneumonia and sepsis- prerenal failure
  • ESR/CRP ? elevated
  • CXR to look for consolidation, collapse or effusion, empyema or any other lesions.
  • ABG ? Type 1 usually or in some Type 2 respiratory failure.
  • Blood and sputum cultures
  • Cold agglutinins - haemolytic anaemia for Mycoplasma.
  • Urinary antigen for pneumococcal and legionella
  • Acute and convalescent sera for antibodies to Legionella, Mycoplasma, Chlamydia.
  • Special culture and staining if TB suspected

Complications

  • Lung abscess, Pleural/parapneumonic effusion and Empyema, Localised fibrotic changes, Systemic inflammatory response syndrome
  • Respiratory failure, ARDS, Renal failure, Cardiac failure
  • Cerebral abscess, Meningitis, Venous thromboembolism, Death
  • Always ensure a follow up CXR done to exclude any complications and underlying tumours behind the consolidation.

Management ? Always consult local antibiotic policies

  • Mild : Oral Amoxycillin + Erythromycin/Clarithyromycin
  • Severe : IV Amoxycillin + Erythromycin/Clarithyromycin
  • Involve HDU or ITU of needs Ventilatory support but determine functional status first

Hospital acquired Pneumonia

  • Definition
    • Pneumonia that comes on more than 48 hours after admission

    Introduction

    • Patients may be immunocompromised, frail, malnourished, comorbidities, alcoholic, post stroke or in ITU. In ITU often called ventilator associated pneumonia.
  • Organisms
    • Haemophilus influenzae, Streptococcus pneumoniae
    • Staphylococcal aureus, Gram negatives e.g Pseudomonas, Acinebacter, Anaerobes and fungi
    • Legionella Outbreak, MRSA

    Management

    • Local policies should be observed
    • Add Metronidazole 500 mg tds
    • Coamoxiclav + flucloxacillin
  • Aspiration Pneumonia

    Definition

    • The microbiology of aspiration involves anaerobic bacteria as well as a chemical pneumonitis
    • May be due to Strep pneumoniae, coliforms or anaerobes.

    Clinical

    • Breathlessness, CXR changes fever, Falling O2 sats and raised CRP in typical patient unable to protect airway e.g obtunded comatose head injury or stroke patient

    Management

    • Observe local policies for antibiotics.
    • Treatment with Coamoxiclav and some add metronidazole
    • Remember treatment also involves mobilising a patient and getting them out of bed and into a chair will improve lung function and airway protection
    • Chest physiotherapy may also help.

    Lung abscess

    Introduction

    • A cavitating pus filed lesion in the lungs due to infection usually bacterial.

    Clinical

    • Seen in the elderly, immunocompromised, aspiration (right lower lobe), Alcoholics, IV drug users and Shares many features with aspiration pneumonia.

    Infective Causes

    • Staphylococcal aureus post Influenza, Klebsiella pneumoniae
    • Pseudomonas, Mycobacterium tuberculosis
    • Legionella, Gram negatives, Anaerobes (aspiration), Fungi, Parasites
    • Bronchial obstruction e.g tumour or inhaled foreign body

    Differential

    • Squamous Carcinoma, Wegener's' granulomatosis, Pulmonary infarction

    Clinical

    • Fever, cachexia, Cough with foul sputum and halitosis, Weight loss, Finger clubbing, Amoebic abscess - brown sputum

    Investigations

    • FBC - elevated WCC and CRP
    • CXR - there is cavitation with an air fluid level in a thin walled cavity
    • HRCT chest

    Management

    • Postural drainage
    • IV Antibiotics, Drainage by Needle aspiration, Thoracotomy may be needed, Bronchoscopy and removal of foreign body where needed,

    Pneumocystis jirovecii pneumonia

    Introduction

    • Subtle onset of breathlessness in untreated AIDS patient

    Microbiology

    • Pneumocystis jirovecii is a fungus that lacks ergosterol and so it is not susceptible to the usual antifungal drugs
    • Is seen in immunosuppressed patients and those infected with HIV with CD4 < 200 cells/mm3

    Clinical

    • Presentation can be subtle initially
    • May present with progressive breathlessness, high fever
    • Dry cough and hypoxia and bibasal crackles
    • Subtle cases - Walk patient and look for exercise induced drop in O2 sats is a useful early sign
    • May be signs suggestive of HIV infection e.g oral candida
    • Pneumothorax is not uncommon

    Investigations

    • Sputum generation using hypertonic saline and Immunofluorescence of sputum will identify organism
    • Bronchoscopy and lavage may be needed
    • HIV test, CD4 count, Viral load
    • CXR shows interstitial shadowing or may be indeed be normal
    • Elevated lactate dehydrogenase level (LDH).
    • ABG may show Type 1 respiratory failure

    Management

    • If patient very unwell - IV co-trimoxazole for up to 3 weeks
    • Alternatives - IV Pentamidine or Dapsone + Pyrimethamine
    • Systemic steroids given if PaO2 < 9.5 KPa
    • Co-trimoxazole is used as prophylaxis if CD4+ < 200 cells/mm3
    • HAART can be used to improve the CD4 count

    Cystic Fibrosis

    Introduction

    • Chronic suppurative lung disease with other clinical sequelae

    Aetiology

    • CF is inherited as an autosomal recessive and there are at least 1300 gene mutations
    • The commonest is the delta F508 mutation on chromosome 7 which codes for the Cystic fibrosis transmembrane conductance regulator (CFTR)
    • There are many genetic mutations that result in Cystic fibrosis
    • Genotype is a poor guide to disease severity even within families possibly due to unknown modifier genes
    • Incidence in the UK is 1 in 2500.

    Clinical

    • Lungs are normal at birth and damage accumulates with time.
    • Gastrointestinal : Meconium ileus - intestinal obstruction at birth, Meconium ileus equivalent, Intussusception (ileocaecal), or rectal prolapse, Fatty liver and focal biliary cirrhosis, Increased incidence of cholecystitis and gallstones, Malabsorption - Osteoporosis and rickets
    • Reproductive : Failure to develop epididymis and vas deferens with male infertility, female infertility
    • Pulmonary : Bronchitis, bronchiolitis, Bronchiectasis, respiratory failure, Rhinitis and nasal polyps
    • Secondary Diabetes develops in 25% of patients and good nutritional status is linked with a better overall prognosis

    Investigations

    • Sweat test in which the concentration of Sodium and Chloride are measured
    • If two sweat Cl concentration > 60 mEq/L this confirms the diagnosis (The sweat Na is elevated too)
    • Genetic counselling and DNA analysis
    • The vas deferens and epididymis are absent

    Management

    • Ensure optimal nutritional status as this is linked with a better overall prognosis
    • Regular postural drainage and chest physiotherapy to aid expectoration
    • Pulmonary infections - mostly pseudomonas causes most of the morbidity and mortality but also Burkholderia cepacia, Staphylococcus aureus.
    • Aerolised DNAse I (Dornase alpha) appears to reduce chest infections.
    • Severe chest disease - lung or heart lung transplantation have been done
    • Avoidance of other sufferers to avoid exposure to Burkholderia cepacia.
    • Gene therapy may hold benefits in the future.

    Bronchiectasis

    Introduction

    • Chronic, debilitating condition with persistent cough, excessive sputum production and recurrent chest infections.

    Aetiology

    • Pathologically there is abnormal and permanent dilatation of the airways with damage to muscle and bronchioles.
    • Impaired normal processes that predispose to chronic infection
    • May be generalised but can indeed be localized causing abnormal dilatation of the airways and elastic layers predisposing to recurrent infections which then cause more localised damage

    Pathologically

    • Saccular or Tubular and fusiform
    • Ulceration, fibrosis and squamous metaplasia of the chronic infection
    • Pus formation distal to some obstructive lesion such as a tumour, foreign body or enlarged lymph nodes

    Cause of Bronchiectasis

    • 50% are unknown
    • Post infections e.g Tuberculosis, Pertussis, Viral
    • Cystic fibrosis
    • Rheumatoid disease
    • Allergic bronchopulmonary disease
    • Ciliary dysfunction - Kartagener's syndrome - Bronchiectasis + Situs inversus
    • Immunodeficiency syndromes
    • Young's syndrome - Bronchiectasis + Male infertility (palpable enlarged epididymis)

    Clinical

    • Cough with large amounts of expectorant mucoid, mucopurulent or purulent sputum - measure volume over 24 hours
    • Finger clubbing
    • Long term amyloidosis
    • Weight loss, tiredness and malaise
    • Massive haemoptysis may be seen
    • Loud persistent crackles on auscultation

    Investigations

    • FBC and CRP for active infection
    • Test for Low IgG levels in immunodeficiency e.g look for IgA deficiency
    • CXR - tram lines and signet ring shadows
    • HRCT - imaging of choice shows cystic or varicose dilatations often affecting multiple lobes
    • Bronchial wall thickening, mucus plugging and segmental and subsegmental collapse can be seen.
    • Spirometry - often a mixed obstructive/restrictive pattern may be seen
    • Saccharin test may be useful to test if Ciliary function working
    • Ciliary dysfunction syndromes such as Kartagener's syndrome or primary Ciliary dyskinesia are then confirmed using electron microscopy
    • Aspergillus precipitins in those with ABPA
    • Sputum cultures - Haemophilus influenzae, Streptococcus pneumonia, Staphylococcus aureus, Moraxella catarrhalis, Pseudomonas aeruginosa (poorer prognosis)

    Management

    • Postural drainage and chest physiotherapy to aid expectoration
    • Influenza and Pneumococcal vaccines and antibiotics when needed for S pneumoniae and H influenzae infections
    • Smoking cessation
    • Inhaled hyperosmolar agents to aid expectoration (7% hypertonic saline) improves expectoration
    • Inhaled mucolytic e.g recombinant human DNAse though non evidence based
    • Inhaled bronchodilators may be tried to improve dyspnoea
    • Inhaled steroids may be tried to improve dyspnoea
    • Long term antibiotics have had mixed results
    • Surgery in individual selected cases with localised disease

    Aspergilloma

    Introduction

    • Spores of Aspergillus fumigatus seed in a preexisting cavity
    • CXR opacity seen usually in the apices which is partly opaque with a crescent or halo
    • Cavities may develop within distorted fibrotic apical tissue and are sometimes colonized by mycobacteria or fungi
    • Aspergillus fumigatus is isolated in up to 60 per cent of patients with apical cavitation.

    Predisposing diseases that cause cavitation

    • Tuberculosis damage to lungs
    • Suppurative pneumonia
    • Sarcoid
    • Lung abscess
    • Carcinoma
    • Fibrosing alveolitis
    • Ankylosing spondylitis with apical disease
    • Histoplasmosis
    • Bronchiectasis due to ABPA

    Complications

    • Life-threatening haemoptysis is an occasional complication of mycetoma formation within cavities
    • This may be controllable by bronchial artery embolisation or the resection of a mycetoma being a treatment of last resort
    • There is a high prevalence of postoperative bronchopleural fistula and empyema
    • Apical cavitation is associated with ankylosing spondylitis

    Investigations

    • CXR and CT chest
    • Sputum for microscopy and culture and exclude TB

    Management

    • Surgical removal
    • Embolectomy for haemoptysis
    • Itraconazole may have some benefits

    Tuberculosis

    Introduction

    • Worldwide killer. Seen in UK in immigrants and immunosuppressed

    Epidemiology

    • Worldwide infects 2 Billion (95% in developing world) with 3 million deaths per year
    • Sub-Saharan Africans, Bangladeshi, Indian, Pakistan and immigrants from these areas into the UK
    • Homeless, alcohol dependent, immunocompromised, HIV
    • Drug and Multidrug resistant (Rifampicin) TB is a problem

    Microbiology

    • Mycobacterium tuberculosis bacilli are gram positive rods (no cell membrane but have a cell wall with high lipid content)
    • Obligate aerobes growing most successfully in tissues with a high oxygen content, such as the lung apices.
    • They are facultative intracellular pathogens usually infecting mononuclear phagocytes (e.g macrophages) and slow-growing with a generation time of 12 to 18 hours (20-30 minutes for Escherichia coli)
    • Impermeable to the usual stains, e.g Gram's stain and are known as "acid-fast bacilli" because of their lipid-rich cell walls, which are relatively impermeable to various basic dyes unless the dyes are combined with phenol. Once stained, the cells resist decolourisation with acidified organic solvents and are therefore called "acid-fast".

    Pathology

    • TB infection is classed as one of the granulomatous inflammatory conditions. The granulomata contain areas which to the naked eye have the texture of soft white cheese and is so termed Caseous necrosis with later calcification

    Immune response

    • There is a Th1 mediated immunity response which is important for Bactericidal killing, Granuloma formation
    • Caseous necrosis and Protective immunity
    • Requires IL-12 and IFN - gamma.

    Clinical - divided into its stages

    • Primary pulmonary disease is mainly seen in children and adolescents without immunity and in many is asymptomatic
      • Manifests as fever and fatigue and arthralgias, chest pain and pleuritic chest pain - enlarged nodes, erythema nodosum, phlyctenular conjunctivitis, pleural effusion, formation of a Ghon focus with lymph node involvement becoes a Ghon complex, dactylitis
      • CXR - Hilar adenopathy and/or pleural effusion. Right middle lobe collapse may complicate the adenopathy
      • It takes 2-12 weeks for tuberculin testing to become positive. The lesion usually heals with some scarring and calcification and may contain dormant bacteria.
    • Post primary TB is seen some time after primary disease when the dormant bacteria overwhelm immune system
      • There is fever and night sweats, malaise, weight loss and breathless, cough and sputum and usually affects lungs mainly
      • Reactivation or reinfection is seen with - HIV, alcohol, Age, malignancy, alcohol, immunodeficiency, malnutrition, use of immunosuppression, Anti TNF alpha drugs
      • CXR shows upper zone shadowing and cavitation which suggests active lung apex disease. May be fibrosis and calcification and trachea may be displaced with hilar lymphadenopathy.
      • Lymph nodes can be involved which suppurate and forms sinuses and even fistulas. >Most notably cervical nodes can be involved causing scrofula. Mediastinal nodes also commonly affected.
    • Miliary disease
      • A poor inflammatory response leads to widespread dissemination by the blood stream with seeding of many organs including lungs, liver, spleen, bone marrow, brain, spine, eyes. CLinical signs include Hepatosplenomegaly, Choroidal tubercles, TB Meningitis
      • There is malaise, weight loss, fever, night sweats. Occurs in the elderly or malnourished patients
      • CXR shows lesions that look like small millet seeds < 5 mm. False negative tuberculin test.
      • CNS : Meningitis and tuberculoma - Can present with headache, confusion, seizures and personality changes and the CSF shows a raised lymphocyte count and protein levels but smears rarely positive. Tuberculomas can cause symptoms of raised pressure and localising signs and Symptoms of a space occupying lesion
      • Epididymitis, endometrial or tubal involvement and infertility, Adrenal - adrenal insufficiency
      • Bone/Joints - Osteomyelitis , arthritis, paravertebral abscesses, vertebral collapse, Spinal cord compression. Classically Pott's disease of the spine due to TB infection of the vertebrae can cause cord compression and paraplegia or form a cold abscess which can track down to the psoas muscle.
      • Skin - lupus vulgaris and erythema induratum
      • Heart - tuberculous pericardial effusion and constrictive pericarditis

    Investigations

    • FBC, U&E LFT's CRP and ESR may all be abnormal.
    • Sputum direct staining and microscopy of a smear from recently expectorated sputum and culture. Use Auramine or Ziehl Nielson stain and if bacilli seen is "Smear positive" and infectious. Inducing sputum is said to be as effective as Bronchoalveolar lavage
    • Cultures are the gold standard but take 3-6 weeks to grow and then identify species. Other techniques have been developed. DNA analysis using PCR of MTB can be made identifying serotype and drug sensitivity
    • Tuberculin testing - Uses purified protein derivative (PPD) to elicit a delayed type hypersensitivity response which is mediated by T lymphocytes. The reaction is maximal at 2-3 days after inoculation. Positive tuberculin testing does not always suggests active disease. It suggests a prior immune response - previous infection or BCG. So only a grade 3/4 (10 mm induration) or a negative test are useful in those with history of BCG. It is important to elicit a wheal to demonstrate that it is intradermal and not subcutaneous. Most with active TB will have a positive skin test (=10 mm) measure the induration, not erythema. Tuberculin skin tests are not contraindicated in BCG-vaccinated persons and skin test reactivity should be interpreted and treated as for unvaccinated persons. False negatives occur in Immunosuppressed, Steroids, Malnourished, HIV, Severe TB (e.g, Miliary disease) , Early primary disease - Becomes positive 2-12 weeks post primary infection
    • Bronchoscopy and BAL may be useful to get samples in difficult cases when there is un unproductive cough and high clinical suspicion. It may help to exclude other causes such as tumours with a potential for biopsy of abnormal tissue
    • Microbiological culture from - Sputum analysis, Gastric aspirate - used in children, Early morning Urine for suspected renal TB, Bone marrow biopsy, CSF, Liver biopsy, Bronchoalveolar lavage
    • A high level of interferon-gamma production is presumed to be indicative of TB infection using certain testing kits.
    • Consider HIV test in all patients with risk factors
    • ECG/Echocardiogram - pericardial disease shows low voltage and ST-T changes
    • Elevated adenosine deaminase levels have high sensitivity and specificity for tuberculous pericardial disease

    Management

    • Isolate smear positives. It is a notifiable disease. Smear positive patients can be considered not infectious after 2 weeks treatment
    • Patients need to have the extent of their disease assessed and commenced on antituberculous therapy
    • Patients should be treated with 4 drug regimen [RIPE] for 2 months and 2 drug regimen for 4 months. Those with a low chance of resistance then Isoniazid, Rifampicin and Pyrazinamide only many be used [RIP] . RIPE 2 months and then RI 4 months or RIP 2 months and then RI 4 months has a low chance of resistance
    • TB of CNS - Treatment is for 12 months. Resistance to any of the drugs (isoniazid or rifampicin) means a 9 month course. Drugs can all be taken once daily on empty stomach before breakfast. Combination tablets are available
    • First line treatment is safe in pregnancy and breastfeeding women. Multidrug resistance TB is much commoner in HIV patients
    • Compliance is the main barrier to successful treatment and Directly Observed treatment is one of the cornerstones of trying to ensure good drug compliance for the treatment of TB especially in homeless, alcohol, mental illness and MDR TB and those with a history of non compliance
    • Rifampicin turns urine red.
    • Prevention through Vaccination with BCG
    • BCG vaccination in infants gives some protection against serious forms of tuberculosis - indeed - reduces disseminated and tuberculous meningitis
    • Multi-drug resistant tuberculosis - suspect if a previously treated case of Tuberculosis or contact with drug resistant TB or HIV or London residence or male or failed treatment - smear positive after 3 months treatment
    • Steroid therapy may be considered for CNS disease.

    Antituberculous drugs

    • Rifampicin ? Bactericidal, Induces liver enzymes, Red urine and contact lenses
    • Isoniazid ? Bactericidal, Enzyme inhibitor, Hepatitis, Avoid alcohol, Peripheral neuropathy so Give Pyridoxine 10 mg/day
    • Pyrazinamide ? Bactericidal, Increased urate, Liver toxicity
    • Ethambutol ? Bacteriostatic, Optic neuritis, Snellen chart assessment or acuity before starting
    • RIP all cause a hepatitic picture. Stop all drugs if AST x5 normal. Then introduce on a single basis at half dosage and slowly increase
    • Second line drugs - Ethionamide, Streptomycin, Propionamide, Cycloserine