The respiratory system - Lung infections Flashcards
How is cystic fibrosis (CF) inherited?
It is an autosomal dominant - both parents must be carriers for child to have it
What gene is affected in CF?
Mutations to the cystic transmembrane conductance regulator (CFTR) gene on the long arm of chromosome 7
What is the role of the cystic fibrosis transmembrane conductance regulator (CTFR) gene?
The CTFR gene encodes for an epithelial chloride channel regulated by cyclic AMP. This channel help maintain the right balance fluid in the airways.
What is the most common CF mutation
Delta F508
What is the description for the following classes of CFTR mutation:
a) stage I
b) Stage II
c) Stage III
d) Stage IV
e) Stage V
a) No functional CFTR is made
b) Defective protein processing
c) Defective regulation
d) Defective conduction
e) Reduced functional CFTR
Describe the pathogenesis of cystic fibrosis
- Defects in the CTFR gene lead to defects in the normal ion transport
- This result in dehydration of airway surface resulting in mucociliary dysfunction
- This leads to reduced mucus clearance, airway obstruction and predisposition to infection
- Recurrent infection leads to chronic bronchitis, damage to the bronchi and eventually bronchiectasis
What are the clinical features of CF in new-borns
Meconium ileus (a bowel obstruction that occurs when the meconium in a child’s intestine is even thicker and stickier than normal meconium)
What are the clinical features of CF in infants/children
- Pancreatic insufficiency (Failure to thrive)
- Hepatic steatosis (Fatty stools)
- Recurrent chest infections
- failure to thrive
- Rectal prolapse
- Dehydration
- Allergic bronchopulmonary aspergillosis (ABPA)
- Renal calculi
- Distal intestinal obstruction syndrome (DIOS)
- Hyponatraemic hypochloraemic metabolic alkalosis
What are the clinical feature of CF in adolescence/adulthood
- Chronic sinusitis
- Nasal polyps
- Bronchiectasis
- Liver disease
- Steatorrhea
- Constipation
- Distal intestinal obstruction syndrome (DIOS)
- Male infertility
- Arthritis/arthralgia
- Delayed puberty, Osteoporosis
- Finger clubbing
- Gallstons
- Pancreatic insufficiency
- Pancreatitis
- Diabetes
- Renal calculi, renal failure
Exacerbation of pulmonary infections in patients with cystic fibrosis
a) Symptoms
b) Signs
a)
- Increased frequency and duration of cough
- Increased sputum production
- Change in appearance of sputum
- Increased SOB
- Decreased exercise tolerance
- Decreased appetite
- Feeling of increased congestion in the chest
b)
- Increased respiratory rate
- Use of accessory muscles for breathing
- Intercostal retractions
- Change in results of auscultatory examination of chest
- Decline in measures of pulmonary function consistent with presence of obstructive airway disease
- Fever and leukocytosis
- Weight loss
- New infiltrate on chest radiograph
Describe the 4 common clinical manifestations of cystic fibrosis
Respiratory disease
- Most common
- Persistent, daily, productive cough
- Recurrent infections result in bronchiectasis
- Complications: cor pulmonale, haemoptysis and pneumothorax
Pancreatic disease
- CF-related disease
- Fatty stools
- Malabsorption
Gastrointestinal disease
- Most common cause of meconium ileum in infants
- Constipation
- Distal intestinal obstruction syndrome (DIOS))
Malignancies
- Increased risk of GI malignancies
Why do CF patients get fatty stools and malabsorption?
Thick secretions block the outflow of exocrine digestive enzymes leading to insufficiency with fatty stools and malabsorption
Describe the screening of CF in the UK
CF is screened for as part of new-born heel prick test
Conducted at day 5 after birth
Give 3 tests that can be used to diagnose CF
Heel prick test (detects immunological-reactive trypsin)
Sweat test
Genetic testing
What are the diagnostic result of the sweat test in CF?
Sodium chloride of > 60 mmol/L is diagnostic
Describe the CXR changes in CF
Hyperinflation
Reticulonodular shadowing
Collapse/atelectasis
Bronchiectasis
Describe the management of pulmonary disease in CF
Conventional
- airway clearance techniques
- Chest physiotherapy
Pharmacological (Mucoactive agents)
1. rhDNase - 1st line and given via nebuliser
2. Hypertonic sodium chloride - may be used alone or with rhDNase. Given via nebuliser
3. Mannitol dry power inhalation - used in patients intolerant, ineligible or not responding to rhDNase. It is inhaled
Pulmonary infection
- Prophylactic antibiotics/antifungal + steroids e.g., ABPA
Lung transplantation
- Can be considered in patients with progressive respiratory failure and usually both lungs
How are CF patients with new infections (psudeomonas aeruginosa) treated?
Treat with eradication therapy with oral/IV antibiotics and inhaled antibiotics.
If clinically unwell then only IV and inhaled antibiotics used
What antibitoic can be offered in CF children from age 3-6 years?
Oral flucloxacillin
Describe the management of nutrition and pancreatic insufficiency in CF
Nutrition
- Nutritional assessment and reviews offered with a specialist dietician
- If wight loss/inadequate weight gain increase portion size + eat high-energy foods. Nutritional supplements can be considered if unsuccessful
- Ongoing deficit may need enteral feeding or trial of oral appetite stimulant
Pancreatic insufficiency
- Oral pancreatic enzyme replacement (e.g., CREON)
Describe the management of liver disease in CF
- Patients screen regularly
- Ursodeoxycholic acid can be given
- Transplantation: may be indicated in those with liver failure (completed alone or as a liver-lung or liver-pancreas transplant)
Describe the management of CF-related diabetes
- Should be screened annually from age of 10 and at any times where symptoms are suggestive
- Treat diabetes e.g., insulin
.Several new therapies for the management of cystic fibrosis known as CFTR modulators have been approved for use in the UK.
a) Describe their mechanism of action
b) Name the 4 drugs available in the UK
a) Target the underlying mechanism in cystic fibrosis
b) Kalydaco, Orkambi, Symkevi and Kaftrio
What is bronchiectasis?
Bronchiectasis is the irreversible and abnormal dilatation of the airways
Describe the epidemiology of bronchiectasis
- Females are more affected than males
- Prevalence increases with age
Describe the pathophysiology of bronchiectasis
Normally results from the inflammatory destruction of the elastic and muscular components of thew airways
This leads to abnormally dilated airways, persistent sputum productive with insufficient clearance and current chest infections
Describe the aetiology of bronchiectasis
Immunodeficiency (predisposed patients ot infection
- Primary: IgA and ig deficiency
- Secondary: HIV, malignancy
Mechanical obstruction
- Foreign bodies, mucus plugging, stenosis, tumours or lymph nodes
Mucociilary cleareance dysfunction
- CF
- Primary ciliary dyskinesia (autosomal recessive pattern, characterised by immotile cilia often resulting in recurrent infections and bronchiectasis)
- Young syndrome (characterised by male infertility, sinusitis and bronchiectasis)
Congenital airways defects
- Williams-Campbell syndrome: a rare disease characterised by defective cartilage in the airways resulting bronchiectasis
- Mounier-Kuhn syndrome: also termed tracheobronchomegaly, it is a rare disease characterised by dilatation of the trachea itself as well as the bronchi
Other causes - RhA, ABPA, COPD, inflammorty bowel disease
Clinical features of CF
a) Symptoms
b) Signs
a)
- Persistent sputum production
- Persistent cough
- Haemoptysis
- Weight loss
b)
- Crackles
- High pitched inspiratory squeaks
- Wheeze
- Clubbing (rare)
The clinical course of bronchiectasis may be interrupted by acute infective exacerbations.
What are the clinical features of an acute infective exacerbation?
Worsening of chronic features (dyspnoea, cough and sputum production)
Systemic infection features e.g., fever, malaise
Describe the investigations for bronchiectasis
Bloods - FBC, renal function, serum immunoglobulines
Cultures - sputum cultures, blood culture
Asperigullis fumigates - serum total IgE, sensitisation assessment (specific IgE or skin prick test)
Other
- In patterns with features of arthritis, vasculitis or CTD: RF, anti-CCP, ANA and ANCA
- Bronchoscopy
- Tets for primary ciliary dyskinesia
- Spirometry - decreased FEV1/FVC ratio
Imaging for bronchiectasis
a) 1st line
b) Diagnostic modality
a) CXR
b) High-resolution CT - diagnostic modality of choice
High resolution CT changes of bronchiectasis
Thickened bronchial walls
Tram-track/tram-line airways
Ring shadows
Describe the management of bronchiectasis
Conservative
- Airway clearance techniques
- chest physiotherapy
- Patient education
- Support group
- Smoking cessation
Medical
1. Mucoactives - Isotonic and hypertonic saline, Oral carbocisteine, (recombinant human DNase not recommended in adults with bronchiectasis)
2. Prophylactic antibiotics (treatment depends on whether or not the patient is colonised by P. aeruginosa)
3. Bronchodilators - used in patients with coexisting asthma/COPD/ABPA or in those wit significant breathlessness
Surgery
- Lung resection
- Lung transplant
What are the indications of lung transplant in bronchiectasis
Patients aged 65 or younger, with an FEV1 < 30% and clinical instability or rapidly deteriorating lung function despite medical intervention
Patients with recurrent exacerbations despite education, treatment of underlying cause, physiotherapy (+/- mucoactives) should be considered for long-term antibiotics.
Treatment depends on whether or not the patient is colonised by P. aeruginosa. What is the treatment if:
a) P.aeruginosa colonised
b) Non-P.aeruginosa colonised
a)
1st line - Colisistn and gentamicin
2nd line - Oral azithromycin or erythromycin (considered in those who don’t tolerate inhaled therapy or in addition to inhaled therapy where it is ineffective)
b)
1st line - Azithromycin or erythromycin
2nd line - Inhaled gentamicin can be considered second line.
Describe the complications of bronchiectasis
- Infective exacerbation
- Chronic respiratory failure
- Haemoptysis
- Cor pulmonale
- Pneumothorax
- Chest bag
What is Pneumonia?
Inflammation of the parenchyma of the lung
Describe the pathophysiology of pneumonia
- Infection the lung (e.g., bacteria, virus)
- Inflammatory response initiated
- Alveolar oedema + exudate formation
3.Alveoli and respiratory bronchioles fill with serous exudate, blood cells, fibrin, bacteria - Consolidation of lung tissues
Pneumonia
a) Symptoms
b) Signs
a)
- Fever
- Malaise
- Productive cough
- Dyspnoea
- Pleuritic pain
- Haemoptysis
- Rigors
b)
- Dull percussion
- Reduced breath sounds
- Bronchial breathing
- Coase crepitaitons
- Increased tactile vocal fremitus
- Tachycardia
- Pyrexia
- Hypotension
- Confusion
- Cyanosis
- Pleural rub
Name the 3 classifications of penumonia
Community acquired
Hospital acquired
Immuno-compromised
Name 5 typical bacterial/viral pathogen of community acquired pneumonia
- Streptococcus pneumoniae (most common)
- Haemophilus influenza
- Moraxella catarrhalis
- Influenza-Staph.A super infection
- Respiratory viruses
Name 6 atypical bacterial/viral pathogens
- Chlamydophila psittaci
- Coxiella burnetii - Q fever
- Mycoplasma pneumonia
- Legionnaires disease
- Mycobacterium tuberculosis
- Pneumocystis jirovecii
How can bacterial pneumonia and viral pneumonia be differentiated?
Bacterial pneumonia - sudden onset of symptoms and rapid illness progression
Viral pneumonia - slow onset of URTI and wheezing
Describe the treatment of community acquired pneumonia
Penicillin (Amoxicillin, Tazobactam) pLUS macrolied (Clarithomycine)
Antivirals e.g., oseltamivir for 7 days (but within 3-5 days of symptoms)
Describe the prevention of community acquired pneumonia
Smoking cessation
Vaccines
What is hospital acquired pneumonia defined by NICE?
HAP is defined by NICE as a contracted > 48 hours after hospital admission that was not incubating at the time of admission