1

Cystic fibrosis –the most common, life-threatening, autosomal

recessive disease in caucasian population
Incidence-1/2500
Carrier frequency – 4%
CF –is a complex multysistem disease caused by defects in a single
gene
The abnormal gene- on the long arm of chromosome 7,was identified
in 1989
Birth prevalence – varies from country to country and with etnic
background

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CF – occurs – 1: 2500 white Americans
- 1: 4000 – 10 000 Hispanic Americans
- 1 :15 000 – 20 000 African Americans

Over 2000 CFTR mutation have been described

The most common mutation is a deletion of three base pairs encoding

phenylalanine at position 508, known as Phe508 del( Phe =
phenylalanine , del = deletion)
There are another 23 relatively common mutations worldwide and a
few mutation with an unusually high frequency in specific
populations indicating founder effect genetic drift

Worldwide no single mutation other than F508 del occurs in a

frequency greater than approximately 5%.

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 Many patient – will be compound heterozygotes(one copy of
F508del + one other mutation)
 Heterozygotes carry one normal + one mutant CF gene

 They are healthy/ but they have a 50% risk of passing the defective
gene on to their offspring

 If 2 partners are carriers they have

- a 25% risk of having a child with CF
- a 50% chance that the child will carry only one of the 2
parental mutations
- a 25% chance that the child will inherit 2 intact genes

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 The gene product , called : Cystic Fibrosis Transmembrane
Regulator (CFTR) is localised to the apical cell membrane

 The protein CFTR comprises 1480 aminoacids

 CFTR is a transmembrane chloride conductance channel which

regulates chloride ion and water movements across the cell
membrane
 CFTR is expressed throughout the body , CF disease affects
multiple systems, including major effect on the lung, pancreas
and gastrointestinal system
 CFTR in a sweat glands is normally responsible for chloride and
hence sodium, reabsorption – in CF IT IS THE FAILURE OF THIS
MECHANISMS – EXCESSIVE EXCRETION OF SALT – SALTY
TASTE

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 Five (six) different classes of mutation are recognised

 Different classes of gene mutation – lead to different types of

abnormality in the CFTR protein :
1. Defective CFTR production
2. Defective CFTR processing within the cytoplasm
3. Defective regulation
4. Defective ion conduction

These may be associated with different degrees of functional

compromise in CFTR
 Certain mutations are associated with enough residual CFTR
activity to allow for normal pancreatic function / patient with
pancreatic sufficiency tend to have a milder pulmonary disease

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CFTR – is expressed in epithelia throughout the body
- affects exocrine ( secretory) function in a number of organs
 Lung

 Liver

 Gut

 Pancreas

 Sweat glands

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CF is a multisystem disorder that primarly affects the :

1. Respiratory tract
2. Gastrointestinal tract
3. Sweat glands
4. Reproductive tract

The most common features leading to evaluation and diagnosis were:

▪ Respiratory symptoms
▪ Malnutrition/failure to thrive
▪ Steatorrhea/abnormal stools
▪ Meconium ileus

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Most patients with CF have the classic TRIAD of:
1. Lung disease
2. Pancreatic insufficiency
3. High sweat chloride

A number of people have milder problems possibly associated with

CFTR disfunction
1. Male infertility
2. Recurrent pancreatitis
3. Primary sclerosing cholangitis
4. Chronic sinusitis
Patients having characteristics suggestive of atypical CF- should
have CFTR mutation analysis performed

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There are several hypothesis – CFTR dysfunction leads to the
phenotypic disease known as Cystic Fibrosis
The most well- accepted is the so-called „low volume hypothesis“
CFTR dysfunction leads to excessive reabsorbtion of sodium and
deficient chloride secretion ,along with passive movement of
water → dehydration of airway surface materials and low airway
surface water volume
Reduced volume of the airway surface liquid causes - failure of
mucociliary clearance → mucus obstruction of the small
airways
The lungs are not able to effectively clear inhaled bacteria , viruses,
fungi, airborne polluants

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 CF LUNG DISEASE
 Chronic bacterial endobronchial infection –is associated with an
intense neutrophilic inflammatory response that - damages the
airway -impairs local host defence mechanisms - faclitates further
infection
Infection and inflammation are detected by bronchoalveolar lavage – a
person with CF will have up to 10 times more inflammation than a
person with a lower respiratory tract inf without disease
CT scans – show the presence of structural airway wall changes
including : -thickened airway walls
- narrowed airway lumen
- air trapping
- bronchiectasis

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 CF LUNG DISEASE
 the„ vicious cycle“ – infection – inflammation - tissue destruction
→bronchiectasis – respiratory failure
 Once present, bronchiectasis persist and is progressive

 Lung function – has been shown to be diminished in infants with CF

 Lung function – decline over time throughout life

 Pulmonary insufficiency is responsible for at least 80% of CF related

deaths

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CFTR - dysfunction

Dehydrated airway surface liquid

Impaired mucociliary clearance

Airway obstruction

Bacterial infection

Neutrophilic inflammation / tissue destruction / bronchiectasis

Respiratory failure

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outside of the airway – abnormalities ion transport lead to

1. - excessive salt content of the sweat

2. - decreased water in pancreatic and male reproductive tract
secretions leading to ductal obstruction with:
- pancreatic insuffiency( PI)
- congenital bilateral absence of the vas
deferens(ABVD)

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 CF LUNG DISEASE – BEGINS EARLY IN LIFE- even in infants
diagnosed through newborn screening
- Is characterized by impaired mucociliary clearance and mucus
obstruction → chronic pulmonary infection and inflammation

 The lungs of children with CF appear normal at birth –quickly

become infected by organisms that are not adequately cleared
 -Staphylococcus aureus
 -Haemophilus influenzae( nontypable)
 -Gram negative bacili
 -Pseudomonas aeruginosa – is the predominant pathogen,
ussually after 3 years age

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 Pulmonary manifestations of the disease appear throughout life with
a great variability
 Upper respiratory tract disease
- chronic sinusitis/is universal in children with CF
- extensive polyposis
 Chronic airway infection – is typically established within the first
year of life; it can be controlled but not eradicated
 Chronic bronchitis progressing to obstructive lung disease and
bronchiectasis is the hallmark of CF lung disease
 Recurrent cough, tachypnea, wheeze → the main clinical signs of
CF lung disease in early stages

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 Infants – do not have more often respiratory virus infections / but the
course of viral infections can be severe (VSR)
 In the first months of life – gastrointestinal symptoms are
predominant (meconium ileus, fatty stools, failure thrive, PI)
 Some children remain asymptomatic for long periods/have only
prolonged acute respiratory infections
 Others have - chronic cough within the first weeks of life
- repeated pneumonias
 Older children – have a persistent moist cough and sputum
production
- expectorated mucus – is usually purulent !!

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 late clinical findings – include
- increased anteroposterior diameter of the chest
- localised or scattered crackles
- digital clubbing
- exercise intolerance/shortness of breath are noted

 Chest radiograph abnormalities:

- infiltrates
- atelectatsis
- bronchiectasis

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Pulmonary exacerbation of CF:
 Increased cough
 Change in sputum colour or quantity
 Decreased appetite or weight
 Change in respiratory rate
 Presence of new wheezes/crackles on ascultation of the chest

Respiratory complication
 Lobar atelectasis – may be asymptomatic
 Allergic bronchopulmonary aspergillosis (ABPA)
 airway infection with Burkholderia cepacia, non-tuberculous
mycobacteria (Mycobacteruim abscesus, M. Avium complex) – rapid
pulmonary deterioration/death

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 Hemoptysis + Pneumothorax – complications in advanced lung
disease
 Acute respiratory failure – resulte of a severe viral illness
 Chronic respiratory failure - slow deterioration of lung function
 Chronic right – sided heart failure (cor pulmonale) – seen in CF
patients with advanced pulmonary disease, especially with severe
hypoxemia

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EXTRAPULMONARY MANIFESTATIONS OF CF
 Exocrine pancreatic insufficiency (PI)
- is present in 85-90% of patients- usually present at birth / may
evolve during the first year of life
- is due to obstruction of intrapancreatic ducts with thickened
secretions
- symptoms: pale, oily, stools(steatorrhea); abdominal pain;
flatulence,poor weight gain
- maldigestion /malabsorbtion – secondary PI with
reduced bicarbonate secretion and decrease in enzyme
secretion (lypase, amylase, tryptase)
- fat – soluble vitamins A,D,E,K – defficiency-which
determine:acrodermatitis, anemia, night blindness, osteoporosis,
bleeding disorders

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GASTROINTESTINAL COMPLICATIONS

In CF the three maine ganstrointestinal functions are inpaired:

digestion, absorbtion, motility

Other luminal factor

-excessive mucus production with abnormal composition
- gut motility is impaired;
- small intestine bacterial overgrowth;
- chronic gut inflammation;
- gut lumen dehidration

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PANCREATIC EXOCRINE AND EXTRAHEPATIC BILIARY
COMPLICATIOS
 PANCREATITIS( recurrent acute or chronic)- occurs in in up to 20%
of pancreatic sufficient patients carrying at least one mild
mutation(clsIV, V)
- is common in adolescents and adults
- abdominal pain, vomiting ,increased amylase and lipase levels(or
normal)
 Gallstones with cholesterol and calcium bilirubinate ( consequence
of chronic bile salt loss and enhanced unconjugated bilirubin in the
colon impairing colonic reabsorbtion)

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GUT MANIFESTATIONS
Meconium ileus – the earliest CF clinical manifestation occuring in up
to 20% of CF newborns
- is secondary to abnormal viscous meconium in the small and large
bowels
-diagnosis can be made – US in utero in second trimester-
polyhydramnios with a dilated , hyperecogenic fetal bowel !
- symptoms: distension, bilious vomiting, failure to pass the
meconium within 48 h of birth
- complicated with peritonitis, volvulus, intestinal atresia- emergency

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 GUT MANIFESTATIONS
Meconium plug syndrome – abnormal meconium accumulation
located in colon
- mild abdominal distension, failure to pass meconium
- 25% of patients present underlying CF
Gastroesophageal reflux (GER)
-is very frequent in CF
- Is a consequence of respiratory disease but there is no corelation
between GER and lung disease severity
- transient lower esophageal relaxation, thoracic distension, coughing
,malnutrition, delayed gastric emptying, postural drainage head-
down

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 GUT MANIFESTATIONS (GER)
- pyrosis, nocturnal cough,vomiting, abdoninal epigastric pain,
dysphagia, unexplained pulmonary deterioration
- May affect both-respiratory function and nutritional status

Distal intestinal obstruction syndrome(DIOS)

- Specific to CF
- Common complication in adolescents and adults
- Accumulation of viscid fecal material in the terminal ileum and/ or
right colon
- Risk of reccurence
- Occurs in CF+ PI or in CF+ PS

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 GUT MANIFESTATIONS
Acute appendicitis- is less common in CF patients;a high rate of
perforation and abscess related to subacute presentation( delayed
diagnosis as a consequence of frequent antibiotic prescriptions)
Fibrosing colonopathy-
- Acute abdominal pain, diarrhea , partial to complete abdominal
obstruction
- Investigation- contrast enema
- Laparotomy with right hemicolectomy
- Strong association between fibrosing colonopathy and excessive
PERT supplementation( ˃ 10 000ui/kg/day)

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 GUT MANIFESTATIONS
Rectal prolapse – occurs mainly in preschool age
- may be a presenting feature of CF / complication of malnutrition

Comorbid gastrointestinal condition

 Milk intolerance –occurs more often in CF
- diarrhea, constipation,vomiting, eczema, failure to thrive
- IgE levels, specific IgE, prick tests may be helpful
 Celliac disease –has a prevalence of 1,2% , higher than in the
general population
- Chronic diarhea, abdominal pain despite adequate PERT
- Antiendomisium ,antitransglutaminase antibodies , duodenal biopsy
 Crohn s disease; risk of digestive tract cancer

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- CF-RELATED LIVER DISEASE(CFLD)

 27-35% develop some sort of liver involvement, 5-10% will develop

multilobular cirrhosis(MLC) with portal hypertension (PHT)
- Only patients with 2 severe mutation(cls I – III) and PI
- Missing CFTR – obstruction of the small intrahepatic bile ducts/ retention
of toxic substances – focal biliary cirrhosis- the most common
histological feature in CFLD
- Focal biliary cirrhosis slowly develops - MLC
 Neonatal hyperbilirubinemia
 Steatosis – differing degrees – related to nutritional deficiencies

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CF- RELATED DIABETES- CFRD

 The prevalence increased with age, ˂ 3% at age of 10 years, 25-30% at

35-40years
 CFRD –mimics some aspects of type 1 and type 2 diabetes
 It is a insulino deficient status with some remaining insulin
secretion
 Is associated with a faster decrease in lung function, weight
loss,reduced survival
 IT IS DIFICULT TO DIAGNOSE AT AN EARLY STAGE
 There is no simple laboratory test to screen for CFRD, HbA1C as a single
laboratory marker will miss 30% of all patient CF + CFRD

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CFRD
 The oral glucose tolerance test is the gold standard for
diagnosis / annual OCTT for screening
 Positive clinical effect with insulin treatment – an increase in lung
function , decreasing risk of exacerbation
 Nutritional advice – CF patients have to maintain a high caloric
intake not to lose weight
 Late complication – microvascular –retinopathy, neuropathy,
nephropathy / but are not describes macrovascular disease
 Ketoacidosis is untypical in CFRD

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NUTRITIONAL STATUS
 Maintaining adequate nutritional status is a cornerstone of the
CF multidisciplinary approach
 Nutritional status is strongly associated with pulmonary function and
survival
 Nutritional management should be started as soon as possible after
diagnosis
 Height, weight, BMI
 PI (PANCREATIC INSUFFICIENCY) should be confirmed-
steatorrhea + / fecal elastase-1 ↓ → PERT should be started
 Fat soluble vitamins need to be given in association with
pancreatic enzymes in PI patients

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NUTRITIONAL STATUS
 Energy for infants with CF – 110 – 150% of the recommended daily
allowance(RDA)
 Additional calories – carbohydrate up to 10-12 g/100ml and fat
density 5g/100 ml – can be added to expressed breast formula or
infant formula can be concentrated rather than increasing milk
volumes
 Protein Hydrolysate formulas – small bowel resection for MI
- severe failure to thrive
- co-existing cow s milk protein intolerance
 Dietary fat intake is considered adequate at 50% of total energy
intake(˂ 6 months), between 40 – 50% in older patients

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 Protein needs – may be higher than normal
 Sodium supplementation – hot climates, fever, sport activity
 Adolescence – need increased energy requirements related to rapid
phhysical growth
 Patients CFRD – to continue eating a diet rich in energy and fat
 PERT –pancreatic enzyme replacement therapy – not exceeding
a daily dose of 10000iu lipase /kg/day
 - 2500-3000uilipase per 120ml breast milk / formula
 - 500 – 2500 ui lipase / kg/ meal or 500 – 4000iu lipase per
gram fat

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Diagnosing is based on
– one or more typical phenotypic features
- a history of CF in a sibling or
- positive newborn screening results
- laboratory confirmation of CFTR disfunction and/ or identification
of two CF causing mutations

The diagnosis of CF will be confirmed by measurement of sweat

chloride concentration using quantitative pilocarpine
iontophoresis – which measures chloride transport through the
CFTR channel
A positive result - ˃ 60 mmol /l Cl – should be confirmed with a second
test + CFTR analysis

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SWEAT CHLORIDE LEVELS

 ˂ 40 mmol/l
Generally not considered consistent with a diagnosis of CF
 40- 60 mmol/l
Considered borderline – require further evaluation; may be associated
with pancreatic sufficient disease / or may develop into clinical CF
over time
 ˃ 60 mmol/l
Consistent with diagnosis of CF

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CLINICAL FEATURES CONSISTENT WITH A CF DIAGNOSIS

SINOPULMONARY DISEASE

 Chronic cough or sputum production

Wheeze
Finger clubbing
Nasal polyposis or chronic sinusitis
Culture of chararacteristic CF organism
eg Pseudomonas aeruginosa in sputum ; "staph" empyema

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CLINICAL FEATURES CONSISTENT WITH A CF DIAGNOSIS
GASTROINTESTINAL SIGNS
Intestinal – Meconium ileus, rectal prolapse, DIOS
Pancreatic – Pancreatic insufficiency, pancreatitis
Hepatic – Focal biliary cirrhosis, prolonged neonatal jaundice
NUTRITIONAL AND SALT-LOSS SEQUELAE
Failure to thrive
Acute salt loss
Pseudo-Bartter syndrome, chronic metabolic alkalosis
Hypoproteinemia-edema syndrome
Kwashiorkor-like disease with skin changes
Vitamin K deficiency
OBSTRUCTIVE AZOOSPERMIA
Bilateral absence of the vas deferens

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Investigations
Standard investigations should include:
 Cough swab
 CXR – bronchial wall thickening and hyperflation
 Sweat test
 Serum immune – reactive trypsin (IRT) can be useful in neonates

Immune – reactive trypsin

IRT – present in blood is an indication of pancreatic injury and is high
in neonates with CF
- high IRT (˃99,5th percentile for the population) is found in 98%
of infants with CF
- IRT falls rapidly over the first few weeks of life – if a second IRT
is also high the posibility of CF is increase

- Newborn screening
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Newborn screening
▪ Several different screening protocols are used; most used an
elevated IRT measured on blood spot taken at 5-7 days of age
▪ If IRT is high – genetic analysis – detection of 2 disease – causing
mutations → sweat test
▪ In UK infants with a high initial IRT + one identified mutation will
have a second IRT test - if the IRT is high → sweat test
- if this is below the cut- off level, the infant
is said to be screen – negative
▪ Programmes differ / no screening programme will identify all
children with CF
▪ A negative result does not exclude CF in a child who presents with
likely symptoms

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Additional investigations
▪ Fecal pancreatic elastase
- level ˂ 200 micrograms/g – suggest pancreatic insufficiency
▪ Chest – CT scan – to look for evidence of bronchiectasis
▪ Nasal potential difference – only in a few specialist centres
- CF patients have a higher nasal potential difference than non
CF subjects
▪ Genetic analysis
- standard testing for the commonest 32 mutations – can be used as
a diagnostic test and will confirm the diagnosis in 70% of patients
- two disease – causing mutations
- with newer sequencing methods it is now posible to screen all of
the coding regions and most the splicing regions of the CFTR gene

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a) b)
▪Early onset ▪Chronic obstructive
▪Chronic obstructive respiratory disease
respiratory disease ▪exocrine pancreatic
▪ Exocrine pancreatic insufficiency
insufficiency ▪Male infertility
▪ male infertility ▪Sweat test positive
▪Sweat test positive

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c) d)
▪Chronic obstructive ▪Male infertility
respiratory disease
▪ pancreatic sufficiency
▪Male infertility
▪Sweat test normal

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 Diagnosis is most common in those with recurrent respiratory
infection and poor weight gain in the first year of life

 CF is a clinical diagn ,supported by an abnormal sweat chloride

level on sweat testing

 Genetic analysis may help confirm a diagn of CF / a very large

number of mutation now identified make some genotype /
phenotype relationship difficult to predict

 Newborn screening programmes generaly test for raised immune

reactive trypsin on blood taken within the first week of life + test for
CF gene mutation – if IRT is elevated

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Blood samples
- full blood count
- urea & electrolytes. Calcium, magnesium and phosphate
- random blood glucose & glucose tolerance, HgbA1c
- liver function test
- total IgE, specific IgE to spergillus & aspergillus precipitins
- other immunoglobulinis: IgG, IgA, IgM
- vitamin A, D, E and K
- pseudomonas antibodies
Pulmonary function
- spirometry +/- reversibility to bronchidilatator
- lung volumes
- transfer factor
- SpO2 on air

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Exercise tolerance
- measure of exercise tolerance (i.e. 6 minute walk or 3 minute step
test)
Respiratory review
- change in symptom frequency over past year (cough, respiratory
exacerbation, perception of breathlessness)
- number, frequency and type of antibiotic courses
- sputum frequency, volume and colour
- evidence of haemoptysis
Microbiology review
- type of organism, frequency of occurrence, change in sensitivity
patterns
- culture for detection of unusual pathogens (aspergillus and
mycobacteria)

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GI/nutrition review

- height and weight , BMI

- review of dietary intake with food diary
- review of dose and frecuency of pancreatic enzyme supplements
- liver ultrasound (annually if abnormal liver function tests or as
clinically indicated)
- bone densiometry every 3 years from early teens
- 72 h stool fat collection

Psychology & social review

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ASSESMENT OF PATIENT
 Full clinical exam( evidence of increased respiratory effort
,retractions,use of accessory muscles, temperature,increased
respiratory rate, oxygen saturations)
 Sputum microbiology / cough swab(if not producing sputum)
 Spirometry(fall in FEV1 by ˃ 10% over usual baseline)
 Blood tests,including full blood count,electrolytes,CRP, liver function,
blood glucose
 Chest X-ray if suspected: pneumotorax, consolidation, lung
collapse, failure to respond to therapy,disproportionat hypoxia

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PULMONARY THERAPIES
 Airway infection and inflammation – begin in the first year of life,
often in the absence of any signs or symptoms.
 A number of preventive and aggresive therapeutic strategies
slows the progression of symptomatic lung disease
 BRONCHIAL OBSTRUCTION
1. Airway clearance augmentation techniques(ACT) – modalities
used by patients to augment clearance of airway secretions:
- percussion and postural drainage
- positive expiratory pressure (PEP) devices
- high-frequency chest wall oscillation devices
- controlled breathing techniques- autogenic drainage, active
cycle of breathing

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 Guidelines recommend the use of twice daily ACT for all patients,
beginning in infancy
 Exercise – aerobic, anaerobic exercise improve quality of life, may
stabilize lung function
 Exercise should complement not suppleant ACT
 Bronchodilators –recommended by the CFF consensus guideline
on pulmonary therapies for patients who demonstrate a response on
pulmonary function testing
 Dornase alfa(recombinant human DNAse, Pulmozyme)
- Breaks down extracellular DNA, improving mucus clearability
- Reduction in the rate of pulmonary exacerbations
- Improved lung function
- Decrease viscoelasticity in the sputum

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 Hypertonic saline –6- 7% , acting as an hyperosmolar agent
,rehydrating the periciliary layer, improving mucociliary clearance;
twice daily
 Inhaled antibiotics – for patients who have chronic persistent
airway infection with Pseudomonas aeruginosa(prophylactic)
- aersolized antibiotics achieve high concentration in the airway
- tobramycin, colistin, aztreonam
- Aerosols do not penetrate into airway that are obstructed – are
probably less efective during pulmonary exacerbations

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 PULMONARY EXACERBATION – TREATMENT
 Antibiotics are the mainstay of therapy against pulmonary
infection
1. Antibiotics – oral, i.v, inhaled
2. Increased use of airway clearance technique
3. Improved nutrition
- i.v antibiotics are indicated in respiratory exacerbations not
responding to oral antib
- Part of the Pseudomonas aeruginosa eradication protocol
- Regular 3-monthly i.v treatment – for some children with persistent
symptoms
- In vitro sensitivity testing should be performed to guide the choice
of antib, although it does not always reflect bacterial susceptibility
to antib in vivo

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 Should always use a combination of 2 antibiotics to avoid the
development resistance
 First line therapy – aminoglycoside + antipseudomonal
cephalosporine(ceftazidime)
 High dose are needed to be effective (increased renal
clearance , high concentrations of antibiotic in the sputum)
 i.v. courses are usually for a minimum of 2weeks and may be
extended
 i.v antibiotics can given at home by family members, either via a
peripheral long line or using a Portacath device

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FIRST INFECTION WITH PSEUDOMONAS
 PA (Pseudomonas Aeruginosa)–initially grows in a nonmucoid form
that can be eradicated by agressive antibiotic treatment
 Tobramycin nebulisation – 1 month- first line of treatment
 Other treatments protocol include oral, inhalation and i.v antib
 Over time PA builds colonies – synthesise an alginate coat and
forms biofilms – difficult/ imposible to eradicate
 If there is chronic infection with PA – maintenance treatment with
chronic supressive antib – 1 month on 1 month off inhalation of
tobramycin ; continuous inhaled colistin

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 ANTIINFLAMMATORY TREATMENT

- AZITHROMYCIN – for antibacterial + antiinflammatory effect

(alternate day , 3 day/week)
- ORAL HIGH DOSE IBUPROFEN – has been shown to slow disease
progression- unfavorabe side-effects !
- SYSTEMIC CORTICOSTEROIDS – in ABPA (aspergillosis
bronchopulmonar y allergie ), severe obstruction with respiratory
failure – with important side effect !
- INHALED CORTICOSTEROIDS – if the patient has concomitant
asthma/ airway reactivity

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INFECTION

- Staphylococcus aureus
- Haemophilus influenzae
- Pseudomonas aeruginosa
- MRSA

- A.fumigatus
- Burkholderia cepacia complex
- Stenotrophomonas maltophilia, Achromobacter xyloxidans,
- Non-tuberculous mycobacteria(M.abscessus, M,avium complex)

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STAFILOCOCCUS AUREUS
- prophilactic: Flucloxacilin
- Infection treatment: iv, 2 antibiotics, 14-21 zile (cefuroxime,
gentamicin, clindamicin, teicoplanin, vancomocina, linezolid)

HAEMOPHILUS INFLUENZAE
- cephaclor, cefuroxime, ceftriaxona, cefotaxim, amoxicillin-
clavulanat iv/po 7-14 zile

PSEUDOMONAS AERUGINOSA
- Acute infection:ciprofloxacin, levofloxacin, ceftazidim, colistin
(aerosoli), tobramicin (iv aerosoli)
- Chronic infection:2 antibiotics iv, 14-28 days, ciprofloxacin 2
week course ,nebulized colistin ,tobramycin

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COMPLICATION

- Acute respiratory failure – oxygen, sistemic corticosteroids,antib,

bronchodilator
- Hemoptysis- no physiotherapy !!, antibiotics, vit K, bronchial artery
embolization
- Lobar atelectasis –aggressive antib,increased chest physiotherapy,
bronchoscopy- aspiration, bronchoalveolar lavage
- Pneumothorax- drainage ,surgical intervention, pleurectomy or
pleurodesis

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ABPA

- SISTEMIC CORTICOSTEROIDS
- ANTIFUNGAL (itraconazol po, voriconazol po, iv,posaconazol etc
amphotericina B nebulis); omalizumab(anti IgE)

LUNG TRANSPLANTATION

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