Transcript Congenital lung diseases

Congenital lung diseases
by
Dr. Wael Abd El-fattah
Lecturer of Chest Diseases
Faculty of Medicine
Ain shams University
Immotile cilia syndrome (1ry ciliary dyskinesia)
1. Kartagener’s syndrome
2. Young’s syndrome
3. Cystic Fibrosis
Alpha 1-Antitrypsin deffeciency
Infant RDS
Kartagener’s syndrome
• (> one gene responsible for defect in cilia structure) by
failure of coordinated sliding and binding of cilia either
due to absence of dynein arms or presence of special
transposition of microtubules  abnormal mucus
transport from bronchial tree to the mouth 
impaired defenses):
• Ccc:
• Recurrent frontal sinusitis ± chronic rhinorrhea and
otitis media (mild deafness)
• LRTI (recurrent diffuse pneumonias)  chronic cough
and acquired bronchiectasis.
• Male infertility (immotile live sperms)
• Dextrocardia (situs inversus totalis in 1/2 cases)
• Diagnosed by:
• History of repeated infections and previous ccc
• Nasal mucosal biopsy  ultra-structural defect by high
speed digital video photography.
• Saccharine test  abnormal mucociliary movement
(place a small particle of saccharin approximately 1 cm
behind the anterior end of the inferior turbinate. In the
presence of normal mucociliary action, the saccharin
will be swept backwards to the nasopharynx and a
sweet taste perceived  normally from 10-15mins,
>28 mins means permanent damage.
• E.M.  for sperm tails and ciliary movement.
Young’s syndrome
• (defect in ciliary function with unknown
mechanism):
• Ccc:
• Recurrent LRTI and bronchiectasis (1/5 cases).
• Recurrent sinusitis.
• Azospermia (due to obstruction in vas
deferens),Poorly motile sperms in epididymis
(not in ejaculate)
Cystic Fibrosis
• Definition:
• Heritable disorder demonstrating an autosomal
recessive pattern in which there is a wide spread
dysfunction of exocrine glands in the form of:
• Chronic pulmonary disease (more presented in
adolescents).
• Pancreatic insufficiency (more presented in
infants).
• Malabsorption (thick sticky secretions in
intestine; mucoviscidosis).
• Abnormally high levels of electrolytes in sweat
(diagnostic test).
• -Etiology:
– Autosomal recessive mutation in CFTR gene (cystic
fibrosis trans-membrane conductance regulator) which is found in all tissues affected- in the middle
part of the long arm of chromosome 7.
– 66% of that mutation is in the form of deletion of
phenylalanine from position 508 of CFTR,
• destroying chloride channels which are anchored
to the outer membrane of cells in sweat glands,
and other  increased trapping of Cl ions outside
those cells attracting Na ions followed by H2O as
well dehydrated thick secretions with higher
incidence of repeated infections.
 Incidence: One every 2000-2500 births/year
in Europe and North America but very rare in Asia and Africa
• Clinical Picture:
• Symptoms:
– Respiratory:
• Upper airways: sinusitis, nasal polyps & otitis media 
↑ dyspnea.
• Lower airways:
– Early: coughing of copious  due to bacteria out of
control.
– Late: Chronic dyspnea, hemoptysis (50%), P++,
Corpulmonale,Rt.sided HF, RF, Pneumothorax .
GIT:
• Pancreas:
• Early: pancreatic auto-destruction  pancreatitis  malabsorption  steatorrhea and osteoporosis (low vitamin D
absorption)  retarded growth and failure to thrive.
• Late: fibrosis  obliteration in islets of langerhans ± D.M.
(12% in adulthood)
• Intestine:
• Abnormal mucins  ↓transit time of intestine + maldigestion  fecal impaction  distal meconium ileus in
newly born (50%) or intestinal obstruction
• Gall bladder and Liver:
• Inspissated bile syndrome in new born  prolonged
neonatal Jaundice 2-8wks).
• Focal biliary cirrhosis in adolescents.
• Chronic calcular cholecystitis and cirrhosis
– Reproductive system:
• ♂: Vas deference is absent or
atretic  no sperms  infertility.
• ♀: ↑↑ Viscosity & abnormal
midcycle cervical mucus only 
can sometimes cause infertility.
– Sweat glands:  no histological changes but abnormal
function.
• Signs:
– General:
• Loss of weight with mal-absorption
and digestion
• Fever (in infective exacerbation)
• Clubbing ± osteoarthropathy (15% in
adults)
• Jaundice in new born
• Cyanosis with RF
• Pallor with repeated hemoptysis
• Congested neck veins in
corpulmonale
• Bilateral lower limb edema in
corpulmonale
• Working ala nasi if distressed child.
– Local:
• Tachypnea
• Hyper inflated chest later in the course of the
disease
• Polyphonic wheezes in 50%
• Inspiratory crepitations (more in the upper
lobe)
• Investigations and Diagnosis:
• Depends on:
clinical background, +ve sweat test and F.H.
• Sweat test: (The Gold Standard Diagnostic Test for
Cystic Fibrosis)
• Pilocarpine iontophoresis technique:
– Mechanism: Pilocarpine of 100 mg is put in 2 electrodes
on the skin (on right arm or thigh or sometimes forearm if
older child) with weak electric current to aid its
penetration for 10 mins  sweat is collected by a sweat
patch in 30-45 mins & analyzed for Na and Cl (no creams is
put on skin before testing)
– Results:
+ve result when Cl > 60 (2 tests are done to confirm)
Borderline when 30-60 (to be repeated)
Normal <30 mmol/liter
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Laboratory investigations:
WBCs: leucocytosis in exacerbations.
Serum Igs due to infections.
Liver functions: AST and ALT might be elevated
but ALP and bilirubin are more likely to elevate.
Glucose level: for diabetes mellitus.
Amylase: for pancreatitis.
PT: in liver affection and mal-absorption.
Serum trypsinogen: screening test.
Stool analysis: for trypsin, chymotrypsin &
secretin stimulation test.
Semen analysis: for infertility (azospermia >97%).
Radiological investigations:
• Conventional CXR:
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Early:
– Mild hyper-inflation.
– Minimal peri-bronchial thickening.
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Late:
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Thickening increase in upper lobe then becoming diffuse.
Bronchiectatic picture (see bronchiectasis).
Atelectasis.
Increase in proximal arteries size.
Enlarged right ventricle.
Pneumothorax.
Pneumomediastinum.
• HRCT: (more sensitive)
– Ground glass opacities
– Early bronchiectatic changes
Functional investigations:
(for monitoring progression only)
Microbiological investigations:
• Sputum collection
• Gram stain and culture ± specific culture media
• Organisms:
– Staphylococcus aureus (in young more)
– H. influenza (in young more)
– Pseudomonas (late & most severe, mucoid cepasium
form):
– Aspergillus fumigates (5-15%)
– Mycobacterium (TB)
– Legionella pneumophilia
Early detection of CF
Pre-natal diagnosis: in the 17th wk searching for:
• It's important for good prognosis (early detection) and gene
therapy.
• Families with CF  one parent can be assessed first if a carrier then
examine the other because 2 copies of the gene must be affected
for a disease to develop
• ↑ level of intestinal iso-enzymes of ALP in amniotic fluid (marker)
• DNA probes are used to localize defective genes using a sample of
chorionic villi.
Screening tests: (for newborn)
• Immuno-reactive trypsinogen measurement (IRT): elevated if CF, a
blood sample taken from foot of a baby or his arm on filter paper
then left to dry then sent to the lab.
• Mutation assessment of the gene: one or two mutations in DNA
detected in 10-21 days.
Treatment:
• [A] General measures:
• Proper nourishment by high caloric diet (double normal) with high
proteins and carbohydrates due to increased need due to high
energy expenditure due to increased work of breathing with
chronic infection  clear secretions and eradicate infections.
• Exercise program to improve PFT.
• [B] Drainage: (90% of patients die of complications)
• Physiotherapy  every 12 hrs in stable stages and more in
exacerbations (same as bronchiectasis).
• Bronchodilator (B2 agonist or ipratropium may help).
• Corticosteroids  reverse airflow obstruction when unresponsive
to BD, in aspergillosis and in severe bronchiolitis in infants.
• Mucolytics
• [C] Antibiotics: for 2 weeks even after improvement
to decrease relapse rate and increase intervals
between exacerbations  mainly anti-staphylococcal
and anti-pseudomonal
• [D] Psychological support
• Early prenatally detected cases:
–Gene therapy (trials are done).
–U.T.P (uridine triphosphate aerosol activates
Cl- channel)
• Others aspects of management:
• Chest complications:
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Pneumothorax:
Corpulmonale: O2 up to BiPAP or IPPV and diuretics.
Nasal inflammation: fluticazone nasal spray.
End stage lung: cardio-pulmonary transplantation (difficult to select
patients because it's a systemic disease).
• Reproductive problems:
– ♂  Intra-cytoplasmic sperm injection.
– ♀  Assisted reproduction techniques.
• GIT problems:
– Meconium ileus: gastric aspiration, IV fluids, enemas and surgical ttt
for DU & gall stones.
– Pancreatic insufficiency: extract of pancreatin and H2 blockers to
prevent its inactivation with gastric acid.
– D.M.: insulin.
– Liver disease: vitamin K (especially if high PT).
– Mal-absorption: correct defects (supplementations).
• Osteoporosis: Vitamin D and Ca intake ± bisphosphonates.
Alpha 1-Antitrypsin deffeciency
• Aggregation of COPD in families have established a role for
genetic predisposition to COPD. The occurrence of reduced
maximal expiratory airflow among nonsmoking first-degree
relatives of individuals with early onset COPD provides further
support.
• However,dissecting specific genetic factors that increase the
risk of COPD has proven difficult.
• α1-AT deficiency illustrates this difficulty. Even among
individuals with this clearly identified genetic risk factor, there
is wide, unexplained, variability in the occurrence of COPD.
• α1-Antitrypsin (a1-AT) or a1-protease inhibitor (α 1-Pi) is a
polymorphic glycoprotein responsible for the majority of the
antiprotease activity in the serum.It is synthesized in the liver,
and most of the lung α 1-AT is derived from the plasma,
although monocytes and macrophages can also manufacture
the protein.
• Chromosome 14 contains a gene that encodes the a1-AT
protein. The gene for a1-AT is polymorphic, with over 70
known alleles, resulting from changes in the amino acid
sequence, none of which alter protein structure, function or
expression.
Alpha1-AT deficiency caused by:
1- An increase in the proteinase burden, due to
either the presence of increased numbers of
inflammatory leucocytes in the airspaces or the
release of excess protease .
2- Functional deficiency of protease inhibitors;
3- Combination of 1 and 2;
4 -Abnormality in the repair mechanisms for lung
connective tissue.
• The most important heterozygous type is PiSZ, where basal
levels are 35–50% of normal values ,the homozygous PiZZ
deficiency, in which serum levels are 10–20% of the average
normal value, is the strongest genetic risk factor for the
development of emphysema and the associated airflow
obstruction.
• The incidence of α1-Pi deficiency in a population study of
patients presenting with COPD was 1–2% but rises to greater
than 50% in patients with severe disease who are less than 40
years of age. The onset of dyspnoea and death occur at a
younger age in smokers with α1-Pi deficiency.
• In a study of deficient subjects in New Zealand, dyspnoea
began on average at age 32 years in smokers compared with
51 years in non-smokers. The mean age at death in this group
was 48 years for smokers and 67 years for non-smokers
Table: Serum a1-proteinase inhibitor concentrations and the
frequency of the more common phenotypes and the risk for
emphysema.
Phenotype
Average concentration
(g/L)
Risk factor for emphysema
MM
2.0
NO
MS
1.6
NO
MZ
1.2
NO
SS
1.2
NO
SZ
0.8
YES
ZZ
0.4
YES
Infant respiratory distress syndrome
• Infant respiratory distress syndrome (IRDS), also called
neonatal respiratory distress syndrome or respiratory
distress syndrome of newborn, previously called hyaline
membrane disease.
• It is a syndrome in premature infants caused by
developmental insufficiency of surfactant production and
structural immaturity in the lungs. It can also result from a
genetic problem with the production of surfactant associated
proteins.
• RDS affects about 1% of newborn infants and is the leading
cause of death in preterm infants.
• The incidence decreases with advancing gestational age, from
about 50% in babies born at 26–28 weeks, to about 25% at
30–31 weeks.
Histopathology
• The characteristic histopathology seen in
babies who die from RDS was the source of
the name "hyaline membrane disease". These
waxy-appearing layers line the collapsed
alveoli of the lung. In addition, the lungs show
bleeding, over-distention of airways and
damage to the lining cells.
Clinical course
• IRDS begins shortly after birth and is manifest by
tachypnea, tachycardia, chest wall retractions (recession),
expiratory grunting, nasal flaring and cyanosis during
breathing efforts.
• As the disease progresses, the baby may develop
ventilatory failure (rising carbon dioxide concentrations in
the blood), and prolonged cessations of breathing
("apnea"). Whether treated or not, the clinical course for
the acute disease lasts about 2 to 3 days.
• Complications include metabolic disorders (acidosis, low
blood sugar), patent ductus arteriosus, low blood pressure,
chronic lung changes, and intracranial hemorrhage. The
disease is frequently complicated by prematurity and its
additional defects in other organ function.
Prevention
• The fetal lung maturity may be tested by sampling the amount
of surfactant in the amniotic fluid,these include the lecithinsphingomyelin ratio ("L/S ratio"), and more recently, the
surfactant/albumin (S/A) ratio.
• For the L/S ratio, if the result is less than 2:1, the fetal lungs
may be surfactant deficient. The presence of PG usually
indicates fetal lung maturity. For the S/A ratio, the result is
given as mg of surfactant per gm of protein. An S/A ratio <35
indicates immature lungs, between 35-55 is indeterminate,
and >55 indicates mature surfactant production
• Most cases of infant respiratory distress syndrome can be
ameliorated or prevented if mothers who are about to deliver
prematurely can be given glucocorticoids, antenatal
glucocorticoid treatment for women at risk for preterm
delivery prior to 34 weeks of gestation.
Treatment
• Oxygen is given with a small amount of
continuous positive airway pressure ("CPAP"),
and intravenous fluids are administered to
stabilize the blood sugar, blood salts, and
blood pressure. If the baby's condition
worsens, an endotracheal tube (breathing
tube) is inserted into the trachea and
intermittent breaths are given by a mechanical
device.
• An exogenous preparation of surfactant, either synthetic or
extracted from animal lungs, is given through the breathing
tube into the lungs. One of the most commonly used
surfactants is Survanta, derived from cow lungs, which can
decrease the risk of death in hospitalized very-low-birthweight infants by 30%.
• Extracorporeal membrane oxygenation (ECMO) is a potential
treatment, providing oxygenation through an apparatus that
imitates the gas exchange process of the lungs. However,
newborns cannot be placed on ECMO if they are under 4.5
pounds (2 kg), because they have extremely small vessels for
cannulation, thus hindering adequate flow because of
limitations from cannula size and subsequent higher
resistance to blood flow.
• Furthermore, in infants aged less than 34
weeks of gestation several physiologic systems
are not well-developed, specially the cerebral
vasculature and germinal matrix, resulting in
high sensitivity to slight changes in pH, PaO2,
and intracranial pressure. Subsequently,
preterm infants are at unacceptably high risk
for intraventricular hemorrhage.
• Therefore, the device cannot be used for most
premature newborns.
Thank you