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Pulmonary Complications of Sickle Cell Disease

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					Pulmonary Complications of
    Sickle Cell Disease
            Aneesa Vanker
          Respiratory Meeting
              17-03-2009
      Tygerberg Children`s Hospital
           Sickle Cell Disease
                  (SCD)
• Caused by the inheritance of 2 copies of a
  mutant beta-globin gene – 1 from each parent.
• Mutation = GAG GTG at position 6 in beta-
  globin chain of HbA  HbS
• One of the most common inherited autosomal
  recessive disorders in the world.
• Certain areas in sub-Saharan Africa – 40-60% of
  population heterozygote  1-4% of babies born
  have disease.
• HbS polymerises on deoxygenation 
  rigidity of erythrocyte, distorts its shape &
  causes structural damage in red cell
  membrane.
• Altered rheologic properties of cell impairs
  blood flow through microvasculature 
  haemolysis &vaso-occlusive episodes.
    Pulmonary Complications
• Pulmonary complications of SCD in
  children remain leading cause of morbidity
  and mortality.
  What does the literature say?
• 2 recent articles on Pulmonary
  complications of (SCD)
      Vaso-occlusive crises
• Recurrent episodes of severe pain in SCD
• Caused by microvascular entrapment of
  RBC & WBC  obstruction in blood flow &
  organ ischaemia
• Microvascular events  episodes of
  explosive pain & inflammation.
• May be accompanied by fever &
  leukocytosis +/- bone marrow necrosis
  with pulmonary emboli.
The Acute Chest Syndrome (ACS)
• Common form of lung injury in SCD
• When severe analogous to acute respiratory
  distress syndrome.
• Defined by development of new pulmonary
  infiltrates consistent with alveolar consolidation
  but not atelectasis involving at least one
  segment.
• Radiographic abnormality accompanied by chest
  pain, fever, tachypnoea, wheezing or cough.
 Causes of Acute Chest Syndrome
• 3 major causes proposed:
  1. pulmonary infection
  2. embolisation of bone marrow fat – ffg
  vaso-occlusive crisis
  3. intravascular pulmonary sequestration
  of sickled erythrocytes lung injury &
  infarction
      Clinical aspects of ACS
• Associated with marked systemic
  inflammation, fever, leukocytosis , abrupt
  drop in Hb and thrombocytopaenia.
• May require ventilatory support
• Rapid simple or exchange blood
  transfusion, removes sickled erythrocytes
   rapid recovery.
    Pulmonary Complications of SCD
              in children
•   Acute chest syndrome
•   Asthma (airway hyperreactivity)
•   Chronic sickle lung disease
•   Pulmonary hypertension
•   Sleep disordered breathing
                 Asthma
• Significant comorbidity in children with
  SCD
• Chronic lung dx can also occur – probably
  result of recurrent episodes of ACS
• High incidence of airway hyperreactivity in
  several studies
• However, low prevelance of asthma – may
  be underdiagnosed
• Children with SCD and asthma have nearly
  twice as many episodes of ACS.
• Several theories: VQ mismatch local tissue
  hypoxia and increased sickling of RBC, increase
  release of inflammatory markers may cause
  increase airway hyperreactivity.
• Further studies warranted to determine if
  aggressive Rx of asthma reduces risk of ACS
  and possibly morbidity & mortality of ACS in
  SCD
      Pulmonary Hypertension
• Prevalence of pulmonary hypertension in
  children with SCD similar to that in adults (+/-
  33%)
• Defined as pulmonary artery systolic pressure:
  greater than 35mmHg (mild)
            greater than 45mmHg (mod-
                                         severe)
OR
• Tricuspid regurgitation velocity jet over
  2.5m/s(mild) or 3.5m/s (mod-severe)
    Calculating pulmonary artery
              pressure
• Pulmonary artery pressure assumed to =
  right ventricular(RV) systolic pressure.
• RV systolic pressure estimated from
  Bernoulli principle = as a fluid jet increases
  velocity, its lateral pressure is reduced.
   Pathophysiology of pulmonary
          hypertension
• Mulitiple mechanisms:
  - Left ventricular dysfunction from chronic
  anaemia
  - Lung damaging infarctions
  - Recurrent pneumonia & ACS
  - Recent interest – role of nitric oxide,
  decreased NO bioavailability  pulmonary
  vasoconstriction.
        Rx of Pulmonary HPT
• Information on Rx remains anecdotal.
• Sildenafil use studied.
• Arginine – substrate of NO shown to reduce
  pulmonary artery pressure in SCD
• Other agents: prostacycline, bosentan
  (endothelin receptor blocker)
• Blood transfusion – lowers plasma Hb by
  reducing hemolysis & suppressing
  hematopoesis of Hb sickle cells  lower
  pulmonary artery pressures.
     Sleep disordered breathing
               (SDB)
• Children with SCD have increased risk of
  SDB and abnormal ventilation during
  sleep.
• 36% of children with SCD have SDB
         Postulated reasons
• Poor sleep quality associated with pain and VOC
  as well as nocturnal oxyhaemoglobin
  desaturations.
• Upper airway obstruction – increased risk of
  obstructive sleep apnoea – thought to be due to
  compensatory lymphoid hyperplasia of tonsil
  and adenoids following splenic infarction.
  Significant reduction in symptoms ffg
  adenotonsillectomy
     Postulated reasons cont..
• Correlation between SDB and elevated cerebral
  blood flow velocity (CBFV) in children with SCD.
• Measured with transcranial doppler ultrasound.
• Related to cerebral artery stenosis, severe
  anaemia & tissue hypoxia.
• Association between elevated CBFV & UAO.
  Adenotonsillectomy can normalisation of
  CBFV and prevention of adverse neurological
  events.
              Conclusion
• Pulmonary dx remains an important cause
  of morbidity & mortality in children with
  SCD.
• Pulmonary complications can interact with
  each other amplifying the adverse effects.
• Further research needed to evaluate these
  relationships.

				
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posted:2/26/2012
language:English
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