Sickle cell disease (SCD) encompasses a group of hemoglobinopathies characterized by a single amino acid substitution in the beta globin chain. Hemoglobin S results from the substitution of a valine for glutamic acid as the sixth amino acid of the beta globin chain. The resulting hemoglobin tetramer (alpha2/betaS2) is poorly soluble when deoxygenated. This deoxygenated hemoglobin polymerizes into sheets of elongated rope-like fibers, causing a marked decrease in red cell deformability and distortion of the cell into the classic crescent or sickle shape. The most frequently occurring form of SCD is sickle cell anemia (HbSS). Acute and chronic pulmonary complications occur frequently in patients with SCD, and represent the most common cause of death from SCD in adult.
The common pulmonary complications are:
1.Infection
2.Embolic phenomena due to bone marrow infarction and fat emboli
3.Infarction caused by in-situ thrombosis
4.Rib and sternal infarctions
5.Pulmonary edema
Acute chest syndrome — The acute chest syndrome (ACS) is the most common form of acute pulmonary disease in patients with SCD.
Signs and symptoms are:
■Presence of a new pulmonary infiltrate
■Chest pain
■Temperature >38.5ºC
■Tachypnea, wheezing, or cough
Etiology of ACS is unclear.
Unknown cause — 46 %
Pulmonary infarction — 16 %
Fat embolism, with or without infection — 9 %
Chlamydophila (formerly Chlamydia) pneumoniae infection — 7 %
Mycoplasma pneumoniae infection — 7 %
Viral infection — 6 %
Mixed infections — 4 %
Other pathogens — 1%
Clinicl findings following symptoms were present at the time of diagnosis of ACS
Fever — 80 %
Cough — 62 %
Tachypnea — 45 %
Chest pain — 44 %
Shortness of breath — 41 %
Arm and leg pain — 37 %
Abdominal pain — 35%
Rib or sternal pain — 21 %
Wheezing — 13 %
Management — The acute treatment of ACS is primarily supportive and is based upon the potential etiology.
Pneumonia — Patients with SCD are predisposed to develop pneumonia due to impaired host defenses, including loss of antibody protection (in the setting of auto-splenectomy), altered phagocytic function, and defective opsonization
Fat and bone marrow embolism — Bone marrow infarction resulting from microvascular occlusion is the probable pathogenic mechanism common to the initiation of both fat and bone marrow embolism in patients with SCD . Patients with SCD and pulmonary fat embolism (PFE) frequently have mental status changes, thrombocytopenia, falling hematocrit, and severe hypoxemia, a clinical presentation similar to that in patients in whom PFE develops following the fracture of long bones
Treatment options
Exchange transfusion
Plasma infusions
Glucocorticoids
Venous thromboembolism — Autopsy data of the lungs of patients with SCD reveal fibrin thromboembolism in larger arteries with or without infarction, and extensive thrombosis in smaller arteries
Sickle cell chronic lung disease — SCCLD may begin to develop as early as the second decade of life. Pulmonary dysfunction rapidly progresses, with death occurring within seven years of diagnosis Patients characteristically progress through four clinical stages based upon physiologic and radiographic data and symptoms
Stage 1 - recurrent chest pain and cough, mild reductions in forced vital capacity (FVC) and total lung capacity (TLC), normal oxygen saturation, and near normal chest radiographs with slightly increased interstitial markings.
Stage 2 - greater pain than stage 1, moderate reductions in FVC and TLC, normal oxygen saturation, and diffuse interstitial fibrosis (all lobes on chest radiograph).
Stage 3 - severe, crushing chest pain, hypoxemia during stable periods (PO2 approximately 70 mmHg), severe reductions in FVC and TLC, and pulmonary fibrosis on chest imaging.
Stage 4 - prolonged chest pain, fixed dyspnea, hypoxemia at rest, severe pulmonary fibrosis on chest radiograph, and elevated pulmonary artery pressure at rest
Obstructive sleep apnea — Upper airway obstruction during sleep due to adenoid and tonsillar enlargement has been found in up to one-third of children with SCD.
Alterations in baseline pulmonary function —Many different parameters of pulmonary function are altered in patients with sickle cell lung disease.
As examples: Total lung capacity and vital capacity may be reduced. Even when corrected for anemia, the diffusing capacity for carbonmonoxide (DLCO) is abnormally low.
Arterial oxygen saturation (SaO2) is reduced.
The alveolar-arterial difference is widened both at rest and with exercise
Mild to moderate airflow obstruction may be present, particularly among patients with recurrent episodes of acute chest syndrome.
Pulmonary hypertension in patients with SCD is 20 to 40 percent
The common pulmonary complications are:
1.Infection
2.Embolic phenomena due to bone marrow infarction and fat emboli
3.Infarction caused by in-situ thrombosis
4.Rib and sternal infarctions
5.Pulmonary edema
Acute chest syndrome — The acute chest syndrome (ACS) is the most common form of acute pulmonary disease in patients with SCD.
Signs and symptoms are:
■Presence of a new pulmonary infiltrate
■Chest pain
■Temperature >38.5ºC
■Tachypnea, wheezing, or cough
Etiology of ACS is unclear.
Unknown cause — 46 %
Pulmonary infarction — 16 %
Fat embolism, with or without infection — 9 %
Chlamydophila (formerly Chlamydia) pneumoniae infection — 7 %
Mycoplasma pneumoniae infection — 7 %
Viral infection — 6 %
Mixed infections — 4 %
Other pathogens — 1%
Clinicl findings following symptoms were present at the time of diagnosis of ACS
Fever — 80 %
Cough — 62 %
Tachypnea — 45 %
Chest pain — 44 %
Shortness of breath — 41 %
Arm and leg pain — 37 %
Abdominal pain — 35%
Rib or sternal pain — 21 %
Wheezing — 13 %
Management — The acute treatment of ACS is primarily supportive and is based upon the potential etiology.
Pneumonia — Patients with SCD are predisposed to develop pneumonia due to impaired host defenses, including loss of antibody protection (in the setting of auto-splenectomy), altered phagocytic function, and defective opsonization
Fat and bone marrow embolism — Bone marrow infarction resulting from microvascular occlusion is the probable pathogenic mechanism common to the initiation of both fat and bone marrow embolism in patients with SCD . Patients with SCD and pulmonary fat embolism (PFE) frequently have mental status changes, thrombocytopenia, falling hematocrit, and severe hypoxemia, a clinical presentation similar to that in patients in whom PFE develops following the fracture of long bones
Treatment options
Exchange transfusion
Plasma infusions
Glucocorticoids
Venous thromboembolism — Autopsy data of the lungs of patients with SCD reveal fibrin thromboembolism in larger arteries with or without infarction, and extensive thrombosis in smaller arteries
Sickle cell chronic lung disease — SCCLD may begin to develop as early as the second decade of life. Pulmonary dysfunction rapidly progresses, with death occurring within seven years of diagnosis Patients characteristically progress through four clinical stages based upon physiologic and radiographic data and symptoms
Stage 1 - recurrent chest pain and cough, mild reductions in forced vital capacity (FVC) and total lung capacity (TLC), normal oxygen saturation, and near normal chest radiographs with slightly increased interstitial markings.
Stage 2 - greater pain than stage 1, moderate reductions in FVC and TLC, normal oxygen saturation, and diffuse interstitial fibrosis (all lobes on chest radiograph).
Stage 3 - severe, crushing chest pain, hypoxemia during stable periods (PO2 approximately 70 mmHg), severe reductions in FVC and TLC, and pulmonary fibrosis on chest imaging.
Stage 4 - prolonged chest pain, fixed dyspnea, hypoxemia at rest, severe pulmonary fibrosis on chest radiograph, and elevated pulmonary artery pressure at rest
Obstructive sleep apnea — Upper airway obstruction during sleep due to adenoid and tonsillar enlargement has been found in up to one-third of children with SCD.
Alterations in baseline pulmonary function —Many different parameters of pulmonary function are altered in patients with sickle cell lung disease.
As examples: Total lung capacity and vital capacity may be reduced. Even when corrected for anemia, the diffusing capacity for carbonmonoxide (DLCO) is abnormally low.
Arterial oxygen saturation (SaO2) is reduced.
The alveolar-arterial difference is widened both at rest and with exercise
Mild to moderate airflow obstruction may be present, particularly among patients with recurrent episodes of acute chest syndrome.
Pulmonary hypertension in patients with SCD is 20 to 40 percent
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