Renal abnormalities in sickle cell disease

Renal abnormalities in sickle cell disease. Sickle cell nephropathy is indicated by sickled erythrocytes, with the consequent effects of decreased medullary blood flow, ischemia, microinfarct and papillary necrosis. Impaired urinary concentrating ability, renal acidification, hematuria, and potassium secretion are also found. There may be a causal relationship between an increase in nitric oxide synthesis and experimental sickle cell nephropathy, and some studies have indicated that the progression of sickle cell nephropathy is hemodynamically mediated. Although there are many studies showing that proteinuria, nephrotic syndrome, chronic progressive renal failure, and acute renal failure syndromes are the outcome of this disease, the pathogenic mechanism(s) and potential therapies remain to be elucidated. Survival of patients with sickle cell nephropathy who progress to end-stage renal disease (ESRD) is equal to non-diabetic ESRD patients, and graft survival rates are also similar for those who undergo renal transplantation. This article presents a historical review of the glomerular and tubular disorders associated with sickle cell nephropathy, and reviews therapeutic indications to slow its progression. Further research is needed.     

Stroke in children with sickle cell disease

Opinion statement Children with sickle disease are at high risk for ischemic stroke and transient ischemic attacks, usually secondary to intracranial arteriopathy involving the terminal internal carotid and proximal middle cerebral and anterior cerebral arteries, which may be diagnosed using transcranial Doppler ultrasound or magnetic resonance angiography (MRA). Other central nervous system (CNS) complications include seizures and coma, which may be secondary to ischemic stroke, sinovenous thrombosis, reversible posterior leukoencephalopathy, or acute demyelination. The immediate priority after an acute CNS event is to improve cerebral oxygenation with oxygen supplementation to maintain peripheral saturation measured using pulse oximetry between 96% and 99%, and a simple transfusion of packed cells within an hour of presentation if the patient’s hemoglobin is less than 10 g/dL. The patient then should have erythrocytapheresis or manual exchange to reduce the hemoglobin S percentage to below 30%. Computed tomography to exclude hemorrhage is mandatory and MR T2-weighted imaging with MRA, fat-saturated imaging of the neck (dissection), MR venography (sinovenous thrombosis), and diffusion-weighted imaging usually distinguishes between arterial ischemic stroke and the differential diagnoses. Comatose patients with widespread focal or global cerebral edema may have good functional outcome after surgical decompression. Anticoagulation may be indicated for dissection or sinovenous thrombosis and steroids for demyelination. Blood pressure should be reduced slowly if raised in patients with reversible posterior leukoencephalopathy. Seizures should be treated aggressively and electroencephalogram monitoring should be done to exclude subclinical seizures if the patient is unconscious. Hemorrhagic stroke may require craniectomy and drainage and/or management of vasospasm. Interventional neuroradiology with coils is an alternative to surgical clipping for aneurysms. For secondary prevention, regular blood transfusion to hemoglobin S of less than 30% reduces the risk of recurrent stroke from approximately 67% to approximately 10%. Hydroxyurea and phlebotomy may be used in patients who are alloimmunized. Moyamoya syndrome is a risk factor for recurrence despite prophylactic blood transfusion. Revascularization may prevent additional stroke. Bone marrow transplantation may be offered to patients with human leukocyte antigen-compatible siblings. Blood transfusion prevents stroke in patients with velocities greater than 200 cm per second on TCD; a phase III trial studying the prevention of the progression of silent infarction is being done. Emerging primary prophylaxis regimens being tested include citrulline and arginine, aspirin, and overnight oxygen supplementation. Physicians caring for children with sickle cell disease also should ensure adequate nutrition, including five servings of fruit and vegetables a day. The role of vitamin supplementation is controversial, particularly when patients must take daily penicillin prophylaxis.     

Renal function in children with sickle cell anemia

BACKGROUND: Patients with sickle cell anemia have various forms of renal dysfunction. SUBJECTS, MATERIALS AND METHODS: The purpose of this study is to demonstrate the abnormalities of HbSS patients' renal function in childhood. Renal function studies were performed in 55 patients with homozygote sickle cell anemia and compared with 13 healthy children. The blood and timed urine samples were obtained for hematological and biochemical determinations. RESULTS: Mean serum creatinine, sodium, phosphorus and calcium levels were not statistically different between patients and controls. Mean serum potassium and uric acid levels were significantly higher in patients than in controls. Mean tubular phosphate reabsorption (p < 0.001) and fractional excretion of potassium (p < 0.05) were lower in patients than in the control. There were no significant differences in fractional excretion of sodium and uric acid between patients and controls. Patients had significantly higher urine pH and significantly lower specific gravity and osmolality than controls. Also, there were no significant differences in urinary protein/ creatinine, urinary N-acetyl-beta-D-glucosaminidase/creatinine and urinary malondialdehyde/creatinine between patients and controls. CONCLUSION: Thus, significant proximal tubular dysfunction is not a common feature but distal tubular abnormality is the most consistent renal functional derangement of patients with SCA in childhood.     

Proteinuria in children with sickle cell disease.

BACKGROUND: Sickle cell nephropathy is characterized by proteinuria that starts in childhood and may lead to renal failure. Microalbuminuria is used as a marker of glomerular damage. There are no data on the extent and type of proteinuria other than microalbuminuria in children with sickle cell disease (SCD). Our goal was characterization of glomerular permselectivity and tubular proteinuria in children with SCD. The improved characterization will allow earlier recognition and prevention of renal damage. METHODS: Thirty-two stable patients with haemoglobin SS (HbSS) (15 boys and 17 girls, age 9.57 +/- 5.45 years, 8 months to 19 years) were investigated. All patients had normal renal function and tested negative for proteinuria with a dipstick method. Markers of glomerular permselectivity used were albumin (marker of charge selectivity and less severe pore-size selectivity) and immunoglobulin G (IgG, marker of more severe pore-size selectivity). The marker of tubular injury used was retinol-binding protein (RBP, marker of proximal tubular dysfunction). These proteins were measured in urine spot samples using nephelometry. We did not include a control group as values in healthy subjects were previously published. RESULTS: Total protein excretion was elevated in 41% (13/32) of all patients and, of these 13 patients, 38.5% (5/13) had increased microalbuminuria, 15% (2/13) had increased excretion of RBP and 23% (3/13) had increased excretion of IgG. Increased total proteinuria that was not detected by testing for microalbuminuria was found in 61.5% (8/13) of patients. The youngest patient was 3 years old. Increased microalbuminuria was present in 25% (8/32) of all patients and was detected as early as 4 years of age. Of these, 62% (5/8) also had increased total protein excretion and 62% (5/8) also had increased IgG excretion. A total of 62.5% were older than 10 years. RBP excretion was elevated in 16% (5/32) of patients, all of whom were 7-14 years old. None of these patients had increased microalbuminuria or increased excretion of IgG. IgG excretion was elevated in 16% (5/32) of patients and was accompanied by increased microalbuminuria. All patients with increased IgG excretion were > or = 13 years old. We found a weak positive correlation between microalbuminuria and age (0.323, P = 0.07). We did not find a significant correlation between any type of proteinuria and disease morbidity. Ten of the thirty-two patients received hydroxyurea treatment and 60% (6/10) had no proteinuria. Twelve of the thirty-two patients received chronic exchange transfusions and 42% (5/12) had no proteinuria. CONCLUSION: We found early glomerular selectivity damage in children with SCD, which is secondary to both size-selectivity and charge-selectivity impairment. Microalbuminuria alone does not adequately detect early renal damage in children with SCD. Proximal tubular dysfunction is seen in younger children and is independent of glomerular damage. We suggest that children with SCD be tested for both total protein and IgG excretion in the urine in addition to albumin. Knowing the extent and type of renal damage may allow earlier recognition of renal injury and prompt earlier initiation of preventive therapies.     

Prevalence of microalbuminuria in children with sickle cell disease

Renal involvement is common in homozygous sickle cell disease (HbSS), including glomerular hypertension and hypertrophy similar to that seen in rodent models of ablative nephrectomy and stage I diabetic nephropathy (DN). The proteinuria in the rodent models is attenuated by angiotensin converting enzyme inhibition (ACEI). Microalbuminuria (MA) is a sensitive marker for renal involvement in DN prior to the development of proteinuria, and is also attenuated with ACEI. Elevated urinary microalbumin/creatinine ratios (U Alb/Cr) >20 mg/g Cr are reported in 39%–43% of adults with HbSS, and studies are ongoing in this age group to assess the effect of attenuated proteinuria by ACEI on long-term renal function. The purpose of this study was to prospectively investigate the prevalence of MA in children with HbSS and determine factors which affect its expression. U Alb/Cr values were measured on spot urine samples in 102 children (aged 2–18 years, mean 9.47±4.62, M:F=53:49) by rate nephelometry. Children with prior known proteinuria, hypertension, or fever/pain episode in the last 15 days were excluded. MA was present in 26.5% of all children with HbSS. However, in children between the ages of 10 and 18 years, the prevalence was 46% (similar to the prevalence in adults). There was a strong correlation between patient age and prevalence of MA (P<0.0001) by both univariate and multivariate analysis. However, pain frequency, hospitalization, transfusion program, ferritin levels, and Cr clearance (C _Cr) did not correlate with prevalence, although C _Cr (as estimated by Schwartz formula) was elevated in all. We conclude that the prevalence of MA in the 2nd decade of life is similar to that in adults. Received April 11, 1998; received in revised form and accepted March 6, 1998     

Regionally specific cortical thinning in children with sickle cell disease

Sickle cell disease (SCD) is a chronic disease with a significant rate of neurological complications in the first decade of life. In this retrospective study, cortical thickness was examined in children with SCD who had no detectable abnormalities on conventional magnetic resonance imaging/magnetic resonance angiography. Regional differences in cortical thickness from SCD were explored using age-matched healthy controls as comparison. A comparison analysis was done for SCD (n = 28) and controls (n = 29) based on age (5-11; 12-21 years), due to the age-dependent variation in cortex maturation. Distinct regions of thinning were found in SCD patients in both age groups. The number, spatial extent, and significance (P < 0.001) of these areas of thinning were increased in the older SCD group. Regions of interest (ROIs) were defined on the areas of highly significant thinning in the older group and then mapped onto the younger cohort; a multiparametric linear regression analysis of the ROI data demonstrated significant (P < 0.001) cortical thinning in SCD subjects, with the largest regions of thinning in the precuneus and the posterior cingulate. The regionally specific differences suggest that cortical thickness may serve as a marker for silent insults in SCD and hence may be a useful tool for identifying SCD patients at risk for neurological sequelae.     

Serum cystatin C levels in children with sickle cell disease

Patients with sickle cell disease (SCD) may develop kidney dysfunction from childhood. The purpose of this study was to examine the value of serum cystatin C as a marker for glomerular filtration rate (GFR) in children with SCD, as compared to serum creatinine and creatinine clearance (CrCl). Twenty children (ages 9–21, ten males) with SCD with and without albuminuria were studied. The mean serum cystatin for the whole group was 0.89 mg/l (0.5–1.7 mg/l). Mean serum cystatin C was significantly different among the children with proteinuria (n=4), microalbuminuria (n=5), and without albuminuria (n=11) (1.25 mg/l, 0.84 mg/l, and 0.78 mg/l, respectively). The mean GFR derived from serum cystatin was significantly different among these subgroups, becoming abnormal in the proteinuric cohort (63 ml/min per 1.73 m²), in contrast to 94 for the microalbuminuric, and 103 for the normal subgroups. Serum creatinine (mean: 0.58 mg/dl, range: 0.3–1.1) did not change significantly with the level of albuminuria. Mean CrCl remained normal to increased within the subgroups, (133 ml/min per 1.73 m² for those with proteinuria, 144 for those with microalbuminuria, and 163 for the normal subgroup). We conclude that serum cystatin C correlates with the level of albuminuria and may be a reliable method to measure renal function in SCD. An erratum to this article can be found at     

Treatment and prevention of stroke in children with sickle cell disease

Opinion statement Stroke is one of the major complications in children with sickle cell disease (SCD). Ischemic stroke is associated with small asymptomatic subcortical infarcts to large territorial lesions causing major disability. Intracranial hemorrhages may be caused by aneurysm rupture or by leakage from moyamoya vessels or venous sources. There have been no acute stroke treatment studies in SCD, but hydration and exchange transfusion are often recommended. However, there is an evidence base for primary and to some extent secondary stroke prevention. Primary prevention of stroke was demonstrated in the Stroke Prevention Trial in Sickle Cell Anemia (STOP), in which children with transcranial Doppler (TCD) mean blood flow velocities of 200 cm/second (previously shown to indicate high stroke risk) or higher were randomized to either regular blood transfusions or no transfusion. The study showed a very significant 90% reduction in first stroke with transfusion. In STOP2, discontinuing transfusions after 30 months or more (even with normal TCD) resulted in a high rate of reversion to abnormal TCD values and stroke. TCD screening of all children with SCD, and initiation and maintenance of chronic transfusion to maintain hemoglobin S below 30% in the high-risk group, is the only proven prevention strategy for stroke in SCD. Hydroxyurea is being studied as secondary stroke prevention at this time. No recommendation specific to SCD regarding the use of antiplatelet agents or anticoagulants in ischemic stroke can be made. Bone marrow transplantation can be curative for SCD, and limited data support its use to prevent stroke in SCD.     

Splenectomy reduces packed red cell transfusion requirement in children with sickle cell disease

Purpose

The purpose of the study was to measure the effect of splenectomy on packed-cell transfusion requirement in children with sickle cell disease.

Methods

Thirty-seven sickle cell children who underwent splenectomies between January 2000 and May 2006 at a children's hospital were reviewed. Data were collected 6 months preoperatively to 12 months postsplenectomy. Paired t test, analysis of variance, and multivariable regression analyses were performed.

Results

Of 37 children with median age 11 years (range, 2-18 years), 34 (21 males) had data that allowed analyses. Twenty-six had Hgb-SS, 5 had Hgb-SC, and 3 had Hgb S-Thal. Laparoscopic splenectomy was attempted in 36 and completed successfully in 34 (94% success). The number of units transfused decreased by 38% for 0 to 6 months and by 45% for 6 to 12 months postsplenectomy. Postoperatively, hematocrit levels increased and reticulocytes concurrently decreased with a reduction in transfusion clinic visits. The decrease in transfusion was not influenced by spleen weight, age, or hemoglobin type. Two children had acute chest syndrome (6%), and 1 had severe pneumonia (3%).

Conclusion

Laparoscopic splenectomy can be successfully completed in sickle cell children. Splenectomy significantly reduces the packed red cell transfusion requirement and frequency of clinic visits, in sickle cell children for at least 12 months postoperatively.     

Acute chest syndrome after splenectomy in children with sickle cell disease

Background/Purpose

The purpose of this study was to determine the incidence of acute chest syndrome (ACS) in children with sickle cell disease (SCD) undergoing laparoscopic or open splenectomy and to assess factors that may predispose to this complication.

Methods

A retrospective review of all patients with SCD undergoing splenectomy between 1999 and 2007 in our institution. Charts were screened for demographics, perioperative clinical status (vaso-occlusive crises, sequestration crises), preoperative hemoglobin electrophoresis and preoperative transfusion, postoperative development of ACS, and need for an intensive care unit (ICU) admission.

Results

Forty-three children with SCD, 17 females and 16 males (mean age 9 years), underwent splenectomy (19 laparoscopy and 24 open). Acute chest syndrome occurred in 9 patients (20%), 1 (5.2%) of 19 in the laparoscopy group, and 8 (33.3%) of the 24 in the open group. All patients with ACS were admitted to the ICU. Acute chest syndrome developed within the first 24 hours in 5 of the 9 patients, on the second postoperative day in 1 patient, and more than 1 month postoperatively in 3 patients. Six of 9 patients with ACS had been transfused preoperatively. All patients with ACS had had vaso-occlusive crises before surgery. Five of 9 patients who developed ACS had previous ACS episodes before surgery. There was no death in our series.

Conclusion

The incidence of ACS is in accordance with the literature. Preoperative transfusions did not prevent ACS . There is a clear tendency for laparoscopically operated patients to experience less ACS postoperatively. In our group of patients, there were no clear benefits for routine perioperative admission to the ICU.     

Perioperative management in children with sickle cell disease undergoing laparoscopic surgery.

OBJECTIVE: The aim of this study was to evaluate our experience with laparoscopic surgery in children with sickle cell disease. METHODS: A retrospective chart review was performed to analyze the indication for surgery, perioperative management, surgical technique, complications, duration of hospitalization, and outcome. One pediatric surgeon performed all procedures. RESULTS: Thirteen children underwent laparoscopic surgery for the following indications: symptomatic cholelithiasis/cholecystitis in 9; recurrent splenic sequestration in 3; and hypersplenism/symptomatic cholelithiasis in 1. The 7 boys and 6 girls had a median age of 7.8 years. Patients undergoing splenectomy only were younger than those undergoing cholecystectomy (median age, 3.6 years versus 11.5 years, respectively). Four children underwent endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy because of common bile duct dilatation and stones. Twelve patients received packed red blood cell transfusions prior to surgery. The median operative time was 150 minutes, and the median hospitalization was 3 days. Four patients suffered postoperative complications (2 with acute chest syndrome, 1 with recurrent abdominal pain, and 1 with priapism). The patient with abdominal pain was found to have a retained stone in the common bile duct, which was retrieved via endoscopic retrograde cholangiopancreatography and sphincterotomy. All complications resolved with medical management. CONCLUSIONS: Laparoscopic surgery is safe in children with sickle cell disease. Meticulous attention to perioperative management, transfusion guidelines, and pulmonary care may decrease the incidence of acute chest syndrome.     

Pulmonary abnormalities in Cowden's disease

Cowden's disease is an inheritable multiple neoplastic syndrome represented by benign and malignant lesions of skin, digestive tract, mucosae, breast and thyroid. The syndrome, first described by Lloyd and Dennis in 1963, includes benign lung lesions, described in the literature only as hamartomas. The unusual condition of our case consists of multiple and bilateral lipomatous lesions of the lung and of adipose colonic polyps, diagnosed respectively by video assisted mini-thoracotomy and by endoscopic biopsies.     

Indications and complications of splenectomy for children with sickle cell disease

Background

Sickle cell anemia (SCA), which is characterized by high hemoglobin (Hb) F level and persistent splenomegaly into the older age group (up to 18 years of age) or even adults, is one of the commonest hemoglobinopathies in the Eastern Province of Saudi Arabia. This makes them liable to develop splenic complications requiring splenectomy. This is a review of our experience in the management of 134 children with SCA who had splenectomy as part of their management at our hospital, with emphasis given to the indications and complications of splenectomy.

Patients and methods

The medical records of all children who had splenectomy at our hospital were retrospectively reviewed for the following: age at splenectomy, sex, Hb electrophoresis, indication for splenectomy, preoperative investigations, type of surgery, spleen weight, histology, perioperative management, and postoperative complications.

Results

From 1990 to 2004, 170 children with various hematologic disorders had splenectomy at our hospital. Of these, 134 had SCA (118 had sickle cell disease and 16 had sickle-β-thalassemia). Recurrent acute splenic sequestration crisis (ASSC) was the commonest indication for splenectomy in 103 (76.9%) patients, followed by hypersplenism in 18 (13.4%). Seven (5.2%) of our patients had splenectomy for splenic abscess (SA) and 2 had splenectomy for massive splenic infarction; 103 (61 boys, 42 girls) patients with a mean age of 7.6 years (range, 1.8-13 years) had splenectomy for ASSC. Their mean Hb F level was 20.5% (range, 9.2%-39.6%). Thirty-two of them had major attacks. Their Hb levels at the time of admission ranged from 1.4 to 4.1 g/dL (mean, 2.5 g/dL). The remaining 71 had minor recurrent attacks. Eighteen had splenectomy for hypersplenism and all had a significant increase in their blood parameters after splenectomy. Seven had splenectomy for SA. In 5 patients, Salmonella was the causative organism; in 1, it was Enterobacter sakazaki, whereas in 1, no organisms were identified. Two of our patients had splenectomy for massive splenic infarction because of persistent left upper quadrant abdominal pain, and 1 had splenectomy for splenomegaly with a nonfunctioning spleen. Twenty-eight (21%) of our patients had splenectomy and cholecystectomy. In 4 patients, this was because of symptomatic gallstones, whereas in the other 24, it was because of asymptomatic gallstones discovered on ultrasound. There was no mortality, but 8 (6%) developed postoperative complications.

Conclusions

With good perioperative management, splenectomy in children with SCA is not only safe, but also beneficial in treating SA, reducing the patients' transfusion requirements, eliminating the risks of ASSC, and eliminating the discomfort and mechanical pressure of the enlarged spleen. Abdominal ultrasound should be done routinely preoperatively for all children with SCA undergoing splenectomy, and if gallstones are discovered, they should undergo concomitant cholecystectomy. This is even so for asymptomatic gallstones. The addition of cholecystectomy to splenectomy does not increase the morbidity, but eliminates the subsequent complications of gallstones and simplifies their future management in case of abdominal crisis as the possibility of cholecystitis is eliminated.     

Prevalence and clinical correlates of microalbuminuria in children with sickle cell disease

Sickle cell disease (SCD) is associated with a large spectrum of renal abnormalities, one of which, microalbuminuria/proteinuria (MA/P), is a known predictor of end-stage renal disease. We studied 90 children with SCD (57% male; mean age 11.4 ± 5.2 years) to determine the prevalence and examine clinical correlates of MA/P. The average of two spot urine microalbumin-to-creatinine samples obtained 6 months apart was recorded. Medical records were reviewed for demographic and biochemical data. Medication use, resting office blood pressures (BP), vaso-occlusive pain crises (VOC), and monthly transfusions were recorded. Fourteen children (15.5%) had MA/P. Hemoglobin (Hb) levels were significantly lower in the children with MA than in those without MA/P (8.8 ± 1.1 vs. 9.8 ± 1.4 g/dL, respectively) and were significantly correlated with MA (rho = 0.24, p = 0.03). Children with MA were more likely to have abnormal BP (p = 0.058), with 5/14 being hypertensive or pre-hypertensive. In a multivariate logistic regression model of MA, both Hb and BP classification remained in the final model. MA is a simple screening biomarker of early kidney injury in children with SCD. Larger studies to evaluate predictive factors of MA and the relationship to BP are needed.     

Fast-track cardiac anesthesia in patients with sickle cell abnormalities.

We conducted a retrospective review of 10 patients with sickle cell trait (SCT) and 30 patients (cohort control) without SCT undergoing first-time coronary artery bypass graft surgery with cardiopulmonary bypass. Demographic, perioperative management, and outcome data were collected. Both groups were matched according to age, weight, duration of surgery, and preoperative hemoglobin (Hb) concentration. Distribution of gender, medical conditions, pharmacological treatment, and preoperative left ventricular function were similar between the groups. The comparisons were analyzed in respect to postoperative blood loss and transfusion rates, as well as duration of intubation, intensive care unit, and hospital length of stay (LOS). All patients underwent fast-track cardiac anesthesia. A combination of cold crystalloid and blood cardioplegia was used. The lowest nasopharyngeal temperature was 33 degrees C. There were no episodes of significant hypoxemia, hypercarbia, or acidosis. None of the patients had sickling crisis during the perioperative period. The postoperative blood loss was 687 +/- 135 vs 585 +/-220 mL in the SCT and control groups, respectively. The trigger for blood transfusion during cardiopulmonary bypass was hematocrit <20% and Hb <75 g/L postoperatively. Three SCT patients (30%) and 10 control patients (33%) received a blood transfusion. Median extubation time was 4.0 vs 3.9 h; intensive care unit LOS was 27 vs 28 h; and hospital LOS was 6.0 vs 5.5 days in the SCT and control groups, respectively. There were no intraoperative deaths. One patient in the SCT group died from multiorgan failure 2 mo after surgery. IMPLICATIONS: Fast-track cardiac anesthesia can be used safely in patients with sickle cell trait undergoing first-time coronary artery bypass graft surgery. Extubation time and intensive care unit and hospital length of stay are comparable to those of matched controls, and blood loss and transfusion requirements are not increased. A hematocrit of 20% seems to be a safe transfusion trigger during cardiopulmonary bypass in these patients.     

Asthma in children with sickle cell disease and its association with acute chest syndrome

BACKGROUND: Pulmonary complications are a major cause of morbidity and mortality in sickle cell disease (SCD). The relationship of asthma with SCD and acute chest syndrome (ACS) remains uncertain. A study was undertaken to test the hypotheses that asthma and bronchial hyperreactivity (BHR) are more common in children with SCD than in ethnic matched controls and that SCD children with atopic asthma are more likely to have recurrent episodes of ACS. METHODS: A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was administered and skin prick tests undertaken in 80 children with SCD and 80 ethnic matched controls aged 5-10 years. BHR was assessed by measurement of forced expiratory volume in 1 second before and after a bronchodilator (albuterol 200 mug) or an exercise challenge. RESULTS: Asthma (48% v 22%, p = 0.002) and BHR (p = 0.02) but not atopy were more common in children with SCD than in controls. Atopy (66.6% v 29%, p = 0.007) and asthma (80% v 40%, p = 0.005), particularly atopic asthma (53% v 12%, p<0.001), were more common in children with SCD who had suffered recurrent episodes of ACS than in those who had suffered a single or no episode. CONCLUSIONS: Asthma and BHR are more common in children with SCD than in ethnic matched controls, and atopic asthma appears to be associated with recurrent ACS. Early and effective anti-asthma therapy might reduce the pulmonary morbidity associated with SCD.