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PEDIATRICS Vol. 112 No. 1 July 2003, pp. 87-95

Mycoplasma Disease and Acute Chest Syndrome in Sickle Cell Disease

Lynne Neumayr, MD*, Evelyne Lennette, PhD{ddagger}, Dana Kelly, MPH*, Ann Earles, RN/PNP*, Stephen Embury, MD§, Paula Groncy, MD, Mauro Grossi, MD||, Ranjeet Grover, MD#, Lillian McMahon, MD§§, Paul Swerdlow, MD**, Peter Waldron, MD{ddagger}{ddagger} and Elliott Vichinsky, MD*

* Hematology/Oncology Department, Children’s Hospital Oakland, Oakland, California
{ddagger} Virolab, Inc, Berkeley, California
§ Department of Medicine, San Francisco General Hospital, San Francisco, California
Hematology Department, Long Beach Memorial Hospital, Long Beach, California
|| Pediatric Hematology Department, Children’s Hospital of Buffalo, Buffalo, New York
# Comprehensive Sickle Cell Center, St Luke’s/Roosevelt Hospital, New York, New York
** Division of Hematology, Wayne State University, Detroit, Michigan
{ddagger}{ddagger} Health Sciences Center, Department of Pediatrics, University of Virginia, Charlottesville, Virginia
§§ Boston Medical Center, Boston, Massachusetts


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Background. Acute chest syndrome (ACS) is the leading cause of hospitalization, morbidity, and mortality in patients with sickle cell disease. Radiographic and clinical findings in ACS resemble pneumonia; however, etiologies other than infectious pathogens have been implicated, including pulmonary fat embolism (PFE) and infarction of segments of the pulmonary vasculature. The National Acute Chest Syndrome Study Group was designed to identify the etiologic agents and clinical outcomes associated with this syndrome.

Methods. Data were analyzed from the prospective study of 671 episodes of ACS in 538 patients with sickle cell anemia. ACS was defined as a new pulmonary infiltrate involving at least 1 complete segment of the lung, excluding atelectasis. In addition, the patients had to have chest pain, fever >38.5C, tachypnea, wheezing, or cough. Samples of blood and deep sputum were analyzed for evidence of bacteria, viruses, and PFE. Mycoplasma pneumoniae infection was determined by analysis of paired serologies. Detailed information on patient characteristics, presenting signs and symptoms, treatment, and clinical outcome were collected.

Results. Fifty-one (9%) of 598 episodes of ACS had serologic evidence of M pneumoniae infection. Twelve percent of the 112 episodes of ACS occurring in patients younger than 5 years were associated with M pneumoniae infection. At the time of diagnosis, 98% of all patients with M pneumoniae infection had fever, 78% had a cough, and 51% were tachypneic. More than 50% developed multilobar infiltrates and effusions, 82% were transfused, and 6% required assisted ventilation. The average hospital stay was 10 days. Evidence of PFE with M pneumoniae infection was seen in 5 (20%) of 25 patients with adequate deep respiratory samples for the PFE assay. M pneumoniae and Chlamydia pneumoniae was found in 16% of patients with diagnostic studies for C pneumoniae. Mycoplasma hominis was cultured in 10 (2%) of 555 episodes of ACS and occurred more frequently in older patients, but the presenting symptoms and clinical course was similar to those with M pneumoniae.

Conclusions. M pneumoniae is commonly associated with the ACS in patients with sickle cell anemia and occurs in very young children. M hominis should be considered in the differential diagnosis of ACS. Aggressive treatment with broad-spectrum antibiotics, including 1 from the macrolide class, is recommended for all patients as well as bronchodilator therapy, early transfusion, and respiratory support when clinically indicated.

Key Words: sickle cell • acute chest syndrome • Mycoplasma pneumoniae • Mycoplasma hominis • pulmonary fat embolism • pneumonia

Abbreviations: ACS, acute chest syndrome • PCR, polymerase chain reaction • PFE, pulmonary fat embolism • SCD, sickle cell disease • VOC, vaso-occlusive crisis • Ig, immunoglobulin • IL, interleukin

Acute chest syndrome (ACS) is the leading cause of mortality and morbidity in patients with sickle cell anemia. Radiographic and clinical findings in ACS resemble pneumonia; however, etiologies other than infectious pathogens have been implicated including pulmonary fat embolism (PFE) and infarction secondary to vaso-occlusion of segments of the pulmonary vasculature. Recently, the findings of the National Acute Chest Syndrome Study Group were reported.1 This multicenter prospective study of 671 episodes of ACS in 538 patients was designed to determine the causes, clinical outcome, and prognostic factors associated with this syndrome. An etiologic agent (either infectious or PFE) was identified in 38% of episodes. One of the most frequent infections associated with ACS was Mycoplasma pneumoniae.

The identification of M pneumoniae infections in studies of community acquired lower respiratory tract infections in previously healthy patient groups has ranged from 1% to 30% and tends to be higher in outpatients and in school-aged children than in other age groups.2–19 Epidemics of M pneumoniae infection have also been reported.20–22 The hospital course of patients with lower respiratory infection secondary to Mycoplasma ranges from outpatient treatment with antibiotics to prolonged hospitalizations in the elderly and patients with underlying medical conditions. Although not common, respiratory failure has been documented even in previously healthy patients.23–25 In addition to pneumonia, M pneumoniae has also been associated with pharyngitis, bronchitis,26 asthma,27,28 bronchiolitis obliterans,29,30 acute respiratory distress syndrome,24,31,32 pericarditis,33–35 mediastinitis,36 arthritis,37,38 Stevens-Johnson syndrome and erythema multiforme,39,40 erythema nodosum,41 meningoencephalitis,42–45 and stroke.46 Rarely, deaths have been attributed to Mycoplasma infections.6,25,33,47

There have been only a few reports where Mycoplasma has been associated with ACS in limited numbers of sickle cell patients,48–55 and in many, the clinical outcome of these cases was not fully characterized. The purpose of this report is to describe the incidence and clinical course of M pneumoniae infection in sickle cell disease (SCD) patients with ACS from the National Acute Chest Study Group. We also summarize the clinical outcome of a small group of patients found to have infection with Mycoplasma hominis.


   METHODS
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 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Patients from 30 centers were eligible if they had an electrophoresis of hemoglobin SS, hemoglobin SC, or hemoglobin SB thalassemia, were diagnosed and hospitalized with ACS, and had signed informed consent. ACS was defined as a new pulmonary infiltrate involving at least 1 complete segment consistent with alveolar consolidation, excluding transient atelectasis. In addition, the patients had to have chest pain, fever >38.5°C, tachypnea, wheezing, or cough. From March 1993 through March 1997, 671 episodes of ACS in 538 hospitalized patients were enrolled.

A standardized treatment and monitoring protocol was used.1 Patients were transfused at the discretion of the attending physician for improvement of respiratory status. Transfusion guidelines and methods for identification of alloantibodies have previously been described.1 Standardized forms were used to document medical history, daily physical examinations, radiographs, oxygenation status, transfusions, bronchoscopy complications, and follow-up.

Blood cultures were obtained before the initiation of therapy whenever possible. Bronchoscopy or sputum samples were obtained when possible for aerobic and anaerobic cultures at the participating centers. A bacterial etiology was determined if there was a positive blood culture or heavy growth of an organism from a bronchial or sputum culture with correlative Gram-stain results. Bronchial, sputum, and nasopharynx samples were also sent to Dr. Lennette’s central laboratory for standard viral and Mycoplasma cultures.56–58 All viral and Mycoplasma culture isolates were identified by immunofluorescent staining with specific reagents. Specifically, M pneumoniae and M hominis were cultured on SP4 medium as described.59 Isolates were identified by immunofluorescence staining with fluorescein isothiocyanate-conjugated monospecific antisera provided by Dr J. Tully from the National Institutes of Health.

Legionella pneumophila serogroups were detected by indirect immunofluorescent staining, and respiratory syncytial virus was detected using a direct immunofluorescent antibody technique.

Infection with M pneumoniae was determined by comparing immunoglobulin (Ig) G antibody titers between the acute and convalescent phase of the illness. Only patients with paired serologies within 3 months after the diagnosis of ACS were included in this analysis; patients with only a single IgG titer were excluded. An immune adherence assay was used,58 and a 4-fold rise in IgG titers was considered evidence of M pneumoniae infection. In those patients with high standing IgG titers (IgG levels ≥1024), acute serum was analyzed for the presence of IgM antibodies with an enzyme immunoassay for M pneumoniae (ImmunoWell; Gen Bio, San Diego, CA). Those patients with high standing titers and detectable IgM antibodies were considered acutely infected with M pneumoniae. Indirect immunofluorescence assays were used for the diagnosis of parvovirus B19 and Epstein-Barr virus.60,61

After the study was already underway, diagnostic techniques became available for the diagnosis of C. pneumoniae infection. Respiratory and paired serology samples were then sent to the laboratory of Dr. J. Schachter for Chlamydia culture and analysis of antibody titers by the microimmunofluorescence technique.62 Nonreplicated nasopharynx samples were further analyzed by Dr. D. Dean using the polymerase chain reaction (PCR) for C. pneumoniae.63 The diagnosis of C. pneumoniae infection was made if there was a positive culture, a positive PCR, a 4-fold change in IgG titers, or a high standing IgG titer.1

Intracellular lipid from alveolar macrophages obtained from bronchial samples was evaluated for evidence of PFE according to a modification of the Corwin index.64 Findings from autopsies and histopathology slides were analyzed by the pathology unit for SCD in Alabama.

Statistical Analysis
For comparisons of categorical clinical data between the patients with M pneumoniae and M hominis, a {chi}2 analysis with a continuity adjustment was used. All confidence intervals were 2-sided and a P value of .05 was considered statistically significant. For comparison of continuous variables, we used the Kruskal-Wallis test.


   RESULTS
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 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
M pneumoniae
Paired serologies were analyzed for M pneumoniae from 598 episodes of ACS in 484 patients: results were positive from 51 episodes (9%). No patient had a documented recurrent M pneumoniae infection. In 31 of these 51 patients, a 4-fold rise in IgG titers from the acute to convalescent phase was documented. In the remaining 20 patients, paired IgG titers were greater than or equal to 1024 and the acute serology was positive for IgM. Of the 51 patients with serologic evidence of M pneumoniae infection, 26 patients underwent bronchoscopy and sputum was collected in another 20. The assay for PFE was not interpretable in 50% of the sputum samples because of inadequate sampling of the lower respiratory tract. However, there was evidence of PFE in 5 (20%) of 25 deep respiratory samples available for analysis. In addition, C pneumoniae was found in 5 (16%) of 32 M pneumoniae patients with diagnostic tests for Chlamydia. Other pathogens identified from bronchial or blood cultures in the 51 patients with M pneumoniae were: rhinovirus, respiratory syncytial virus, Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. A total of 9 patients with M pneumoniae had evidence of infection with other pathogens.

The incidence of M pneumoniae was higher in younger patients. M pneumoniae was diagnosed in 12% of the 112 episodes in patients below the age of 5, 14% of the 181 episodes in patients ages 5 to 9.9, 6% of the 98 episodes in patients 10 to 14.9, and in only 3% of the 207 episodes in the 15 and over age group. The demographic characteristics of the patients with M pneumoniae infection are given in Table 1. The average age of the patients with M pneumoniae was 9.7 years (range: 1.6–47.9 years). Fifty-three percent of the patients were female. Most patients had prior serious complications of SCD. Seventy-six percent of the patients had a history of ACS, 72% vaso-occlusive crisis (VOC), and 24% major surgery. At the time of diagnosis of ACS, 98% of patients had a fever, 78% had a cough, 51% were tachypneic, 44% had chest pain, and 39% had abdominal pain. The patients’ hemoglobin had declined 1.0 g/dL on average, and the mean white blood cell count was 21 300. Two thirds of the patients were admitted to the hospital with the diagnosis of ACS, whereas 33% developed ACS after admission for another problem (mostly VOC). Only 1 patient in this study was admitted for elective surgery and went on to develop ACS.


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  		TABLE 1. Demographic and Clinical Characteristics of SCD Patients With ACS Associated With M pneumoniae or M hominis

 
During their hospitalizations, patients developed multilobar disease which was associated with effusions in over half of the patients (Table 2). Empyema was diagnosed in 1 patient and necessitated chest tube placement. Eighty-four percent of patients required oxygen, and 78% were administered bronchodilators. All patients were treated with antibiotic: 92% were treated with erythromycin and 94% with a cephalosporin. Eighty-two percent received transfusions. Complications recorded during the patients’ hospitalization are shown in Table 2. Three of the patients (6%) with M pneumoniae required mechanical ventilation. All 3 were started on erythromycin and bronchodilators, and received transfusions early in their course. Despite this, one 3-year-old boy went on to develop acute respiratory distress syndrome, was intubated for 3 weeks, and was diagnosed with global cognitive impairment presumed to be secondary to anoxic brain injury. A 7-year-old girl developed respiratory failure on the second hospital day and required high-frequency jet ventilation. S aureus was cultured from a bronchoscopy specimen, and in addition to ceftriaxone and clarithromycin, she was treated with nafcillin. A third patient was intubated for 1 day after developing laryngospasm and significant hypoxia after bronchoscopy. The average hospital stay for patients infected with M pneumoniae was 9.8 days.


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  		TABLE 2. Hospital Course of Patients With ACS Associated With M pneumoniae or M hominis Infection

 
M hominis
Cultures were positive for Mycoplasma species in 12 of 555 of these episodes of ACS. In 10 episodes, M hominis was identified by culture and serologies were not consistent with an acute M pneumoniae infection; M pneumoniae was identified in the remaining 2 episodes. Eight of the 10 patients grew M hominis from deep sputum and 2 from bronchoscopy samples. Three of these 10 patients had been previously enrolled in the study, and other etiologies of ACS had been identified; none of the patients had evidence of recurrent M hominis. Multiple pathogens were identified in 2 patients with M hominis: M hominis with rhinovirus in 1 patient and M hominis with Enterobacter, S aureus, and PFE in the other. PFE alone with M hominis was found in a third patient.

The average age of the 10 patients with M hominis was significantly higher than those with M pneumoniae (18.6 vs 9.7, P = .004). The rate of VOC was higher (60% vs 39%) and the duration of hospitalization was longer in the M hominis group (13.1 vs 9.8 days), but these differences were not statistically significant. One patient required mechanical ventilation for 3 weeks, was diagnosed with multi-organ dysfunction, and discharged after a 2-month hospitalization.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Using paired serologies, we identified M pneumoniae in 9% of the episodes of ACS. The current reference laboratory diagnosis of M pneumoniae is by serology based on 4-fold titer changes.65 Our immune adherence assay is a complement fixation assay modified to increase the sensitivity by 8-fold, on par with enzyme immunoassays. Culturing M pneumoniae is problematic, as the organism is both fastidious and difficult to recover from mixed flora because of its slow growth (only microcolonies in weeks). In contrast, M hominis is a much faster growing organism. The combination of an insensitive culture and the very short window during which the organisms are recoverable are the reasons why cultures are considered unreliable, and most likely why we were only able to isolate M pneumoniae from 2 of the respiratory samples in this study. Also, many of the patients were begun on macrolide antibiotics when diagnosed with ACS (before bronchoscopy or sputum sampling). Previous studies of pneumonia in pediatric patients without SCD reported rates of M pneumoniae infection from 9% to 27%.2,8,13,66 This range of estimates may reflect different patient populations (inpatient vs outpatient), diagnostic methods, and seasonal variation.5,20–22 In addition, recent studies have employed PCR techniques for the identification of M pneumoniae; however, there isn’t always agreement between serologic methods and the newer PCR techniques, which have not been standardized.2,44,66–71 Clearly, there are limitations to all of these diagnostic techniques and caution must be used when interpreting data based solely on serologic methods, as in our study.

Several studies have identified M pneumoniae in small groups of SCD patients with ACS.49,53–55,72–75 Incidences of M pneumoniae associated with ACS have been in the range of 13% to 18% of episodes.55,73–75 These studies were in smaller groups of patients and employed different diagnostic criteria than those used in our study. In patients with pneumonia, mixed infections with M pneumoniae have been previously reported.9,76 In our study, we also had several patients with evidence of other infectious pathogens, such as C pneumoniae. In these cases, it is difficult to conclude which pathogen is primarily associated with ACS, or if these are truly "mixed infections". To our knowledge, PFE and Mycoplasma infection have not been previously reported in patients with SCD. Unfortunately, our sample size did not permit a comparison of disease severity between this group and those without PFE.

The youngest patient with M pneumoniae in this study was 1.6 years. Although M pneumoniae is rarely seen in infants,77,78 Waris et al16 did identify it in a 6-month-old with pneumonia. In contrast to other reports where M pneumoniae was more common in older children and adolescents,8,13,16,75 the incidence of M pneumoniae in children under 5 (12%) in our population was similar to that in the 5- to 10-year-olds (14%).

Pneumonia associated with M pneumoniae infection is commonly treated on an outpatient basis,2,12,77,79 and this organism has been identified in asymptomatic children in child care.80 However, some reports have documented respiratory failure and death attributed to M pneumoniae infections.6,23,25,47,81 One study of adults hospitalized for pneumonia documented a respiratory failure rate of 10% in patients presumed to have M pneumoniae. Several of these patients were elderly or had underlying illnesses. There are also case reports of severe M pneumoniae infection in children with SCD.50,53,82,83 We found even higher rates of multilobe involvement, pleural effusion, and transfusion requirements in our patients with ACS associated with M pneumoniae than in previous studies.53,74,75 Additionally, 3 patients (6%) in our study developed respiratory failure despite aggressive therapy. The average hospital stay of 10 days and associated complications reflect the severity of this syndrome.

Evidence of the cytotoxic effects of M pneumoniae in the respiratory tract has been previously deduced from electron microscopy, biopsy, and autopsy studies.84–87 This process and the subsequent inflammatory response—including infiltration of lung parenchyma with lymphocyte, monocyte, and natural killer cells and the production of proinflammatory cytokines88,89—may lead to damage of vascular endothelium, alteration of cellular adhesion properties, regional hypoxia, and further stimulation of cytokine release. In sickle cell patients, these factors can precipitate irreversible sickling and pulmonary entrapment of erythrocytes.90–92 The ability of M pneumoniae to stimulate cytokine production has been documented in several recent reports. In one study, total white blood cell count and cytokines involved in regulation of neutrophil function, interleukin (IL)-8, and granulocyte colony-stimulating factor were found to be higher in patients with bacterial pneumonia; the subset of patients with M pneumoniae had similar IL-8 levels to those with pneumococcal pneumonia.93 Other cytokines, such as IL-6, have been shown to be associated with severity of pneumonia secondary to M pneumoniae infection94 and indicators of clinical recovery.95 Serum adenosine deaminase and free IL-2 receptor levels have been reported to be high in cases of M pneumoniae and useful in distinguishing them from other causes of bacterial pneumonia.96 Furthermore, in a study of cytokine levels in bronchalveolar lavage fluid, IL-2, IL-4, and IL-4/interferon-{gamma} ratios were higher in patients with Mycoplasma than in controls, a response consistent with promotion of IgE production.97 In contrast, depressed cellular immunity in patients with M pneumoniae has been previously shown.98 In his review, Overturf99 described a variety of immunologic abnormalities in patients with SCD. Recently, lymphocytic blastogenic responses and interferon-{gamma} production in vitro have been shown to be significantly decreased in SCD patients with acute pulmonary infections.100 Although the interpretation of the data on the role of cell-mediated and humoral immunity in response to M pneumoniae infection is controversial, the immunologic abnormalities exhibited by patients with SCD likely contribute to the clinical severity of M pneumoniae infection in this population.

Three fourths of the children in this study had experienced major complications of SCD, including VOC and previous episodes of ACS. Twelve percent also had a history of asthma and 36% had wheezing during their hospitalization. Mycoplasma may exacerbate asthma2,27,68,101 and precipitate wheezing in nonasthmatic patients who may then exhibit abnormal lung function years after the initial infection.101–103 The association between reactive airway disease and M pneumoniae infection suggests a role for bronchodilator treatment in the management of ACS attributed to M pneumoniae. The most widely recommended treatment of M pneumoniae infection is the use of macrolide antibiotics. Although it has occasionally been shown to be resistant to erythromycin,102,104–108 the clinical efficacy of erythromycin and other macrolide antibiotics has been repeatedly demonstrated.2,8,109,110 Several reports have also shown better outcomes in patients treated with erythromycin early in the course of their infection.102,111 The duration of treatment is unclear as studies have shown clinical efficacy in the face of persistent positive cultures from upper airway sites.8,107,108 Standard regimens for treatment of M pneumoniae have been 30 to 50 mg/kg divided 2 to 4 times per day for 10 days.112 Azithromycin, 10 mg/kg on the first day and 5 mg/kg per day for 4 additional days, has also been shown to be equally efficacious.8 Other antibiotics for the treatment of M pneumoniae, including fluoroquinolones, have been studied.14,113–117 We recommend that all patients, even infants, with ACS be treated with an antibiotic from the macrolide class and a broad spectrum cephalosporin as well as bronchodilators, oxygen, and transfusion when necessary. However, tetracycline should not be used in children under the age of 8,112 and fluoroquinolones have not been approved for use in children. High-dose prednisone has also been used for the treatment of major complications from M pneumoniae.31,118,119

M hominis infection is most commonly seen in the genitourinary tract. Uncommonly, M hominis has been associated with infections outside the genitourinary tract and has been seen in immunocompromised patients and those recovering from thoracic or transplant surgery.34,36,120–123 In his review, Mufson123 noted that isolation of M hominis from the upper respiratory tract in adults and children with chronic tonsillitis may represent carriage of but not infection with this organism. M hominis pneumonia is seen in neonates and recently has been identified in a few cases of lower respiratory infections in older children and adults.77,124 Although less likely, deep sputum and bronchoscopy samples may be contaminated by organisms in the oropharynx, so isolation of M hominis from these samples may not represent a true pathogen. Interestingly, the average age of the patients in our study with M hominis was 19.

M hominis has been shown to be resistant to erythromycin in vitro.114,117 The minimum inhibitory concentrations of tetracycline appear to be superior, but there is a concern for resistant organisms.114,125,126 Other classes of antibiotics such as the glycylcyclines and fluoroquinolones have shown in vitro activity against M hominis.110,113,115,126–128 Although M hominis was cultured in only 2% of the episodes of ACS in our study, it was associated with significant morbidity and should be considered in the treatment of ACS. Given the small number of patients in whom M hominis was isolated, the comparison of patient demographics, presenting symptoms, response to antibiotics, and clinical course between those patients with M pneumoniae and those with M hominis is inadequate. Clearly, further studies are needed.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
We found serologic evidence of M pneumoniae in 51 (9%) of 598 episodes of ACS in patients with SCD. In fact, 12% of episodes of ACS in patients younger than 5 years were associated with M pneumoniae. All patients were hospitalized for an average of 10 days, and there was a high rate of complications including assisted ventilation in 6%. Nine patients with M pneumoniae also had evidence of infection with other pathogens, and 5 had PFE. M hominis was cultured in 10 additional patients and they tended to be older than those with M pneumoniae. Although serologic methods are limited and isolation of an organism from respiratory samples may represent colonization, we believe M pneumoniae and M hominis should be considered in the treatment of ACS. ACS is a multifactorial syndrome often precipitated by an infectious process that causes cellular destruction, inflammation, and regional hypoxia that leads to erythrocyte sickling and further sickle cell-related injury. All SCD patients with ACS, including children under the age of 5 years, should be treated with broad-spectrum antibiotics, including 1 from the macrolide class. Additionally, bronchial hyperreactivity is common and bronchodilator therapy is usually indicated. We recommend early leukocyte-depleted, matched, simple transfusions for patients with significant anemia, multilobar pneumonia, any signs of respiratory distress on oxygen, and those at risk for complications.


   ACKNOWLEDGMENTS
 
We extend our profound thanks to Shanda Robertson for developing and managing the database for the National Acute Chest Study and for editorial assistance. We also thank Klara Kleman for tracking the shipments of laboratory specimens and recording the results of these studies, and Dr Julius Schachter and his laboratory for analyzing the chlamydia serologies and cultures.

The following investigators also participated in the National Acute Chest Syndrome Study Group: Charles Daeschner (East Carolina University, Greenville, NC), Paula Groncy (Long Beach Memorial Hospital, Long Beach, CA), Rathi Iyer (University of Mississippi, Jackson, MS), Thomas Kinney (Duke University Medical Center, Durham, NC), Mabel Koshy (University of Illinois, Chicago, IL), Wayne Rackoff (Indiana University Medical Center, Indianapolis, IN), Charles Pegelow (University of Miami, Miami, FL), Heather Hume (St Justine Hospital, Montreal, Quebec, Canada), James Parke (Carolinas Medical Center, Charlotte, NC), Lillian McMahon (Boston Medical Center, Boston, MA), Lennette Benjamin and Marc Bestak (Albert Einstein College of Medicine-Montefiore Hospital, Bronx, NY), Felicia Little and Yih Ming-Yang (University of South Alabama, Mobile, AL), Peter Waldron (University of Virginia, Charlottesville, VA), Doris Wethers and Gloria Ramirez (St Luke’s-Roosevelt Hospital, New York, NY), Neil Grossman (Medical College of Virginia, Richmond, VA), Stephen Embury and William Mentzer (San Francisco General Hospital, San Francisco, CA), Mauro Grossi (Children’s Hospital of Buffalo, Buffalo, NY), Susan Claster (Summit Medical Center, Oakland, CA), Ludovico Guarini (Interfaith Medical Center, Bronx, NY), Maria Koehler (Children’s Hospital of Pittsburgh, Pittsburgh, PA), James Eckman and Tom Adamkiewicz (Emory University, Atlanta, GA), Elizabeth Lowenthal (University of Alabama at Birmingham, Birmingham, AL), Paul Swerdlow (Wayne State University, Detroit, MI), and Cage Johnson (University of Southern California Medical Center, Los Angeles, CA).


   FOOTNOTES
 
Received for publication Jul 2, 2002; Accepted Nov 22, 2002.

Address correspondence to Lynne Neumayr, MD, Children’s Hospital Oakland, Department of Hematology, 747 52nd Street, Oakland, CA 94609. E-mail: lneumayr{at}mail.cho.org


   REFERENCES
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 DISCUSSION
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M. pneumoniae, a Common Cause of Acute Chest Syndrome in Children with SCD
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