- Email: [email protected]
Asthma Management by Monitoring Sputum Neutrophil Count
Asthma Management by Monitoring Sputum Neutrophil Count* Shelley Pallan, BSc; ]anles B. Mahony, PhD; Paul M . O'Byrne, MB, FCCP; and Paralneswaran Nair, MD, PhD, FCCP
We report the utility of quantitative cell counts in sputum in monitoring therapy of a patient with poorly controlled asthma. Recurrent neutrophilic bronchitis without an eosinophilic bronchitis led to the identification of Chkmydophdla pneumoniae as the cause of bronchitis and asthma exacerbation. Serial examination of blood and sputum by polymerase chain reaction for C pneumoniae helped to prevent exacerbations by prophylactic antibiotic therapy, reduce the dose of prednisone and inhaled corticosteroids, and improve asthma control.
(CHEST 2008; 134:628-630) Key words: asthma; Chlamydophtla pnaimoniae; neutrophils; sputum cell counts Abbreviations: IL = interleukin; PCR = polymerase chain reaction; TCC = totd cell cvunt
xacerbation of asthma has various etiologies. The bronchitis associated with these exacerbations depends on the cause of the exacerbation.' This can be now be accurately measured by quantitative sputum cell counts.2 An eosin-
E
For editorial comment see page 475 ophilic bronchitis is generally associated with hypersensitivity to environmental antigens, whereas a neutrophilic bronchitis usually suggests an infection.2 We present a case of recurrent asthma exacerbations in a patient whose sputum cell counts showed neutrophilic bronchitis. This
led to the identification of Chlamydophila pneumoizine as the cause of bronchitis and asthma exacerbations that were prevented by prophylactic antibiotic therapy. We also discuss investigation and management of exacerbations of asthma associated with neutrophilic bronchitis.
CASEREPORT A 47-year-old woman had asthma since childhood and a history of nasal polyps, aspirin sensitivity, and gastroesophageal reflw. She was a lifetime nonsmoker with no reported occupational exposures. Her asthma was well controlled with budesonide, 200 pg three for four puffs bid, and formoterol, 12 pg two puffs bid, until 2 years ago. Over the last 2 years, she had three episodes of cough and yellow sputum. A highresolution CT scan of the thorax did not show my ahnormalities. Most recently, the patient presented with a 10-day history of nocturnal wheezing and mucopurulent sputum. She had started herself on prednisone, 30 mg/d. as had been the previous practice. This did not relieve her symptoms. Sputum induction with a hypertonic saline solution aerosol as described previously3 revealed a total cell count of 98.4 X 10' cells/g, of which 93% were neutrophils and there were no eosinophils (healthy adults: < 9.7 X loficells/g, < 64.4%, and < 2% reupectively).4 Sputum routine culture findings were negative for seven common respiratory viruses and bacteria. The CBC count showed mildly low total lymphocytes and a low CD4+ component. Microimmunofluorescence assay for Chlamydia and Mycoplasina species were negative. A quantitative polymerase chain reaction (PCR) analysis5 of blood and sputum was positive for C prieurnoniue and negative for Chlamydophila trachomutis. The patient was prescribed azithromycin, 500 mg qd for 3 days, and 500 mg 1 day per week for the following 5 weeks. She was advised to discontinue prednisone Over the following 4 years, monitoring of sputum cells and prophylactic macrolide therapy with increasing C pneuinonfue titers prevented exacerbations without the need for systemic corticosteroids and enabled the reduction of hudesonide dose to 1,200 to 1,600 p g d . A summary of the course of the symptoms, lung function tests, and treatment is provided in Table 1.
DISCUSSION 'From the Firestone Institute for Respiratory Health and Department of Medicine (Ms. Pallan, Dr. O'Byrne, and Dr. Nair) .uid Department of Molecular Medicine (Dr. Mahony), McMaster Universitr, Hamilton, ON, Canada. Dr. Nair ha ds a Canada Research Chair in Airway Regulation and Inflammation The authors have no conflicts of interest to disclose. Manuscript received January 10, 2008; revision accepted March 6 , 2008. Reproduction of this article is rolrihited without written permission from the American College ofchest Physicians (www.chestjoumal. org/misc/re rints shtml) Correqx)n&nc;io: Par&teswaran Nair, MD, PhD, FCCP, Fireytorze Institute fur Re.rpiratoy Health, St. ]o.seph's Heulthcare, Haniilton ON, LRN4A6, C a n a h , e-mail: [email protected] DOI: 10.1378/chest.08-0400 ~
028
This case report illustrates the utility of identifying the presence and cellular type of bronchitis associated with asthma exacerbation. Exacerbations associated with eosinophilic bronchitis respond to treatment with corticosteroids, whereas noneosinophilic (usually neutrophilic) exacerbations usually do not." The nature of bronchitis may change in the same patient depending on the cause.' An eosinophilic bronchitis (sputum eosinophils 2%)is treated by increasing the dose of antiinflammatory therapy. If the eosinophil count is between 1%and 2%, current dose of antiinflammatory drugs is unchanged. If no eosinophils are detected, we recommend reducing the dose of corticosteroids.fi Selected Reports
-. IC ?
01
www.chestjournal.org
A neutrophilic bronchitis with a raised total cell count can be arbitrarily graded as mild if the total count is > 9.7 million cells/g but < 20 (noninfective), moderate if 20 to <50 (viral or bacterial), and intense if 2 5 0 million celldg, and suggests bacterial infectionz; however, this requires further validation. When there i s a persistent or recurrent intense neutrophilia, bronchiectasis with infective bronchitis should be suspected.8 In such situations, an eosinophilic bronchitis may be masked, and therefore it is useful to check the sputum cell counts after the neutrophilia has resolved to decide changes to corticosteroid dosage.9 A combination of eosinophilic and persistent neutrophilic bronchitis may suggest allergic sensitization to fungi such as aspergillus and consequent bronchiectasis. l o Noninfectitious causes such as exposure to endotoxins, contaminated metal-working fluids,ll and inflammatory bowel disease may also be associated with a neutrophilic bronchitis (Table 2). Treatment is thus directed against the specific cause that is identified. Increased expression of the receptors Toll-like receptor 2, Toll-like receptor 4, and CD14, as well as the proinflammatory cytokines interleukin (IL)-8 and IL-lp, along with high airway levels of endotoxin, have been reported in such patients, suggesting a disordered innate inimune response." Novel therapies such as antagonism of leukotriene B,, and inhibition of the neutrophil chemoattractant IL-8 using specific monoclonal antibodies directed against its receptor, CXCR2, are currently being evaluated. In this patient, the recurrent neutrophilic bronchitis was due to infection with C pneurnoniae. It is an obligate intracellular Gram-negative bacterium that has been found in the airways of patients with stable asthma13 and during exacerbations.l4 Treatment of acute exacerbations of asthma and treatment of severe refractory noneosinophilic asthma with macrolides are reported to improve asthma outcomes.'5.16 C pneurnoniae bacteria can replicate within neutrophils, which may exacerbate neutrophlic inflammation.l7 Although microimmunofluorescence test is the recommended serological test, evidence of infection by PCR but not by serology is predictive of response to treatment with clarithromycin.18 Since approximately 20% of the population does not seroconvert to C pneurnoniae despite repeated community exposure it is possible to have PCR positive patients that lack antibody. Our PCR assay detects bacterial DNA and therefore does not distinguish between live or dead chlamydia. It is possible that treatment of our patient with antibiotics induced a nonreplicating state (persistent bodies) that remains transcriptionally active, secreting chlamydia1 lipopolysaccharide that can stimulate the immune response. In summary, identification of neutrophilic bronchitis and C pneuinoniae ainvay infection led to prevention of asthma exacerbations and, more importantly, to reduction of excessive treatment with corticosteroids. We recommend examination for evidence of chlamydial infection in patients with asthma who have recurrent or persistent neutrophilic bronchitis and exacerbations despite being on high doses of corticosteroids, particularly if there is a history of clinical response to macrolide antibiotics. CHEST I 134 J 3 I SEPTEMBER, 2008
629
Table 2-Znvestigation and Management of Persistent Neutrophilic Bronchitis in Patients With h t h m a Etiology Occupational exposure Bronchiectasis Immune deficiency disorders Cystic fibrosis Chronic aspiration Inflammatory bowel diseases Specific organisms, eg, nontubercular mycobacteria, chlamydia
Investigation
ManaEement
Sweat chloride, genotype, nasal electrical potential High-resolution CT of chest, CT of sinus, ciliary motility studies, fungal precipitins Quantitative Igs, neutrophil phagocytosis function
Removal from exposure Surgical resection, postural drainage and physiotherapy, antibiotics, antifungals Ig replacement, long-term antibiotics, specific therapies Specific antibiotics, physiotherapy, nutrition Specific measures to minimize aspiration
Sweat chloride, genotype, nasal electrical potential History, swallowing assessment, lipid index in sputum macrophages History, duodenojejunoscopy, colonoscopy, and biopsy Sputum culture, PCR
REFERENCES 1 Hargreave FE, Parameswaran K. Asthma, COPD and bron-
chitis are just components of ainvay disease: Eur Respir J 2006; 28:264-267 2 Hargreave FE. Quantitative sputum cell counts as a marker of ainvay inflammation in clinical practice. Curr Opin Allergy Clin Immunol 2007; 7:102-106 3 Pizzichini E, Pizzichini MM, Efthimiadis A, et al. Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination. Eur Respir J 1996; 6:1174-1180 4 Belda J, Leigh R, Parameswaran K, et al. Induced sputum cell counts in healthy adults. Am J Respir Crit Care Med 2000; 161:475-478 5 Smieja M, Chong S, Natarajan M. et al. Circulating nucleic acids of Chlamydia pneumoniae and cytomegalovirus in patients undergoing coronary angiography. J Clin Microbiol 2001; 39:596-80 6 Jayaram L, Pizzichini MM, Cook RJ, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J 2006; 27:483-494 7 D'silva L, Cook RJ. Allen CJ, et al. Changing pattern of sputum cell counts during successive exacerbations of airway disease. Respir Med 2007; 101:2217-2220 8 Nair P, Allen CJ, Hargreave FE. Sputum cell counts in bronchiectasis. Eur Respir J 2005; 26(suppl 49):484s 9 D'silva L, Allen CJ, Hargreave FE, et al. Sputum neutrophilia can mask eosinophilic bronchitis during exacerbations. Can Respir J 2007; 14:281-284 10 Wmk PA, Saltos N, Simpson J, et al. Induced sputum eosinophils and neutrophils and bronchiectasis severity in allergic bronchopulmonary aspergi'llosis. Eur Respir J 2000; 16:1095-1101 11 Leigh R, Hargreave FE. Occupational neutrophilic asthma. Can Respir J 1999; 6:194-196 12 Simpson JL, Grissell TV, Douwes J, et al. Innate immune activation in neutrophilic asthma and bronchiectasis. Thorax 2007; 62:211-218 13 Johnston SL, Martin RJ. Chlamydophila pneumoniae and Mycoplasma pnewnoniae: a role in asthma pathogenesis? Am J Respir Crit Care Med 2005; 172:1078-1089 14 Nlegra L, Blasi F, Centanni S, et al. Acute exacerbations of asthma in adults: role of Chlainydia pneumoiiiae infection. Eur Respir J 1994; 7:2165-2168 15 Johnston SL, Blasi F, Black PN, et al. The effect of telithromycin in acute exacerbations of asthma. N Engl J Med 2006; 354:1589-1600 16 Simpson JL, Powell H, Boyle MJ, et al. Clarithromycin targets 630
Specific therapy, consider anti-tumor necrosis factor for patients with refractory asthma Specific antimicrobial chemotherapy
neutrophilic ainvay inflammation in refractory asthma. Am J Respir Crit Care Med 2008; 177:148-155 17 Rodriguez N, Fend F, Jennen L, et al. Polymorphonuclear neutrophils improve replication of Chlamydia pneuruniae in v i m upon MyD88-dependent attraction. J Iminunol 2005; 17434836-4844 18 Kraft M, Casse'll GH, Pak J, et al. Mycoplruma pneumnoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin. Chest 2002; 121:1782-1788
Utility of Virtual BronchoscopyGuided Transbronchial Biopsy for the Diagnosis of Pulmonary Sarcoidosis* Report of Two Cases Myrna C. B. Godoy, MD; David Ost, MD, FCCP; Bernhard Geiger, PhD; Carol Novak, PhD; Daisuke Nonaka, MD; Ioannis Vlahos, MRCP; and David P. Naidich, MD, FCCP
Sarcoidosis is a multisystem granulomatous disease
of unknown etiology that usually affects the lungs. Although flexible fiberoptic bronchoscopy with transbronchial lung biopsy (TBBx) has a high diag~
'From Department of Radiology (Drs. Godoy, Vlahos, and Naidich) and Pathology (Dr. Nonaka), New York University Medical Center, and Department of Pulmonary Medicine (Dr. Ost), New York University School of Medicine, New, York, NY; and Siemens Corporate Research (Drs. Geiger and Novak), Princeton, NJ. The authors have no conflicts of interest to disclose. Manuscript received January 13, 2098; revision acoepted March 13, 2008. Reproductionof this article is rohibited without written permission from the American College o!Chest Physicians (w.chestjournal. org/misc/re rints.shtm1). CorresponLnce to: David P. Naidich, MD, FCCP, Departnzent of Radiolog N e u York Universit Medical Center, 560 First Ave, New Y o r i NY 10016; e-inail: ~vid.noidich9nyunlc.org DOI: 10.13 78/chest.08-O052 Selected Reports
We report the utility of quantitative cell counts in sputum in monitoring therapy of a patient with poorly controlled asthma. Recurrent neutrophilic bronchitis without an eosinophilic bronchitis led to the identification of Chkmydophdla pneumoniae as the cause of bronchitis and asthma exacerbation. Serial examination of blood and sputum by polymerase chain reaction for C pneumoniae helped to prevent exacerbations by prophylactic antibiotic therapy, reduce the dose of prednisone and inhaled corticosteroids, and improve asthma control.
(CHEST 2008; 134:628-630) Key words: asthma; Chlamydophtla pnaimoniae; neutrophils; sputum cell counts Abbreviations: IL = interleukin; PCR = polymerase chain reaction; TCC = totd cell cvunt
xacerbation of asthma has various etiologies. The bronchitis associated with these exacerbations depends on the cause of the exacerbation.' This can be now be accurately measured by quantitative sputum cell counts.2 An eosin-
E
For editorial comment see page 475 ophilic bronchitis is generally associated with hypersensitivity to environmental antigens, whereas a neutrophilic bronchitis usually suggests an infection.2 We present a case of recurrent asthma exacerbations in a patient whose sputum cell counts showed neutrophilic bronchitis. This
led to the identification of Chlamydophila pneumoizine as the cause of bronchitis and asthma exacerbations that were prevented by prophylactic antibiotic therapy. We also discuss investigation and management of exacerbations of asthma associated with neutrophilic bronchitis.
CASEREPORT A 47-year-old woman had asthma since childhood and a history of nasal polyps, aspirin sensitivity, and gastroesophageal reflw. She was a lifetime nonsmoker with no reported occupational exposures. Her asthma was well controlled with budesonide, 200 pg three for four puffs bid, and formoterol, 12 pg two puffs bid, until 2 years ago. Over the last 2 years, she had three episodes of cough and yellow sputum. A highresolution CT scan of the thorax did not show my ahnormalities. Most recently, the patient presented with a 10-day history of nocturnal wheezing and mucopurulent sputum. She had started herself on prednisone, 30 mg/d. as had been the previous practice. This did not relieve her symptoms. Sputum induction with a hypertonic saline solution aerosol as described previously3 revealed a total cell count of 98.4 X 10' cells/g, of which 93% were neutrophils and there were no eosinophils (healthy adults: < 9.7 X loficells/g, < 64.4%, and < 2% reupectively).4 Sputum routine culture findings were negative for seven common respiratory viruses and bacteria. The CBC count showed mildly low total lymphocytes and a low CD4+ component. Microimmunofluorescence assay for Chlamydia and Mycoplasina species were negative. A quantitative polymerase chain reaction (PCR) analysis5 of blood and sputum was positive for C prieurnoniue and negative for Chlamydophila trachomutis. The patient was prescribed azithromycin, 500 mg qd for 3 days, and 500 mg 1 day per week for the following 5 weeks. She was advised to discontinue prednisone Over the following 4 years, monitoring of sputum cells and prophylactic macrolide therapy with increasing C pneuinonfue titers prevented exacerbations without the need for systemic corticosteroids and enabled the reduction of hudesonide dose to 1,200 to 1,600 p g d . A summary of the course of the symptoms, lung function tests, and treatment is provided in Table 1.
DISCUSSION 'From the Firestone Institute for Respiratory Health and Department of Medicine (Ms. Pallan, Dr. O'Byrne, and Dr. Nair) .uid Department of Molecular Medicine (Dr. Mahony), McMaster Universitr, Hamilton, ON, Canada. Dr. Nair ha ds a Canada Research Chair in Airway Regulation and Inflammation The authors have no conflicts of interest to disclose. Manuscript received January 10, 2008; revision accepted March 6 , 2008. Reproduction of this article is rolrihited without written permission from the American College ofchest Physicians (www.chestjoumal. org/misc/re rints shtml) Correqx)n&nc;io: Par&teswaran Nair, MD, PhD, FCCP, Fireytorze Institute fur Re.rpiratoy Health, St. ]o.seph's Heulthcare, Haniilton ON, LRN4A6, C a n a h , e-mail: [email protected] DOI: 10.1378/chest.08-0400 ~
028
This case report illustrates the utility of identifying the presence and cellular type of bronchitis associated with asthma exacerbation. Exacerbations associated with eosinophilic bronchitis respond to treatment with corticosteroids, whereas noneosinophilic (usually neutrophilic) exacerbations usually do not." The nature of bronchitis may change in the same patient depending on the cause.' An eosinophilic bronchitis (sputum eosinophils 2%)is treated by increasing the dose of antiinflammatory therapy. If the eosinophil count is between 1%and 2%, current dose of antiinflammatory drugs is unchanged. If no eosinophils are detected, we recommend reducing the dose of corticosteroids.fi Selected Reports
-. IC ?
01
www.chestjournal.org
A neutrophilic bronchitis with a raised total cell count can be arbitrarily graded as mild if the total count is > 9.7 million cells/g but < 20 (noninfective), moderate if 20 to <50 (viral or bacterial), and intense if 2 5 0 million celldg, and suggests bacterial infectionz; however, this requires further validation. When there i s a persistent or recurrent intense neutrophilia, bronchiectasis with infective bronchitis should be suspected.8 In such situations, an eosinophilic bronchitis may be masked, and therefore it is useful to check the sputum cell counts after the neutrophilia has resolved to decide changes to corticosteroid dosage.9 A combination of eosinophilic and persistent neutrophilic bronchitis may suggest allergic sensitization to fungi such as aspergillus and consequent bronchiectasis. l o Noninfectitious causes such as exposure to endotoxins, contaminated metal-working fluids,ll and inflammatory bowel disease may also be associated with a neutrophilic bronchitis (Table 2). Treatment is thus directed against the specific cause that is identified. Increased expression of the receptors Toll-like receptor 2, Toll-like receptor 4, and CD14, as well as the proinflammatory cytokines interleukin (IL)-8 and IL-lp, along with high airway levels of endotoxin, have been reported in such patients, suggesting a disordered innate inimune response." Novel therapies such as antagonism of leukotriene B,, and inhibition of the neutrophil chemoattractant IL-8 using specific monoclonal antibodies directed against its receptor, CXCR2, are currently being evaluated. In this patient, the recurrent neutrophilic bronchitis was due to infection with C pneurnoniae. It is an obligate intracellular Gram-negative bacterium that has been found in the airways of patients with stable asthma13 and during exacerbations.l4 Treatment of acute exacerbations of asthma and treatment of severe refractory noneosinophilic asthma with macrolides are reported to improve asthma outcomes.'5.16 C pneurnoniae bacteria can replicate within neutrophils, which may exacerbate neutrophlic inflammation.l7 Although microimmunofluorescence test is the recommended serological test, evidence of infection by PCR but not by serology is predictive of response to treatment with clarithromycin.18 Since approximately 20% of the population does not seroconvert to C pneurnoniae despite repeated community exposure it is possible to have PCR positive patients that lack antibody. Our PCR assay detects bacterial DNA and therefore does not distinguish between live or dead chlamydia. It is possible that treatment of our patient with antibiotics induced a nonreplicating state (persistent bodies) that remains transcriptionally active, secreting chlamydia1 lipopolysaccharide that can stimulate the immune response. In summary, identification of neutrophilic bronchitis and C pneuinoniae ainvay infection led to prevention of asthma exacerbations and, more importantly, to reduction of excessive treatment with corticosteroids. We recommend examination for evidence of chlamydial infection in patients with asthma who have recurrent or persistent neutrophilic bronchitis and exacerbations despite being on high doses of corticosteroids, particularly if there is a history of clinical response to macrolide antibiotics. CHEST I 134 J 3 I SEPTEMBER, 2008
629
Table 2-Znvestigation and Management of Persistent Neutrophilic Bronchitis in Patients With h t h m a Etiology Occupational exposure Bronchiectasis Immune deficiency disorders Cystic fibrosis Chronic aspiration Inflammatory bowel diseases Specific organisms, eg, nontubercular mycobacteria, chlamydia
Investigation
ManaEement
Sweat chloride, genotype, nasal electrical potential High-resolution CT of chest, CT of sinus, ciliary motility studies, fungal precipitins Quantitative Igs, neutrophil phagocytosis function
Removal from exposure Surgical resection, postural drainage and physiotherapy, antibiotics, antifungals Ig replacement, long-term antibiotics, specific therapies Specific antibiotics, physiotherapy, nutrition Specific measures to minimize aspiration
Sweat chloride, genotype, nasal electrical potential History, swallowing assessment, lipid index in sputum macrophages History, duodenojejunoscopy, colonoscopy, and biopsy Sputum culture, PCR
REFERENCES 1 Hargreave FE, Parameswaran K. Asthma, COPD and bron-
chitis are just components of ainvay disease: Eur Respir J 2006; 28:264-267 2 Hargreave FE. Quantitative sputum cell counts as a marker of ainvay inflammation in clinical practice. Curr Opin Allergy Clin Immunol 2007; 7:102-106 3 Pizzichini E, Pizzichini MM, Efthimiadis A, et al. Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination. Eur Respir J 1996; 6:1174-1180 4 Belda J, Leigh R, Parameswaran K, et al. Induced sputum cell counts in healthy adults. Am J Respir Crit Care Med 2000; 161:475-478 5 Smieja M, Chong S, Natarajan M. et al. Circulating nucleic acids of Chlamydia pneumoniae and cytomegalovirus in patients undergoing coronary angiography. J Clin Microbiol 2001; 39:596-80 6 Jayaram L, Pizzichini MM, Cook RJ, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J 2006; 27:483-494 7 D'silva L, Cook RJ. Allen CJ, et al. Changing pattern of sputum cell counts during successive exacerbations of airway disease. Respir Med 2007; 101:2217-2220 8 Nair P, Allen CJ, Hargreave FE. Sputum cell counts in bronchiectasis. Eur Respir J 2005; 26(suppl 49):484s 9 D'silva L, Allen CJ, Hargreave FE, et al. Sputum neutrophilia can mask eosinophilic bronchitis during exacerbations. Can Respir J 2007; 14:281-284 10 Wmk PA, Saltos N, Simpson J, et al. Induced sputum eosinophils and neutrophils and bronchiectasis severity in allergic bronchopulmonary aspergi'llosis. Eur Respir J 2000; 16:1095-1101 11 Leigh R, Hargreave FE. Occupational neutrophilic asthma. Can Respir J 1999; 6:194-196 12 Simpson JL, Grissell TV, Douwes J, et al. Innate immune activation in neutrophilic asthma and bronchiectasis. Thorax 2007; 62:211-218 13 Johnston SL, Martin RJ. Chlamydophila pneumoniae and Mycoplasma pnewnoniae: a role in asthma pathogenesis? Am J Respir Crit Care Med 2005; 172:1078-1089 14 Nlegra L, Blasi F, Centanni S, et al. Acute exacerbations of asthma in adults: role of Chlainydia pneumoiiiae infection. Eur Respir J 1994; 7:2165-2168 15 Johnston SL, Blasi F, Black PN, et al. The effect of telithromycin in acute exacerbations of asthma. N Engl J Med 2006; 354:1589-1600 16 Simpson JL, Powell H, Boyle MJ, et al. Clarithromycin targets 630
Specific therapy, consider anti-tumor necrosis factor for patients with refractory asthma Specific antimicrobial chemotherapy
neutrophilic ainvay inflammation in refractory asthma. Am J Respir Crit Care Med 2008; 177:148-155 17 Rodriguez N, Fend F, Jennen L, et al. Polymorphonuclear neutrophils improve replication of Chlamydia pneuruniae in v i m upon MyD88-dependent attraction. J Iminunol 2005; 17434836-4844 18 Kraft M, Casse'll GH, Pak J, et al. Mycoplruma pneumnoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin. Chest 2002; 121:1782-1788
Utility of Virtual BronchoscopyGuided Transbronchial Biopsy for the Diagnosis of Pulmonary Sarcoidosis* Report of Two Cases Myrna C. B. Godoy, MD; David Ost, MD, FCCP; Bernhard Geiger, PhD; Carol Novak, PhD; Daisuke Nonaka, MD; Ioannis Vlahos, MRCP; and David P. Naidich, MD, FCCP
Sarcoidosis is a multisystem granulomatous disease
of unknown etiology that usually affects the lungs. Although flexible fiberoptic bronchoscopy with transbronchial lung biopsy (TBBx) has a high diag~
'From Department of Radiology (Drs. Godoy, Vlahos, and Naidich) and Pathology (Dr. Nonaka), New York University Medical Center, and Department of Pulmonary Medicine (Dr. Ost), New York University School of Medicine, New, York, NY; and Siemens Corporate Research (Drs. Geiger and Novak), Princeton, NJ. The authors have no conflicts of interest to disclose. Manuscript received January 13, 2098; revision acoepted March 13, 2008. Reproductionof this article is rohibited without written permission from the American College o!Chest Physicians (w.chestjournal. org/misc/re rints.shtm1). CorresponLnce to: David P. Naidich, MD, FCCP, Departnzent of Radiolog N e u York Universit Medical Center, 560 First Ave, New Y o r i NY 10016; e-inail: ~vid.noidich9nyunlc.org DOI: 10.13 78/chest.08-O052 Selected Reports