- Email: [email protected]
Hypopnea Scoring in the Sleep Heart Health Study
Therefore, in combination with other noninvasive studies, CT may still have some utility in helping clinicians identify those patients in whom right-heart catheterization is either unnecessary or low yield. Hubert Chen, MD, MPH Teresa De Marco, MD Jeffrey A. Golden, MD, FCCP University of California, San Francisco San Francisco, CA Michael K. Gould, MD, FCCP Stanford University School of Medicine Palo Alto, CA The authors have no conflicts of interest to disclose. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Hubert Chen, MD, MPH, 350 Parnassus Ave, Suite 609, San Francisco, CA 94143; e-mail: [email protected] DOI: 10.1378/chest.07-2761
References 1 Zisman DA, Karlamangla AS, Ross DJ, et al. High-resolution chest CT findings do not predict the presence of pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Chest 2007; 132:773–779 2 Tan RT, Kuzo R, Goodman LR, et al. Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease: medical College of Wisconsin Lung Transplant Group. Chest 1998; 113:1250 –1256
Response To the Editor: Chen and colleagues1 examined the diagnostic value of mean pulmonary artery diameter (MPAD) ⱖ 29 mm to predict pulmonary hypertension using Figure 2 from our study.2 Given the relatively high sensitivity and negative predictive value obtained by this approach, they astutely point out that CT may have a role in screening for pulmonary hypertension in patients with idiopathic pulmonary fibrosis. This assertion has merit; however, any test can be made sensitive by selecting a low-enough cutoff but, as in this case, at the expense of specificity. Figure 2 only shows 56 of the 65 observations (9 are superimposed). With the entire data set, a MPAD cutoff ⱖ 29 mm had sensitivity, specificity, positive predictive value, and negative predictive value for pulmonary hypertension (defined as mean pulmonary artery pressure [MPAP] from rightheart catheterization ⬎ 25 mm Hg) of 85 to 100%, 10 to 38%, 34 to 61%, and 60 to 100%, respectively. Only 8 of 65 patients (12%) in the data set had MPADs ⬍ 29 mm, and this is reflected by a wide confidence interval for the negative predictive value estimate. Accordingly, the negative predictive value could be as low as 60%; in our opinion, this figure is too small to accept MPAD as a screening tool for a condition with potentially devastating consequences in idiopathic pulmonary fibrosis. Furthermore, as reflected by an unacceptably low specificity, of those without pulmonary hypertension, only 8 of 38 patients (21%) had MPADs ⬍ 29 mm. Simpler and less expensive clinical measurements (oxygen saturation using pulse oximetry, percentage of predicted FVC, and percentage of predicted diffusion capacity of the lung for carbon monoxide) can be used to screen for pulmonary hypertension in patients with idiopathic pulmonary fibrosis.3,4 Recently, we validated a formula to predict MPAP from standard lung function measurements.4 A 1054
formula-predicted MPAP ⬎ 21 mm Hg was associated with a sensitivity, specificity, positive predictive value, and negative predictive value of 74 to 99%, 41 to 73%, 35 to 70%, and 78 to 100%, respectively, for pulmonary hypertension defined as MPAP from right-heart catheterization ⬎ 25 mm Hg. We recommend this method over MPAD from CT to screen for pulmonary hypertension in patients with advanced idiopathic pulmonary fibrosis. David A. Zisman, MD, MS, FCCP Arun S. Karlamangla, PhD, MD David Geffen School of Medicine University of California, Los Angeles Los Angeles, CA The authors have no conflicts of interest to disclose. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: David A. Zisman, MD, MS, FCCP, Interstitial Lung Disease Center, David Geffen School of Medicine at UCLA, 37-131 Center for Health Sciences, Los Angeles, CA 90095; e-mail: [email protected] DOI: 10.13678/chest.07-2993
References 1 Chen H, Gould MK, De Marco T, et al. Utility of CT for predicting pulmonary hypertension in patients with parenchymal lung disease: similar results, different conclusion? Chest 2008; 133:1053–1054 2 Zisman DA, Karlamangla A, Ross DJ, et al. High-resolution chest computed tomography findings do not predict the presence of pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Chest 2007; 132:773–779 3 Zisman DA, Ross DJ, Belperio JA, et al. Prediction of pulmonary hypertension in idiopathic pulmonary fibrosis. Respir Med 2007; 101:2153–2159 4 Zisman DA, Karlamangla A, Kawut SM, et al. Validation of a method to screen for pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Chest 2008; 133:640 – 645
Hypopnea Scoring in the Sleep Heart Health Study To the Editor: It has come to our attention that the American College of Chest Physicians CD, “Sleep: Study Lessons in Education; product code 6633” has misinterpreted some of the findings from the Sleep Heart Health Study (SHHS). In the section, “Sleep-Disordered Breathing Events: Question 5, A. Hypopnea,” it is stated that “In fact, the scorers of the polysomnographies in the SHHS required a 4% oxyhemoglobin desaturation in order to score either apneas or hypopneas, because they could not achieve inter-rater reliability of apneas and hypopneas otherwise. Thus, the SHHS outcome data are essentially based on oximetry.” These two sentences are incorrect. Although it is true that the SHHS requires a 4% oxygen desaturation as one of its criteria to identify a hypopnea in most of its publications, this desaturation criterion was not chosen because we were unable to otherwise obtain interrater reliability using other criteria. Rather, a 4% oxygen desaturation was chosen because we wished to be consistent with the scoring criteria used by the Wisconsin Sleep Cohort so that comparisons could be made between the studies. Moreover, in the article by Whitney et al,1 we demonstrated that the intraclass correlation coefficients using various oxygen desaturation criteria were all ⬎ 0.90. We hope that this error will not be perpetuated in future editions of the education CDs on polysomnography, and that readers of CHEST who also use the Sleep Study Lessons CD will realize that this statement is not correct. Correspondence
Stuart F. Quan, MD, FCCP Harvard Medical School Boston, MA Susan Redline, MD, MPH Case Western Reserve University Cleveland, OH The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Stuart F. Quan, MD, FCCP, Harvard Medical School, Division of Sleep Medicine, 401 Park Dr, 2nd Floor, Boston, MA 02215; e-mail: [email protected] DOI: 10.1378/chest.07-2877
Reference 1 Whitney CW, Gottlieb DJ, Redline S, et al. Reliability of scoring respiratory disturbance indices and sleep staging. Sleep 1998; 21:749 –757
Response To the Editor: In response to the letter of Drs. Quan and Redline regarding the American College of Chest Physicians (ACCP) product No. 6633, “SLEEP 2-Study Lessons in the Education and Evaluation of Polysomnography,” it is noted that question 5 in the “SleepDisordered Breathing Events” section contains a statement pertaining to oxygen desaturation as it was used to identify hypopneas by a study cited as a reference in the product. The ACCP acknowledges the inaccuracy, and that the criterion in question was included as a means to make comparisons with the data of other studies. Nancy A. Collop, MD, FCCP Chair and Editor-in-Chief, SLEEP 2 (Study Lessons in Education and Evaluation of Polysomnography) Baltimore, MD The author has reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Nancy A. Collop, MD, FCCP, Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, DOM, 1830 E Monument St, Room 555, Baltimore, MD 21205; e-mail: [email protected] DOI: 10.1378/chest.07-3108
Remembering Other Causes of Alveolar Siderophages Macrophage Activation Syndrome To the Editor: We read the interesting article of Dr. Ksienski and colleagues1 that talks about cocaine, pulmonary edema, and siderophages.
www.chestjournal.org
These cells are hemosiderin-laden alveolar macrophages characteristically found in BAL fluid or lung biopsy from patients with diffuse alveolar hemorrhage. Classically, diffuse alveolar hemorrhages are classified based on histologic appearance as capillaritis (Wegener granulomatosis, systemic lupus erythematosus, and propylthiouracil related), bland hemorrhage (coagulopathies, congestive heart failure, and rapamycin related), diffuse alveolar damage (ARDS and Crack cocaine inhalation), and miscellaneous conditions (lymphangioleiomyomatosis and pulmonary capillary hemangiomatosis). However, we consider that macrophage activation syndrome should be included in the differential diagnosis of alveolar siderophages.2–5 Macrophage activation syndrome is a rare disease characterized by an immune dysregulation with excessive hemophagocytosis in lung/bone marrow/spleen (producing hemosiderin-laden macrophages), splenomegaly, bicytopenia, hypertriglyceridemia, hyperferritinemia ⬎ 500 g/L, low natural killer-cell activity, increased plasma serum CD25, and fever.2 In addition, macrophage activation syndrome usually occurs in response to a triggering agent, such as tumors or infections (especially Epstein-Barr virus). Furthermore, macrophage activation syndrome may present with the triad of diffuse alveolar hemorrhage (lung infiltrates, a falling hemoglobin level, and worsening dyspnea).3–5 Therefore, chest physicians and pathologists should remember macrophage activation syndrome in patients with pulmonary infiltrates and falling hemoglobin levels and/or alveolar siderophages. Alfredo N. C. Santana, MD Ronaldo A. Kairalla, PhD Carlos R. R. Carvalho, PhD University of Sa˜o Paulo Medical School Pulmonary Division and PSM-HC/PS-HU Sa˜o Paulo, Brazil The authors have no conflicts of interest to disclose. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Alfredo N. C. Santana, MD, Rua Oscar Freire, 2121, ap602, CEP:05409-011, Sa˜o Paulo, SP, Brazil; e-mail: [email protected] DOI: 10.1378/chest.07-2668
References 1 Ksienski D, Malhotra S, Walker B, et al. Chest pain and cough in a 33-year-old postpartum woman. Chest 2007; 132:1389 –1392 2 Emmenegger U, Schaer DJ, Larroche C, et al. Haemophagocytic syndromes in adults: current concepts and challenges ahead. Swiss Med Wkly 2005; 135:299 –314 3 Popper HH, Zenz W, Mache C, et al. Familial haemophagocytic lymphohistiocytosis: a report of three cases with unusual lung involvement. Histopathology 1994; 25:439 – 445 4 Tateishi U, Nishihara H, Okano M, et al. High resolution CT findings of macrophage activation syndrome: a case report. Pediatr Radiol 2000; 30:699 –701 5 Brandao-neto RA, Santana ANC, Danilovic DLS, et al. A very rare cause of dyspnea with a unique presentation on chest CT: macrophage activation syndrome. J Bras Pneumol 2008 (in press)
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References 1 Zisman DA, Karlamangla AS, Ross DJ, et al. High-resolution chest CT findings do not predict the presence of pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Chest 2007; 132:773–779 2 Tan RT, Kuzo R, Goodman LR, et al. Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease: medical College of Wisconsin Lung Transplant Group. Chest 1998; 113:1250 –1256
Response To the Editor: Chen and colleagues1 examined the diagnostic value of mean pulmonary artery diameter (MPAD) ⱖ 29 mm to predict pulmonary hypertension using Figure 2 from our study.2 Given the relatively high sensitivity and negative predictive value obtained by this approach, they astutely point out that CT may have a role in screening for pulmonary hypertension in patients with idiopathic pulmonary fibrosis. This assertion has merit; however, any test can be made sensitive by selecting a low-enough cutoff but, as in this case, at the expense of specificity. Figure 2 only shows 56 of the 65 observations (9 are superimposed). With the entire data set, a MPAD cutoff ⱖ 29 mm had sensitivity, specificity, positive predictive value, and negative predictive value for pulmonary hypertension (defined as mean pulmonary artery pressure [MPAP] from rightheart catheterization ⬎ 25 mm Hg) of 85 to 100%, 10 to 38%, 34 to 61%, and 60 to 100%, respectively. Only 8 of 65 patients (12%) in the data set had MPADs ⬍ 29 mm, and this is reflected by a wide confidence interval for the negative predictive value estimate. Accordingly, the negative predictive value could be as low as 60%; in our opinion, this figure is too small to accept MPAD as a screening tool for a condition with potentially devastating consequences in idiopathic pulmonary fibrosis. Furthermore, as reflected by an unacceptably low specificity, of those without pulmonary hypertension, only 8 of 38 patients (21%) had MPADs ⬍ 29 mm. Simpler and less expensive clinical measurements (oxygen saturation using pulse oximetry, percentage of predicted FVC, and percentage of predicted diffusion capacity of the lung for carbon monoxide) can be used to screen for pulmonary hypertension in patients with idiopathic pulmonary fibrosis.3,4 Recently, we validated a formula to predict MPAP from standard lung function measurements.4 A 1054
formula-predicted MPAP ⬎ 21 mm Hg was associated with a sensitivity, specificity, positive predictive value, and negative predictive value of 74 to 99%, 41 to 73%, 35 to 70%, and 78 to 100%, respectively, for pulmonary hypertension defined as MPAP from right-heart catheterization ⬎ 25 mm Hg. We recommend this method over MPAD from CT to screen for pulmonary hypertension in patients with advanced idiopathic pulmonary fibrosis. David A. Zisman, MD, MS, FCCP Arun S. Karlamangla, PhD, MD David Geffen School of Medicine University of California, Los Angeles Los Angeles, CA The authors have no conflicts of interest to disclose. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: David A. Zisman, MD, MS, FCCP, Interstitial Lung Disease Center, David Geffen School of Medicine at UCLA, 37-131 Center for Health Sciences, Los Angeles, CA 90095; e-mail: [email protected] DOI: 10.13678/chest.07-2993
References 1 Chen H, Gould MK, De Marco T, et al. Utility of CT for predicting pulmonary hypertension in patients with parenchymal lung disease: similar results, different conclusion? Chest 2008; 133:1053–1054 2 Zisman DA, Karlamangla A, Ross DJ, et al. High-resolution chest computed tomography findings do not predict the presence of pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Chest 2007; 132:773–779 3 Zisman DA, Ross DJ, Belperio JA, et al. Prediction of pulmonary hypertension in idiopathic pulmonary fibrosis. Respir Med 2007; 101:2153–2159 4 Zisman DA, Karlamangla A, Kawut SM, et al. Validation of a method to screen for pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Chest 2008; 133:640 – 645
Hypopnea Scoring in the Sleep Heart Health Study To the Editor: It has come to our attention that the American College of Chest Physicians CD, “Sleep: Study Lessons in Education; product code 6633” has misinterpreted some of the findings from the Sleep Heart Health Study (SHHS). In the section, “Sleep-Disordered Breathing Events: Question 5, A. Hypopnea,” it is stated that “In fact, the scorers of the polysomnographies in the SHHS required a 4% oxyhemoglobin desaturation in order to score either apneas or hypopneas, because they could not achieve inter-rater reliability of apneas and hypopneas otherwise. Thus, the SHHS outcome data are essentially based on oximetry.” These two sentences are incorrect. Although it is true that the SHHS requires a 4% oxygen desaturation as one of its criteria to identify a hypopnea in most of its publications, this desaturation criterion was not chosen because we were unable to otherwise obtain interrater reliability using other criteria. Rather, a 4% oxygen desaturation was chosen because we wished to be consistent with the scoring criteria used by the Wisconsin Sleep Cohort so that comparisons could be made between the studies. Moreover, in the article by Whitney et al,1 we demonstrated that the intraclass correlation coefficients using various oxygen desaturation criteria were all ⬎ 0.90. We hope that this error will not be perpetuated in future editions of the education CDs on polysomnography, and that readers of CHEST who also use the Sleep Study Lessons CD will realize that this statement is not correct. Correspondence
Stuart F. Quan, MD, FCCP Harvard Medical School Boston, MA Susan Redline, MD, MPH Case Western Reserve University Cleveland, OH The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Stuart F. Quan, MD, FCCP, Harvard Medical School, Division of Sleep Medicine, 401 Park Dr, 2nd Floor, Boston, MA 02215; e-mail: [email protected] DOI: 10.1378/chest.07-2877
Reference 1 Whitney CW, Gottlieb DJ, Redline S, et al. Reliability of scoring respiratory disturbance indices and sleep staging. Sleep 1998; 21:749 –757
Response To the Editor: In response to the letter of Drs. Quan and Redline regarding the American College of Chest Physicians (ACCP) product No. 6633, “SLEEP 2-Study Lessons in the Education and Evaluation of Polysomnography,” it is noted that question 5 in the “SleepDisordered Breathing Events” section contains a statement pertaining to oxygen desaturation as it was used to identify hypopneas by a study cited as a reference in the product. The ACCP acknowledges the inaccuracy, and that the criterion in question was included as a means to make comparisons with the data of other studies. Nancy A. Collop, MD, FCCP Chair and Editor-in-Chief, SLEEP 2 (Study Lessons in Education and Evaluation of Polysomnography) Baltimore, MD The author has reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Nancy A. Collop, MD, FCCP, Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, DOM, 1830 E Monument St, Room 555, Baltimore, MD 21205; e-mail: [email protected] DOI: 10.1378/chest.07-3108
Remembering Other Causes of Alveolar Siderophages Macrophage Activation Syndrome To the Editor: We read the interesting article of Dr. Ksienski and colleagues1 that talks about cocaine, pulmonary edema, and siderophages.
www.chestjournal.org
These cells are hemosiderin-laden alveolar macrophages characteristically found in BAL fluid or lung biopsy from patients with diffuse alveolar hemorrhage. Classically, diffuse alveolar hemorrhages are classified based on histologic appearance as capillaritis (Wegener granulomatosis, systemic lupus erythematosus, and propylthiouracil related), bland hemorrhage (coagulopathies, congestive heart failure, and rapamycin related), diffuse alveolar damage (ARDS and Crack cocaine inhalation), and miscellaneous conditions (lymphangioleiomyomatosis and pulmonary capillary hemangiomatosis). However, we consider that macrophage activation syndrome should be included in the differential diagnosis of alveolar siderophages.2–5 Macrophage activation syndrome is a rare disease characterized by an immune dysregulation with excessive hemophagocytosis in lung/bone marrow/spleen (producing hemosiderin-laden macrophages), splenomegaly, bicytopenia, hypertriglyceridemia, hyperferritinemia ⬎ 500 g/L, low natural killer-cell activity, increased plasma serum CD25, and fever.2 In addition, macrophage activation syndrome usually occurs in response to a triggering agent, such as tumors or infections (especially Epstein-Barr virus). Furthermore, macrophage activation syndrome may present with the triad of diffuse alveolar hemorrhage (lung infiltrates, a falling hemoglobin level, and worsening dyspnea).3–5 Therefore, chest physicians and pathologists should remember macrophage activation syndrome in patients with pulmonary infiltrates and falling hemoglobin levels and/or alveolar siderophages. Alfredo N. C. Santana, MD Ronaldo A. Kairalla, PhD Carlos R. R. Carvalho, PhD University of Sa˜o Paulo Medical School Pulmonary Division and PSM-HC/PS-HU Sa˜o Paulo, Brazil The authors have no conflicts of interest to disclose. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Alfredo N. C. Santana, MD, Rua Oscar Freire, 2121, ap602, CEP:05409-011, Sa˜o Paulo, SP, Brazil; e-mail: [email protected] DOI: 10.1378/chest.07-2668
References 1 Ksienski D, Malhotra S, Walker B, et al. Chest pain and cough in a 33-year-old postpartum woman. Chest 2007; 132:1389 –1392 2 Emmenegger U, Schaer DJ, Larroche C, et al. Haemophagocytic syndromes in adults: current concepts and challenges ahead. Swiss Med Wkly 2005; 135:299 –314 3 Popper HH, Zenz W, Mache C, et al. Familial haemophagocytic lymphohistiocytosis: a report of three cases with unusual lung involvement. Histopathology 1994; 25:439 – 445 4 Tateishi U, Nishihara H, Okano M, et al. High resolution CT findings of macrophage activation syndrome: a case report. Pediatr Radiol 2000; 30:699 –701 5 Brandao-neto RA, Santana ANC, Danilovic DLS, et al. A very rare cause of dyspnea with a unique presentation on chest CT: macrophage activation syndrome. J Bras Pneumol 2008 (in press)
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