- Email: [email protected]
BAL Fluid Surfactant Protein C Level Is Related to Parenchymal Lung Disease in Children With Sarcoidosis
possibility that clinician bias played a role in this disparity in willingness to switch.
Response To the Editor: We appreciate the interest of Dr Barbarito and colleagues in our recent study1 comparing the total face mask (TFM) with oronasal mask (ONM) for the treatment of acute respiratory failure in patients receiving noninvasive ventilation (NIV). Our primary (mask comfort and time to apply) and secondary (vital signs and gas exchange parameters over time) end points showed no differences. In the interest of conserving space, we did not show the data for the time course of Paco2 in the two groups. Figure 1 shows that data after purging of early discontinuers (ie, those who discontinued NIV while still requiring ventilatory assistance) to provide a better idea of evolution over time. Dr Barbarito and colleagues also requested information on the total duration of mechanical ventilation. As they mention, the median duration of NIV use was longer with the ONM than the TFM, excluding the duration of use after switching to the alternative mask. However, when that duration is included, the total duration of NIV was similar. If, as Barbarito and colleagues request, we exclude those who discontinued early, the median duration of NIV tended to be shorter in the ONM group (23 h; interquartile range, 4.6-51.3; n 5 18) than in the TFM group (56.9 h; interquartile range, 15.7-98.4; n 5 12). The reason for these disparities is that more patients discontinued NIV early with a shorter duration of use in the TFM than the ONM group (n 5 16 vs 12, 0.7 vs 3.7 h), and patients using ONM were more apt to switch to the alternative mask (n 5 8 of 16 patients using TFM vs 0 of 12 patients using ONM, P , .05). This disparity in willingness to switch between the two groups is remarkable, and Barbarito and colleagues ask for more detail on the reasons. Of the 12 patients using ONM who discontinued NIV early, five required prompt intubation. Two other patients had do-not-intubate orders and died while using the mask. The other five patients were offered the TFM but declined. One was claustrophobic and refused any other masks; the other four were frightened by the large appearance of the TFM and declined. One of the patients using ONM compared with none of the patients using TNM had previously used NIV at home. As mentioned in the article,1 respiratory therapists were instructed to apply every effort to encourage patients to use either mask type. However, since blinding was not possible, we cannot exclude the
Aylin Ozsancak, MD Adana, Turkey Samy Sidhom, MD, MPH Boston, MA Timothy N. Liesching, MD, FCCP Burlington, MA William Howard, RRT Nicholas S. Hill, MD, FCCP Boston, MA Affiliations: From the Baskent University Hospital (Dr Ozsancak); Tufts Medical Center (Drs Sidhom and Hill and Mr Howard); the Lahey Clinic (Dr Liesching); and Rhode Island Hospital (Dr Hill), Providence, RI. Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Hill has received research grants from Respironics, Inc and Breathe Technologies, Inc. Drs Ozsancak, Sidhom, Liesching and Mr Howard have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Nicholas S. Hill MD, FCCP, Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts Medical Center, 800 Washington St # 257, Boston MA 02111; e-mail: [email protected] © 2011 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.11-1735
References 1. Ozsancak A, Sidhom SS, Liesching TN, Howard W, Hill NS. Evaluation of the total face mask for noninvasive ventilation to treat acute respiratory failure. Chest. 2011;139(5):1034-1041.
BAL Fluid Surfactant Protein C Level Is Related to Parenchymal Lung Disease in Children With Sarcoidosis To the Editor:
Figure 1. Data after removal of those who discontinued noninvasive ventilation while still requiring ventilatory assistance. ONM 5 oronasal mask; TFM 5 total face mask.
Surfactant protein C (SP-C) is a hydrophobic protein exclusively synthesized by type 2 alveolar epithelial cells from a 197 amino acid propeptide form (proSP-C) after a complex multistep posttranscriptional processing.1 Sarcoidosis is a systemic disease of unknown cause characterized by noncaseating epithelioid granulomas2 that may disturb the synthesis of SP-C. We aimed to assess the relationship between alveolar SP-C expression and parenchymal lung disease in children with pulmonary sarcoidosis. Eighteen children with histologic proven sarcoidosis (white, n 5 8; black African, n 5 5; French Antilles, n 5 5) were evaluated for parenchymal lung disease by high-resolution CT scans and respiratory function tests, including measurements of FVC and dynamic lung compliance (Cl,dyn).3 Patients were divided, after radiographic staging,4 in two groups based on the absence of pulmonary infiltrations (API group; stages 0 and I, nine patients) or the presence of pulmonary infiltrations (PI group; stages II and III, nine patients). All patients underwent fiberoptic bronchoscopy with BAL before treatment onset for 17 of the 18 patients. BAL fluid (BALF) proSP-C and mature SP-C expression levels were assessed by Western blot using proSP-C and mature SP-C antibodies (Seven Hills Bioreagents; Cincinnati, Ohio) as previously
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Correspondence
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on October 7, 2011 © 2011 American College of Chest Physicians
Table 1—Functional and BALF Features in Patients With or Without Parenchymal Lung Disease Parameter Sex, male (female) Mean age at BAL, y Lung functions VC, % predicted Cl,dyn, % predicted BALF parameters Total cell, 3 105/mL Macrophages, % Lymphocytes, % Neutrophils, % ProSP-C, AU Mature SP-C, AU ProSP-C/mature SP-C ratio
Sarcoidosis API Group (n 5 9)
Sarcoidosis PI Group (n 5 9)
P Valuesa
7 (2) 12 ⫾ 1
7 (2) 12 ⫾ 1
… …
89 ⫾ 5 69 ⫾ 6
70 ⫾ 9 45 ⫾ 7
… .03
2.1 ⫾ 0.2 65 ⫾ 7 27 ⫾ 5 2.0 ⫾ 0.8 8⫾5 18 ⫾ 4 0.7 ⫾ 0.2
3.1 ⫾ 0.4 47 ⫾ 6 42 ⫾ 7 1.0 ⫾ 0.4 26 ⫾ 13 5⫾1 9.3 ⫾ 3.2
… … … … .009 .03 .0009
Data are expressed as mean ⫾ SEM. API 5 absence of pulmonary infiltration; AU 5 arbitrary unit; BALF 5 BAL fluid; Cl,dyn 5 dynamic compliance; PI 5 presence of pulmonary infiltration; proSP-C 5 surfactant protein propeptide form; SP-C 5 surfactant protein; VC 5 vital capacity. aP values . .05 are not shown.
described.5 Signals were scanned, analyzed by Quantity One software (Bio-Rad; Marnes-La-Coquette, France), and expressed as arbitrary units. We have shown that BALF proSP-C levels were significantly higher in the PI group compared with the API group, whereas BALF mature SP-C levels were significantly lower in the PI group compared with API group (Table 1). The ProSP-C/mature SP-C ratio was also significantly higher in the PI group compared with the API group. Furthermore, elevated proSP-C (or decreased mature SP-C) levels were associated with lower Cl,dyn, and we observed a strong correlation between both proSP-C and SP-C BALF expression and Cl,dyn (r 5 20.52, P 5 .03 for proSP-C and r 5 0.681, P 5 .007 for mature SP-C). No correlation was shown between proSP-C or mature SP-C levels and FVC (r 5 20.18, P 5 .48 for proSP-C and r 5 0.375, P 5 .16 for mature SP-C). Our results highlight the relation among SP-C expression, parenchymal lung disease, and Cl,dyn in children with sarcoidosis. Although a change in SP-C expression levels is usually observed in SFTPC mutation-associated disorders,5 no mutation in the SFTPC gene was identified in our patients. Furthermore, proSP-C and mature SP-C levels in the API group are similar to those observed in our control subjects (without interstitial lung disease) from a previous study.5 Hence, changes observed in individuals with parenchymal lesions likely reflect damage or release of proSP-C from epithelial cells as a consequence of granulomatous inflammation. This study suggests that assessment of SP-C levels in BALF may represent a complementary tool for therapeutic orientation and follow-up of pediatric sarcoidosis. Loïc Guillot, PhD Florence Flamein, MD Guillaume Thouvenin, MD Michèle Boulé, MD, PhD Hubert Ducou le Pointe, MD, PhD Laurence Jonard, PharmD, PhD Annick Clement, MD, PhD Paris, France Ralph Epaud, MD Créteil, France Affiliations: From INSERM U938 (Drs Guillot, Flamein, Thouvenin, Boulé, and Clement); UPMC, University of Paris 6 (Drs Guillot, Flamein, Thouvenin, Boulé, Ducou le Pointe, www.chestpubs.org
Jonard, and Clement); AP-HP, Hôpital Trousseau (Drs Thouvenin, Boulé, Ducou le Pointe, Jonard, and Clement); the Pediatric Pulmonary Department (Drs Thouvenin and Clement), the Radiology Department (Dr Ducou le Pointe), and the Biochemistry Department (Dr Jonard), the Université Paris-Est Créteil Val de Marne (Dr Epaud); INSERM, Unité U955 (Dr Epaud); and Centre Hospitalier Intercommunal (Dr Epaud). Funding/Support: This work was supported by Assistance PubliqueHôpitaux de Paris and INSERM. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Ralph Epaud, MD, Pediatric Department, Centre Hospitalier Intercommunal, 40 avenue de Verdun, 94000 Créteil, France; e-mail: [email protected] © 2011 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.11-0681
Acknowledgments Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript. Other contributions: We thank Harriet Corvol, MD, PhD; Katarina Chadelat, MD; and Céline Charlier, PhD, for their helpful comments on study design and manuscript. We also thank Marie Claude Miesch for technical assistance on Western blot.
References 1. Weaver TE, Conkright JJ. Function of surfactant proteins B and C. Annu Rev Physiol. 2001;63:555-578. 2. Milman N, Hoffmann AL. Childhood sarcoidosis: long-term follow-up. Eur Respir J. 2008;31(3):592-598. 3. Baculard A, Blanc N, Boulé M, et al. Pulmonary sarcoidosis in children: a follow-up study. Eur Respir J. 2001;17(4):628-635. 4. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999;160(2):736-755. 5. Thouvenin G, Abou Taam R, Flamein F, et al. Characteristics of disorders associated with genetic mutations of surfactant protein C. Arch Dis Child. 2010;95(6):449-454. CHEST / 140 / 4 / OCTOBER, 2011
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on October 7, 2011 © 2011 American College of Chest Physicians
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Response To the Editor: We appreciate the interest of Dr Barbarito and colleagues in our recent study1 comparing the total face mask (TFM) with oronasal mask (ONM) for the treatment of acute respiratory failure in patients receiving noninvasive ventilation (NIV). Our primary (mask comfort and time to apply) and secondary (vital signs and gas exchange parameters over time) end points showed no differences. In the interest of conserving space, we did not show the data for the time course of Paco2 in the two groups. Figure 1 shows that data after purging of early discontinuers (ie, those who discontinued NIV while still requiring ventilatory assistance) to provide a better idea of evolution over time. Dr Barbarito and colleagues also requested information on the total duration of mechanical ventilation. As they mention, the median duration of NIV use was longer with the ONM than the TFM, excluding the duration of use after switching to the alternative mask. However, when that duration is included, the total duration of NIV was similar. If, as Barbarito and colleagues request, we exclude those who discontinued early, the median duration of NIV tended to be shorter in the ONM group (23 h; interquartile range, 4.6-51.3; n 5 18) than in the TFM group (56.9 h; interquartile range, 15.7-98.4; n 5 12). The reason for these disparities is that more patients discontinued NIV early with a shorter duration of use in the TFM than the ONM group (n 5 16 vs 12, 0.7 vs 3.7 h), and patients using ONM were more apt to switch to the alternative mask (n 5 8 of 16 patients using TFM vs 0 of 12 patients using ONM, P , .05). This disparity in willingness to switch between the two groups is remarkable, and Barbarito and colleagues ask for more detail on the reasons. Of the 12 patients using ONM who discontinued NIV early, five required prompt intubation. Two other patients had do-not-intubate orders and died while using the mask. The other five patients were offered the TFM but declined. One was claustrophobic and refused any other masks; the other four were frightened by the large appearance of the TFM and declined. One of the patients using ONM compared with none of the patients using TNM had previously used NIV at home. As mentioned in the article,1 respiratory therapists were instructed to apply every effort to encourage patients to use either mask type. However, since blinding was not possible, we cannot exclude the
Aylin Ozsancak, MD Adana, Turkey Samy Sidhom, MD, MPH Boston, MA Timothy N. Liesching, MD, FCCP Burlington, MA William Howard, RRT Nicholas S. Hill, MD, FCCP Boston, MA Affiliations: From the Baskent University Hospital (Dr Ozsancak); Tufts Medical Center (Drs Sidhom and Hill and Mr Howard); the Lahey Clinic (Dr Liesching); and Rhode Island Hospital (Dr Hill), Providence, RI. Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Hill has received research grants from Respironics, Inc and Breathe Technologies, Inc. Drs Ozsancak, Sidhom, Liesching and Mr Howard have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Nicholas S. Hill MD, FCCP, Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts Medical Center, 800 Washington St # 257, Boston MA 02111; e-mail: [email protected] © 2011 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.11-1735
References 1. Ozsancak A, Sidhom SS, Liesching TN, Howard W, Hill NS. Evaluation of the total face mask for noninvasive ventilation to treat acute respiratory failure. Chest. 2011;139(5):1034-1041.
BAL Fluid Surfactant Protein C Level Is Related to Parenchymal Lung Disease in Children With Sarcoidosis To the Editor:
Figure 1. Data after removal of those who discontinued noninvasive ventilation while still requiring ventilatory assistance. ONM 5 oronasal mask; TFM 5 total face mask.
Surfactant protein C (SP-C) is a hydrophobic protein exclusively synthesized by type 2 alveolar epithelial cells from a 197 amino acid propeptide form (proSP-C) after a complex multistep posttranscriptional processing.1 Sarcoidosis is a systemic disease of unknown cause characterized by noncaseating epithelioid granulomas2 that may disturb the synthesis of SP-C. We aimed to assess the relationship between alveolar SP-C expression and parenchymal lung disease in children with pulmonary sarcoidosis. Eighteen children with histologic proven sarcoidosis (white, n 5 8; black African, n 5 5; French Antilles, n 5 5) were evaluated for parenchymal lung disease by high-resolution CT scans and respiratory function tests, including measurements of FVC and dynamic lung compliance (Cl,dyn).3 Patients were divided, after radiographic staging,4 in two groups based on the absence of pulmonary infiltrations (API group; stages 0 and I, nine patients) or the presence of pulmonary infiltrations (PI group; stages II and III, nine patients). All patients underwent fiberoptic bronchoscopy with BAL before treatment onset for 17 of the 18 patients. BAL fluid (BALF) proSP-C and mature SP-C expression levels were assessed by Western blot using proSP-C and mature SP-C antibodies (Seven Hills Bioreagents; Cincinnati, Ohio) as previously
1104
Correspondence
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on October 7, 2011 © 2011 American College of Chest Physicians
Table 1—Functional and BALF Features in Patients With or Without Parenchymal Lung Disease Parameter Sex, male (female) Mean age at BAL, y Lung functions VC, % predicted Cl,dyn, % predicted BALF parameters Total cell, 3 105/mL Macrophages, % Lymphocytes, % Neutrophils, % ProSP-C, AU Mature SP-C, AU ProSP-C/mature SP-C ratio
Sarcoidosis API Group (n 5 9)
Sarcoidosis PI Group (n 5 9)
P Valuesa
7 (2) 12 ⫾ 1
7 (2) 12 ⫾ 1
… …
89 ⫾ 5 69 ⫾ 6
70 ⫾ 9 45 ⫾ 7
… .03
2.1 ⫾ 0.2 65 ⫾ 7 27 ⫾ 5 2.0 ⫾ 0.8 8⫾5 18 ⫾ 4 0.7 ⫾ 0.2
3.1 ⫾ 0.4 47 ⫾ 6 42 ⫾ 7 1.0 ⫾ 0.4 26 ⫾ 13 5⫾1 9.3 ⫾ 3.2
… … … … .009 .03 .0009
Data are expressed as mean ⫾ SEM. API 5 absence of pulmonary infiltration; AU 5 arbitrary unit; BALF 5 BAL fluid; Cl,dyn 5 dynamic compliance; PI 5 presence of pulmonary infiltration; proSP-C 5 surfactant protein propeptide form; SP-C 5 surfactant protein; VC 5 vital capacity. aP values . .05 are not shown.
described.5 Signals were scanned, analyzed by Quantity One software (Bio-Rad; Marnes-La-Coquette, France), and expressed as arbitrary units. We have shown that BALF proSP-C levels were significantly higher in the PI group compared with the API group, whereas BALF mature SP-C levels were significantly lower in the PI group compared with API group (Table 1). The ProSP-C/mature SP-C ratio was also significantly higher in the PI group compared with the API group. Furthermore, elevated proSP-C (or decreased mature SP-C) levels were associated with lower Cl,dyn, and we observed a strong correlation between both proSP-C and SP-C BALF expression and Cl,dyn (r 5 20.52, P 5 .03 for proSP-C and r 5 0.681, P 5 .007 for mature SP-C). No correlation was shown between proSP-C or mature SP-C levels and FVC (r 5 20.18, P 5 .48 for proSP-C and r 5 0.375, P 5 .16 for mature SP-C). Our results highlight the relation among SP-C expression, parenchymal lung disease, and Cl,dyn in children with sarcoidosis. Although a change in SP-C expression levels is usually observed in SFTPC mutation-associated disorders,5 no mutation in the SFTPC gene was identified in our patients. Furthermore, proSP-C and mature SP-C levels in the API group are similar to those observed in our control subjects (without interstitial lung disease) from a previous study.5 Hence, changes observed in individuals with parenchymal lesions likely reflect damage or release of proSP-C from epithelial cells as a consequence of granulomatous inflammation. This study suggests that assessment of SP-C levels in BALF may represent a complementary tool for therapeutic orientation and follow-up of pediatric sarcoidosis. Loïc Guillot, PhD Florence Flamein, MD Guillaume Thouvenin, MD Michèle Boulé, MD, PhD Hubert Ducou le Pointe, MD, PhD Laurence Jonard, PharmD, PhD Annick Clement, MD, PhD Paris, France Ralph Epaud, MD Créteil, France Affiliations: From INSERM U938 (Drs Guillot, Flamein, Thouvenin, Boulé, and Clement); UPMC, University of Paris 6 (Drs Guillot, Flamein, Thouvenin, Boulé, Ducou le Pointe, www.chestpubs.org
Jonard, and Clement); AP-HP, Hôpital Trousseau (Drs Thouvenin, Boulé, Ducou le Pointe, Jonard, and Clement); the Pediatric Pulmonary Department (Drs Thouvenin and Clement), the Radiology Department (Dr Ducou le Pointe), and the Biochemistry Department (Dr Jonard), the Université Paris-Est Créteil Val de Marne (Dr Epaud); INSERM, Unité U955 (Dr Epaud); and Centre Hospitalier Intercommunal (Dr Epaud). Funding/Support: This work was supported by Assistance PubliqueHôpitaux de Paris and INSERM. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Ralph Epaud, MD, Pediatric Department, Centre Hospitalier Intercommunal, 40 avenue de Verdun, 94000 Créteil, France; e-mail: [email protected] © 2011 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.11-0681
Acknowledgments Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript. Other contributions: We thank Harriet Corvol, MD, PhD; Katarina Chadelat, MD; and Céline Charlier, PhD, for their helpful comments on study design and manuscript. We also thank Marie Claude Miesch for technical assistance on Western blot.
References 1. Weaver TE, Conkright JJ. Function of surfactant proteins B and C. Annu Rev Physiol. 2001;63:555-578. 2. Milman N, Hoffmann AL. Childhood sarcoidosis: long-term follow-up. Eur Respir J. 2008;31(3):592-598. 3. Baculard A, Blanc N, Boulé M, et al. Pulmonary sarcoidosis in children: a follow-up study. Eur Respir J. 2001;17(4):628-635. 4. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999;160(2):736-755. 5. Thouvenin G, Abou Taam R, Flamein F, et al. Characteristics of disorders associated with genetic mutations of surfactant protein C. Arch Dis Child. 2010;95(6):449-454. CHEST / 140 / 4 / OCTOBER, 2011
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on October 7, 2011 © 2011 American College of Chest Physicians
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