Impact of Lymphocytosis in Bronchoalveolar Lavage Fluid on Corticosteroid Treatment in Fibrotic Hypersensitivity Pneumonitis

Background and purpose. Bronchoalveolar lavage (BAL) lymphocytosis is considered when deciding whether or not to perform corticosteroid treatment for fibrotic hypersensitivity pneumonitis (HP). However, there is scant evidence as to whether or not the BAL lymphocyte percentage can predict the posttr...

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Published inThe Journal of the Japan Society for Respiratory Endoscopy Vol. 44; no. 4; pp. 259 - 267
Main Authors Okamoto, Tsukasa, Miyazaki, Yasunari, Ejima, Masaru, Shimamura, Takashi, Suzuki, Takafumi
Format Journal Article
LanguageJapanese
Published The Japan Society for Respiratory Endoscopy 25.07.2022
特定非営利活動法人 日本呼吸器内視鏡学会
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ISSN0287-2137
2186-0149
DOI10.18907/jjsre.44.4_259

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Abstract Background and purpose. Bronchoalveolar lavage (BAL) lymphocytosis is considered when deciding whether or not to perform corticosteroid treatment for fibrotic hypersensitivity pneumonitis (HP). However, there is scant evidence as to whether or not the BAL lymphocyte percentage can predict the posttreatment response and prognosis in fibrotic HP. Methods. We conducted a retrospective single-center study of 62 cases of fibrotic HP who had undergone corticosteroid treatment and received a BAL analysis within 1 year before the treatment. The association of the BAL lymphocyte percentage with the posttreatment mortality was evaluated using a multivariate analysis. Treatment responses were compared among the 3 stratified groups with high (≥40%, n=14), medium (10-39%, n=26), and low (<10%, n=22) lymphocyte percentages, in terms of the change in radiological scores, percent predicted forced vital capacity (%FVC), and survival rates from the date of initiating corticosteroids. Results. In the entire cohort, a multivariate Cox proportional regression analysis revealed that a low BAL lymphocyte percentage or medium (10-39%) to low (<10%) lymphocyte percentage was significantly associated with a high mortality, independent of the %FVC and presence of extensive ground-glass attenuation (GGA). There were significant or improving trends in one-year GGA scores and six-month FVCs from baseline in all three stratified groups. In contrast, the significant deterioration of the 1-year fibrosis scores from baseline was observed in the medium (10-39%) and low (<10%) lymphocyte percentage groups, showing poor survival rates compared to the high group (≥40%) (median survival time: not-reached, 69 months; P=0.089, and 37 months; P=0.049, respectively). Furthermore, a subgroup analysis of each of the three groups stratified by the presence or absence of extensive GGA revealed that its absence contributed to poor survival rates in all three groups. Conclusion. A low BAL lymphocyte percentage at the time of corticosteroid treatment in fibrotic HP may predict unfavorable outcomes, including continuous fibrotic progression and high mortality. Careful management may be required for corticosteroid therapy in fibrotic HP patients with a poor prognosis, especially those with a BAL lymphocyte percentage <40% and the absence of GGA.
AbstractList Background and purpose. Bronchoalveolar lavage (BAL) lymphocytosis is considered when deciding whether or not to perform corticosteroid treatment for fibrotic hypersensitivity pneumonitis (HP). However, there is scant evidence as to whether or not the BAL lymphocyte percentage can predict the posttreatment response and prognosis in fibrotic HP. Methods. We conducted a retrospective single-center study of 62 cases of fibrotic HP who had undergone corticosteroid treatment and received a BAL analysis within 1 year before the treatment. The association of the BAL lymphocyte percentage with the posttreatment mortality was evaluated using a multivariate analysis. Treatment responses were compared among the 3 stratified groups with high (≥40%, n=14), medium (10-39%, n=26), and low (<10%, n=22) lymphocyte percentages, in terms of the change in radiological scores, percent predicted forced vital capacity (%FVC), and survival rates from the date of initiating corticosteroids. Results. In the entire cohort, a multivariate Cox proportional regression analysis revealed that a low BAL lymphocyte percentage or medium (10-39%) to low (<10%) lymphocyte percentage was significantly associated with a high mortality, independent of the %FVC and presence of extensive ground-glass attenuation (GGA). There were significant or improving trends in one-year GGA scores and six-month FVCs from baseline in all three stratified groups. In contrast, the significant deterioration of the 1-year fibrosis scores from baseline was observed in the medium (10-39%) and low (<10%) lymphocyte percentage groups, showing poor survival rates compared to the high group (≥40%) (median survival time: not-reached, 69 months; P=0.089, and 37 months; P=0.049, respectively). Furthermore, a subgroup analysis of each of the three groups stratified by the presence or absence of extensive GGA revealed that its absence contributed to poor survival rates in all three groups. Conclusion. A low BAL lymphocyte percentage at the time of corticosteroid treatment in fibrotic HP may predict unfavorable outcomes, including continuous fibrotic progression and high mortality. Careful management may be required for corticosteroid therapy in fibrotic HP patients with a poor prognosis, especially those with a BAL lymphocyte percentage <40% and the absence of GGA. 背景と目的.線維性過敏性肺炎(hypersensitivity pneumonitis:HP)の治療において,気管支肺胞洗浄液(BALF)中のリンパ球分画はステロイド治療の適応判断に用いられている.一方で,BALF中のリンパ球分画がステロイド治療後の生命予後に影響するのか,またリンパ球分画に応じた治療反応性は異なるかについては報告が乏しいことから,今回検討を行った.方法.ステロイド治療を行った線維性HP 62例を対象とした.BALF中のリンパ球分画と治療後の生命予後の関連について,多変量解析を行った.治療反応性の評価として,リンパ球分画の高値群(≧40%, n=14),中間値群(10~39%, n=26),低値群(<10%, n=22)に層別化し,治療から1年後の画像スコア(ground-glass attenuation[GGA]score,fibrosis score)の変化,1年間の努力肺活量(percent predicted forced vital capacity:%FVC)の推移,生存率について比較を行った.結果.全体集団の多変量解析では,低いリンパ球分画や,リンパ球分画の中間値(10~39%)や低値(<10%)は,%FVCやextensive GGAなどと独立した生命予後不良因子であった.リンパ球分画のサブグループ解析では,GGA scoreと6カ月後の%FVCはいずれの群でも改善を認めた.一方で,中間値群と低値群ではfibrosis scoreは悪化し,高値群と比較して生存率は低く,生存期間中央値は高値群,中間値群,低値群で順に未到達,69カ月(P=0.089),37カ月(P=0.049)であった.さらに各群をextensive GGAの有無で層別化すると,3群いずれでもextensive GGAがないと生命予後は不良であった.結論.線維性HPにおいて,BALF中のリンパ球分画40%未満の症例ではステロイド治療後も線維化は進行し,中でもGGAが乏しい症例は特に生命予後不良な可能性があり,治療開始後も慎重な管理が必要である.
Background and purpose. Bronchoalveolar lavage (BAL) lymphocytosis is considered when deciding whether or not to perform corticosteroid treatment for fibrotic hypersensitivity pneumonitis (HP). However, there is scant evidence as to whether or not the BAL lymphocyte percentage can predict the posttreatment response and prognosis in fibrotic HP. Methods. We conducted a retrospective single-center study of 62 cases of fibrotic HP who had undergone corticosteroid treatment and received a BAL analysis within 1 year before the treatment. The association of the BAL lymphocyte percentage with the posttreatment mortality was evaluated using a multivariate analysis. Treatment responses were compared among the 3 stratified groups with high (≥40%, n=14), medium (10-39%, n=26), and low (<10%, n=22) lymphocyte percentages, in terms of the change in radiological scores, percent predicted forced vital capacity (%FVC), and survival rates from the date of initiating corticosteroids. Results. In the entire cohort, a multivariate Cox proportional regression analysis revealed that a low BAL lymphocyte percentage or medium (10-39%) to low (<10%) lymphocyte percentage was significantly associated with a high mortality, independent of the %FVC and presence of extensive ground-glass attenuation (GGA). There were significant or improving trends in one-year GGA scores and six-month FVCs from baseline in all three stratified groups. In contrast, the significant deterioration of the 1-year fibrosis scores from baseline was observed in the medium (10-39%) and low (<10%) lymphocyte percentage groups, showing poor survival rates compared to the high group (≥40%) (median survival time: not-reached, 69 months; P=0.089, and 37 months; P=0.049, respectively). Furthermore, a subgroup analysis of each of the three groups stratified by the presence or absence of extensive GGA revealed that its absence contributed to poor survival rates in all three groups. Conclusion. A low BAL lymphocyte percentage at the time of corticosteroid treatment in fibrotic HP may predict unfavorable outcomes, including continuous fibrotic progression and high mortality. Careful management may be required for corticosteroid therapy in fibrotic HP patients with a poor prognosis, especially those with a BAL lymphocyte percentage <40% and the absence of GGA.
Author Miyazaki, Yasunari
Suzuki, Takafumi
Okamoto, Tsukasa
Ejima, Masaru
Shimamura, Takashi
Author_FL Suzuki Takafumi
岡本 師
惠島 将
宮﨑 泰成
Shimamura Takashi
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DocumentTitle_FL 線維性過敏性肺炎のステロイド治療における気管支肺胞洗浄液中のリンパ球分画と予後との関連
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特定非営利活動法人 日本呼吸器内視鏡学会
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5. De Sadeleer LJ, Hermans F, De Dycker E, et al. Effects of corticosteroid treatment and antigen avoidance in a large hypersensitivity pneumonitis cohort: a single-centre cohort study. J Clin Med. 2018;8:14.
1. Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202:e36-e69.
12. De Sadeleer LJ, Hermans F, De Dycker E, et al. Impact of BAL lymphocytosis and presence of honeycombing on corticosteroid treatment effect in fibrotic hypersensitivity pneumonitis: a retrospective cohort study. Eur Respir J. 2020;55:1901983.
18. Kinder BW, Brown KK, Schwarz MI, et al. Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis. Chest. 2008;133:226-232.
10. Best AC, Meng J, Lynch AM, et al. Idiopathic pulmonary fibrosis: physiologic tests, quantitative CT indexes, and CT visual scores as predictors of mortality. Radiology. 2008;246:935-940.
17. Morisset J, Johannson KA, Jones KD, et al. Identification of diagnostic criteria for chronic hypersensitivity pneumonitis: an international modified Delphi survey. Am J Respir Crit Care Med. 2018;197:1036-1044.
16. Adderley N, Humphreys CJ, Barnes H, et al. Bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: a systematic review and meta-analysis. Eur Respir J. 2020;56:2000206.
2. Salisbury ML, Gu T, Murray S, et al. Hypersensitivity Pneumonitis: Radiologic Phenotypes Are Associated With Distinct Survival Time and Pulmonary Function Trajectory. Chest. 2019;155:699-711.
6. Ejima M, Okamoto T, Suzuki T, et al. Efficacy of treatment with corticosteroids for fibrotic hypersensitivity pneumonitis: a propensity score-matched cohort analysis. BMC Pulm Med. 2021;21:243.
22. Morisset J, Johannson KA, Vittinghoff E, et al. Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis. Chest. 2017;151:619-625.
20. Goh NS, Veeraraghavan S, Desai SR, et al. Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis-associated interstitial lung disease are not predictive of disease progression. Arthritis Rheum. 2007;56:2005-2012.
13. Raimundo S, Pimenta AC, Cruz-Martins N, et al. Insights on chronic hypersensitivity pneumonitis' treatment: Factors associated with a favourable response to azathioprine. Life Sci. 2021;272:119274.
11. Ojanguren I, Morell F, Ramón MA, et al. Long-term outcomes in chronic hypersensitivity pneumonitis. Allergy. 2019;74:944-952.
14. Gimenez A, Storrer K, Kuranishi L, et al. Change in FVC and survival in chronic fibrotic hypersensitivity pneumonitis. Thorax. 2018;73:391-392.
9. Goh NS, Desai SR, Veeraraghavan S, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177:1248-1254.
7. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824.
19. Suzuki A, Kondoh Y, Brown KK, et al. Acute exacerbations of fibrotic interstitial lung diseases. Respirology. 2020;25:525-534.
21. Wells AU, Rubens MB, du Bois RM, et al. Serial CT in fibrosing alveolitis: prognostic significance of the initial pattern. AJR Am J Roentgenol. 1993;161:1159-1165.
4. Salisbury ML, Myers JL, Belloli EA, et al. Diagnosis and treatment of fibrotic hypersensitivity pneumonia. Where we stand and where we need to go. Am J Respir Crit Care Med. 2017;196:690-699.
15. Chung JH, Montner SM, Adegunsoye A, et al. CT findings associated with survival in chronic hypersensitivity pneumonitis. Eur Radiol. 2017;27:5127-5135.
8. Tateishi T, Johkoh T, Sakai F, et al. High-resolution CT features distinguishing usual interstitial pneumonia pattern in chronic hypersensitivity pneumonitis from those with idiopathic pulmonary fibrosis. Jpn J Radiol. 2020;38:524-532.
References_xml – reference: 7. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824.
– reference: 6. Ejima M, Okamoto T, Suzuki T, et al. Efficacy of treatment with corticosteroids for fibrotic hypersensitivity pneumonitis: a propensity score-matched cohort analysis. BMC Pulm Med. 2021;21:243.
– reference: 9. Goh NS, Desai SR, Veeraraghavan S, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177:1248-1254.
– reference: 13. Raimundo S, Pimenta AC, Cruz-Martins N, et al. Insights on chronic hypersensitivity pneumonitis' treatment: Factors associated with a favourable response to azathioprine. Life Sci. 2021;272:119274.
– reference: 14. Gimenez A, Storrer K, Kuranishi L, et al. Change in FVC and survival in chronic fibrotic hypersensitivity pneumonitis. Thorax. 2018;73:391-392.
– reference: 12. De Sadeleer LJ, Hermans F, De Dycker E, et al. Impact of BAL lymphocytosis and presence of honeycombing on corticosteroid treatment effect in fibrotic hypersensitivity pneumonitis: a retrospective cohort study. Eur Respir J. 2020;55:1901983.
– reference: 1. Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202:e36-e69.
– reference: 4. Salisbury ML, Myers JL, Belloli EA, et al. Diagnosis and treatment of fibrotic hypersensitivity pneumonia. Where we stand and where we need to go. Am J Respir Crit Care Med. 2017;196:690-699.
– reference: 16. Adderley N, Humphreys CJ, Barnes H, et al. Bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: a systematic review and meta-analysis. Eur Respir J. 2020;56:2000206.
– reference: 10. Best AC, Meng J, Lynch AM, et al. Idiopathic pulmonary fibrosis: physiologic tests, quantitative CT indexes, and CT visual scores as predictors of mortality. Radiology. 2008;246:935-940.
– reference: 11. Ojanguren I, Morell F, Ramón MA, et al. Long-term outcomes in chronic hypersensitivity pneumonitis. Allergy. 2019;74:944-952.
– reference: 18. Kinder BW, Brown KK, Schwarz MI, et al. Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis. Chest. 2008;133:226-232.
– reference: 3. Kokkarinen JI, Tukiainen HO, Terho EO. Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung. Am Rev Respir Dis. 1992;145:3-5.
– reference: 19. Suzuki A, Kondoh Y, Brown KK, et al. Acute exacerbations of fibrotic interstitial lung diseases. Respirology. 2020;25:525-534.
– reference: 20. Goh NS, Veeraraghavan S, Desai SR, et al. Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis-associated interstitial lung disease are not predictive of disease progression. Arthritis Rheum. 2007;56:2005-2012.
– reference: 2. Salisbury ML, Gu T, Murray S, et al. Hypersensitivity Pneumonitis: Radiologic Phenotypes Are Associated With Distinct Survival Time and Pulmonary Function Trajectory. Chest. 2019;155:699-711.
– reference: 15. Chung JH, Montner SM, Adegunsoye A, et al. CT findings associated with survival in chronic hypersensitivity pneumonitis. Eur Radiol. 2017;27:5127-5135.
– reference: 8. Tateishi T, Johkoh T, Sakai F, et al. High-resolution CT features distinguishing usual interstitial pneumonia pattern in chronic hypersensitivity pneumonitis from those with idiopathic pulmonary fibrosis. Jpn J Radiol. 2020;38:524-532.
– reference: 17. Morisset J, Johannson KA, Jones KD, et al. Identification of diagnostic criteria for chronic hypersensitivity pneumonitis: an international modified Delphi survey. Am J Respir Crit Care Med. 2018;197:1036-1044.
– reference: 21. Wells AU, Rubens MB, du Bois RM, et al. Serial CT in fibrosing alveolitis: prognostic significance of the initial pattern. AJR Am J Roentgenol. 1993;161:1159-1165.
– reference: 22. Morisset J, Johannson KA, Vittinghoff E, et al. Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis. Chest. 2017;151:619-625.
– reference: 5. De Sadeleer LJ, Hermans F, De Dycker E, et al. Effects of corticosteroid treatment and antigen avoidance in a large hypersensitivity pneumonitis cohort: a single-centre cohort study. J Clin Med. 2018;8:14.
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Snippet Background and purpose. Bronchoalveolar lavage (BAL) lymphocytosis is considered when deciding whether or not to perform corticosteroid treatment for fibrotic...
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StartPage 259
SubjectTerms Bronchoalveolar lavage fluid
Corticosteroid treatment
Fibrotic hypersensitivity pneumonitis
Lymphocytosis
Prognosis
ステロイド
リンパ球分画
予後
気管支肺胞洗浄液
線維性過敏性肺炎
Title Impact of Lymphocytosis in Bronchoalveolar Lavage Fluid on Corticosteroid Treatment in Fibrotic Hypersensitivity Pneumonitis
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