Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung Diseases
<b>Objective</b>: Antifibrotics can improve the outcome of patients with idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung diseases (F-ILDs), but predictive biomarkers at diagnosis are needed to guide the use of immunomodulating and antifibrotic therapies. <b&g...
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2024-10-01
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| author | Erika M. Novoa-Bolivar José A. Ros Sonia Pérez-Fernández José A. Campillo Ruth López-Hernández Rosana González-López Almudena Otalora-Alcaraz Cristina Ortuño-Hernández Lourdes Gimeno Inmaculada Ruiz-Lorente Diana Ceballos-Francisco Manuel Muro Pablo Martínez-Camblor Alfredo Minguela |
| author_facet | Erika M. Novoa-Bolivar José A. Ros Sonia Pérez-Fernández José A. Campillo Ruth López-Hernández Rosana González-López Almudena Otalora-Alcaraz Cristina Ortuño-Hernández Lourdes Gimeno Inmaculada Ruiz-Lorente Diana Ceballos-Francisco Manuel Muro Pablo Martínez-Camblor Alfredo Minguela |
| author_sort | Erika M. Novoa-Bolivar |
| collection | DOAJ |
| description | <b>Objective</b>: Antifibrotics can improve the outcome of patients with idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung diseases (F-ILDs), but predictive biomarkers at diagnosis are needed to guide the use of immunomodulating and antifibrotic therapies. <b>Methods</b>: Flow cytometry quantification of lymphocytes and neutrophils in bronchoalveolar lavage (BAL) of 145 IPFs, 561 non-IPF-ILDs (125 F-ILDs), and 112 BAL controls were retrospectively correlated with the incidence of fibrosis and third-quartile overall survival (Q3–OS). <b>Results</b>: The incidence of IPF was directly proportional (9.6%, 22.2%, and 42.6%, <i>p</i> < 0.001) to BAL neutrophil counts (<5%, 5–15%, and >15%), but inversely proportional (34.1%, 18.6%, and 8.8%, <i>p</i> < 0.001) to BAL lymphocyte counts (<7%, 7–20%, and >20%). Elevated neutrophils (>5%) with low lymphocytes (<7%) were associated with an increasingly higher incidence of IPF (10.0–56.3%, <i>p</i> < 0.001) in patients aged 40 to 80, compared to the rest of patients (13.0–17.1%). Lymphocytes >20% compared to lymphocytes <7% strongly protected patients with neutrophils >15% (59.7% vs. 20.7%, <i>p</i> < 0.001) from IPF. In contrast, the incidence of F-ILD was not clearly related to BAL lymphocyte/neutrophil counts. Although, IPF and F-ILD showed a shorter Q3–OS (1.8 ± 0.3 and 4.6 ± 0.8 years; <i>p</i> < 0.001) than non-fibrotic-ILDs (11.1 ± 1.3 years), lymphocyte and neutrophil counts were associated with a longer and shorter Q3–OS of non-fibrotic-ILDs (<i>p</i> < 0.03) and F-ILDs (<i>p</i> < 0.04), respectively, but not with a Q3–OS of IPF patients (<i>p</i> < 0.708). Corticosteroids in patients with fibrosis showed a shorter Q3–OS than other immunomodulators (2.4 ± 0.3 vs. 4.0 ± 1.8 years, <i>p</i> = 0.011). <b>Conclusions</b>: Accurate counting of BAL lymphocytes and neutrophils by flow cytometry in ILD patients at diagnosis could help guide immunomodulatory and antifibrotic therapies. |
| format | Article |
| id | doaj-art-08b169c284d64b09899af5c44b7e376c |
| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-08b169c284d64b09899af5c44b7e376c2025-08-20T01:53:49ZengMDPI AGBiomedicines2227-90592024-10-011211243910.3390/biomedicines12112439Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung DiseasesErika M. Novoa-Bolivar0José A. Ros1Sonia Pérez-Fernández2José A. Campillo3Ruth López-Hernández4Rosana González-López5Almudena Otalora-Alcaraz6Cristina Ortuño-Hernández7Lourdes Gimeno8Inmaculada Ruiz-Lorente9Diana Ceballos-Francisco10Manuel Muro11Pablo Martínez-Camblor12Alfredo Minguela13Immunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainPneuomology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainDepartment of Statistics and Operations Research and Mathematics Didactics, University of Oviedo, 33007 Asturias, SpainImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainDepartment of Biomedical Data Science, Geisel School of Medicine at Dartmouth, 7 Lebanon Street, Suite 309, Hinman Box 7261, Hanover, NH 03755, USAImmunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain<b>Objective</b>: Antifibrotics can improve the outcome of patients with idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung diseases (F-ILDs), but predictive biomarkers at diagnosis are needed to guide the use of immunomodulating and antifibrotic therapies. <b>Methods</b>: Flow cytometry quantification of lymphocytes and neutrophils in bronchoalveolar lavage (BAL) of 145 IPFs, 561 non-IPF-ILDs (125 F-ILDs), and 112 BAL controls were retrospectively correlated with the incidence of fibrosis and third-quartile overall survival (Q3–OS). <b>Results</b>: The incidence of IPF was directly proportional (9.6%, 22.2%, and 42.6%, <i>p</i> < 0.001) to BAL neutrophil counts (<5%, 5–15%, and >15%), but inversely proportional (34.1%, 18.6%, and 8.8%, <i>p</i> < 0.001) to BAL lymphocyte counts (<7%, 7–20%, and >20%). Elevated neutrophils (>5%) with low lymphocytes (<7%) were associated with an increasingly higher incidence of IPF (10.0–56.3%, <i>p</i> < 0.001) in patients aged 40 to 80, compared to the rest of patients (13.0–17.1%). Lymphocytes >20% compared to lymphocytes <7% strongly protected patients with neutrophils >15% (59.7% vs. 20.7%, <i>p</i> < 0.001) from IPF. In contrast, the incidence of F-ILD was not clearly related to BAL lymphocyte/neutrophil counts. Although, IPF and F-ILD showed a shorter Q3–OS (1.8 ± 0.3 and 4.6 ± 0.8 years; <i>p</i> < 0.001) than non-fibrotic-ILDs (11.1 ± 1.3 years), lymphocyte and neutrophil counts were associated with a longer and shorter Q3–OS of non-fibrotic-ILDs (<i>p</i> < 0.03) and F-ILDs (<i>p</i> < 0.04), respectively, but not with a Q3–OS of IPF patients (<i>p</i> < 0.708). Corticosteroids in patients with fibrosis showed a shorter Q3–OS than other immunomodulators (2.4 ± 0.3 vs. 4.0 ± 1.8 years, <i>p</i> = 0.011). <b>Conclusions</b>: Accurate counting of BAL lymphocytes and neutrophils by flow cytometry in ILD patients at diagnosis could help guide immunomodulatory and antifibrotic therapies.https://www.mdpi.com/2227-9059/12/11/2439lung fibrosisBAL lymphocyte and neutrophilsinterstitial lung diseaseidiopathic pulmonary fibrosispatient outcomeflow cytometry |
| spellingShingle | Erika M. Novoa-Bolivar José A. Ros Sonia Pérez-Fernández José A. Campillo Ruth López-Hernández Rosana González-López Almudena Otalora-Alcaraz Cristina Ortuño-Hernández Lourdes Gimeno Inmaculada Ruiz-Lorente Diana Ceballos-Francisco Manuel Muro Pablo Martínez-Camblor Alfredo Minguela Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung Diseases Biomedicines lung fibrosis BAL lymphocyte and neutrophils interstitial lung disease idiopathic pulmonary fibrosis patient outcome flow cytometry |
| title | Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung Diseases |
| title_full | Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung Diseases |
| title_fullStr | Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung Diseases |
| title_full_unstemmed | Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung Diseases |
| title_short | Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung Diseases |
| title_sort | neutrophils and lymphocytes yin and yang of lung fibrosis and patient outcome in diffuse interstitial lung diseases |
| topic | lung fibrosis BAL lymphocyte and neutrophils interstitial lung disease idiopathic pulmonary fibrosis patient outcome flow cytometry |
| url | https://www.mdpi.com/2227-9059/12/11/2439 |
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