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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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/11/2439 |
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| Summary: | <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. |
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| ISSN: | 2227-9059 |