Monocyte and neutrophil levels are potentially linked to progression to IPF for patients with indeterminate UIP CT pattern

Abstract

RationaleIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Identifying patients early may allow intervention which could limit progression. The ‘indeterminate for usual interstitial pneumonia’ (iUIP) CT pattern, defined in the 2018 IPF guidelines, could be a precursor to IPF but there is limited data on how patients with iUIP progress over time.ObjectiveTo evaluate the radiological progression of iUIP and explore factors linked to progression to IPF.MethodsWe performed a retrospective analysis of a lung fibrosis clinic cohort (n=230) seen between 2013 and 2017. Cases with iUIP were identified; first ever CTs for each patient found and categorised as 'non-progressor' or 'progressors' (the latter defined as increase in extent of disease or to 'definite' or 'probable' UIP CT pattern) during their follow-up. Lung function trends, haematological data and patient demographics were examined to explore disease evolution and potential contribution to progression.Results48 cases with iUIP CT pattern were identified. Of these, 32 had follow-up CT scans, of which 23 demonstrated progression. 17 patients in this cohort were diagnosed with IPF over a mean (SD) period of 3.9 (±1.9) years. Monocyte (HR: 23, 95% CI: 1.6 to 340, p=0.03) and neutrophil levels (HR: 1.8, 95% CI: 1.3 to 2.3, p<0.001), obtained around the time of initial CT, were associated with progression to IPF using Cox proportional hazard modelling.Conclusion53% of our evaluable patients with iUIP progressed to IPF over a mean of 4 years. Monocyte and neutrophil levels at initial CT were significantly associated with progression in disease. These data provide a single-centre analysis of the evolution of patients with iUIP CT pattern, and first signal for potential factors associated with progression to IPF.

Neutrophil lymphocyte ratio as an indicator for disease progression in Idiopathic Pulmonary Fibrosis

“…Fraser et al showed that monocyte levels were associated with the amount of fibrosis on CT scan,8 and large cohort studies from Scott linked blood monocyte levels to all-cause mortality,4 while Kreuter found an association with IPF progression (defined as ≥10% absolute decline in forced vital capacity (FVC%) predicted, ≥50 m decline in 6-min-walk distanc or death) within a year 9. In a smaller study, we found that neutrophil levels were highly significantly associated with progression of indeterminate UIP to diagnosis of IPF 10. These findings are supported by increasing understanding of the immune pathogenesis of IPF where innate immune cells like monocytes, monocyte-derived macrophages and neutrophils are likely to have a role in promoting fibroblast activity 11…”

“…First, we examined all the three main parameters of the blood leucocyte profile—neutrophils, lymphocytes and monocytes while Scott and Kreuter focused on monocyte levels only. We did this in part, because of our previous findings of correlation between neutrophils and progression of iUIP to definite/probable UIP on CT scans, 10 but also because there is ample evidence that neutrophils are involved in the immune-pathogenesis of IPF (described further below). 11 Although Scott also examined the transcriptome of blood immune cells, these were on RNA from stored peripheral blood mononuclear cells, where the neutrophil component would not have survived storage.…”

“… 9 In a smaller study, we found that neutrophil levels were highly significantly associated with progression of indeterminate UIP to diagnosis of IPF. 10 These findings are supported by increasing understanding of the immune pathogenesis of IPF where innate immune cells like monocytes, monocyte-derived macrophages and neutrophils are likely to have a role in promoting fibroblast activity. 11 …”

Increased monocyte level is a risk factor for radiological progression in patients with early fibrotic interstitial lung abnormality

“…We have previously demonstrated in a cohort of patients with CT scans demonstrating iUIP that peripheral blood monocyte and neutrophil counts are implicated in progression to IPF [ 37 ], and the association of NLR, MLR and SIRI with mortality in IPF [ 38 ]. MLR has been used primarily to prognosticate in cancer studies in recognition that host systemic inflammatory responses influence tumour proliferation and disease progression [ 39 ].…”

Increased Interleukin-17 and Glucocorticoid Receptor-β Expression in Interstitial Lung Diseases and Corticosteroid Insensitivity

“…IL-17 facilitates the release of IL-6 and IL-8 from structural cells and augments neutrophilia ( 28 ). Monocyte and neutrophil levels were positively associated with progression from ‘indeterminate for usual interstitial pneumonia’ to IPF ( 29 ). A bronchoalveolar lavage (BAL) lower neutrophil-to-lymphocyte ratio has been demonstrated in sarcoidosis and chronic hypersensitivity pneumonitis compared to IPF patients ( 30 ).…”