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

Abstract

BackgroundInterstitial lung abnormalities (ILA) are specific spatial patterns on computed tomography scan (CT), potentially compatible with early interstitial lung disease (ILD). A proportion will progress; management involves risk stratification and surveillance. Elevated blood monocyte levels have been shown to associate with progression of IPF.AimsTo (i) estimate the proportion of “early fibrotic” ILAs (EF-ILA; reticular +/− ground glass opacities, excluding traction bronchiectasis and honeycombing) on CTs of patients attending all-indications thoracic CTs, and proportion demonstrating radiological progression and (ii) explore association between peripheral blood leukocyte levels and ILA progression.MethodsWe analysed all thoracic CT reports in individuals aged 45–75 performed between January-2015 and December-2020 in one large teaching hospital (Oxford, UK) to identify patient CT reports consistent with EF-ILA. CT-contemporaneous blood leukocyte counts were examined to explore contribution to progression and all-cause mortality, using multivariate Cox regression.Results40 711 patients underwent thoracic CT imaging during this period. 1259 (3.1%) demonstrated the EF-ILA pattern. Mean age; 65.4 (±7.32), male; 735 (47.8%). EF-ILA was significantly associated with all-cause mortality [HR 1.87, 95%CI 1.25–2.78, p=0.002]. 362 cases underwent at least one follow-on CT. Radiological progression was observed in 157 cases (43.4%); increase in reticulation; 51, new traction bronchiectasis; 84, and honeycombing; 22. Monocyte count, neutrophil count, monocyte:lymphocyte ratio, neutrophil:lymphocyte ratio and 'systemic inflammatory response index' were significantly associated with radiological progression.Conclusion3.1% of subjects requiring thoracic CT during a 6-year period demonstrated EF-ILA. Monocyte levels, and blood leukocyte-derived indexes were associated with radiological progression and could indicate which patients may require closer follow up.

A meta-analysis of the clinical significance of neutrophil-to-lymphocyte ratios in interstitial lung disease

“…Adverse outcomes included mortality, worsening radiological lung interstitial change, progressive dyspnea and hypoxemia, and FVC decline ≥ 10% per year. Among the included studies, 15 articles (ILD:n = 2,912, Non-ILD: n = 2,868) compared NLR between patients with and without ILD [ 5 , 8 , 11 , 13 , 15 , 17 – 22 , 29 , 31 , 32 , 34 ], and eight articles (favorable outcomes of ILD: n = 340, unfavorable outcomes of ILD: n = 407) compared NLR between ILD patients with favorable and unfavorable outcomes [ 6 , 8 – 10 , 15 , 16 , 32 , 33 ] (Tables 1 and 2 ). The adjusted RR/HR/OR (95% CI) values of ILD patients with adverse outcomes were collected from nine studies [ 6 , 7 , 9 – 12 , 30 – 32 ].…”

“…Fifteen studies compared NLR levels in patients with and without ILD [ 5 , 8 , 11 , 13 , 15 , 17 – 22 , 29 , 31 , 32 , 34 ]. A random-effects model was utilized because the heterogeneity test showed statistical differences (I 2 = 66.3%; p = 0.000).…”

“…Nine articles [ 6 , 7 , 9 – 12 , 30 – 32 ] evaluated the correlation between elevated NLR and adverse prognosis in ILD. Six studies [ 7 , 9 – 11 , 30 , 31 ] found a link between high NLR levels and a poor prognosis, whereas three studies [ 6 , 12 , 32 ] found no association. The included literature exhibited apparent heterogeneity(I 2 = 80.2%, p = 0.000), and a random effects model was used for statistical analysis.…”

Cigarette Smoking, and Blood Monocyte Count Correlate with Chronic Lung Injuries and Mortality

“…16,17,[64][65][66][67] Monocyte levels were also associated with disease progression in IPF and its precursor lesions of ILAs. 11,12 Consequently, monocyte count can function as an inexpensive prognostic biomarker in a smoking population.…”

“…[8][9][10] Accordingly, circulating blood monocyte counts have been associated with lung cancer, COPD, IPF, and ILAs. [11][12][13][14][15][16][17] Monocytes are a heterogenous population of myeloid cells with well-characterized subsets to maintain tissue integrity and functions of innate and adaptive immunity. 18 Classical CD14 ++ CD16 − monocytes represent a transient cell population, which contributes to early inflammatory response, whereas non-classical CD14 DIM CD16 + monocytes (5-8% of blood monocytes) expand markedly following infection or other inflammatory stimuli.…”