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

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease. Patients present at different stages and disease course is varied. Blood monocytes have been linked to all-cause mortality, and neutrophils to progression to IPF in patients with the indeterminate for usual interstitial pneumonia CT pattern. OBJECTIVE: To determine association between blood monocytes, neutrophils and lymphocytes levels (and their derived indexes), with lung function decline and mortality in IPF. METHODS: We performed a retrospective analysis of an IPF cohort (n=128) who had their first clinical visit at the Oxford Interstitial Lung Disease Service between 2013 and 2017. Association between blood monocytes, neutrophils, lymphocytes and derived indexes (within 4 months of visit) and decline in forced vital capacity (FVC) and all-cause mortality were assessed using Cox proportional hazard regression analysis. Kaplan-Meier analysis was used to assess time-to-event for 10% FVC decline and mortality for patients dichotomised to high and low leucocyte counts. RESULTS: Median length of follow-up was 31.0 months (IQR 16.2-42.4); 41.4% demonstrated FVC decline >10% per year and 43.8% died. In multivariate models (incorporating age, gender and initial FVC%), raised neutrophils, lymphopaenia and neutrophil:lymphocyte ratio were associated with FVC decline (p≤0.01); while both monocytes and neutrophil levels (and their derived indexes) were associated with all-cause mortality (p≤0.01). Kaplan-Meier analysis also showed association between neutrophils and its derived indexes but not monocyte, with FVC decline. CONCLUSION: Blood neutrophil and lymphopaenia are more sensitive than monocytes as prognostic indicators of disease progression in those with established IPF.

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

RATIONALE: Idiopathic 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. OBJECTIVE: To evaluate the radiological progression of iUIP and explore factors linked to progression to IPF. METHODS: We 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. RESULTS: 48 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. CONCLUSION: 53% 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.

Financial interests of patient organisations contributing to technology assessment at England's National Institute for Health and Care Excellence: policy review.

OBJECTIVE: To investigate the prevalence of financial interests among patient organisations contributing to health technology assessment at the National Institute for Health and Care Excellence (NICE) in England and the extent to which NICE's disclosure policy ensures that decision making committees are aware of these interests. DESIGN: Policy review using accounts, annual reports, and websites of patient organisations; payments declared by pharmaceutical manufacturers on their websites and a centralised database (Disclosure UK); declarations of interests by nominated representatives of patient organisations; and responses from patient organisations. SETTING: Appraisals of medicines and treatments (technologies) for use in the English and Welsh National Health Service. PARTICIPANTS: 53 patient organisations contributing to 41 NICE technology appraisals published in 2015 and 2016, with 117 separate occasions that a patient organisation contributed to the appraisal of a technology. MAIN OUTCOME MEASURES: Prevalence of specific interests (that is, funding from manufacturer(s) of a technology under appraisal or competitor products); proportion of specific interests of which NICE's decision making committees were aware; proportion of unknown specific interests for which disclosure was not required by NICE's policy RESULTS: 38/53 (72%) patient organisations had accepted funding from the manufacturer(s) of a technology or a competitor product in the same year that they had contributed to the appraisal of that technology or the previous year. Specific interests were present on 92/117 (79%) occasions that patient organisations contributed to appraisals in 2015 and 2016. NICE's decision making committees were aware of less than a quarter of specific interests (30/144; 21%). For nearly two thirds of the specific interests not known to committees (71/114; 62%), disclosure by patient organisations was not required by NICE's policy. CONCLUSIONS: Financial interests are highly prevalent among patient organisations contributing to health technology assessment. NICE should review its disclosure policy to ensure that decision making committees are aware of all relevant interests.