Neutrophil-lymphocyte ratio being associated with mortality risk in patients receiving antifibrotic therapy.

BACKGROUND: Antifibrotic therapy is widely used for patients with progressive fibrotic interstitial lung disease (ILD), regardless of etiology. There is an urgent need for a simple, inexpensive, and repeatable biomarker to evaluate disease severity and mortality risk. METHODS: This retrospective multicohort study assessed the neutrophil-lymphocyte ratios (NLRs) of 416 patients with ILD who received antifibrotic therapy (Hamamatsu cohort, n = 217; Seirei cohort, n = 199). The mortality risk vs. NLR relationship was evaluated at therapy initiation and 1 year. The optimal NLR cutoff of 2.7 was selected according to the mortality risk. RESULTS: Survival was shorter in patients with high NLR than with low NLR (median: 2.63 vs. 4.01 years). The NLR classification results (cutoff: 2.7) were longitudinally preserved in >70 % of the patients, and patients with consistently high NLR had a higher risk of mortality than others (median, 2.97 vs. 4.42 years). In multivariate analysis, high NLR was significantly associated with mortality independent of age, sex, forced vital capacity, lung diffusing capacity for carbon monoxide (DLCO), or the gender-age-physiology (GAP) index. A combined GAP index-NLR assessment classified mortality risk into four groups. Subset analyses revealed that NLR assessment was more applicable to patients without advanced disease, not taking steroids, and with idiopathic pulmonary fibrosis (IPF) than to patients with advanced disease, taking steroids, and patients with Non-IPF. CONCLUSION: High NLR was associated with an increased mortality risk in patients with ILDs receiving antifibrotic therapy. Assessment of NLR may help predict disease severity and mortality risk in antifibrotic therapy.

Standardized 3D-CT lung volumes for patients with acute exacerbation of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: Fibrotic interstitial lung disease (ILD) is a progressive lung disease characterized by loss of lung volume, resulting in a leading cause of death in patients with RA. Crucially, acute exacerbation (AE) of ILD shows higher morbidity and mortality with rapid deterioration of the lungs. However, a quantitative assessment for physiological changes at AE has yet to be performed. This study hypothesized that quantitative assessments of lung volume (LV) accurately indicate disease severity and mortality risk in patients with AE-RA-ILD. METHODS: This multicentre cohorts study quantitatively assessed physiological changes of RA-ILD at diagnosis (n = 54), at AE (discovery-cohorts; n = 20, and validation-cohort; n = 33), and controls (n = 35) using 3D CT (3D-CT) images. LV was quantitatively measured using 3D-CT and standardized by predicted forced vital capacity. RESULTS: Patients with RA-ILD at diagnosis showed decreased LV, predominantly in lower lobes, compared with controls. Further substantial volume loss was found in upper- and lower lobes at AE compared with those at diagnosis. During AE, decreased standardized 3D-CT LV was associated with a worse prognosis in both cohorts. Subsequently, standardized 3D-CT LV was identified as a significant prognostic factor independent of age, sex and the presence of UIP pattern on CT by multivariate analyses. Notably, a composite model of age and standardized 3D-CT LV successfully classified mortality risk in patients with AE-RA-ILD. CONCLUSION: Volume loss at AE in patients with RA-ILD was associated with increased mortality. Assessing physiological change using standardized 3D-CT might help evaluate disease severity and mortality risk in patients with AE-RA-ILD.

Neutrophil-lymphocyte ratio in patients with idiopathic pleuroparenchymal fibroelastosis.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (iPPFE), a progressive fibrotic disease, is characterised by upper lobe-dominant lung fibrosis involving the pleura and subpleural lung parenchyma. However, no prognostic markers have been established for this condition. Associations between blood leucocyte levels and mortality have been reported in patients with idiopathic pulmonary fibrosis; therefore, we hypothesised that peripheral leucocyte levels are associated with mortality risk in patients with iPPFE. METHODS: This retrospective study longitudinally assessed peripheral leucocyte counts at the time of diagnosis and 1 year after diagnosis in two cohorts of 127 patients with iPPFE (69 and 58 patients in Seirei and Hamamatsu cohorts, respectively). RESULTS: A comprehensive assessment of peripheral leucocytes revealed that the neutrophil-lymphocyte ratio (NLR) was associated with mortality in patients with iPPFE after adjusting for age, sex and forced vital capacity in multivariate analyses (adjusted HR, 1.131; 95% CI, 1.032 to 1.227). When the patients were classified based on the median NLR, those with a high NLR had shorter survival than those with a low NLR (median, 32.2 vs 79.8 months; HR, 2.270; 95% CI, 1.416 to 3.696). Interestingly, the results of the NLR classification by median were longitudinally preserved in >70% of patients, and patients with consistently high NLR were at a higher risk of mortality than others (median, 24.8 vs 79.6 months; HR, 3.079; 95% CI, 1.878 to 5.031). Compared with the gender-age-physiology model, a composite model comprising age, sex and NLR could successfully stratify patients with iPPFE into three groups according to mortality risk. CONCLUSION: The assessment of peripheral leucocyte counts is easy and might be useful in evaluating disease severity and mortality risk in patients with iPPFE. Our study suggests the importance of focusing on peripheral leucocyte levels in daily practice.

Assessment of malnutrition-related risk in patients with idiopathic pleuroparenchymal fibroelastosis.

Background: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is characterised by upper lobe-dominant fibrosis involving the pleura and subpleural lung parenchyma, with advanced cases often complicated by progressive weight loss. Therefore, we hypothesised that nutritional status is associated with mortality in IPPFE. Methods: This retrospective study assesses nutritional status at the time of diagnosis and 1 year after diagnosis in 131 patients with IPPFE. Malnutrition-related risk was evaluated using the Geriatric Nutritional Risk Index (GNRI). Results: Of the 131 patients, 96 (73.8%) were at malnutrition-related risk at the time of diagnosis according to the GNRI. Of these, 21 patients (16.0%) were classified as at major malnutrition-related risk (GNRI <82). Patients at major malnutrition-related risk were significantly older and had worse pulmonary function than patients at low (GNRI 92- <98) and moderate (GNRI 82- <92) malnutrition-related risk. GNRI scores decreased significantly from the time of diagnosis to 1 year after diagnosis. Patients with a lower GNRI (<91.8) had significantly shorter survival than patients with a median GNRI or higher (≥91.8). Patients with declines in annual GNRI scores of ≥5 had significantly shorter survival than patients with declines in annual GNRI scores of <5. In multivariate analysis, major malnutrition-related risk was significantly associated with increased mortality after adjustment for age, sex and forced vital capacity (hazard ratio 1.957). A composite scoring model including age, sex and major malnutrition-related risk was able to separate mortality risk in IPPFE. Conclusion: Assessment of nutritional status by the GNRI provides useful information for managing patients with IPPFE by predicting mortality risk.

Geriatric Nutritional Risk Index is a predictor of tolerability of antifibrotic therapy and mortality risk in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung fibrosis of unknown aetiology. Epidemiological studies have suggested that IPF progression may negatively affect nutritional status. Weight loss during antifibrotic therapy is also frequently encountered. The association of nutritional status and outcome has not been fully evaluated in IPF patients. METHODS: This retrospective multicohort study assessed nutritional status of 301 IPF patients receiving antifibrotic therapy (Hamamatsu cohort, n = 151; Seirei cohort, n = 150). Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). The GNRI was calculated based on body mass index and serum albumin. The relationship between nutritional status and tolerability of antifibrotic therapy as well as mortality was explored. RESULTS: Of 301 patients, 113 (37.5%) had malnutrition-related risk (GNRI < 98). Patients with malnutrition-related risk were older, had increased exacerbations and worse pulmonary function than those without a GNRI status <98. Malnutrition-related risk was associated with a higher incidence of discontinuation of antifibrotic therapy, particulary due to gastrointestinal disturbances. IPF patients with malnutrition-related risk (GNRI < 98) had shorter survival than those without such risk (median survival: 25.9 vs. 41.1 months, p < 0.001). In multivariate analysis, malnutrition-related risk was a prognostic indicator of antifibrotic therapy discontinuation and mortality, independent of age, sex, forced vital capacity, or gender-age-physiology index. CONCLUSION: Nutritional status has significant effects on the treatment and outcome in patients with IPF. Assessment of nutritional status may provide important information for managing patients with IPF.

Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by worsening dyspnoea and exercise intolerance. RESEARCH QUESTION: Does a long-term pulmonary rehabilitation improve exercise tolerance in patients with IPF treated with standard antifibrotic drugs, which are expected to reduce disease progression? METHODS: This open-label randomised controlled trial was performed at 19 institutions. Stable patients receiving nintedanib were randomised into pulmonary rehabilitation and control groups (1:1). The pulmonary rehabilitation group underwent initial rehabilitation which included twice-weekly sessions of monitored exercise training for 12 weeks, followed by an at-home rehabilitation programme for 40 weeks. The control group received usual care only, without pulmonary rehabilitation. Both groups continued to receive nintedanib. The primary and main secondary outcomes were change in 6 min walking distance (6MWD) and change in endurance time (using cycle ergometry) at week 52. RESULTS: Eighty-eight patients were randomised into pulmonary rehabilitation (n=45) and control (n=43) groups. Changes in 6MWD were -33 m (95% CI -65 to -1) and -53 m (95% CI -86 to -21) in the pulmonary rehabilitation and control groups, respectively, with no statistically significant difference (mean difference, 21 m (95% CI -25 to 66), p=0.38). Changes in endurance time were significantly better in the pulmonary rehabilitation (64 s, 95% CI -42.3 to 171)) than in the control (-123 s (95% CI -232 to -13)) group (mean difference, 187 s (95% CI 34 to 153), p=0.019). INTERPRETATION: Although pulmonary rehabilitation in patients taking nintedanib did not improve 6MWD in the long term, it led to prolonged improvement in endurance time. TRIAL REGISTRATION NUMBER: UMIN000026376.

Idiopathic pleuroparenchymal fibroelastosis: three-dimensional computed tomography assessment of upper-lobe lung volume.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare interstitial lung disease characterised by predominant upper-lobe fibrosis involving the pleura and subpleural lung parenchyma. Despite its poor prognosis, there is no consensus on prognostic determinants of iPPFE to date. Because volume loss in the upper lobe is a distinct feature of iPPFE, we hypothesised that the lung volume of the bilateral upper lobes (upper-lobe volume) accurately indicates disease severity and mortality risk in iPPFE patients. METHODS: This retrospective study assessed two cohorts of 132 patients with iPPFE (69 in Hamamatsu cohort; 63 in Seirei cohort) and 45 controls. Each lobe volume was quantitatively measured using three-dimensional computed tomography at the time of iPPFE diagnosis and standardised using predicted forced vital capacity. RESULTS: The standardised upper-lobe volume in iPPFE patients was less than half that of controls, whereas the lower-lobe volume did not decrease. iPPFE patients with lower standardised upper-lobe volume had significantly shorter survival rates than those with higher volume (median survival: 6.08 versus 2.48 years, p<0.001). In multivariate analysis, the lower standardised upper-lobe volume was significantly associated with increased mortality adjusting for age, sex and forced vital capacity (HR 0.939). A composite scoring model, including age, sex and standardised upper-lobe volume, better predicted risk of death than the gender-age-physiology model. CONCLUSION: Assessment of upper-lobe volume provides useful information for managing iPPFE by evaluating disease severity and mortality risk in clinical practice.

Chemotherapy for patients with advanced lung cancer with interstitial lung disease: a prospective observational study.

Introduction: Although recent advances in chemotherapy for lung cancer are remarkable, most clinical trials have excluded patients with interstitial lung disease (ILD) due to the concern of developing acute exacerbation (AE) of ILD. Hence, accumulating original evidence of cancer treatment for this population is important. Methods: Between 2016 and 2020, a prospective observational study was conducted across 11 Japanese hospitals. Patients with chemotherapy-naïve, inoperable, advanced lung cancer with ILD were included. The primary outcome was the frequency of AE-ILD after registration; the secondary outcomes were the risk factor of AE-ILD and the efficacy of chemotherapy. Results: Among 124 patients enrolled, 109 patients who received chemotherapy were analyzed. The median age was 72 years, and the majority showed usual interstitial pneumonia (UIP)/probable UIP pattern upon chest computed tomography. The median percent-predicted forced vital capacity (%FVC) was 81% (interquartile range: 66-95%). After registration, 23 patients (21.1%; 95% confidence interval [CI]: 14.4-29.7%) developed AE-ILD. The logistic analysis revealed that lower %FVC slightly but significantly increased the risk of AE-ILD (odds ratio per 10% decrease: 1.27; 95% CI: > 1.00-1.62). Overall response rates/median overall survival times in non-small-cell lung cancer and small-cell lung cancer for the first-line chemotherapy were 41% (95% CI: 31-53)/8.9 months (95% CI: 7.6-11.8) and 91% (95% CI: 76-98)/12.2 months (95% CI: 9.2-14.5), respectively. Conclusion: AE-ILD during chemotherapy is a frequent complication among patients with lung cancer with ILD, particularly those with lower %FVC. Conversely, even in this population, passable treatment response can be expected.

Standardised 3D-CT lung volumes for patients with idiopathic pulmonary fibrosis.

BACKGROUND: The assessment of lung physiology via pulmonary function tests (PFTs) is essential for patients with idiopathic pulmonary fibrosis (IPF). However, PFTs require active participation, which can be challenging for patients with severe respiratory failure, such as during moments of acute exacerbation (AE) of IPF. Recent advances have enabled the re-construction of 3-dimensional computed-tomography (3D-CT) images. This study established a standardisation method and quantitative analysis of lung volume (LV) based on anthropometry using 3D-CT images. METHODS: This is a retrospective multi-center cohort study. The standardised 3D-CT LV in patients with IPF at diagnosis (n = 140) and during AE (cohort1; n = 61 and cohort2; n = 50) and those of controls (n = 53) were assessed. RESULTS: The standardised 3D-CT LVs at IPF diagnosis were less than those of control patients, especially in the lower lung lobes. The standardised 3D-CT LVs were correlated with forced vital capacity (FVC) and validated using the modified Gender-Age-Physiology (GAP) index. The standardised 3D-CT LVs at IPF diagnosis were independently associated with prognosis. During AE, PFTs were difficult to perform, 3D-CT analyses revealed reduced lung capacity in both the upper and lower lobes compared to those obtained at diagnosis. Lower standardised 3D-CT LVs during AE were independently associated with worse outcomes in the two independent cohorts. In particular, volume loss in the upper lobe at AE had prognostic values. CONCLUSIONS: A novel image quantification method for assessing pulmonary physiology using standardised 3D-CT-derived LVs was developed. This method successfully predicts mortality in patients with IPF and AE of IPF, and may be a useful alternative when PFTs cannot be performed.

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model.

BACKGROUND: Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), like those with idiopathic pulmonary fibrosis (IPF), might develop an unexpected acute exacerbation (AE)-a rapidly progressing and deadly respiratory decline. Although AE incidence and risk factors in RA-ILD patients are known, their post-AE clinical course remains unknown owing to the rarity of AE-RA-ILD. This multicentre retrospective study evaluated post-AE mortality and prognostic variables in AE-RA-ILD patients and created a mortality prediction model for AE-RA-ILD. METHODS: This research comprised 58 patients with AE-RA-ILD and 96 with AE-IPF (a control disease). Multivariate Cox regression analysis was performed to identify prognostic variables. A prediction model was created with recursive partitioning (decision tree). RESULTS: The post-AE 90-day mortality rate in the overall AE-RA-ILD group was 48.3%; percent predicted forced vital capacity within 12 months before AE onset (baseline %FVC) and PaO2/FiO2 ratio at AE onset (P/F at AE) were independent predictors of mortality. Post-AE 90-day mortality rates were 40.6% and 43.8%, respectively, in AE-RA-ILD and AE-IPF patients propensity score-matched for age, sex, baseline %FVC and P/F at AE (P = 1.0000). In AE-RA-ILD patients, C-indices of baseline %FVC and P/F at AE to predict post-AE 90-day mortality were 0.604 and 0.623, respectively. A decision tree model based on these prognostic factors classified AE-RA-ILD patients into mild, moderate and severe groups (post-AE 90-day mortality rates: 20.8%, 64.0% and 88.9%, respectively; P = 0.0002); the C-index improved to 0.775. CONCLUSIONS: Post-AE mortality was high in AE-RA-ILD patients similar to AE-IPF patients. The discovered prognostic factors and our mortality prediction model may aid in the management of AE-RA-ILD patients.

Impact of antifibrotic therapy on lung cancer development in idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are at a high risk of lung cancer (LC). Antifibrotic therapy slows disease progression and possibly prolongs survival. However, whether antifibrotic therapy affects LC development in patients with IPF remains unknown. This multicentre retrospective study evaluated 345 patients with IPF. The incidence and prevalence of LC were significantly lower in patients with IPF receiving antifibrotic therapy than those not receiving. Subsequently, LC-related mortality was significantly lower in patients with IPF receiving antifibrotic therapy. These results suggest that antifibrotic therapy was possibly associated with a reduced risk of LC development in patients with IPF, which may be partly associated with its survival benefit.

Combined assessment of the GAP index and body mass index at antifibrotic therapy initiation for prognosis of idiopathic pulmonary fibrosis.

Antifibrotic therapy (AFT) slows disease progression in patients with idiopathic pulmonary fibrosis (IPF). The Gender-Age-Physiology (GAP) index, was developed based on data at IPF diagnosis before the introduction of AFT and has not been evaluated in the AFT context. Further, recent advances have revealed the importance of body-composition factors in prognosis of IPF treated with AFT. This multi-centre, retrospective study aimed to evaluate the GAP index and body mass index (BMI) at the time of AFT initiation for predicting prognosis in patients with IPF. This study included two patient cohorts of IPF receiving AFT, Hamamatsu cohort (n = 110) and Seirei cohort (n = 119). The distribution of GAP stages I, II, and III was 38.2%, 43.6%, and 18.2%, respectively, in Hamamatsu cohort; in Seirei cohort, it was 41.2%, 50.4%, and 8.4%, respectively. In both cohorts, the GAP index distinctly classified prognosis into three groups (log-rank test). Interestingly, a lower BMI showed prognostic value independent of the GAP index in multivariate analyses. Subsequently, combining the GAP index with BMI at AFT initiation successfully divided the patients with IPF into four distinct prognoses. Assessment of the GAP index and BMI measurement at AFT initiation are important for predicting prognosis in patients with IPF.

Switching antifibrotics in patients with idiopathic pulmonary fibrosis: a multi-center retrospective cohort study.

BACKGROUND: Currently, there are two antifibrotics used to treat idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. Antifibrotics slow disease progression by reducing the annual decline of forced vital capacity (FVC), which possibly improves outcomes in IPF patients. During treatment, patients occasionally switch antifibrotic treatments. However, prognostic implication of changing antifibrotics has not yet been evaluated. METHODS: This multi-center retrospective cohort study examined 262 consecutive IPF patients who received antifibrotic therapy. Antifibrotic agents were switched in 37 patients (14.1%). The prognoses were compared between the patient cohort that switched antifibrotics (Switch-IPF) and those without (Non-Switch-IPF) using propensity-score matched analyses. RESULTS: The median period between the initiation of antifibrotic therapy and the drug switch was 25.8 (12.7-35.3) months. The most common reasons for the switch were disease progression (n = 17) followed by gastrointestinal disorders (n = 12). Of the 37 patients that switched antifibrotics, only eight patients disrupted switched antifibrotics by their adverse reactions. The overall prognosis of the Switch-IPF cohort was significantly better than the Non-Switch-IPF cohort (median periods: 67.2 vs. 27.1 months, p < 0.0001). In propensity-score matched analyses that were adjusted to age, sex, FVC (%), history of acute exacerbation, and usage of long-term oxygen therapy, the Switch-IPF cohort had significantly longer survival times than the Non-Switch-IPF group (median 67.2 vs. 41.3 months, p = 0.0219). The second-line antifibrotic therapy showed similar survival probabilities than those in first-line antifibrotic therapy in multistate model analyses. CONCLUSION: Switching antifibrotics is feasible and may improve prognosis in patients with IPF. A further prospective study will be required to confirm clinical implication of switching the antifibrotics.

Prognostic classification in acute exacerbation of idiopathic pulmonary fibrosis: a multicentre retrospective cohort study.

Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) is a major prognostic determinant. However, evidence for its prognostic strength is mainly based on the results of small cohort studies with statistical limitations. This retrospective study, which included 108 patients with a first episode of AE-IPF, aimed to identify prognostic factors and to develop prognostic classification models. Multivariate Cox regression analysis revealed that a lower percent-predicted forced vital capacity within 12 months before AE onset (baseline %FVC) and a lower PaO2/FiO2 ratio at AE onset were independent mortality predictors. If the value of each predictor was lower than the cutoff determined by receiver-operating characteristic analysis, 1 point was assigned. Classification of patients into mild, moderate, and severe groups based on total score showed post-AE 90-day cumulative survival rates of 83.3%, 66.2%, and 22.2%, respectively (model 1: C-index 0.702). Moreover, a decision tree-based model was created with the recursive partitioning method using baseline %FVC and PaO2/FiO2 ratio at AE onset from among multivariable; accordingly, patients were classified into 3 groups with post-AE 90-day cumulative survival rates of 84.1%, 64.3%, and 24.0%, respectively (model 2: C-index 0.735). These models can guide clinicians in determining therapeutic strategies and help design future studies on AE-IPF.

Clinical Significance of Interstitial Lung Disease and Its Acute Exacerbation in Microscopic Polyangiitis.

BACKGROUND: Presence of interstitial lung disease (ILD) is thought to be associated with mortality in microscopic polyangiitis (MPA); however, evidence on MPA-ILD remains lacking. Acute exacerbation (AE) refers to rapidly progressive, fatal respiratory deterioration that may develop in patients with various ILDs. No study has investigated the clinical significance of AE in MPA-ILD. RESEARCH QUESTION: We aimed to determine the clinical picture and prognostic factors, the incidence of AE, and the risk factors in patients with MPA-ILD. STUDY DESIGN AND METHODS: Eighty-four consecutive patients with MPA-ILD and 95 patients with MPA-non-ILD were analyzed. We also compared 80 patients with MPA-ILD and 80 patients with idiopathic interstitial pneumonia without myeloperoxidase-antineutrophil cytoplasmic antibody positivity (ILD alone), who were matched for age, sex, and chest high-resolution CT scan pattern. RESULTS: The MPA-ILD group had a higher frequency of men and smokers and was associated with higher mortality than the MPA-non-ILD group. The matched MPA-ILD group had a higher mortality rate than the matched ILD alone group. There was no significant difference in AE incidence between the matched MPA-ILD and ILD alone groups (1-year AE cumulative incidence rate, 7.5% and 5.2%, respectively; P = .75). In the MPA-ILD group, a lower percent predicted FVC (%FVC) was independently associated with a higher mortality rate (hazard ratio [HR], 0.96 per 1% increase; P < .01) and a higher AE incidence rate (HR, 0.96 per 1% increase; P = .01). On multivariable Cox regression analysis with time-dependent covariates, developing AE during their clinical course was strongly associated with shorter survival (HR, 17.1; P < .001). INTERPRETATION: MPA-ILD represented a distinct phenotype with poor prognosis. Lower %FVC was an independent prognostic factor. Patients with lower %FVC had a risk of developing AE, which was a strong prognostic determinant. The specific management for MPA-ILD and AE should be established.

Cause of mortality and sarcopenia in patients with idiopathic pulmonary fibrosis receiving antifibrotic therapy.

BACKGROUND AND OBJECTIVE: Recent research has highlighted the fundamental role of sarcopenia, characterized by loss of skeletal muscle mass and strength, with a risk of poor outcomes. AFT preserves lung function by preventing the annual decline in FVC and is associated with improved outcomes in patients with IPF. However, altered cause of death and prognostic implications of sarcopenia in patients with IPF receiving AFT remain unknown. METHODS: This study comprised two cohorts of patients with IPF receiving AFT, historical cohort of IPF patients without AFT and controls. The cause of mortality was compared with a historical cohort. Sarcopenia was assessed by measuring the ESMCSA and ESMMA via CT. RESULTS: Patients with IPF had smaller ESMCSA and lower ESMMA but similar BMI than controls, suggesting patients with IPF had skeletal muscle loss without any obvious body weight loss. The most common cause of mortality in patients receiving AFT was chronic respiratory failure, accounting for approximately 60%, and decreased proportions of LC were found. Subsequently, low ESMCSA was an independent prognostic factor associated with worse survival rates. Furthermore, combined assessment of ESMCSA , %FVC predicted and BMI values provided clear prognostic distinction. CONCLUSION: Patients with IPF receiving AFT showed skeletal muscle loss without obvious weight loss. These patients mostly died by chronic respiratory failure, and skeletal muscle wasting has prognostic significance, suggesting that preventing sarcopenia as well as preserving lung function are important for managing these patients.

Pulse oximetric saturation to fraction of inspired oxygen (SpO2/FIO2) ratio 24 hours after high-flow nasal cannula (HFNC) initiation is a good predictor of HFNC therapy in patients with acute exacerbation of interstitial lung disease.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy provides effective respiratory management in patients with hypoxemic respiratory failure. However, the efficacy and tolerability of HFNC for patients with acute exacerbation of interstitial lung disease (AE-ILD) have not been established. This study was performed to assess the efficacy and tolerability of HFNC for patients with AE-ILD and identify the early predictors of the outcome of HFNC treatment. METHODS: We retrospectively reviewed the records of patients with AE-ILD who underwent HFNC. Overall survival, the success rate of HFNC treatment, adverse events, temporary interruption of treatment, discontinuation of treatment at the patient's request, and predictors of the outcome of HFNC treatment were evaluated. RESULTS: A total of 66 patients were analyzed. Of these, 26 patients (39.4%) showed improved oxygenation and were successfully withdrawn from HFNC. The 30-day survival rate was 48.5%. No discontinuations at the patient's request were observed, and no serious adverse events occurred. The pulse oximetric saturation to fraction of inspired oxygen (SpO2/FIO2) ratio 24 h after initiating HFNC showed high prediction accuracy (area under the receiver operating characteristic curve, 0.802) for successful HFNC treatment. In the multivariate logistic regression analysis, an SpO2/FIO2 ratio of at least 170.9 at 24 h after initiation was significantly associated with successful HFNC treatment (odds ratio, 51.3; 95% confidence interval, 6.13-430; p < 0.001). CONCLUSIONS: HFNC was well tolerated in patients with AE-ILD, suggesting that HFNC is a reasonable respiratory management for these patients. The SpO2/FIO2 ratio 24 h after initiating HFNC was a good predictor of successful HFNC treatment. The reviews of this paper are available via the supplemental material section.

Efficacy of corticosteroid and intravenous cyclophosphamide in acute exacerbation of idiopathic pulmonary fibrosis: A propensity score-matched analysis.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) is a leading cause of death in patients with idiopathic pulmonary fibrosis (IPF). Although optimal treatment for AE-IPF remains unclear, high-dose corticosteroids (CS) with/without immunosuppressants, including intravenous cyclophosphamide (IVCY), are often used as empirical therapy. However, the survival benefit of adding IVCY to CS therapy is unknown. We investigated the efficacy of this therapy in patients with AE-IPF. METHODS: Overall, 102 consecutive patients with IPF with a first idiopathic AE were included. Post-AE survival rates and treatment safety were retrospectively assessed. Efficacy of CS + IVCY therapy for the first AE was compared with that of CS monotherapy using a propensity score-matched analysis. RESULTS: The post-AE 90-day survival rate of the entire cohort was 64.7%. On the basis of the propensity scores, 26 matched patient pairs were made. Characteristics of matched patients with AE-IPF treated with CS (matched CS group) and those with CS + IVCY (matched CS + IVCY group) were well balanced. No significant between-group differences were observed in post-AE 90-day survival rates (84.6% vs 76.9%; P = 0.70), cumulative survival rates (P = 0.57 by log-rank test) or incidence of adverse events ≥ CTCAE (Common Terminology Criteria for Adverse Events) v5.0 grade 3 (61.5% vs 65.4%; P = 1.00). CONCLUSION: The propensity score-matched analysis demonstrated that compared with CS monotherapy, CS + IVCY therapy did not significantly improve post-AE survival in patients with AE-IPF. Further studies are warranted to assess the efficacy of CS + IVCY therapy for AE-IPF.

Preexisting Interstitial Lung Disease and Lung Injury Associated with Irinotecan in Patients with Neoplasms.

BACKGROUND/AIM: The aim of this study was to reveal risk factors for lung injury following irinotecan administration for the treatment of neoplasms. PATIENTS AND METHODS: This study included 204 patients who received irinotecan from October 2005 to November 2014 and had evaluable chest CT images before initiation of irinotecan. RESULTS: Six (2.9%) patients developed lung injury and, of these, 2 had preexisting interstitial lung disease (pre-ILD). The frequency of lung injury in patients with pre-ILD was 11% (2 of 19) while that in patients without pre-ILD was 2.2%. Risk factor analysis for the lung injury showed pre-ILD was the most predictable factor [odds ratio (OR) 5.00, p=0.07]. Combination with other agents, origin of neoplasms (lung or not), initial dose or minimum interval were not observed to be related to risk. CONCLUSION: The risk of lung injury with irinotecan was high when pre-ILD was present and the risk was comparable with previously reported other agents.