Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD. METHODS: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed. RESULTS: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 202 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg. CONCLUSIONS: Mild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.

Disease progression and changes in KL-6 in patients with limited cutaneous systemic sclerosis-associated interstitial lung disease.

BACKGROUND: Little is known about the annual change in Krebs von Lungen-6 (KL-6) and its correlation with forced vital capacity (FVC) in limited cutaneous systemic sclerosis-associated interstitial lung disease (lcSSc-ILD). We aimed to clarify the correlation during the clinical course. METHODS: We retrospectively reviewed data from consecutive patients with lcSSc-ILD. We measured FVC and KL-6 annually and calculated their annual changes using the difference in absolute values. Decline in FVC was defined as annual decline in FVC ≥5 %. RESULTS: Thirty-eight patients with SSc-ILD were included. The median age was 62 years and 58 % were female. The median FVC was 87.3 % and the median KL-6 was 1629 U/ml. The median observation period was 55.2 months and the annual changes in FVC and KL-6 were evaluated 151 times simultaneously. The annual change in KL-6 had a significant negative correlation with that in FVC in the first year from the initial evaluation (from the baseline to one-year follow-up) (r = -0.819, p < 0.01), but not after the first year. In the multivariable analysis adjusted by age, sex, and FVC at each year, the annual change of KL-6 (per 100 U/ml) was significantly associated with decline in FVC in the first year (odds ratio: 3.03, 95 % confidence interval: 1.21-7.59, p = 0.02), but not after the first year. CONCLUSIONS: Only in the first year from the initial evaluation, there was negative correlation between the annual change in FVC and that in KL-6 and the annual elevation in KL-6 was associated with decline in FVC in patients with lcSSc-ILD.

Physical activity in idiopathic pulmonary fibrosis: Longitudinal change and minimal clinically important difference.

BACKGROUND AND OBJECTIVE: Reference values of physical activity to interpret longitudinal changes are not available in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to define the minimal clinical important difference (MCID) of longitudinal changes in physical activity in patients with IPF. METHODS: Using accelerometry, physical activity (steps per day) was measured and compared at baseline and 6-months follow-up in patients with IPF. We calculated MCID of daily step count using multiple anchor-based and distribution-based methods. Forced vital capacity and 6-minute walk distance were applied as anchors in anchor-based methods. Effect size and standard error of measurement were used to calculate MCID in distribution-based methods. RESULTS: One-hundred and five patients were enrolled in the study (mean age: 68.5 ± 7.5 years). Step count significantly decreased from baseline to 6-months follow-up (-461 ± 2402, p = .031). MCID calculated by anchor-based and distribution-based methods ranged from 570-1358 steps. CONCLUSION: Daily step count significantly declined over 6-months in patients with IPF. MCID calculated by multiple anchor-based and distribution-based methods was 570 to 1358 steps/day. These findings contribute to interpretation of the longitudinal changes of physical activity that will assist its use as a clinical and research outcome in patients with IPF.

Changes in patient-reported outcomes in patients with non-idiopathic pulmonary fibrosis fibrotic interstitial lung disease and progressive pulmonary fibrosis.

Background: Health-related quality of life (HRQoL) captures different aspects of the fibrotic interstitial lung disease (FILD) evaluation from the patient's perspective. However, little is known about how HRQoL changes in patients with non-idiopathic pulmonary fibrosis (IPF) FILD, especially in those with progressive pulmonary fibrosis (PPF). The aim of this study is to clarify whether HRQoL deteriorates in patients with non-IPF FILD and to evaluate the differences in the changes in HRQoL between those with and without PPF. Methods: We collected data from consecutive patients with non-IPF FILD and compared annual changes in HRQoL over 2 years between patients with PPF and those without. The St George's respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were used to assess HRQoL. Changes in the SGRQ and CAT scores for 24 months from baseline were evaluated with a mixed-effect model for repeated measures. Results: A total of 396 patients with non-IPF FILD were reviewed. The median age was 65 years and 202 were male (51.0%). The median SGRQ and CAT scores were 29.6 and 11, respectively. Eighty-six (21.7%) showed PPF. Both SGRQ and CAT scores were significantly deteriorated in patients with PPF compared to those without PPF (p < 0.01 for both). Clinically important deterioration in the SGRQ and CAT scores were observed in 40.0 and 35.7% of patients with PPF and 11.7 and 16.7% of those without, respectively. PPF was significantly associated with clinically important deterioration in the SGRQ score (odds ratio 5.04; 95%CI, 2.61-9.76, p < 0.01) and CAT score (odds ratio 2.78; 95%CI, 1.27-6.06, p = 0.02). Conclusion: The SGRQ and CAT scores were significantly deteriorated in patients with non-IPF FILD and PPF. Considering an evaluation of HRQoL would be needed when assessing PPF.

Interstitial pneumonia with autoimmune features and histologic usual interstitial pneumonia treated with anti-fibrotic versus immunosuppressive therapy.

BACKGROUND: Therapeutic strategies in patients with interstitial pneumonia with autoimmune features (IPAF) and histological usual interstitial pneumonia (UIP) pattern (IPAF-UIP) have not been thoroughly evaluated. We compared the therapeutic efficacy of anti-fibrotic therapy with that of immunosuppressive treatment for patients with IPAF-UIP. METHODS: In this retrospective case series, we identified consecutive IPAF-UIP patients treated with anti-fibrotic therapy or immunosuppressive therapy. Clinical characteristics, one-year treatment response, acute exacerbation, and survival were studied. We performed a stratified analysis by the pathological presence or absence of inflammatory cell infiltration. RESULTS: Twenty-seven patients with anti-fibrotic therapy and 29 with immunosuppressive treatment were included. There was a significant difference in one-year forced vital capacity (FVC) change between patients with anti-fibrotic treatment (4 in 27 improved, 12 stable, and 11 worsened) and those with immunosuppressive treatment (16 in 29 improved, eight stable, and five worsened) (p = 0.006). There was also a significant difference in one-year St George's Respiratory Questionnaire (SGRQ) change between patients with anti-fibrotic therapy (2 in 27 improved, ten stable, and 15 worsened) and those with immunosuppressive treatment (14 in 29 improved, 12 stable, and worsened) (p < 0.001). There was no significant difference in survival between the groups (p = 0.32). However, in the subgroup with histological inflammatory cell infiltration, survival was significantly better with immunosuppressive therapy (p = 0.02). CONCLUSION: In IPAF-UIP, immunosuppressive therapy seemed to be superior to anti-fibrotic treatment in terms of therapeutic response, and provided better outcomes in the histological inflammatory subgroup. Further prospective studies are needed to clarify the therapeutic strategy in IPAF-UIP.

Real-World Experience of the Comparative Effectiveness and Safety of Molnupiravir and Nirmatrelvir/Ritonavir in High-Risk Patients with COVID-19 in a Community Setting.

Molnupiravir (MOV) and nirmatrelvir/ritonavir (NMV/r) are efficacious oral antiviral agents for patients with the 2019 coronavirus (COVID-19). However, little is known about their effectiveness in older adults and those at high risk of disease progression. This retrospective single-center observational study assessed and compared the outcomes of COVID-19 treated with MOV and NMV/r in a real-world community setting. We included patients with confirmed COVID-19 combined with one or more risk factors for disease progression from June to October 2022. Of 283 patients, 79.9% received MOV and 20.1% NMV/r. The mean patient age was 71.7 years, 56.5% were men, and 71.7% had received ≥3 doses of vaccine. COVID-19-related hospitalization (2.8% and 3.5%, respectively; p = 0.978) or death (0.4% and 3.5%, respectively; p = 0.104) did not differ significantly between the MOV and NMV/r groups. The incidence of adverse events was 2.7% and 5.3%, and the incidence of treatment discontinuation was 2.7% and 5.3% in the MOV and NMV/r groups, respectively. The real-world effectiveness of MOV and NMV/r was similar among older adults and those at high risk of disease progression. The incidence of hospitalization or death was low.

Two cases of acute respiratory failure following SARS-CoV-2 vaccination in post-COVID-19 pneumonia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is a very effective method of preventing infection and is recommended for people having recovered from coronavirus disease 2019 (COVID-19). In this novel case report, we describe two patients with post-COVID-19 pneumonia who experienced acute respiratory failure and new bilateral ground-glass opacities several days after receiving SARS-CoV-2 vaccination. Both patients were treated with methylprednisolone pulse therapy and recovered from the disease successfully. Indeed, post-COVID-19 patients can gain benefits from the vaccine, but vaccination at the early stage of recovery from COVID-19 might be a risk for certain populations. These cases highlight a potential association between vaccination, interstitial lung disease and worsening of post-COVID-19 pneumonia. Further investigation and research examining the relationship between the timing of SARS-CoV-2 vaccination and potential risks in post-COVID-19 patients is recommended.

Prevalence and prognosis of chronic fibrosing interstitial lung diseases with a progressive phenotype.

BACKGROUND AND OBJECTIVE: The development of clinically progressive fibrosis complicates a wide array of interstitial lung diseases (ILDs). However, there are limited data regarding its prevalence and prognosis. METHODS: We analysed consecutive patients seen for initial evaluation of a fibrosing form of ILD (FILD). Patients were evaluated for evidence of progressive fibrosis over the first 24 months of follow-up. We defined a progressive phenotype as the presence of at least one of the following: a relative decline in forced vital capacity (FVC) of ≥10%; a relative decline in FVC of ≥5%-<10% with a relative decline in diffusing capacity of the lung for carbon monoxide of ≥15%, increased fibrosis on HRCT or progressive symptoms. RESULTS: Eight hundred and forty-four patients (397 with idiopathic pulmonary fibrosis [IPF] and 447 non-IPF FILD) made up the final analysis cohort. Three hundred and fifty-five patients (42.1%) met the progressive phenotype criteria (59.4% of IPF patients and 26.6% of non-IPF FILD patients, p <0.01). In both IPF and non-IPF FILD, transplantation-free survival differed between patients with a progressive phenotype and those without (p <0.01). Multivariable analysis showed that a progressive phenotype was an independent predictor of transplantation-free survival (hazard ratio [HR]: 3.36, 95% CI: 2.68-4.23, p <0.01). Transplantation-free survival did not differ between non-IPF FILD with a progressive phenotype and IPF (HR: 1.12, 95% CI: 0.85-1.48, p = 0.42). CONCLUSION: Over one-fourth of non-IPF FILD patients develop a progressive phenotype compared to approximately 60% of IPF patients. The survival of non-IPF FILD patients with a progressive phenotype is similar to IPF.

Weekly nanoparticle albumin-bound paclitaxel and paclitaxel for relapsed small cell lung cancer: A retrospective observational study.

ABSTRACT: In addition to advanced non-small cell lung cancer, nanoparticle albumin-bound paclitaxel (nab-PTX) may also harbor potential benefit for patients with relapsed small cell lung cancer (SCLC), since weekly paclitaxel (PTX) shows modest activity for relapsed SCLC. We evaluated the efficacy and safety of both weekly nab-PTX and PTX for relapsed SCLC.We retrospectively reviewed 52 consecutive relapsed SCLC patients who were treated with weekly nab-PTX or PTX at our hospital.The response rate, median progression-free survival and overall survival with nab-PTX and PTX were 5.6 vs 8.8%, 3.2 vs 1.7 months, and 5.4 vs 4.5 months, respectively. No statistically significant differences were observed. There was no statistical difference between the 2 groups for ≥Grade 3 adverse events.Weekly nab-PTX and PTX showed similar activity for relapsed SCLC. The toxicity profile of nab-PTX was equally tolerable to that of PTX.

Effectiveness of monoclonal antibody therapy for COVID-19 patients using a risk scoring system.

INTRODUCTION: Monoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021. METHODS: According to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan. RESULTS: During Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12-0.53) and 0.10 (95% CI: 0.01-0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event. CONCLUSIONS: The administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.

The prognostic value of the COPD Assessment Test in fibrotic interstitial lung disease.

BACKGROUND: The COPD Assessment Test (CAT) has been studied as a measure of health status in idiopathic pulmonary fibrosis (IPF) and interstitial lung disease associated with connective tissue disease. However, its prognostic value is unknown. The present study explored the association between CAT score and mortality in fibrotic interstitial lung disease (FILD), including IPF and other forms of ILD. METHODS: We retrospectively analyzed 501 consecutive patients with FILD who underwent clinical assessment, including pulmonary function test and CAT. The association between CAT score and 3-year mortality was assessed using Cox proportional hazard analysis, Kaplan-Meier plots, and the log-rank test for trend. To handle missing data, the imputed method was used. RESULTS: The patients' median age was 68 years, and 320 were male (63.9%). Regarding CAT severity, 203 patients had a low impact level (score <10), 195 had a medium level (10-20), 80 had a high level (21-30), and 23 had a very high level (31-40). During the 3-year study period, 118 patients died. After adjusting for age, sex, forced vital capacity, diffusion capacity for carbon monoxide, IPF diagnosis, and usual interstitial pneumonia pattern on high-resolution computed tomography, the CAT score was significantly associated with 3-year mortality (hazard ratio in increments of 10 points: 1.458, 95% confidence interval 1.161-1.830; p < 0.001). In addition, patients with high and very high impact levels had twofold and threefold higher mortality risk than those with low levels, respectively. CONCLUSION: The CAT has prognostic value in FILD.

Anti-MDA5 antibody-positive clinically amyopathic dermatomyositis with diffuse alveolar damage diagnosed by transbronchial lung cryobiopsy: A case report.

Diffuse alveolar damage (DAD) is known to be a pathological hallmark of acute respiratory distress syndrome or acute interstitial pneumonia, and to have a poor prognosis. We report a case of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD), in which DAD was confirmed by transbronchial lung cryobiopsy at an early stage without respiratory failure. Although this patient initially did not show respiratory failure, his respiratory condition gradually worsened despite intensive immunosuppression therapy and he died 3 months later. Therefore, the early pathological findings of DAD did not match the clinical picture, which showed no respiratory failure. However, these findings were consistent with the subsequent course and poor outcome. Histological DAD, even in the absence of respiratory failure, may indicate a subsequent poor prognosis and explain the refractory course of RP-ILD with anti-MDA5 antibody-positive CADM.

Pulmonary rehabilitation for idiopathic pleuroparenchymal fibroelastosis: A retrospective study on its efficacy, feasibility, and safety.

BACKGROUND: The beneficial effects of pulmonary rehabilitation (PR) for patients with idiopathic pleuroparenchymal fibroelastosis (IPPFE) remain unknown. This study aimed to examine the efficacy, feasibility, and safety of PR for IPPFE. METHODS: We retrospectively investigated 25 patients with IPPFE referred for PR between April 2007 and March 2017. The PR mainly consisted of a 10-week exercise training program. The primary outcome was a change in 6-min walk distance (6MWD). Secondary outcomes included changes in dyspnea (transition dyspnea index [TDI]), anxiety and depression (hospital anxiety and depression scale [HADS]), and health-related quality of life (HRQoL) (St George's respiratory questionnaire [SGRQ]). RESULTS: Thirteen patients participated in the PR program (PRP). Recurrent pneumothorax was the most common reason for patients not participating in the PRP. Four patients discontinued the PRP due to the recurrence of pneumothorax, new onset of pneumomediastinum, stroke, and another reason, respectively. Nine patients completed the PRP. Significant improvement was observed in 6MWD (median [interquartile range], 90 m [55-116 m]; P = 0.033). Clinically important improvements in the 6MWD, and TDI, HADS-anxiety, HADS-depression, and SGRQ total domain scores were observed in seven (78%), five (56%), four (44%), four (44%), and five (56%) of the nine patients, respectively. CONCLUSIONS: Patients with IPPFE benefited from PR in terms of exercise capacity, dyspnea, anxiety, depression, and HRQoL. Pneumothorax and pneumomediastinum may impede the implementation of a PRP for patients with IPPFE. While careful patient selection is required, PR may be an efficacious non-pharmacological approach for managing disabilities in patients with IPPFE.

Cutoff Points for Step Count to Predict 1-year All-Cause Mortality in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Although physical activity is associated with mortality in patients with idiopathic pulmonary fibrosis (IPF), reference values to interpret levels of physical activity are lacking. OBJECTIVES: This study aimed to investigate the prognostic significance of physical activity assessed by step count and its cutoff points for all-cause mortality. METHODS: We measured physical activity (steps per day) using an accelerometer in patients with IPF at the time of diagnosis. Relationships among physical activity and mortality, as well as cutoff points of daily step count to predict all-cause mortality were examined. RESULTS: Eighty-seven patients (73 males) were enrolled. Forty-four patients (50.1%) died during the follow-up (median 54 months). In analysis adjusting for Gender-Age-Physiology stage and 6-min walk distance, daily step count was an independent predictor of all-cause mortality (hazard ratio (HR) = 0.820, 95% confidence interval (CI) = 0.694-0.968, p = 0.019). The optimal cutoff point (receiving operating characteristic analysis) for 1-year mortality was 3,473 steps per day (sensitivity = 0.818 and specificity = 0.724). Mortality was significantly lower in patients with a daily step count exceeding 3,473 steps than in those whose count was 3,473 or less (HR = 0.395, 95% CI = 0.218-0.715, p = 0.002). CONCLUSIONS: Step count, an easily interpretable measurement, was a significant predictor of all-cause mortality in patients with IPF. At the time of diagnosis, a count that exceeded the cutoff point of 3,473 steps/day more than halved mortality. These findings highlight the importance of assessing physical activity in this patient population.

Serial 6-month change in forced vital capacity predicts subsequent decline and mortality in Japanese patients with newly diagnosed idiopathic pulmonary fibrosis.

BACKGROUND: The clinical course of idiopathic pulmonary fibrosis (IPF) is characterized by a progressive decline in lung function; however, predicting changes in lung function is difficult. We sought to determine whether the prior 6-month trend in forced vital capacity (FVC) could predict mortality and the subsequent 6-month trend in FVC. METHODS: We retrospectively analyzed consecutive patients with newly diagnosed IPF who underwent serial pulmonary function tests. The immediate two years after the initial evaluation were divided into four terms of six months each and stratified on the basis of presence or absence of a ≥10% relative decline in FVC at six months (declined and stable groups, respectively). RESULTS: We included 107 patients with %predicted FVC of 80.8% and %predicted diffusing capacity of the lung for carbon monoxide of 58.9%. In multivariate analysis, a decline in %predicted FVC in the initial six months was found to be an independent prognostic factor (hazard ratio 4.45, 95% confidence interval 2.62-7.56, p < 0.01). Among the 46 terms in which the FVC declined during the initial 1.5-year study period, a decline in FVC was exhibited in 23 (50.0%) of the subsequent terms. Among 231 terms in which FVC remained stable, a decline was observed in 32 (13.9%) of the subsequent terms (relative risk 3.61, p < 0.01). The frequency of FVC decline in each term was 16-27%. FVC was stable or declined in all four terms in 50.5% and 15.9% of cases, respectively. CONCLUSIONS: Six-month decline in FVC predicts subsequent FVC change and mortality in IPF patients in the era of antifibrotic agents.

Mesalazine-induced lung injury with severe respiratory failure successfully treated with steroids and non-invasive positive pressure ventilation.

Drug-induced lung injury (DLI) has become more common because of the increasing number of therapeutic agents in use. Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is one of the key drugs for the treatment of ulcerative colitis (UC). Although mesalazine-induced lung injury has been previously reported, few cases have included severe respiratory failure. In this report, we present a case of mesalazine-induced lung injury with severe respiratory failure, which was improved by discontinuation of mesalazine and introduction of corticosteroid therapy and ventilation support with non-invasive positive pressure ventilation (NPPV). We also review the previous literature on mesalazine-induced lung injury.

Pulse oximetry saturation can predict prognosis of idiopathic pulmonary fibrosis.

BACKGROUND: In Japan, the severity staging system for idiopathic pulmonary fibrosis (IPF) has been used to determine medical care subsidies. However, this system requires invasive procedures to measure arterial oxygen tension. Recently, noninvasive and simple measurements of oxygen saturation by pulse oximetry (SpO2) have been used for severity assessments. We propose a pulse oximetry saturation (POS) staging system consisting of SpO2 parameters to predict prognosis. METHODS: We developed four prototype staging systems based on SpO2 at rest and desaturation, and adopted the system with the highest C-statistic as the POS staging system. The cutoff SpO2 values at rest were 96% and 90%, and desaturation was defined as SpO2 < 90% at the end of the 6-min-walk test. RESULTS: Two-hundred and nineteen IPF patients were studied and the C-statistic values of models 1, 2, 3, and 4 were 0.633, 0.643, 0.630, and 0.673, respectively. We judged model 4 to be a superior POS staging system; it defined SpO2 ≥ 96% at rest without desaturation as stage Ⅰ; SpO2 ≥ 96% at rest with desaturation or SpO2 90%-95% at rest without desaturation as stage Ⅱ; and SpO2 90%-95% at rest with desaturation or SpO2 < 90% at rest as stage Ⅲ. The hazard ratios of POS stage Ⅰ, Ⅱ, and Ⅲ were 1.00, 2.25, and 4.99, respectively. The C-statistic of the POS staging system produced from 1000 bootstrap samples was similar (0.673), suggesting good internal validation. CONCLUSION: A noninvasive and simple POS staging system defined by SpO2 can easily predict prognosis.