BACKGROUND Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) presents as episodes of acute respiratory worsening closely associated with endothelial damage and disordered coagulopathy. ...Recombinant human soluble thrombomodulin (rhTM) regulates the coagulation pathway mainly by reducing thrombin-mediated clotting and enhancing protein C activation. We investigated the efficacy of rhTM for the treatment of patients with AE-IPF. METHODS This historical control study comprised 40 patients with AE-IPF. Twenty patients treated with rhTM (0.06 mg/kg/d) for about 6 days (rhTM group) and 20 patients treated without rhTM (control group) were evaluated. The predictors of 3-month mortality (logistic regression model) were evaluated. RESULTS There was no difference in baseline characteristics between the control group and the rhTM group. Three-month mortality of the rhTM group and control group was 30.0% and 65.0%, respectively. In univariate analysis, C-reactive protein and rhTM therapy were significant determinants for 3-month survival. In multivariate analysis, rhTM therapy (OR, 0.219;95% CI, 0.049-0.978; P = 0.047) was an independent significant determinant for 3-month survival. CONCLUSIONS We found that rhTM therapy improved 3-month survival of AE-IPF. The results observed here warrant further investigation of rhTM in randomized control trials.
ABSTRACT
Background and objective
Acute exacerbation (AE) is a severe complication of idiopathic pulmonary fibrosis (AE‐IPF). In 2016, an international working group revised its definition and ...diagnostic criteria; however, few studies have assessed the frequency and prognosis of AE in patients with other fibrotic interstitial lung diseases (FILD).
Methods
We used data from 1019 consecutive interstitial lung disease (ILD) patients initially evaluated between January 2008 and July 2015. All subject diagnoses were made by multidisciplinary discussion in December 2018. ILD was categorized as IPF (n = 462) and other FILD which included non‐specific interstitial pneumonia (n = 22), chronic hypersensitivity pneumonitis (n = 29), connective tissue disease‐associated ILD (n = 205) and unclassifiable ILD (n = 209). Using the 2016 definition of AE‐IPF, we identified all subjects with an AE.
Results
During the observational period, 193 patients experienced a first AE (AE‐FILD n = 69, AE‐IPF n = 124). The time to first AE was significantly longer in FILD than IPF (log‐rank test, P < 0.001). After adjusting for potentially influential confounders, FILD remained a significant predictor of longer time to first AE compared with IPF (hazard ratio: 0.453; 95% CI: 0.317–0.647, P = 0.006). In a multivariate Cox proportional analysis, baseline disease severity was closely associated with the incidence of AE‐ILD. Even after adjustment for other clinical variables, AE had a negative impact on overall survival. AE‐FILD and AE‐IPF showed similar poor short‐term outcomes.
Conclusion
All forms of ILD are at risk of AE and have a similar outcome to AE‐IPF.
This study reveals that all forms of fibrotic interstitial lung diseases (FILD) are at risk of acute exacerbations (AE) and have similar outcomes to AE of idiopathic pulmonary fibrosis (AE‐IPF). Clinicians are recommended to consider all forms of FILD to be at risk of AE.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and coronavirus disease 2019 remains a major health concern. Several SARS-CoV-2 vaccines have been produced ...and are playing important roles in the prevention of infection and worsening to a severe state, and in improving mortality 1. However, some concerns about adverse effects related to SARS-CoV-2 vaccination have been raised. Recently, various adverse effects have been reported, but there is little data on adverse effects on the lungs 2.
Although the association between acute exacerbation of interstitial lung disease and vaccination is not yet clarified, this is the first case report describing the possibility that SARS-CoV-2 vaccination may trigger acute exacerbation
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Patients with fibrotic interstitial lung disease (FILD) often experience gas exchange abnormalities and ventilatory limitations, resulting in reduced exercise capacity. High-flow nasal cannula (HFNC) ...oxygen therapy is a novel treatment, whose physiological beneficial effects have been demonstrated in various clinical settings. We hypothesized that HFNC oxygen therapy might be superior to conventional oxygen therapy for improving exercise capacity in FILD patients.
We performed a prospective randomized controlled crossover trial with a high-intensity constant work-rate endurance test (CWRET) using HFNC (50 L/min, FiO
0.5) and a venturi mask (VM) (15 L/min, FiO
0.5) for oxygen delivery in FILD patients. The primary outcome variable was endurance time. The secondary outcome variables were SpO
, heart rate, Borg scale (dyspnea and leg fatigue), and patient's comfort.
Seven hundred and eleven patients were screened and 20 eligible patients were randomized. All patients completed the trial. The majority of patients were good responders to VM and HFNC compared with the baseline test (VM 75%; HFNC 65%). There was no significant difference in endurance time between HFNC and VM (HFNC 6.8 95% CI 4.3-9.3 min vs VM 7.6 95% CI 5.0-10.1 min, p = 0.669). No significant differences were found in other secondary endpoints. Subgroup analysis with HFNC good responders revealed that HFNC significantly extended the endurance time compared with VM (VM 6.4 95%CI 4.5-8.3 min vs HFNC 7.8 95%CI 5.8-9.7 min, p = 0.046), while no similar effect was observed in the VM good responders.
HFNC did not exceed the efficacy of VM on exercise capacity in FILD, but it may be beneficial if the settings match. Further large studies are needed to confirm these findings.
UMIN-CTR: UMIN000021901.
Summary Objectives The identification of early phase interstitial changes may influence the understanding of idiopathic interstitial pneumonitis. This study aimed to clarify its radiological patterns ...and the association with smoking. Methods The subjects underwent low-dose computed tomography to screen lung cancer. The selected subjects with interstitial changes were monitored for the precise morphology of interstitial changes using a high-resolution computed tomography (HRCT) scan. The subjects were classified into normal and abnormal HRCT subjects. The radiological findings on the HRCT scan, serum Klebs von der Lungen-6 (KL-6), surfactant protein (SP)-A, SP-D, pulmonary function, and computed tomography (CT) scores were analyzed. Abnormal HRCT subjects were classified based on the radiological patterns, and were followed-up over a 4-year period. Results HRCT abnormalities suggesting interstitial changes were identified in 80 of 3079 subjects. Seven subjects with honeycombing and 14 with combined pulmonary fibrosis and emphysema (CPFE) were identified. The frequencies of sex (male) and smoking in the subjects with honeycombing was higher than that of other patterns. The smoking history and the levels of serum KL-6, SP-A, and SP-D in abnormal HRCT subjects were significantly higher than those in normal HRCT subjects. Thirty-two of 73 abnormal HRCT subjects showed a progression of the CT scores in a chest HRCT over a 4-year period. Eighteen abnormal HRCT current smokers were included in the progression of CT scores. Conclusions HRCT patterns, excluding interlobular septal thickening, show the progression of CT scores. Smokers with CT abnormalities may have a tendency to demonstrate worsening interstitial changes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Introduction The mortality of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is high. Anticoagulation therapy (recombinant human soluble thrombomodulin (rhTM)) is recognized as ...a potential new strategy for treating disseminated intravascular coagulation in Japan. This preliminary study was to evaluate whether the coagulation factors increase or decrease in AE-IPF-patients, and whether the additional administration of rhTM for AE-IPF-patients has any beneficial effects on inflammatory mediators and activated coagulation. Methods We retrospectively compared the clinical data of AE-IPF-patients, idiopathic pulmonary fibrosis (IPF) with pneumonia-patients and slowly progressive IPF-patients. As a subsequent study, AE-IPF-patients were prospectively treated with a bolus of rhTM intravenously for six days under mechanical ventilation. We historically investigated the improvement of the serial clinical data in both oxygenation and intravascular coagulation disturbance between treated AE-IPF-patients and untreated AE-IPF-patients. Results Eleven AE-IPF, 21 IPF with pneumonia and 16 slowly progressive IPF-patients were enrolled, and the coagulatory levels of the AE-IPF-patients were found to be significantly higher than in the other patients. In 20 treated AE-IPF-patients, the 28-day mortality and in-hospital mortality were 35% and 45%, respectively. The levels of oxygenation rapidly increased on day 1 and continued to improve until day 7 in the survival AE-IPF-patients. The thrombin–antithrombin complex levels and inflammatory cytokine levels in the survivors on day 7 were significantly different from those observed in the nonsurvivors. Conclusion AE-IPF-patients were found to have significantly higher levels of coagulation. The rhTM administration in the surviving AE-IPF-patients led to significant differences in the oxygenation and intravascular coagulation disturbance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Anti-synthetase syndrome (ASS) is characterized by the presence of anti-aminoacyl-tRNA synthetase antibody and ASS-associated interstitial lung disease (ILD) often recurs. The effectiveness of ...remission induction therapy with corticosteroids and calcineurin inhibitor (CNI) and the predictive factors for ASS-ILD recurrence were examined.
We retrospectively identified consecutive patients with ASS-ILD treated with corticosteroids and CNI during 2006–2017 and evaluated the predictive factors for recurrence using logistic regression analysis.
Of the 57 patients included in this study, 54 (94.7%) exhibited improved response to remission induction therapy. There were 32 recurrence patients during maintenance therapy. The median period until recurrence was 27 months. There were no significant differences in the baseline characteristics between the recurrence and nonrecurrence groups. In the recurrence group, respiratory function and St. George's Respiratory Questionnaire score deteriorated over the clinical course. The Krebs von den Lungen-6 (KL-6) level changed with disease behavior. The multivariate analysis revealed that KL-6 increase rate from remission (odds ratio: 3.21, 95% CI: 1.17–8.86, p = 0.02) and CNI discontinuation (odds ratio: 8.09, 95% CI: 1.39–47.09, p = 0.02) were independent predictive factors for recurrence. The receiver operating characteristics analysis revealed that the optimal cut-off point of KL-6 increase rate was 2.0. The positive predictive values of the KL-6 increase rate from remission of >2.0 and CNI discontinuation were 90.0 and 88.9%, respectively. The CNI treatment duration and recurrence were not related.
Recurrence influenced long-term deterioration. KL-6 was a serum biomarker for disease behavior and recurrence prediction. The results suggest the importance of CNI continuation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background and Objective The outcome of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is usually very poor, and it has been suggested that mechanical ventilation does not benefit ...AE-IPF patients. Noninvasive ventilation (NIV) has attracted attention as a means to avoid intubation in acute respiratory failure, including acute respiratory distress syndrome (ARDS). This study describes the outcome of patients with AE-IPF who were treated with NIV. Methods Patients included in the study were those who fulfilled the criteria for AE-IPF during the periods between April 1998 and June 2004 at Tosei General Hospital, and in whom NIV was introduced. Clinical data were obtained retrospectively from patient records. Results This study included 11 patients. The initial NIV settings were continuous positive airway pressure (CPAP) mode in 6 patients (mean 10.1±2.5 cmH2O) and Spontaneous/Timed mode in 5 (mean inspiratory positive airway pressure/expiratory positive airway pressure; 15.0±3.3/10.2±2.9 cmH2O). Five patients avoided intubation and survived more than 3 months after AE-IPF. Six patients who failed NIV died within 3 months. In these 6 patients, 4 required intubation. The other 2 patients, who refused endotrachial intubation, died without intubation. Median survival time and 3-month survivals after acute exacerbation were 30 days, and 45.5%, respectively. Conclusion Considering extremely poor prognosis of AE-IPF, our findings suggest that NIV is a viable option for the respiratory management in AE-IPF, and should be studied in a large, well-controlled trial.
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;
= 0.978) or death (0.4% and 3.5%, respectively;
= 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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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