Acute Exacerbation Of Interstitial Pneumonia Research Articles

Efficacy and safety of a low-dose sulfamethoxazole/trimethoprim regimen in preventing pneumocystis pneumonia: A retrospective study using a large-scale electronic medical record database

IntroductionSulfamethoxazole/trimethoprim (ST) is a first-line drug for preventing pneumocystis pneumonia (PCP). Several small-scale studies have suggested the usefulness of the low-dose regimen of ST (200/40 mg/day) over the standard-dose one (400/80 mg/day). Thus, this study aimed to investigate the efficacy and safety of low-dose and standard-dose regimens of ST in preventing PCP in patients with non human immunodeficiency virus infection using a large-scale electronic medical record database. MethodsThis retrospective study included patients who received ST prophylaxis for PCP registered in the RWD database between June 2007 and February 2023. Patients received either standard-dose (400/80 mg/day) or low-dose (200/40 mg/day) regimen groups. The incidence of cases initiated PCP therapeutic dose (ci-PCPTD) (ST ≥ 3600/720 mg/day) and adverse events (AEs) was evaluated, and risk factors for ci-PCPTD were investigated. ResultsA total of 11,384 patients received the standard-dose, whereas 7973 received the low-dose regimen groups. No significant difference in the cumulative incidence of ci-PCPTD was observed between the standard-dose (0.67%) and low-dose regimen group (0.47%). Lung disease was a significant risk factor for ci-PCPTD. The cumulative incidence of ci-PCPTD in patients with acute exacerbation of interstitial pneumonia was 1.3% in both groups, and no significant difference was observed between the two groups. The low-dose regimen group had a lower incidence of all AEs than the standard-dose regimen group. ConclusionThese results based on a large-scale electronic medical record database provide important evidence supporting the clinical significance of low-dose regimen of ST.

Assessing the efficacy of hemoperfusion for dermatomyositis-associated acute exacerbation of interstitial pneumonia: a multicenter retrospective study.

Hemoperfusion (HP) is used to treat various diseases, including sepsis and acute respiratory distress syndrome. However, few studies have explored the efficiency of HP in dermatomyositis-associated acute exacerbation of interstitial lung disease. We conducted a retrospective study. Two hundred and sixteen patients with dermatomyositis-associated acute exacerbation of interstitial lung disease were included. Patients were divided into the HP group (treatment group) and the control group. Changes in oxygenation, hemodynamic parameters, lung ultrasound scores, and inflammatory cytokine levels were evaluated before and after HP in the treatment group. The length of intensive care unit (ICU) stays, duration of ventilator therapy, mortality rate, and incidence of complications were compared between the treatment and control groups. Hemodynamic and oxygenation variables in the treatment group significantly improved after treatment. However, the levels of the inflammatory factors significantly decreased after treatment. The length of ICU stay and the duration of ventilator therapy were significantly shorter in the treatment group than in the control group. The mortality rate of the treatment group was significantly lower than that of the control group. This study demonstrated that HP could improve treatment efficacy in patients with dermatomyositis-associated acute exacerbation of interstitial lung disease.

Predictors for acute exacerbation of interstitial pneumonia following lung cancer surgery: a multicenter study

BackgroundAcute exacerbation (AE) of interstitial lung disease (ILD) is one of the most serious complications during perioperative period of lung cancer resection. This study aimed to investigate the correlation between preoperative 2- deoxy-2-[18F]fluoro-D-glucose (18F-FDG) PET/CT findings and AE in lung cancer patients with ILD.MethodsWe retrospectively reviewed the data of 210 patients who underwent lung resection for non-small cell lung cancer. Relationships between clinical data and PET images and AE were evaluated. The patients were divided into an AE(+) and an AE(-) group for multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was conducted and the area under curve (AUC) was used to assess the predictive values.ResultsAmong 210 patients, 48 (22.8%) were diagnosed with ILD based on chest CT. Among them, 9 patients (18.75%) developed AE after lung resection and were defined as AE(+) group. The course of ILD was longer in AE(+) group compared to AE(-) group. More patients in AE(+) group had a history of AE and chronic obstructive pulmonary disease (COPD) than in AE(-) group. The maximum standardized uptake value (SUVmax) of the noncancerous interstitial pneumonia (IP) area and cancers in AE(+) group was significantly higher compared to AE(-) group. Univariate logistic regression analysis showed that AE, COPD, SUVmax of the noncancerous IP area, SUVmax of cancer, surgical method were significantly correlated with AE. The course of ILD[OR(95%CI) 2.919; P = 0.032], SUVmax of the noncancerous IP area[OR(95%CI) 7.630;P = 0.012] and D-Dimer level[OR(95%CI) 38.39;P = 0.041] were identified as independent predictors for AE in patients with ILD after lung cancer surgery. When the three indicators were combined, we found significantly better predictive performance for postoperative AE than that of SUVmax of the noncancerous IP area alone [0.963 (95% CI 0.914-1.00); sensitivity, 100%, specificity 87.2%, P < 0.001 vs. 0.875 (95% CI 0.789 ~ 0.960); sensitivity, 88.9%, specificity, 76.9%, P = 0.001; difference in AUC = 0.088, Z = 1.987, P = 0.04].ConclusionThe combination of the course of ILD, SUVmax of the noncancerous IP area and D-Dimer levels has high predictive value for the occurrence of AE in patients with concomitant interstitial lesions.

Deleterious impact of trivial to severe interstitial pneumonia and emphysema on mortality and acute exacerbation of interstitial pneumonia in patients with lung cancer: a retrospective cohort study

BackgroundInterstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer.MethodsThis retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates.ResultsAmong 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P < 0.001). After adjustment, the ILA and Goddard scores remained significant variables for increased hazard ratios (HR) for mortality: no ILA (HR, 1.00: reference), equivocal ILA (HR, 1.31; 95% confidence interval [CI], 1.18–1.46; P < 0.001), ILA (HR, 1.71; 95% CI, 1.39–2.12; P < 0.001), ILD (HR, 2.24; 95% CI, 1.63–3.09; P < 0.001), and Goddard score (HR, 1.03; 95% CI, 1.01–1.06; P < 0.010). Moreover, both scores were associated with increased cause-specific HRs for AEIP.ConclusionOur results revealed that approximately one-third of patients with lung cancer had interstitial pneumonia when incorporating trivial and mild cases. Because interstitial pneumonia and emphysema, ranging from trivial to severe, significantly impact mortality and AEIP in patients with lung cancer, we should identify even trivial and mild cases of these pulmonary abnormalities among patients with lung cancer in addition to the advanced ones.

Algorithms Identifying Patients With Acute Exacerbation of Interstitial Pneumonia and Acute Interstitial Lung Diseases Developed Using Japanese Administrative Data.

We aimed to develop algorithms to identify patients with acute exacerbation of interstitial pneumonia and acute interstitial lung diseases using Japanese administrative data. This single-center validation study examined diagnostic algorithm accuracies. We included patients >18 years old with at least one claim that was a candidate for acute exacerbation of interstitial pneumonia, acute interstitial lung diseases, and pulmonary alveolar hemorrhage who were admitted to our hospital between January 2016 and December 2021. Diagnoses of these conditions were confirmed by at least two respiratory physicians through a chart review. The positive predictive value was calculated for the created algorithms. Of the 1,109 hospitalizations analyzed, 285 and 243 were for acute exacerbation of interstitial pneumonia and acute interstitial lung diseases, respectively. As there were only five cases of pulmonary alveolar hemorrhage, we decided not to develop an algorithm for it. For acute exacerbation of interstitial pneumonia, acute interstitial lung diseases, and acute exacerbation of interstitial pneumonia or acute interstitial lung diseases, algorithms with high positive predictive value (0.82, 95% confidence interval: 0.76-0.86; 0.82, 0.74-0.88; and 0.89, 0.85-0.92, respectively) and algorithms with slightly inferior positive predictive value but more true positives (0.81, 0.75-0.85; 0.77, 0.71-0.83; and 0.85, 0.82-0.88, respectively) were developed. We developed algorithms with high positive predictive value for identifying patients with acute exacerbation of interstitial pneumonia and acute interstitial lung diseases, useful for future database studies on such patients using Japanese administrative data.

Acute Hemorrhagic Rectal Ulcer Complicated by Cytomegalovirus Enteritis following Steroid Pulse Therapy for Acute Exacerbation of Interstitial Pneumonia: A Case Report.

We herein report a rare case of acute hemorrhagic rectal ulcer (AHRU) complicated by cytomegalovirus enteritis following steroid pulse therapy for interstitial pneumonia. An 86-year-old woman underwent steroid pulse therapy for interstitial pneumonia. She was bedridden with dyspnea and suddenly developed melena. Colonoscopy revealed AHRU, which did not improve with conservative treatment, but did improve with ganciclovir administration for cytomegalovirus enteritis. Pulmonologists administer steroid pulse therapy for interstitial pneumonia; however, this gastrointestinal complication does not receive its due attention. Delayed treatment of this complications can be fatal. Caution should be taken when administering steroid pulse therapy to bedridden patients with interstitial pneumonia.

Hemodiafiltration combined with polymyxin B-immobilized fiber column direct hemoperfusion is effective for acute postoperative exacerbation of interstitial pneumonia: a case report

BackgroundPostoperative acute exacerbation of interstitial pneumonia has a high mortality rate; however, its treatment methods have not been standardized.Case presentationA 72-year-old man with rheumatoid arthritis developed acute respiratory failure about 3 weeks after lung cancer surgery. There were increased diffuse frosted shadows in both lung fields. His condition was diagnosed as an acute exacerbation of interstitial pneumonia associated with rheumatoid arthritis, and he was started on steroid pulse therapy; however, his respiratory condition deteriorated. He was urgently intubated and started on veno-venous extracorporeal membrane oxygenation. Further, intensive care, including blood purification therapy, was initiated. The blood purification therapy comprised a combination of hemodiafiltration and 6-h polymyxin B-immobilized fiber column direct hemoperfusion. The patient was weaned off veno-venous extracorporeal membrane oxygenation, extubated, and discharged from the intensive care unit on the ninth day.ConclusionsBlood purification therapy was effective for acute exacerbation of interstitial pneumonia.

Intravenous immunoglobulin for acute exacerbation of fibrotic idiopathic interstitial pneumonias.

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition with no established treatment. Intravenous immunoglobulin (IVIG) is a unique therapy with both anti-inflammatory and anti-infective effects. Therefore, we hypothesized that IVIG may have a positive effect on AE of interstitial pneumonia. This study aimed to determine the effect of IVIG in patients with AE of fibrotic idiopathic interstitial pneumonias (IIPs), including IPF. We retrospectively analyzed consecutive patients who were diagnosed with AE of fibrotic IIPs and treated with pulse corticosteroid therapy (methylprednisolone 500-1000 mg/day for 3 days) between April 2018 and May 2021 at Kagawa Rosai Hospital and KKR Takamatsu Hospital. This study included 52 patients with AE of fibrotic IIPs (IPF,41; fibrotic IIPs other than IPF,11). Thirteen patients received IVIG (5 g/day for 3-5 days) concurrently with pulse corticosteroid therapy. The remaining 39 patients were assigned to the control group. The survival rate on day 90 was significantly higher in the IVIG group than that in the control group (76.9% vs. 38.5%, p = 0.02). IVIG administration (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02-0.69; p = 0.02) and C- reactive protein (OR, 1.19; 95% CI, 1.06-1.33, p < 0.01) were independently associated with 90-day mortality. The results indicate that administration of IVIG may improve the survival of patients with AE of fibrotic IIPs. We are now conducting a prospective study to confirm the effect of IVIG on AE of IPF since May 2022 (jRCT1061220010).

Usefulness of serum S100A4 and positron-emission tomography on lung cancer accompanied by interstitial pneumonia.

The S100 calcium-binding protein A4 (S100A4) and the accumulation of [18F]-fluoro-2-deoxy-D-glucose (FDG) in noncancerous interstitial pneumonia (IP) area are predictors of postoperative acute exacerbation (AE) of IP after pulmonary resection for lung cancer with IP. However, the significance of combining these markers for predicting short-term outcome and long-term prognosis is not known. Patients diagnosed with IP on preoperative high-resolution computed tomography and who had undergone pulmonary resection for primary lung cancer between April 2010 and March 2019 at Hiroshima University were included in this study. Predictive factors for the cumulative incidence of death from other than lung cancer (CIDOL) were investigated using the Fine and Gray model. CIDOL, perioperative outcome, and cumulative incidence of all death (CIAD) were retrospectively compared based on serum S100A4 and FDG accumulation. A total of 121 patients were included in this study. High S100A4 (hazard ratio [HR], 2.541; p=0.006) and FDG accumulation (HR, 3.199; p=0.038) were significant predictors of CIDOL. AE of IP occurred only in patients with high S100A4/FDG (+). CIDOL of patients with high S100A4/FDG (+) was higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) (p < 0.001), and CIAD of patients with high S100A4/FDG (+) was also higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) patients (p=0.021). Serum S100A4 and FDG accumulation in the noncancerous IP area were significant predictors of CIDOL after lung resection for lung cancer with IP and may help decide the treatment strategy.

Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study.

Polymyxin B-immobilized fiber column (PMX; Toraymyxin column) was approved for the relief of systemic inflammatory response syndrome caused by bacterial infection or endotoxemia. PMX reduces lung damage by removing leukocytes and cytokines in addition to endotoxin removal in the setting of idiopathic pulmonary fibrosis. Acute exacerbation of interstitial pneumonia pathologically presents with diffuse alveolar damage (DAD). PMX direct hemoperfusion (PMX-DHP) demonstrated efficacy, improving oxygenation. The SARS-CoV-2 virus causes COVID-19, which emerged in December 2019. The condition may become severe about 1 week after onset, and respiratory failure rapidly develops, requiring intensive care management. A characteristic of COVID-19-related severe pneumonia is ground-glass opacities rapidly progressing in both lungs, which subsequently turn into infiltrative shadows. This condition could be classified as DAD. As for the congealing fibrinogenolysis system, D-dimer, fibrin/fibrinogen degradation product quantity, and prolonged prothrombin time were significant factors in nonsurviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted, but except for remdesivir and dexamethasone, no treatments have yet been approved. COVID-19 aggravates with the deterioration of oxygen saturation, decrease in lymphocytes, and the occurrence of an abnormal congealing fibrinogenolysis system, leading to diffuse lung damage. Once the condition transitions from moderate to severe, it is necessary to prevent further exacerbation by providing treatment that will suppress the aforementioned symptoms as soon as possible. This study aims to access treatment options to prevent the transition from acute exacerbation of interstitial pneumonia to DAD. The mechanism of action envisioned for PMX-DHP is to reduce congealing fibrinogenolysis system abnormalities and increase oxygenation by removing activated leukocytes and cytokines, which are risk factors for the aggravation of COVID-19-related pneumonia. We will conduct a multicenter, prospective, intervention, single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for patients with COVID-19. Efficacy will be evaluated by the primary end point, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4, 5, or 6 on day 15. The effect of PMX-DHP will be estimated by setting a control group with background factors from non-PMX-DHP patients enrolled in the COVID-19 registry. This study will be carried out as a single-group open-label study and will be compared with a historical control. The historical control will be selected from the COVID-19 registry according to age, gender, and severity of pneumonia. The study period is scheduled from September 28, 2020, through April 30, 2023. Patient enrollment was scheduled from the Japan Registry of Clinical Trials publication for March 31, 2022. Data fixation is scheduled for October 2022, with the publication of the results by March 2023. From a clinical perspective, PMX-DHP is expected to become an adjunctive therapy to address unmet medical needs and prevent the exacerbation from moderate to severe acute respiratory distress syndrome in COVID-19 cases. DERR1-10.2196/37426.

Feasibility and safety of percutaneous cryoablation under local anesthesia for the treatment of malignant lung tumors: a retrospective cohort study.

In our institution, computed tomography (CT)-guided percutaneous cryoablation has been performed in patients with malignant lung tumors under local anesthesia. This study aimed to examine the feasibility and safety of percutaneous cryoablation for the treatment of malignant lung tumors. From July 2002 to December 2016, 227 patients (56 with primary lung cancer and 171 with metastatic lung tumor) underwent percutaneous cryoablation for the treatment of malignant lung tumors using a cryosurgical unit at our institution. Demographic factors, duration of post-treatment hospitalization, and adverse event and mortality rates were retrospectively investigated in 366 treatment sessions targeting 609 lesions. The median diameter of the targeted tumor was 1.3 cm. All the cryoablation procedures were completed under local anesthesia, and the median duration of post-treatment hospitalization was two days. Adverse events (grade 2 or higher) were observed in 79 sessions (21.6%), with pneumothorax being the most common. In five sessions (1.4%), patients had grade 3 adverse events. There was no 30-day mortality; however, there were two 60-day mortality (0.5%) due to acute exacerbation of interstitial pneumonia. In multivariate analysis, independent predictors of adverse events were comorbid interstitial pneumonia [odds ratio (OR) =2.20; 95% confidence interval (CI): 1.04-4.64] and no history of pulmonary resection on the treated side (OR =3.04; 95% CI: 1.65-5.62). Cryoablation is a feasible and safe treatment for malignant lung tumors with acceptable adverse event rates. However, the mortality risk in patients with comorbid interstitial pneumonia should be fully recognized.

Lung cancer surgery after COVID-19 infection in a patient with severe interstitial pneumonia and restrictive ventilatory impairment

BackgroundThe spread of COVID-19 infection increased the number of patients who underwent pulmonary resection for lung cancer after COVID-19 infection. It is unclear how previous infection with COVID-19 affects perioperative complications and acute exacerbation of interstitial pneumonia after surgery in patients with interstitial pneumonia.Case presentationAn 80-year-old man was referred to our hospital because of a tumor in his left lung. Chest computed tomography showed a 28-mm nodule in the lower lobe of the left lung and usual interstitial pneumonia in bilateral lungs. Bronchoscopic examination was performed, which diagnosed squamous cell carcinoma. Pulmonary function testing revealed restrictive ventilatory impairment, and we planned to perform basal segmentectomy of the left lung. However, before the planned surgery, the patient contracted symptomatic COVID-19. Chest computed tomography revealed ground-glass opacities owing to COVID-19. The patient was admitted for surgery 7 weeks after COVID-19 infection. Preoperatively, pulmonary function testing was repeated, which revealed decreased % vital capacity (%VC) and % diffusing capacity for carbon monoxide (%DLco). The 6-min walk test indicated a distance of 500 m, and the percutaneous oxygen saturation at the end of the test was 94%. Basal segmentectomy of the left lung was performed by video-assisted thoracoscopic surgery. The patient’s postoperative course was favorable, and he was discharged without the need for oxygen inhalational therapy 12 days after the surgery. Pathological examination of the resected specimen revealed usual interstitial pneumonia in the non-cancerous areas of the lung. Additionally, the infiltration of immature fibroblasts in the alveoli and perivascular infiltration of inflammatory cells were observed, which were consistent with fibrotic change after inflammation owing to COVID-19. Three months after the surgery, the patient was alive without recurrence or acute exacerbation of the interstitial pneumonia. Pulmonary function testing 6 weeks after surgery revealed decreased %VC and %DLco. Testing 12 weeks after surgery revealed persistently decreased %VC and improved %DLco (Table 1).Table 1Pulmonary function test results before and after COVID-19 infection and 6 and 12 weeks after surgeryVC (ml)%VC (%)%DLco (%)Before COVID-19 infection207071.974.97 weeks after COVID-19 infection170059.651.96 weeks after surgery150052.653.112 weeks after surgery151053.061.7%VC % vital capacity, %DLco % diffusing capacity for carbon monoxideConclusionWe successfully performed basal segmentectomy of the left lung for lung cancer 7 weeks after COVID-19 infection in a patient with severe interstitial pneumonia and restrictive ventilatory impairment.

Assessment of diagnostic utility of serum hemeoxygenase-1 measurement for acute exacerbation of interstitial pneumonias

The present study aimed to evaluate whether serum heme oxygenase (HO)-1 could be a reliable blood biomarker for diagnosing acute exacerbations (AEs) of both idiopathic interstitial pneumonia (IIP) and secondary interstitial pneumonia (SIP). Serum HO-1 levels of newly diagnosed patients with IP were measured, and the relationships between serum HO-1 and other serum biomarkers and high-resolution CT scores, were evaluated. Blood samples were collected from 90 patients with IIP, including 32 having an AE, and 32 with SIP, including 9 having an AE. The patients having an AE had significantly higher HO-1 levels than those not having an AE (35.2 ng/mL vs. 16.4 ng/mL; p < 0.001). On receiver operating characteristics (ROC) curve analysis for serum HO-1 ability to detect an AE, the area under the ROC curve (AUC) was 0.87 in patients with IIPs and 0.86 in those with SIPs. Also, in patients with both IIPs and SIPs, the combination of the serum HO-1 level and the GGO score showed favorable AUCs (IIPs: 0.92, SIPs: 0.83), though HO-1-not-including model (combination of LDH and GGO) also showed acceptable AUCs. Serum HO-1 could be a clinically useful biomarker for the accurate diagnosis of patients with AEs.

Safety of salvage lung resection after immunotherapy for unresectable non-small cell lung cancer.

The safety of salvage lung resection after immune checkpoint inhibitor (ICI) therapy in patients with advanced non-small cell lung cancer (NSCLC) is not well understood. In this retrospective multicenter study, we reviewed perioperative morbidity and mortality rates in 11 patients (8 men, 3 women; median age 70years) who underwent salvage lung resection for unresectable NSCLC after ICI therapy in the 4years since 2017. Operative factors were also compared according to operating time (> 6h, n = 7; < 6h, n = 4). The clinical stage at the time of diagnosis was IIIA in 2 patients, IIIB in 4, IVA in 2, and IVB in 3. Eight patients received pembrolizumab and 3 received durvalumab. Two patients received an ICI agent alone, 3 underwent chemoradiotherapy, and 6 received chemotherapy. Lobectomy was performed in 10 cases and bilobectomy in 1 case. All patients underwent complete resection. Median operating time was 429 (range 169-570) min with a median blood loss of 199 (range 10-5, 140) mL. The only intraoperative complication was damage to the pulmonary artery. The perioperative morbidity and mortality rates were 27% and 0%, respectively. The 90-day mortality rate was 9% (1 patient died of acute exacerbation of interstitial pneumonia). Patients in whom the operating time was > 6h more frequently had lymph node metastasis at the time of initial diagnosis (100% vs 25%, p = 0.02). Salvage lung resection was tolerated after ICI therapy in these patients. Lymph node metastasis at the time of initial diagnosis might make salvage surgery difficult.

Simultaneous occurrence of accelerated nodulosis in lungs, liver, and kidneys, and acute exacerbation of interstitial pneumonia in a patient with rheumatoid arthritis: an autopsy case report

BackgroundAccelerated nodulosis (ARN) is a rare variant of rheumatoid nodules (RNs) that is characterized by a rapid onset or the worsening of RNs. It generally develops at the fingers in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX). Few case reports have described ARN at an extracutaneous location.Case presentationAn elderly patient with long-standing RA was admitted to our hospital with acute respiratory failure. Computed tomography upon admission showed diffuse ground-glass opacities superimposed with subpleural reticular shadowing and honeycombing and multiple nodules in the lungs and liver. Despite the discontinuation of MTX and introduction of an immunosuppressive regimen with pulse methylprednisolone followed by a tapering dose of prednisolone and intravenous cyclophosphamide, the patient died due to the acute exacerbation (AE) of RA-related interstitial lung disease (ILD) following the parallel waxing and waning of a diffuse interstitial shadow and pulmonary and liver nodules. At autopsy, RNs were scattered throughout both lung fields in addition to extensive interstitial changes. RNs were also detected in the liver and kidneys. The foci of cryptococcosis were mainly identified in alveolar spaces. Based on the clinical and pathological findings, these nodules were most consistent with ARN because of acute increases in the size and number of previously detected pulmonary nodules.ConclusionThe present case is noteworthy because ARN was concurrently detected in multiple internal organs and may be associated with the AE of RA-related ILD.

The role of high flow nasal cannula oxygen therapy in patients with acute exacerbation of interstitial pneumonia

The role of high flow nasal cannula oxygen therapy in patients with acute exacerbation of interstitial pneumonia

Nintedanib-Mediated Improvement in CT Imaging in Pulmonary Fibrosis Associated with Systemic Scleroderma

Nintedanib is an antifibrotic drug that has an inhibitory effect on growth factor tyrosine kinases. In patients with idiopathic pulmonary fibrosis and systemic scleroderma-associated interstitial pneumonia (SSc-IP), nintedanib has been effective in suppressing the decline in forced vital capacity over time and the onset of acute exacerbation of interstitial pneumonia. Here, we report a SSc-IP patient who showed an improvement on CT images following nintedanib treatment. To our knowledge, this is the first report of such a case. Although SSc-IP patients are very rare, additional clinical experience and understanding will be required to prove the therapeutic benefit of nintedanib in these cases in relation to improved chest images.

Current Treatment Strategies for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia.

Simple SummaryInterstitial pneumonia is a poor prognostic comorbidity in patients with non-small-cell lung cancer. No matter how effective the treatment for lung cancer is, once an acute exacerbation of pre-existing interstitial pneumonia occurs, it will be fatal to the patient at a high rate. Therefore, it is important to choose a therapy that is unlikely to induce acute exacerbation of interstitial pneumonia. In this review article, we summarize the current evidence on pharmacotherapy, surgery and perioperative treatment, and radiation therapy for non-small-cell lung cancer with comorbid interstitial pneumonia, and discuss future perspectives.Of patients with advanced non-small-cell lung cancer (NSCLC), 5–10% have interstitial pneumonia (IP) at the time of diagnosis. To avoid fatal acute exacerbations of pre-existing IP, appropriate patient selection and low-risk treatment choices are warranted. Risk factors for acute exacerbation of pre-existing IP with cytotoxic drugs include honeycomb lungs on computed tomography (CT) and low forced vital capacity, but risk factors with immune checkpoint inhibitors (ICIs) have not been fully investigated. For advanced or recurrent NSCLC with comorbid IP, carboplatin plus nanoparticle albumin-bound paclitaxel is the standard of care for first-line treatment, but second-line or later treatment has not been established. ICI holds great promise for long-term survival, but many challenges remain, including safety and appropriate patient selection. Since the indications for pharmacotherapy and radiotherapy for NSCLC with comorbid IP are quite limited, surgical resection should be considered as much as possible for patients with operable stages. A scoring system has been reported to predict the risk of postoperative acute exacerbation of pre-existing IP, but perioperative treatment has not been established. In the future, it is necessary to accumulate more cases and conduct further research, not only in Japan but also worldwide.

Serum S100 calcium-binding protein A4 as a novel predictive marker of acute exacerbation of interstitial pneumonia after surgery for lung cancer

BackgroundAcute exacerbation (AE) of interstitial pneumonia (IP) is the most fatal complication after lung resection for lung cancer. To improve the prognosis of lung cancer with IP, the risk factors of AE of IP after lung resection should be assessed. S100 calcium-binding protein A4 (S100A4) is a member of the S100 family of proteins and is a known marker of tissue fibrosis. We examined the usefulness of S100A4 in predicting AE of IP after lung resection for lung cancer.MethodsThis study included 162 patients with IP findings on preoperative high-resolution computed tomography scan who underwent curative-intent lung resection for primary lung cancer between April 2007 and March 2019. Serum samples were collected preoperatively. Resected lung tissue from 76 patients exhibited usual IP (UIP) pattern in resected lung were performed immunohistochemistry (IHC). Relationship between S100A4 and the incidence of AE of IP and short-term mortality was analyzed.ResultsThe receiver operating characteristic area under the curve for serum S100A4 to predict postoperative AE of IP was 0.871 (95% confidence interval [CI], 0.799–0.943; P < 0.001), with a sensitivity of 93.8% and a specificity of 75.3% at the cutoff value of 17.13 ng/mL. Multivariable analysis revealed that a high serum S100A4 level (> 17.13 ng/mL) was a significant risk factor for AE of IP (odds ratio, 42.28; 95% CI, 3.98–449.29; P = 0.002). A 1-year overall survival (OS) was significantly shorter in patients with high serum levels of S100A4 (75.3%) than in those with low serum levels (92.3%; P = 0.003). IHC staining revealed that fibroblasts, lymphocytes, and macrophages expressed S100A4 in the UIP area, and the stroma and fibrosis in the primary tumor expressed S100A4, whereas tumor cells did not.ConclusionsSerum S100A4 had a high predictive value for postoperative AE of IP and short-term mortality after lung resection.

P44.02 Mild Interstitial Pneumonia as a Risk Factor for Chemotherapy-Induced Acute Exacerbation of Interstitial Pneumonia in Patients with Lung Cancer

Co-existing of interstitial pneumonia is reported to be a risk factor for chemotherapy-induced acute exacerbation of interstitial pneumonia in patients with lung cancer (LC). Although it has been recently demonstrated that co-existing of interstitial lung abnormalities on chest CT is associated with poor prognosis in patients with advanced non-small cell lung cancer, it has not been clarified the association between mild interstitial pneumonia and chemotherapy-induced acute exacerbation of interstitial pneumonia in detail. The goal of this study was to determine the clinical significance of mild interstitial pneumonia shadows on chest CT prior to the initiation of chemotherapy in patients with advanced LC. We retrospectively analyzed the patients with advanced LC treated with chemotherapy in our department from 2014 to 2016. Chest CT findings at the diagnosis of LC (baseline CT) were reviewed, and the patients were divided into three groups; 1) patients without interstitial pneumonia shadows, 2) with interstitial pneumonia shadows which was recognized (RIPS), and 3) with mild interstitial pneumonia shadows which had not been recognized (UMIPS) by treating physicians on baseline CT. The frequency of chemotherapy-induced acute exacerbation of interstitial pneumonia in patients with RIPS and UMIPS was compared with that of chemotherapy-induced lung injury in patients without interstitial pneumonia shadows. We included 112 patients with treatment naïve IIIB/IV LC in this study. The median age was 69 years (37-87 years), and the frequency of non-small cell lung cancer was 79%. The number of advanced LC patients with RIPS and UMIPS were 26 (23%) and 13 (12%), respectively. Chemotherapy-induced acute exacerbation of interstitial pneumonia was found in 7 (27%) RIPS and 2 (13%) UMIPS patients. On the other hand, chemotherapy-induced lung injury was occurred in only 3 out of 73 (4%) patients without interstitial pneumonia shadows on baseline CT. In patients with advanced LC, interstitial pneumonia shadows on chest CT, even in instances of mild shadows, should be considered as a risk factor of chemotherapy-induced acute exacerbation of interstitial pneumonia.