Pre-existing Interstitial Lung Disease Research Articles

A modified Delphi exercise in physician-perceived risk factors for drug-induced pneumotoxicity in patients with rheumatological disease

BackgroundDrugs used to treat rheumatic disease are associated with pneumotoxicity (drug-induced lung disease), but little is known about associated risk factors.AimTo determine expert physician-perceived risk factors for developing pneumotoxicity in patients with rheumatologic conditions.MethodsA modified international 3-tier Delphi exercise was performed. Tier 1 determined patient and drug variables that physicians perceive to be risk factors. Tier 2 determined degree of risk associated with the Tier-1 derived variables. Tier 3 aimed to internally validate and stratify exemplar cases into risk categories.Results134 pulmonologists and 49 rheumatologists responded to Tier 1;157 physicians completed all tiers. Perceived risk factors included: drug type; history of previous pneumotoxicity; age; smoking; underlying rheumatic disease type and activity; renal function; pulmonary hypertension; left ventricular failure;presence, nature, severity and progression of pre-existing interstitial lung disease. Tier 2 data stratified these variables into risk profiles e.g. never versus current smoking was perceived as low and high risk respectively. An example of perceived high risk resulting from Tier 3 is a 75-year-old current smoker with high-activity rheumatoid arthritis (RA) with severe, progressive ILD being started on methotrexate. A perceived low risk is a 75-year-old currentsmoker with moderate-activity RA and emphysema with no cardiac or renal disease and no pre-existing ILD being started on rituximab. A risk prediction scoring tool is being developed to be used in validation studies.ConclusionThis modified Delphi exercise defined and stratified the perceived risk factors for developing pneumotoxicity. Age, current smoking, high underlying rheumatological disease activity, HRCT definite UIP and honeycombing, severity and progression of pre-existing ILD were perceived to be the highest risk-factors.

Impact of docetaxel plus ramucirumab therapy on interstitial lung disease in recurrent advanced non-small cell lung cancer patients.

Few studies have examined the safety and efficacy of docetaxel/ramucirumab (DOC/RAM) therapy in advanced non-small cell lung cancer (NSCLC) complicated by interstitial lung disease (ILD). Given the potential of vascular endothelial growth factor inhibitors to prevent drug-induced pneumonia, we aimed to clarify the role of this therapy in NSCLC with ILD. This retrospective observational study evaluated the incidence of ILD in stage IV NSCLC patients receiving DOC/RAM therapy at our institution, stratified by ILD status. We also assessed the efficacy of this treatment. The primary objective was to investigate the incidence of ILD, while secondary objectives included evaluating the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), stratified by ILD status. Among patients with pre-existing ILD, 7 out of 28 (25%) developed DOC/RAM-induced interstitial pneumonia, while none of the 40 patients without pre-existing ILD developed this condition (P<0.001). Comparing historical controls (DOC only) with the DOC/RAM group, RAM did not significantly alter the incidence of interstitial pneumonia (P=0.33). There were no significant differences in ORR, PFS, or OS between patients with and without ILD. Subgroup analysis of smokers showed a non-significant trend toward worse survival in those with pre-existing ILD (P=0.20). DOC/RAM therapy significantly increased the incidence of interstitial pneumonia in NSCLC patients with pre-existing ILD but did not significantly affect efficacy outcomes such as ORR, PFS, or OS.

Prognostic analysis of Pneumocystis jirovecii pneumonia in patients with systemic vasculitides: a retrospective cohort study

ObjectivesPneumocystis jirovecii pneumonia (PJP) is a serious complication of autoimmune and inflammatory diseases. This study aimed to describe the characteristics of PJP in patients with various systemic vasculitides and explore potential prognostic factors.MethodData on 62 enrolled PJP patients with systemic vasculitis were analyzed. Patients were stratified based on the outcomes. Prognostic factors were investigated using Cox-regression models. Characteristics of patients with and without interstitial lung disease (ILD) were compared.ResultsAmong 62 vasculitis-PJP patients, 48 had anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), with microscopic polyangiitis (MPA) being the most common subtype (28 patients). MPA (HR 4.33, p = 0.001), concomitant aspergillosis (HR 2.68, p = 0.019), and higher D-dimer at PJP diagnosis (HR 1.07, p = 0.004) were independent adverse prognostic factors for overall survival. Stable disease activity of vasculitis was an independent favorable prognostic factor (HR 0.28, p = 0.027). Patients with MPA were older than non-MPA patients (median age: 69 vs. 58 years, p = 0.001); both ILD and fibrotic ILD were more prevalent in MPA patients (ILD: 78.6% vs. 35.3%, p = 0.001; fibrotic ILD: 57.1% vs. 11.8%, p < 0.001). At the diagnosis of PJP, patients with preexisting ILD had higher counts of white cells, lymphocytes, and neutrophils, as well as higher levels of immunoglobulin (Ig) G and IgA, than patients without preexisting ILD.ConclusionsMPA was associated with a higher risk of death in patients with vasculitis-PJP, possibly due to a higher prevalence of ILD. In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA.Key Points• Data from this study showed that MPA was the most common subtype of vasculitis among vasculitis-PJP patients.• Compared with non-MPA patients in this study, patients with MPA were older, had more ILD and fibrotic ILD, and had a poorer prognosis.• In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA.

Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial

ObjectivesCertain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). MethodsIn this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. ResultsTwenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3–99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6–6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). ConclusionsChemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.

4 Treatment Toxicity and Outcomes Following Definitive Radiotherapy for Patients with Early-Stage Non-Small Cell Lung Cancers and Pre-Existing Interstitial Lung Disease: A Systematic Review

4 Treatment Toxicity and Outcomes Following Definitive Radiotherapy for Patients with Early-Stage Non-Small Cell Lung Cancers and Pre-Existing Interstitial Lung Disease: A Systematic Review

Impact of preexisting interstitial lung disease on outcomes of lung cancer surgery: A monocentric retrospective study

IntroductionInterstitial lung disease (ILD) is a known risk factor for lung cancer (LC). However, the surgical risk of LC in patients with ILD remains unclear. Therefore, we conducted a single-center retrospective study to assess clinical features and outcomes of LC population who underwent surgery with or without ILD. MethodsPatients who underwent surgery for LC between January 2006 and June 2023 in our center were assessed using data extracted from the nationwide EPITHOR thoracic surgery database. Suspicion of ILD was based on patients’ records. Confirmation of ILD was then made on the patient's medical and radiological history. Patients were classified according to the pattern of ILD. The study aimed to describe the outcomes after lung cancer resection in patients with confirmed LC-ILD group compared to those without ILD (LC-non-ILD): post-operative complications, disease-free survival (DFS) and overall survival (OS). A subgroup analysis was also performed on patients with idiopathic pulmonary fibrosis and lung cancer (LC-IPF). Results4073 patients underwent surgery for LC at Assistance Publique des Hôpitaux de Marseille between January 2006 and June 2023. Of these, 4030 were in the LC-non-ILD group and 30 were LC-ILD patients. In the LC-ILD group, the predominant CT scan pattern was probable UIP (50 %). OS was not significantly lower in the LC-ILD group (45 months versus 84 months, p = 0.068). Dyspnea and tumor size were identified as potential univariate predictors of OS. No significant differences were observed on post-operative complications or their severity. The most common post-operative complications in the LC-ILD group were prolonged air leak, respiratory failure, or pneumonia. 13 patients had cancer recurrence in the LC-ILD group. ConclusionOur study provides a comprehensive analysis of a LC-ILD population features and outcome when undergoing surgery for LC. Patients with LC-ILD appeared to have a reduced OS compared with LC-non-ILD. Further investigations with larger prospective studies could be useful to confirm and develop these preliminary findings.

Risk factors for severe immune-related pneumonitis after nivolumab plus ipilimumab therapy for non-small cell lung cancer.

The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune-related adverse events. However, our understanding of associations among pre-existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population. We focused on patients (n = 76) with pre-existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography-confirmed fibrosis, serum markers, and respiratory function test results. Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP-D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre-existing ILD. Conversely, in cases without pre-existing fibrosis, severe pneumonitis was not associated with %DLCO or SP-D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm). Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP-D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.

P108 Filgotinib for Rheumatoid Arthritis: an observational cohort to assess clinical effectiveness in a single centre

Abstract Background/Aims Filgotinib, a Janus-kinase (JAK) 1 preferential inhibitor, was approved for use in the UK in moderate or severe rheumatoid arthritis (RA) in 2021, as monotherapy or in combination with Methotrexate. Evidence of real-world effectiveness is currently limited. Methods Patients prescribed Filgotinib between December 2021 and August 2022 in NHS Lothian were identified from pharmacy registration data. All underwent clinical efficacy assessment at three months. Electronic patient records (EPR) were reviewed to record baseline data including previous and current treatments. Duration of Filgotinib treatment was recorded, and discontinuation reason if applicable. DAS-28 scores within six months prior to starting Filgotinib were recorded, along with available subsequent scores. Pre-existing interstitial lung disease (ILD), venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy were recorded, along with incident events during treatment. Results 145 patients were prescribed Filgotinib; 106 (73.1%) females and 39 (26.9%) males, with median age 64 years. Median treatment duration was 447 days. 35 (24.1%) were treated with the reduced 100mg dose. 81 (55.9%) received conventional disease-modifying anti-rheumatic drugs (DMARDs) alongside Filgotinib. 41 (28.3%) patients discontinued treatment: 10 (6.9%) due to loss of effect; 16 (11.0%) due to lack of efficacy; six (4.1%) experienced side effects leading to cessation; five (3.4%) stopped for alternative reasons; one (0.7%) experienced a severe allergic drug reaction; three (2.1%) developed lung cancer and treatment was stopped in each case. 12 (8.3%) patients had ILD prior to treatment. 10 (6.9%) had prior major cardiovascular events, eight (5.5%) had previously treated malignancy, and six (4.1%) had previous VTE. During treatment, 1 (0.7%) patient developed ILD and two (1.4%) developed VTE. There were three (2.1%) new malignancies, all lung cancer. No new MACE occurred. 120 (82.8%) patients were previously treated with biologic or targeted synthetic DMARDs. 59 (40.7%) had failed multiple biologic DMARDs of different classes. 19 (13.1%) switched to Filgotinib from another JAK inhibitor. Pre-treatment DAS-28 scores were recorded in 55 (37.9%) patients with mean 5.1, and during treatment in 44 patients (30.3%) with mean 3.5. 17 (11.7%) patients had DAS-28 recorded both before and during treatment, with pre-treatment mean 5.0 and subsequent mean 2.9. Of these, 10 (58.8%) were classified as a good response by EULAR disease activity criteria, and four (23.5%) as a moderate response. Three (17.6%) were non-responders. Conclusion Our cohort includes 40.7% difficult-to-treat RA. Drug survival as a clinical efficacy surrogate was 71.7% at median duration 447 days, demonstrating patient acceptability and clinical effectiveness. Our service is poor at DAS-28 recording in the EPR, which may partly reflect imaging use at response assessment. Since this cohort was established, the European Medicines Agency has issued guidance advising caution using JAK inhibitors in high-risk groups to minimise the chance of serious side effects. Disclosure C.D. Box: None. S. Ramsay: None. N.D. McKay: Other; N.D.M. has received funding for conference registrations from Abbvie, UCB and Novartis, fees for lecturing from Gilead, and has taken part in advisory board meetings for UCB and Gilead.

Impact of preexisting interstitial lung disease on mortality in COVID-19 patients from the early pandemic to the delta variant epidemic: a nationwide population-based study

BackgroundCOVID-19 patients with preexisting interstitial lung disease (ILD) were reported to have a high mortality rate; however, this was based on data from the early stages of the pandemic. It is uncertain how their mortality rates have changed with the emergence of new variants of concern as well as the development of COVID-19 vaccines and treatments. It is also unclear whether having ILD still poses a risk factor for mortality. As COVID-19 continues to be a major concern, further research on COVID-19 patients with preexisting ILD is necessary.MethodsWe extracted data on COVID-19 patients between January 2020–August 2021 from a Japanese nationwide insurance claims database and divided them into those with and without preexisting ILD. We investigated all-cause mortality of COVID-19 patients with preexisting ILD in wild-type-, alpha-, and delta-predominant waves, to determine whether preexisting ILD was associated with increased mortality.ResultsOf the 937,758 adult COVID-19 patients, 7,333 (0.8%) had preexisting ILD. The proportion of all COVID-19 patients who had preexisting ILD in the wild-type-, alpha-, and delta-predominant waves was 1.2%, 0.8%, and 0.3%, respectively, and their 60-day mortality was 16.0%, 14.6%, and 7.5%, respectively. The 60-day mortality significantly decreased from the alpha-predominant to delta-predominant waves (difference − 7.1%, 95% confidence intervals (CI) − 9.3% to − 4.9%). In multivariable analysis, preexisting ILD was independently associated with increased mortality in all waves with the wild-type-predominant, odds ratio (OR) 2.10, 95% CI 1.91–2.30, the alpha-predominant wave, OR 2.14, 95% CI 1.84–2.50, and the delta-predominant wave, OR 2.10, 95%CI 1.66–2.66.ConclusionsAll-cause mortality rates for COVID-19 patients with preexisting ILD decreased from the wild-type- to the more recent delta-predominant waves. However, these patients were consistently at higher mortality risk than those without preexisting ILD. We emphasize that careful attention should be given to patients with preexisting ILD despite the change in the COVID-19 environment.

Current pharmacotherapies for advanced lung cancer with pre-existing interstitial lung disease : A literature review and future perspectives.

Patients with interstitial lung disease (ILD), especially those with idiopathic pulmonary fibrosis, are at increased risk of developing lung cancer (LC). Pharmacotherapy for advanced LC has dramatically progressed in recent years;however, management of LC with pre-existing ILD (LC-ILD) is challenging due to serious concerns about the risk of acute exacerbation of ILD (AE-ILD). As patients with LC-ILD have been excluded from most prospective clinical trials of advanced LC, optimal pharmacotherapy remains to be elucidated. Although the antitumor activity of first-line platinum-based cytotoxic chemotherapy appears to be similar in advanced LC patients with or without ILD, its impact on the survival of patients with LC-ILD is limited. Immune checkpoint inhibitors may hold promise for long-term survival, but many challenges remain, including safety and appropriate patient selection. Further understanding the predictive factors for AE-ILD after receiving pharmacotherapy in LC-ILD may lead to appropriate patient selection and lower treatment risk. The aim of this review was to summarize the current evidence related to pharmacotherapy for advanced LC-ILD and discuss emerging areas of research. J. Med. Invest. 71 : 9-22, February, 2024.

Risk of 30-Day All-Cause Readmission in Interstitial Lung Disease Patients after COVID-19: National-Level Data.

Rationale: Hospital readmission within 30 days poses challenges for healthcare providers, policymakers, and patients because of its impact on care quality, costs, and outcomes. Patients with interstitial lung disease (ILD) are particularly affected by readmission, which is associated with increased morbidity and mortality and reduced quality of life. Because small sample sizes have hindered previous studies, this study seeks to address this gap in knowledge by examining a large-scale dataset. Objective: To determine the rate and probability of 30-day all-cause readmission and secondary outcomes in patients with coronavirus disease (COVID-19) or ILD admitted to the hospital. Methods: This study is a nested cohort study that used the PearlDiver patient records database. Adult patients (age ⩾18 yr) who were admitted to hospitals in 28 states in the United States with COVID-19 or ILD diagnoses were included. We defined and analyzed two separate cohorts in this study. The first cohort consisted of patients with COVID-19 and was later divided into two groups with or without a history of ILD. The second cohort consisted of patients with ILD and was later divided into groups with COVID-19 or with a non-COVID-19 pneumonia diagnosis at admission. We also studied two other subcohorts of patients with and without idiopathic pulmonary fibrosis within the second cohort. Propensity score matching was employed to match confounders between groups. The Kaplan-Meier log rank test was applied to compare the probabilities of outcomes. Results: We assessed the data of 2,286,775 patients with COVID-19 and 118,892 patients with ILD. We found that patients with COVID-19 with preexisting ILD had an odds ratio of 1.6 for 30-day all-cause readmission. Similarly, an odds ratio of 2.42 in readmission rates was observed among hospitalized individuals with ILD who contracted COVID-19 compared with those who were hospitalized for non-COVID-19 pneumonia. Our study also found a significantly higher probability of intensive care admission among patients in both cohorts. Conclusions: Patients with ILD face heightened rates of hospital readmissions, particularly when ILD is combined with COVID-19, resulting in adverse outcomes such as decreased quality of life and increased healthcare expenses. It is imperative to prioritize preventive measures against COVID-19 and establish effective postdischarge care strategies for patients with ILD.

Expert consensus on the management of interstitial lung disease during the COVID-19 epidemic

Expert consensus on the management of interstitial lung disease during the COVID-19 epidemic

Risk factors associated with COVID-19 pneumonia in Chinese patients with pre-existing interstitial lung disease during the SARS-CoV-2 pandemic.

In China, the emergence of a nationally widespread epidemic infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has appeared within a month since December 7, 2022. To evaluate the risk factors for suffering from coronavirus disease 2019 (COVID-19) pneumonia due to infection with SARS-CoV-2 in different kinds of interstitial lung disease (ILD) patients with diverse immunizations, we conducted this retrospective study on 525 patients with ILDs who underwent regular follow-up in our ILD clinic. Among them, 128 ILD patients (24.4%) suffered from COVID-19 pneumonia after SARS-CoV-2 infection. Patients were older with a male predominance in the pneumonia group than in the nonpneumonia group (65.0 ± 10.0 yearsvs. 56.4 ± 11.7 years, p < 0.001, 55.5% vs. 39.5%, p = 0.002, respectively). Connective tissue disease-associated ILD(CTD-ILD) (25%), idiopathic pulmonary fibrosis(23.4%), and interstitial pneumonia with autoimmune features(21.1%) were the main pre-existing ILDs in the pneumonia group. In Cox multivariable analysis, only male sex and corticosteroid use were risk factors for COVID-19 pneumonia after infection. Two or threedoses of vaccination were a protective factor for pre-existing ILD patients suffering from COVID-19 pneumonia. More than twodoses of vaccination were strongly recommended for pre-existing ILD patients, particularly for males who were administered corticosteroids.

Clinicoradiological outcomes after radical radiotherapy for lung cancer in patients with interstitial lung disease.

Interstitial lung disease (ILD) is relatively common in patients with lung cancer with an incidence of 7.5%. Historically pre-existing ILD was a contraindication to radical radiotherapy owing to increased radiation pneumonitis rates, worsened fibrosis and poorer survival compared with non-ILD cohorts. Herein, the clinical and radiological toxicity outcomes of a contemporaneous cohort are described. Patients with ILD treated with radical radiotherapy for lung cancer at a regional cancer centre were collected prospectively. Radiotherapy planning, tumour characteristics, and pre- and post-treatment functional and radiological parameters were recorded. Cross-sectional images were independently assessed by two Consultant Thoracic Radiologists. Twenty-seven patients with co-existing ILD received radical radiotherapy from February 2009 to April 2019, with predominance of usual interstitial pneumonia subtype (52%). According to ILD-GAP scores, most patients were Stage I. After radiotherapy, localised (41%) or extensive (41%) progressive interstitial changes were noted for most patients yet dyspnoea scores (n = 15 available) and spirometry (n = 10 available) were stable. One-third of patients with ILD went on to receive long-term oxygen therapy, which was significantly more than the non-ILD cohort. Median survival trended towards being worse compared with non-ILD cases (17.8 vs 24.0 months, p = 0.834). Radiological progression of ILD and reduced survival were observed post-radiotherapy in this small cohort receiving lung cancer radiotherapy, although a matched functional decline was frequently absent. Although there is an excess of early deaths, long-term disease control is achievable. For selected patients with ILD, long-term lung cancer control without severely impacting respiratory function may be possible with radical radiotherapy, albeit with a slightly higher risk of death.

COVID-19 in Patients with Pre-Existing Interstitial Lung Disease: Potential Value of a Steroid-Based Treatment Strategy.

The prognosis of patients with coronavirus disease 2019 (COVID-19) and pre-existing interstitial lung disease (preILD) is poor, and no effective treatment strategy has been determined. The aim of this study was to assess the effectiveness of a steroid-based treatment strategy for patients with COVID-19 and preILD. We retrospectively reviewed the medical records of 610 consecutive patients with COVID-19 treated at our institution between 1 March 2020 and 30 October 2021 and identified 7 patients with preILD, all of whom were treated with corticosteroids and remdesivir. All the patients were men with a median age of 63 years. Three of four patients with severe disease required invasive positive-pressure ventilation (n = 2) or nasal high-flow therapy (n = 1). All three patients could be weaned from respiratory support; however, one died in hospital. The remaining patient with severe COVID-19 had a do-not-resuscitate order in place and died while hospitalized. All three patients with moderate COVID-19 were discharged. The 30-day mortality was 0%, and the mortality rate during the entire observation period was 28.5%. The prognosis of our patients with COVID-19 and preILD has been better than in previous reports. Our management strategy using corticosteroids may have improved these patients' prognosis.

Radiological evaluation of interstitial lung disease in patients with rheumatoid arthritis treated with abatacept or JAK inhibitors for 1 year

BackgroundWe evaluated the radiological deterioration of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with abatacept (ABT) or Janus-kinase inhibitors (JAKi) for 1 year. MethodsThis study enrolled 84 patients with RA who had started treatment with ABT (48 patients) or JAKi (36 patients) between 2017 and 2020. All patients underwent chest CT before administration and at 1 year post-treatment. ResultsIn all patients, the rate of deterioration of ILD in ABT and JAKi was 4.2% and 5.6%, respectively (p = 0.847). In the patients with pre-existing ILD, the rates of deterioration of ILD in the ABT and JAKi groups were 10.5% and 18.2%, respectively (p = 0.611). Meanwhile, newly developed ILD did not occur in the two groups without pre-existing ILD. ConclusionThe present study demonstrated that the safety of pulmonary toxicity with ABT and JAKi treatments was similar in patients with RA. JAKi may be a potentially acceptable treatment option for patients with RA.

Amiodarone for the Treatment of Arrhythmias in COVID-19 Patients Does Not Increase the Risk of Pulmonary Fibrosis: A Retrospective Cohort Study.

Amiodarone is a class III antiarrhythmic medication used to treat atrial and ventricular tachyarrhythmias. Pulmonary fibrosis from amiodarone use is a well-documented side effect. Pre-COVID-19 pandemic studies have shown that amiodarone-induced pulmonary fibrosis occurs in 1%-5% of patients and usually occurs between 12 to 60 months after initiation. The risk factors associated with amiodarone-induced pulmonary fibrosis include a high total cumulative dose (treatment longer than two months) and high maintenance dose (>400 mg/day). COVID-19 infection is also a known risk factor for developing pulmonary fibrosis and occurs in approximately 2%-6% of patients after a moderate illness. This study aims to assess the incidence of amiodarone in COVID-19 pulmonary fibrosis (ACPF). This is a retrospective cohort study with 420 patients with COVID-19 diagnoses between March 2020 and March 2022, comparing two populations, COVID-19 patients with exposure to amiodarone (N=210) and COVID-19 patients without amiodarone exposure (N=210). In our study, pulmonary fibrosis occurred in 12.9% ofpatients in the amiodarone exposure group compared to 10.5% of patients in the COVID-19 control group (p=0.543). In multivariate logistic analysis, which controlled for clinical covariates, amiodarone use in COVID-19 patients did not increase the odds of developing pulmonary fibrosis (odds ratio (OR): 1.02, 95% confidence interval (CI): 0.52-2.00). The clinical factors associated with the development of pulmonary fibrosis in both groups included a history of preexisting interstitial lung disease (ILD) (p=0.001), exposure to prior radiation therapy (p=0.021), and higher severity of COVID-19 illness (p<0.001). In conclusion, our study found no evidence that amiodarone use in COVID-19 patients increased the odds of developing pulmonary fibrosis at six-month follow-up. However, long-term amiodarone usage in the COVID-19 population should be based on the physician's discretion.

Outcome following nivolumab treatment in patients with advanced non-small cell lung cancer and comorbid interstitial lung disease in a real-world setting.

Up to 10% of patients with advanced non-small cell lung cancer (aNSCLC) have pre-existing interstitial lung disease (ILD). These patients are usually excluded from immunotherapy clinical trials. Consequently, knowledge on outcomes following nivolumab treatment in these patients remains limited. The primary objective of this study was to evaluate survival outcome following nivolumab treatment in ILD patients with pre-treated aNSCLC in the real-world setting. The study included all patients with aNSCLC recorded in the French hospital database, starting nivolumab in 2015-2016. Patients were stratified by pre-existing ILD and three subgroups were studied [auto-immune or granulomatous (AI/G) ILD, other known causes ILD and idiopathic ILD]. Time to discontinuation of nivolumab treatment [time to treatment duration (TTD)] and overall survival (OS) were estimated using Kaplan-Meier survival analysis. Of 10,452 aNSCLC patients initiating nivolumab, 148 (1.4%) had pre-existing ILD. Mean age at nivolumab initiation was 64.6 ± 9.4 years in ILD and 63.8 ± 9.6 years in non-ILD. Compared to non-ILD, patients in the ILD group were more frequently men (p < 0.05) and had more comorbidities (p < 0.001). There was no significant difference between ILD and non-ILD groups for median TTD (2.5 versus 2.8 months; p = 0.6) or median OS (9.6 versus 11.9 months; p = 0.1). Median OS in AI/G ILD (n = 14), other known causes ILD (n = 75), and idiopathic ILD (n = 59) were 8.6, 10.7, and 9.6 months, respectively. In this large cohort of aNSCLC patients with ILD, outcomes are similar to those obtained in the non-ILD population. Immunotherapy could be beneficial for these patients.

Prognostic Analysis of Pneumocystis Jirovecii Pneumonia in Interstitial Lung Disease Patients: A Retrospective Clinical Study.

(1) Background: The clinical characteristics and the prognostic factors of HIV-negative Pneumocystis jirovecii pneumonia (PJP) patients (non-HIV-PJP) with interstitial lung disease (ILD) remain unclear. Our objectives were to describe the clinical characteristics and to explore the prognostic factors of non-HIV-ILD-PJP patients. (2) Methods: The enrolled patients in this retrospective study were stratified based on the presence or absence of ILD and fibrotic ILD (FILD). The log-rank test and Cox regression models were used to analyze the prognostic factors. (3) Results: Among 378 non-HIV-PJP patients, there were 133 patients with ILD-PJP, and 70 patients were classified as having FILD-PJP. The all-cause mortality rate for the ILD-PJP group is higher than that of the ILD-PJP group (57.9% vs. 38.4%, p < 0.001). However, the all-cause mortality is similar between the FILD-PJP group and non-FILD-PJP group. Preexisting ILD (HR: 2.156, p = 0.003) and honeycomb appearance on the chest HRCT (HR = 16.3, p < 0.001) are independent survival risk factors for ILD-PJP. Non-invasive ventilation is an independent survival risk factor for ILD-PJP patients (HR = 928.56, p < 0.01) and FILD-PJP patients (HR = 33.86, p < 0.001). (4) Conclusions: Pre-existing ILD and honeycomb appearance on the chest HRCT are independent survival risk factors for PJP patients. Non-invasive ventilation is associated with poor survival for both ILD-PJP and FILD-PJP patients.

The safety and efficacy of durvalumab consolidation therapy in the management of patients with stage III non-small-cell lung cancer and preexisting interstitial lung disease

Some lung cancer patients have preexisting interstitial lung disease (ILD), which is considered a risk factor for lung cancer treatment. This study investigated the safety and efficacy of durvalumab consolidation therapy for patients with stage III non-small-cell lung cancer (NSCLC) and preexisting ILD. Fifty consecutive patients who were judged to be tolerable to concurrent chemoradiotherapy (CCRT) for stage III NSCLC were enrolled. Differences in the incidence rate of radiation pneumonitis (RP) and progression-free survival (PFS) were assessed in patients with or without ILD of which CT showed non-usual interstitial pneumonia pattern between the durvalumab consolidation group and chemotherapy (combination of carboplatin and paclitaxel [CP]) consolidation group. The incidence of RP was higher in patients with preexisting ILD (40% and 20% in the durvalumab and CP groups, respectively) than in those without ILD (26% and 8% in the durvalumab and CP groups, respectively). Univariate analysis showed that durvalumab therapy tended to increase the incidence of RP; however, preexisting ILD did not significantly increase the incidence of RP. The condition of all patients who developed RP improved with the administration of oral prednisolone. Among patients without ILD, the median PFS was 17 and 16 months in the durvalumab and CP groups, respectively. Among patients with preexisting ILD, median PFS was not achieved in the durvalumab group and was 8 months in the CP group. Although durvalumab consolidation therapy tended to increase the incidence of RP, it might be tolerable in stage III NSCLC patients with preexisting ILD.