Pre-existing Interstitial Lung Disease Research Articles

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].

Coronavirus disease 2019(COVID-19) is prevalent around the world, and pre-existing ILD is associated with increased severity and mortality of COVID-19. However, the current knowledge on the management strategy for COVID-19 patients with pre-existing interstitial lung disease (ILD) is very limited. There is still a need for consensus on treatments for these patients. In addition, ILD that occurs after the acute phase of COVID-19 (Post-acute Covid-19 ILD, PC-ILD) is also very common, and how to manage PC-ILD is also under debate. Therefore, a consensus was established by experts from the related disciplines in the field of ILD based on available scientific evidence and experience of the expert working group. This consensus elucidated 22 practical questions for practicing physicians, such as clinical characteristics, risk factors and treatment of COVID-19 patients with pre-existing ILD and PC-ILD patients. Finally, 15 recommendations were made regarding the diagnosis and management of COVID-19 patients with pre-existing ILD and PC-ILD patients. We hope to assist physicians in making appropriate decisions, thereby improving the management of COVID-19 with pre-existing ILD and PC-ILD.Recommendation 1: It is recommended to differentiate COVID-19 from ILD with acute/subacute onset based on duration, exposure history, symptoms and signs, chest high-resolution CT (HRCT) features, and laboratory tests.Recommendation 2: According to the guidelines on the diagnosis and treatment of new coronavirus pneumonia (version 10) issued by the National Health Commission of China on January 6th, 2023, we recommended the following disease severity definition and management for the COVID-19 patients with pre-existing ILD.Recommendation 3: ILD is an independent risk factor for severe/critical COVID-19. We recommend antiviral treatment for COVID-19 patients with pre-existing ILD as early as possible after symptoms onset, ideally within 5 days.Recommendation 4: We recommend that the use of systemic corticosteroids in COVID-19 patients with pre-existing ILD who had no indications for corticosteroids therapy should follow the guidelines of COVID-19 for the general population. Those with pre-existing ILD who need to start or are already on systemic corticosteroids are recommended to start or continue corticosteroids if they develop COVID-19. The dose adjustment is based on the severity of COVID-19 with pre-existing ILD: For the patients with severe/critical COVID-19 with pre-existing ILD but no AE-ILD, the use of corticosteroids should follow the guidelines of COVID-19 in the general population; the patients with AE-ILD are recommended to follow the use of corticosteroids in AE-ILD.Recommendation 5: There is no evidence available for the use of interleukin-6 receptor blockers in COVID-19 patients with pre-existing ILD. Recommendations regarding interleukin-6 receptor blockers in COVID-19 patients with pre-existing ILD may follow the guideline of COVID-19 in the general population.Recommendation 6: There is no evidence to support the use of Janus kinase inhibitors in COVID-19 patients with pre-existing ILD. The use of Janus kinase inhibitors in COVID-19 patients with pre-existing ILD is recommended to follow the guideline of COVID-19 in the general population.Recommendation 7: For patients who have not started immunosuppressants/biological agents for pre-existing ILD at the time of COVID-19, delayed initiation of immunosuppressants/biological agents is recommended, if the risk of ILD progression in the short term is low. For patients who are already on immunosuppressants/biological agents, a multidisciplinary discussion with rheumatologists is recommended to weigh the benefits and risks of discontinuing immunosuppressants/biological agents. It is recommended to discontinue immunosuppressants/biological agents for pre-existing ILD in acute phase of COVID-19 unless short-term discontinuation affects control of underlying ILD or connective tissue disease.Recommendation 8: It is recommended that the COVID-19 patients with pre-existing ILD who are on anti-fibrotic medication should continue to take anti-fibrotic medication. For COVID-19 patients with newly diagnosed fibrotic ILD who need to start anti-fibrotic therapy, it is recommended to start anti-fibrotic treatment as early as possible.Recommendation 9: It is recommended to investigate and monitor co-infections and secondary infections in COVID-19 patients with pre-existing ILD, and to promptly prevent and treat co-infections and secondary infections such as bacteria, fungi, Pneumocystis jirovecii, and cytomegalovirus.Recommendation 10: Anticoagulation therapy for the COVID-19 patients with pre-existing ILD is recommended to be used in accordance with guideline of COVID-19 in general population.Recommendation 11: For COVID-19 patients with pre-existing ILD, we recommend follow-up at 4 weeks after recovery (non-hospitalized patients) or 4 weeks after discharge (hospitalized patients), and then the routine monitoring frequency for ILD once stable, i.e. every 3 to 6 months. Pulmonary function testing is a routine investigation. Chest HRCT is suggested when clinically indicated. Arterial blood gas analysis, echocardiography, CT pulmonary angiography, and blood examinations can be selected when necessary.Recommendation 12: Severe/critical COVID-19 survivors are the main target population for rehabilitation intervention. Rehabilitation therapy should be administered individualized.Recommendation 13: Healthcare providers should fully inform patients with pre-existing ILD about the benefits and risks of vaccination, and involve patients in a shared decision-making process to discuss whether or not to receive a COVID-19 vaccine.Recommendation 14: For PC-ILD patients with persistent or progressive respiratory symptoms, persistent interstitial lung abnormalities and lung function impairment following acute COVID-19 pneumonia, may be treated with glucocorticoids after exclusion of other causes such as infection.Recommendation 15: For PC-ILD patients who have recovered from severe/critical COVID-19, anti-fibrotic medications may be administered after discussing disease-and treatment-related factors with patients. The optimal timing and duration of anti-fibrotic treatment are still uncertain. We conditionally recommend against anti-fibrotic medications in patients who have recovered from mild or moderate COVID-19. This recommendation does not apply to patients with pre-existing fibrotic ILD.

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.

Immunotherapy-related pneumonitis and the synergic impact of thoracic radiation and preexisting interstitial lung disease.

Immune checkpoint inhibitors (ICIs) are the frontline of therapy for most cancers. Although ICIs are sometimes considered to be less harmful than systemic chemotherapies, ICIs may cause immune-related adverse events, which are cases of off-target inflammation in healthy tissues. Pneumonitis, an immune-related adverse event, is the leading cause of therapy-related mortality with ICIs. The aim of this review is to discuss how preexisting interstitial lung disease (ILD) and thoracic radiation increase the risk for ICI-pneumonitis. We discuss potential mechanisms of lung injury and how pneumonitis may impact cancer treatments. Preexisting ILD and thoracic radiation are major risk factors for ICI-pneumonitis. The mechanisms of injury are still not fully understood but may involve the same inflammatory and profibrotic cytokines as those seen in sporadic ILD. Thoracic radiation increases the risk for ICI-pneumonitis and may synergize with preexisting ILD to worsen toxicity. Preexisting ILD and thoracic radiation may increase the risk for the future development of ICI-pneumonitis. However, while these should not preclude potentially life-saving immunotherapy, in some cases, an alternative treatment strategy may be advisable. A multidisciplinary approach is required involving oncologists, pulmonologists, and radiation oncologists to guide in the selection of cancer treatment and in the diagnosis and treatment of pneumonitis.

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 &lt; 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 &lt; 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 &lt; 0.01) and FILD-PJP patients (HR = 33.86, p &lt; 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.

Mortality and Its Predictors in COVID-19 Patients With Pre-existing Interstitial Lung Disease.

BackgroundThe data on the impact of coronavirus disease 2019 (COVID-19) on interstitial lung disease (ILD) is still limited. To the best of our knowledge, there has been no study from India to date to assess the impact of COVID-19 in patients with preexisting ILD. We undertook this study to assess the clinical outcome of ILD patients admitted to our hospital with COVID-19.MethodsIn this retrospective observational study, records of reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients with preexisting ILD who were admitted to the hospital in the period from May 1, 2020, to April 30, 2021, were obtained from the hospital database. The clinical outcomes of the patients were recorded. Univariate analysis was performed to find relation between various predetermined risk factors for mortality and those with significant p values (p<0.05) were subjected to multiple logistic regression to determine independent risk factors.ResultsIn our study of 28 patients, the overall mortality was 35.7%. On comparing the parameters associated with increased mortality, there was no effect of age, gender, comorbidities, type of ILD, CT thorax findings on diagnosis, use of corticosteroids and antifibrotics in the past, spirometric findings on mortality. On multivariate analysis, the significant parameters were interleukin 6 (IL-6), p=0.02, OR=1.020 (1.006-1.043) and D-dimer, p=0.04, OR=2.14 (5.55-1.14).ConclusionCOVID-19 in patients with pre-existing ILD has a comparatively higher mortality. D-dimer and IL-6 are significant predictors of mortality in ILD patients infected with COVID-19.

Pulmonary adverse events following immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have rapidly become a mainstay of cancer treatment. However, immune modulation resulting from checkpoint inhibition can cause inflammation in any organ system, with pneumonitis being one of the most severe immune-related adverse events (irAEs). Here, we review the most recent literature on pulmonary adverse events following ICIs. Several systematic reviews and meta-analyses of data from trials of antiprogrammed death-1 (PD-1; nivolumab, pembrolizumab), anti-PD-ligand-1 (PD-L1; atezolizumab, avelumab, durvalumab) and anticytotoxic T lymphocyte antigen-4 (CTLA-4; ipilimumab or tremelimumab) in patients with advanced cancer have explored the relative risk and incidence of lung toxicity among different tumor types and therapeutic regimens. They have showed that the incidence of all-grade (1-4) and high-grade (3-4) pneumonitis is significantly higher in nonsmall cell lung cancer (NSCLC) compared with other tumor types. In addition, they have demonstrated that immunotherapy, especially monoimmunotherapy, has a significantly lower risk of irAEs compared to immune-chemotherapy. Treatment for lung cancer, preexisting interstitial lung disease, smoking history and male sex appear to increase the risk for ICI-related pneumonitis. Lung toxicity is an uncommon but potentially severe and even fatal complication of ICIs. Timely recognition is critically important but challenging, particularly in patients with lung cancer wherein drug toxicity can mimic disease progression or recurrence.

Outcome of COVID-19 in interstitial lung disease patients treated with anti-inflammatory drugs and antiviral drugs

A recent study reported that patients with interstitial lung disease (ILD) are at increased risk of death from coronavirus disease 2019 (COVID-19). However, there are no studies on the outcome of COVID-19 patients with preexisting ILD treated with corticosteroids or antiviral drugs. We extracted 26 patients with preexisting ILD by medical records and HRCT pattern. Of 503 patients with COVID-19, we selected 52 patients as control matched for age and sex. Twenty out of the 26 ILD patients (76.9%) received corticosteroid therapy, and 23 patients (88.5%) also received antiviral treatment with remdesivir or favipiravir. Although no statistical difference was found, the proportion of severe patients in ILD group tended to be higher than in non-ILD group (23.1% vs. 42.3%; p = 0.114). Also, mortality rate in ILD group tended to be higher than in non-ILD patients (11.5% vs. 3.8%; p = 0.326). In univariate analysis to evaluate risk factors for severe condition, diagnosis of idiopathic pulmonary fibrosis, usual interstitial pneumonia pattern, and honeycomb lung were not risk factors of severe disease. Treatment with corticosteroids, antiviral drugs, and immunosuppressive agents may affect the outcome of COVID-19 patients with ILD.

How COVID-19 interacts with interstitial lung disease.

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had far-reaching impacts on patients with interstitial lung disease (ILD), from diagnosis to management. In addition, after infection, persistent parenchymal change is associated with ongoing symptoms and functional impairment even in patients without pre-existing lung disease. The challenge of investigating and treating these patients has often fallen to ILD physicians. This review therefore seeks to explore the relationship between COVID-19 and the interstitium, as well as the model of care for patients with pre-existing ILD and those patients with persistent disease following recovery from their initial infection.Educational aimsTo understand the impact of the COVID-19 pandemic on patients with existing interstitial lung disease.To explore the development of interstitial lung disease after COVID-19 infection.

Clinical Outcomes of Immune Checkpoint Inhibitor Therapy in Patients With Advanced Non-small Cell Lung Cancer and Preexisting Interstitial Lung Diseases: A Systematic Review and Meta-analysis

Patients with non-small cell lung cancer (NSCLC) and preexisting interstitial lung disease (ILD) are often excluded from clinical trials of immune checkpoint inhibitors (ICIs), leaving a gap in knowledge. What are the clinical outcomes of ICIs in patients with NSCLC and preexisting ILD? Systematic searches were conducted of PubMed, EMBASE, and Cochrane Library through April 2021 with no language or study design restrictions. Studies reporting the safety and efficacy data among patients with cancer and ILD receiving ICI therapy were collected. The primary end points were clinical efficacy to immunotherapy and the incidence of immune-related adverse events, especially for checkpoint inhibitor pneumonitis (CIP). A total of 179 patients in 10 studies were included. The pooled overall response rate (ORR) and pooled disease control rate (DCR) were 34%(95%CI, 20-47) and 66%(95%CI, 56-75), respectively. The ORR in patients with preexisting ILD was significantly higher than that in patients without ILD (OR, 1.99; 95%CI, 1.31-3.00). The DCR and progression-free survival in patients with preexisting ILD were not inferior to those without ILD (pooled OR, 1.46; 95%CI, 0.94-2.25 for DCR). The pooled incidences of any grade and grade 3 or higher CIP were 27%(95%CI, 17-37) and 15%(95%CI, 9-22) in patients with preexisting ILD, and 10%(95%CI, 6-13) and 4%(95%CI, 2-6) in patients without ILD. Meta-analysis found a significantly higher incidence rate of any grade and grade 3 or higher CIP in patients with NSCLC and preexisting ILD than in those patients without ILD (OR, 3.23 [95%CI, 2.06-5.06]; OR, 2.91 [95%CI, 1.47-5.74]). Programmed cell death protein 1/programmed cell death ligand 1 inhibitors had favorable efficacy in NSCLC with preexisting ILD. CIP is frequent in patients with preexisting ILD who receive ICI therapy but is often mild and easily manageable. Clinicians should be cautious when using ICIs in patients with preexisting ILD.

Characteristic clinical features of rheumatic patients with COVID-19 infection in mataria teaching hospital

ObjectiveThe patients who have rheumatic diseases and have coronavirus disease 2019 (COVID-19) infection, their clinical features have not been reported. This study aims to identify the characteristic clinical features of COVID-19 in patients with rheumatic diseases admitted either inside or outside the ICU and present data to handle these conditions in clinical practice.Patients and methodsWe conducted a retrospective study, including data about the sex, age, laboratory and radiographic findings, clinical symptoms and signs, ICU admission, and drug history, from 180 patients having COVID-19 infection, and includes 61 patients having in combination of rheumatic diseases, in the period between April and June 2020 in Mataria Teaching Hospital.ResultsThe risk of admission in the ICU in the rheumatic group 20 (32.8%) did not exceed those expected in the nonrheumatic group 59 (49.6%). Nevertheless, the mortality of these patients was lower three (15%) than nonrheumatic group who were admitted in the ICU 33 (55.9%). Patients with rheumatic diseases presented with less symptoms and signs of respiratory failure, in comparison with those not having rheumatic diseases (rheumatic group vs. nonrheumatic group: 34.4 vs. 49.6%, P < 0.005). Comorbidities were similar in those with rheumatic diseases and comparators [25 (41.0%) vs. 48 (40.3%), respectively]. Symptoms of fever, fatigue, and diarrhea were seen in 55.7, 78.7, and 41% of patients, respectively. Nine patients with rheumatic diseases developed rheumatic disease flare during their hospital stay, represented in muscle aches, rash, and pain in the back and joints. Lymphocytopenia was seen in 16.7% of patients with rheumatic diseases, but 14.8% of patients presented with leukopenia. Patients with rheumatic diseases experienced same radiographic findings of ground-glass opacity and consolidation. Patients who have preexisting interstitial lung disease presented at an early stage with massive fibrous stripes and crazy-paving signs.ConclusionsSymptoms of respiratory failure were less common in patients with rheumatic diseases infected with COVID-19. The ICU admission in the rheumatic group did not exceed those expected in the nonrheumatic group. Differential diagnosis should be considered between COVID-19 infection and rheumatic disease flare.