Respiratory Research Review Issue 213 - 2023 - Interstitial Lung Disease PDF

Respiratory RESEARCH REVIEW ™ Making Education Easy In this issue: Silicosis in US engineered stone countertop fabrication workers Association of statin use with ILD/IPF risk Pirfenidone in RA-associated ILD Rituximab vs. cyclophosphamide in CTD-associated ILD Rituximab + mycophenolate mofetil in...

Respiratory RESEARCH REVIEW ™ Making Education Easy In this issue: Silicosis in US engineered stone countertop fabrication workers Association of statin use with ILD/IPF risk Pirfenidone in RA-associated ILD Rituximab vs. cyclophosphamide in CTD-associated ILD Rituximab + mycophenolate mofetil in ILD Treatment outcomes for RA-associated ILD Incidence of interstitial lung abnormalities Association of PM2.5 exposure with lung function and mortality in fibrotic ILD Trends in US hospitalisations and inpatient mortality for pulmonary sarcoidosis Palliative care for ILD Abbreviations used in this issue CTD = connective tissue disease CV = cardiovascular DLCO = diffusing capacity for carbon monoxide FVC = forced vital capacity HR = hazard ratio ILD = interstitial lung disease IPF = idiopathic pulmonary fibrosis K-BILD = King’s Brief Interstitial Lung Disease PM2.5 = particular matter ≤2.5µm in diameter RA = rheumatoid arthritis UIP = usual interstitial pneumonia RACP MyCPD Program participants can claim the time Issue 213 – 2023 Welcome to this issue of Respiratory Research Review with the topic of ILD (interstitial lung disease); it is certainly one of the hot topics, with active research and an ongoing unmet clinical need. ‘Interstitial lung disease: a decade of progress and hope’ (Lancet Respir Med 2023;11:510–2) is the title of Ayodeji Adegunsoye’s editorial as part of Lancet Respir Med’s tenth anniversary roundup series. He reflects on our tools for earlier diagnosis, the two antifibrotic medications available, and the standard of delivering treatment decisions via multidisciplinary meetings. The editorial also has a nicely structured list of the ongoing clinical trials looking to establish much needed new treatments for IPF. David Smith and Gisli Jenkins echo the achievements in their ‘Contemporary concise review 2022: interstitial lung disease’ (Respirology 2023;28:627–35). These authors also highlight our knowledge and research gaps: we do not know how to influence genetic variants associated with IPF to affect change, we have no established biomarker for IPF, we need a randomised trial on the role of sildenafil in the treatment of pulmonary hypertension secondary to ILD, and we know that 11% of patients admitted with long COVID have residual lung abnormalities but have no treatment. One such gap, around the evidence base for oxygen therapy in patients with ILD, is addressed by Elisabetta Renzoni and colleagues in their review ‘Oxygen in interstitial lung disease’ (Breathe 2023;19:220271). ‘Pleuroparenchymal fibroelastosis: so many unmet needs’ (Eur Respir J 2022;60:2201798) laments our French colleagues in an editorial in the Eur Respir J. We have only recognised and labelled this illness, which has a poor prognosis, in its own right in the 21st century, and we remain uncertain as to what issues to tackle as a priority. Patients with PPFE (pleuroparenchymal fibroelastosis) often have underlying autoimmune disorders and are best diagnosed via imaging, but treatment options remain elusive. The article that the editorial is based on suggests a new imaging algorithm: ‘Idiopathic pleuroparenchymal fibroelastosis: three-dimensional computed tomography assessment of upperlobe lung volume’ (Eur Respir J 2022;60:2200637). Hayley Barnes and colleagues carefully reflect that much of the reading of CT scans in ILD may be improved by integrating artificial intelligence in ‘Machine learning in radiology: the new frontier in interstitial lung diseases’ (Lancet Digital Health 2023;5:e41–50). After a promising start with two antifibrotic medications for IPF, drug development has stalled over the last decade or so. Harold Collard reflects on this in his paper ‘Three wishes for improving clinical drug development in pulmonary fibrosis’ (Eur Respir J 2023;61:2202355). ‘Usual interstitial pneumonia as a stand-alone diagnostic entity: the case for a paradigm shift?’ (Lancet Respir Med 2023;11:188–96) is an ever-thoughtful deliberation by Moisés Selman, Annie Pardo and Athol Wells. The authors make the case that it simplifies the diagnosis, unifies a disease group with similar clinical trajectory, and would arguably allow for focused treatment and research. Vincent Cottin and Claudia Valenzuela touch on it in their editorial ‘Progressive pulmonary fibrosis: all roads lead to Rome (but not all at the same speed)’ (Eur Respir J 2022;60:2201449). Further background physiology to these concepts is in the article and accompanying editorial ‘What is hidden behind a pulmonary hypertensive, fibrotic and inflammatory phenotype?’ (Eur Respir J 2022;60:2201301). The most positive and clinically practical article is the article on ‘Home monitoring in interstitial lung diseases’ (Lancet Respir Med 2023;11:97–110) where smartphones, wearable technology and lockdown conditions have made a tangible difference. Our Italian colleagues give practical hints in ‘Treatable traits in interstitial lung diseases: a call to action’ (Lancet Respir Med 2023;11:125–8). ‘Pregnancy considerations for patients with interstitial lung disease’ (Chest 2022;162:1093–105) is the first of my three articles for further reading. ‘Diagnosis and management of myositis-associated lung disease (Chest 2023;163:1476– 91) is the second, a practical review article. The final article, which I enjoyed reading, was a reflection on what help general practitioners need to get through the COVID crisis: ‘Resilience among primary care professionals in a time of pandemic: a qualitative study in the Spanish context’ (BMJ Open 2023;13:e069606). The authors provide evidence for: i) active participation in COVID strategies to reach our communities; and ii) regaining a sense of purpose when opening practices. Does this hold true for the Aotearoa situation? Thanks for your readership, comments and feedback. We hope you enjoy the selection. Kind regards, Professor Lutz Beckert [email protected] KINDLY SUPPORTED BY spent reading and evaluating research reviews as CPD in the online MyCPD program. Please contact [email protected] for any assistance. www.researchreview.co.nz a RESEARCH REVIEW™ publication 1 Respiratory RESEARCH REVIEW ™ Silicosis among immigrant engineered stone (quartz) countertop fabrication workers in California Authors: Fazio JC et al. Summary: This case series from the US reported on 52 men, all but one being Latino immigrants and 19% uninsured, who had been diagnosed with silicosis associated with fabrication of engineered stone countertops. The median work tenure for the men was 15 years, and 45% reported use of water suppression for dust mitigation. Alternative initial diagnoses of bacterial pneumonia or tuberculosis led to 58% of these men receiving a delay in their silicosis diagnosis, and 38% had advanced disease at diagnosis, with 18% and 11% having a severe or very severe reduction in forced expiratory volume in 1 sec, respectively. The fatality rate was 19%, with a median age at death of 46 years, while 12% remained alive with chronic resting hypoxia at the time of analysis. Eleven men were referred for lung transplantation, but seven were declined, six of whom died; there was also one death among the three who received their transplant, and another prior to listing. Nearly half the men (48%) continued to work fabricating stone after their silicosis diagnosis. Comment: Silicosis is one of the oldest occupational diseases, and its recurrence in the engineered stone industry is a failure of our medical surveillance systems, public health policies and regulators. As the accompanying editorial details, up to 25% of Australian workers have silicosis and 15% of these progressive massive fibrosis. In this article, the authors describe the dire situation of Latino immigrant workers, who are often uninsured and experience diagnostic delay, 38% of whom first present with progressive massive fibrosis. Bottom line: silicosis is entirely preventable, and the death of 20% of workers, at a mean age of 46 years, is tragic. Reference: JAMA Intern Med 2023;183:991–8 Abstract Claim your CPD points for reading Research Reviews FIND OUT MORE For more information, please go to www.medsafe.govt.nz www.researchreview.co.nz a RESEARCH REVIEW™ publication 2 Respiratory RESEARCH REVIEW ™ Association between the use of statins and risk of interstitial lung disease/idiopathic pulmonary fibrosis Authors: Jang HJ et al. Summary: The association of statin use with development of ILD or IPF was explored in this time-dependent analysis of population-based data from the Korean National Health Insurance Service-Health Screening Cohort. Compared with statin nonusers, statin users had lower incidences of both ILD and IPF (20.0 vs. 48.85 and 15.6 vs. 19.3 per 100,000 person-years, respectively), with a dose dependent effect when cumulative daily doses of <182.5, 182.5–365.0, 365.0–547.5 and ≥547.5 mg per 2-year interval were compared with never-use (respective adjusted HRs for ILD, 1.02 [95% CI 0.87, 1.20], 0.60 [0.47, 0.77], 0.27 [0.16, 0.45] and 0.24 [0.13, 0.42], and for IPF, 1.29 [1.07, 1.57], 0.74 [0.57, 0.96], 0.40 [0.25, 0.64] and 0.21 [0.11, 0.41]). Once a day for 24 hour continuous efficacy 1 25% more patients improve their level of asthma control vs. other commonly used ICS/LABAs *2 no p-value Easy to use device with fewer critical errors ‡ than other commonly used inhalers 3-4** breoellipta.co.nz Find out how being proactive with Breo can help your patients Breo Ellipta is contraindicated in patients with severe milk-protein allergy or who have demonstrated hypersensitivity to fluticasone furoate, vilanterol or any of the excipients. Breo should not be used to treat acute asthma symptoms. Adverse reactions: Very common: Headache and Nasopharyngitis; Common: Pneumonia, Upper Respiratory Tract Infection, Bronchitis, Influenza, Candidiasis of mouth and throat, Oropharyngeal pain, Sinusitis, Pharyngitis, Rhinitis, Cough, Dysphonia, Abdominal pain, Arthralgia, Back pain, Fractures, and Pyrexia. *This was an open-label, randomised, controlled, two-arm effectiveness study of patients aged ≥18 years with symptomatic asthma at 74 general practice clinics in Salford and South Manchester, UK. Patients were assigned to either FF/VI 100/25 or 200/25 OD, or optimised usual care and followed up for 12 months. The primary endpoint was the proportion of ACT responders (improvement from baseline of ≥3 or achieving a total ACT score ≥20) in patients initiated on Breo vs. continuing on usual care (as prescribed by GP) at month 6 in the primary effectiveness analysis population. The primary endpoint was met (p<0.001). Data presented are from a subset of patients prescribed ICS/LABA at baseline initiated on Breo or continued on their ICS LABA: 25% relative difference in responders; 14% absolute difference. In this study there was no difference in serious adverse events reported between Breo and usual care. The most common serious adverse events of special interest were cardiovascular disease, asthma and bronchospasm, and pneumonia.2 ‡ At randomisation, investigators reported that 95% of patients used the inhaler correctly after the initial demonstration of correct usage (week 0), and did not require additional instruction.4 **Fewer asthma patients made critical errors with the Ellipta inhaler after reading the patient information leaflet vs Accuhaler (3/70 (4%) vs 9/70 (13%), p=0.221 NS); MDI (2/32 (6%) vs 8/32 (25%), p=0.074 NS) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60 (33%), p<0.001). References: 1. GlaxoSmithKline New Zealand. Breo Ellipta Data Sheet. GSK NZ; 2021. Available at: https:// medsafe.govt. nz/profs/Datasheet/b/breoelliptainhalation.pdf (Last Accessed on Nov 2021). 2. Woodcock A, et al. Lancet 2017;390:2247–2255. 3. van der Palen J, et al. NJP Prim Care Respir Med 2016;26:1–8 4. Svedsater H, et al. NPJ Prim Care Respir Med 2014;24:14019 ABBREVIATIONS: ACT, Asthma Control Test; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist. Breo Ellipta (fluticasone furoate 100mcg/vilanterol trifenatate 25mcg) is a prescription medicine for the regular treatment of asthma in adults and adolescents aged 12 years and older and for the regular treatment of COPD in adults with a FEV1<70% predicted normal in patients with an exacerbation history. Before prescribing please review the data sheet for information on dosage, contraindications, precautions, interactions and adverse effects. The data sheet is available at www.medsafe.govt.nz. A separate reliever inhaler may be required. Breo Ellipta is not for the relief of acute symptoms. Trademarks are property of their respective owners. ©2023 GSK group companies or its licensor. Breo Ellipta was developed in collaboration with Innoviva Inc. Marketed by GlaxoSmithKline NZ Limited, Auckland. Adverse events involving GlaxoSmithKline products should be reported to GSK Medical Information on 0800 808 500. GlaxoSmithKline NZ Limited, Auckland. TAPS DA2301VL-PM-NZ-FFV-ADVT-220002 Date of Approval: 04 2023 Date of Expiry: 04 2025 GSK00994R CLICK HERE Comment: Both ILD and heart disease are common in older age. Research around whether statins are protective of, or contribute to, ILD is conflicting. These Korean authors used data from more than 500,000 patients with ILD. The authors reported that patients who were not taking statins had almost twice the incidence of developing ILD compared with patients who were taking statins. Although biologically plausible because of its anti-inflammatory activity, I don’t think we should use statins to treat ILD. Bottom line: statin use was associated with a decreased risk of developing ILD or IPF. Reference: Eur Respir J 2023;62:2300291 Abstract Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease Authors: Solomon JJ et al., for the TRAIL1 Network Investigators Summary: Patients aged 18–85 years with RA (rheumatoid arthritis) and ILD were randomised to receive pirfenidone 2403mg (n=63) or placebo (n=60) each day in the phase 2 TRAIL1 trial; slow recruitment in the setting of the COVID-19 pandemic led to early trial termination. There was no significant difference between pirfenidone versus placebo recipients for the proportion who met the composite primary endpoint of decline in FVC percent predicted from baseline of ≥10% or death (11% vs. 15% [p=0.48]), including for the FVC decline component only (8% vs. 12% [p=0.32]), or for the frequency of progression according to Outcome Measures in Rheumatoid Arthritis Clinical Trials (p=0.35); however the rate of lung function decline did significantly favour the pirfenidone arm according to both estimated annual change in absolute FVC (p=0.0082) and FVC percent predicted (p=0.0028). Treatmentemergent serious adverse event rates did not differ significantly between the two groups, and no treatment-related deaths were reported. Comment: Clinically, it makes perfect sense to treat progressive fibrotic lung disease with antifibrotic medications. Athol Wells and colleagues articulated this sentiment in their viewpoint articles ‘Usual interstitial pneumonia as a stand-alone diagnostic entity: the case for a paradigm shift?’ (Lancet Respir Med 2023;11:188–96). Producing the evidence is hard for both nintedanib (Respiratory Research Review Issue 189) and pirfenidone. Because of the slow recruitment during the COVID-19 pandemic, this trial did not meet its primary endpoint. However, it did demonstrate a slowing decline in FVC. Considering more than 16 million people suffer from RA globally, the bottom line is: pirfenidone can be used to treat RA-related ILD. Reference: Lancet Respir Med 2023;11:87–96 Abstract to view the full Healthcare Mandatory Information For more information, please go to www.medsafe.govt.nz www.researchreview.co.nz a RESEARCH REVIEW™ publication 3 Respiratory RESEARCH REVIEW ™ Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL) Authors: Maher TM et al., on behalf of the RECITAL Investigators Summary: Patients aged 18–80 years with severe or progressive ILD related to scleroderma, idiopathic inflammatory myositis or mixed CTD (connective tissue disease) were randomised to intravenous rituximab 1000mg at weeks 0 and 2 (evaluable n=49) or six doses of intravenous cyclophosphamide 600 mg/m2 every 4 weeks (evaluable n=48) in this phase 2b trial. There was no significant difference between rituximab versus cyclophosphamide recipients for 24-week mean improvement in FVC (primary endpoint; 97 vs. 99mL [p=0.49]) or for secondary endpoints (including improvements in lung function and respiratory-related quality of life measures and survival rates), except for change in global disease activity score at week 48, which favoured cyclophosphamide recipients. All on-study deaths were due to CTD or ILD complications. There were numerically fewer adverse events among rituximab recipients than cyclophosphamide recipients (445 vs. 646), with gastrointestinal and respiratory disorders the most commonly reported in both groups. Serious adverse events were reported for 29 rituximab recipients and 33 cyclophosphamide recipients. Comment: Cyclophosphamide has been used for about 60 years and rituximab for about 25 years. This trial was designed to assess the superiority of rituximab over cyclophosphamide in treatment of ILD in patients with CTD. Rituximab was not superior in improving FVC, walking distance, DLCO, K-BILD (Respiratory Research Review Issue 201) or survival. The accompanying editorial puts this RECITAL trial into context of data from the INBUILD studies, and points out some design weaknesses. Bottom line: while not superior to cyclophosphamide, rituximab was associated with fewer side effects and can be considered a therapeutic alternative in patients with CTD-ILD. Reference: Lancet Respir Med 2023;11:45–54 Abstract Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD) Authors: Mankikian J et al., on behalf of the EVER-ILD investigators and the OrphaLung network Summary: Patients with CTD-associated ILD or idiopathic interstitial pneumonia and a nonspecific interstitial pneumonia pattern were randomised to receive rituximab 1000mg (n=63) or placebo (n=59) on days 1 and 15, both with mycophenolate mofetil 2 g/day, for 6 months. Compared with the placebo arm, the rituximab arm had a significant improvement from baseline in FVC percent predicted at 6 months (primary endpoint; least-squares mean change +1.60 vs. –2.01 [p=0.0273]) and significantly better progression-free survival (crude HR 0.47 [95% CI 0.23, 0.96]). The respective incidences of serious adverse events in the rituximab and placebo arms were 41% and 39%, with nine and four infections reported in the respective arms. Comment: Both mycophenolate mofetil and rituximab have been shown to be effective in treating CTD-ILD using different immune pathways. This group of French researchers published a relatively small study of 122 patients with CTD-ILD who received mycophenolate mofetil alone or in combination with rituximab for 6 months. As Elizabeth Volkmann points out in her accompanying editorial, the number of infections almost doubled in the dual treatment group. No deaths were reported in the combination group. Bottom line: the combination of rituximab and mycophenolate mofetil was superior to mycophenolate mofetil alone in patients with CTD-ILD. Reference: Eur Respir J 2023;61:2202071 Abstract Treatment outcomes for rheumatoid arthritis-associated interstitial lung disease Authors: Matson SM et al. Summary: The impact of immunosuppression on pulmonary function trajectory was assessed in a retrospective cohort of real-world patients with RAassociated ILD who had received azathioprine (n=92), mycophenolate mofetil (n=77) or rituximab (n=43). For all three immunosuppressive agents, percent predicted values of FVC and DLCO had increased by 3.90 and 4.56 percentage points, respectively, after 12 months of treatment when compared with the potential 12-month response without treatment (both p≤0.001). The pulmonary function trajectory on immunosuppressants was not affected by UIP pattern of ILD or choice of immunosuppressant. Comment: In the absence of randomised trials, these US researchers pooled data from more than 200 patients with RA-associated ILD from five US centres. The authors reported on the lung function trajectories pre- and post-treatment. Most patients were treated with azathioprine, followed by mycophenolate and rituximab. All three agents improved the FVC and DLCO to a similar degree. Interestingly, neither the choice of agent nor the UIP or non-UIP pattern had an impact on the improvement of the pulmonary function trajectory. Bottom line: these data support the current use of immunosuppressive therapy in patients with RA-associated ILD. Reference: Chest 2023;163:861–9 Abstract This Research Review has been endorsed by The Royal New Zealand College of General Practitioners (RNZCGP) and has been approved for up to 1 CME credit for the General Practice Educational Programme (GPEP) and Continuing Professional Development (CPD) purposes. You can record your CME credits in your RNZCGP Dashboard. Time spent reading this publication has been approved for CNE by The College of Nurses Aotearoa (NZ) for RNs and NPs. For more information on how to claim CNE hours please CLICK HERE. Pharmacy Council of New Zealand - Te Pou Whakamana Kaimatū o Aotearoa Journal reading (including Pharmacy Research Review and other Research Reviews) and completing online activities may be considered a professional development activity as part of the ‘Keeping up to Date Recertification Guidance’. For more information go to - https://pharmacycouncil.org.nz/pharmacist/recertification/ New Zealand Research Review subscribers can claim CPD/CME points for time spent reading our reviews from a wide range of local medical and nursing colleges. Find out more on our CPD page. Independent commentary by Professor Lutz Beckert Professor Lutz Beckert is the Associate Dean Medical Education with the University of Otago, Christchurch. He is also a Respiratory Physician at Canterbury District Health Board with particular clinical interests in interstitial lung disease, pulmonary vascular disease, respiratory physiology and COPD (chronic obstructive pulmonary disease). Lutz is happy to be contacted to discuss research ideas either as a sounding board or with the view of future collaborations. www.researchreview.co.nz Independent Content: The selection of articles and writing of summaries and commentary in this publication is completely independent of the advertisers/ sponsors and their products. Privacy Policy: Research Review will record your email details on a secure database and will not release them to anyone without your prior approval. Research Review and you have the right to inspect, update or delete your details at any time. Disclaimer: This publication is not intended as a replacement for regular medical education but to assist in the process. The reviews are a summarised interpretation of the published study and reflect the opinion of the writer rather than those of the research group or scientific journal. It is suggested readers review the full trial data before forming a final conclusion on its merits. Research Review publications are intended for New Zealand health professionals. a RESEARCH REVIEW™ publication 4 Respiratory RESEARCH REVIEW ™ Incidence of interstitial lung abnormalities Authors: McGroder CF et al. Summary: Trained thoracic radiologists reviewed cardiac CT scan data from 6197 MESA (Multi-Ethnic Study of Atherosclerosis) lung study participants aged >45 years to determine the incidences of newly developed and fibrotic interstitial lung abnormalities; 5% of scans were re-read by the same or a different observer in a blinded manner. The respective intra- and inter-reader agreement values for interstitial lung abnormalities were 92.0% and 83.5%. The respective incidences of interstitial lung abnormalities and fibrotic interstitial lung abnormalities were estimated at 13.1 and 3.5 cases per 1000 person-years. Multivariable analyses revealed that predictors of incident and fibrotic interstitial lung abnormalities were age (respective HRs 1.06 [CI 1.05, 1.08] and 1.08 [1.06, 1.11]), a high attenuation area at baseline (1.05 [1.03, 1.07] and 1.06 [1.02, 1.10]) and the MUC5B promoter single nucleotide polymorphism (1.73 [1.17, 2.56] and 4.96 [2.68, 9.15]); factors associated only with fibrotic interstitial lung abnormalities were ever smoking (2.31 [1.34, 3.96]) and an IPF polygenic risk score (2.09 [1.61, 2.71]). Comment: Up to 20 per 100,000 people develop IPF, the most severe ILD. These authors reviewed the CT scans of more than 10,000 patients who had a cardiac CT scan performed. After careful double reading, they found evidence of some interstitial lung abnormalities in 13 per 1000 cases, i.e. more than 100-fold more common than IPF. When focussing on interstitial lung abnormality findings with a fibrotic nature, risk factors, smoking history and MUC5B promotor gene polymorphism were similar to IPF patients. Bottom line: fibrotic interstitial lung abnormalities were found in 3.5 per 100 person-years, similar to the incidence of chronic obstructive pulmonary disease. Reference: Eur Respir J 2023;61:2201950 Abstract Each month we highlight a particularly excellent paper with our butterfly symbol. Association of particulate matter exposure with lung function and mortality among patients with fibrotic interstitial lung disease Authors: Goobie GC et al. Summary: Associations of PM2.5 (particular matter ≤2.5µm in diameter) exposure with mortality and lung function were examined across three prospective cohorts comprising 6683 patients with fibrotic ILD. Over a median of 2.9 years of followup, 28% died and 10% underwent lung transplantation. The mortality risk was significantly higher for individuals with PM2.5 exposure of ≥8 µg/m3 (HRs 1.71– 4.40 across cohorts). The most adverse mortality and lung function outcomes tended to be associated with exposure to sulfates, nitrates and ammonium. Metaanalyses revealed consistent associations of sulfate or ammonium exposure with mortality and declines in FVC and DLCO, as well as associations between increasing PM2.5 multiconstituent mixture exposure levels and all outcomes. Comment: According to the Global Burden Studies, diseases attributable to ambient air pollution and fine airborne particles are estimated to be responsible for 4.2–8.9 million premature deaths annually. Satellite-derived models have tracked this pollution to fossil fuel industries and agriculture. PM2.5 is associated with adverse outcomes in IPF. These US authors reviewed data from more than 5000 patients with fibrotic ILD and correlated clinical outcomes with the degree of PM2.5 exposure across North America. Bottom line: the higher the PM2.5, the worse the baseline fibrosis, disease progression and mortality. Reference: JAMA Intern Med 2022;182:1248–59 Abstract National temporal trends in hospitalization and inpatient mortality in patients with pulmonary sarcoidosis in the United States between 2007 and 2018 Authors: Alqalyoobi S et al. Summary: These researchers explored temporal trends in hospitalisation and inpatient mortality in patients with pulmonary sarcoidosis and respiratory failure in an analysis of US hospitalisation data. They found that over the period from 2007 to 2018, hospitalisations in patients with pulmonary sarcoidosis increased from 258.5 to 705.7 per 1,000,000, hospitalisations for respiratory failure increased from 25.9 to 239.4 per 1,000,000 hospitalisations, and the need for mechanical ventilation increased from 9.4 per to 29.4 per 1,000,000. The any-cause inpatient mortality rate was 2.6%, but patients with respiratory failure and those requiring mechanical ventilation had higher rates (10.6% vs. 0.8% and 31.2% vs. 1.2%, respectively). A decline was seen for inpatient mortality associated with respiratory failure from 17.2% in 2007 to 6.6% in 2018. Independent predictors of inpatient mortality were older age (adjusted HR 1.025), respiratory failure (3.12), need for mechanical ventilation (6.01), pulmonary hypertension (1.44), pulmonary embolism (1.61) and frailty (3.10). Comment: Sarcoidosis is a rare inflammatory, granulomatous disease of unknown origin that predominantly affects the lungs. Clinical manifestations vary from being asymptomatic to chronic progressive life-threatening fibrosis. The life-time risk of death in patients with sarcoidosis is between 2% and 9%. These US authors reviewed the admission data of almost 250,000 patients with pulmonary sarcoidosis over a 10-year period. Although the hospitalisation rate increased three-fold during the study interval, the overall mortality more than halved. Bottom line: prospective studies need to confirm these findings. It appears that patients with sarcoidosis are now older with more comorbidities like low BMI, pulmonary emboli and frailty. Reference: Chest 2022;161:152–68 Abstract Palliative care for interstitial lung disease Authors: Fujisawa T et al. Summary: This nationwide survey of pulmonary specialists from Japan evaluated palliative care for ILD; of 3423 specialists sent the survey, 1032 completed it and provided data for analysis. Most respondents stated that patients with ILD often or always reported dyspnoea and cough to them, but only 25% provided a palliative care team referral. There was a tendency for the timing of end-oflife communication to be later than the ideal timing perceived by physicians. Respondents reported that symptomatic relief and decision-making in palliative care was more difficult for patients with ILD when compared with those with lung cancer, and patients with ILD were prescribed opioids for dyspnoea less frequently. The respondents reported the following barriers to palliative care for patients with ILD: inability to predict prognosis, lack of established dyspnoea treatments, shortage of psychological and social support, and difficulty for patients/families to accept the poor prognosis of ILD. Comment: Patients with advanced fibrotic lung diseases have a poor prognosis and high symptom burden despite appropriate pharmacotherapy. IPF patients have poorer access to palliative care and lower quality of dying and death. In this article, the authors contacted half of all certified respiratory physicians in Japan to explore current practice, optimal practice, comparisons with lung cancer and perceived barriers in providing palliative care for patients with ILD. This article contains beautiful graphs on the aspirations and realities of care. Bottom line: respiratory specialists experience more difficulties providing palliative care for patients with ILD than patients with lung cancer. Reference: Respirology 2023;28:659–68 Abstract CLICK HERE to read previous issues of Respiratory Research Review www.researchreview.co.nz © 2023 RESEARCH REVIEW a RESEARCH REVIEW™ publication 5