Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases.

BACKGROUND: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD). METHODS: Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure. RESULTS: The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results. CONCLUSION: By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.

Perceptions of Individuals With Chronic Lung Disease on Home Use of Pulse Oximetry.

BACKGROUND: Pulse oximeters are often used at home by patients with chronic respiratory diseases and more recently for remote monitoring of patients with COVID-19. There are no published data outside a supervised telemedicine setting regarding patients' experiences with these devices. Our objective was to explore patients' usage patterns and perceptions of using pulse oximetry at home. METHODS: Patients with chronic respiratory disease who had a pulse oximeter at home were recruited to complete a structured survey. RESULTS: Thirty participants with a range of chronic respiratory diseases (mean age 71 y, 16 females) were recruited. Most participants (83%) used home oxygen therapy. Pulse oximeters were bought online (46.7%), at a pharmacy (40%), at a medical equipment store (6.7%), through a clinic (3.3%), or from an oxygen supplier (3.3%). Use was self-initiated in 56.7% of cases and was based on a health care-related recommendation in 26.7% of cases. Sixty percent of participants used the oximeter daily, with 90% expressing confidence in interpreting their oximeter readings primarily due to education from health care professionals and in-patient experiences. Almost all participants adjusted their activity levels or management based upon oximeter readings. Most participants reported that using a pulse oximeter at home was helpful in judging their physical limitations and provided reassurance and confidence in their disease management. CONCLUSIONS: Subjects appeared confident in their use of home pulse oximetry. Health professionals should identify patients who use pulse oximeters for monitoring and ensure that they are able to interpret readings correctly and, if appropriate, adjust management safely.

Multidisciplinary Care and Prognosis in Patients With COPD and Interstitial Lung Disease Prescribed Long-Term Oxygen Therapy.

BACKGROUND: Home oxygen therapy is prescribed for patients with advanced lung disease based on the criteria established in landmark trials in subjects with COPD. In clinical practice, its use has been extrapolated to other diseases, including interstitial lung disease (ILD). Patients with COPD and ILD experience a high symptom burden and require access to specialized multidisciplinary care. We aimed to evaluate the health-related outcomes and supportive care needs of patients with COPD and ILD receiving home oxygen therapy. METHODS: This was a retrospective cohort study using the oxygen database of a quaternary metropolitan teaching hospital. Patients with a diagnosis of COPD or ILD who were prescribed home oxygen therapy between January 2012-December 2018 were identified. Demographic information, results of physiologic testing, comorbidities, hospitalizations, and mortality data were collected. RESULTS: Three hundred and eighty-four subjects were included for analysis, of whom 56% were male. The median age was 75 y. The majority (59%) had a diagnosis of COPD. Long-term oxygen therapy (LTOT) was prescribed for 187 (48.7%), with no significant demographic differences between those with COPD or ILD. Another 187 were prescribed ambulatory oxygen alone, with 55 transitioning to LTOT during the study period. Most subjects (65.4%) were referred for pulmonary rehabilitation; however, palliative care referrals were generally low (22.9%). Referrals to other medical specialties and allied health were common (82%). Transplant-free survival after commencement of LTOT was poor, with 38% of subjects surviving at 5 y. The 5-y survival of subjects with ILD after commencing on LTOT was 10% compared to 52% for those with COPD. Multivariable Cox regression analyses showed that the only predictor of survival after commencing LTOT was the principal respiratory diagnosis. CONCLUSIONS: This study found that subjects prescribed LTOT had poor transplant-free survival after initiation, which was significantly worse for those with ILD compared to those with COPD. Despite their poor overall survival, worse than many cancers, only a minority were referred for palliative care input. Referrals to pulmonary rehabilitation were also suboptimal. This patient population had complex care needs requiring multidisciplinary management. Appropriate and early referrals to palliative care and improved care coordination for this complex group of patients are key areas for improvement in clinical practice.

Excess iron promotes emergence of foamy macrophages that overexpress ferritin in the lungs of silicosis patients.

BACKGROUND AND OBJECTIVE: Inhalation of high concentrations of respirable crystalline silica (RCS) can lead to silicosis. RCS contains varying levels of iron, which can cause oxidative stress and stimulate ferritin production. This study evaluated iron-related and inflammatory markers in control and silicosis patients. METHODS: A cohort of stone benchtop industry workers (n = 18) were radiologically classified by disease severity into simple or complicated silicosis. Peripheral blood and bronchoalveolar lavage (BAL) were collected to measure iron, ferritin, C-reactive protein, serum amyloid A and serum silicon levels. Ferritin subunit expression in BAL and transbronchial biopsies was analysed by reverse transcription quantitative PCR. Lipid accumulation in BAL macrophages was assessed by Oil Red O staining. RESULTS: Serum iron levels were significantly elevated in patients with silicosis, with a strong positive association with serum ferritin levels. In contrast, markers of systemic inflammation were not increased in silicosis patients. Serum silicon levels were significantly elevated in complicated disease. BAL macrophages from silicosis patients were morphologically consistent with lipid-laden foamy macrophages. Ferritin light chain (FTL) mRNA expression in BAL macrophages was also significantly elevated in simple silicosis patients and correlated with systemic ferritin. CONCLUSION: Our findings suggest that elevated iron levels during the early phases of silicosis increase FTL expression in BAL macrophages, which drives elevated BAL and serum ferritin levels. Excess iron and ferritin were also associated with the emergence of a foamy BAL macrophage phenotype. Ferritin may represent an early disease marker for silicosis, where increased levels are independent of inflammation and may contribute to fibrotic lung remodelling.

Online Patient Information on Domiciliary Oxygen Therapy: An Evaluation of Quality, Suitability, Reliability, Readability, and Content.

BACKGROUND: Domiciliary oxygen therapy (DOT) is a complex intervention and has significant impact on patients' daily activities, quality of life, and mental well-being. Suitable education is pertinent in improving patients' understanding and use of DOT, because those receiving appropriate education have a better knowledge of their prescription, clearer expectations, and improved adherence to DOT. RESEARCH QUESTION: Do currently available online patient resources on DOT provide high-quality information for patients? STUDY DESIGN AND METHODS: We evaluated the first 100 results of three major search engines (Google, Yahoo, and Bing) using the terms home oxygen therapy and information or education. Website content was assessed based on Thoracic Society of Australia and New Zealand and British Thoracic Society domiciliary oxygen guidelines. Validated tools were used to evaluate resource quality (DISCERN instrument), suitability (Suitability Assessment of Materials [SAM]), reliability (Journal of the American Medical Association [JAMA] benchmarks and the Health on the Net [HON] code], and readability (Flesch Reading Ease and Flesch-Kincaid Grade Level). RESULTS: Thirty-six websites met study inclusion criteria. Websites from foundation or advocacy organizations scored the highest in quality and suitability, with a median DISCERN total score of 48.0 (interquartile range [IQR], 43.5-60.0), or fair, and a median SAM suitability score of 70% (IQR, 53.0%-71.0%), or superior. Industry or for-profit websites had the best content score of 7.8 (IQR, 5.0-8.6). The HON accreditation seal was present on 14% of the websites, and only five websites met the four JAMA benchmarks. The median readability scores exceeded the recommended reading grades of sixth to eighth level for consumer health-related educational resources. INTERPRETATION: The overall quality, suitability, reliability, and content of online health resources for DOT are of a low to moderate standard, with the reading grade at an unsuitable level for the general population. Health professionals should be aware of the limitations of currently available online DOT patient resources.

Nocturnal hypoxaemia in interstitial lung disease: a systematic review.

BACKGROUND: Patients with interstitial lung disease (ILD) are at risk of developing nocturnal hypoxaemia due to ventilatory restriction and impaired gas exchange that worsen with supine posture and reduced ventilatory drive during sleep. This systematic review synthesised literature on the diagnostic evaluation, epidemiology, associations, management and prognosis of nocturnal hypoxaemia in ILD. METHODS: Ovid MEDLINE, Embase and CENTRAL databases were searched for eligible studies. Meta-analyses with subgroup analyses were conducted, where possible. RESULTS: Fifty-three studies were included (total participant number=2590). The most common definition for clinically significant nocturnal hypoxaemia was ≥10% of total sleep time with oxyhaemoglobin saturation <90%, with pooled prevalence of 37%. There were no significant differences in pooled prevalence according to ILD subtype and comorbid obstructive sleep apnoea status. Study heterogeneity precluded meta-analysis of associations and prognosis. Diffusing capacity for carbon monoxide (DLCO) and echocardiographic features for pulmonary hypertension were consistently associated with nocturnal hypoxaemia. There were inconsistent associations between nocturnal hypoxaemia with ILD subtype and severity. Multivariable analyses in most studies demonstrated significant associations of nocturnal hypoxaemia with survival. Two small short-term intervention studies demonstrated that supplemental oxygen of 1-3 L/min corrected nocturnal hypoxaemia, with improved heart rate control during in-laboratory observation and increased serum antioxidant levels after 1 month of therapy. CONCLUSION: Nocturnal hypoxaemia is common, associated with DLCO impairment and markers suggestive of pulmonary hypertension, and a potential prognostic factor in patients in ILD. There is a need to establish a consensus definition of nocturnal hypoxaemia and evaluate long-term effects of nocturnal supplemental oxygen in ILD.

Cough in Idiopathic Pulmonary Fibrosis.

Chronic cough is experienced by most patients with idiopathic pulmonary fibrosis (IPF). It is often the first symptom and is associated with reduced quality of life, increased rates of depression and anxiety, more severe physiological impairment, and disease progression. Although not fully understood, recent gains in understanding the pathophysiology of chronic cough in IPF have been made. The pathophysiology is likely multifactorial and includes alterations in mucous production and clearance, architectural distortion, and increased cough reflex sensitivity, suggesting a role for targeted therapies and multidisciplinary treatment. Modifiable comorbidities can also induce cough in patients with IPF. There is a renewed emphasis on measuring cough in IPF, with clinical trials of novel and repurposed therapies for chronic cough emerging in this population. This review provides an update on the clinical characteristics, pathophysiology, and measurement of chronic cough in patients with IPF and summarizes recent developments in non-pharmacological and pharmacological therapies.

Post-Hospitalization Short-Term Oxygen Therapy: Use of a Clinical Management Pathway and Long-Term Follow-Up.

BACKGROUND: Home oxygen therapy is commonly prescribed for patients who remain hypoxemic at hospital discharge, although evidence supporting this practice is lacking. This study aimed to evaluate oxygen prescription and follow-up for patients who were prescribed post-discharge short-term oxygen therapy (STOT) and to assess their long-term outcome. METHODS: A retrospective audit was undertaken of subjects prescribed STOT following hospitalization at a single site in Melbourne, Australia, between January 2011 and December 2015. During the study period, a designated clinical pathway for STOT prescription and follow-up after hospital discharge was in place. Chart review was performed to collect subject demographics and comorbidities, results of oxygen assessment (arterial blood gas and 6-min walk tests) and prescription, and results at follow-up re-assessment and mortality. RESULTS: Over five 5 years, 205 subjects were prescribed STOT upon hospital discharge. Common indications for oxygen treatment were chronic lung disease (54%) and dyspnea palliation (26%). Of the 152 subjects who were discharged with non-palliative oxygen therapy, 28% did not fulfil the recommended prescribing criteria or did not have recommended assessments. Among the 118 subjects who returned for re-assessment 4 weeks after initial oxygen provision, 47 (40%) did not fulfill criteria for long-term oxygen therapy. The 1-y cumulative survival rate for the study population was 56%. CONCLUSIONS: A significant proportion of subjects who were prescribed post-discharge STOT did not fulfill the recommended prescribing criteria. The long-term prognosis for subjects who were prescribed post-discharge STOT was poor.

Exertional Desaturation and Prescription of Ambulatory Oxygen Therapy in Interstitial Lung Disease.

BACKGROUND: Exertional desaturation is an important predictor of mortality in patients with interstitial lung disease. We evaluated the prevalence of exertional desaturation in subjects with interstitial lung disease and determined its relationship with the prescription of ambulatory oxygen therapy. METHODS: Our retrospective analysis examined prospectively collected data from interstitial lung disease registries of 2 Melbourne hospitals: Alfred Health and Austin Health. All patients with baseline the 6-min walk tests on room air were included. We evaluated the prescription of ambulatory oxygen therapy, up to 3 months after 6-min walk tests, among those with exertional desaturation. RESULTS: Of the 400 subjects, 214 (54%) had exertional desaturation. The prevalence of desaturation increased with the severity of lung function impairment (FVC measurement: 33% for > 75% predicted, 69% for 50-75% predicted, 86% for < 50% predicted; diffusing capacity of the lung for carbon monoxide measurement: 20% for > 55% predicted, 64% for 36-55% predicted, 93% for ≤ 35% predicted, P < .001 for both severity classifications). There was no difference in the prevalence of exertional desaturation among common disease subtypes (P = .17). Among the desaturators, 14 (7%) had resting hypoxemia and all were prescribed long-term oxygen therapy. Of the remaining 200 with exertional desaturation only, 58 (29%) were prescribed ambulatory oxygen therapy. Multiple logistic regression showed independent associations between the ambulatory oxygen therapy prescription and shorter 6-min walk distance (P < .001) as well as worse FVC (% predicted, P = .037). CONCLUSIONS: Exertional desaturation is common in subjects with interstitial lung disease. More severely impaired exercise capacity and worse lung function are associated with the prescription of ambulatory oxygen therapy in interstitial lung disease.