Epidemiology and Prognostic Significance of Cough in Fibrotic Interstitial Lung Disease.

Rationale: Cough is a key symptom in patients with fibrotic interstitial lung disease (ILD). Objective: This study evaluated the prevalence, longitudinal change, associations, and prognostic significance of cough severity in patients with fibrotic ILD. Methods: We included consecutive patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD who completed the 100mm-Cough Severity Visual Analog Scale (VAS) from the prospective multi-center Canadian Registry for Pulmonary Fibrosis. Baseline cough severity and associations with patient demographics and clinical factors were determined. Relationships between baseline cough severity and health outcomes were evaluated. Measurements and Main Results: Patients with IPF (n=1061) had higher median baseline cough severity than those with non-IPF fibrotic ILD (n=2825) [24 vs 20mm, p<0.001], with worse cough associated with gastroesophageal reflux disease for both cohorts. Worse cough severity was independently associated with worse health-related quality of life at baseline, larger annualized decline in DLCO, development of disease progression, and reduced transplant-free survival in both IPF and non-IPF fibrotic ILD cohorts. The IPF cohort (2.2mm, 95% CI 1.6-2.9mm) had larger annualized increments in cough severity compared to the non-IPF fibrotic ILD cohort (1.1mm, 95% CI 0.8-1.4mm; p=0.004). There was no difference in worsening cough over time comparing those receiving and not receiving ILD-targeted therapy or with and without lung function decline. Conclusion: Cough is common in patients with IPF and non-IPF fibrotic ILD, with increasing cough severity over time irrespective of ILD-targeted therapy. Patient-reported cough severity has prognostic implications on health-related quality of life, disease progression, and survival in fibrotic ILD.

Arterial blood gas analysis or venous blood gas analysis for adult hospitalised patients with respiratory presentations: a systematic review.

BACKGROUND: Identification of hypoxaemia and hypercapnia is essential for the diagnosis and treatment of acute respiratory failure. While arterial blood gas (ABG) analysis is standard for PO2 and PCO2 measurement, venous blood gas (VBG) analysis is increasingly used as an alternative. Previous systematic reviews established that VBG reporting of PO2 and PCO2 is less accurate, but the impacts on clinical management and patient outcomes are unknown. AIMS: This study aimed to systematically review available evidence of the clinical impacts of using ABGs or VBGs and examine the arteriovenous difference in blood gas parameters. METHODS: A comprehensive search of the MEDLINE, Embase and Cochrane Library databases since inception was conducted. Included studies were prospective or cross-sectional studies comparing peripheral ABG to peripheral VBG in adult non-critical care inpatients presenting with respiratory symptoms. RESULTS: Of 15 119 articles screened, 15 were included. No studies were found that examined clinical impacts resulting from using VBG compared to ABG. Included studies focused on the agreement between ABG and VBG measurements of pH, PO2, PCO2 and HCO3 -. Due to the heterogeneity of the included studies, qualitative evidence synthesis was performed. While the arteriovenous difference in pH and HCO3 - was generally predictable, the difference in PO2 and PCO2 was more significant and less predictable. CONCLUSIONS: Our study reinforces the notion that VBG is not comparable to ABG for physiological measurements. However, a key revelation from our research is the significant lack of data regarding the clinical implications of using VBG instead of ABG, a common scenario in clinical practice. This highlights a critical knowledge gap.

Navigating the COVID-19 pandemic: Experiences and self-management approaches adopted by people with interstitial lung disease.

BACKGROUND: People with interstitial lung disease (ILD) were deemed more vulnerable to the SARS-CoV-2 virus and isolated as a means of reducing risk of infection. This study examined the impact of the pandemic on daily life, psychological wellbeing and access to healthcare and identified approaches undertaken to remain safe. METHODS: Four specialist clinics in tertiary centres in Australia (Victoria: two sites; New South Wales: one site; Western Australia: one site) recruited patients with ILD during an 8-week period from March 2021. Semi-structured telephone interviews were conducted with transcripts analysed using principles of grounded theory. RESULTS: Ninety participants were interviewed between April and December 2021. Participants were predominantly female, former smokers with an average age of 66 years. IPF and connective tissue-ILD being the most common subtypes. Five main themes were identified: vulnerability reduced social interaction and isolation, access to healthcare services and support, staying active, emotional and psychological impact. Self-management strategies included staying active both physically and mentally. DISCUSSION: Self-management was key to managing the impact of the pandemic. In combination with advances in technology, implementation of strategies for monitoring wellbeing and support for self-management provides an opportunity to leverage the lessons learnt to ensure a more individualised model of care for people with ILD.

Treatable traits: a comprehensive precision medicine approach in interstitial lung disease.

Interstitial lung disease (ILD) is a diverse group of inflammatory and fibrotic lung conditions causing significant morbidity and mortality. A multitude of factors beyond the lungs influence symptoms, health-related quality of life, disease progression and survival in patients with ILD. Despite an increasing emphasis on multidisciplinary management in ILD, the absence of a framework for assessment and delivery of comprehensive patient care poses challenges in clinical practice. The treatable traits approach is a precision medicine care model that operates on the premise of individualised multidimensional assessment for distinct traits that can be targeted by specific interventions. The potential utility of this approach has been described in airway diseases, but has not been adequately considered in ILD. Given the similar disease heterogeneity and complexity between ILD and airway diseases, we explore the concept and potential application of the treatable traits approach in ILD. A framework of aetiological, pulmonary, extrapulmonary and behavioural and lifestyle treatable traits relevant to clinical care and outcomes for patients with ILD is proposed. We further describe key research directions to evaluate the application of the treatable traits approach towards advancing patient care and health outcomes in ILD.

Eligibility criteria from pharmaceutical randomised controlled trials of idiopathic pulmonary fibrosis: a registry-based study.

BACKGROUND: Little is known about generalisability of randomised controlled trials (RCTs) for idiopathic pulmonary fibrosis (IPF). We evaluated eligibility criteria for phase III IPF RCTs to determine their representativeness in clinical registries, and calculated forced vital capacity (FVC) changes according to eligibility criteria. METHODS: Common eligibility criteria used in >60% of IPF RCTs were identified from a literature search and applied to patients with IPF from prospective Australian and Canadian registries. Additional pre-specified criteria of 6-min walk distance (6MWD) and different measures of preceding disease progression were also evaluated. Joint longitudinal-survival modelling was used to compare FVC decline according to eligibility for individual and composite criteria. RESULTS: Out of 990 patients with IPF, 527 (53%) met all common RCT eligibility criteria at the first clinic visit, including 343 with definite IPF and 184 with radiological probable usual interstitial pneumonia pattern without histological confirmation (i.e. provisional IPF). The percentages of eligible patients for landmark RCTs of nintedanib and pirfenidone were 19-50%. Adding 6MWD ≥150 m and different measures of preceding disease progression to the composite common criteria reduced the percentages of patients meeting eligibility to 52% (n=516) and 4-18% (n=12-61), respectively. Patients meeting the composite common criteria had less-rapid 1-year FVC decline than those who did not (-90 versus -103 mL, p=0.01). Definite IPF generally had more-rapid 1-year FVC decline compared to provisional IPF. CONCLUSIONS: Eligibility criteria of previous IPF RCTs have limited generalisability to clinical IPF populations, with FVC decline differing between eligible and ineligible populations.

Telerehabilitation in pulmonary diseases.

PURPOSE OF REVIEW: Telerehabilitation is an alternative delivery model for pulmonary rehabilitation, an evidence-based nonpharmacological intervention, in people with chronic pulmonary disease. This review synthesizes current evidence regarding the telerehabilitation model for pulmonary rehabilitation with an emphasis on its potential and implementation challenges, as well as the clinical experiences from the COVID-19 pandemic. RECENT FINDINGS: Different models of telerehabilitation for delivering pulmonary rehabilitation exist. Current studies comparing telerehabilitation to centre-based pulmonary rehabilitation primarily focus on the evaluation in people with stable chronic obstructive pulmonary disease, which demonstrated equivalent improvements in exercise capacity, health-related quality of life and symptoms with improved programme completion rates. Although telerehabilitation may improve access to pulmonary rehabilitation by addressing travel burden, improving schedule flexibility and geographic disparity, there are challenges of ensuring satisfaction of healthcare interactions and delivering core components of initial patient assessment and exercise prescription remotely. SUMMARY: Further evidence is needed on the role of telerehabilitation in various chronic pulmonary diseases, as well as the effectiveness of different modalities in delivering telerehabilitation programmes. Economic and implementation evaluation of currently available and emerging models of telerehabilitation in delivering pulmonary rehabilitation are needed to ensure sustainable adoption into clinical management for people with chronic pulmonary disease.

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

Clinical assessment for pulmonary hypertension in interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) is an important complication of interstitial lung disease (ILD), as its development confers a poor prognosis. There are no specific recommendations for methods of assessment for PH in ILD populations. AIMS: To determine current assessment practices for PH in an Australian ILD centre. METHODS: In the Austin Health ILD database, 162 consecutive patients with idiopathic pulmonary fibrosis or connective tissue disease-associated ILD were identified and retrospectively evaluated for methods of PH assessment with transthoracic echocardiography (TTE), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and right heart catheterisation (RHC) in relation to patient demographic and physiological parameters. RESULTS: The median follow-up was 30 (14.4-56.4) months. At baseline, vital capacity was 80.0 ± 18.4% predicted, and diffusing capacity for carbon monoxide was 59.6 ± 15.2% predicted. Evaluation for PH was performed in 147 (90.7%) patients, among whom 105 (64.8%) had TTE performed at least once. At the initial TTE, 33.7% patients had high probability of PH, defined as RVSP >40 mmHg + RAp and/or right ventricular dysfunction. At the time of the most recent TTE, these criteria were met in 45 (52.3%) patients. Elevated serum NT-proBNP levels during the first year were observed in 47 (38.8%) patients. Only 14 (8.6%) patients had RHC. CONCLUSION: Our institutional PH assessment practice in ILD demonstrates a substantial prevalence of probable PH at baseline. As new therapies emerge for the treatment of PH in ILD, well-defined screening practices are important in this population for early identification and optimal management.

Understanding the telehealth experience of care by people with ILD during the COVID-19 pandemic: what have we learnt?

INTRODUCTION: The COVID-19 pandemic resulted in a rapid transformation of health services. This study aimed to understand the experiences of healthcare by people with interstitial lung disease (ILD), to inform future service delivery. METHODS: Four specialist clinics in tertiary centres in Australia (Victoria:2 sites; New South Wales: 1 site; Western Australia: 1 site) recruited patients with ILD during an 8-week period from March 2021. Participants completed a COVID-specific questionnaire focused on health-related experiences during 2020. RESULTS: Ninety nine (65% of 153) participants completed the questionnaire. 47% had idiopathic pulmonary fibrosis or connective tissue disease-associated ILD, 62% were female and the average age was 66 years. Whilst 56% rated their overall health in 2020 as the same as months prior, 38% indicated a worsening in health attributed to reduced physical activity and fear of contracting the virus. Access to healthcare professionals was 'good' in 61%, and 'fair-to-poor' for 37% due to missed respiratory assessments, with telehealth (mainly telephone) being perceived as less effective. 89% had contact with respiratory physicians, 68% with general practitioners, predominantly via telephone, with few video consultations. High satisfaction with care was reported by 78%, with lower satisfaction attributed to delays in assessments, disruption to usual services such as pulmonary rehabilitation, and dissatisfaction with telehealth. CONCLUSION: People with ILD were generally satisfied with their care during 2020, however reduced access to healthcare professionals was challenging for those experiencing a deterioration in health. Telehealth was largely well received but did not always meet the needs of people with ILD particularly when unwell.

Oxygen for interstitial lung diseases.

PURPOSE OF REVIEW: Supplemental oxygen therapy is prescribed for management of hypoxaemia in patients with interstitial lung disease (ILD). This review summarizes current evidence and implications of the use of supplemental oxygen therapy at home and during exercise training in ILD. RECENT FINDINGS: Despite the significance of hypoxaemia in patients with ILD, there is a lack of high-quality evidence to guide the use of oxygen therapy in this population. Recent studies suggest that ambulatory oxygen may improve symptoms and health-related quality of life in patients with ILD. Long-term oxygen therapy for resting hypoxaemia in ILD is recommended by international guidelines. Supplemental oxygen during exercise may augment training effects, whereas therapeutic effects of nocturnal oxygen therapy are yet to be evaluated in patients with ILD. Nevertheless, it is important to consider the potential burden imposed by oxygen therapy on patients' daily activities of living. SUMMARY: Ambulatory oxygen may be considered in ILD patients with exertional hypoxaemia, with long-term oxygen therapy being a standard care for resting hypoxaemia. Trials are currently underway to clarify therapeutic potentials of supplemental oxygen for exertional hypoxaemia and during exercise training in ILD patients, with additional research needed for the evaluation of nocturnal oxygen therapy.

Peer Connect Service for people with pulmonary fibrosis in Australia: Participants' experiences and process evaluation.

BACKGROUND AND OBJECTIVE: People living with pulmonary fibrosis (PF) report unmet needs for information and support. Lung Foundation Australia (LFA) have developed the Peer Connect Service to facilitate telephone support for people with PF across Australia. This project documented the experiences of participants and the resources required to support the service. METHODS: Consenting participants took part in semi-structured interviews by telephone. Primary peers (peers who agreed to initiate contact) and secondary peers (eligible patients who sought a peer match) were interviewed. Thematic analysis was undertaken by two independent researchers. Data were collected on the number of matches and contacts required to establish each match. RESULTS: Interviews were conducted with 32 participants (16 primary peers, 15 secondary peers and 1 who was both), aged from 53 to 89 years with 56% being male. Major themes included the value of shared experiences, providing mutual support and the importance of shared personal characteristics (e.g. gender and hobbies) in allowing information and emotional support needs to be met. Participants saw face-to-face contact with peers as highly desirable whilst acknowledging the practical difficulties. Primary peers were cognizant that their role was not to provide medical advice but to listen and share experiences. In the 12-month period, 60 peer matches were made, each match requiring a minimum of seven staff contacts. CONCLUSION: The Peer Connect Service provides a unique opportunity for people with PF to share experiences and offer mutual support. This telephone matching model may be useful in providing peer support for individuals with rare diseases who are geographically dispersed.

Therapeutic burden in interstitial lung disease: Lessons to learn.

BACKGROUND AND OBJECTIVE: Patients with interstitial lung disease (ILD) are often prescribed disease-targeted and symptomatic therapies, both of which can cause significant treatment burden due to polypharmacy and drug-disease interactions. This study aimed to evaluate medication regimen complexity before and after introduction of ILD-specific therapies. Potential drug-disease interactions were evaluated for patients who were prescribed prednisolone. METHODS: In this study, 214 patients with ILD were assessed for demographic information, co-morbidities and medication use. Medication lists were reviewed prior to and after the introduction of ILD-specific therapies. Complexity of treatment regimen was examined using the validated Medication Regimen Complexity Index (MRCI). RESULTS: Of the 214 patients, 75 had idiopathic pulmonary fibrosis (IPF) while the rest had inflammatory ILD (chronic hypersensitivity pneumonitis: 45; connective tissue disease-related ILD: 41). Polypharmacy was common at baseline (IPF: 51%, inflammatory ILD: 63%). Following introduction of ILD-specific therapies, median total MRCI scores significantly increased from 8 (interquartile range (IQR) = 8-15) to 22.5 (17.5-27.5) and 14.5 (8.5-21) to 21.5 (16-30) for IPF and inflammatory ILD groups, respectively (P < 0.0001 for both). Complex dosing instructions contributed the most to total MRCI scores for ILD-specific therapies. Among patients receiving prednisolone (n = 113), 88% had ≥1 co-morbidity which may be impacted. Common co-morbidities included gastrointestinal diseases (56%), obesity (37%), osteoporosis (24%) and diabetes mellitus (18%). CONCLUSION: Polypharmacy and complex medication regimen are common in patients with ILD of different aetiologies. There is a high frequency of potential drug-disease interactions among patients who are prescribed systemic corticosteroids. These findings highlight the need for careful evaluation of the impact of therapeutic complexity and burden in patients with ILD.

Portable oxygen concentrators versus oxygen cylinder during walking in interstitial lung disease: A randomized crossover trial.

BACKGROUND AND OBJECTIVE: Ambulatory oxygen therapy is often provided to patients with interstitial lung disease (ILD). Lightweight portable oxygen concentrators (POCs) provide an alternative to traditional portable systems such as compressed oxygen cylinders; however, their efficacy in patients with ILD has not been assessed. This study aimed to evaluate the clinical performance of three ambulatory oxygen systems (two different POCs and a compressed oxygen cylinder) during 6-min walk tests (6MWTs) in patients with ILD and exertional desaturation. METHODS: A total of 20 participants with ILD of varying aetiologies who demonstrated exertional desaturation to <90% on room air during 6MWT were recruited. Each participant performed two 6MWTs while breathing room air. On a subsequent day, two further 6MWTs were performed, in random order: one breathing oxygen via a POC (either the Inogen One G2 POC or the EverGo POC at the setting of 6) and one with a compressed oxygen cylinder (at 5 L/min). RESULTS: There were no significant differences in nadir oxygen saturation (SpO2 ) during 6MWTs using different portable oxygen devices (Trial 1: mean SpO2 for Inogen One G2 POC: 82.3 ± 3.5% vs oxygen cylinder: 80.3 ± 2.2%, P = 0.14; Trial 2: mean SpO2 for EverGo POC: 85.7 ± 7.7% vs oxygen cylinder: 86.1 ± 6.1%, P = 0.79). The mean 6-min walk distances were not significantly different among the three devices. CONCLUSION: The performance of the Inogen One G2 POC and the EverGo POC had comparable performance with that of the compressed oxygen cylinder during walking in patients with ILD and exertional desaturation.