The Clinical Frailty Scale for Risk Stratification in Patients With Fibrotic Interstitial Lung Disease.

BACKGROUND: Previous studies have shown the importance of frailty in patients with fibrotic interstitial lung disease (ILD). RESEARCH QUESTION: Is the Clinical Frailty Scale (CFS) a valid tool to improve risk stratification in patients with fibrotic ILD? STUDY DESIGN AND METHODS: Patients with fibrotic ILD were included from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. The CFS was assessed using available information from initial ILD clinic visits. Patients were stratified into fit (CFS score 1-3), vulnerable (CFS score 4), and frail (CFS score 5-9) subgroups. Cox proportional hazards and logistic regression models with mixed effects were used to estimate time to death or lung transplantation. A derivation and validation cohort was used to establish prognostic performance. Trajectories of functional tests were compared using joint models. RESULTS: Of the 1,587 patients with fibrotic ILD, 858 (54%) were fit, 400 (25%) were vulnerable, and 329 (21%) were frail. Frailty was a risk factor for early mortality (hazard ratio, 5.58; 95% CI, 3.64-5.76, P < .001) in the entire cohort, in individual ILD diagnoses, and after adjustment for potential confounders. Adding frailty to established risk prediction parameters improved the prognostic performance in derivation and validation cohorts. Patients in the frail subgroup had larger annual declines in FVC % predicted than patients in the fit subgroup (-2.32; 95% CI, -3.39 to -1.17 vs -1.55; 95% CI, -2.04 to -1.15, respectively; P = .02). INTERPRETATION: The simple and practical CFS is associated with pulmonary and physical function decline in patients with fibrotic ILD and provides additional prognostic accuracy in clinical practice.

Lung imaging patterns in connective tissue disease-associated interstitial lung disease impact prognosis and immunosuppression response.

OBJECTIVES: Interstitial lung disease (ILD) in connective tissue diseases (CTD) have highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality and immunosuppression response. METHODS: Patients with CTD-ILD had high-resolution chest computed tomography (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern (usual interstitial pneumonia [UIP]; non-specific interstitial pneumonia [NSIP]; organizing pneumonia [OP]; fibrotic hypersensitivity pneumonitis [fHP]; and other). Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. RESULTS: Of 645 CTD-ILD patients, the frequent CTDs were systemic sclerosis (n = 215), rheumatoid arthritis (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with UIP, FVC decline was slower for NSIP (1.1%/year, 95%CI 0.2, 1.9) and OP (3.5%/year, 95%CI 2.0, 4.9), and mortality was lower for NSIP (HR 0.65, 95%CI 0.45, 0.93) and OP (HR 0.18, 95%CI 0.05, 0.57), but higher in fHP (HR 1.58, 95%CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95%CI 1.4, 2.8), with no change for UIP or fHP. CONCLUSION: Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

Characteristics and risk factors of interstitial pneumonia with autoimmune features.

BACKGROUND: Interstitial pneumonia with autoimmune features (IPAF) has features of connective tissue disease-associated interstitial lung disease (CTD-ILD), but without meeting criteria for a specific CTD. We compared baseline characteristics, survival, and response to treatment of IPAF to both CTD-ILD and unclassifiable ILD. METHODS: Measurements were extracted from a prospective registry. Baseline features and survival were compared in IPAF against both CTD-ILD and unclassifiable ILD. Linear trajectory of lung function decline (%-predicted forced vital capacity [FVC%] and diffusion capacity of the lung for carbon monoxide [DLCO%]) before and after initiation of mycophenolate or azathioprine were compared in IPAF against both CTD-ILD and unclassifiable ILD using linear mixed models. RESULTS: Compared to CTD-ILD (n = 1240), patients with IPAF (n = 128) were older, more frequently male, and had greater smoking history. Compared to unclassifiable ILD (n = 665), patients with IPAF were younger, more frequently female, and had worse baseline lung function. IPAF had higher mortality compared to CTD-ILD and similar risk of mortality compared to unclassifiable ILD. Mycophenolate initiation was associated with stabilization of FVC% and DLCO% in all ILD subtypes except for FVC% in patients with IPAF, and azathioprine initiation with stabilization of FVC% and DLCO% in all ILD subtypes except for FVC% decline in IPAF and DLCO% decline in CTD-ILD. CONCLUSION: Patients with IPAF had worse survival compared to those with CTD-ILD and similar mortality to unclassifiable ILD, with treatment being associated with stabilization in lung function in all three ILDs. It is uncertain whether IPAF should be considered a distinct ILD diagnostic subgroup.

Predicting New-onset Exertional and Resting Hypoxemia in Fibrotic Interstitial Lung Disease.

Rationale: Hypoxemia in fibrotic interstitial lung disease (ILD) indicates disease progression and is of prognostic significance. The onset of hypoxemia signifies disease progression and predicts mortality in fibrotic ILD. Accurately predicting new-onset exertional and resting hypoxemia prompts appropriate patient discussion and timely consideration of home oxygen. Objectives: We derived and externally validated a risk prediction tool for both new-onset exertional and new-onset resting hypoxemia. Methods: This study used ILD registries from Canada for the derivation cohort and from Australia and the United States for the validation cohort. New-onset exertional and resting hypoxemia were defined as nadir oxyhemoglobin saturation < 88% during 6-minute-walk tests, resting oxyhemoglobin saturation < 88%, or the initiation of ambulatory or continuous oxygen. Candidate predictors included patient demographics, ILD subtypes, and pulmonary function. Time-varying Cox regression was used to identify the top-performing prediction model according to Akaike information criterion and clinical usability. Model performance was assessed using Harrell's C-index and goodness-of-fit (GoF) likelihood ratio test. A categorized risk prediction tool was developed. Results: The best-performing prediction model for both new-onset exertional and new-onset resting hypoxemia included age, body mass index, a diagnosis of idiopathic pulmonary fibrosis, and percent predicted forced vital capacity and diffusing capacity of carbon monoxide. The risk prediction tool exhibited good performance for exertional hypoxemia (C-index, 0.70; GoF, P = 0.85) and resting hypoxemia (C-index, 0.77; GoF, P = 0.27) in the derivation cohort, with similar performance in the validation cohort except calibration for resting hypoxemia (GoF, P = 0.001). Conclusions: This clinically applicable risk prediction tool predicted new-onset exertional and resting hypoxemia at 6 months in the derivation cohort and a diverse validation cohort. Suboptimal GoF in the validation cohort likely reflected overestimation of hypoxemia risk and indicated that the model is not flawed because of underestimation of hypoxemia.

Integration and Application of Radiologic Patterns From Clinical Practice Guidelines on Idiopathic Pulmonary Fibrosis and Fibrotic Hypersensitivity Pneumonitis.

BACKGROUND: Clinical practice guidelines separately describe radiologic patterns of usual interstitial pneumonia (UIP) and fibrotic hypersensitivity pneumonitis (fHP), without direction on whether or how to apply these approaches concurrently within a single patient. RESEARCH QUESTION: How can we integrate guideline-defined radiologic patterns to diagnose interstitial lung disease (ILD) and what are the pitfalls associated with described patterns that require reassessment in future guidelines? STUDY DESIGN AND METHODS: Patients from the Canadian Registry for Pulmonary Fibrosis underwent detailed reevaluation in standardized multidisciplinary discussion. CT scan features were quantified by chest radiologists masked to clinical data, and guideline-defined patterns were assigned. Clinical data then were provided to the radiologist and an ILD clinician, who jointly determined the leading diagnosis. RESULTS: Clinical-radiologic diagnosis in 1,593 patients was idiopathic pulmonary fibrosis (IPF) in 26%, fHP in 12%, connective tissue disease-associated ILD (CTD-ILD) in 34%, idiopathic pneumonia with autoimmune features in 12%, and unclassifiable ILD in 10%. Typical and probable UIP patterns corresponded to a diagnosis of IPF in 66% and 57% of patients, respectively. Typical fHP pattern corresponded to an fHP clinical diagnosis in 65% of patients, whereas compatible fHP was nonspecific and associated with CTD-ILD or IPAF in 48% of patients. No pattern ruled out CTD-ILD. Gas trapping affecting > 5% of lung parenchyma on expiratory imaging was an important feature broadly separating compatible and typical fHP from other patterns (sensitivity, 0.77; specificity, 0.91). INTERPRETATION: An integrated approach to guideline-defined UIP and fHP patterns is feasible and supports > 5% gas trapping as an important branch point. Typical or probable UIP and typical fHP patterns have moderate predictive values for a corresponding diagnosis of IPF and fHP, although occasionally confounded by CTD-ILD; compatible fHP is nonspecific.

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.

Creating a Process for the Implementation of Tiered Huddles in a Veterans Affairs Medical Center.

INTRODUCTION: In 2019, the Veteran's Health Administration began its journey in pursuit of becoming an enterprise-wide High Reliability Organization (HRO). Improving the delivery of safe, high quality patient care is a central focus of HROs. Requisite to meeting this goal is the timely identification and resolution of problems. This is best achieved by empowering and engaging both clinical and non-clinical staff across the healthcare organization through the promotion of robust collaboration and communication between various disciplines. Improved care coordination and increased accountability are two important subsequent outcomes. One method for accomplishing this is through the implementation of tiered huddles. MATERIALS AND METHODS: An extensive review of the current literature from 2013 until June 2021 was conducted for evidence highlighting the experiences of other healthcare organizations during implementation of huddles. Following the review, a tiered huddle proposal was developed and presented to the executive leadership team of a healthcare system for approval. Pilot testing of the tiered huddle implementation plan began in October 2021 over a 12-week period with three services. On average, the pilot services had between three to four tiers from frontline staff to the executive level of leadership. RESULTS: Over the 12-week period, out of the possible 120 tiered huddles that could have been conducted, 68% (n = 81) were completed. Of the tiered huddles conducted, 99% (n = 80) started and ended on time. During the pilot test, seven issues were identified by frontline staff: coordination of pre-procedural coronavirus testing, equipment/computer issues, rooms out of service, staffing levels, and lack of responsiveness from other departments. Issues related to staffing, unresponsiveness from other departments, and equipment concerns required elevation to a higher-level tier with no issues remaining open. Delays in patient care, or prolongation of shift hours for staff because of tiered huddles, was low at 2.5% (n = 2). For the duration of the pilot test, a total of 75 minutes accounted for shifts being extended among five staff members. CONCLUSIONS: The success of this initiative demonstrates the importance of thoughtfully creating a robust process when planning for the implementation of tiered huddles. The findings from this initiative will be of immense value with the implementation of tiered huddles across our healthcare system. We believe that this approach can be used by other healthcare institutions along their journey to improving patient safety and quality.

Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial.

BACKGROUND: Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set. METHODS: In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model. RESULTS: We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants. CONCLUSIONS: We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02076672 . Registered 03/03/2014.

Inhalational exposures in patients with fibrotic interstitial lung disease: Presentation, pulmonary function and survival in the Canadian Registry for Pulmonary Fibrosis.

BACKGROUND AND OBJECTIVE: Inhalational exposures are a known cause of interstitial lung disease (ILD), but little is understood about their prevalence across ILD subtypes and their relationship with pulmonary function and survival. METHODS: Patients with fibrotic ILD were identified from the multicentre Canadian Registry for Pulmonary Fibrosis. Patients completed questionnaires regarding ILD-related occupational and environmental exposures. The relationship between exposures and the outcomes of baseline age, gender, family history, pulmonary function and survival was analysed using linear and logistic regression models, linear mixed-effect regression models and survival analysis using multivariable Cox proportional hazards along with the log-rank test. RESULTS: There were 3820 patients included in this study, with 2385 (62%) having ILD-related inhalational exposure. Exposed patients were younger, particularly in the idiopathic pulmonary fibrosis subgroup. Inhalational exposure was associated with male gender (adjusted OR 1.46, 95% CI 1.28-1.68, p < 0.001) and family history of pulmonary fibrosis (adjusted OR 1.73, 95% CI 1.40-2.15, p < 0.001). Patients with any inhalational exposure had improved transplant-free survival (hazard ratio 0.81, 95% CI 0.71-0.92, p = 0.001); this effect persisted across diagnostic subtypes. The relationship between exposures and annual change in forced vital capacity varied by ILD subtype. CONCLUSION: Patients with fibrotic ILD report high prevalence of inhalational exposures across ILD subtypes. These exposures were associated with younger age at diagnosis, male gender and family history of pulmonary fibrosis. Identification of an inhalational exposure was associated with a survival benefit. These findings suggest that inhaled exposures may impact clinical outcomes in patients with ILD, and future work should characterize the mechanisms underlying these relationships.

Prevalence and characteristics of progressive fibrosing interstitial lung disease in a prospective registry.

BACKGROUND: Progressive fibrosing interstitial lung disease (PF-ILD) is characterised by progressive physiological, symptomatic and/or radiographic worsening. The real-world prevalence and characteristics of PF-ILD remain uncertain. METHODS: Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015 and 2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation or any two of: relative FVC decline ≥5% and <10%, worsening respiratory symptoms or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression. RESULTS: Of 2746 patients with fibrotic ILD (mean±sd age 65±12 years; 51% female), 1376 (50%) met PF-ILD criteria in the first 24 months of follow-up. PF-ILD occurred in 427 (59%) patients with idiopathic pulmonary fibrosis (IPF), 125 (58%) with fibrotic hypersensitivity pneumonitis (HP), 281 (51%) with unclassifiable ILD (U-ILD) and 402 (45%) with connective tissue disease-associated ILD (CTD-ILD). Compared with IPF, time to progression was similar in patients with HP (hazard ratio (HR) 0.96, 95% CI 0.79-1.17), but was delayed in patients with U-ILD (HR 0.82, 95% CI 0.71-0.96) and CTD-ILD (HR 0.65, 95% CI 0.56-0.74). Background treatment varied across diagnostic subtypes, with 66% of IPF patients receiving antifibrotic therapy, while immunomodulatory therapy was utilised in 49%, 61% and 37% of patients with CHP, CTD-ILD and U-ILD, respectively. Increasing age, male sex, gastro-oesophageal reflux disease and lower baseline pulmonary function were independently associated with progression. CONCLUSIONS: Progression is common in patients with fibrotic ILD, and is similarly prevalent in HP and IPF. Routinely collected variables help identify patients at risk for progression and may guide therapeutic strategies.

Infliximab therapy in refractory sarcoidosis: a multicenter real-world analysis.

BACKGROUND: Infliximab is a monoclonal antibody that binds and neutralizes circulating tumor necrosis factor-alpha, a key inflammatory cytokine in the pathophysiology of sarcoidosis. Despite the paucity of randomized clinical trials, infliximab is often considered a therapeutic option for refractory disease. Our study aimed to investigate the effectiveness of infliximab in patients with refractory sarcoidosis. METHODS: Sarcoidosis patients from three tertiary centres were retrospectively identified by pharmacy records based on treatment with infliximab. Treatment with Infliximab was initiated in patients who failed first and second line immunomodulators as determined by a multidisciplinary team of Respirologists, Dermatologists, ENT specialists, Rheumatologists, and Neurologists. Participants were characterized by the primary organ for which infliximab was initiated and the total number of organs involved. Clinical outcomes were categorized as treatment success versus failure. We defined treatment success as (A) improvement of cutaneous, upper airway, lymph node, gastrointestinal, eye, or joint manifestations; or (B) improvement or no change in central nervous system (CNS) or pulmonary manifestations. RESULTS: 33 patients with refractory sarcoidosis were identified. The proportion of treatment success was 100% (95% CI 54.1-100) in CNS, 91.7% (95% CI 61.5-99.8) in cutaneous, 78.6% (95% CI 49.2-95.3) in pulmonary and 71.5% (95% CI 29.0-96.3) in upper airway disease. The use of infliximab was associated with a reduction prednisone dose by 50%. CONCLUSION: Infliximab is possibly an effective therapy for refractory sarcoidosis, with the greatest value in neurologic and cutaneous manifestations. Across all disease presentations, infliximab facilitated a clinically relevant reduction in corticosteroid dose. Relapse is common after discontinuation of infliximab.

Travel Distance to Subspecialty Clinic and Outcomes in Patients with Fibrotic Interstitial Lung Disease.

Rationale: Early access to subspecialty care is associated with improved outcomes for patients with fibrotic interstitial lung disease (ILD). Access to ILD care may be limited for patients living far from subspecialty clinics. Objectives: To test the hypothesis that greater travel distance to access ILD clinical care would be associated with more severe disease at time of referral and worse clinical outcomes. Methods: Patients with fibrotic ILD were recruited from a multicenter national pulmonary fibrosis registry. Residential postal codes were geocoded to estimate travel distance from the home to the clinic. Travel distance was dichotomized at ⩽70 km (near) and >70 km (far). Demographics and disease severity at the initial referral, changes in lung function, and the risk of death or lung transplant were analyzed in unadjusted and adjusted models for their association with travel distance. Results: The cohort included 1,162 patients, of whom 856 lived near to their ILD clinic and 306 lived far from their ILD clinic. Patients residing farther from their clinic were younger, more likely to have smoked, had a greater 6-minute-walk distance, and had lower composite risk scores than patients residing closer to their clinic. In models adjusted for age, sex, and baseline forced vital capacity, patients from farther away had a greater risk of death or lung transplant than patients residing closer (hazard ratio, 1.52; 95% confidence interval [CI], 1.10-2.11), a finding predominantly driven by patients with connective tissue disease-related ILD (hazard ratio, 2.14; 95% CI, 1.16-3.94). Conclusions: Patients with fibrotic ILD with a longer travel distance to their ILD clinic had better prognostic indices at baseline but had a higher risk of death or lung transplant in the total cohort and in patients with connective tissue disease-related ILD. Assuming that disease epidemiology and severity are distributed evenly across geographic regions, these findings raise important questions about equitable access to patient care in large healthcare regions with centralized subspecialty programs.

Association of BMI and Change in Weight With Mortality in Patients With Fibrotic Interstitial Lung Disease.

BACKGROUND: Mortality risk assessment in interstitial lung disease (ILD) is challenging. Our objective was to determine the prognostic significance of BMI and change in weight in the most common fibrotic ILD subtypes. RESEARCH QUESTION: Could BMI and weight loss over time be reliable prognostic indicators in patients with fibrotic ILD? STUDY DESIGN AND METHODS: This observational retrospective multicenter cohort study enrolled patients with fibrotic ILD from the six-center CAnadian REgistry for Pulmonary Fibrosis (CARE-PF, derivation) and the ILD registry at the University of California, San Francisco (UCSF, validation). Patients were subcategorized as underweight (BMI < 18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), or obese (BMI > 30). Annual change in weight was calculated for all years of follow-up as the slope of best fit using the least square method based on every available measurement. Separate multivariable analyses evaluated the associations of BMI and change in weight with mortality, adjusting for common prognostic variables. RESULTS: The derivation and validation cohorts included 1,786 and 1,779 patients, respectively. Compared with patients with normal BMI, mortality was highest in patients who were underweight (hazard ratio [HR], 3.19; 95% CI, 1.88-5.43; P < .001) and was lowest in those who were overweight (HR, 0.52; 95% CI, 0.36-0.75; P < .001) or obese (HR, 0.55; 95%CI, 0.37-0.83; P < .001) in the analysis adjusted for the ILD-GAP (gender, age, physiology) Index. Patients who had a weight loss of at least 2 kg within 1 year had increased risk of death in the subsequent year (HR, 1.41; 95% CI, 1.01-1.97; P = .04) after adjustment for the ILD-GAP Index and baseline BMI category, with a plateau in risk for patients with greater weight loss. Consistent results were observed in the validation cohort. INTERPRETATION: Both BMI and weight loss are independently associated with 1-year mortality in fibrotic ILD. BMI and weight loss may be clinically useful prognostic indicators in fibrotic ILD.

Effect of continued antifibrotic therapy after forced vital capacity decline in patients with idiopathic pulmonary fibrosis; a real world multicenter cohort study.

RATIONALE: Longitudinal data on the impact of continued, switched or discontinued antifibrotic therapy in patients with idiopathic pulmonary fibrosis (IPF) who have disease progression is needed. OBJECTIVE: We hypothesized that ongoing antifibrotic use (versus discontinuation) in the setting of forced vital capacity (FVC) decline would be associated with less future decline and lower likelihood of a composite outcome of FVC decline, lung transplant, or death. METHODS: We performed a multicenter cohort study using data from the Canadian Registry for Pulmonary Fibrosis in patients with IPF with FVC decline ≥10% over 6 months on antifibrotic therapy. The association of continued, switched or discontinued therapy with (1) further change in FVC and (2) a composite of FVC decline ≥10%, transplant, or death, in the subsequent 6 months, was assessed using adjusted linear and logistic regression modelling, respectively. Generalized estimating equations accounted for repeated observations per patient. RESULTS: 165 patients had a decline in FVC ≥10% over 6 months while receiving antifibrotic therapy. Compared to continued use, antifibrotic discontinuation after FVC decline was associated with greater additional FVC decline (-207 mL 95%CI -353 to -62, p = 0.005) and higher odds of FVC decline ≥10%, transplant, or death (odds ratio 12.2 95%CI 1.2 to 130.5, p = 0.04). There was no difference between continued versus switched antifibrotic therapy. CONCLUSIONS: Ongoing antifibrotic therapy in the setting of FVC decline is associated with less future FVC decline and lower odds of FVC decline ≥10%, transplant, or death in a real-world cohort of IPF.

Bronchial thermoplasty guided by hyperpolarised gas magnetic resonance imaging in adults with severe asthma: a 1-year pilot randomised trial.

Patient-specific localisation of ventilation defects using hyperpolarised gas magnetic resonance imaging (MRI) introduces the possibility of regionally targeted bronchial thermoplasty (BT) for the treatment of severe asthma. We aimed to demonstrate that BT guided by MRI to ventilation defects reduces the number of radiofrequency activations while resulting in improved asthma quality-of-life and control scores that are non-inferior to standard BT. In a 1-year pilot randomised controlled trial, 14 patients with severe asthma who were clinically eligible to receive BT underwent hyperpolarised gas MRI to characterise ventilation defects and were randomised to MRI-guided or standard BT. End-points were improved Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) scores, the proportion of AQLQ and ACQ responders and the number of radiofrequency activations and bronchoscopy sessions. Participants who underwent MRI-guided BT received 53% fewer radiofrequency activations than those who had standard BT (p=0.003). At 12 months, the mean improvement from baseline was similar between the MRI-guided group (n=5) and the standard group (n=7) for AQLQ score (MRI-guided: 1.8, 95% CI 0.1-3.5, p=0.04; standard: 0.7, 95% CI -0.9-2.3, p=0.30) (p=0.25) and ACQ-5 score (MRI-guided: -1.4, 95% CI -2.6- -0.2, p=0.03; standard: -0.7, 95% CI -1.3-0.0, p=0.04) (p=0.17). A similar proportion of participants in both groups achieved a clinically relevant improvement in AQLQ score (MRI-guided: 80%; standard: 71%) and ACQ-5 score (MRI-guided: 80%; standard: 57%). Hyperpolarised gas MRI-guided BT reduced the number of radiofrequency activations, and resulted in asthma quality of life and control improvements at 12 months that were non-inferior to standard BT.

Comprehensive Care Management in Conjunction with Sputum Cytometry-Guided Pharmacotherapy in a Post-Discharge Clinic for Patients with COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are amongst the most common reasons for hospital admission, and recurrent episodes occur frequently. Comprehensive care management (CCM) strategies have modest effect in preventing re-admissions. The objectives of this study were to examine the utility of optimizing anti-inflammatory therapy guided by sputum cytometry in the post-hospitalization setting, and to assess the feasibility and effectiveness of a clinic combining CCM and sputum-guided therapy. This is an observational study examining patients who received open-label CCM and sputum cytometry-guided pharmacotherapy in a COPD post-discharge clinic. Referral was based on high risk for readmission after hospitalization for AECOPD. The primary outcome was the change in COPD-related healthcare utilization before and after Visit 1, and this was analyzed with a mixed-effects negative binomial model controlling for age, number of follow-up clinic visits, pack years, current smoking and FEV1. Of 138 patients referred to the clinic, 73% attended at least one visit. Mean FEV1 was 42.8 (19.3) % predicted. Of the patients attending clinic, 42.6% produced an adequate sputum sample, and 32.7% had an abnormal sputum. By individual, infectious bronchitis was the most common (25.7%), followed by eosinophilic bronchitis (13.9%). Comparing the 6-months prior to and after the first clinic visit, there was a lower incidence rate ratio after visit 1 for COPD-related healthcare utilization (0.26 (95%CI 0.22,0.33; p < 0.001)). A COPD post-discharge clinic combining sputum-guided treatment and CCM was feasible and associated with a nearly 75% reduction in the incidence of COPD-related healthcare utilization.

Validation and minimum important difference of the UCSD Shortness of Breath Questionnaire in fibrotic interstitial lung disease.

RATIONALE: The University of California, San Diego Shortness of Breath Questionnaire (UCSDSOBQ) is a frequently used domain-specific dyspnea questionnaire; however, there is little information available regarding its use and minimum important difference (MID) in fibrotic interstitial lung disease (ILD). We aimed to describe the key performance characteristics of the UCSDSOBQ in this population. METHODS: UCSDSOBQ scores and selected anchors were measured in 1933 patients from the prospective multi-center Canadian Registry for Pulmonary Fibrosis. Anchors included the St. George's Respiratory Questionnaire (SGRQ), European Quality of Life 5 Dimensions 5 Levels questionnaire (EQ-5D-5L) and EQ visual analogue scale (EQ-VAS), percent-predicted forced vital capacity (FVC%), diffusing capacity of the lung for carbon monoxide (DLCO%), and 6-min walk distance (6MWD). Concurrent validity, internal consistency, ceiling and floor effects, and responsiveness were assessed, followed by estimation of the MID by anchor-based (linear regression) and distribution-based methods (standard error of measurement). RESULTS: The UCSDSOBQ had a high level of internal consistency (Cronbach's alpha = 0.97), no obvious floor or ceiling effect, strong correlations with SGRQ, EQ-5D-5L, and EQ-VAS (|r| > 0.5), and moderate correlations with FVC%, DLCO%, and 6MWD (0.3 < |r| < 0.5). The MID estimate for UCSDSOBQ was 5 points (1-8) for the anchor-based method, and 4.5 points for the distribution-based method. CONCLUSION: This study demonstrates the validity of UCSDSOBQ in a large and heterogeneous population of patients with fibrotic ILD, and provides a robust MID estimate of 5-8 points.