Objective. CTD-associated interstitial lung disease (ILD) often fails to respond to conventional immunomodulatory agents. There is now considerable interest in the use of rituximab in systemic autoimmune CTD in patients refractory to standard treatments. The aim of this study was to review the experience of North Bristol NHS Trust managing patients with CTD-associated ILD with rituximab and explore possible associations with treatment response.

The clinical syndrome of acute lung injury (ALI) occurs as a result of an initial acute systemic inflammatory response. This can be consequent to a plethora of insults, either direct to the lung or indirect. The insult results in increased epithelial permeability, leading to alveolar flooding with a protein-rich oedema fluid. The resulting loss of gas exchange leads to acute respiratory failure and typically catastrophic illness, termed acute respiratory distress syndrome (ARDS), requiring ventilatory and critical care support. There remains a significant disease burden, with some estimates showing 200,000 cases each year in the USA with a mortality approaching 50%. In addition, there is a significant burden of morbidity in survivors. There are currently no disease-modifying therapies available, and the most effective advances in caring for these patients have been in changes to ventilator strategy as a result of the ARDS network studies nearly 15 years ago. Here, we will give an overview of more recent advances in the understanding of the cellular biology of ALI and highlight areas that may prove fertile for future disease-modifying therapies.

Purpose: Pirfenidone and nintedanib are two novel antifibrotic agents licensed for the treatment IPF. Prior to being approved for use in England for patients with FVC >50% and <80%, these were made available for all IPF patients under the Mild Patient Program (MPP) and Patient In Need Scheme (PIN). Prescribing of these medications is restricted to specialist centers. We sought to characterize the population of patients prescribed antifibrotics and determine the drug tolerability of these medications in the Northern hub of the Southwest of England regional ILD network. Methods: A retrospective analysis of all patients treated with antifibrotics between August 2012 and July 2017 was undertaken. Baseline characteristics including patient demographics and pulmonary physiology, in addition to drug tolerability and reasons for treatment cessation were collated. Data were compared using unpaired student’s t-test, Chi-squared, Mann–Whitney rank sum or ANOVA as appropriate. Logistic regression analysis evaluated clinical characteristics associated with discontinuation of pirfenidone therapy. P < 0.05 was considered statistically significant. Findings: A total of 164 patients, all with consensus diagnoses of IPF, were identified. Of these, 70.1% (115/164) received pirfenidone as their initial therapy. Baseline age, gender and pulmonary physiology did not differ significantly between groups. Drug discontinuation occurred most commonly due to adverse drug reactions events (ADRs) for both pirfenidone [40.0% (46/115)] and nintedanib [16.3% (8/49)]. Anorexia, rash and gastrointestinal disturbance were reported most commonly as the reason for cessation of pirfenidone; anorexia, nausea and weight loss for nintedanib. Duration of therapy prior to discontinuation because of ADRs did not differ significantly between medication groups but patients with a baseline FVC < 65% predicted, had a significantly shorter duration of pirfenidone prior to discontinuation due to ADRs, compared to those with a FVC 65–80% predicted. Multivariate logistic regression did not identify any independent baseline characteristics that predicted discontinuation of pirfenidone therapy prior to 52 weeks. Implications: Idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib had comparable treatment emergent adverse event (TEAE) profiles in clinical practice to those reported in clinical trials. The TEAE profile of pirfenidone was higher than clinical trial data would suggest, although comparable to real-world datasets. Further work is required to explore the possible reasons underpinning this finding, including whether this is related to population co-morbidities or center threshold. No new safety concerns were identified.

Introduction: There is increasing interest in technologies that may enable remote monitoring of respiratory disease. Traditional methods for assessing respiratory function such as spirometry can be expensive and require specialist training to perform and interpret. Remote, non-contact tracking of chest wall movement has been explored in the past using structured light, accelerometers and impedance pneumography, but these have often been costly and clinical utility remains to be defined. We present data from a 3-Dimensional time-of-flight camera (found in gaming consoles) used to estimate chest volume during routine spirometry manoeuvres. Methods: Patients were recruited from a general respiratory physiology laboratory. Spirometry was performed according to international standards using an unmodified spirometer. A Microsoft Kinect V2 time-of-flight depth sensor was used to reconstruct 3-dimensional models of the subject's thorax to estimate volume-time and flow-time curves following the introduction of a scaling factor to transform measurements to volume estimates. The Bland-Altman method was used to assess agreement of model estimation with simultaneous recordings from the spirometer. Patient characteristics were used to assess predictors of error using regression analysis and to further explore the scaling factors. Results: The chest volume change estimated by the Kinect camera during spirometry tracked respiratory rate accurately and estimated forced vital capacity and vital capacity to within +/-150ml difference. Linear regression including age, gender, height, weight and pack years of smoking explained 37.0% of the variance in the scaling factor for volume estimation. This technique had a positive predictive value of 0.833 to detect obstructive spirometry. Conclusion: These data illustrate the potential of 3D time-of-flight cameras to remotely monitor respiratory rate. This is not a replacement for conventional spirometry and needs further refinement. Further algorithms are being developed to allow its independence from spirometry. Benefits include simplicity of set-up, no specialist training and cost. This technique warrants further refinement and validation in larger cohorts.

Cross-reactivity of murine and recently human CD8⁺ T cells between different viral peptides, i.e., heterologous immunity, has been well characterized. However, the directionality and quality of these cross-reactions is critical in determining their biological importance. Herein we analyzed the response of human CD8⁺ T cells that recognize both a hepatitis C virus peptide (HCV-NS3) and a peptide derived from the influenza neuraminidase protein (Flu-NA). To detect the cross-reactive CD8⁺ T cells, we used peptide-MHC class I complexes (pMHCs) containing a new mutant form of MHC class I able to bind CD8 more strongly than normal MHC class I complexes. T cell responses against HCV-NS3 and Flu-NA peptide were undetectable in normal donors. In contrast, some responses against the Flu-NA peptide were identified in HCV⁺ donors who showed strong HCV-NS3–specific reactivity. The Flu-NA peptide was a weak agonist for CD8⁺ T cells in HCV⁺ individuals on the basis of novel pMHCs and functional assays. These data support the idea of cross-reactivity between the 2 peptides, but indicate that reactivity toward the Flu-NA peptide is highly CD8-dependent and occurs predominantly after priming during HCV infection. Our findings indicate the utility of the novel pMHCs in dissecting cross-reactivity and suggest that cross-reactivity between HCV and influenza is relatively weak. Further studies are needed to relate affinity and functionality of cross-reactive T cells.

Introduction Patients with progressive idiopathic fibrotic interstitial lung disease (ILD), such as those with idiopathic pulmonary fibrosis (IPF), can have an aggressive disease course, with a median survival of only 3–5 years from diagnosis. The palliative care needs of these patients are often unmet. There are calls for new models of care, whereby the patient’s usual respiratory clinician remains central to the integration of palliative care principles and practices into their patient’s management, but the optimal model of service delivery has yet to be determined. Methods We developed a novel, collaborative, multidisciplinary team (MDT) meeting between our palliative care, psychology and ILD teams with the principal aim of integrating specialist care to ensure the needs of persons with ILD, and their caregivers were identified and met by referral to the appropriate service. The objective of this study was to assess the effectiveness of this novel MDT meeting on the assessment of a patient’s palliative care needs. Results Significant increases in advance care planning discussions were observed, in conjunction with increased referrals to community courses and teams, following introduction of this novel MDT. Conclusions Our results suggest that our collaborative MDT is an effective platform to address patients’ unmet palliative care needs. Further work is required to explore the effect of our model on achieving the preferred place of death and reductions in unplanned hospital admissions.