Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.

SPUR-27 - Psychometric Properties of a Patient-Reported Outcome Measure of Medication Adherence in Chronic Obstructive Pulmonary Disease.

Purpose: People living with COPD who struggle to take their medicines often experience poorer health outcomes such as exacerbations of symptoms, more frequent and lengthy hospital admissions, and worsening mortality rates. This study aimed to evaluate the psychometric properties of the previously validated SPUR-27 model, a multi-factorial model of medication adherence. Patients and Methods: This cross-sectional study was conducted with 100 adult patients living with COPD in a hospital setting in Southwest London. Medication adherence was assessed using a shortened SPUR model (SPUR-27) against the validated Inhaler Adherence Scale (IAS) as a comparator. In addition, objective medication adherence data, presented as the Medication Possession Ratio (MPR), were derived from patient medical and pharmacy records. The COPD Assessment Tool (CAT) score was used to examine the relationship between medication adherence and COPD symptom severity. Reliability of SPUR-27 was assessed using internal consistency estimates. Exploratory factor analysis, partial confirmatory factor analysis, and maximum likelihood analysis were conducted in conjunction with construct, concurrent, and known-group validity testing to explore the psychometric properties of the SPUR model in this population. Results: A 7-factor model for SPUR-27 was derived with adequate factor loadings. SPUR (α=0.893) observed strong internal consistency (>0.8). The model was significantly positively correlated with IAS score (p<0.001) as well as MPR (p<0.01). A significant (p<0.01) relationship between poor medication adherence and worsening symptom severity, as defined by the CAT score, was identified for SPUR (χ 2 = 8.570) using Chi-Square analysis. Furthermore, SPUR-27 demonstrated early evidence of validity with good incremental fit indices: NFI (0.96), TFI (0.97), and CFI (0.93) were all reported as >0.9 in addition to the RMSEA, which was <0.08 (0.059). Conclusion: SPUR demonstrated strong psychometric properties in patients living with COPD. Further work should look to examine the test-retest reliability of the model and its application in broader sample populations.

Treatments in idiopathic pulmonary fibrosis: time for a more targeted approach?

Idiopathic pulmonary fibrosis (IPF) is a progressive age-related lung disease, the cause of which is not been fully understood. IPF is a devastating disease with mortality worse than many cancers, and treatment options are limited. IPF is thought to occur after recurrent injury to the alveolar epithelium followed by abnormal repair characterized by the formation of fibroblast and myofibroblast foci and excessive deposition of extracellular matrix. An updated classification of the idiopathic interstitial pneumonias has encouraged a large number of clinical trials. On the whole, these have disappointed. Improvements in molecular techniques have developed our understanding of IPF and with it identified new pathways and potential targets for therapeutic intervention. These insights are leading to interest in biomarkers of disease progression and prognosis and to novel anti-fibrotic agents and a more targeted approach to the treatment of IPF.

ATP and UTP at low concentrations strongly inhibit bone formation by osteoblasts: a novel role for the P2Y2 receptor in bone remodeling.

There is increasing evidence that extracellular nucleotides act on bone cells via multiple P2 receptors. The naturally-occurring ligand ATP is a potent agonist at all receptor subtypes, whereas ADP and UTP only act at specific receptor subtypes. We have reported that the formation and resorptive activity of rodent osteoclasts are stimulated powerfully by both extracellular ATP and its first degradation product, ADP, the latter acting at nanomolar concentrations, probably via the P2Y1 receptor subtype. In the present study, we investigated the actions of ATP, ADP, adenosine, and UTP on osteoblastic function. In 16-21 day cultures of primary rat calvarial osteoblasts, ADP and the selective P2Y1 agonist 2-methylthioADP were without effect on bone nodule formation at concentrations between 1 and 125 microM, as was adenosine. However, UTP, a P2Y2 and P2Y4 receptor agonist, known to be without effect on osteoclast function, strongly inhibited bone nodule formation at concentrations >or= 1 microM. ATP was inhibitory at >or= 10 microM. Rat osteoblasts express P2Y2, but not P2Y4 receptor mRNA, as determined by in situ hybridization. Thus, the low-dose effects of extracellular nucleotides on bone formation and bone resorption appear to be mediated via different P2Y receptor subtypes: ADP, signalling through the P2Y1 receptor on both osteoclasts and osteoblasts, is a powerful stimulator of osteoclast formation and activity, whereas UTP, signalling via the P2Y2 receptor on osteoblasts, blocks bone formation by osteoblasts. ATP, the 'universal' agonist, can simultaneously stimulate resorption and inhibit bone formation. These findings suggest that extracellular nucleotides could function locally as important negative modulators of bone metabolism, perhaps contributing to bone loss in a number of pathological states.