Management of interstitial lung disease (ILD) in myositis syndromes: A practical guide for clinicians

Inflammatory myopathies are heterogeneous clinico-serological syndromes, with variable clinical manifestations. Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with myositis. The clinical manifestation of myositis-ILD is heterogeneous, e.g., with acute-on-chronic presentations, as well as the chronic aftermath of acute disease. Here, we have largely divided myositis-ILD into three main prognostic groups which require different treatment approaches: mild-moderate (subacute), severe or progressive (acute or subacute) and rapidly progressive, life-threatening. In current clinical practice, the treatment of myositis-ILD involves immunomodulation in an induction-maintenance treatment paradigm. There is now an option to add antifibrotics to slow the progression of established fibrosis in selected cases with chronic progressive phenotype. Here, we describe current concepts in myositis-ILD and aim to provide a practical guide for clinicians on how to approach assessment, including early identification of ILD, phenotyping of patients according to clinical trajectory and likely prognosis and stratified management adopting multi-disciplinary cross-speciality expertise, with close collaboration between rheumatology and respiratory physicians

A combined microfinance and training intervention can reduce HIV risk behaviour in young female participants.

OBJECTIVE: To assess effects of a combined microfinance and training intervention on HIV risk behavior among young female participants in rural South Africa. DESIGN: : Secondary analysis of quantitative and qualitative data from a cluster randomized trial, the Intervention with Microfinance for AIDS and Gender Equity study. METHODS: Eight villages were pair-matched and randomly allocated to receive the intervention. At baseline and after 2 years, HIV risk behavior was assessed among female participants aged 14-35 years. Their responses were compared with women of the same age and poverty group from control villages. Intervention effects were calculated using adjusted risk ratios employing village level summaries. Qualitative data collected during the study explored participants' responses to the intervention including HIV risk behavior. RESULTS: After 2 years of follow-up, when compared with controls, young participants had higher levels of HIV-related communication (adjusted risk ratio 1.46, 95% confidence interval 1.01-2.12), were more likely to have accessed voluntary counseling and testing (adjusted risk ratio 1.64, 95% confidence interval 1.06-2.56), and less likely to have had unprotected sex at last intercourse with a nonspousal partner (adjusted risk ratio 0.76, 95% confidence interval 0.60-0.96). Qualitative data suggest a greater acceptance of intrahousehold communication about HIV and sexuality. Although women noted challenges associated with acceptance of condoms by men, increased confidence and skills associated with participation in the intervention supported their introduction in sexual relationships. CONCLUSIONS: In addition to impacts on economic well being, women's empowerment and intimate partner violence, interventions addressing the economic and social vulnerability of women may contribute to reductions in HIV risk behavior

Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.

Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB

Interstitial lung disease:A review of classification, aetiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment

IInterstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases

Home monitoring of physiology and symptoms to detect interstitial lung disease exacerbations and progression:a systematic review

Background: Acute exacerbations (AEs) and disease progression in interstitial lung disease (ILD) pose important challenges to clinicians and patients. AEs of ILD are variable in presentation but may result in rapid progression of ILD, respiratory failure and death. However, in many cases AEs of ILD may go unrecognised so that their true impact and response to therapy is unknown. The potential for home monitoring to facilitate early, and accurate, identification of AE and/or ILD progression has gained interest. With increasing evidence available, there is a need for a systematic review on home monitoring of patients with ILD to summarise the existing data. The aim of this review was to systematically evaluate the evidence for use of home monitoring for early detection of exacerbations and/or progression of ILD. Method: We searched Ovid-EMBASE, MEDLINE and CINAHL using Medical Subject Headings (MeSH) terms in accordance with the PRISMA guidelines (PROSPERO registration number CRD42020215166). Results: 13 studies involving 968 patients have demonstrated that home monitoring is feasible and of potential benefit in patients with ILD. Nine studies reported that mean adherence to home monitoring was &gt;75%, and where spirometry was performed there was a significant correlation (r=0.72–0.98, p&lt;0.001) between home and hospital-based readings. Two studies suggested that home monitoring of forced vital capacity might facilitate detection of progression in idiopathic pulmonary fibrosis. Conclusion: Despite the fact that individual studies in this systematic review provide supportive evidence suggesting the feasibility and utility of home monitoring in ILD, further studies are necessary to quantify the potential of home monitoring to detect disease progression and/or AEs.</p

Nalbuphine Tablets for Cough in Patients with Idiopathic Pulmonary Fibrosis

BACKGROUND There are no approved therapies for cough in patients with idiopathic pulmonary fibrosis (IPF). In this small crossover trial we administered nalbuphine extended-release tablets (NAL ER) as a potential cough therapy for such patients. METHODS This randomized, double-blind, placebo-controlled, crossover trial involved two 22-day treatment periods (NAL ER!placebo and placebo!NAL ER) separated by a 2-week washout period. NAL ER was started at a dose of 27 mg once daily and was titrated up to 162 mg twice daily at day 16. The primary end point was percent change from baseline in hourly daytime objective cough frequency as measured by an electronic cough monitor. The daytime period was defined as the patient-reported time of awakening and bedtime. Secondary end points included change in objective 24-hour cough frequency, changes in cough frequency, cough severity, and breathlessness, per patient-reported outcomes. RESULTS A total of 41 patients were randomly assigned and received one or more doses of study medication. There was a 75.1% reduction in daytime objective cough frequency during the NAL ER treatment period versus the placebo treatment period of 22.6%, a 52.5 percentage point placebo-adjusted decrease from baseline (P<0.001) at day 21. There was a 76.1% (95% confidence interval, 83.1 to 69.1) decrease in the 24-hour objective cough frequency with NAL ER, versus a 25.3% (43.9 to 6.7) decrease with placebo, a 50.8 percentage point placebo-adjusted change. Nausea, fatigue, constipation, and dizziness were more common with NAL ER than with placebo. CONCLUSIONS In this short-term crossover trial, NAL ER reduced cough in individuals with IPF. Larger and longer trials are needed to assess the impact on cough versus drug adverse effects. (Funded by Trevi Therapeutics; ClinicalTrials.gov number, NCT04030026.

Filtration-histogram based texture analysis and CALIPER based pattern analysis as quantitative CT techniques in idiopathic pulmonary fibrosis: head-to-head comparison

OBJECTIVE: To assess the prognostic performance of two quantitative CT (qCT) techniques in idiopathic pulmonary fibrosis (IPF) compared to established clinical measures of disease severity (GAP index). METHODS: Retrospective analysis of high-resolution CT scans for 59 patients (age 70.5 ± 8.8 years) with two qCT methods. Computer-aided lung informatics for pathology evaluation and ratings based analysis classified the lung parenchyma into six different patterns: normal, ground glass, reticulation, hyperlucent, honeycombing and pulmonary vessels. Filtration histogram-based texture analysis extracted texture features: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPPs), skewness and kurtosis at different spatial scale filters. Univariate Kaplan-Meier survival analysis assessed the different qCT parameters' performance to predict patient outcome and refine the standard GAP staging system. Multivariate cox regression analysis assessed the independence of the significant univariate predictors of patient outcome. RESULTS: The predominant parenchymal lung pattern was reticulation (16.6% ± 13.9), with pulmonary vessel percentage being the most predictive of worse patient outcome (p = 0.009). Higher SD, entropy and MPP, in addition to lower skewness and kurtosis at fine texture scale (SSF2), were the most significant predictors of worse outcome (p < 0.001). Multivariate cox regression analysis demonstrated that SD (SSF2) was the only independent predictor of survival (p < 0.001). Better patient outcome prediction was achieved after adding total vessel percentage and SD (SSF2) to the GAP staging system (p = 0.006). CONCLUSION: Filtration-histogram texture analysis can be an independent predictor of patient mortality in IPF patients. ADVANCES IN KNOWLEDGE: qCT analysis can help in risk stratifying IPF patients in addition to clinical markers

Voice and Agency: Empowering women and girls for shared prosperity

This document presents Voice and Agency: Empowering women and girls for shared prosperity is a major new report by the World Bank that shines a spotlight on the value of voice and agency, the patterns of constraints that limit their realization, and the associated costs, not only to individual women but to their families, communities, and societies. It highlights promising policies and interventions, and it identifies priority areas where further research and more and better data and evidence are needed. Underlining that agency has both intrinsic and instrumental, concrete value, this report puts advancing women's voice and agency squarely on the international development agenda