Evaluation of a novel method to assess corticosteroid responsiveness in chronic obstructive pulmonary disease

<b>Background</b> : Some patients with chronic obstructive pulmonary disease (COPD) may benefit from oral steroid therapy. These steroid-responsive patients are diagnosed based on laboratory spirometry. We hypothesize that daily, home-based spirometry is a better tool. <b>Methods</b> : Thirty patients with COPD underwent a single-blinded study, with a crossover design. They received 2 weeks of placebo followed by 2 weeks of prednisone therapy (40 mg/day). Laboratory spirometry was done at the beginning and end of the study and daily home-based spirometry was done twice a day. <b>Results</b> : Analysis of variance model was used. The variability of the median day-to-day forced expiratory volume in 1 s (FEV ₁ ) was 72.5 mL (25th percentile of 40 mL and 75th percentile of 130 mL). The daily FEV ₁ variation was 70 mL (25th percentile of 50 mL and 75th percentile of 100 mL). The overall laboratory FEV ₁ variability was larger after the steroid course (<i>P</i> &lt; 0.001), but not clinically significant. The variability was not significant postplacebo treatment compared with the baseline values. For home-based spirometry, steroid treatment was not significantly different. The majority (97&#x0025;) completed more than 80&#x0025; of the measurements. Ninety percent of the performed tests were considered acceptable. Only 53&#x0025; of the tests were considered accurate. Overall both laboratory and home-based measurements did not show significant association between airway responsiveness and dyspnea or exercise capacity. <b>Conclusion</b> : Twice-daily home measurements of FEV ₁ might be better than the conventional approach to identify steroid responsive COPD patients. However, this finding was only statistically but not clinically significant. Therefore, we would not recommend this approach to identify COPD patients with steroid responsiveness

Pleuroparenchymal Lung Disease Secondary to Nonoccupational Exposure to Vermiculite

An unusual case of pleuroparenchymal lung disease caused by the inhalation of vermiculite dust, presumably containing asbestos fibers is described. The uniqueness of the case lies in the very indirect nature of exposure – the wife of a factory owner, rather than a worker exposed to asbestos, whose factory manufactured vermiculite. The present case illustrates the importance of taking careful occupational histories of all household members when presented with a patient whose chest radiograph exhibits features consistent with asbestos exposure.Peer Reviewe

Pleuroparenchymal lung disease secondary to nonoccupational exposure to vermiculite

An unusual case of pleuroparenchymal lung disease caused by the inhalation of vermiculite dust, presumably containing asbestos fibers is described. The uniqueness of the case lies in the very indirect nature of exposure – the wife of a factory owner, rather than a worker exposed to asbestos, whose factory manufactured vermiculite. The present case illustrates the importance of taking careful occupational histories of all household members when presented with a patient whose chest radiograph exhibits features consistent with asbestos exposure

Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation

Abstract Background Expression profile of the toll like receptors (TLRs) on PBMCs is central to the regulation of proinflammatory markers. An imbalance in the TLRs expression may lead to several types of inflammatory disorders. Furthermore, the dynamic regulation of inflammatory activity and associated impaired production of cytokines by peripheral blood mononuclear cells (PBMCs) in obese individulas remain poorly understood. Therefore, we determined the perturbation in TLRs (TLR2 and TLR4), their adaptor proteins (MyD88, IRAK1 and TRAF6) expression in PBMCs/subcutaneous adipose tissue (AT) as well as inflammatory cytokines changes in obese individuals. Methods mRNA expression levels of TLR2, TLR4, IL-6, TNF-α and adaptor proteins were determined by RT-PCR. TLR2, TLR4 and adaptor proteins expression in AT was determined by immunohistochemistry. Results Obese and overweight individuals showed significantly increased expression of TLR2, TLR4 and MyD88 in both PBMCs and AT as compared with lean individuals (P  Conclusions TLRs and adapter proteins were overexpressed in PBMCs from obese subjects, which correlated with increased expression of TNF-α and IL-6. This association may explain a potential pathophysiological link between obesity and inflammation leading to insulin resistance.</p

A Biomarker Based Severity Progression Indicator for COVID-19: The Kuwait Prognosis Indicator Score.

COVID-19 is a worldwide pandemic that is mild in most patients but can result in a pneumonia like illness with progression to acute respiratory distress syndrome and death. Predicting the disease severity at time of diagnosis can be helpful in prioritizing hospital admission and resources. We prospectively recruited 1096 consecutive patients of whom 643 met the inclusion criterion with COVID-19 from Jaber Hospital, a COVID-19 facility in Kuwait, between 24 February and 20 April 2020. The primary endpoint of interest was disease severity defined algorithmically. Predefined risk variables were collected at the time of PCR based diagnosis of the infection. Prognostic model development used 5-fold cross-validated regularized logit regression. The model was externally validated against data from Wuhan, China. There were 643 patients with clinical course data of whom 94 developed severe COVID-19. In the final model, age, CRP, procalcitonin, lymphocyte percentage, monocyte percentages and serum albumin were independent predictors of a more severe illness course. The final prognostic model demonstrated good discrimination, and both discrimination and calibration were confirmed with an external dataset. We developed and validated a simple score calculated at time of diagnosis that can predict patients with severe COVID-19 disease reliably and that has been validated externally. The KPI score calculator is now available online at

Interaction of osteopontin with IL-18 in obese individuals: implications for insulin resistance.

BACKGROUND/OBJECTIVE: Osteopontin (OPN) and IL-18 are known inflammatory mediators and both participate in a wide range of biological processes linked to immunological disorders. Since an interaction between OPN and IL-18 has not been studied in obesity, we investigated whether: (i) their levels were simultaneously elevated in obese individuals; (ii) OPN was associated with IL-18 in obese individuals and (iii) their levels associated with fasting blood glucose (FBG) and BMI. SUBJECTS AND METHODS: PBMCs and plasma samples were isolated from 60 individuals including lean as well as overweight and obese individuals. Subcutaneous adipose tissue samples were obtained. OPN and IL-18 were measured by ELISA. OPN and IL-18 mRNA expression was quantified by real time quantitative RT-PCR. RESULTS: Obese individuals exhibited significantly increased circulating OPN levels as compared with lean individuals (obese 2865±101; lean 1681±116 pg/ml; P<0.0001). IL-18 levels were also high in obese individuals (obese 491±39, lean 301±26 pg/ml; P = 0.0009). OPN and IL-18 expression were simultaneously up-regulated (OPN: 5.4-Fold; IL-18: 8.9-Fold; P<0.05) in PBMCs from obese individuals compared to lean group. Adipose tissue from obese individuals had high expression of OPN (7.3-Fold) and IL-18 (9.6-Fold). Plasma OPN levels correlated positively with FBG levels (r = 0.32, P = 0.02). Similarly, IL-18 correlated positively with FBG levels (r = 0.406, P = 0.0042). Stepwise multiple regression analysis showed an independent association of BMI with OPN and IL-18. Interestingly, OPN levels increased progressively with an increase in IL-18 levels (r = 0.52, P = 0.0004). We also examined the regulatory role of IL-18 in OPN secretion from PBMCs. Neutralizing anti-IL-18Rα mAb reduced OPN secretion. CONCLUSION: These findings represent the first observation that plasma, PBMC and adipose tissue OPN and IL-18 are simultaneously increased and correlate with each other in overweight/obese individuals which may trigger the development of obesity-associated insulin resistance. Moreover, these results provide the direct evidence that IL-18 regulates OPN production in PBMCs