Novel Perspectives of TSLP and RXR Signaling in Corticosteroid-Resistant Asthma: Updates on TSLP Blockers.

Previous studies described that asthma patients who received corticosteroid therapy have been constrained by the corticosteroid resistance subsequently fostered to severe refractory asthma. In this review, we discussed the implications of TSLP, RXR, the role of STAT5-activating cytokines, and IL-33/NH-cell signaling pathways, and recent clinical evidence on TSLP blockers in steroid-resistant asthma. We have searched several public databases such as Pubmed, Scopus, and Relemed and obtained information pertinent to the TSLP, RXR, TSLP blockers, the STAT5-activating cytokines, and IL-33. We discussed the multiple cell signaling mechanisms underlying steroid resistance. Blocking the TSLP and other key signaling molecules like STAT5 can retrieve the sensitivity of natural helper-cells to corticosteroids. RXR derivatives treatment can modulate the activity of TSLP, which further modulates steroid resistance in severe asthmatic patients and in patients with refractory asthma. We discussed the steroid-resistance mediated by the Th2 cells and Th2-driven eosinophilia upon corticosteroid intake. Thus, this review will be beneficial for clinicians and molecular biologists to explore the inflammatory pathways associated with refractory asthma conditions and develop novel therapies against corticosteroid-resistant asthma.

Evaluation for airway obstruction in adult patients with stable ischemic heart disease.

BACKGROUND: Ischemic heart disease (IHD) and chronic airway disease (COPD and Asthma) are major epidemics accounting for significant mortality and morbidity. The combination presents many diagnostic challenges. Clinical symptoms and signs frequently overlap. There is a need for airway evaluation in these patients to plan appropriate management. METHODS: Consecutive stable IHD patients attending the cardiology OPD in a tertiary care centre were interviewed for collecting basic demographic information, brief medical, occupational, personal history and risk factors for coronary artery disease and airway disease, modified medical research centre (MMRC) grade for dyspnea, quality of life-St. George respiratory questionnaire (SGRQ), spirometry and six-min walk tests. Patients with chronic airway obstruction were treated as per guidelines and were followed up at 3rd month with spirometry, six-minute walk test and SGRQ. RESULTS: One hundred fourteen consecutive patients with stable cardiac disease were included (Males-88, Females-26). Mean age was 58.89±12.24years, 53.50% were smokers, 31.56% were alcoholics, 40.35% diabetics, 47.36% hypertensive. Twenty five patients had airway obstruction on spirometry (COPD-13 and Asthma-12) and none were on treatment. Thirty-one patients had cough and 48 patients had dyspnea. Patients with abnormal spirometry had higher symptoms, lower exercise tolerance and quality of life. Treatment with appropriate respiratory medications resulted in increase in lung function, quality of life and exercise tolerance at 3rd month. CONCLUSION: Chronic respiratory disease in patients with stable IHD is frequent but often missed due to overlap of symptoms. Spirometry is a simple tool to recognize the underlying pulmonary condition and patients respond favorably with appropriate treatment.

Management of chronic obstructive pulmonary disease in India: a systematic review.

OBJECTIVES: Chronic diseases are fast becoming the largest health burden in India. Despite this, their management in India has not been well studied. We aimed to systematically review the nature and efficacy of current management strategies for chronic obstructive pulmonary disease (COPD) in India. METHODS: We used database searches (MEDLINE, EMBASE, IndMED, CENTRAL and CINAHL), journal hand-searches, scanning of reference lists and contact with experts to identify studies for systematic review. We did not review management strategies aimed at chronic diseases more generally, nor management of acute exacerbations. Due to the heterogeneity of reviewed studies, meta-analysis was not appropriate. Thus, narrative methods were used. SETTING: India. PARTICIPANTS: All adult populations resident in India. MAIN OUTCOME MEASURES: 1. Trialled interventions and outcomes 2. Extent and efficacy of current management strategies 3. Above outcomes by subgroup. RESULTS: We found information regarding current management - particularly regarding the implementation of national guidelines and primary prevention - to be minimal. This led to difficulty in interpreting studies of management strategies, which were varied and generally of positive effect. Data regarding current management outcomes were very few. CONCLUSIONS: The current understanding of management strategies for COPD in India is limited due to a lack of published data. Determination of the extent of current use of management guidelines, availability and use of treatment, and current primary prevention strategies would be useful. This would also provide evidence on which to interpret existing and future studies of management outcomes and novel interventions.