Role of Galectin-3 in the pathophysiology underlying allergic lung inflammation in a tissue inhibitor of metalloproteinases 1 knockout model of murine asthma.

Asthma is a chronic inflammatory respiratory disease characterized by airway inflammation, airway hyperresponsiveness and reversible airway obstruction. Understanding the mechanisms that underlie the various endotypes of asthma could lead to novel and more personalized therapies for individuals with asthma. Using a tissue inhibitor of metalloproteinases 1 (TIMP-1) knockout murine allergic asthma model, we previously showed that TIMP-1 deficiency results in an asthma phenotype, exhibiting airway hyperreactivity, enhanced eosinophilic inflammation and T helper type 2 cytokine gene and protein expression following sensitization with ovalbumin. In the current study, we compared the expression of Galectins and other key cytokines in a murine allergic asthma model using wild-type and TIMP-1 knockout mice. We also examined the effects of Galectin-3 (Gal-3) inhibition on a non-T helper type 2 cytokine interleukin-17 (IL-17) to evaluate the relationship between Gal-3 and the IL-17 axis in allergic asthma. Our results showed a significant increase in Gal-3, IL-17 and transforming growth factor-ß1 gene expression in lung tissue isolated from an allergic asthma murine model using TIMP-1 knockout. Gal-3 gene and protein expression levels were also significantly higher in lung tissue from an allergic asthma murine model using TIMP-1 knockout. Our data show that Gal-3 may regulate the IL-17 axis and play a pivotal role in the modulation of inflammation during experimental allergic asthma.

Counseling patients with asthma and allergy about electronic cigarettes: an evidence-based approach.

OBJECTIVE: To provide an evidence-based review of common safety concerns and emerging potential benefits deriving from the regular use of electronic cigarettes (ECs) and thus improve counseling between physicians and their patients with asthma and allergy using or intending to use ECs. DATA SOURCES: Peer-reviewed articles from the National Center for Biotechnology Information's PubMed about ECs, risk reduction, and harm reversal were appraised. STUDY SELECTION: Keywords used in the search were smoking cessation, electronic cigarette, counseling, asthma, allergy, nicotine, tobacco harm reduction, and harm reversal. RESULTS: Vapor toxicology is far less problematic compared with combustible cigarettes, with exclusive EC users having substantial lower risk of exposure to tobacco smoke toxicants and carcinogens compared with cigarette smokers. Moreover, there is emerging evidence that switching to regular EC use could produce significant respiratory health gains. CONCLUSION: Inaccurate and inconsistent information about EC safety and efficacy, tobacco harm reduction, and nicotine toxicity is being offered to smokers and EC users. In particular, most health care professionals cannot communicate a clear and consistent message to their patients with respiratory problems and allergy who use or intend to use ECs. Therefore, it is important for the medical community to take an active role in considering all the pathways available to a smoking patient and recommend those that provide the greatest probability of eliminating exposure to tobacco smoke, including ECs.

Respiratory infections and pneumonia: potential benefits of switching from smoking to vaping.

Abstaining from tobacco smoking is likely to lower the risk of respiratory infections and pneumonia. Unfortunately, quitting smoking is not easy. Electronic cigarettes (ECs) are emerging as an attractive long-term alternative nicotine source to conventional cigarettes and are being adopted by smokers who wish to reduce or quit cigarette consumption. Also, given that the propylene glycol in EC aerosols is a potent bactericidal agent, switching from smoking to regular vaping is likely to produce additional lung health benefits. Here, we critically address some of the concerns arising from regular EC use in relation to lung health, including respiratory infections and pneumonia. In conclusion, smokers who quit by switching to regular ECs use can reduce risk and reverse harm from tobacco smoking. Innovation in the e-vapour category is likely not only to further minimise residual health risks, but also to maximise health benefits.

Localization of matrix metalloproteinase (MMP)-9 in lung tissue of a murine model of allergic asthma.

MMP-9 (gelatinase B) is recognized in chronic obstructive pulmonary disease (COPD) and now asthma as playing a central role in matrix degradation in injury, as well as contributing to the remodeling process. The increasing focus on MMP-9 in human and animal research supports the need for a reliable immunostain in lung tissue. However, MMP-9 immunostaining in murine systems is hampered by several factors. First, many of the anti-human antibodies do not readily cross-react with murine MMP-9 despite the high degree of conservation between human and murine MMP-9. Secondly, the availability of detailed protocols is limited. Lung MMP-9 immunostaining is further complicated by technical issues such as edge effect, availability of positive and negative controls, antigen retrieval, staining specificity, and the need to achieve a delicate balance of primary and secondary antibody concentrations, and colorimetric reagents which will allow visualization of specific cell expression in highly delicate lung tissue, while also demonstrating adequate uptake in (extra-pulmonary) tissue controls. We describe a detailed method for immunostaining MMP-9 in mouse lung paraffin-embedded tissue utilizing human ovary as a control since MMP-9 is known to be over-expressed in human ovarian carcinomas.

Asthma in the elderly: Current understanding and future research needs--a report of a National Institute on Aging (NIA) workshop.

Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population.

Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma.

Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma.