Differential lung tissue gene expression in males and females: implications for the susceptibility to develop COPD (original) (raw)
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Female phenotype and COPD exacerbation
2015
Conclusion: Current data showed that female COPD patients might be more prone to have severe exacerbations, a higher number of hospitalizations, and prolonged length of stay for hospitalization. Read this original research and sign up to receive International Journal of Chronic Obstructive Pulmonary Disease here: http://www.dovepress.com/articles.php?article\_id=21474
American Journal of Respiratory and Critical Care Medicine, 2020
hoc test odds would be 0.076 [0.25 3 0.303] and corresponding to a post hoc test probability of 7.6% [0.076/(1 1 0.076)]) (8). We designed the classifier to assess organ quality for donor pool expansion strategies, to identify organs for possible rehabilitation on ex vivo lung perfusion, and to identify potential targets for directed therapies in clinical trials. The validation of the pathways identified in this transcript panel highlights the importance of the innate immune system in the development of PGD and identifies its constituent genes as potential therapeutic targets. This work builds on previous work identifying associated pathways and developing clinical predictors important in PGD to assess risk prior to procurement to facilitate decision making for potential therapeutics and advanced surgical therapies (3, 4, 7). Although these results are promising, there are limitations to consider. The cohort sample size was small, therefore reducing overall power. Nonetheless, this study represents a temporal validation in tissue of prior findings in blood and BAL using a conventional machine learning approach. Tissue biopsy is an invasive procedure with associated risks. We validated our classifier in tissue to ensure that all lung compartments were sampled (endothelial, epithelial, and lymphoid), and we acknowledge that further refinement will be necessary to scale to clinical practice. Additionally, translating gene expression prediction to the bedside will require development of point-of-care technologies using abbreviated gene sets, such as those using microfluidics (9). As this study cohort did not overlap with our prior cohorts, we were unable to assess interactions between blood, BAL, and tissue compartments. Although this work is supported by several other studies that show association (3, 4, 10), additional validation will be necessary to confirm discriminant and diagnostic validity and generalizability. In summary, we have demonstrated that transcript analysis of donor lung tissue, using an innate immunity pathway classifier, can be used in conjunction with clinical variables to predict PGD with excellent discrimination and precision. With the ability to identify organ risk, this panel has the potential to alter future PGD clinical trial designs and lead to the development of precision medical approaches. As PGD drives morbidity and mortality associated with lung transplant, further research in this area has the potential to improve outcomes following transplantation. n Author disclosures are available with the text of this letter at www.atsjournals.org.
Widespread Sexual Dimorphism in the Transcriptome of Human Airway Epithelium in Response to Smoking
Epidemiological studies have shown that female smokers are at higher risk of chronic obstructive pulmonary disease (COPD). Female patients have worse symptoms and health status and increased risk of exacerbations. We determined the differences in the transcriptome of the airway epithelium between males and females at baseline and in response to smoking. We processed public gene expression data of human airway epithelium into a discovery cohort of 211 subjects (never smokers n=68; current smokers n=143) and two replication cohorts of 104 subjects (21 never, 52 current, and 31 former smokers) and 238 subjects (99 current and 139 former smokers. We analyzed gene differential expression with smoking status, sex, and smoking-by-sex interaction and used network approaches for modules' level analyses. We identified and replicated two differentially expressed modules between the sexes in response to smoking with genes located throughout the autosomes and not restricted to sex chromosome...
Sex and race factors in early-onset COPD
Current Opinion in Pulmonary Medicine, 2013
Purpose of review-Unlike other major diseases, mortality for chronic obstructive pulmonary disease (COPD) continues to increase. In recent years, COPD has evolved to increasingly affect women, minorities, and individuals from low socioeconomic groups. In women and African-Americans, evidence exists supporting the earlier development of COPD after less lifetime smoking. This review highlights new information on racial and sex differences in COPD. Recent findings-Sex and related hormonal changes affect T-cell phenotypes, immunity, and smoking-related metabolism of toxic intermediate metabolites. Alterations in the bronchoalveolar lavage proteome of women, but not of men, have allowed the differentiation of healthy female smokers from smokers with COPD. Sex significantly influences levels of inflammatory cytokines and correlates with different clinical and physiological parameters in female COPD patients. African-Americans with COPD are younger, smoke less, are more likely to currently smoke, and have worse health-related quality of life (QOL). African-Americans are more likely to report hospitalized exacerbations that impact QOL. African-Americans with COPD and asthma are nearly four times more likely to experience exacerbations. Summary-There are sex-specific and race-related differences in the manifestation of COPD. These differences warrant further physiologic, biologic, and genetic investigations.
Gender and Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, 2007
The prevalence of chronic obstructive pulmonary disease (COPD) in women is increasing, as is hospitalization for COPD. The number of women dying of COPD in the United States now surpasses men. Despite this, research suggests that physicians are still more likely to correctly diagnose men with COPD than women. Increased tobacco use in women likely explains some of the increase in the prevalence of COPD in women, but data suggest that women may actually be at greater risk of smoking-induced lung function impairment, more severe dyspnea, and poorer health status for the same level of tobacco exposure. The degree to which these observations represent biologic, physiologic, or sociologic differences is not known. Nonsmokers with COPD are also more likely to be female. In addition, new evidence is emerging that men and women may be phenotypically different in their response to tobacco smoke, with men being more prone to an emphysematous phenotype and women an airway predominant phenotype. Inasmuch as COPD is a disease of inflammation, it is also possible that sexual dimorphism of the human immune response may also be responsible for gender differences in the disease. More data are still needed on what the implications of these findings are on therapy. In this clinical commentary, we present current knowledge regarding how gender influences the epidemiology, diagnosis, and presentation of COPD in addition to physiologic and psychologic impairments and we attempt to offer insight into why these differences might exist and how this may influence therapeutic management.
Impact of gender on COPD expression in a real-life cohort
Respiratory Research, 2014
Reports regarding gender-related differences in COPD expression have provided conflicting results. In the French Initiatives BPCO real-world cohort, which contained 688 patients (146 women) when data were extracted, women were matched with men (1:3 ratio: n = 107:275) on age (5-year intervals) and FEV 1 (5% predicted intervals) and comparisons were performed using univariate logistic regressions. For a given age and level of airflow obstruction, women with COPD had higher BOD scores due to more pronounced dyspnea and lower BMI, suggesting worse prognosis, and were more likely to exhibit anxiety, suggesting the need for specific assessment and care.