Asthma and lower airway diseaseGender differences in the bronchoalveolar lavage cell proteome of patients with chronic obstructive pulmonary disease
Section snippets
Methods
Detailed descriptions of the methods used in this study are provided in the Methods section in this article's Online Repository at www.jacionline.org.
Results
Statistical analyses were performed by comparing smoking and nonsmoking subjects separately to limit the confounding effects of smoking. Hence the group comparisons were made between healthy smokers versus actively smoking patients with COPD and healthy nonsmoking control subjects versus exsmokers with COPD. In addition, we compared intergroup and intragroup gender differences. Additional exclusion criteria specifically designed for the proteome analyses were applied to the Karolinska COSMIC
Discussion
COPD is increasing in incidence and mortality worldwide, an increase that is primarily driven by the female population. In spite of its prevalence, neither efficacious treatments nor reliable diagnostic tools are available to date.1 In part, this might be due to COPD being an umbrella diagnosis, with a number of various clinical manifestations resulting in different disease phenotypes.5 The heterogeneous disease characteristics of COPD thus require the discovery of novel molecular markers
References (57)
- et al.
Not 15 but 50% of smokers develop COPD?—report from the Obstructive Lung Disease in Northern Sweden studies
Respir Med
(2003) - et al.
Sex differences in emphysema and airway disease in smokers
Chest
(2009) - et al.
Racial and gender differences in susceptibility to tobacco smoke among patients with chronic obstructive pulmonary disease
Respir Med
(2006) - et al.
Clinical proteomics in lung diseases
Pathol Res Pract
(2004) - et al.
Proteomic analysis in lung tissue of smokers and COPD patients
Chest
(2009) - et al.
Biologic and pharmacologic therapies in clinical development for the inflammatory response in COPD
Drug Discov Today
(2010) - et al.
An approach to correlate tandem mass-spectral data of peptides with amino-acid-sequences in a protein database
J Am Soc Mass Spectrom
(1994) - et al.
Systemic effects of COPD
Respir Med
(2005) - et al.
Associations of muscle depletion with health status. Another gender difference in COPD?
Clin Nutr
(2011) - et al.
Prevalence of nutritional depletion in a large out-patient population of patients with COPD
Respir Med
(2006)
Global and regional causes of death
Br Med Bull
The global burden of disease, 1990-2020
Nat Med
Reconsidering sex-based stereotypes of COPD
Prim Care Respir J
Burden and pathogenesis of chronic obstructive pulmonary disease
Proc Am Thorac Soc
Chronic obstructive pulmonary disease surveillance—United States, 1971-2000
MMWR Surveill Summ
Chronic obstructive pulmonary disease: does gender really matter?
Lung India
Quantitative computed tomography: emphysema and airway wall thickness by sex, age and smoking
Eur Respir J
Sex Differences and Sex Steroids in Lung Health and Disease
Endocr Rev
Female smokers beyond the perimenopausal period are at increased risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis
Respir Res
Gender differences in COPD: are women more susceptible to smoking effects than men?
Thorax
Sputum proteomics identifies elevated PIGR levels in smokers and mild-to-moderate COPD
J Proteome Res
Advances in proteomic techniques for biomarker discovery in COPD
Expert Rev Clin Immunol
Proteomics-based biomarkers in chronic obstructive pulmonary disease
J Proteome Res
Identification of novel diagnostic biomarkers for asthma and chronic obstructive pulmonary disease
Am J Respir Crit Care Med
Identification of differentially expressed proteins in blood plasma of control and cigarette smoke-exposed mice by 2-D DIGE/MS
Proteomics
From proteomics to prescription-the search for COPD biomarkers
COPD
Heat shock protein 27 and cyclophilin A associate with the pathogenesis of COPD
Respirology
Proteome analysis of bronchoalveolar lavage in lung diseases
Proteomics
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Metabolomics in COPD
2023, Archivos de BronconeumologiaHigher susceptibility of males to bleomycin-induced pulmonary inflammation is associated with sex-specific transcriptomic differences in myeloid cells
2022, Toxicology and Applied PharmacologyCitation Excerpt :Recently, Choudhary et al., reported sex-associated gene expression differences in the alveolar macrophages harvested from male and female mice, basally as well as after repetitive ozone exposure (Choudhary et al., 2021). Kohler et al., analyzed the proteome of BAL cells of chronic obstructive pulmonary disease (COPD) patients and showed significant gender-specific differences (Kohler et al., 2013). Furthermore, Sadeleer et al., recently clustered IPF patients based on their BAL gene expression signatures and showed that the cluster enriched for increased epithelial and immune signatures was associated with worse gender-age-physiology corrected survival (De Sadeleer et al., 2022).
Differences Between Men and Women with Chronic Obstructive Pulmonary Disease
2021, Clinics in Chest MedicineCitation Excerpt :At a cellular level, there are many potential metabolic and hormonal pathways that are significantly different in men and women that could potentially influence susceptibility to the effects of cigarette smoke.31 In proteomic analyses of bronco-alveolar lavage (BAL), significant gender differences were seen in the cell proteome in female but not male patients with COPD.32 In a related study,33 the investigators confirmed these findings showing that cells from female smokers with normal lung function and early-stage COPD showed more pronounced alterations compared with male smokers in whom alterations were minor.
Protein Biomarkers for COPD Outcomes
2021, ChestProteomics: An advanced tool to unravel the role of alveolar macrophages in respiratory diseases
2021, International Journal of Biochemistry and Cell BiologyCitation Excerpt :An in vitro study involving infection of primary human AMs with influenza A virus has shown dysregulation of proteins related to IFN-mediated responses, inflammatory responses, and apoptosis, which is consistent with findings that type-I IFNs play an essential role in mediating influenza infection (Liu et al., 2012). The proteome of AMs also shows altered protein profiles based on gender differences, and studies on AMs isolated from BAL fluid of both HIV-infected smokers and smokers with COPD show dysregulation of lysosomal proteins in female patients, but not in males (Kohler et al., 2013; Rahmanian et al., 2014). Due to the difficulties of isolating AMs from either lung or BAL fluid, a modest number of publications have reported proteomics characterization of AMs using current MS-based technologies.
Vulnerability of women to tobacco: The broncho-pulmonary consequences (asthma, COPD)
2019, Revue des Maladies Respiratoires
Supported by the Swedish Heart-Lung Foundation, the Swedish Foundation for Strategic Research (SSF), VINNOVA (VINN-MER), EU Fp6 Marie Curie, the Karolinska Institutet, AFA Insurances for financial support, the King Oscar II Jubilee Foundation, the Mats Kleeberg Foundation, King Gustaf V's, and Queen Victoria's Freemasons, and Hesselman’s Foundations, the regional agreement on medical training and clinical research (ALF) between Stockholm County Council, and the Karolinska Institutet.
Disclosure of potential conflict of interest: M. Kohler has received grants from the Karolinska Institutet and AFA Insurances. S. Kjellqvist has received grants from the Swedish Research Council. A. Eklund has received grants from the Swedish Heart Lung Foundation. A. M. Wheelock has received grants from the Swedish Heart Lung Foundation, the Swedish Foundation for Strategic Research, VINNOVA, EU Fp6 Marie Curie, and the King Oscar II Jubilee Foundation. The rest of the authors declare that they have no relevant conflicts of interest.
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Previously Sanela Kurtovic.