| 1. |
- Nwaru, Bright I, 1978, et al.
(författare)
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Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study.
- 2020
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Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 146:2, s. 438-446
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Tidskriftsartikel (refereegranskat)abstract
- Despite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma.We sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women.Using the Optimum Patient Care Research Database, a UK national primary care database, we constructed an open cohort of 16- to 45-year-old women (N= 564,896) followed for up to 17 years (ie, January 1, 2000, to December 31, 2016). We fitted multilevel Cox regression models to analyze the data.At baseline, 26% of women were using any hormonal contraceptives. During follow-up (3,597,146 person-years), 25,288 women developed asthma, an incidence rate of 7.0 (95% CI, 6.9-7.1) per 1000 person-years. Compared with nonuse, previous use of any hormonal contraceptives (hazard ratio [HR], 0.70; 95% CI, 0.68-0.72), combined (HR, 0.70; 95% CI, 0.68-0.72), and progestogen-only therapy (HR, 0.70; 95% CI, 0.67-0.74) was associated with reduced risk of new-onset asthma. For current use, the estimates were as follows: any (HR, 0.63; 95% CI, 0.61-0.65), combined (HR, 0.65; 95% CI, 0.62-0.67), and progestogen-only therapy (HR, 0.59; 95% CI, 0.56-0.62). Longer duration of use (1-2 years: HR, 0.83; 95% CI, 0.81-0.86; 3-4 years: HR, 0.64; 95% CI, 0.61-0.67; 5+ years: HR, 0.46; 95% CI, 0.44-0.49) was associated with a lower risk of asthma onset than nonuse.Hormonal contraceptive use was associated with reduced risk of new-onset asthma in women of reproductive age. Mechanistic investigations to uncover the biological processes for these observations are required. Clinical trials investigating the safety and effectiveness of hormonal contraceptives for primary prevention of asthma will be helpful to confirm these results.
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| 2. |
- Pfeffer, Paul E., et al.
(författare)
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Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes
- 2018
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Ingår i: Immunology. - : John Wiley & Sons. - 0019-2805 .- 1365-2567. ; 153:4, s. 502-512
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) -stimulated CD4 T lymphocytes have been investigated previously, but little work has focused on CD8 T-lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naive CD8 T-cell responses. Expression of the maturation/activation markers CD83, CCR7, CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow cytometry after stimulation with UPM in vitro in the presence/absence of granulocyte-macrophage colony-stimulating factor (GM-CSF). The capacity of these mDCs to stimulate naive CD8 T-lymphocyte responses in allogeneic co-culture was then assessed by measuring T-cell cytokine secretion using cytometric bead array, and proliferation and frequency of interferon-γ (IFN-γ)-producing T lymphocytes by flow cytometry. Treatment of mDCs with UPM increased expression of CD83 and CCR7, but not MHC class I. In allogeneic co-cultures, UPM treatment of mDCs enhanced CD8 T-cell proliferation and the frequency of IFN-γ+ cells. The secretion of tumour necrosis factor-α, interleukin-13, Granzyme A and Granzyme B were also increased. GM-CSF alone, and in concert with UPM, enhanced many of these T-cell functions. The PM-induced increase in Granzyme A was confirmed in a human experimental diesel exposure study. These data demonstrate that UPM treatment of mDCs enhances priming of naive CD8 T lymphocytes and increases production of pro-inflammatory cytokines. Such UPM-induced stimulation of CD8 cells may potentiate T-lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.
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