The Effect of Smoking on the Transcriptional Regulation of Lung Inflammation in Patients with Chronic Obstructive Pulmonary Disease

Szulakowski, Patryk; Crowther, Ann J. L.; Jiménez, Luis A.; Donaldson, Kenneth; Mayer, Ruth; Leonard, Thomas B.; MacNee, William; Drost, Ellen

doi:10.1164/rccm.200505-725oc

Cited by 166 publications

(154 citation statements)

References 38 publications

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“…The hypothesis of increased exposure among smokers (and hence higher true prevalence of LTBI) might not be adequate to account for such observations. As smoking has been well associated with inflammatory responses within the lungs [18][19][20], there remains a possibility that it could boost reactivity to tuberculin and the more specific antigens. The dissociation of the tuberculin reaction size from the T-Spot.TB spot counts among current smokers could also suggest that the magnitude of such boosting differs for different antigens.…”

Section: Discussionmentioning

confidence: 99%

“…The median (interquartile range) tuberculin reaction sizes were 0 (0.0-6.3) mm and 16 (14)(15)(16)(17)(18)(19)(20) mm for subjects with a tuberculin reaction size ,10 and o10 mm, respectively. Of the 86 subjects with a positive T-Spot.TB test, 29 (33.7%) had a net spot count (peptides well count-control well count) of six or more for the early secretary antigenic target (ESAT)6 peptides well alone, 18 (20.9%) for the culture filtrate protein (CFP)10 peptides well alone, and 39 (45.3%) for both.…”

Section: From December 1 2004mentioning

confidence: 97%

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Comparison of T-Spot.TB and tuberculin skin test among silicotic patients

Leung

Yam²,

Yew³

et al. 2008

European Respiratory Journal

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In the present study, T-Spot.TB and the tuberculin skin test (TST) were compared in the screening of latent tuberculosis infection among silicotic patients.A conditional probability model was used to compare the potential clinical utilities of T-Spot.TB and TST performed on 134 silicotic subjects from December 1, 2004 to January 31, 2007. Data from a historical cohort were also reanalysed for further comparison.Agreement with T-Spot.TB was best using a TST cut-off of 10 mm. Age o65 yrs independently predicted a tuberculin reaction ,10 mm (odds ratio53), but not a negative T-Spot.TB response. Lower measures of agreement were observed among current smokers and those aged o65 yrs. Tuberculin reaction size was well correlated with both early secretary antigenic target 6 and culture filtrate protein 10 spot counts, except among current smokers. Within the current estimates of sensitivity (88-95%) and specificity (86-99%) for T-Spot.TB, the positive likelihood ratio for T-Spot.TB test would be substantially higher (6.29-95.0 versus 1.65-1.94) and negative likelihood ratio substantially lower (0.05-0.14 versus 0.32-0.41) than the corresponding ratios for the tuberculin test. A low tuberculosis risk differential was similarly observed between tuberculinnegative and untreated tuberculin-positive subjects in the historical cohort.T-Spot.TB is likely to perform better than tuberculin test in the screening of latent tuberculosis infection among silicotic subjects.

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Section: Discussionmentioning

confidence: 99%

Section: From December 1 2004mentioning

confidence: 97%

Comparison of T-Spot.TB and tuberculin skin test among silicotic patients

Leung

Yam²,

Yew³

et al. 2008

European Respiratory Journal

View full text Add to dashboard Cite

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“…HDAC2 activity is reduced in the lungs and in lung macrophages of patients with COPD, the degree of reduction being related to severity of COPD [85]; this may result in CS insensitivity through lack of repression of NF-κB-mediated gene expression [7]. Since HDAC2 is important for deacetylation of histone H3 [86], the increase in histone H3 acetylation in COPD [87] may result from a reduction in HDAC2 activity. Theophylline, which has been used for the treatment of asthma and COPD as a bronchodilator and as a potential anti-inflammatory agent, can recruit HDAC and restore CS sensitivity of macrophages in vitro [88,89].…”

Section: Corticosteroid Insensitivity In Airways Diseasementioning

confidence: 99%

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Chung

Caramori

Adcock

2009

Eur J Clin Pharmacol

119

106

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International audienceInhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting β-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 μg daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 μg daily, and addition of the LABA formoterol to budesonide (800 μg) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV and the rate of exacerbations. A reduction in the rate of decline in FEV of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases

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“…It is believed that cigarette smoking strongly affects both cell-mediated and humoral immune response, leading to both the release and inhibition of various pro-and anti-inflammatory mediators (27). It seems that the molecular mechanism at least partially responsible for immunomodulating capabilities of smoking involves activation of inhibitor of IκB kinase (IKK), fosforylation of IκB (inhibitor of nuclear factor NF-κB), NF-κB nuclear translocation and histone acetylation (17,18,28). NF-κB is a key transcription factor regulating the expression of various proinflammatory cytokines and numerous studies have linked its activation to elevated cytokine expression in smokers (29).…”

Section: Discussionmentioning

confidence: 99%

Different effect of smoking on genders in Crohn’s disease

Karczewski

Poniedziałek²,

Rzymski³

et al. 2015

Turk J Gastroenterol

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Background/Aims: Smoking is a well-established environmental risk factor in Crohn's disease (CD). The study was aimed to investigate possible gender differences in the effect of smoking on the course of CD, with a special focus on selected immune parameters such as Th1/Th2/Th17 cytokines and regulatory T cells (Tregs). Materials and Methods: A group of 55 adults with CD was enrolled to the study. The analysis of clinical, demographic and immunological characteristics of patients was performed according to their smoking status and gender. Values were considered significant when p≤0.05. Results: Patients who smoked, particularly females, more frequently suffered from a moderate-to-severe form of the disease, requiring glucocorticoid and immunosuppressive therapies. Smokers, particularly females, were also hospitalized and underwent surgeries more frequently than non-smokers. Cytometric analysis showed higher levels of serum proinflammatory cytokines and lower levels of peripheral Tregs in female smokers and former smokers, comparing to males from these subgroups.Conclusion: Presented results demonstrate that in all investigated subgroups, particularly however among current smokers and former smokers, female patients seemed to be more affected by CD. Females developed more severe form of the disease and experienced the onset earlier than men. The imbalance between pro-and anti-inflammatory factors observed in CD patients was also more distinct in female smokers and former smokers, comparing to males, and could substantially contribute to the severity of the disease. Exposure to smoking seems to be one of the environmental factors contributing to the gender differences in CD.

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The Effect of Smoking on the Transcriptional Regulation of Lung Inflammation in Patients with Chronic Obstructive Pulmonary Disease

Cited by 166 publications

References 38 publications

Comparison of T-Spot.TB and tuberculin skin test among silicotic patients

Comparison of T-Spot.TB and tuberculin skin test among silicotic patients

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Different effect of smoking on genders in Crohn’s disease

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