Effects of salmeterol on cilia and mucus in COPD and pneumonia patients

Piatti, G.; Ambrosetti, Umberto; Santus, Pierachille; Allegra, L.

doi:10.1016/j.phrs.2004.07.006

Cited by 47 publications

(40 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The inhibitory effect of P4 on CBF does not necessarily translate directly to a decrement in mucociliary clearance in vivo; however, the 40% fall in CBF is noteworthy relative to previous studies. Freshly isolated epithelia from patients with chronic obstructive pulmonary disease and pneumonia showed a 27% decrease in CBF relative to healthy control subjects, cigarette smoke condensate decreased forskolin-stimulated CBF by 21% in human sinonasal epithelia, and alcohol increased CBF by roughly 40% in isolated, demembranated cilia from bovine trachea (42,49,50). In those reports, the effect of sex was not studied, and we are not aware of studies that have specifically assessed sex differences in mucociliary clearance.…”

Section: Discussionmentioning

confidence: 99%

Sex Hormone–Dependent Regulation of Cilia Beat Frequency in Airway Epithelium

Jain

Ray

Pan

et al. 2012

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Previous studies have demonstrated a female disadvantage in airway diseases, such as asthma and bronchiectasis. The basis for this sex disparity is unknown. We hypothesized that the female sex hormone, progesterone (P4), inhibits functions of the normal airway mucociliary apparatus. P4 receptor (PR) expression was evaluated in human lung and cultured primary human airway epithelial cells isolated from male and female lung transplant donors. PR expression was restricted to the proximal region of the cilia of airway epithelia, and was similar in men and women. Expression of isoform PR-B was more abundant than PR-A in cells from both sexes. Airway epithelial cell exposure to P4 decreased cilia beat frequency (CBF) by 42.3% (67.2). Inhibition of CBF was prevented by coadministration of P4 with the active form of estrogen, 17b-estradiol, or the PR antagonist, mifepristone. P4 inhibition was time and dose dependent, with a significant decrease by 8 hours and maximal effect at 24 hours, accompanied by translocation of PR from the cilia to the nucleus. Inhibition of cilia beat was also prevented by treatment of cells with actinomycin D, suggesting that CBF inhibition is a transcriptionally mediated event. Together, these findings indicate that sex hormones influence the function of a key component of the mucociliary apparatus. These mechanisms may contribute to the sex disparity present in airway diseases and provide therapeutic targets for the treatment of these debilitating airway diseases.Keywords: cilia; progesterone receptor; cilia beat frequency; sex disparity; lung diseaseMultiple epidemiologic studies have established that women have more severe airway disease than men (1, 2). Women with asthma and chronic obstructive lung disease have more frequent and severe exacerbations than men, and a lower disease-specific quality of life (1, 3). Bronchiectasis affects women more commonly, and is more aggressive than in men (2, 4). For example, in cystic fibrosis (CF), a disease in which the impact of bronchiectasis has been extensively studied, women have worse outcomes and a decreased life expectancy compared with men, despite a similar cause of disease. This has been attributed specifically to a greater severity of lung disease, and is present even after adjusting for potentially confounding morphometric, nutritional, compliance, and microbial factors (4, 5). In addition, in models of Pseudomonas aeruginosa infection, one of the most common pathogens found in bronchiectasis, female mice are more affected than males, again for unclear reasons (6). Defects in mucociliary clearance are a central component to the development of bronchiectasis. We, therefore, hypothesize that female sex hormones regulate the mucociliary apparatus.The major female sex hormones, estrogen and progesterone (P4), vary in levels during ovulatory cycles, pregnancy, menopause, and with exogenous delivery. Although their roles in the uterus, ovary, oviduct, and breast have been well studied, expression and function in other tissues are less well desc...

show abstract

Section: Discussionmentioning

confidence: 99%

Sex Hormone–Dependent Regulation of Cilia Beat Frequency in Airway Epithelium

Jain

Ray

Pan

et al. 2012

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…Similarly, there is no clinical evidence to support the use of bronchodilators in chronic bronchitis in the absence of airflow obstruction, however, long acting 2 agonists have been shown to increase ciliary beat frequency, which could enhance sputum clearance (166). Phosphodiesterase 4 (PDE4) inhibitors are effective anti-inflammatory agents in animal models and have been shown to reduce inflammation in COPD and chronic bronchitis (167).…”

Section: Treatments For Stable Diseasementioning

confidence: 99%

The Importance of Chronic Bronchitis in Chronic Obstructive Pulmonary Disease

Sapey¹,

Stockley²

2011

Bronchitis

View full text Add to dashboard Cite

show abstract

“…The STT of smokers with COPD (16.5 [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] [6 -16] min) (P Ͻ .001). There was no difference in STT values between smokers with COPD and current smokers, and these values in ex-smokers with COPD were similar to those for the control group (Fig.…”

Section: Saccharin Transit Time Datamentioning

confidence: 99%

“…14 Some studies found modified mucociliary function in subjects with COPD, 15,16 and ciliary beat frequency was markedly lower in these subjects. 17 It is known that smoking cessation reduces the decline in FEV 1 , respiratory symptoms, and airway inflammation and that it improves longterm prognosis. [18][19][20] However, it is still unknown whether smoking cessation may modify MCC in patients with COPD and whether this might contribute to fewer exacerbations.…”

Section: Introductionmentioning

confidence: 99%