Physiopathology Of Asthma Pdf Download PORTABLE
CLICK HERE >>> https://bltlly.com/2tqhXx
Asthma can deteriorate during the perimenstrual period, a phenomenon known as perimenstrual asthma (PMA), which represents a unique, highly symptomatic asthma phenotype. It is distinguished from traditional allergic asthma by aspirin sensitivity, less atopy, and lower lung capacity.
PMA incidence is reported to vary between 19 and 40 % of asthmatic women. The presence of PMA has been related to increases in asthma-related emergency department visits, hospitalizations and emergency treatment including intubations.
This paper will focus on the pathophysiology of hormone triggered cycle related inflammatory/allergic events and their relation with asthma. We reviewed the scientific literature on Pubmed database for studies on PMA. Key word were PMA, mastcells, estrogens, inflammation, oral contraception, hormonal replacement therapy (HRT), and hormone free interval (HFI).
Special attention will be devoted to the possibility of reducing the perimenstrual worsening of asthma and associated symptoms by reducing estrogens fluctuations, with appropriate hormonal contraception and reduced HFI. This novel therapeutical approach will be finally discussed.
PMA represents a unique, highly symptomatic, and exacerbation-prone asthma phenotype associated with aspirin sensitivity, less atopy (less IgE level), and lower forced vital capacity, that distinguish it from traditional allergic asthma .
The presence of PMA has been related to increases in asthma-related Emergency Department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, intubations, and near-fatal and fatal events [13, 26].
The physiology of the menstrual cycle is characterized by fluctuating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol, progesterone and testosterone. The perimenstrual phase is characterized by a decline in progesterone and oestradiol levels , which triggers MC degranulation at the basal layer of the endometrium. This induces a local (with endometrial tissue breakdown and menstruation) and a systemic inflammation (with MC and eosinophil degranulation and consequent increase in inflammatory markers in tissues where hyperactive MC are already present, such as the lung/bronchial tissues of an asthmatic woman) .
A study from Tan et al. compared airway reactivity to adenosine monophosphate (AMP) in female asthmatics with natural menstrual cycles and those taking the OC (with 21 days of active treatment followed by a seven-day break). There was a significant increase in airway reactivity in the group with natural menstrual cycles in the luteal phase, coincident with the increase in progesterone and estradiol. In the OC group the hormonal profile was stable, and so was bronchial reactivity. They concluded that asthmatic patients receiving the OC had attenuated cyclical change in airway reactivity as well as reduced diurnal peak expiratory flow rate variability, which was associated with suppression of the normal luteal phase rise in sex-hormones .
Understanding that the menstrual fall of estradiol and progesterone triggers asthmatic crises in vulnerable women may suggest new preventive strategies which are pathophysiologically oriented, such as stabilizing estradiol and progesterone/progestins levels and reducing the hormone free interval (HFI), when OC is considered. Prospective controlled studies are needed to test this working hypothesis.
The effect of E2V/DNG on maintaining iron levels has a positive effect on the dopaminergic system, which is involved in ameliorating mood, assertiveness, physical and mental energy, and reducing the risk of depression. Moreover, it can reduce the periodical asthmatic crisis, which may be so important to cause a post-traumatic stress disorder , and the need of corticosteroids boluses and chronic therapy thus reducing the collateral effects such as weight augmentation 
PMA is usually described as cyclical deterioration of asthma during the luteal phase and/or during the first days of menstruation [25, 26], and is reported to be about 19 % of asthmatic women, while other studies reported the incidence to be as high as 40 % .
Women today have many more periods in their lifetime than their ancestors. Menstrual bleeding is not biologically necessary in women taking hormonal contraceptives. Furthermore, it may be advantageous for the women to have more stable levels of hormones throughout the cycle. The monthly fluctuations in oestrogens, progesterone and androgens are associated with a range of symptoms, both genital (i.e. vaginal bleeding, heavy menstrual bleeding, dysmenorrhoea and pelvic pain) and systemic (depression, fatigue, headache, IBS symptoms, asthma and allergy), triggered by a local and systemic rise in inflammatory molecules released by MC when estrogens drop. These symptoms arise through a complex interaction between the endocrine and immune systems.
OCs traditionally feature a 7-day HFI, during which menstruation occurs. Formulations with a shorter HFI have recently been developed with the aim of offering a reduction in hormone withdrawal-associated symptoms together with more powerful ovarian suppression. E2V/DNG is administered on a 26/2 regimen and has been shown to offer high contraceptive efficacy together with a reduction in heavy menstrual bleeding, improvement in hormone withdrawal-associated symptoms and improvement in sexual function. E2V/DNG may, therefore, be a good alternative to conventional 21/7 COCs for women with bothersome COC- or menstruation-related symptoms, as exacerbation of asthma crisis.
Anticholinergics are widely used for the treatment of COPD, and to a lesser extent for asthma. Primarily used as bronchodilators, they reverse the action of vagally derived acetylcholine on airway smooth muscle contraction. Recent novel studies suggest that the effects of anticholinergics likely extend far beyond inducing bronchodilation, as the novel anticholinergic drug tiotropium bromide can effectively inhibit accelerated decline of lung function in COPD patients. Vagal tone is increased in airway inflammation associated with asthma and COPD; this results from exaggerated acetylcholine release and enhanced expression of downstream signaling components in airway smooth muscle. Vagally derived acetylcholine also regulates mucus production in the airways. A number of recent research papers also indicate that acetylcholine, acting through muscarinic receptors, may in part regulate pathological changes associated with airway remodeling. Muscarinic receptor signalling regulates airway smooth muscle thickening and differentiation, both in vitro and in vivo. Furthermore, acetylcholine and its synthesizing enzyme, choline acetyl transferase (ChAT), are ubiquitously expressed throughout the airways. Most notably epithelial cells and inflammatory cells generate acetylcholine, and express functional muscarinic receptors. Interestingly, recent work indicates the expression and function of muscarinic receptors on neutrophils is increased in COPD. Considering the potential broad role for endogenous acetylcholine in airway biology, this review summarizes established and novel aspects of muscarinic receptor signaling in relation to the pathophysiology and treatment of asthma and COPD.
Acetylcholine is the primary parasympathetic neurotransmitter in the airways, and is traditionally associated with inducing airway smooth muscle contraction and mucus secretion. Parasympathetic activity is increased in airway inflammation, which is the basis for the use of anticholinergic therapy in asthma and chronic obstructive pulmonary disease (COPD) . Anticholinergics constitute a particularly important bronchodilator therapy in COPD, as vagal tone appears to be the only reversible component of airflow limitation in this condition . Recent evidence indicates that acetylcholine production in the airways is not restricted to the parasympathetic nervous system: acetylcholine is also released from non-neuronal origins such as the bronchial epithelium and inflammatory cells . Furthermore, accumulating evidence suggests acetylcholine (either neuronal or non-neuronal) may play an essential regulatory role in the mechanisms that drive the structural changes in the airways, called airway remodeling, that are associated with chronic airway inflammation [3, 4]. These recent findings indicate that acetylcholine, acting on muscarinic receptors, may contribute to the pathophysiology and pathogenesis of asthma and COPD to a much larger extent than is currently appreciated. This concept is underscored by findings that the recently introduced long-acting anticholinergic agent, tiotropium bromide , markedly inhibits accelerated lung function decline in COPD patients . This article will review the established and novel muscarinic receptor signaling mechanisms in airway physiology, and discuss their involvement in the pathophysiology of asthma and COPD. Though nicotinic cholinergic receptors are present throughout the airways (see  for review), their function will not be discussed in view of the muscarinic receptor specificity of the current clinically used anticholinergics.
Pathways central in muscarinic receptor mediated airway smooth muscle contraction. Muscarinic receptor (MR) agonists induce contraction of airway smooth muscle by Ca2+ dependent and Ca2+ independent pathways. Through associated Gq alpha subunits, the muscarinic M3 receptor activates phospholipase C (PLC), which releases inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) after hydrolytic conversion of phosphatidylinositol-4,5-bisphosphate (PIP2). IP3 induces the release of Ca2+ from internal sarcoplasmatic reticulum (SR) stores. Coupling of M3 receptor to CD38 through as yet undefined mechanisms contributes to the production of cyclic ADP ribose (cADPR) and the release of Ca2+ through ryanodine receptor channels in the SR. Ca2+ release increases free cytosolic Ca2