Risk factors and characteristics associated with severe and difficult to treat asthma phenotype: an analysis of the ENFUMOSA group of patients based on the ECRHS questionnaire

Gaga, Mina; Papageorgiou, Niki; Yiourgioti, G; Karydi, P; Liapikou, Adamantia; Bitsakou, H.; Ζervas, Εleftherios; Koulouris, Nikolaos; Holgate, Stephen T.

doi:10.1111/j.1365-2222.2005.02281.x

Cited by 50 publications

(56 citation statements)

References 37 publications

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“…Despite optimal medical management, many asthmatics are treatment-resistant and/or have progressive disease (4). For example, β-agonists can paradoxically cause clinical decline (5).…”

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confidence: 99%

RETRACTED: Gastrin-releasing peptide blockade as a broad-spectrum anti-inflammatory therapy for asthma

Zhou¹,

Potts

Cuttitta

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Gastrin-releasing peptide (GRP) is synthesized by pulmonary neuroendocrine cells in inflammatory lung diseases, such as bronchopulmonary dysplasia (BPD). Many BPD infants develop asthma, a serious disorder of intermittent airway obstruction. Despite extensive research, early mechanisms of asthma remain controversial. The incidence of asthma is growing, now affecting >300 million people worldwide. To test the hypothesis that GRP mediates asthma, we used two murine models: ozone exposure for air pollution-induced airway hyperreactivity (AHR), and ovalbumin (OVA)-induced allergic airway disease. BALB/c mice were given small molecule GRP blocking agent 77427, or GRP blocking antibody 2A11, before exposure to ozone or OVA challenge. In both models, GRP blockade abrogated AHR and bronchoalveolar lavage (BAL) macrophages and granulocytes, and decreased BAL cytokines implicated in asthma, including those typically derived from Th1 (e.g., IL-2, TNFα), Th2 (e.g., IL-5, IL-13), Th17 (IL-17), macrophages (e.g., MCP-1, IL-1), and neutrophils (KC = IL-8). Dexamethasone generally had smaller effects on all parameters. Macrophages, T cells, and neutrophils express GRP receptor (GRPR). GRP blockade diminished serine phosphorylation of GRPR with ozone or OVA. Thus, GRP mediates AHR and airway inflammation in mice, suggesting that GRP blockade is promising as a broad-spectrum therapeutic approach to treat and/or prevent asthma in humans.

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“…Despite optimal medical management, many asthmatics are treatment-resistant and/or have progressive disease (4). For example, β-agonists can paradoxically cause clinical decline (5).…”

mentioning

confidence: 99%

RETRACTED: Gastrin-releasing peptide blockade as a broad-spectrum anti-inflammatory therapy for asthma

Zhou¹,

Potts

Cuttitta

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Adult asthma affects more women than men, and women may be predisposed to greater severity. [1][2][3][4] Additionally, women report onset of asthma later in life, often associated with times of hormonal change.In small studies, about 30% to 40% of women report worsening of asthma symptoms in relation to menstruation. [5][6][7][8] The presence of perimenstrual asthma (PMA) has been related to increases in asthmarelated ED visits, hospitalizations, ICU admissions, intubations, and near-fatal and fatal events.…”

mentioning

confidence: 99%

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confidence: 99%

Characteristics of Perimenstrual Asthma and Its Relation to Asthma Severity and Control

Rao

Moore

Bleecker

et al. 2013

Chest

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A sthma is a complex disease with recognized sex differences. Adult asthma affects more women than men, and women may be predisposed to greater severity. [1][2][3][4] Additionally, women report onset of asthma later in life, often associated with times of hormonal change.In small studies, about 30% to 40% of women report worsening of asthma symptoms in relation to menstruation. [5][6][7][8] The presence of perimenstrual asthma (PMA) has been related to increases in asthmarelated ED visits, hospitalizations, ICU admissions, intubations, and near-fatal and fatal events. 5 Unfortunately, the small nature of previous studies limits the ability to characterize contributing factors or implications of PMA.There is growing support for the concept that asthma consists of multiple phenotypes, which may be more easily recognized in severe asthma. 9,10 Although the National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP), a large network to study severe asthma mechanisms, recently identifi ed a female-predominant, late-onset phenotype, 11Background: Although perimenstrual asthma (PMA) has been associated with severe and diffi cultto-control asthma, it remains poorly characterized and understood. The objectives of this study were to identify clinical, demographic, and infl ammatory factors associated with PMA and to assess the association of PMA with asthma severity and control. Methods: Women with asthma recruited to the National Heart, Lung, and Blood Institute Severe Asthma Research Program who reported PMA symptoms on a screening questionnaire were analyzed in relation to basic demographics, clinical questionnaire data, immunoinfl ammatory markers, and physiologic parameters. Univariate comparisons between PMA and non-PMA groups were performed. A severity-adjusted model predicting PMA was created. Additional models addressed the role of PMA in asthma control. Results: Self-identifi ed PMA was reported in 17% of the subjects (n 5 92) and associated with higher BMI, lower FVC % predicted, and higher gastroesophageal refl ux disease rates. Fifty-two percent of the PMA group met criteria for severe asthma compared with 30% of the non-PMA group. In multivariable analyses controlling for severity, aspirin sensitivity and lower FVC % predicted were associated with the presence of PMA. Furthermore, after controlling for severity and confounders, PMA remained associated with more asthma symptoms and urgent health-care utilization. Conclusions: PMA is common in women with severe asthma and associated with poorly controlled disease. Aspirin sensitivity and lower FVC % predicted are associated with PMA after adjusting for multiple factors, suggesting that alterations in prostaglandins may contribute to this phenotype. CHEST 2013; 143(4):984-992Abbreviations: F eno 5 fraction of exhaled nitric oxide; GERD 5 gastroesophageal refl ux disease; HCU 5 health-care utilization; PG 5 prostaglandin; PMA 5 perimenstrual asthma; SARP 5 Severe Asthma Research Program

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“…Exposure to triggers, such as allergens, smoke, environmental and work-related irritants, as well as a sedentary lifestyle and poor diet, may be related to poor asthma control [26]. Avoidance of triggers is essential where possible, and this includes advice about allergen avoidance (house dust mites, pets, moulds) and change of work environment if necessary, while smoking cessation should be advocated at each visit.…”

Section: Risk Factors For Poor Asthma Controlmentioning

confidence: 99%

Control of asthma in real life: still a valuable goal?

et al. 2015

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Although studies show that control of asthma can be achieved in the majority of patients, surveys repeatedly show that this is not the case in real life. Important measures to implement in order to achieve asthma control are trained healthcare professionals, a good patient-doctor relationship, patient education, avoidance of exposure to triggers, personalised management and adherence to treatment. These measures help the majority of asthma patients but have not yet been widely implemented and there should be a concerted action for their implementation. Moreover, further and focused research is needed in severe/refractory asthma. @ERSpublications Achieving asthma control requires implementation of evidence-based guidelines and further research into severe asthma http://ow.ly/KzrOp

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Risk factors and characteristics associated with severe and difficult to treat asthma phenotype: an analysis of the ENFUMOSA group of patients based on the ECRHS questionnaire

Cited by 50 publications

References 37 publications

RETRACTED: Gastrin-releasing peptide blockade as a broad-spectrum anti-inflammatory therapy for asthma

RETRACTED: Gastrin-releasing peptide blockade as a broad-spectrum anti-inflammatory therapy for asthma

Characteristics of Perimenstrual Asthma and Its Relation to Asthma Severity and Control

Control of asthma in real life: still a valuable goal?

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