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A large subgroup of mild-to-moderate asthma is persistently noneosinophilic.

ABSTRACT: Airway eosinophilia is typical of asthma, and many controller treatments target eosinophilic disease. Asthma is clinically heterogeneous, however, and a subgroup of people with asthma do not have airway eosinophilia. The size of this subgroup is uncertain because prior studies have not examined repeated measures of sputum cytology to determine when people with asthma have intermittent versus persistent sputum eosinophila and when they are persistently noneosinophilic.To determine the prevalence and clinical characteristics of the noneosinophilic asthma phenotype.We analyzed sputum cytology data from 995 subjects with asthma enrolled in clinical trials in the Asthma Clinical Research Network where they had undergone sputum induction and measures of sputum cytology, often repeatedly, and assessment of responses to standardized asthma treatments.In cross-sectional analyses, sputum eosinophilia (?2% eosinophils) was found in only 36% of subjects with asthma not taking an inhaled corticosteroid (ICS) and 17% of ICS-treated subjects with asthma; an absence of eosinophilia was noted frequently, even in subjects with asthma whose disease was suboptimally controlled. In repeated measures analyses of people with asthma not taking an ICS, 22% of subjects had sputum eosinophilia on every occasion (persistent eosinophilia); 31% had eosinophilia on at least one occasion (intermittent eosinophilia); and 47% had no eosinophilia on every occasion (persistently noneosinophilic). Two weeks of combined antiinflammatory therapy caused significant improvements in airflow obstruction in eosinophilic asthma, but not in persistently noneosinophilic asthma. In contrast, bronchodilator responses to albuterol were similar in eosinophilic and noneosinophilic asthma.Approximately half of patients with mild-to-moderate asthma have persistently noneosinophilic disease, a disease phenotype that responds poorly to currently available antiinflammatory therapy.

SUBMITTER: McGrath KW

PROVIDER: S-EPMC3326288 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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A large subgroup of mild-to-moderate asthma is persistently noneosinophilic.

McGrath Kelly Wong KW Icitovic Nikolina N Boushey Homer A HA Lazarus Stephen C SC Sutherland E Rand ER Chinchilli Vernon M VM Fahy John V JV

American journal of respiratory and critical care medicine 20120120 6

<h4>Rationale</h4>Airway eosinophilia is typical of asthma, and many controller treatments target eosinophilic disease. Asthma is clinically heterogeneous, however, and a subgroup of people with asthma do not have airway eosinophilia. The size of this subgroup is uncertain because prior studies have not examined repeated measures of sputum cytology to determine when people with asthma have intermittent versus persistent sputum eosinophila and when they are persistently noneosinophilic.<h4>Object ...[more]

PMID: 22268133

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Project description:Noneosinophilic airway inflammation occurs in approximately 50% of patients with asthma. It is subdivided into neutrophilic or paucigranulocytic inflammation, although the proportion of each subtype is uncertain because of variable cut-off points used to define neutrophilia. This article reviews the evidence for noneosinophilic inflammation being a target for therapy in asthma and assesses clinical trials of licensed drugs, novel small molecules and biologics agents in noneosinophilic inflammation. Current symptoms, rate of exacerbations and decline in lung function are generally less in noneosinophilic asthma than eosinophilic asthma. Noneosinophilic inflammation is associated with corticosteroid insensitivity. Neutrophil activation in the airways and systemic inflammation is reported in neutrophilic asthma. Neutrophilia in asthma may be due to corticosteroids, associated chronic pulmonary infection, altered airway microbiome or delayed neutrophil apoptosis. The cause of poorly controlled noneosinophilic asthma may differ between patients and involve several mechanism including neutrophilic inflammation, T helper 2 (Th2)-low or other subtypes of airway inflammation or corticosteroid insensitivity as well as noninflammatory pathways such as airway hyperreactivity and remodelling. Smoking cessation in asthmatic smokers and removal from exposure to some occupational agents reduces neutrophilic inflammation. Preliminary studies of 'off-label' use of licensed drugs suggest that macrolides show efficacy in nonsmokers with noneosinophilic severe asthma and statins, low-dose theophylline and peroxisome proliferator-activated receptor gamma (PPAR?) agonists may benefit asthmatic smokers with noneosinophilic inflammation. Novel small molecules targeting neutrophilic inflammation, such as chemokine (CXC) receptor 2 (CXCR2) antagonists reduce neutrophils, but do not improve clinical outcomes in studies to date. Inhaled phosphodiesterase (PDE)4 inhibitors, dual PDE3 and PDE4 inhibitors, p38MAPK (mitogen-activated protein kinase) inhibitors, tyrosine kinase inhibitors and PI (phosphoinositide) 3kinase inhibitors are under development and these compounds may be of benefit in noneosinophilic inflammation. The results of clinical trials of biological agents targeting mediators associated with noneosinophilic inflammation, such as interleukin (IL)-17 and tumor necrosis factor (TNF)-? are disappointing. Greater understanding of the mechanisms of noneosinophilic inflammation in asthma should lead to improved therapies.

Project description:BackgroundAlthough obesity has been hypothesized to worsen asthma, data from studies of subjects with well-characterized asthma are lacking.ObjectiveWe sought to evaluate the relationship between body mass index (BMI), asthma impairment, and response to therapy.MethodsBMI (in kilograms per meter squared) and asthma phenotypic and treatment response data were extracted from Asthma Clinical Research Network studies. The cross-sectional relationship between BMI and asthma impairment was analyzed, as was the longitudinal relationship between BMI and response to asthma controller therapies.ResultsOne thousand two hundred sixty-five subjects with mild-to-moderate persistent asthma were evaluated. Analyses of lean versus overweight/obese asthmatic subjects demonstrated small differences in FEV1 (3.05 vs 2.91 L, P = .001), FEV1/forced vital capacity ratio (mean, 83.5% vs 82.4%; P = .01), rescue albuterol use (1.1 vs 1.2 puffs per day, P = .03), and asthma-related quality of life (5.77 vs 5.59, P = .0004). Overweight/obese asthmatic subjects demonstrated a smaller improvement in exhaled nitric oxide levels with inhaled corticosteroid (ICS) treatment than did lean asthmatic subjects (3.6 vs 6.5 ppb, P = .04). With ICS/long-acting beta-agonist treatment, overweight/obese asthmatic subjects demonstrated smaller improvements in lung function than lean asthmatic subjects, with an 80 mL (P = .04) and 1.7% (P = .02) lesser improvement in FEV1 and FEV1/forced vital capacity ratio, respectively. Significant differences in therapeutic response to leukotriene modifiers between BMI categories were not observed.ConclusionsIncreased BMI is not associated with clinically significant worsening of impairment in subjects with mild-to-moderate persistent asthma. There is a modest association between increased BMI and reduced therapeutic effect of ICS-containing regimens in this patient population. Prospective studies evaluating the effect of being overweight or obese on treatment response in asthma are warranted.

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A large subgroup of mild-to-moderate asthma is persistently noneosinophilic.

Publications

A large subgroup of mild-to-moderate asthma is persistently noneosinophilic.

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