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Severe adult-onset asthma: A distinct phenotype.

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Severe adult-onset asthma: A distinct phenotype.

J Allergy Clin Immunol. 2013 Jun 24;

Authors: Amelink M, de Groot JC, de Nijs SB, Lutter R, Zwinderman AH, Sterk PJ, Ten Brinke A, Bel EH

Abstract
BACKGROUND: Some patients with adult-onset asthma have severe disease, whereas others have mild transient disease. It is currently unknown whether patients with severe adult-onset asthma represent a distinct clinical phenotype.
OBJECTIVE: We sought to investigate whether disease severity in patients with adult-onset asthma is associated with specific phenotypic characteristics.
METHODS: One hundred seventy-six patients with adult-onset asthma were recruited from 1 academic and 3 nonacademic outpatient clinics. Severe refractory asthma was defined according to international Innovative Medicines Initiative criteria, and mild-to-moderate persistent asthma was defined according to Global Initiative for Asthma criteria. Patients were characterized with respect to clinical, functional, and inflammatory parameters. Unpaired t tests and χ(2) tests were used for group comparisons; both univariate and multivariate logistic regression were used to determine factors associated with disease severity.
RESULTS: Apart from the expected high symptom scores, poor quality of life, need for high-intensity treatment, low lung function, and high exacerbation rate, patients with severe adult-onset asthma were more often nonatopic (52% vs 34%, P = .02) and had more nasal symptoms and nasal polyposis (54% vs 27%, P ≤ .001), higher exhaled nitric oxide levels (38 vs 27 ppb, P = .02) and blood neutrophil counts (5.3 vs 4.0 10(9)/L, P ≤ .001) and sputum eosinophilia (11.8% vs 0.8%, P ≤ .001). Multiple logistic regression analysis showed that increased blood neutrophil (odds ratio, 10.9; P = .002) and sputum eosinophil (odds ratio, 1.5; P = .005) counts were independently associated with severe adult-onset disease.
CONCLUSION: The majority of patients with severe adult-onset asthma are nonatopic and have persistent eosinophilic airway inflammation. This suggests that severe adult-onset asthma has a distinct underlying mechanism compared with milder disease.

PMID: 23806634 [PubMed - as supplied by publisher]

Microbial content of household dust associated with exhaled NO in asthmatic children.

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Microbial content of household dust associated with exhaled NO in asthmatic children.

Environ Int. 2013 Jun 24;59C:141-147

Authors: Johansson E, Reponen T, Vesper S, Levin L, Lockey J, Ryan P, Bernstein DI, Villareal M, Khurana Hershey GK, Schaffer C, Lemasters G

Abstract
Exhaled nitric oxide (eNO) is increasingly used as a non-invasive measure of airway inflammation. Despite this, little information exists regarding the potential effects of indoor microbial components on eNO. We determined the influence of microbial contaminants in house dust and other indoor environmental characteristics on eNO levels in seven-year-olds with and without a physician-diagnosis of asthma. The study included 158 children recruited from a birth cohort study, and 32 were physician-diagnosed as asthmatic. The relationship between eNO levels and exposures to home dust streptomycetes, endotoxin, and molds was investigated. Streptomycetes and endotoxin were analyzed both as loads and concentrations in separate models. Dog, cat, and dust mite allergens also were evaluated. In the multivariate exposure models, high streptomycetes loads and concentrations were significantly associated with a decrease in eNO levels in asthmatic (p<0.001) but not in healthy children. The presence of dog allergen, however, was associated with increased levels of eNO (p=0.001). Dust endotoxin was not significant. The relationship between eNO and indoor exposure to common outdoor molds was u-shaped. In non-asthmatic children, none of the exposure variables was significantly associated with eNO levels. To our knowledge, this is the first study demonstrating a significant association between microbial components in the indoor environment and eNO levels in asthmatic children. This study demonstrates the importance of simultaneously assessing multiple home exposures of asthmatic children to better understand opposing effects. Common components of the indoor Streptomyces community may beneficially influence airway inflammation.

PMID: 23807177 [PubMed - as supplied by publisher]

Iatrogenic Cushing's Syndrome in Patients Receiving Inhaled Budesonide and Itraconazole or Ritonavir: Two Cases and Literature Review.

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Iatrogenic Cushing's Syndrome in Patients Receiving Inhaled Budesonide and Itraconazole or Ritonavir: Two Cases and Literature Review.

Endocr Pract. 2013 Jun 27;:1-11

Authors: Blondin MC, Beauregard H, Serri O

Abstract
Objective: To present two cases of iatrogenic Cushing's syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with Ritonavir and itraconazole.Methods: Ae present the clinical and biochemical data of two patients in whom diagnosis of Cushing's syndrome was caused by this interaction. We also reviewed the pertinent literature and management options. ]Results: A 71 year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient developed rapidly a typical Cushing's syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 A.M. cortisol concentrations were suppressed at 0.76 and 0.83 μg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46 year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of HIV. In the following months, she developed typical signs of Cushing's syndrome. Her morning serum cortisol concentration was 1.92 μg/dL. A cosyntropin stimulation test showed values of serum cortisol of <1.10, 2.65 and 5.36 μg/dL at 0, 30 and 60 minutes confirming an adrenal insufficiency. Because the patient was unable to stop budesonide she was advised to reduce the frequency of its administration and eventually taper the dose until cessation.Conclusion: clinicians should be aware of the potential occurrence of iatrogenic Cushing's syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir.

PMID: 23807527 [PubMed - as supplied by publisher]

Curcumin inhibits the proliferation of airway smooth muscle cells in vitro and in vivo.

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Curcumin inhibits the proliferation of airway smooth muscle cells in vitro and in vivo.

Int J Mol Med. 2013 Jun 27;

Authors: Zeng X, Cheng Y, Qu Y, Xu J, Han Z, Zhang T

Abstract
The inhibition of the proliferation of airway smooth muscle cells (ASMCs) is crucial for the prevention and treatment of asthma. Recent studies have revealed some important functions of curcumin; however, its effects on the proliferation of ASMCs in asthma remain unknown. Therefore, in this study, we performed in vitro and in vivo experiments to investigate the effects of curcumin on the proliferation of ASMCs in asthma. The thickness of the airway wall, the airway smooth muscle layer, the number of ASMCs and the expression of extracellular signal-regulated kinase (ERK) were significantly reduced in the curcumin-treated group as compared with the model group. Curcumin inhibited the cell proliferation induced by platelet-derived growth factor (PDGF) and decreased the PDGF-induced phosphorylation of ERK1/2 in the rat ASMCs. Moreover, the disruption of caveolae using methyl-β-cyclodextrin (MβCD) attenuated the anti-proliferative effects of curcumin in the ASMCs, which suggests that caveolin is involved in this process. Curcumin upregulated the mRNA and protein expression of caveolin-1. The data presented in this study demonstrate that the proliferation of ASMCs is inhibited by curcumin in vitro and in vivo; curcumin exerts these effects by upregulating the expression of caveolin-1 and blocking the activation of the ERK pathway.

PMID: 23807697 [PubMed - as supplied by publisher]

Oral hygiene boost could reduce elderly pneumonia risk

Findings from a US study suggest that improving oral hygiene could reduce rates of pneumonia in community-dwelling older adults. (Source: MedWire News - Respiratory)

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