Role of Bronchoscopy in Asthma Research

Kavuru, Mani S.; Dweik, Raed A.; Thomassen, Mary Jane

doi:10.1016/s0272-5231(05)70133-7

Cited by 34 publications

(18 citation statements)

References 174 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While bronchoscopy is routinely performed for research purposes (Adelroth, 1998;Djukanovic, Dahl, Jarjour, & Aalbers, 1998;Jarjour, Peters, Djukanovic, & Calhoun, 1998;Kavuru, Dweik, & Thomassen, 1999), practical considerations limit the number of subjects that can be evaluated in a given study. It is unlikely that a study of this size and duration could detect toxic effects due to changes in CO levels.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of subclinical respiratory tract inflammation in heavy smokers who switch to a cigarette-like nicotine delivery device that primarily heats tobacco

Rennard

Umino

Millatmal

et al. 2002

Nicotine & Tobacco Research

View full text Add to dashboard Cite

Cigarette smoking remains a major public health problem. For smokers who cannot or do not wish to quit, few options exist to reduce health risks. A cigarette-like nicotine delivery device that heats rather than burns tobacco might deliver nicotine with fewer toxins. The current study was designed to determine whether asymptomatic heavy smokers who did not wish to quit had improvement in lower respiratory tract inflammation after switching to Eclipse, a cigarette-like nicotine delivery device that primarily heats rather than burns tobacco. Twelve smokers of at least 40 cigarettes daily, asymptomatic and in good health, underwent paired bronchoscopies, bronchoalveolar lavages and endobronchial biopsies before and after 2 months of using Eclipse. Eight normal non-smoking individuals were evaluated on one occasion for comparison. Inflammation was assessed by direct inspection and by cytological parameters. Goblet cell metaplasia was assessed histologically. Compared to non-smokers, smokers had increased visible inflammation, increased recovery of inflammatory cells and increased percentage of goblet cells. There were significant reductions in all these parameters following a switch to Eclipse use, although the improvement did not reach the normal range. No significant differences were observed in peripheral blood measures. Nicotine levels were generally maintained, and exhaled carbon monoxide (CO) levels trended strongly upward. One individual experienced a transient twofold increase in CO and concurrently experienced transient headaches. Eclipse use may be a strategy to reduce the health risks for heavy smokers unwilling or unable to quit.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of subclinical respiratory tract inflammation in heavy smokers who switch to a cigarette-like nicotine delivery device that primarily heats tobacco

Rennard

Umino

Millatmal

et al. 2002

Nicotine & Tobacco Research

View full text Add to dashboard Cite

show abstract

“…Several types of tissues have been used for human microarray studies of asthma, such as bronchial epithelium, nasal mucosa, and airway inflammatory cells from both patients and healthy subjects (Lilly et al 2005;Gelb et al 2010;Chamberland et al 2009;Baines et al 2009;Guajardo et al 2005). Although the analysis of gene expression in the airway can provide more exact information, obtaining airway tissues is not easy, especially in cases of severe asthma (Kavuru et al 1999). Thus, peripheral blood mononuclear cells (PBMCs) have been used as an alternative (Hanselb et al 2005;Aoki et al 2009;Subrata et al 2009).…”

mentioning

confidence: 99%

Differential gene expression profile in PBMCs from subjects with AERD and ATA: a gene marker for AERD

et al. 2012

View full text Add to dashboard Cite

Aspirin-exacerbated respiratory disease (AERD) is associated with severe asthma and aspirin can cause asthma to worsen, often in the form of a severe and sudden attack. The oral aspirin challenge is the gold standard to confirm the diagnosis of AERD, but it is time consuming and produces serious complications in some cases. Therefore, more efficient and practical method is needed to predict AERD patients. The aim of the present study was to identify AERD-related gene expression in peripheral blood mononuclear cells (PBMCs) and examine the diagnostic potential of these candidate gene(s) for predicting AERD. To do this, RNAs from 24 subjects with AERD and 18 subjects with aspirin-tolerant asthma (ATA) were subjected to microarray analysis of ~34,560 genes. In total, 10 genes were selected as candidate gene markers by applying p ≤ 0.001(t test) and ≥8-fold change, and to correct for multiple comparisons, the false discovery rate analyses were performed. By applying multiple logistic regression analysis, among possible 1,023 models (2(10)-1), a model consisting of CNKSR3, SPTBN2, and IMPACT was selected as candidate set, because this set showed the best AUC (0.98) with 88 % sensitivity and 89 % specificity. For validation, mRNA levels by real-time PCR on PBMCs from two population sets in a gene-chip study and another replication sample, 20 AERD, 20 ATA, and 8 normal controls, were significantly different between groups with 100 % sensitivity and 100 % specificity in each of the two population sets. However, IMPACT gene did not differentiate between AERD and normal controls. The set of the two genes (CNKSR3 and SPTBN2) showed the best AUC (0.96) with 88 % sensitivity and 94 % specificity in a gene-chip study sample. In addition, this set showed perfect discriminative power with AUC (1.0, 100 % sensitivity and 100 % specificity) in each of the two population sets: the gene-chip samples and the replication samples. It also showed perfect discrimination for AERD from NC (AUC: 1.0) and ATA from NC (AUC: 1.0). In conclusion, we developed the two gene markers (CNKSR3 and SPTBN2) of PBMC which differentiate between AERD and ATA with a perfect discriminative power. These gene markers may be an efficient and practical method for predicting AERD.

show abstract

“…The study of pathogenic mechanisms requires a thorough understanding of functional roles of different proteins involved in normal pulmonary homeostasis as well as the specific disease process. Bronchoalveolar lavage (BAL) 1 conducted with fiberoptic bronchoscopy has been widely used to collect cells and other soluble components from the thin layer of epithelial lining fluid that covers the airway and the alveoli (6). Bronchoalveolar lavage fluid (BALF) thus collected contains different cell types as well as a wide variety of proteins that either originate from the blood stream or are released locally by epithelial and inflammatory cells (7)(8)(9).…”

mentioning

confidence: 99%

Differential Proteomic Analysis of Bronchoalveolar Lavage Fluid in Asthmatics following Segmental Antigen Challenge

Wu¹,

Kobayashi

Sousa³

et al. 2005

Molecular & Cellular Proteomics

Self Cite

158

142

View full text Add to dashboard Cite

Allergic asthma is characterized by persistent airway inflammation and remodeling. Bronchoalveolar lavage conducted with fiberoptic bronchoscopy has been widely used for investigating the pathogenesis of asthma and other lung disorders. Identification of proteins in the bronchoalveolar lavage fluid (BALF) and their expression changes at different stages of asthma could provide further insights into the complex molecular mechanisms involved in this disease. In this report, we describe the first comprehensive differential proteomic analysis of BALF from both asthmatic patients and healthy subjects before and 24 h after segmental allergen challenge. Our proteomic analysis involves affinity depletion of six abundant BALF proteins, SDS-PAGE fractionation, protein in-gel digestion, and subsequent nano-LC-MS/MS analysis in conjunction with database searching for protein identification and semiquantitation. More than 1,500 distinct proteins were identified of which about 10% displayed significant up-regulation specific to the asthmatic patients after segmental allergen challenge. The differentially expressed proteins represent a wide spectrum of functional classes such as chemokines, cytokines, proteases, complement factors, acute phase proteins, monocyte-specific granule proteins, and local matrix proteins, etc. The majority of these protein expression changes are closely associated with many aspects of the pathophysiology of asthma, including inflammation, eosinophilia, airway remodeling, tissue damage and repair, mucus production, and plasma infiltration. Importantly a large portion of these proteins and their expression changes were identified for the first time from BALF, thus providing new insights for finding novel pathological mediators and biomarkers of asthma.

show abstract

Role of Bronchoscopy in Asthma Research

Cited by 34 publications

References 174 publications

Evaluation of subclinical respiratory tract inflammation in heavy smokers who switch to a cigarette-like nicotine delivery device that primarily heats tobacco

Evaluation of subclinical respiratory tract inflammation in heavy smokers who switch to a cigarette-like nicotine delivery device that primarily heats tobacco

Differential gene expression profile in PBMCs from subjects with AERD and ATA: a gene marker for AERD

Differential Proteomic Analysis of Bronchoalveolar Lavage Fluid in Asthmatics following Segmental Antigen Challenge

Contact Info

Product

Resources

About