Markers of exacerbation severity in chronic obstructive pulmonary disease

Franciosi, Luigi G.; Page, Clive; Celli, Bartolomé R.; Cazzola, Mario; Walker, Michael J.; Danhof, Meindert; Rabe, Klaus F.; Pasqua, Oscar Della

doi:10.1186/1465-9921-7-74

Cited by 57 publications

(46 citation statements)

References 54 publications

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“…This rapid breathing coupled with hypoxemia/hypercapnia and an increase in HR is somewhat similar to COPD exacerbation. Dyspnea characterized by faster breathing (20% increase), increase in HR and appearance of hypoxemic hypercapnia have been reported in patients with COPD exacerbation (Pauwels et al 2004;Franciosi et al 2006). Third, AVR to hypoxia and hypercapnia was observed in CS-exposed mice.…”

Section: It Is Novel That the Major Symptoms Of Anesthetized C3h/hen mentioning

confidence: 89%

“…They are hypercapnia (Pa CO 2 > 50 torr) coupled with hypoxemia (Pa O 2 < 60 torr) (Pauwels et al 2001); rapid breathing (Altose et al 1977;Fahey et al 1983;Gorini et al 1990;van de Ven et al 2002); and an attenuated ventilatory response (AVR) to hypercapnia/hypoxia (Schaefer 1949;Fahey et al 1983;Franciosi et al 2006;Ucgun et al 2006). It is generally accepted that the AVR is correlated with mechanical limitation of ventilatory capacity (Cherniack et al 1956;Pauwels et al 2001).…”

Section: Introductionmentioning

confidence: 99%

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Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke-induced emphysema

Zhuang

Wang

et al. 2007

Respiratory Physiology & Neurobiology

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It has been reported that the degree of emphysema induced by chronic cigarette smoke (CS) is greater in female C3H/HeN mice as compared to other mouse strains. We hypothesized that these mice would develop the similar major characteristics seen in hypercapnic patients with chronic obstructive pulmonary disease (COPD), including emphysema, pulmonary inflammation, hypercapnia/ hypoxemia, rapid breathing, and attenuated ventilatory response (AVR). Mice were exposed either to CS or filtered air (FA) for 16 wk. After exposure, arterial blood gases and minute ventilation were measured before and during chemical challenges in anesthetized and spontaneously breathing mice. We found that as compared to FA, CS exposure caused emphysema and pulmonary inflammation associated with: (1) hypercapnia and hypoxemia, (2) rapid breathing, and (3) AVR to 25 breaths of pure N 2 , 5% CO 2 alone, and 5% CO 2 coupled with 10% O 2 . The similarity of these pathophysiological characteristics between our mouse model and COPD patients suggests that this model could be effectively applied to study COPD pathophysiology, especially central mechanisms of the AVR genesis.

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Section: It Is Novel That the Major Symptoms Of Anesthetized C3h/hen mentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke-induced emphysema

Zhuang

Wang

et al. 2007

Respiratory Physiology & Neurobiology

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“…Plasma biomarkers are discussed in the Nonpulmonary markers section. A review of .600 published studies suggests that few of these biomarkers have been validated and there is little information about reproducibility and the relationship to disease development, severity or progression [177,472]. In evaluating pulmonary biomarkers it is important to compare findings in patients with COPD with cigarette smokers matched for exposure who do not have significant airflow limitation (normal smokers) and with age-matched nonsmoking normal subjects.…”

Section: Introductionmentioning

confidence: 99%

Outcomes for COPD pharmacological trials: from lung function to biomarkers

Cazzola¹,

MacNee²,

Martínez³

et al. 2008

Eur Respir J

751

566

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The American Thoracic Society/European Respiratory Society jointly created a Task Force on “Outcomes for COPD pharmacological trials: from lung function to biomarkers” to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

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“…As with other diseases, much hope has been placed in the discovery of biomarkers that would help understand the mechanisms of COPD (6)(7)(8)(9)(10). It is also hoped that some of these could speed up drug discovery by serving as surrogate markers that respond to novel drugs within a shorter time span than spirometric measurements of lung function, currently the main clinical outcome in drug trials.…”

mentioning

confidence: 99%

Identification of Lipocalin and Apolipoprotein A1 as Biomarkers of Chronic Obstructive Pulmonary Disease

Nicholas

Skipp²,

Barton³

et al. 2010

Am J Respir Crit Care Med

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Rationale: Much effort is being made to discover noninvasive biomarkers of chronic airway disease that might enable better management, predict prognosis, and provide new therapeutic targets. Objectives: To undertake a comprehensive, unbiased proteomic analysis of induced sputum and identify novel noninvasive biomarkers for chronic obstructive pulmonary disease (COPD). Methods: Induced sputum was obtained from patients with COPD with a spectrum of disease severity and from control subjects. Twodimensional gel electrophoresis and mass spectrometric identification of differentially expressed proteins were first applied to induced sputum from patients with GOLD stage 2 COPD and healthy smoker control subjects. Initial results thus obtained were validated by a combination of immunoassays (Western blotting and ELISA) applied to a large subject cohort. The biomarkers were localized to bronchial mucosa by immunohistochemistry. Measurements and Main Results: Of 1,325 individual protein spots identified, 37 were quantitatively and 3 qualitatively different between the two groups (P , 0.05%). Forty protein spots were subjected to tandem mass spectrometry, which identified 15 separate protein species. Seven of these were further quantified in induced sputum from 97 individuals. Using this sequential approach, two of these potential biomarkers (apolipoprotein A1 and lipocalin-1) were found to be significantly reduced in patients with COPD when compared with healthy smokers. Their levels correlated with FEV 1 /FVC, indicating their relationship to disease severity. Conclusions: A potential role for apolipoprotein A1 and lipocalin-1 in innate defense has been postulated previously; our discovery of their reduction in COPD indicates a deficient innate defense system in airway disease that could explain increased susceptibility to infectious exacerbations.

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Markers of exacerbation severity in chronic obstructive pulmonary disease

Cited by 57 publications

References 54 publications

Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke-induced emphysema

Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke-induced emphysema

Outcomes for COPD pharmacological trials: from lung function to biomarkers

Identification of Lipocalin and Apolipoprotein A1 as Biomarkers of Chronic Obstructive Pulmonary Disease

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