Small Airway Mucous Metaplasia and Inflammation in Chronic Obstructive Pulmonary Disease

Kim, Victor; Kelemen, Sheri E.; Abuel-Haija, Mohammad; Gaughan, John; Sharafkaneh, Amir; Evans, Christopher M.; Dickey, Burton F.; Solomides, Charalambos; Rogers, Thomas J.; Criner, Gerard J.

doi:10.1080/15412550802522445

Cited by 40 publications

(35 citation statements)

References 29 publications

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“…Saetta and colleagues found that current smokers with moderate COPD and CB had an increased number of goblet cells in the peripheral airways on surgical lung biopsies (41). In a small study of subjects with COPD, mucous metaplasia in the small airways increased as the degree of airflow obstruction worsened (42). A larger pathologic study found that a greater number of small airways were occluded by mucus as disease severity increased (38).…”

Section: Pathophysiologymentioning

confidence: 97%

Chronic Bronchitis and Chronic Obstructive Pulmonary Disease

Kim

Criner

2013

Am J Respir Crit Care Med

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388

276

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Chronic bronchitis (CB) is a common but variable phenomenon in chronic obstructive pulmonary disease (COPD). It has numerous clinical consequences, including an accelerated decline in lung function, greater risk of the development of airflow obstruction in smokers, a predisposition to lower respiratory tract infection, higher exacerbation frequency, and worse overall mortality. CB is caused by overproduction and hypersecretion of mucus by goblet cells, which leads to worsening airflow obstruction by luminal obstruction of small airways, epithelial remodeling, and alteration of airway surface tension predisposing to collapse. Despite its clinical sequelae, little is known about the pathophysiology of CB and goblet cell hyperplasia in COPD, and treatment options are limited. In addition, it is becoming increasingly apparent that in the classic COPD spectrum, with emphysema on one end and CB on the other, most patients lie somewhere in the middle. It is known now that many patients with severe emphysema can develop CB, and small airway pathology has been linked to worse clinical outcomes, such as increased mortality and lesser improvement in lung function after lung volume reduction surgery. However, in recent years, a greater understanding of the importance of CB as a phenotype to identify patients with a beneficial response to therapy has been described. Herein we review the epidemiology of CB, the evidence behind its clinical consequences, the current understanding of the pathophysiology of goblet cell hyperplasia in COPD, and current therapies for CB.Keywords: chronic obstructive pulmonary disease; chronic bronchitis; goblet cell hyperplasia; N-acetylcysteine; roflumilast Chronic obstructive pulmonary disease (COPD) is a common disease characterized by irreversible airflow obstruction and persistent inflammation to noxious environmental stimuli, usually cigarette smoke. It affects 12 to 16 million people in the United States and is the third leading cause of death and disease burden worldwide (1). COPD encompasses a spectrum of diseases, with chronic bronchitis (CB) at one end and emphysema at the other, with most individuals having some characteristics of both. The CB definition used in epidemiologic studies has been variable, but the classic definition is chronic cough and sputum production for at least 3 months per year for two consecutive years (2). CB has numerous clinical consequences, including an increased exacerbation rate, accelerated decline in lung function, worse health-related quality of life (HRQoL), and possibly increased mortality (3-6). We review the clinical phenotype of CB, the current understanding of its pathophysiology, and treatment options. EPIDEMIOLOGYCB is common in the general population. Table 1 provides an overview of the prevalence of cough and sputum production in population-based studies. CB is seen in 3.4 to 22.0% of adults (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). This wide range of prevalence estimates may be due to varying definitions of CB (i.e., chronic phlegm ver...

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Section: Pathophysiologymentioning

confidence: 97%

Chronic Bronchitis and Chronic Obstructive Pulmonary Disease

Kim

Criner

2013

Am J Respir Crit Care Med

Self Cite

388

276

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“…As the severity of disease, i.e. extent of airway obstruction, worsens in COPD, the degree of mucous metaplasia and occlusion of the small airways by mucus tends to increase [49,50]. Mucus hypersecretion is caused by increased goblet cell degranulation due to neutrophil elastase [51].…”

Section: Pathologymentioning

confidence: 98%

Causes of chronic productive cough: An approach to management

Martin

Harrison

2015

Respiratory Medicine

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A chronic 'productive' or 'wet' cough is a common presenting complaint for patients attending the adult respiratory clinic. Most reviews and guidelines suggest that the causes of a productive cough are the same as those of a non-productive cough and as such the same diagnostic pathway should be followed. We suggest a different diagnostic approach for patients with a productive cough, focussing on the conditions that are the most likely causes of this problem. This review is intended to briefly summarise the epidemiology, clinical features, pathophysiology and treatment of a number of conditions which are often associated with chronic productive cough to aid decision making when encountering a patient with this often distressing symptom. The conditions discussed include bronchiectasis, chronic bronchitis, asthma, eosinophilic bronchitis and immunodeficiency. We also propose an adult version of the paediatric diagnosis of protracted bacterial bronchitis (PBB) in patients with idiopathic chronic productive cough who appear to respond well to low dose macrolide therapy.

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“…Five μm thick transverse sections were obtained using a microtome, collected onto positively charged glass slides and stained with periodic acid fluorescent Schiff’s stain (PAFS). Images of bronchial airway sections were captured at 40× magnification as explained previously [7, 25, 26]. For images measured on a μm scale, the mucin volume density was calculated in a blinded manner using ImageJ software (National Institutes of Health) by dividing the area of mucin staining by the product of the length of basement membrane and 4/π, and expressed as nl/mm 2 .…”

Section: Methodsmentioning

confidence: 99%

Effects of β-blockers on house dust mite-driven murine models pre- and post-development of an asthma phenotype

Joshi

Valdez

Kim

et al. 2017

Pulmonary Pharmacology & Therapeutics

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Background Our previous studies suggested certain β-adrenoceptor blockers (β-blockers) attenuate the asthma phenotype in ovalbumin driven murine models of asthma. However, the ovalbumin model has been criticized for lack of clinical relevance. Methods We tested the non-selective β-blockers, carvedilol and nadolol, in house dust mite (HDM) driven murine asthma models where drugs were administered both pre- and post- development of the asthma phenotype. We measured inflammation, mucous metaplasia, and airway hyper-responsiveness (AHR). We also measured the effects of the β-blockers on extracellular-signal regulated kinases (ERK 1/2) phosphorylation in lung homogenates. Results We show that nadolol, but not carvedilol, attenuated inflammation and mucous metaplasia, and had a moderate effect attenuating AHR. Following HDM exposure, ERK1/2 phosphorylation was elevated, but the level of phosphorylation was unaffected by β-blockers, suggesting ERK1/2 phosphorylation becomes dissociated from the asthma phenotype. Conclusion Our findings in HDM models administering drugs both pre- and post-development of the asthma phenotype are consistent with previous results using ovalbumin models and show differential effects for nadolol and carvedilol on the asthma phenotype. Lastly, our data suggest that ERK1/2 phosphorylation may be involved in development of the asthma phenotype, but may have a limited role in maintaining the phenotype.

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Small Airway Mucous Metaplasia and Inflammation in Chronic Obstructive Pulmonary Disease

Cited by 40 publications

References 29 publications

Chronic Bronchitis and Chronic Obstructive Pulmonary Disease

Chronic Bronchitis and Chronic Obstructive Pulmonary Disease

Causes of chronic productive cough: An approach to management

Effects of β-blockers on house dust mite-driven murine models pre- and post-development of an asthma phenotype

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