Adverse Effects of Eosinophilia and Smoking on the Natural History of Newly Diagnosed Chronic Bronchitis

doi:10.1378/chest.108.1.55

Chest

Volume 108, Issue 1, July 1995, Pages 55-61

https://doi.org/10.1378/chest.108.1.55 Get rights and content

Background: Little is known about risk factors for the progression of disease in individuals with newly developed chronic bronchitis (CB). In addition to the effects of smoking, there was specific clinical and epidemiologic interest in the importance of traits such as eosinophilia and wheezing, more commonly associated with asthma, in the progression of this disease.

Methods: We evaluated adult individuals with and without diagnosed CB longitudinally in a representative community population in Tucson, Ariz. These subjects were followed up for 13 years since 1972. Because we were interested in CB specifically, those with diagnoses of emphysema and asthma were removed from the data set. Initial level of FEV₁ (%FEV₁) and slopes in FEV₁were corrected for covariates and other important variables.

Results: As expected, persistent and newly diagnosed CB was significantly more common in current and ex-smokers. Furthermore, initial lung function was lower, and decline in FEV₁ was steeper in smokers with persistent and newly diagnosed CB. Newly diagnosed cases had steeper declines in FEV₁ (–6.84 mL/yr below grand mean of –11.18 mL/yr) than normal subjects (+0.95 mL/yr). The incidence rate of newly diagnosed CB was significantly higher in those with eosinophilia (13.7%) than without eosinophilia (6.7%). Finally, new cases with eosinophilia had similar initial %FEV₁(95.4 ± 1%) but much larger declines in function than new cases without eosinophilia: –24.5 versus –16.6 mL/yr. Adverse effects of wheeze were largely explained by smoking and eosinophilia.

Conclusion: Eosinophilia is an important aspect of CB in addition to smoking, and it should be considered in its evaluation. The presence of eosinophilia in newly diagnosed CB, with or without wheeze, may warn the clinician of the possibility of a rapid decline in FEV₁.

Section snippets

Materials and Methods

The study population was derived from all non-Hispanic white adults (ages 20 and older) enrolled in the Tucson Epidemiological study of AOD in a community population described elsewhere.⁷^,⁸ Data used for these analyses are on subjects studied from 1972 through 1985 during the nine conducted surveys. Characteristics of the study population have been presented previously.⁷^,⁸ Briefly, the proportion of males and the average age within each gender did not differ significantly by survey. However,

Results

A total of 1,763 adults had satisfactory initial lung function determinations; 1,408 had sufficient longitudinal lung function determinations (without having had chest or lung surgery) for calculations of slopes, and 1,148 were without diagnoses of emphysema or asthma; 1,015 met both criteria.

Table 1 presents the rates (percentages) of persistent and newly diagnosed CB by categories of gender, initial smoking habit, and eosinophilia. The rate of persistent CB was somewhat higher in females with

Discussion

This study shows that in individuals with newly diagnosed CB the presence of eosinophilia may indicate a risk for more rapid decline in FEV₁ even in the absence of asthma. This was the case both in current smokers and in ex- and never-smokers. As expected, those with persistent CB had lower lung function and more rapid declines in FEV₁, especially if they were current smokers. However, new cases of CB had comparable increased declines, although their initial %FEV₁ after adjustments was higher

Acknowledgments

We wish to thank B. Boyer, C. Holberg, W. Kaltenborn, other staff, and the subjects for all their contributions. Many of our colleagues also have made constructive comments, including Drs. R. Barbee, J. Bloom, M. Halonen, M. Krzyzanowski, S. Quan, and D. Sherrill.

References (49)

KrzyzanowskiM et al.
Relationships between pulmonary function and changes in chronic respiratory symptoms—comparison of Tucson and Cracow longitudinal studies
Chest
(1990)
HalonenM et al.
An epidemiologic study of the interrelationships of total serum IgE, allergy skin test reactivity and eosinophilia
J Allergy Clin Immunol
(1982)
BurrowsB et al.
Characteristics of asthma among elderly adults in a sample of the general population
Chest
(1991)
MensingaTT et al.
The relationship of eosinophilia and positive skin test reactivity to respiratory symptom prevalence
J Allergy Clin Immunol
(1990)
LacosteJL et al.
Eosinophilic and neutrophilic inflammation in asthma, chronic bronchitis, and chronic obstructive pulmonary disease
J Allergy Clin Immunol
(1993)
WempeJB et al.
Blood eosinophil numbers and activity during 24 hours: effects of treatment with budesonide and bambuterol
J Allergy Clin Immunol
(1992)
ShimC et al.
Response to corticosteroids in chronic bronchitis
J Allergy Clin Immunol
(1978)
WatsonA et al.
Failure of inhaled corticosteroids to modify bronchoconstrictor or bronchodilator responsiveness in middle-aged smokers with mild airflow obstruction
Chest
(1992)
VermaVK et al.
Airway responsiveness to inhaled histamine in chronic obstructive airways disease (chronic bronchitis vs
emphysema). Chest
(1988)
LebowitzMD et al.
Risk factors in induction of lung disease: an epidemiologic approach
In: Stein RP, Weinbaum G, eds. Mechanisms of lung injury. Philadelphia: Stickley Publishing
(1986)

BurrowsB

Airways obstructive diseases: pathogenetic mechanisms and natural histories of the disorders

Med Clin North Am

(1990)

SluiterHJ et al.

The Dutch hypothesis (CNSLD) revisited

Eur Respir J

(1991)

VermeirePA et al.

A “splitting” look at CNSLD: common features but diverse pathogenesis

Eur Respir J

(1991)

BurrowsB et al.

A reexamination of risk factors for ventilatory impairment

Am Rev Respir Dis

(1988)

BurrowsB et al.

Characteristics of chronic bronchitis in a warm, dry climate

Am Rev Respir Dis

(1975)

LebowitzMD et al.

The Tucson epidemiology study of chronic obstructive lung disease: I

Methodology and prevalence of disease. Am J Epidemiol

(1975)

LebowitzMD

The trends in airway obstructive disease morbidity in the Tucson epidemiological study

Am Rev Respir Dis

(1989)

LebowitzMD et al.

Methodological considerations of epidemiological diagnoses in respiratory diseases

Eur J Epidemiol

(1985)

KnudsonRJ et al.

Changes in the normal maximum expiratory flow-volume curve with growth and aging

Am Rev Respir Dis

(1983)

BurrowsB et al.

Epidemiological observations on eosinophilia and its relationship to respiratory disorders

Am Rev Respir Dis

(1980)

OrieNGM et al.

The host factor in bronchitis. In: Bronchitis: an international symposium

Assen, the Netherlands: Royal Gorcum

(1961)

FletcherCM

Bronchial infection and reactivity in chronic bronchitis

J R Coll Physicians Lond

(1968)

BarterCE et al.

Factors affecting the decline in FEV₁ in chronic bronchitis

Aust N Z J Med

(1974)

CampbellAH et al.

Factors affecting the decline of ventilatory function in chronic bronchitis

Thorax

(1985)

Cited by (28)

Reactive oxygen species and antioxidant therapeutic approaches
2009, Asthma and COPD
This chapter reviews the evidence for the role of reactive oxygen species (ROS) in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD), and discusses the molecular mechanisms (cell signaling and gene expression) and pathophysiological consequences of increased ROS release in these conditions. Moreover, it also highlights the antioxidant mechanisms in place to protect against the damaging effects of ROS. ROS and reactive nitrogen species (RNS) can also be generated intracellularly from several sources such as mitochondrial respiration, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, and xanthine/xanthine oxidase (XO). However, the primary ROS generating system is NADPH oxidase, a complex enzyme system that is present in phagocytes and epithelial cells. Oxygen species, such as superoxide anion and hydroxyl radical are highly reactive, and when generated close to cell membranes they oxidize membrane phospholipids (lipid peroxidation), a process which may continue as a chain reaction. Thus, a single hydroxyl radical can result in the formation of many molecules of lipid hydroperoxides in the cell membrane. There is now increasing evidence that ROS generation plays a major pathophysiological role in asthma and COPD, and it is important for the severity of these conditions. ROS generation through endogenous mechanisms or exogenous cigarette smoke/environmental oxidants is critical to the inflammatory response through activation of redox-sensitive transcription factors and pro-inflammatory signaling pathways. A variety of oxidants, free radicals, and aldehydes are implicated in the pathogenesis of COPD, therefore it is possible that the therapeutic administration of multiple antioxidants will be effective in the treatment of COPD. Finally, the chapter explores possible therapeutic approaches that involve the use of a variety of antioxidants.
Reactive oxygen species and antioxidant therapeutic approaches
2008, Asthma and COPD: Basic Mechanisms and Clinical Management
This chapter reviews the evidence for the role of reactive oxygen species (ROS) in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD), and discusses the molecular mechanisms (cell signaling and gene expression) and pathophysiological consequences of increased ROS release in these conditions. Moreover, it also highlights the antioxidant mechanisms in place to protect against the damaging effects of ROS. ROS and reactive nitrogen species (RNS) can also be generated intracellularly from several sources such as mitochondrial respiration, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, and xanthine/xanthine oxidase (XO). However, the primary ROS generating system is NADPH oxidase, a complex enzyme system that is present in phagocytes and epithelial cells. Oxygen species, such as superoxide anion and hydroxyl radical are highly reactive, and when generated close to cell membranes they oxidize membrane phospholipids (lipid peroxidation), a process which may continue as a chain reaction. Thus, a single hydroxyl radical can result in the formation of many molecules of lipid hydroperoxides in the cell membrane. There is now increasing evidence that ROS generation plays a major pathophysiological role in asthma and COPD, and it is important for the severity of these conditions. ROS generation through endogenous mechanisms or exogenous cigarette smoke/environmental oxidants is critical to the inflammatory response through activation of redox-sensitive transcription factors and pro-inflammatory signaling pathways. A variety of oxidants, free radicals, and aldehydes are implicated in the pathogenesis of COPD, therefore it is possible that the therapeutic administration of multiple antioxidants will be effective in the treatment of COPD. Finally, the chapter explores possible therapeutic approaches that involve the use of a variety of antioxidants.
Oxidative stress indices in COPD-Broncho-alveolar lavage and salivary analysis
2007, Archives of Oral Biology
Citation Excerpt :
Multiple salivary components are derived from the serum while the remainder are derived from the salivary gland cells themselves. Accordingly, the saliva composition represents to some extent the systemic reaction to a given condition.24–33 One way to evaluate alterations of the oxidative stress in conditions such as COPD is by lavage fluid analysis, an invasive procedure with a substantial complication rate.
: It has been suggested that oxidative stress plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD), though this role has yet to be fully elucidated. The purpose of this study was to further evaluate this role as concomitantly expressed in the saliva and broncho-alveolar lavage (BAL/‘lavage’).
: Forty consenting patients (mean age 62 ± 13-year-old), with/without COPD and/or smoking habit, participated in the study. The following antioxidant profile was examined both in saliva and lavage of the patients: total antioxidant status (TAS), uric acid (UA), peroxidase and super oxide dismutase (SOD). Total protein (TP) and albumin (Alb) were also evaluated in both saliva and lavage while amylase was measured only in saliva.
: Increase of TAS (by 100%) and of SOD activity levels (by 60%) in the lavage of COPD patients indicated oxidative stress. The salivary UA in COPD patients was 125% higher (p = 0.05) while the peroxidase was 20% higher. Another novel finding was that levels of salivary antioxidants in smoking versus non-smoking COPD patients were lower by 25–48% (for all four: TAS, UA, peroxidase and SOD) while the albumin was significantly reduced by 60% (p = 0.018).
: Oxidative-stress-related changes demonstrated both in the lavage and saliva of the COPD and/or smoking patient indicate cumulative effects of both, also emphasizing the pathogenetic role of free radicals in COPD. Salivary analysis, which is less invasive and much easier to perform as compared with lavage analysis, is suggested as a new and effective diagnostic tool in COPD patients.
Oxidative stress in asthma and COPD: Antioxidants as a therapeutic strategy
2006, Pharmacology and Therapeutics
Asthma and chronic obstructive pulmonary disease (COPD) are inflammatory lung diseases that are characterized by systemic and chronic localized inflammation and oxidative stress. Sources of oxidative stress arise from the increased burden of inhaled oxidants, as well as elevated amounts of reactive oxygen species (ROS) released from inflammatory cells. Increased levels of ROS, either directly or via the formation of lipid peroxidation products, may play a role in enhancing the inflammatory response in both asthma and COPD. Moreover, in COPD it is now recognized as the main pathogenic factor for driving disease progression and increasing severity. ROS and lipid peroxidation products can influence the inflammatory response at many levels through its impact on signal transduction mechanisms, activation of redox-sensitive transcriptions factors, and chromatin regulation resulting in pro-inflammatory gene expression. It is this impact of ROS on chromatin regulation by reducing the activity of the transcriptional co-repressor, histone deacetylase-2 (HDAC-2), that leads to the poor efficacy of corticosteroids in COPD, severe asthma, and smoking asthmatics. Thus, the presence of oxidative stress has important consequences for the pathogenesis, severity, and treatment of asthma and COPD. However, for ROS to have such an impact, it must first overcome a variety of antioxidant defenses. It is likely, therefore, that a combination of antioxidants may be effective in the treatment of asthma and COPD. Various approaches to enhance the lung antioxidant screen and clinical trials of antioxidant compounds are discussed.
Diagnosis of bronchial eosinophilic inflammation: An important step
2004, Medicina Clinica
Early diagnosis of airway inflammation in smokers: Still a challenge
2003, Archivos de Bronconeumologia

View all citing articles on Scopus

This work was supported by US NHLBI SCOR grant No. HL 14136 and by funas from the Dutch Asthma Foundation.

Manuscript revision accepted November 14.

View full text

Chest

Clinical InvestigationsAdverse Effects of Eosinophilia and Smoking on the Natural History of Newly Diagnosed Chronic Bronchitis

Section snippets

Materials and Methods

Results

Discussion

Acknowledgments

Chest

J Allergy Clin Immunol

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

emphysema). Chest

Risk factors in induction of lung disease: an epidemiologic approach

In: Stein RP, Weinbaum G, eds. Mechanisms of lung injury. Philadelphia: Stickley Publishing

Airways obstructive diseases: pathogenetic mechanisms and natural histories of the disorders

Med Clin North Am

The Dutch hypothesis (CNSLD) revisited

Eur Respir J

A “splitting” look at CNSLD: common features but diverse pathogenesis

Eur Respir J

A reexamination of risk factors for ventilatory impairment

Am Rev Respir Dis

Characteristics of chronic bronchitis in a warm, dry climate

Am Rev Respir Dis

The Tucson epidemiology study of chronic obstructive lung disease: I

Methodology and prevalence of disease. Am J Epidemiol

The trends in airway obstructive disease morbidity in the Tucson epidemiological study

Am Rev Respir Dis

Methodological considerations of epidemiological diagnoses in respiratory diseases

Eur J Epidemiol

Changes in the normal maximum expiratory flow-volume curve with growth and aging

Am Rev Respir Dis

Epidemiological observations on eosinophilia and its relationship to respiratory disorders

Am Rev Respir Dis

The host factor in bronchitis. In: Bronchitis: an international symposium

Assen, the Netherlands: Royal Gorcum

Bronchial infection and reactivity in chronic bronchitis

J R Coll Physicians Lond

Factors affecting the decline in FEV1 in chronic bronchitis

Aust N Z J Med

Factors affecting the decline of ventilatory function in chronic bronchitis

Thorax

Clinical Investigations
Adverse Effects of Eosinophilia and Smoking on the Natural History of Newly Diagnosed Chronic Bronchitis

Factors affecting the decline in FEV₁ in chronic bronchitis