Chronic Bronchitis Increases Mortality Risk in Ever-Smokers

Non-obstructive chronic bronchitis (CB) is associated with an increased risk of mortality, but only in ever-smokers, not in those who never smoked, the first systematic review and meta-analysis of its kind suggests.

“Non-obstructive chronic bronchitis may be a precursor of chronic obstructive pulmonary disease (COPD) as people with non-obstructive chronic bronchitis have a chronic productive cough but normal lung function, [although] they may progress to COPD,” Spyridon Fortis, MD, clinical associate professor of medicine, University of Iowa Hospitals and Clinics, Iowa City, told Medscape Medical News in an email.

“I would hypothesize that non-obstructive CB in people with smoking exposure may be associated with progression to COPD, and for that reason, they have an increased [risk] of mortality,” he speculated.

The study was published online February 9 in the journal Chest.

General Population Studies

Eight studies were included in the review and meta-analysis. “All of the studies were prospective general population studies,” the authors note. In five of the studies, chronic bronchitis was defined as sputum production lasting for at least 3 months; in the other three, it was part of a broader definition of respiratory symptoms, such as dyspnea and wheezing. All eight studies were considered to be of high quality, the authors point out.

“The overall pooled results showed a significant association between non-obstructive CB and all cause mortality,” they report. Specially, mortality risk was 37% higher for patients with non-obstructive CB than it was for patients without non-obstructive CB, at a hazard ratio (HR) of 1.37 (95% CI, 1.26 – 1.50), the authors report.

However, in the three studies in which CB was part of a broader definition of any respiratory symptom, non-obstructive CB was associated with a slightly lower 28% increase in mortality, at an HR of 1.28 (95% CI, 1.10 – 1.48), they add. In studies in which non-obstructive CB was not part of a broader definition, it was associated with a slightly higher 40% increased mortality risk, at an HR of 1.40 (95% CI, 1.26 – 1.56). Only four studies stratified findings by smoking status.

In those studies that did, non-obstructive CB was associated with a 49% increase in mortality risk in ever-smokers, at an HR of 1.49 (95% CI, 1.35 – 1.64), Fortis and colleagues report. In contrast, non-obstructive CB was not associated with an increased mortality risk in never-smokers, at an HR of 1.22 (95% CI, 0.90 – 1.66).

As the authors point out, CB is a typical symptom for patients with COPD resulting from a combination of overproduction of mucus and decreased mucus clearance in the airways. “Mucus hypersecretion and stasis can increase the risk for respiratory infections and obstruct primarily small airways causing further respiratory symptoms,” the authors explain.

Complex Associations

The lack of association of mortality and non-obstructive CB in never-smokers may indicate a different pathology with a benign cause, such as allergic rhinitis, in which treatment is not critical, the authors speculate. On the other hand, in current and former smokers, non-obstructive CB may indicate chronic lung disease that has not yet progressed to COPD. This finding may also result from the fact that the subgroup analysis with never-smokers had a smaller number of participants and even a smaller number of participants with CB than the analysis with ever-smokers, and hence the statistical power to demonstrate an association was lower, according to the authors.

Non-obstructive CB may also be associated with progression of COPD, which in turn increases mortality risk, they add. That said, the link between non-obstructive CB and mortality identified in the current meta-analysis may not be causal. As the investigators explain, non-obstructive CB may be confounded by smoking exposure.

For example, smokers with COPD have evidence of systemic arterial stiffness — a predictor of cardiovascular mortality — but this is not present in never-smokers with COPD that is due to other causes. Heavy smoking exposure may thus result in non-obstructive CB, but it’s also a risk factor for cardiovascular death and lung cancer.

On the other hand, non-obstructive CB may reflect the fact that current and former smokers already have chronic lung disease — just one that has not yet progressed to COPD, the authors speculate. Given that non-obstructive CB is a risk factor for mortality, “this population should be considered as a target group for potential therapeutic interventions,” the authors also suggest. Most importantly, smoking cessation efforts should focus on those with non-obstructive CB to slow down COPD progression.

Improvement of diagnostic criteria may also help identify COPD earlier, when interventions may be more effective.

Fortis has received grants from Fisher & Paykel and has served as a consultant for Genentech.

Chest. Published online February 9, 2022. Abstract

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