Patients with mild COPD have higher all-cause mortality and respiratory disease-related death than individuals with normal spirometry, according to systematic review and meta-analysis findings published in Pulmonology.

There is conflicting evidence regarding whether risk of all-cause death in patients with mild COPD is higher than the risk among patients with normal spirometry. Therefore, investigators sought compare rates of all-cause mortality and respiratory-related mortality in individuals with mild COPD vs those with normal spirometry.

The investigators conducted a systematic review and meta-analysis of cohort studies reporting an association between mild COPD and all-cause mortality in adult patients, searching the Web of Science, Embase, and PubMed databases from inception through February 2023. Mild COPD was defined as pre-bronchodilator or post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than 0.70 and FEV1 at least 80% of the predicted value. Normal spirometry was defined as pre- or post-bronchodilator FEV1/FVC at least 0.70 and FEV1 at least 80% of the predicted value.

The investigators found 12 studies published between 2003 and 2023 (all graded as good quality) that met eligibility requirements (N=9973 participants with mild COPD; N=255,527 participants with normal spirometry). All data were adjusted for body mass index and age. Most of the studies used the pre-bronchodilator definition of mild COPD. Average follow-up was less than 10 years in 5 studies and at least 10 years in 7 studies.

[P]atients with mild COPD have higher all-cause mortality and respiratory disease-related mortality than individuals with normal spirometry.

Patients with mild COPD vs those with normal spirometry had higher risk of all-cause mortality (pre-bronchodilator hazard ratio [HR], 1.21; 95% CI, 1.11-1.32; I2=47.1%; P =.023; post-bronchodilator HR, 1.19; 95% CI, 1.02-1.39; I2=0.0%; P =.365).

There was no suggestion of publication bias in funnel plots or Egger’s line regression. Omit-one meta-analysis showed HRs and corresponding CIs were greater than 1.

A higher risk for respiratory disease-related death was noted among individuals with mild COPD vs those with normal spirometry (HR, 1.71; 95% CI, 1.03-2.82; I2=0.0%). No higher risk for cardiovascular disease-related death was found among individuals with mild COPD vs those with normal spirometry (HR, 1.22; 95% CI, 0.87-1.71; I2=27.1%) nor was there a higher risk for cancer-related mortality (HR, 1.19; 95% CI, 0.93-1.51; I2=0.0%).

Among those who currently smoked, risk of all-cause mortality was higher among people with mild COPD vs those with normal spirometry (HR, 1.31; 95% CI, 1.04-1.64; I2=62.0%; P =.021).

In citing limitations their analysis, the researchers noted that most included studies used pre-bronchodilator spirometry to diagnose mild COPD whereas Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend use of post-bronchodilator spirometry. Additionally, the number of studies in each subgroup was too small to obtain clear results.

“[P]atients with mild COPD have higher all-cause mortality and respiratory disease-related mortality than individuals with normal spirometry,” the review authors concluded. The investigators wrote, “Further research is required to determine whether early pharmacological or nonpharmacological intervention and treatment are beneficial in mild COPD.”

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